Foreground Demo

Cardiovascular diseases (CVDs) remain a leading cause of mortality worldwide, motivating reproducible benchmark studies on accurate classification methods with calibrated probability estimates. In this paper, we propose a deep learning framework based on a Variational Recurrent Autoencoder (VRAE) with uncertainty estimation for CVD classification from static tabular clinical records represented as synthetic noise-augmented pseudo-sequences. The two datasets used in this study are static tabular datasets rather than real longitudinal clinical time-series. Therefore, the constructed pseudo-sequence dimension is used for denoising latent representation learning under simulated measurement perturbation and missingness, not for modeling observed clinical temporal dependencies, patient trajectories, disease progression, or treatment dynamics. The model integrates Gated Recurrent Unit (GRU)-based encoding, variational latent sampling, and Monte Carlo (MC) dropout to learn robust latent representations and quantify predictive uncertainty. We evaluate the model on two publicly available datasets: the Heart Failure Prediction dataset (918 samples) and the Cardiovascular Disease dataset (70,000 samples). The model achieves an accuracy of 95.8% and F1-score of 95.7% on the heart failure dataset, and an accuracy of 96.1% with F1-score of 96.0% on the larger cardiovascular dataset, outperforming traditional classifiers, calibrated tabular baselines, and deep learning baselines including regularized logistic regression, calibrated XGBoost, calibrated LightGBM, calibrated CatBoost, Long Short-Term Memory (LSTM), and GRU-Attention. The proposed VRAE model also demonstrates robustness under synthetic noise and provides improved calibration, as indicated by the lowest Brier scores (0.061 and 0.059) across both datasets. Additional calibration, selective prediction, and threshold-based utility analyses support the reliability of the benchmark results. These findings support uncertainty-aware representation learning for benchmark-level static tabular CVD classification, while independent validation on real-world longitudinal electronic health record cohorts is required before claims about prospective risk prediction, early intervention, clinical time-series prediction, or clinical deployment can be made.

BACKGROUND: This exploratory study aimed to describe characteristics associated with pediatric drowning and to examine the socioeconomic context, rather than to establish socioeconomic effects, by conducting a retrospective analysis at the sole tertiary facility with a pediatric intensive care unit in Okinawa Prefecture, Japan. METHODS: Information from electronic medical records was collated for 75 drowning-related hospitalizations involving individuals aged less than 20 years at the Okinawa Prefectural Nanbu Medical Center and Children's Medical Center from April 1, 2006, to May 31, 2021. Data on patient gender, drowning or hospitalization duration, drowning timing and settings, pre-existing medical conditions, and zip code were extracted from electronic medical records. RESULTS: Among the 75 hospitalized patients, 64 were discharged without any morbidity, whereas 11 either perished or sustained severe morbidity. The submersion time (2.9 min, standard deviation [SD]: 4.6, in the no morbidity group vs. 44.1 min, SD: 87.0 in the severe group) and length of stay (4.1 days, SD: 3.7 vs. 46.4 days, SD: 64.9, respectively) were markedly extended in the severe group. Additionally, in patients under four years of age, drownings frequently occurred in bathrooms (p = 0.008), with incidents predominantly taking place between 17:00 and 23:00 (p = 0.021). Among hospitalized pediatric drowning patients, supervision was associated with lower odds of severe morbidity (odds ratio 0.17 (95% confidence interval 0.03-0.81)). This association persisted after adjustment for potential confounders such as the Area Deprivation Index and time of day. The interaction between supervision and the Area Deprivation Index was of borderline statistical significance (p = 0.050) and is considered hypothesis-generating. CONCLUSIONS: Within this cohort of hospitalized pediatric drowning patients, the presence of supervision was associated with less severe outcomes. These exploratory findings highlight the potential value of preventive strategies tailored to regional attributes, but do not establish socioeconomic or causal effects.

BackgroundComputed tomography-derived body composition parameters, including sarcopenia and adipose tissue distribution, have been proposed as prognostic markers in surgical patients; however, their role in AMI remains unclear. This study aimed to evaluate the association of sarcopenia, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) with short-term outcomes in surgically treated AMI.MethodsThis retrospective cohort study included consecutive adult patients who underwent surgery for AMI between 2015 and 2025 at a tertiary referral center. Preoperative CT scans were used to assess skeletal muscle index (SMI), VAT, and SAT at the third lumbar vertebra level. Sarcopenia was defined using established CT-based SMI thresholds. Visceral adipose tissue and SAT adiposity were defined as areas ≥100 cm2. The primary outcome was 30-day mortality, and the secondary outcome was length of hospital stay (LOS).ResultsSarcopenia was present in 76.7% of patients. The 30-day mortality rate was 54.8%. Sarcopenia was not associated with 30-day mortality or LOS (P > 0.05). Similarly, neither VAT nor SAT adiposity was associated with mortality or LOS. Patients who died within 30 days were significantly older (P = 0.004) and had significantly lower serum albumin levels (P = 0.008). Length of hospital stay was significantly shorter in non-survivors (P < 0.001).DiscussionAlthough sarcopenia and abnormal adipose tissue distribution were highly prevalent, CT-derived morphometric parameters did not independently discriminate short-term outcomes in surgically treated AMI. These findings suggest that in fulminant operative AMI, acute ischemic burden, and systemic physiologic deterioration may outweigh the prognostic contribution of baseline body composition metrics.

BackgroundAccess to surgical care in the United States varies widely across geographic regions, producing measurable differences in diagnosis, treatment timelines, and outcomes. This review examines whether distance from a functioning operating room acts as an independent clinical risk factor rather than a logistical inconvenience, and what structural reforms follow if it does.MethodsWe conducted a narrative review of the peer-reviewed literature on distance-to-care, rural surgical access, surgical workforce distribution, and surgical outcomes. We searched PubMed and MEDLINE for English-language studies published between January 2008 and January 2026, giving priority to national analyses, population-based cohorts, and recent workforce projections relevant to rural surgical care in the United States.ResultsGreater distance to surgical care is associated with more advanced stage at presentation, greater operative complexity, more frequent interhospital transfer, higher postoperative morbidity, and higher mortality across emergency, elective, adult, and pediatric surgical populations. These associations persist after adjustment for socioeconomic and clinical variables. Geographic risk is amplified by the loss of local surgical capacity, an aging and maldistributed surgical workforce, constrained anesthesia coverage, and financing models that tie revenue to volume.ConclusionsDistance-to-care is a quantifiable clinical determinant of surgical prognosis, not merely a background disparity. Stable financing for surgical readiness, rural-embedded workforce training, and coordinated regional networks are required to ensure that place of residence no longer dictates the probability of surviving a surgical illness.

PURPOSE: To compare treatment outcomes of tongue base-targeting interventions-transoral robotic surgery (TORS), plasma ablation tongue base reduction (PATBR), implantable upper airway stimulation (UAS)-and continuous positive airway pressure (CPAP) in moderate-to-severe obstructive sleep apnea (OSA) patients. METHODS: The PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases were systematically searched through January 2026. A network meta-analysis was conducted to compare tongue-directed surgical procedures (TORS and PATBR), UAS, and CPAP. Outcomes included changes in the apnea-hypopnea index (AHI), Epworth Sleepiness Scale (ESS), lowest oxygen saturation, postoperative hospital stay, success rate (postoperative AHI < 20 with > 50% reduction), and cure rate (postoperative AHI < 5). RESULTS: Ten studies comprising 758 patients were included. UAS demonstrated significantly greater AHI reduction than TORS (standardized mean difference [SMD] = 1.36 [0.27-2.46]) and significantly improved lowest oxygen saturation (SMD = 1.46 [0.30-2.62]). CPAP showed greater, though not statistically significant, AHI improvement compared with TORS (SMD = 1.17 [- 0.32-2.66]). ESS improvement did not differ significantly among treatments. Both PATBR (SMD = - 1.30 [- 1.80--0.79]) and UAS (SMD = - 5.49 [- 6.65--4.33]) were associated with significantly shorter hospital stays than TORS. Success rates were higher with CPAP (odds ratio [OR] = 3.73 [1.38-10.13]) and UAS (OR = 5.58 [1.97-15.84]) compared to TORS, whereas cure rates were significantly higher with UAS (OR = 12.13 [1.98-74.50]). Ranking analysis indicated overall superiority of UAS across objective outcomes. CONCLUSIONS: UAS provides superior objective outcomes with shorter hospitalization and comparable subjective improvement, supporting its role as an effective treatment option for moderate-to-severe OSA.

BACKGROUND: Lightweight breast implants (B-Lite) integrate air-filled microspheres into silicone gel to reduce implant weight by up to 30% while maintaining volume and mechanical properties. Long-term prospective data in primary augmentation remain limited. OBJECTIVES: To evaluate clinical performance, safety, satisfaction, and quality of life (QoL) outcomes following primary augmentation with B-Lite implants. METHODS: This multicenter, prospective, single-arm manufacturer-sponsored postmarketing clinical follow-up (PMCF) study enrolled genetically female patients (18-60 years) undergoing bilateral primary breast augmentation. Implants (round or anatomical; POLYsmoooth, POLYtxt, MESMO, or Microthane; 200-755 cc) were placed through inframammary incisions using a standardized technique. The primary endpoint was ≥1 bra-cup increase at 12 months; secondary endpoints included QoL (Body Esteem, Rosenberg, shortened Tennessee, RAND SF-36), satisfaction, and adverse events (AEs) such as capsular contracture (Baker III-IV), rupture, breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), and reoperation. RESULTS: In all, 101 patients (mean age 32.7 ± 8.0 years; BMI 20.9 ± 1.8) underwent augmentation. At 12 months, ≥1-cup increase occurred in 92% (95% CI, 84%-97%). No Baker III/IV contracture, rupture, or BIA-ALCL occurred. The most frequent AE was transient sensory change (8.9%); others were infrequent and mainly procedure related. Kaplan-Meier reoperation risk was 6.9% at 1 year and 9.9% at 5 years. Patient satisfaction averaged 98.6% with 0% regret; surgeons were satisfied or very satisfied at 97% to 100%. QoL showed durable gains in Body Esteem-sexual attractiveness and Rosenberg; SF-36 composites remained stable. CONCLUSIONS: Lightweight B-Lite implants showed high effectiveness, very high satisfaction, and a favorable safety profile through 3 to 5 years.

OBJECTIVES: This paper aims to design an explainable machine learning model capable of predicting postoperative quality of life in elderly NSCLC patients by integrating CT derived body composition metrics with standard clinical indicators. METHODS: A total of 200 elderly NSCLC patients undergoing lobectomy were retrospectively analyzed and divided into High QoL (n=124) and Low QoL (n=76) groups based on 6-month FACT-L scores. The cohort was split into training (n=140) and validation (n=60) sets. CT derived features (PMA, SMI, muscle attenuation, LAMA), clinical variables, and functional indicators (including 6 min walk distance [6MWD] decline) were collected. Multivariate regression identified independent predictors. Machine learning models (Logistic regression, Random Forest, and XGBoost) were developed and evaluated using ROC curves. SHAP analysis assessed model interpretability. RESULTS: Low QoL patients showed lower PMA, SMI, and muscle attenuation, but higher LAMA and greater 6MWD decline (all p<0.001). Multivariate analysis identified 6MWD decline, PMA, and muscle attenuation as independent predictors (all p<0.001). XGBoost achieved the best performance (AUC: 0.892 training, 0.854 validation). SHAP analysis highlighted 6MWD decline as the most influential factor. CONCLUSIONS: Multimodal integration of CT body composition and functional indicators accurately predicts postoperative QoL, supporting personalized perioperative care.

BackgroundLow rectal tumors present significant technical challenges due to confined pelvic anatomy and limited maneuverability. Robotic surgery offers improved visualization and instrument articulation, which may mitigate these challenges. Studies have shown comparable results between robotic, laparoscopic, or open surgery for low rectal tumors; however, the impact of tumor height on outcomes within robotic colorectal surgery alone remains unclear.MethodsA retrospective cohort study was conducted on patients undergoing robotic rectal resection at a single institution. Tumors were categorized by distance from the anal verge into low/medium high groups. Outcomes included oncologic measures (distal margin, radial margin positivity, and lymph node yield >12), intraoperative variables (diversion, port number, operative time, and estimated blood loss), and postoperative outcomes (anastomotic leak, 30-day readmission, and length of stay). Multivariable models adjusted for age, BMI, comorbidity burden, and whether patients received neoadjuvant therapy.ResultsTumor height was not associated with differences in radial margin positivity (P = 0.809) or lymph node yield ≥ 12 (P = 0.652). High tumors were associated with a greater distal margin (P = 0.019) and shorter operative time (P = 0.047). Other intraoperative and postoperative outcomes were comparable between groups. Length of stay trended shorter in high tumors but did not reach statistical significance (P = 0.056).DiscussionRobotic rectal cancer resection achieves equivalent oncologic and perioperative outcomes across tumor heights, despite the increased technical complexity of lower rectal tumors, supporting its use in challenging pelvic surgery. In our cohort, tumor distance predicts operative demands without compromising outcomes or oncological adequacy.

BACKGROUND: The aim of the study was to evaluate the spectrum and the antimicrobial susceptibility of microorganisms causing bloodstream infections (BSIs) in a cohort of patients of a pediatric cancer unit. In addition, we evaluated the effectiveness of preventive antimicrobial lock therapy with taurolidine-citrate solution in reducing BSI rates. METHODS: We prospectively assessed demographic, clinical and microbiological data of BSIs during a 5-year period from January 2019 to December 2023. Preventive lock treatment with instillation of taurolidine-citrate solution into the central venous catheter (CVC) was performed from January 2019 to April 2022, interrupted from May to December 2022 and, after a suspected increase in BSI episodes, reintroduced from January 2023. RESULTS: In 45 patients, a total of 57 BSI episodes were recorded and 60 microorganisms were cultured. The most frequently isolated bacteria belonged to Staphylococcus spp. (n = 20, 33.3%) and Enterobacterales (n = 17, 28.3%). Regarding the antimicrobial susceptibility, all Gram-positive bacteria were susceptible to vancomycin. Among the Gram-negative bacteria, only 4 isolates (17.4%) showed a resistance against piperacillin/tazobactam and only 1 isolate a resistance against meropenem (4.3%). Incidence of BSIs was highest from May to December 2022 (19.6 per 100 patient months; 95% confidence intervals: 11.0-32.4 per 100 patient months) when CVCs were locked with saline instead of taurolidine-citrate solution. CONCLUSIONS: In this study, Staphylococcus spp. and Enterobacterales were the most frequently isolated microorganisms. The lock of CVCs with taurolidine apparently contributed to the prevention of BSIs in the above-mentioned patients.

In a case of a patient with postoperative septic arthritis and hardware-associated osteomyelitis due to methicillin-susceptible Staphylococcus aureus that is susceptible to multiple oral agents, the clinician must navigate not only a treatment decision between oral and intravenous antibiotics but also the ethical tension between evidence-based practice and the patient's social instability. We examined 3 interrelated ethical conflicts: balancing clinician-patient relationship with organizational priorities, weighing the benefits and harms of competing treatment decisions, and considering how patient vulnerability may shape professional duties.

Acute cholecystitis affects approximately 200,000 individuals annually in the United States and may result in significant morbidity if not appropriately managed. The Infectious Diseases Society of America (IDSA) recommends cefazolin, ceftriaxone, or cefuroxime as first-line therapy for mild-to-moderate community-acquired biliary infections; however, adherence to these guidelines remains variable. Within our institution's Emergency General Surgery process improvement program, antibiotic stewardship in acute biliary disease was identified as an opportunity for quality optimization. We performed a retrospective review of the EGS Registry at our military treatment facility from 2017 to 2021. Adult patients with mild-to-moderate acute cholecystitis were included. A total of 143 patients met the inclusion criteria; 62% were female, with a mean age of 52 ± 18 years. Guideline-recommended antibiotics were administered to 45% of patients. Adherence to IDSA guideline-recommended antibiotic therapy for mild-to-moderate acute cholecystitis was suboptimal at our institution, highlighting the need for standardized protocols and ongoing provider education to improve antibiotic stewardship.

BACKGROUND: Large left atrial volume (LAV) is a strong predictor of advanced left atrial substrate and is associated with less successful outcomes following pulmonary vein isolation (PVI) alone. Prespecified variables of the aMAZE trial were evaluated to access for the impact of LAV and left atrial appendage ligation on atrial fibrillation (AF) outcomes. METHODS: The aMAZE trial (REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02513797) was a multicenter, randomized-controlled study evaluating the effects of LAV on freedom from atrial arrhythmias (AA) following PVI-only compared with LARIAT and PVI (LARIAT+PVI). In total, 610 drug-refractory patients with nonparoxysmal AF were randomized 2:1 to LARIAT versus PVI alone. Freedom from AA was assessed 12 months postprocedure. LAV was independently assessed by a core laboratory from cardiac computed tomography performed before ablation. RESULTS: There were 404 patients in the LARIAT+PVI group and 206 in the PVI-only group. Logistic regression performed within each subgroup for primary effectiveness with LAV demonstrated that the recurrence of AA after PVI was directly related to increasing LAV. Freedom from recurrence of AA in the LARIAT+PVI arm was independent and preserved irrespective of LAV. Similar results were seen with LAV index. A tercile analysis of early persistent AF (perAF) patients (AF >7 days and <6 months) and LARIAT+PVI in the highest (>148 cm3) LAV tercile showed statistically significant freedom from AA compared with PVI-only (69% versus 49%; P=0.02). Significant differences (P<0.04) between groups in the early perAF cohort began at an LAV of 130 cm3 and an LAV index of 65 cm3/m2. CONCLUSIONS: The correlation of LAV with PVI effectiveness in this study demonstrates that AA recurrence after PVI alone is directly related to increasing LAV. Freedom from AA after left atrial appendage ligation in addition to PVI is independent of increasing LAV, and left atrial appendage ligation may therefore provide an adjunctive benefit in patients with nonparoxysmal AF and enlarged LAV.

BACKGROUND: Screening for atrial fibrillation (AF) on the basis of AF risk may be more effective. We aimed to develop, externally validate, and prospectively test a machine learning prediction model using electronic health records (EHRs) to guide AF screening. METHODS: We developed and validated a random forest prediction model for new AF within 6 months, using age, sex, and 10 comorbidities (Future Innovations in Novel Detection of Atrial Fibrillation [FIND-AF] 2.0) in EHRs in the United Kingdom (n=2 081 139), Japan (n=7 795 244), Israel (n=2 166 795), Canada (n=627 919), and China (n=149 145). We conducted a prospective study where participants ≥30 years old without AF and with a CHA2DS2-VASc score ≥2 in men and ≥3 in women, stratified by FIND-AF 2.0 into high and low risk, undertook 4 ECG recordings per day for 3 weeks using a handheld ECG recorder, with a primary outcome of newly diagnosed AF. We estimated stroke risk associated with nonanticoagulated AF in patients with high FIND-AF 2.0 risk in the FinACAF (Finnish Anticoagulation in Atrial Fibrillation) registry of patients with AF (n=229 565). RESULTS: FIND-AF 2.0 was applicable to all EHRs and showed good to excellent prediction performance (United Kingdom: area under the receiver operating characteristic curve [AUROC], 0.819 [95% CI, 0.809-0.829]; Israel: AUROC, 0.835 [95% CI, 0.828-0.842]; Japan: AUROC, 0.751 [95% CI, 0.745-0.757]; Canada: AUROC, 0.747 [95% CI, 0.741-0.753]; China: AUROC, 0.753 [95% CI, 0.725-0.771]), with AUROC>0.7 in men and women in all cohorts, and improved performance compared with CHA2DS2-VASc and C2HEST. Of 1923 participants from 15 sites in the prospective study (mean age, 70.2 [SD 9.4] years), with a mean of 74.8 (SD, 19.4) ECG recordings, AF was diagnosed in 5 of 902 (0.6%) with low FIND-AF 2.0 risk and 46 of 1021 (4.5%) with high FIND-AF 2.0 risk (odds ratio, 8.46 [95% CI, 3.35-21.40], P<0.001). Median AF burden among high FIND-AF 2.0 risk-detected cases was 33.4% (interquartile range, 5.1%-91.6%), and 96.1% initiated oral anticoagulants. In the FinACAF registry, the rate of ischemic stroke for patients with high FIND-AF 2.0 risk, AF, and no anticoagulants was 6.0 events per 100 patient-years. CONCLUSIONS: The EHR-based machine learning model, FIND-AF 2.0, identifies a high-risk subpopulation for AF diagnosis among patients at elevated risk of stroke and could enable

BACKGROUND: Impella is increasingly used as mechanical circulatory support (MCS) during high-risk percutaneous coronary interventions (HR-PCI). Registry-based data provide insights into the efficacy and safety of Impella-assisted HR-PCI. AIMS: We aimed to evaluate 1-year outcomes of Impella-assisted HR-PCI compared to HR-PCI without MCS. METHODS: One hundred and thirty-eight patients undergoing Impella-assisted PCI, included in the IMPELLA-PL registry, were propensity score-matched with controls from the retrospective CardioSilesia registry who underwent HR-PCI without MCS. Study endpoints included 1-year post-discharge all-cause mortality, myocardial infarction (MI), stroke, rehospitalization for heart failure (HF), and repeat coronary revascularization. RESULTS: Clinical and angiographic characteristics were comparable in both groups, with higher rates of dyslipidemia (78.3% vs. 37.7%, p < 0.001), chronic kidney disease (39.9% vs. 16.7%, p < 0.001), and peripheral artery disease (34.1% vs. 8.0%, p < 0.001) in the IMPELLA-PL cohort. Intravascular ultrasound was more frequently used in the Impella-supported patients (44.2% vs. 25.4%, p = 0.002), while staged revascularization was more common among controls (30.4% vs. 15.9%, p = 0.007). At 1 year, rates of post-discharge all-cause mortality, stroke, and repeat coronary revascularization were similar in both groups. MI was less frequent in the IMPELLA-PL cohort (1.4% vs. 10.9%, p = 0.003), alongside a trend toward lower incidence of rehospitalizations for HF (9.4% vs. 18.1%, p = 0.055). CONCLUSIONS: Despite an unfavorable cardiovascular risk profile, patients who underwent Impella-assisted HR-PCI had similar 1-year post-discharge survival, with a lower rate of MI, compared to propensity score-matched controls who underwent HR-PCI without MCS. Impella may improve HR-PCI outcomes in selected patients, but further randomized controlled trials are required to confirm this finding.

BACKGROUND: Supersaturated oxygen (SSO2) is a novel adjunctive treatment aims to reduce reperfusion injury after primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI). We conducted this study to evaluate the efficacy and safety of SSO2 therapy in patients with STEMI. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we systematically searched Cochrane Central, Embase, PubMed, Scopus, and Web of Science for studies comparing SSO2 therapy post-PCI with PCI alone in adults with STEMI. Primary efficacy outcomes were infarct size and all-cause death. A random-effects model was used for analysis. RESULTS: Six unique studies that enrolled 1591 patients were included [518 (32.5%) of whom received SSO2]. SSO2 therapy was associated with a reduction in infarct size compared with the control group [mean difference = -4.7% of left ventricular mass, 95% confidence interval (CI): -8.3 to -1.1%; P = 0.01], with the greatest benefit observed in patients reperfused within 6 h of symptom onset (mean difference = -6.0% of left ventricular mass, 95% CI: -8.9 to -3.0%). SSO2 therapy was also associated with reduced left ventricular end-systolic volume (mean difference = -19.9 ml, 95% CI: -33.7 to -6.2). The between-group difference in all-cause mortality was NS (P = 0.58); however, an association between SSO2 use and reduced all-cause death was present in the two studies with long-term (1-year) follow-up (risk ratio = 0.10, 95% CI: 0.01-0.77). No safety concerns were identified. CONCLUSION: SSO2 administration in patients with STEMI after primary PCI was safe and was associated with reduced infarct size, particularly when administered within 6 h of symptom onset. This myocardial salvage was associated with improvement in left ventricular function Further randomized trials are needed to definitively establish the impact of SSO2 on mortality and heart failure.

BACKGROUND: Recent meta-analyses of randomized controlled trials have raised concerns that treatment with omega-3 fatty acids may increase the risk of atrial fibrillation (AF). However, these meta-analyses included at most 8 trials. The aim of this current meta-analysis was to expand the search by including other eligible omega-3 randomized controlled trials with AF incidence data, incorporating both published and unpublished data. METHODS: Eligible studies were randomized controlled trials investigating daily doses of ≥500 mg/d of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Additional inclusion criteria included ≥12 months of treatment with EPA/DHA, participants ≥50 years of age, and, where possible, the absence of known AF/atrial flutter at baseline. The primary outcome was the occurrence of new-onset AF. Our primary hypothesis was that risk for AF would simultaneously depend on both omega-3 dose (above or below 1500 mg/d) and background cardiovascular disease risk status, and that their combined impact on AF risk would be synergistic. RESULTS: A total of 35 randomized controlled trials (37 data sets; n=114 592) were included in this meta-analysis. Only studies including patients at high-risk for cardiovascular disease who were treated with high-doses of EPA/DHA (>1500 mg/d) showed a statistically significant increase in AF risk with a pooled odds ratio (OR) of 1.43 (95% CI, 1.14-1.79) and an absolute risk difference of 0.8% (0.40%-1.1%). None of the other 3 groups showed statistically significant levels of AF risk (odds ratios, 1.07 [high risk-low dose], 1.06 [low risk-low dose], and 1.03 [low risk-high dose]). CONCLUSIONS: This meta-analysis suggests that high-dose EPA/DHA treatment is associated with an increased risk of AF in patients at high cardiovascular disease risk, whereas low-dose EPA/DHA does not appear to increase AF risk, even in high-risk populations. Further prospective studies are needed to evaluate any potential increased risk of higher doses balanced against potential benefits.

Although hospital finance can often seem like the purview of the C-Suite, it is essential that hospitalist leaders and hospitalists understand the financial forces that impact hiring, expansion, and innovation. A strong understanding of division finances allows leaders to advocate for the patients for whom they care as well as their teams. Identifying budgetary sources (both actual and potential) will establish the key drivers of financial success. Leaders must then be able to decode and use budgetary language when reviewing key financial documents with their administrative team. Then they can make key financial arguments for their program. Here we expand on these concepts so that hospitalist leaders, along with a strong administrative partner, can succeed, and every hospitalist can be a part of that success.

Psychiatric illnesses and intellectual disabilities commonly occur in the criminal justice system and may impair an individual's ability to participate effectively in legal proceedings. Fitness to stand trial (FST) is an important safeguard for ensuring fair trial processes. This retrospective chart review examined the demographic, clinical, and legal profiles of 159 court-referred individuals assessed for FST at a major tertiary forensic psychiatry centre in New Delhi (India) between January 2017 and December 2022. Data on sociodemographic variables, ICD-10 diagnoses, current mental status, alleged offences, and FST outcomes were analysed using chi-square/Fisher's exact tests and multivariate logistic regression. The sample was predominantly male (81.1%) with a mean age of 37.9 years (SD 14.2). Psychotic disorders were the most frequent diagnosis (35.2%), followed by bipolar affective disorder and intellectual disability. Violent offences constituted 62.9% of alleged crimes. Overall, 54.7% were found fit to stand trial. Active psychiatric symptoms (adjusted OR 47.2, 95% CI 6.1-365.3) and organic mental disorder or intellectual disability (adjusted OR 22.5, 95% CI 4.8-105.6) independently predicted unfitness. Active psychopathology and cognitive impairment were the strongest determinants of unfitness, highlighting the need for structured assessment tools and restoration programmes under the Bharatiya Nagarik Suraksha Sanhita 2023.

ObjectiveTo examine the utility and limitations of remote supervision in a rural psychiatry training program through narrative review and dual reflective accounts.ConclusionsConsistent, well-structured remote supervision can nurture clinical expertise, ensure good clinical governance, improve patient safety, and promote graded trainee autonomy. Limitations can include reduced opportunity for direct observation, challenges processing complex relational dynamics, and heightened trainee isolation. Clear pedagogical structures, reliable technology, and a strong local multidisciplinary team are key to remote supervision providing effective containment and supporting progressive independence; and a hybrid model incorporating regular onsite and in-person contact deepens professional development and relational quality.

Psychiatry on call occupies a distinct and formative space within mental health services, shaped by moments of uncertainty, responsibility, and relational decision-making. In Ireland, non-consultant hospital doctors continue to deliver the majority of out-of-hours emergency psychiatric care, often as the sole on-site psychiatric clinician, working across multiple settings and managing high levels of clinical and organisational risk. This paper situates contemporary psychiatry on call within its wider clinical, societal, and service context, drawing on the College of Psychiatrists of Ireland's 2025 position paper and emerging evidence on emergency mental health care. We argue that emergency psychiatry differs from other acute specialties, being characterised by distress rather than disease, uncertainty rather than diagnosis, and time-intensive relational work rather than protocol-driven intervention. Rising demand reflects broader systemic pressures, including unmet social need, reduced inpatient capacity, uneven crisis alternatives, and increasing regulatory burden. We examine the service-user experience of out-of-hours care, highlighting issues of environment, equity, trust, and safety, particularly for marginalised groups. While high-quality supervision and training remain essential, we contend that sustainable improvement requires system-level reform, including strengthened multidisciplinary crisis responses, clearer role delineation, and coordinated investment in and also beyond mental health services. Attending to psychiatry on call offers a critical lens through which to understand and improve emergency mental health care for both clinicians and service users.

BACKGROUND: Behavioral alcohol use disorder therapy (bAUDT) is increasingly used to improve eligibility and outcomes for liver transplant (LT) among patients with alcohol-associated liver disease (ALD), especially as more centers consider LT for patients with <6 months of sobriety. This study evaluates the impacts of bAUDT in the peri-LT setting in a multicenter cohort of patients with early sobriety. METHODS: RESOLVE-ALD is a multicenter retrospective cohort study including adults with ALD and <6 months of abstinence undergoing liver transplant evaluation (LTE) between 2018-2021 at six United States LT centers. Multivariable logistic regression identified predictors of bAUDT participation during LTE and assessed its impact on LT waitlisting. Competing risk analyses examined how bAUDT affected risk of return to alcohol use pre- and post-LT. RESULTS: Among 545 patients analyzed (median sobriety time 79 days; 52.8% inpatient evaluations), 22.4% participated in bAUDT during LTE and 43% received LT. Prior alcohol-related illness (aOR=1.93, p=0.03) and heavier daily drinking (aOR=1.90, p=0.04) were associated with increased adjusted odds of bAUDT during LTE, while older age (aOR=0.41, p=0.006), underinsurance (aOR=0.42, p=0.01), and hospitalization during LTE (aOR=0.42, p=0.02) were associated with reduced adjusted odds. bAUDT participation during LTE significantly increased adjusted odds of LT waitlisting (aOR=3.40, p=0.006), but did not predict return to use pre- or post-LT. CONCLUSION: bAUDT is more common among patients with risk factors for return to use and with the medical and financial stability to participate in therapy. Although associated with increased waitlisting adjusted odds, bAUDT does not significantly predict return to alcohol use pre- or post-LT. Future research should explore optimal methods of integrating bAUDT into the LTE process to improve access and minimize barriers to LT.

Cardiovascular diseases, particularly stroke, are leading causes of dementia. Several common cardiac interventions such as coronary artery bypass grafting and transcatheter aortic valve implantation are also associated with cognitive decline. However, cognitive outcomes continue to be poorly collected in clinical trials of cardiovascular diseases. In this article, we review the limitations of current approaches to cognitive assessment in cardiovascular disease studies. When assessed, there is wide variation in cognitive tasks used, and tasks have limited population-specific validation, are subject to floor and ceiling effects, and may suffer from sociocultural and linguistic biases. Many tasks are not available in multilingual formats and often rely on face-to-face testing with trained coordinators. All conventional cognitive outcomes in cardiovascular trials are associated with substantial incompletion, especially among older and more impaired individuals, the very people most important to capture. This nonrandom missingness generates survivor and attrition biases, an unacceptable situation for any trial outcome. Last, the meaning of measured cognitive outcomes is often unclear for patients, caregivers, clinicians, and regulators. To help address these limitations, we propose a new framework, major adverse cognitive events (MACE-Cog), to better capture cognitive outcomes in stroke and other cardiovascular populations. As an inclusive construct reflecting the multidimensional nature of cognitive decline, major adverse cognitive events do not rely solely on performance on cognitive testing but also consider inability to complete cognitive testing due to cognitive-behavioral factors, reported symptoms of cognitive decline, impairment in activities of daily living as a result of cognitive impairment, new clinical diagnoses of dementia, and care home admission. We hope that the proposed composite outcome and multiple use cases presented spark progress in cardiovascular research toward more inclusive approaches to the study of cognitive outcomes that move beyond the confines of cognitive tests alone.

OBJECTIVE: GNAO1-related disorder is a severe childhood-onset hyperkinetic movement disorder punctuated by life-threatening dyskinetic crises. Small series suggest benefit from bilateral globus pallidus internus deep brain stimulation (GPi-DBS), but optimal timing, patient selection, long-term outcomes, and genotype-specific response remain unclear. We define the clinical impact of GPi-DBS in the largest cohort assembled to date. METHODS: Retrospective multicenter cohort study conducted through the DBSMatchMaker platform, including children and young adults with genetically confirmed GNAO1-related disorder treated with bilateral GPi-DBS across 17 centers. The primary outcome was change in dyskinetic crisis burden; secondary outcomes included BFMDRS, Clinical Global Impression (CGI), functional classifications, medication burden, and complications. RESULTS: Forty-six patients underwent implantation at a mean age of 10.4 ± 4.8 years with mean follow-up of 4.5 ± 3.7 years (longest = 17 years). Over half (52.2%) were implanted emergently during dyskinetic status. Dyskinetic crises were reduced in 38 of 40 patients (95%) and intensive care unit (ICU) admissions in 86.1%. The Burke Fahn Marsden Dystonia Rating Scale (BFMDRS) motor scores improved by 27.5% (p < 0.001, Cohen's d = 1.12); CGI was improved in 93.5%, with greater benefit for chorea than dystonia. Pain, sleep, and medication burden improved; functional classification was largely unchanged. Complications occurred in 19.6%, predominantly in emergent cases. INTERPRETATION: Bilateral GPi-DBS was associated with sustained prevention of dyskinetic crises and reduction of overall disease burden in GNAO1-related disorder, with limited impact on functional classification. These findings support earlier elective neuromodulation before recurrent crises drive cumulative morbidity and identify GPi-DBS as a crisis-preventive, symptom-modifying intervention rather than a restorative one. ANN NEUROL 2026.

Hospitalised adults with advanced HIV disease in sub-Saharan Africa experience high mortality, with tuberculosis, often disseminated and undiagnosed, being a leading cause. Despite this, initiation of antituberculous therapy is frequently delayed pending diagnostic confirmation, which may be unavailable in this population. Evidence from recent trials and cohort studies suggests that even short delays in antituberculous therapy are associated with substantial increases in mortality, whereas empiric therapy might improve survival in people at high risk. Applying the therapeutic threshold framework, the high pre-test probability of tuberculosis in severely ill inpatients with advanced HIV disease often exceeds the threshold at which treatment benefits outweigh risks, even in the absence of confirmatory testing. Although concerns regarding toxicity, drug interactions, and overtreatment are valid, short-term empiric antituberculous therapy appears safe and these risks might be outweighed by the consequences of untreated disease. We argue for a paradigm shift towards earlier empiric antituberculous therapy, with parallel diagnostic evaluation and structured reassessment in selected patients, and for adequately powered randomised controlled trials of empiric therapy powered for mortality.

In this reflective essay, a primary care physician describes practicing within the Department of Veterans Affairs during a period of workforce reductions, policy shifts, and changing institutional priorities. Drawing on frontline experience, the essay illustrates how these changes shape care for veterans with complex medical, psychological, and social needs. The narrative traces the cumulative effects of staffing shortages, administrative burden, and diminished support on both patients and clinicians. It culminates in the death by suicide of a veteran, prompting reflection on missed opportunities, system constraints, and the limits of individual clinical effort within strained conditions. The essay explores themes of moral injury, professional responsibility, and the tension between bureaucratic demands and patient-centered care. It argues that sustaining effective care for vulnerable veterans requires institutional trust, adequate staffing, and alignment between policy decisions and the realities of clinical practice.

BACKGROUND AND OBJECTIVES: United States labeling of the newest robotic surgical platform contraindicates the use of force feedback instruments during hysterectomy and myomectomy because of a theoretical, clinically unexamined bleeding risk. We describe real-world outcomes and quantified intraoperative force during continuous force feedback use throughout these procedures, including closure, in a setting where this restriction does not apply. METHODS: This single-surgeon observational cohort comprised 93 consecutive patients undergoing robotic hysterectomy or myomectomy between December 2024 and April 2026, classified into 3 groups: force feedback active throughout (43), the same instruments with the feature disabled (13), and conventional instruments (37). The primary outcome was a composite of vaginal cuff dehiscence, uterine wound disruption, or readmission or reintervention for bleeding within 30 days. RESULTS: Baseline characteristics were comparable across groups. Mean intraoperative force in the active group was 2.1 newtons for hysterectomy and 2.2 newtons for myomectomy. The composite event occurred in 1 of 43 active-group patients (a readmission for bleeding) and in no patient in the other groups; no cuff dehiscence or uterine wound disruption occurred in any group. After adjustment for procedure, higher mean force was associated with shorter operative time. CONCLUSION: Continuous force feedback through the closure phases of robotic hysterectomy and myomectomy was not associated with cuff dehiscence or uterine wound disruption, and mean operative force clustered near 2 newtons. These hypothesis-generating findings warrant larger studies before safety equivalence can be inferred.

BACKGROUND: The adoption of pure laparoscopic donor right hepatectomy (PLDRH) has been limited by a perceived steep learning curve, traditionally estimated at 60-70 cases. This study evaluates whether "second-generation" laparoscopic surgeons can achieve proficiency more rapidly in a low-volume transplant center using structured training and standardized techniques. METHODS: We analyzed 29 consecutive, non-selective PLDRH cases performed by a single surgeon. A multimodal CUSUM analysis, incorporating operative time, estimated blood loss, and the Comprehensive Complication Index, was used to define the learning curve, alongside a donor complexity score. Outcomes were compared with a cohort of 21 conventional open donor right hepatectomies. RESULTS: A three-phase learning progression was identified. Competency and proficiency were reached at cases 10 and 20, respectively. Phase 2 (cases 11-20) was characterized by a "second learning curve" as the team encountered more complex anatomical variations within the consecutive cohort. By Phase 3 (cases 21-29), surgical metrics stabilized with zero complications, even as case complexity increased. Compared to CODRH, the PLDRH group achieved similar safety profiles but significantly shorter hospital stays (p < 0.05). CONCLUSIONS: PLDRH can be safely implemented in low-volume centers with an accelerated learning curve. For surgeons with prior advanced laparoscopic expertise, institutional proficiency may be achieved within 20 cases. These findings suggest that standardized "second-generation" approaches may broaden the accessibility of laparoscopic donor surgery without compromising safety.

STUDY OBJECTIVE: To evaluate whether the type of anatomical distortion-spatial or adhesive-determines the relative performance of the energy device in complex total laparoscopic hysterectomy (TLH). DESIGN: Retrospective cohort study. SETTING: Single tertiary referral center. PATIENTS: A total of 167 women who underwent complex TLH between 2018 and 2025 were included. Cases were classified according to intraoperatively confirmed distortion type as spatial (uterine enlargement), adhesive (previous cesarean delivery or endometriosis), or combined. INTERVENTIONS: TLH performed with conventional bipolar electrosurgery (CBP, n = 94) or LigaSure (LG, n = 73). Device selection was based on real-time availability. MEASUREMENTS AND MAIN RESULTS: Primary outcome was operative time. Overall operative time (136 ± 18 vs. 140 ± 17 min, p = 0.761), hemoglobin change, and length of hospital stay were comparable between groups. Subgroup analysis revealed a significant interaction between device type and distortion subgroup (F (1,90) = 18.0, p < 0.001). In the spatial distortion subgroup, LG was associated with shorter operative time (90 ± 23 vs. 110 ± 17 min, p = 0.004). In the adhesive distortion subgroup, CBP outperformed LG (140 ± 23 vs. 155 ± 19 min, p = 0.003). Multivariable regression confirmed that the device-distortion interaction remained significant after adjustment for potential confounders (B = 18.9, p < 0.001). Bladder injury was more frequent in the LG group (8.2% vs. 1.1%, p = 0.031), exclusively in patients with prior cesarean delivery. All conversions to laparotomy occurred in the spatial distortion subgroup, with no significant difference between devices (4.3% vs. 4.1%, p = 0.961). CONCLUSION: Device efficiency in complex TLH is determined by the type of anatomical distortion. LG offers operative advantages when complexity is defined by uterine enlargement, whereas CBP electrosurgery is superior in the presence of adhesive disease. These findings support anatomy-driven device selection in complex TLH.

BACKGROUND: Minimally invasive bunion surgery relies on controlled lateral translation of the first metatarsal capital fragment, but the relationship between translation magnitude and postoperative outcomes remains unclear. PURPOSE: To evaluate the association between percentage lateral translation of the first metatarsal capital fragment and postoperative complications following minimally invasive bunionectomy. Secondary aims included radiographic union, first metatarsal regeneration patterns, and preoperative deformity severity. STUDY DESIGN: Retrospective cohort study. METHODS: Sixty-two consecutive minimally invasive bunionectomy procedures performed in 53 patients were retrospectively reviewed. Mean follow-up was 9.3 ± 7.6 months. Outcomes included hardware-related complications, wound complications, revision surgery, radiographic union, and metatarsal regeneration patterns. Translation was analyzed as a continuous variable and by a threshold of ≥100% versus <100% of metatarsal shaft width. RESULTS: Hardware-related complications occurred in 26% (16/62) of procedures. Translation ≥100% was associated with a higher complication rate than <100% translation (3/5 [60%] vs 13/57 [23%]; OR 4.61, p = 0.080). No statistically significant association was identified between translation percentage and complications across the cohort. Radiographic union occurred in 94% (58/62) of cases and was not influenced by translation magnitude. Increasing translation was not significantly associated with first metatarsal regeneration type nor was preoperative deformity severity associated with complication risk. CONCLUSION: Complete loss of cortical apposition, ≥100% translation, was associated with higher observed hardware-related complication rates, although this finding did not reach statistical significance and was based on a small subgroup (n = 5). These results warrant further investigation in larger studies to define safe limits of capital fragment translation.

BACKGROUND: Direct surgical supply costs are a modifiable component of operating room spending, but it is unclear whether variation reflects reproducible hospital- and surgeon-level practice patterns and whether stewardship opportunity is broadly distributed or concentrated. STUDY DESIGN: Retrospective observational study of 298,723 operative encounters from April 1, 2019, to March 31, 2025, across 15 hospitals in a single integrated health system. Hierarchical mixed-effects linear regression modeled log supply cost per case with random intercepts for hospitals and surgeons nested within hospitals, adjusting for CPT3 procedural family, calendar year, COVID-era indicator, and, in a complete-case subset, operative duration. Modeled excess cost benchmarked adjusted supply costs to internally observed top-quartile performance within each CPT3 family. RESULTS: In the baseline model (n = 298,723), hospital-level factors accounted for 35.4% and surgeon-within-hospital factors for 32.7% of total variance (cumulative intraclass correlation coefficient [ICC], 0.681). After operative time adjustment (n = 150,461), hospital variance was 38.1% and surgeon-within-hospital variance was 26.9% (cumulative ICC, 0.650). Benchmarking corresponded to a 20-25% reduction in mean supply cost per case, with approximately 62% persisting after time adjustment. Fewer than 15% of CPT3 families accounted for more than half of modeled opportunity, and the top 5% of surgeons accounted for 56.1% of modeled excess cost. Higher adjusted supply costs were not consistently associated with 30-day readmission (adjusted odds ratio per 1-SD increase, 1.03; 95% CI 0.97-1.09). CONCLUSIONS: Surgical supply cost variation was reproducible, concentrated, and only partly explained by operative duration. These findings support targeted supply stewardship focused on high-impact procedure families and surgeons.

ObjectiveTo assess the relationship between neighborhood-level social disadvantage, as measured by Area Deprivation Index (ADI) and Childhood Opportunity Index (COI), and postoperative outcomes and follow-up care after primary or secondary cleft lip repair.DesignRetrospective cohort study.SettingSingle academic tertiary care center.Patients, ParticipantsA total of 171 pediatric patients (<18 years of age) with cleft lip with or without cleft palate (CL ± P) who underwent primary or secondary cheiloplasty from 2013 to 2022.InterventionsNeighborhood deprivation was assessed during treatment using two composite measures of relative socioeconomic disadvantage, the ADI and the COI.Main Outcome MeasuresPostoperative outcomes and clinic follow-up adherence.ResultsAmong the 171 total patients, there was only a moderate correlation between patients' ADI and COI quintiles (R2 = 0.552, p < .001). Among all patients, ADI and COI were found to be associated with significant delay in follow-up and public insurance type was found to be associated with increased loss to follow-up. Patients with public insurance undergoing primary and secondary repair were more likely to have postoperative no-show appointments and have younger age at time of procedure. Neither ADI or COI correlated with surgical complications nor hospital readmission within 30 days for primary or secondary repair patients.ConclusionsNeighborhood-level social disadvantage indices were associated with delays in postoperative follow-up but were not associated with short-term surgical complications or readmissions following cleft lip repair. These indices may help identify patients who could benefit from targeted outreach and care coordination to improve follow-up adherence.

OBJECTIVE: > To compare concordance between physicians and coders in their assignment of diagnoses under International Classification of Diseases, 11th Revision (ICD-11). METHODS: A pilot study was conducted at San Juan de Dios Hospital in Curicó, Chile, between March and June 2025, incorporating ICD-11 coding into the clinical services of internal medicine and psychiatry. Eight physicians and two coders were trained in the use of ICD-11, and the domestically developed "Deisy CIE-11" platform was used to validate diagnoses. A total of 457 hospital discharges were analyzed, comparing diagnostic coding performed by physicians, coders, and a national reference expert. RESULTS: For the principal diagnoses, concordance was 96% (439/457) between physicians and coders and 93% (424/457) between physicians and the national reference expert. For secondary diagnoses, concordance exceeded 90% in all fields evaluated. Cohen's kappa coefficient for concordance between physicians and coders was 0.963. The main errors were associated with omissions in postcoordination and incorrect assignment of the external cause code. The national reference expert reviewed 100% of the records for which information was available. CONCLUSIONS: The pilot study demonstrated a high level of diagnostic concordance among physicians, coders, and the national reference expert in the assignment of diagnostic codes to hospital discharges. However, significant gaps were identified in postcoordination, the recording of external causes, and the standardization of review criteria. These findings provide preliminary evidence to inform future strategies for implementing ICD-11 in hospital morbidity coding.

BACKGROUND Drug abuse is a global public health concern with substantial medical, psychological, and social consequences. Drug abuse monitoring (DAM) systems help identify patterns of substance misuse and support regulatory interventions. Current monitoring systems mainly rely on fixed-point reporting from addiction treatment centers, detention facilities, and compulsory detoxification institutions, which can lead to delayed detection and incomplete data coverage. Additionally, there is increasing misuse of prescription medications, over-the-counter drugs, and emerging psychoactive substances in medical settings. Therefore, establishment of a structured DAM approach within medical institutions is important to improve early detection and reporting of drug abuse. MATERIAL AND METHODS A single-center retrospective observational study was conducted at Wuxi Mental Health Centre to monitor patients diagnosed with drug/substance abuse between September 2020 and December 2024. A DAM research group was established to standardize reporting procedures, define staff responsibilities, and implement monitoring protocols linked to the national reporting system. RESULTS In total, 146 patients with drug/substance abuse were monitored: 41 male individuals (28.08%) and 105 female individuals (71.92%). Nineteen drugs or substances across 5 categories were identified. Sedative-hypnotic drugs represented the largest proportion of cases (98.63%). Antipyretic and analgesic drugs containing caffeine were abused in 4.11% of cases; dextromethorphan or Yumei tablets were involved in 3.42% of cases. Nitrous oxide abuse was identified in 2.05% of all monitored cases; affected patients were aged 17 to 25 years. CONCLUSIONS The proposed DAM approach was successfully implemented in a hospital setting and demonstrated feasibility for systematic monitoring of drug abuse in medical institutions.

INTRODUCTION: In South Africa, which has the world's highest prevalence of HIV, intimate partner violence (IPV) and common mental health conditions are barriers to retention in HIV treatment and achieving viral suppression. The Common Elements Treatment Approach (CETA), a cognitive-behavioural-therapy-based intervention designed for lay healthcare worker delivery, is effective in reducing mental and behavioural health problems but has not been trialled for effectiveness in improving HIV outcomes. We conducted a randomized control trial to evaluate the effectiveness of CETA in improving HIV treatment outcomes among women experiencing IPV in South Africa. METHODS: This was a single-blind trial conducted among women living with HIV on antiretroviral therapy (ART) who experienced sexual and/or physical IPV in the last 12 months and had either an unsuppressed viral load or were at risk for poor medication adherence in the past year (e.g. defaulted on treatment, late or missed clinic visit). Women were randomized 1:1 to receive either 8-12 CETA counselling sessions or weekly safety text messages. The primary outcome was viral suppression (≤50 copies/mL) (which requires retention) at 12 months after baseline, which was evaluated using routinely collected medical records. A linear regression model was estimated to calculate risk differences and 95% confidence intervals (CI). RESULTS: Participants were enrolled from 11 November 2021 to 19 July 2023, with 202 women randomized to CETA and 197 randomized to the control arm. Median age was 41.0 years (interquartile range [IQR]: 34.0, 47.0) with a median time on ART of 8.2 years (IQR: 4.3, 12.5). Receiving CETA was associated with a 1-percentage point (95% CI: -0.11, 0.09) decrease in retention and viral suppression compared to the control. When restricted to individuals who completed CETA (N = 144) compared to all controls, we observed a 7-percentage point (95% CI: -0.03, 0.18) increase in retention and viral suppression. CONCLUSIONS: Our estimates suggest overall there was no meaningful difference in retention and viral suppression at 12 months between individuals who received CETA compared to individuals who received the active safety control. Future work should seek to determine if CETA can be effective among those who complete the intervention.

INTRODUCTION: Early rehabilitation guidelines lack a consensus on the optimal early rehabilitation regimen; hence, the impact of rehabilitation timing and dose on stroke recovery outcomes remains unclear. Using Japanese medical claims data within a target trial emulation framework, this study evaluated the safety of early in-hospital rehabilitation after stroke. PATIENTS AND METHODS: This study analyzed patients aged ≥ 18 years who were admitted to an acute hospital for acute stroke and received in-hospital rehabilitation within 2 days after admission, using the Japan Diagnosis Procedure Combination database (2018-2022). Rehabilitation exposures were defined as 6 predefined regimens (20-60 min/day initiated on days 1 or 2) and continued up to day 14. The outcome was the cumulative incidence of composite adverse events within 15 days after admission. A sequential, doubly robust estimator with a longitudinal modified treatment policy was applied, accounting for time-varying exposures and reducing potential time-related biases. RESULTS: Using a target trial emulation framework with doubly robust estimation, the incidence under the reference regimen was 11.2% (95% CI: 9.75%-12.60%). The highest incidence was 26.20% (95% CI: 24.30%-28.20%), corresponding to a risk ratio (RR) of 2.35 (95% CI: 2.03-2.72) compared with the reference. In contrast, several higher-intensity regimens were associated with lower incidences, with the lowest incidence of .49% (95% CI: .28%-.71%), yielding an RR of .04 (95% CI: .03-.07) versus the reference. However, intermediate-dose regimens showed variable associations across scenarios. DISCUSSION AND CONCLUSION: In this emulated trial, higher early rehabilitation doses were generally associated with a lower incidence of in-hospital adverse events. Regimens involving 60 min/day, particularly when initiated on day 1, showed the lowest estimated risk. However, the associations were not strictly linear, as intermediate-dose regimens demonstrated variable results across analyses. These findings suggest a potential benefit of adequately dosed early rehabilitation when clinically appropriate, while highlighting the importance of careful patient selection and monitoring.

BACKGROUND: Peer-supported self-management at discharge from early intervention in psychosis services (EIPS) has received limited attention. The MyPREPED (My Personal Recovery Plan for Early Discharge) trial will evaluate a co-designed, digital and paper-based, peer-delivered recovery and self-management focused intervention, tailored for young people exiting EIPS. AIMS: This protocol describes a hybrid type 2 effectiveness-implementation trial designed to assess MyPREPED's impact, feasibility, real-world implementation and cost-utility. METHOD: This multi-site, mixed-method, two-arm (1:1), parallel-group, randomised controlled trial (MyPREPED versus treatment as usual) trial will be delivered across eight Australian EIPS that deliver ultra-high risk and/or first-episode psychosis streams, using a hybrid type 2 implementation-effectiveness design. Eligible participants are young people aged 16 years and over within 6 months of planned discharge from EIPS. Peer coaches will deliver up to ten sessions of using a self-management plan (modules: discharge, recovery, well-being, relapse prevention, goal-setting, service navigation). Co-primary outcomes include (a) mental health recovery (Recovery Assessment Scale - Domains and Stages; effectiveness outcome) and (b) feasibility (Feasibility of Implementation Measure; implementation outcome). Secondary outcomes assess broader effectiveness domains (mental health quality of life, clinical and functional outcomes) and other implementation outcomes. A cost-utility analysis will estimate incremental costs and quality-adjusted life-years associated with MyPREPED, alongside a secondary cost-effectiveness analysis. Analyses will follow intention-to-treat principles, using mixed-effects models. CONCLUSIONS: This study will provide the first rigorous test of a co-designed, peer-delivered recovery and self-management focused intervention specifically targeting EIPS discharge.

BACKGROUND: Cancer therapy-related cardiovascular toxicity (CTR-CVT) is a leading non-cancer cause of morbidity and mortality in oncology patients. Implementation of the 2022 ESC Guidelines on cardio-oncology in German inpatient care remains poorly characterised. METHODS: Cross-sectional online survey of 1,435 German hospital departments (February-October 2025). Cardiologists, internists, gynaecologists and oncologists answered items on risk stratification, diagnostics, biomarkers, communication and care quality. RESULTS: 120 physicians responded (cardiologists 36.7%, oncologists 23.3%, gynaecologists 22.5%, internists 17.5%; 73.3% academic/university hospitals). Pre-chemotherapy risk stratification was reported by 85.4% of oncologists and gynaecologists, yet cardiologists were involved in only 28-35%, with heterogeneous risk parameters across specialties. Pre-chemotherapy N-terminal pro-B-type natriuretic peptide (NT-proBNP) use ranged from 85.3% (cardiology) to 15.8% (gynaecology; p < 0.001); 52.6% of gynaecologists used no biomarker. In high-risk patients (anthracyclines plus pre-existing heart failure), gynaecologists monitored significantly less than oncologists at every time point, with 12-month surveillance at 5.3% versus 54.2% (p = 0.001); acute cardiac events were the predominant trigger (36.8%), reflecting reactive rather than proactive practice. Cardiological co-management was median 100% (IQR 50-100) in gynaecology versus 70% (IQR 30-100) in oncology. Dedicated cardio-oncology boards existed in only 1.3% of institutions despite > 70% endorsement; median perceived deficit to optimal care was 50-63%. Top-requested interventions were digital risk-stratification tools (up to 81.8%) and interdisciplinary continuing education (up to 72.7%). CONCLUSION: This survey shows that, among participating hospitals, inpatient cardio-oncology care had substantial guideline-practice gaps. Structured solutions were broadly endorsed: digital risk-stratification tools, post-treatment surveillance and cardio-oncology boards are concrete implementation targets.

BACKGROUND: Employers are increasingly seeking strategies to manage rising health care costs, including bundling or carving out specific benefits like pharmacy coverage. Although some studies suggest that integrating medical and pharmacy benefits leads to reduced medical costs, the mechanism remains unclear. OBJECTIVE: To evaluate the impact of bundling medical and pharmacy benefits on medical costs and utilization among self-funded employer groups and explore the potential role of population health management programs (PHMPs) as a mechanism for driving savings. METHODS: This retrospective, propensity score-matched, longitudinal cohort analysis used administrative claims data from a large health plan in Southeastern Pennsylvania. Self-funded group plan participants were included in the analysis if they had integrated medical and pharmacy benefits in both 2022 and 2023 (integrated group) or if they lacked integrated benefits in either year (comparison group). We additionally required that these plan participants did not experience major changes to their population health management benefits. Doubly robust models, adjusting for concurrent risk scores, were used to compare changes in per-member per-month (PMPM) medical costs and per-1,000-members per-year utilization between the integrated and nonintegrated groups. Propensity score matching was employed to create balanced comparison groups. RESULTS: Members with integrated pharmacy benefits experienced a statistically significant reduction of $32.48 PMPM (7.5%) in total medical cost growth relative to the nonintegrated benefits group. This reduction was largely driven by lower inpatient ($13.27 PMPM, 13.5%) and emergency department ($1.35 PMPM, 4.7%) spending. For members with a PHMP benefit, integrated pharmacy was associated with greater estimated savings ($39.28 PMPM, 9.0%) compared with those without integrated pharmacy. Additionally, members with integrated benefits were estimated to have a greater probability (10.9%) of outreach by a PHMP nurse compared with those without integrated pharmacy. CONCLUSIONS: Bundling medical and pharmacy benefits was associated with reduced medical cost growth, particularly in inpatient and outpatient settings. Coordination activities like PHMPs, enabled by data integration from bundled benefits, may be a key mechanism for achieving cost savings. These results support th

OBJECTIVES: To evaluate whether a stent-plus-irrigation protocol reduces complication rates following hypospadias repair in adolescents compared with catheter drainage alone. PATIENTS AND METHODS: In this multicentre randomised controlled trial, adolescents (Tanner Stage II-V) undergoing hypospadias repair were randomly assigned to either a stent-plus-irrigation group or a catheter-drainage group. The catheter-drainage group received standard urethral catheter drainage alone, whereas the stent-plus-irrigation group received an additional small-calibre urethral stent positioned within the reconstructed urethra and twice-daily saline irrigation. The primary outcome was the overall postoperative complication rate; secondary outcomes included urinary function and cosmetic outcomes. RESULTS: A total of 172 adolescents were assessed for eligibility, with 150 participants (75 in the stent-plus-irrigation group and 75 in the catheter-drainage group) included in the final analysis. Compared with the catheter-drainage group, the stent-plus-irrigation group demonstrated a significantly lower overall complication rate (risk ratio [RR] 0.33, 95% confidence interval [CI] 0.20-0.56; P < 0.001), urethral fistula rate (RR 0.27, 95% CI 0.14-0.51; P < 0.001), and surgical site infection (SSI) rate (RR 0.43, 95% CI 0.21-0.87; P = 0.020). CONCLUSIONS: A postoperative stent-plus-irrigation protocol was associated with lower rates of postoperative complications, particularly urethral fistula and SSI, compared with catheter drainage alone after adolescent hypospadias repair. Because the intervention included both an additional urethral stent and saline irrigation, the independent contribution of irrigation cannot be determined in this two-arm trial.

BACKGROUND: Advanced donor lung preservation strategies such as portable ex vivo lung perfusion (pEVLP) and controlled hypothermic storage at 4-8oC (CHS) have revolutionized the practice of lung transplantation, allowing for prolonged preservation and expansion of the donor pool compared to ice. However, it remains unclear how to integrate different strategies in the modern era, especially the role of pEVLP vs CHS. METHODS: We reviewed all adult lung transplants performed at our institution from January 2016 to January 2025, excluding multiorgan transplants. Patients were grouped by preservation method: ice (n=282), pEVLP (n=139), or CHS (n=76). We compared perioperative outcomes across the three strategies. Subanalyses were performed comparing pEVLP to CHS in cases of extended criteria donor lungs and prolonged preservation times (out of body time >8 hrs). RESULTS: The pEVLP and CHS groups had higher risk recipient and donor characteristics compared to ice. There was no difference in primary graft dysfunction grade 3 at 48-72 hrs among groups, but there was a higher incidence of postoperative extracorporeal membrane oxygenation and prolonged ventilator support in the pEVLP and CHS groups. However, in multivariable logistic regression, preservation strategy was not associated with allograft graft dysfunction despite significantly longer preservation times. CONCLUSIONS: Overall, pEVLP and CHS achieved similar outcomes to ice despite significantly longer preservation times. Accordingly, pEVLP and CHS both represent viable strategies to expand the donor pool and enable extended preservation times.

IMPORTANCE: Portable high-efficiency particulate air (HEPA) filters effectively remove airborne microbes. OBJECTIVE: To investigate whether HEPA filters reduce respiratory infection episodes in care home residents. DESIGN, SETTING, AND PARTICIPANTS: This 2-arm cluster randomized clinical trial included care homes for older adults in England, with or without nursing and dementia care provision, and capacity for 20 or more residents in individual bedrooms. Data were collected between September 2021 and May 2024, with each care home participating for 1 winter. INTERVENTIONS: Up to 5 HEPA filters for communal areas (clean air delivery rate set at 160 m3/h) and up to 16 filters for bedrooms (clean air delivery rate set at 60 m3/h). Both groups continued usual infection prevention and control measures. MAIN OUTCOMES AND MEASURES: The primary outcome was respiratory infection rate per winter per bedroom resident (exposed to bedroom and communal room filters). Secondary outcomes included staff absenteeism. All outcomes were also explored for residents exposed only to communal room filters. RESULTS: During the study period, 91 care homes were randomized, 47 to receive communal room filters, with 569 bedroom residents (median [IQR] age, 87 [81-92] years; 398 [70.0%] female), and 44 without communal room filters, with 589 residents without bedroom filters (median [IQR] age, 88 [82-92] years; 23 [71.8%] female). There was no evidence of a difference in the number of respiratory infections per winter per intervention vs control bedroom residents (0.99 vs 1.04; adjusted incident rate ratio, 0.92; 95% CI, 0.64-1.33; P = .67). There was also no evidence of a difference in the rates of staff absenteeism (adjusted incident rate ratio, 0.80 95% CI, 0.55-1.16; P = .24). Results were similar for the residents exposed only to communal room HEPA filters. CONCLUSIONS AND RELEVANCE: In this cluster randomized clinical trial, there was no difference in resident respiratory infection rates in care homes with HEPA filters in communal areas and bedrooms. Care homes should continue existing recommended prevention measures to control respiratory and other infections. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN63437172.

BACKGROUND: Clinically significant depression and anxiety disorders are common in different phases of first-episode psychosis (FEP). These comorbidities can be undervalued in clinical practice. We studied how often comorbid depression and anxiety disorders are diagnosed using the SCID-I interview in FEP patients and explored the corresponding clinical diagnoses for the same sample. METHOD: As a part of the Turku Early Psychosis Study (TEPS), we screened 3772 consecutive admissions during 5 years to the clinical psychiatric services of Turku Psychiatry. The final FEP sample in this study consisted of 94 patients with nonaffective (n = 67) and affective (n = 27) psychoses. Research diagnoses (SCID-I) were compared with clinical diagnoses (ICD-10) obtained from patient records 1 year from admission. RESULTS: SCID-I indicated that 42% (n = 28) and 9% (n = 6) of nonaffective FEP patients fulfilled the diagnostic criteria for lifetime (LT) and current (C) major depression. Depression diagnosis (F32 or F33) was recorded in only half of these cases in clinical practice during the 1-year follow-up. The SCID-I also indicated that 45% (n = 42) and 48% (n = 45) of the whole FEP sample had LT and C anxiety disorders according to the SCID-I. An anxiety disorder diagnosis (F40-48) was recorded for only 40% of the patients with SCID-based LT or C anxiety disorder in clinical practice during the 1-year follow-up period. CONCLUSION: Comorbid depression and anxiety disorders are common in FEP patients but are often not clinically diagnosed. A systematic diagnostic procedure in clinical practice will characterise the full syndromic nature of FEP for personalised treatment strategy.

BACKGROUND: Despite the high prevalence of comorbid cannabis use at first onset of psychotic symptoms, high transition rates from cannabis-induced psychosis to schizophreniform psychoses and bipolar disorder, and evidence of cannabis use as a risk factor in developing primary psychosis, only a few studies have addressed the difficulties in differential diagnosis focusing on the early stages of the disease. AIMS: The present study is the first to date to examine clinical and sociodemographic characteristics of individuals with early psychosis, comparing cannabis-induced psychotic disorder (CIPD), non-substance-induced psychotic disorder with concurrent cannabis use (NSIPD+C), and non-substance-induced psychotic disorder (NSIPD). METHOD: A retrospective chart review of patients aged 18-35 with early psychosis who received inpatient treatment at FRITZ Early Intervention Center between December 2016 and September 2021 was conducted. Sociodemographic characteristics included age, biological sex, family history of psychiatric illness, migration background, living status, education/work status. Clinical characteristics included insight into illness, duration of untreated psychosis (DUP), social functioning, pathway to treatment, treatment motivation, treatment recommendation, and type of discharge. RESULTS: Of 509 participants, 42.6% had a diagnosis of NSIPD, 33.3% of CIPD, 7% of NSIPD+C. NSIPD had a significantly longer treatment duration compared to CIPD, a higher treatment motivation, and a higher discharge in accordance with clinicians' recommendation compared to both CIPD and NSIPD+C. No significant group differences were found in sociodemographic characteristics, DUP, and functioning scores. CONCLUSIONS: The examined sociodemographic parameters as well as level of functioning and DUP do not aid in the differential diagnostic classification when cannabis use and psychotic symptoms occur simultaneously. The absence of differences in DUP across diagnoses may reflect the efficacy of low-threshold access provided by FRITZ and further supports the need for comprehensive implementation of early intervention services.

INTRODUCTION: Children with CHD require ICU admissions, putting them at risk for Post-intensive Care Syndrome in Paediatrics defined as physical, cognitive, social, and emotional health impairments following ICU discharge. There are few studies assessing Post-intensive Care Syndrome in Paediatrics in the CHD population. This study assessed the presence of Post-intensive Care Syndrome in Paediatrics in the CHD community and its relationship with health-related quality of life. METHODS: CHD patients 5-18 years having 1 or more cardiac ICU admissions were evaluated in the Newborn ICU-Cardiac Neurodevelopmental Program from 9/2017 to 9/2020. Physical, cognitive, social, and emotional questionnaires measured each domain. Patients were considered impaired if 2 or more domain questionnaires were abnormal. If any domain showed impairment, Post-intensive Care Syndrome in Paediatrics was present. Predictors included demographic, disease severity, and ICU variables. Health-related quality of life was measured using the Paediatric Cardiac Quality of Life Inventory. Models were created using logistic and linear regression. RESULTS: Of the 117 CHD patients, 50% were male having a mean age of 8.4 and a 5 year median time since last ICU admission. Post-Intensive Care syndrome in Pediatrics was found in 80% of the cohort: 36% physical, 70% cognitive, 26% social, and 33% emotional impairment. Patients with a longer time since last ICU admission showed less physical and emotional impairment (p < 0.05) with emotional impairment associated with worse health-related quality of life (p < 0.001). CONCLUSIONS: Post-intensive Care Syndrome in Paediatrics was present in most CHD patients. Worse emotional health was associated with lower health-related quality of life.

OBJECTIVES: No studies examining clinical outcomes for patients transferred to an acute palliative care unit (APCU) from an intensive care unit (ICU) versus a non-ICU exist. The objectives were to determine the proportions and outcomes of patients being discharged alive from an APCU after being transferred from an ICU versus a non-ICU. METHODS: All patients transferred to our APCU from an ICU from 1 September 2021 to 31 August 2023 and an equally sized random sample of patients transferred from a non-ICU during the same period were identified. Demographics, clinical characteristics and outcomes were compared between the two groups. RESULTS: 400 patients (214 ICU and 186 non-ICU) were included (mean age, 62 years (SD, 14.3); 51.3% women; 63.8% in a relationship; 67.8% white). Non-ICU patients were more likely to be discharged alive than were ICU patients (32.8% (95% CI 26.5 to 39.8%) vs 22.4% (95% CI 17.4 to 28.5%); p=0.02). Of the 109 patients discharged from our APCU, most went either to hospice care at home (54.1%, n=59) or to inpatient hospice care (40.4%, n=44), and there was no difference in discharge location between the ICU and the non-ICU groups (p=0.93). On multivariable analysis, APCU mortality was more likely in the group overall among patients who were receiving oxygen via a high-flow nasal cannula (HFNC) (OR, 2.47 (1.25 to 4.90); p=0.01). CONCLUSIONS: Despite the APCU mortality in this cohort being high, 22.4% of patients transferring from the ICU were successfully discharged to the community. HFNC use at the time of APCU transfer was independently associated with increased odds of APCU mortality.

BACKGROUND AND OBJECTIVES: This study examined the association between prediagnostic anticoagulant use and stage at diagnosis, surgical outcomes, and mortality in patients with renal cell carcinoma (RCC). METHODS: In a nationwide register-based Danish cohort study, we included RCC patients undergoing partial or radical nephrectomy in Denmark in 2009-2020. We compared stage distribution, readmission and reoperation rates, length of hospital stay (LOS), and mortality by anticoagulant use status (current, former, and non-users), using regression analyses and cumulative incidence rates. RESULTS: Among 5730 RCC patients, 21.0% were current and 11.4% former anticoagulant users. At diagnosis, the odds of having higher stage (stage III/ IV) was slightly lower among anticoagulant users (adjusted ORs were 0.90 [95% CI 0.71-1.00] for current users and 0.85 [95% CI 0.73-0.90] for former users). The cumulative 30-day readmission rate was higher in current (18.5%) and former users (19.2%) than non-users (13.5%), while LOS and reoperation rates were similar. Current users had slightly higher 90-day mortality (adjusted hazard ratio [aHR] 1.10 [95% CI 0.65-1.88]), but lower one-year mortality (aHR 0.81 [95% CI 0.60-1.07]) compared with non-users. Former users had slightly higher one-year mortality (aHR 1.12 [95% CI 0.82-1.54]). CONCLUSIONS: RCC patients with prediagnostic anticoagulant use had higher 30-day readmission rates but otherwise comparable perioperative outcomes and mortality to non-users, suggesting that prediagnostic anticoagulant use is not, in itself, a strong marker of poorer surgical prognosis.

Study DesignRetrospective National Cohort Study.ObjectivesThis study aimed to evaluate complication profiles in myasthenia gravis (MG) versus non-MG patients across four routine spine surgeries: lumbar interbody fusion (LIF), lumbar decompression (LD), anterior cervical discectomy and fusion (ACDF), and posterior cervical decompression and fusion (PCDF).MethodsFrom 2010 to 2023, all LIF, LD, ACDF, or PCDF patients were queried from the PearlDiver Mariner Database using ICD-9/10 and CPT procedure codes. MG patients with prior thymectomy were excluded. Nearest-neighbor 3:1 propensity score matching based on age, sex, and comorbidity burden was performed. Postoperative complication rates were assessed during index hospitalization and 90 days postoperatively.ResultsAmong those included, 829, 1198, 527, and 129 MG patients underwent LIF, LD, ACDF, and PCDF, respectively. Understandably, MG patients had elevated rates of myasthenic crisis (5.4-8.5%) across all four cohorts at both time points. During initial hospital stay, MG patients had increased rates of pneumonia (4.0% vs 2.3%, p=0.017) and respiratory failure (4.9% vs 3.3%, p=0.016) following LIF and LD, respectively. Conversely, ACDF MG patients had decreased rates of CVA (0.9% vs 2.7%, p=0.028) and AKI (1.3% vs 3.5%, p=0.017). Similar trends were observed 90 days postoperatively. Length of stay was comparable across cohorts.ConclusionsMyasthenia gravis patients undergoing routine spine surgery face elevated risk of respiratory complications postoperatively. Other systemic complications rates were comparable following matching suggesting complication profiles may be surgery-specific rather than uniformly increased with MG. Appropriate preoperative optimization and multidisciplinary perioperative management allows for safe spine surgery in MG patients.

BACKGROUND: Virtual care is increasingly used for preoperative assessment. We aimed to estimate the noninferiority of virtual vs in-person anaesthesiology consultations with respect to 90-day morbidity and mortality in at-risk adults having noncardiac surgery. METHODS: We conducted a retrospective observational comparative effectiveness study using a target trial emulation framework. Eligible participants were aged ≥40 yr, with an ASA physical status ≥3, having elective, noncardiac, non-orthopaedic, moderate- to high-risk surgery, and attended a preoperative anaesthesiology consultation in Ontario, Canada, between October 2020 and March 2022. Exposures were receipt of virtual vs in-person preoperative anaesthesiology consultation in the 60 days preceding surgery. The primary outcome was 90-day major morbidity or mortality (noninferiority margin of upper 95% confidence interval [CI] <1.10 on relative scale). Secondary outcomes included 90-day mortality, length of hospital stay, costs of care, and days alive and at home within 90 days (DAH90). Travel-attributable carbon emissions were also estimated. Analyses used instrumental variable and propensity score methods. RESULTS: Among 17 027 patients, 8399 (49.3%) received a virtual consultation. The primary outcome occurred in 2212 (26.3%) virtual consult patients and 2147 (24.9%) of 8628 in-person consult patients. Primary outcome noninferiority was inconclusive based on both instrumental variable (adjusted odds ratio [adj-OR] 1.02, 95% CI 0.92-1.13) and propensity-score adjusted (adj-OR 0.99, 95% CI 0.89-1.101) analyses. Noninferiority was observed for length of hospital stay, costs of care, and DAH90. In-person care was associated with an estimated increase of 8618 (SD 17 200) g CO2 per visit. CONCLUSIONS: Before moderate-to-high-risk noncardiac, non-orthopaedic elective surgery, the noninferiority of virtual vs in-person anaesthesiology consultation for major morbidity or mortality was inconclusive. Virtual care was noninferior for several secondary outcomes and associated with reduced carbon emissions. Further research is required to refine triage models and increase certainty regarding morbidity.

IMPORTANCE: Nutrition insecurity is a major driver of poor cardiovascular health in Indigenous communities. Medically tailored meals that reclaim traditional foods may improve heart failure outcomes and quality of life. Community-based participatory methods were used to design Medically Utilized Tailored Traditional Foods to Optimize Nutrition in Heart Failure (MUTTON-HF), a culturally and medically tailored meal program incorporating traditional Navajo foods and recipes. OBJECTIVE: To determine the efficacy of a culturally and medically tailored meal program on the incidence of hospitalizations and emergency department visits. DESIGN, SETTING, AND PARTICIPANTS: This pragmatic, open-label randomized clinical trial was conducted from May to November 2025 at 2 Indian Health Service sites in rural Navajo Nation. Eligible patients were adults with heart failure who were receiving care at the study sites and had a hospitalization or emergency department visit during the last 12 months. All patients were followed for 12 weeks for outcomes, death, and adverse events. The data were analyzed from December 2025 to February 2026. INTERVENTION: Patients were randomized in a 1:1 ratio to 8 weeks of a culturally and medically tailored meal program or usual dietary advice. MAIN OUTCOMES AND MEASURES: The primary end point was the proportion of patients with an all-cause hospitalization or emergency department visit within 90 days. Secondary outcomes included hospitalizations or emergency department visits separately, and for heart failure specifically, and change in Kansas City Cardiomyopathy Questionnaire scores, food insecurity, financial strain, blood pressure, and weight from enrollment to 8 weeks. RESULTS: A total of 206 patients (mean [SD] age, 65.8 [14.2] years; 87 female individuals [42%] and 119 male individuals [58%]; 203 American Indian individuals [99%], 2 American Indian or Alaskan Native and White individuals [0.97%], and 1 White individual [0.03%]; ejection fraction, 48%) were randomized. The primary outcome was significantly less frequent in the intervention arm (43 [40.6%] vs 57 [57.0%]; relative risk, 0.72; 95% CI, 0.54-0.96; P = .02), which was driven mainly by reduced hospitalizations (13 [12.3%] vs 26 [26.0%]). There was a lower incidence of heart failure hospitalizations specifically (4 [3.8%] vs 13 [13.0%]). The Kansas City Cardiomyopathy Questi

BACKGROUND/OBJECTIVES: The transition of the neurologically injured patient from the intensive care unit (ICU) environment toward recovery often requires placement of a ventriculo-peritoneal shunt (VPS) and a gastrostomy tube (g-tube). Prior work has demonstrated a significant association between g-tube placement and shunt infection, however, both procedures are typically performed during the same hospitalization. Thus, there remains a question regarding the optimal timing of g-tube relative to VPS placement and the risk of subsequent complications. The objective of this study is to examine the risk of complications on the basis of relative timing of VPS and g-tube placement. METHODS: Patients admitted for intracranial hemorrhage who underwent both VPS and g-tube placement within 10 days of each other were retrospectively identified in the Nationwide Readmissions Database from 2016 to 2022. Patients were divided into three groups: VPS > 1 day before g-tube, g-tube > 1 day before VPS, and both procedures within 1 day. Primary outcomes were inpatient shunt infection or revision and delayed infection or revision within 180-days post-discharge. RESULTS: Overall, 3334 patients met the inclusion criteria. The most common period for the procedures to occur was within 24 h of each other. Excluding patients who received both VPS and g-tube within 1 day of separation (n = 530, 15.9%), 1254 (44.7%) received VPS first while 1550 (55.3%) received VPS second. Patients who received VPS first were significantly more likely to experience inpatient central nervous system (CNS) infection (10.5% vs. 9.5%, adjusted odds ratio (aOR): 1.52; 95% confidence interval (CI) 1.10-2.10; p = 0.012) and shunt failure requiring revision (6.8% vs. 4.9%, aOR 1.57 [95%CI 1.03-2.41], p = 0.038). Compared with the g-tube first group, those who received VPS within 1 day of g-tube had no significant differences in CNS infection or shunt failure (p > 0.05). There were no differences in delayed complications between groups within 180 days post-discharge (all p > 0.05). CONCLUSIONS: While our results are primarily hypothesis generating, in this nationwide analysis, we demonstrate that g-tube placement before or within 24 h of VPS is associated with significantly lower odds of shunt failure or infection.

Robot-assisted kidney transplantation (RAKT) has emerged as a minimally invasive alternative to open kidney transplantation (OKT). However, the comparative benefits and limitations of both approaches remain unclear. To compare the outcomes of RAKT and OKT through an umbrella review of published systematic reviews and meta-analyses. This umbrella review was written following PRISMA guidelines. Only meta-analysis and systematic review were included. Many outcomes were studied such as warm (WIT) and cold ischemia times (CIT), rewarming time, total ischemia time, blood loss, blood transfusion, delayed graft function, surgical site infections (SSI), hospital stay, graft rejection, graft failure, all-cause mortality, operation time, incision length, hospital readmission, vascular and ureteral anastomosis time, and other complications. We assessed methodological quality via the AMSTAR-2 tool. Consistency and strength of evidence were also evaluated. 6 studies were included: four meta-analyses and two systematic reviews. Studies were of low to moderate quality. Robotic kidney transplant surgery yields better outcomes in terms of blood loss (MDs ranging from - 16 to - 55 mL across studies), post-operative pain, incision length, SSI and ureteral leak. On the other hand, CIT, rewarming time, total ischemia time, operative time and ileus rate were favored in open surgery. Same rejection rates, graft failure, mortality and hospital readmission rate were found between both techniques. RAKT appears to improve several perioperative outcomes while maintaining comparable graft and patient survival outcomes to OKT. However, the available evidence remains limited by the low-to-moderate quality of existing reviews, highlighting the need for high-quality prospective studies.

INTRODUCTION: Healthcare systems face increasing strain from population ageing, multimorbidity and rising emergency department (ED) attendances. Acute medical units (AMUs) have been adopted internationally to improve patient flow and reduce hospital length of stay, but prospective evidence on their clinical and economic effectiveness remains limited, particularly in Singapore. This study aims to evaluate the clinical outcomes and cost-effectiveness of an AMU model compared with usual care in the general ward at a Singapore tertiary hospital. METHODS AND ANALYSIS: This is an ongoing single-centre prospective observational cohort study conducted at the National University Hospital, Singapore. Adults admitted non-electively under medical services, whose first admission ward is either the AMU or a general ward, will be recruited and followed for 6 months after index discharge. Recruitment commenced in September 2024 and will continue through December 2025, with final follow-up expected in July 2026. The primary endpoint is total acute-care bed-days within 6 months of index admission, including bed-days accrued during the index admission and any subsequent non-elective acute-care admissions within 6 months of the index admission date. Secondary endpoints include ED reattendance, unplanned readmission, mortality, patient-reported outcomes (EuroQol Five-Dimension Five-Level, WHO-Five Well-being Index, Patient Activation Measure-13, Patient Health Questionnaire-9, Barthel Index and Rapid Estimate of Adult Literacy in Medicine-Short Form), healthcare utilisation and healthcare costs. Because allocation to AMU or general ward care is determined by routine service processes rather than randomisation, comparative analyses will use propensity score inverse probability weighting to reduce measured confounding. Repeated patient-reported outcomes will be analysed using mixed-effects models. The economic evaluation will estimate incremental costs and quality-adjusted life years associated with AMU care compared with usual care over a 6-month period. ETHICS AND DISSEMINATION: Ethics approval has been granted by the National Healthcare Group Domain Specific Review Board, Singapore (Reference: 2023/00590). Written informed consent will be obtained from participants or their legally authorised representatives. Findings will be disseminated through peer-reviewed publications, c

PURPOSE: Protein-energy malnutrition (PEM) is common in gastrointestinal (GI) cancers and may worsen inpatient outcomes. Contemporary national data describing the impact of PEM among young adults with GI malignancies are limited. METHODS: We conducted a retrospective cohort study using HCUP NIS data from 2018 to 2021. We identified hospitalizations of adults aged 18 to 39 years with GI cancers using ICD 10 CM codes C15 to C26. We defined PEM using ICD-10-CM diagnosis codes recorded during the index hospitalization; therefore, PEM reflects clinically documented/coded malnutrition rather than the full burden of nutritional risk or clinically undiagnosed malnutrition. Primary outcomes were in hospital mortality and discharge disposition. Secondary outcomes were LOS and total hospital charges. We used survey weighted multivariable logistic and linear regression to estimate adjusted associations, accounting for age, sex, race or ethnicity, payer, income quartile, admission type, calendar year, and age adjusted CCI. RESULTS: Among 58,910 weighted hospitalizations of young adults with gastrointestinal cancers, 11,915 (20.2%) had protein-energy malnutrition (PEM). Compared with those without PEM, hospitalizations with PEM had a higher burden of advanced disease and acute illness, including a greater prevalence of metastatic disease (71.8% vs. 53.1%), and experienced worse unadjusted outcomes, including higher in-hospital mortality (8.4% vs. 3.2%), longer length of stay (10.43 vs. 5.63 days), and higher total hospital charges ($133,790 vs. $83,702). In adjusted analyses, PEM was independently associated with increased odds of in-hospital mortality (aOR 2.13, 95% CI 1.72-2.56; p < 0.001) and higher odds of non-home discharge (aOR 1.67, 95% CI 1.47-1.89; p < 0.001). PEM was also associated with substantially greater resource utilization, including an adjusted increase of 4.49 hospital days (β + 4.492; SE 0.248; p < 0.001) and $53,513 higher total hospital charges (β +$53,512.6; SE $5,527.6; p < 0.001). CONCLUSION: PEM affected one in five hospitalizations among young adults with GI cancers and was independently associated with increased mortality, non-home discharge, LOS, and hospital charges. These findings support routine inpatient nutritional assessment and early intervention in this high risk population.

BACKGROUND: Allogeneic hematopoietic cell transplantation (allo-HCT) improves survival in patients with acute myeloid leukemia (AML); however, posttransplant relapse remains the most common cause of treatment failure and death. Limited data exist on posttransplant health care resource utilization (HCRU) and costs, particularly for patients initiating maintenance therapy. OBJECTIVE: To describe HCRU and costs among commercially insured patients, Medicaid enrollees from participating US states, and Medicare-eligible beneficiaries with employer-sponsored supplemental coverage who received maintenance therapy after allo-HCT compared with those receiving allo-HCT alone. METHODS: We conducted a retrospective cohort study of patients with AML who underwent allo-HCT using claims data from the Merative MarketScan database from October 1, 2015, to March 31, 2024. Patients receiving maintenance therapy were identified by a claim for 1 of the following agents after allo-HCT: azacitidine, decitabine, enasidenib, gemtuzumab ozogamicin, gilteritinib, glasdegib, ivosidenib, midostaurin, quizartinib, sorafenib, or venetoclax. Groups were balanced using inverse probability treatment weighting (IPTW) based on baseline characteristics. We assessed differences in all-cause monthly HCRU and costs. HCRU included emergency department (ED) visits, inpatient (IP) admissions, outpatient (OP) visits, and hospital length of stay throughout the 12-month follow-up period. Poisson and negative binomial regression models estimated event rates. Per patient per month mean costs were reported with SEs, and between-group differences were assessed using mean differences, bootstrapped 95% CIs, and P values. Cumulative costs were summarized using the mean with bootstrapped 95% CIs and the median. IPTW-weighted mean monthly costs were also calculated for each cohort. Transfusion burden was also evaluated. RESULTS: Of the 373 patients who met the inclusion criteria, 43 were prescribed maintenance therapy following allo-HCT. The maintenance therapy group demonstrated significantly higher HCRU across service types. Both office (incidence rate ratio [IRR] = 3.23, P = 0.004) and OP visits (IRR = 4.26, P < 0.001) were more than tripled compared with the allo-HCT-only group, and IP admissions rose by 34% (IRR = 1.34, P = 0.034). Specialist clinic and ED visit rates were higher but not statistically sig

BACKGROUND: Optimal ventilatory settings during general anaesthesia are unknown. The goal of this trial was to test different ventilatory settings and blood pressure targets during general anaesthesia. This manuscript focuses on the ventilatory interventions. METHODS: This was a multicentre, randomised factorial trial conducted at eight hospitals in Denmark. Four hundred and eighty-three patients ASA 3-5, scheduled for major surgery under general anaesthesia, were included. Patients were randomised to positive end-expiratory pressure (PEEP) of 5, 8, or 10 cm H2O, tidal volume of 6, 8, or 10 mL/kg, and fraction of inspired oxygen (FiO2) of 30% or 80%. The primary outcome was feasibility of delivering the ventilatory interventions, while secondary outcomes included intra- and postoperative complications, hospital length of stay, quality of life and recovery, and mortality. RESULTS: Feasibility goals were not met, but clear separation within each intervention was achieved. There were no differences between groups in most postoperative outcomes. Cardiac arrhythmias appeared more frequently in the PEEP-8- and 10-cm-H2O groups (OR 9.32, 95% CI 1.59; 178 and OR 6.71, 95% CI 1.00; 134), compared to the PEEP-5-cm-H2O group. Outcomes did not differ between tidal volume interventions. Pneumonia (OR 4.04, 95% CI 1.40; 14.6) and emergence delirium (OR 5.56, 95% CI 1.94; 20.4) were more frequent in patients allocated to FiO2 of 80% than 30%. CONCLUSION: Adherence to interventions was acceptable, although below feasibility goals. Few postoperative complications were more frequent in patients receiving PEEP 8 and 10, and in patients receiving FiO2 of 80%. These findings should be interpreted with caution given the uncertainty of the estimates. TRIAL REGISTRATION: Clinicaltrials.gov: NCT06047119.

INTRODUCTION: Community-acquired pneumonia (CAP) is common and remains the leading infectious cause of death worldwide. Antibiotics remain the mainstay of treatment, but organisms are often not identified, necessitating empirical treatment. Current treatment guidelines recommend combination therapy with beta-lactams and macrolides or monotherapy with fluoroquinolones for non-severe CAP. However, rising antibiotic resistance and safety concerns have led to increased doxycycline use, despite limited evidence supporting its efficacy. Our goal is to conduct a pragmatic, open-label, randomised clinical trial comparing the effectiveness of azithromycin with that of doxycycline in combination with beta-lactam therapy in adult patients hospitalised for CAP. METHODS AND ANALYSIS: Patients presenting to the emergency department or directly referred to the hospital with a clinical presentation concerning for CAP and need for hospitalisation are eligible. We plan to enrol 1120 adults hospitalised at six hospitals across four states, including rural, suburban and urban settings and academic and community hospitals. Randomisation will be 1:1 using an electronic health record (EHR)-embedded screening and randomisation tool triggered by the treating clinician's orders for azithromycin or doxycycline. Outcomes will be ascertained pragmatically via EHR-based data retrieval and will not require additional study visits. Our primary outcome is days alive and out of the hospital through day 28. Secondary outcomes include oxygen-free days; a composite of a need for advanced respiratory support or in-hospital mortality with analyses of each component separately; an ordinal measure of clinical deterioration defined by a prespecified severity scale; and 60-day and 180-day mortality. Safety outcomes are the incidence of Clostridioides difficile infection and QT prolongation. Analyses will follow an intention-to-treat framework, with per-protocol analyses for sensitivity. The primary endpoint will be compared between groups using a stratified van Elteren test, with supportive analyses using proportional odds regression and analysis of covariance adjusted for key covariates. ETHICS AND DISSEMINATION: The Mayo Clinic Institutional Review Board reviewed and approved this protocol with a waiver of written consent, requiring verbal consent to be obtained by the clinician initiating the an

BACKGROUND: Intrathecal drug delivery (IDD) offers a therapeutic option for patients suffering from refractory pain or severe spasticity. By allowing targeted and continuous infusion directly into the intrathecal space, IDD bypasses the blood-brain barrier and enhances therapeutic effectiveness of the drug. Following the implantation of an IDD pump, the most commonly performed postoperative maintenance procedure is the pump refill (at regular intervals). This process can be burdensome for patients, affects their comfort, and carries significant risks. The current aim of this study is to evaluate whether intrathecal pump refills performed at home provide a difference in patient comfort compared to refills conducted in the hospital. METHODS: The IMPROVE study is a monocentric, randomized controlled crossover trial, including 82 patients. For this study, each patient will undergo four intrathecal pump refill procedures (two at home and two in the outpatient clinic) allocated in a randomized order. The primary objective of this study is to determine whether at-home refills provide a difference in patient comfort compared to hospital-based refills. Secondary objectives include assessing differences in quality of life, pain, stress, anxiety, self-efficacy, caregiver burden, patient preferences, safety, and overall cost-effectiveness between the two settings. Patients will be followed over the course of four intrathecal pump refills, which is estimated to span approximately one year. DISCUSSION: Within the IMPROVE project, pump refills will be performed through hospital at home. If at-home intrathecal pump refills prove more comfortable for patients and cost-effective for society, this would strengthen the patient-centred care model and support adopting this approach as the new standard treatment for IDD patients. A graphical abstract is provided in the supplementary materials (S1 Fig). TRIAL REGISTRATION: Details on the study site can be found at ISRCTN with identifier: ISRCTN18031921; [href:https://doi.org/10.1186/ISRCTN18031921]https://doi.org/10.1186/ISRCTN18031921. The trial was registered in the ISRCTN registry on 18 November 2025.

PURPOSE: Nasal necrosis is a rare but potentially devastating manifestation of diverse conditions, including fulminant infection, immune-mediated vasculopathy, drug toxicity, neoplasia and device-related pressure injury. Surgical intervention is often prioritized; however, a subset of patients is managed non-surgically and evidence-based guidance remains limited. The objective is to systematically synthesize non-surgical etiologies, clinical patterns, diagnostic workup, and management strategies reported in cases of nasal necrosis. METHODS: A systematic search of PubMed, Scopus and ScienceDirect from inception to December 7, 2025 identified case reports and case series involving human patients with nasal skin or soft-tissue necrosis not primarily attributable to surgery or cosmetic procedures. Non-human studies, systematic reviews and non english records were excluded. Data on demographics, etiology, presentation, investigations, management and outcomes were extracted. Methodological quality was appraised using Joanna Briggs Institute (JBI) tools. RESULTS: Thirty-nine publications comprising 45 cases were included. Infectious etiologies were most frequent (44.4%), followed by mechanical or traumatic (20.0%), immune-mediated (13.3%), drug-induced (13.3%), neoplastic (6.7%), and congenital causes (2.2%). Isolated nasal involvement occurred in 57.8% of cases. Non-surgical management included antimicrobials, corticosteroids, immunosuppressive agents, anticoagulation, wound care, and adjunctive hyperbaric oxygen therapy, with better outcomes in cases where the underlying cause was identified early. CONCLUSION: Nasal necrosis represents a heterogeneous clinicopathologic endpoint in which prompt etiologic diagnosis is critical for effective, organ-preserving dermatologic management.

UNLABELLED: Assessment of cytomegalovirus (CMV) cell-mediated immunity (CMV-CMI) using standardized, commercially available interferon-gamma release assays (IGRAs) may improve the clinical management of CMV infection in allogeneic hematopoietic stem cell transplant recipients (allo-HCT). Studies comparing the performance of CMV IGRA assays have been conducted in this setting, revealing frequent discrepancies between assays. Here, we compared the performance of a newly released VIDAS CMV IGRA (bioMérieux) and the T-SPOT. CMV (Oxford Immunotec) was evaluated in a cohort of 85 allo-HCT recipients who received letermovir prophylaxis. A total of 107 whole blood samples were collected at either day +100 (n = 53) or day +180 (n = 54) after allo-HCT and analyzed in parallel. A moderate qualitative agreement between assays was observed (Cohen's kappa coefficient, 0.47; 95% CI, 0.30-0.63). Discrepant results were obtained in 29 specimens, most of which were collected at day +100. A moderate correlation (rho, 0.54; P < 0.001) was observed between T-SPOT pp65-SPC and IFN-γ levels measured by the VIDAS CMV assay, whereas the correlation was weaker for T-SPOT IE-1 SPC and VIDAS IFN-γ levels (rho, 0.32; P < 0.001). The previously described booster effect of CMV DNAemia on the magnitude of CMV-CMI was captured by the VIDAS CMV assay. Neither the qualitative nor the quantitative results obtained with either IGRA predicted protection from CMV DNAemia following LMV discontinuation. While our data support the validity of the VIDAS CMV assay for the assessment of CMV-CMI in allo-HCT, they reinforce the idea that results from commercially available IGRA assays are not interchangeable, particularly in allo-HCT recipients with impaired CMV-CMI reconstitution. IMPORTANCE: This is the first study comparing a new interferon-gamma release assay (IGRA), the VIDAS cytomegalovirus (CMV), performed on whole blood and based on an enzyme-linked immunofluorescent assay detection technique, with a commercially available ELISpot assay (T-SPOT CMV) for measuring CMV-specific T-cell responses (CMV-CMI). Our cohort included allogeneic hematopoietic stem cell transplant recipients who underwent letermovir prophylaxis. In this clinical setting, tailoring the duration of LMV prophylaxis based on CMV-CMI at the time of drug discontinuation has emerged as a promising application of these assays. Our d

BACKGROUND: Acute heart failure (AHF) carries high morbidity and mortality and is traditionally managed with diuretics, vasodilators, and inotropes. Although guidelines recommend SGLT-2 inhibitors for chronic heart failure to reduce morbidity and mortality, their efficacy and safety when initiated during AHF hospitalization remain incompletely defined. To address this gap, we performed the largest, most contemporary meta-analysis focused exclusively on in-hospital initiation, including the first comprehensive pooled evaluation of decongestion outcomes. METHODS: We systematically searched PubMed, Scopus, Cochrane CENTRAL, and Google Scholar from inception to February 7, 2026, following PRISMA 2020 guidelines and a pre-registered PROSPERO protocol. Eligible studies were randomized controlled trials enrolling adults hospitalized with AHF receiving in-hospital SGLT-2 inhibitors versus placebo/standard care. Random-effects models (REML) pooled clinical, decongestion, and safety outcomes. RESULTS: Eighteen RCTs (n = 15,560) were included. In-hospital SGLT-2 initiation significantly reduced heart failure worsening or hospitalization (RR 0.77, 95% CI 0.67-0.88; NNT = 48) and improved quality of life (KCCQ-12 MD + 2.88 points, p = 0.01). Decongestion outcomes favored SGLT-2 inhibitors, with improved diuretic efficiency (SMD 0.52, p = 0.001), greater weight loss (MD - 0.94 kg, p < 0.001), and lower NT-proBNP (MD - 313.6 pg/mL, p = 0.04). All-cause mortality showed a modest reduction (RR 0.74, p = 0.035) but demonstrated potential publication bias and was attenuated in trim-and-fill analysis. Cardiovascular and non-cardiovascular death, and hospitalization length, were not significantly different. Critically, no increase was detected in AKI, hypotension, hypoglycemia, ketoacidosis, genitourinary infections, or other serious adverse events. CONCLUSIONS: In-hospital SGLT-2 inhibitor initiation appears safe and is associated with reduced clinical events and modest improvements in decongestion markers. These findings support early in-hospital initiation as a feasible and safe strategy, although the current evidence, while promising, highlights the need for further long-term confirmatory data and provides a basis for potential updates to acute heart failure guidelines. PROSPERO ID: CRD420261297253.

The intestinal microbiome is a key regulator of immune homeostasis, metabolism, and epithelial barrier integrity. In patients with malignant hematological diseases, particularly those undergoing hematopoietic stem cell transplantation, microbiome perturbations by reduced diversity, pathobiont expansion, and loss of beneficial metabolites are common as a consequence of exposure to cytotoxic therapy and broad-spectrum antimicrobials. Accordingly, enteral microbiome manipulation has emerged as a promising strategy. We performed a narrative review of the literature in PubMed/MEDLINE, Embase, and the Web of Science from inception to October 2025. We focused on adult hematology and HSCT populations and synthesized evidence across microbiome-directed interventions, including fecal microbiota transplantation (FMT) and emerging standardized microbiota products, as well as adjunctive strategies such as pre-, pro-, and postbiotics, dietary modulation, and microbiome-sparing antimicrobial practices. Available clinical evidence, predominantly from case series, small cohorts and a limited number of randomized trials, suggests that FMT is feasible in selected immunocompromised patients and may be beneficial for recurrent Clostridioides difficile infection, multidrug-resistant organism decolonization and steroid-refractory gastrointestinal GvHD. Mechanistic data support pleiotropic effects of microbiome restoration, including replenishment of immunoregulatory metabolites, improved colonization resistance and reinforcement of mucosal function. While most reported adverse events are mild, rare transmission events and product variability necessitate for rigorous donor screening, standardized manufacturing and regulatory oversight. Key knowledge gaps include patient selection, optimal timing, dosing strategies, durability of benefit and integration with concurrent medications. In conclusion, microbiome-based interventions may transition from rescue therapy toward a structured component of supportive care in hematologic malignancy management.

OBJECTIVES: To identify risk factors for carbapenem resistance in Enterobacterales bacteremia and predictors of 14- and 28-day mortality. METHODS: Adult patients (≥18 years) with Enterobacterales bacteremia admitted to a tertiary-care center between January 2015 and January 2024 were retrospectively analyzed. Isolates were classified as carbapenem-resistant Enterobacterales (CRE), extended-spectrum β-lactamase-producing (ESBL), or non-ESBL (nESBL). Independent predictors of CRE were identified using multivariable logistic regression. Model calibration, internal validation, and a nomogram were used to assess predictive performance. Cox proportional hazards models identified predictors of 14- and 28-day mortality. RESULTS: Of 895 patients, 14.9% had CRE bacteremia. Independent predictors of CRE were intensive care unit (ICU) admission (OR 4.87, 95% CI 3.18-7.57), hospitalization for ≥14 days before index blood culture (OR 2.67, 95% CI 1.74-4.09), and prior carbapenem exposure (OR 2.79, 95% CI 1.84-4.25). Twenty-eight-day mortality was higher in the CRE than ESBL and nESBL groups (63.9% vs. 32.3% vs. 28.3%; p<0.001). ICU admission, sepsis, and inappropriate empirical antimicrobial therapy independently predicted mortality. The prediction model showed good discrimination (Harrell's C-index, 0.79). CONCLUSIONS: CRE bacteremia was associated with high mortality and occurred predominantly in critically ill patients with prolonged hospitalization and prior carbapenem exposure. Mortality was driven primarily by illness severity and inappropriate empirical antimicrobial therapy rather than carbapenem resistance itself. Early appropriate empirical therapy independently improved survival regardless of resistance profile.

BACKGROUND: Distinguishing possible from definite infective endocarditis (IE) is challenging and may affect clinical decisions. A better understanding of how possible and definite IE differ, according to the ESC Duke criteria, may clarify the clinical relevance of this distinction. PURPOSE: To compare clinical characteristics and outcomes in patients with possible and definite IE. METHODS: We included all patients with a first episode of possible or definite left-sided IE from the NatIonal Danish endocarditis stUdieS (NIDUS) registry (2016-2021), classified according to the 2015 ESC modified Duke criteria. We assessed baseline characteristics and management, as well as six-month rates of IE-related outcomes and all-cause mortality. RESULTS: Among 3017 patients, 587 (19.5%) had possible IE and 2430 (80.5%) definite IE. Patients with possible IE were older and more often had left-sided prosthetic valves (35.4% vs. 25.8%) and culture-negative IE (30.0% vs. 2.2%), but less often vegetations >10 mm (13.6% vs. 32.8%) (all p < 0.001). Complications and cardiac surgery (10.9% vs. 24.6%) were less frequent in the possible IE group. Antibiotic treatment was shorter in possible IE (median days 37 vs. 40; p = 0.01). Six-month all-cause mortality was similar: 27.4% [95% CI: 23.8-31.1] vs. 28.1% [95% CI: 26.3-29.9], as were IE-related outcomes. CONCLUSION: Patients with possible IE more often had left-sided prosthetic valves and culture-negative IE, but less often vegetations >10 mm, complications or cardiac surgery, and received shorter antibiotic treatment. Clinical outcomes were similar. These findings highlight diagnostic challenges and the need for tailored diagnostic and treatment strategies.

OBJECTIVE: To invasively validate the 2024 and 2013 British Society of Echocardiography (BSE) recommendations for diastolic function (DF) and left ventricular filling pressure (LVFP) detection using LV end-diastolic pressure (LVEDP) ≥ 16 mmHg and LV pre-A > 15 mmHg in patients undergoing left heart catheterization (LHC) and to propose a complementary algorithm to improve diagnostic performance. METHODS: In this prospective multicenter study, 716 patients in sinus rhythm underwent echocardiography within 120 min before clinically indicated LHC (401 derivations and 315 temporally independent validation cohort). Patients with conditions that could interfere with the reliability of the algorithms were excluded. Both guidelines and proposed algorithms estimated DF and LVFP. The diagnostic classifications were compared with invasively-measured LVEDP and LV pre-A pressure. RESULTS: BSE-2024 classified patients as (0.7%) indeterminate, (49.1%) normal and (50.1%) impaired DF, compared with (60.6%), (14.2%) and (25.2%), respectively, using BSE-2013. After excluding indeterminate cases, area under the curve (AUC) for detecting LVFP was comparable (e.g. for LVEDP, BSE-2024: 0.602 vs. BSE-2013: 0.630, P = 0.459). Updated guidelines achieved higher specificity for LVEDP (93.5% vs. 81.9%) but substantially lower sensitivity (27.8% vs. 44.2%), similar to that for LV pre-A (specificity: 92.1% vs. 79.4% and sensitivity 38.2% vs. 50.8%). BSE-2024 reclassified (82.3%) of indeterminate cases and (60.8%) of elevated LVFP under BSE-2013 as normal, with no significant change in overall reclassification (NRI: -0.056, P = 0.41; IDI: -0.056, P = 0.40). The proposed algorithm performance results were {LVEDP: (78.8%) sensitivity and (79.8%) specificity, while LV pre-A: (85.5%) sensitivity and (67.3%) specificity}. The independent validation cohort confirmed the robustness and reproducibility of the complementary algorithm {LVEDP: (88.3%) sensitivity and (87.9%) specificity and LV pre-A: (95.7%) sensitivity and (64.3%) specificity}. CONCLUSIONS: BSE-2024 markedly reduced indeterminate classifications but showed reduced sensitivity and modest diagnostic discrimination against invasive reference standards. Comparisons should be interpreted cautiously because BSE-2013 excludes many indeterminate cases from performance analyses, whereas BSE-2024 retains nearly all patients. The complement

AIMS: Accurate age- and sex-specific T1 and T2 reference values are critical for differentiating myocardial pathologies, yet existing data are inconsistent due to methodological variability. This study proposes standardized T1 and T2 mapping protocols with clinically feasible breath-hold durations and reports site-, sequence-, age-, sex-, and segment-specific reference values. METHODS AND RESULTS: This prospective, single-center study enrolled 183 healthy Caucasian subjects (median age 34 y [IQR 22, 50], range 11-70 y, 98 females) who underwent both global and AHA segment-based native T1 and T2 mapping at 3 T. T1 was assessed using Modified Look-Locker Inversion-Recovery sequence, MOLLI 5s(3s)3s, while T2 was performed using a gradient spin-echo (GraSE) protocol with echo-planar-imaging readout. Assessment of T1 and T2 relaxation times was highly reproducible, with low intra- and interobserver, scan-rescan, and test-retest variability. Mean global T1 was 1238 ± 28 ms, and median global T2 was 45.4 ms [44.3, 46.8]. T1 was significantly higher in women than in men (1245 ± 28 ms vs. 1230 ± 7 ms, P < 0.001), while T2 did not differ significantly (45.3 ms [44.2, 46.6] vs. 45.6 ± 2.2 ms, P = 0.453). Segmental analysis showed higher T1 and T2 values in the septum than in the lateral wall (P < 0.005). Subtle associations of age with T1 and T2 were observed. CONCLUSION: This single-center study supports the use of sex- and segment-specific reference values for standardized T1-MOLLI and T2-GraSE mapping at 3 T to facilitate the characterization of myocardial pathologies, while age seems to be negligible.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is associated with marked inter-patient heterogeneity in ventricular electrophysiology, contributing to arrhythmic risk that is insufficiently captured by current clinical methods. Electrocardiographic imaging (ECGI) provides high-density body surface potential (BSP) measurements but remains largely descriptive. Computational modelling offers a mechanistic framework to interpret BSP signals in terms of underlying tissue-level properties. METHODS AND FINDINGS: We developed a BSP-driven workflow to construct patient-specific electrophysiology (EP) models of HCM by integrating multimodal clinical imaging with Bayesian model calibration. Anatomically detailed torso-heart finite-element models were generated for 17 HCM patients using thoracic computed tomography (CT), cardiac magnetic resonance imaging (CMR), and 252-electrode BSP recordings. Ventricular depolarisation and repolarisation were simulated using a reaction-eikonal (RE) formulation coupled to a biophysically detailed ToR-ORd-dynCl ionic model. Emulator-based Bayesian history matching (HM) was used to personalise EP parameters, with staged calibration of QRS and T-wave morphology informed by targeted sensitivity analysis. The calibrated cohort reproduced clinical BSP morphology with Pearson correlation coefficient (PCC) [Formula: see text] for a median of 94.0% (IQR: 91.6 to 96.8%) of electrodes, achieving a median PCC of 0.89 (IQR: 0.80 to 0.94) across the full 252-electrode vest. Calibration substantially reduced uncertainty in the high-dimensional EP parameter space while yielding physiologically plausible conduction and repolarisation properties. Models calibrated exclusively to sinus rhythm robustly generalised to right-ventricular (RV) apical pacing without parameter retuning, reproducing clinically observed pacing-induced trends in depolarisation and repolarisation. Exploratory analysis revealed biologically consistent associations between inferred EP parameters and patient demographics. CONCLUSIONS: This study demonstrates that high-density BSP data can be used to functionally personalise mechanistic EP in HCM. The framework captures intrinsic patient-specific EP properties and generalises beyond the calibration condition, supporting its use for mechanistic investigation of arrhythmogenic substrate.

Cardiac lipid metabolism is fundamental to myocardial energy homeostasis, with fatty acid oxidation (FAO) supplying the majority of ATP in the healthy adult heart. This review synthesizes the core regulatory network governing cardiac lipid metabolism, encompassing lipid droplet dynamics mediated by perilipins (e.g., Plin5, Plin2), fatty acid uptake via CD36, systemic lipid modulation by apolipoproteins (e.g., APOC3), and the central energy-sensing AMPK/PGC-1α/PPARα axis. Dysregulation of this network initiates a self-perpetuating lipotoxic cycle, characterized by the accumulation of toxic lipid intermediates (e.g., diacylglycerols, ceramides), oxidative stress, and inflammatory activation, which serves as a common pathological mechanism across diverse cardiovascular diseases (CVDs), including atherosclerosis, heart failure, diabetic cardiomyopathy, and ischemic injury. Emerging from this mechanistic understanding is a promising landscape of biomarkers-such as specific ceramide species, the ApoB/ApoA-1 ratio, and circulating perilipins-and targeted therapeutic strategies, including APOC3 inhibitors, SGLT2 inhibitors, and Plin5-directed therapies. Future advances will depend on integrating multi-omics technologies and precision medicine approaches to tailor interventions to specific metabolic phenotypes, thereby opening new avenues for the prevention and treatment of CVDs.

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) refers to further damage to myocardial cells caused by multiple factors after blood flow is restored to the ischemic myocardium. Currently, there is a lack of effective treatment strategies in clinical practice. While microRNA (miRNA) is recognized as pivotal regulators, current therapeutic strategies rarely harness its network properties or systemic communicative roles. PURPOSE: To summarize how traditional Chinese medicine (TCM) employs multi-target mechanisms to modulate miRNA networks against MIRI, and to elucidate its systemic cardioprotective effects mediated by extracellular vesicle (EV)-carried miRNAs, thereby providing a rational framework for future drug development. METHODS: Following PRISMA guidelines, a systematic review of preclinical studies (2015-2025) from PubMed, Web of Science, CNKI, Wanfang, and VIP was conducted, focusing on miRNA-mediated mechanisms in MIRI. RESULTS: Analysis of 53 studies indicates that pharmacological agents-notably various TCM compounds-can coordinately regulate clusters of cardiac miRNAs (e.g., miR-21, miR-133) to synergistically attenuate apoptosis, oxidative stress, and inflammation. Beyond direct cardiac modulation, evidence also indicates that medicines can remotely affect the heart by altering the EV miRNAs secreted by cells in different tissues or organs. CONCLUSIONS: A two-tiered therapeutic framework is proposed: 1) network synergy targeting: simultaneously modulating interrelated miRNA hubs within the heart; and 2) systemic communication targeting: guiding EV miRNA cargo to restore systemic signaling. TCM research strongly supports this paradigm, offering a novel roadmap for developing MIRI therapeutics that combine direct cardiac repair with systemic crosstalk.

Cardiac sarcoidosis is a potentially fatal inflammatory disorder with the tendency to mostly affect the myocardial tissues. It is commonly associated with extra-cardiac structures such as the lungs and the thoracic lymph nodes; however, when it manifests as an isolated disease, it can be insidious. The clinical presentation is variable depending on the location and extent of the cardiac tissues involved, including asymptomatic cases, conduction abnormalities, arrhythmia, heart failure and sudden cardiac death (SCD). It is an enigmatic disease to diagnose owing to the variable clinical presentation; as a result, most centres are adopting a multidisciplinary approach to diagnosis, risk stratification and management. The mainstay of treatment in CS is immunosuppression, guideline-directed medical therapy for patients with heart failure in addition to device therapy for individuals at high risk of SCD, and heart transplantation for patients with advanced heart failure. We synthesise the existing evidence in the diagnosis and management of cardiac sarcoidosis in our review.

Ischemic stroke is a serious complication of atrial fibrillation that is associated with substantial morbidity and mortality. For patients with non-valvular atrial fibrillation, treatment with a direct oral anticoagulant (DOAC) is first line treatment for stroke prevention. Ischemic strokes can still occur, however, despite appropriate anticoagulation-an event known as a breakthrough stroke. In this review, we provide an examination of breakthrough stroke through its epidemiology, mechanisms by which breakthrough strokes happen, and a framework for classification. We then propose a systematic, stepwise algorithm to investigate breakthrough stroke, including standardized criteria to identify an ideal population for future clinical trials using the AF-BREACH criteria (Atrial Fibrillation related BReakthrough Embolic Stroke despite appropriate anticoagulation without alternative Cause identified). Lastly, we discuss the emerging evidence for pharmacological and non-pharmacological management strategies.

BACKGROUND: This study evaluates national trends in heart failure (HF) and psychoactive substance abuse-related mortality among adults aged 25 years and older in the United States (US) from 1999 to 2023, stratified by sex, age, race/ethnicity, geographic regions, and the COVID-19 pandemic period. METHODS: Data from 1999 to 2023 were extracted from the CDC WONDER database. Age-adjusted mortality rates (AAMR) and annual percentage changes (APC) were calculated using Joinpoint regression. ICD-10 codes I50, I50.1, I50.9 (Heart Failure), and F10-19 (Psychoactive Substance Use) were used to identify the conditions. RESULTS: A total of 771 739 deaths were recorded from 1999 to 2023 among individuals aged 25 and older. Most deaths occurred in medical facilities (39.24%), followed by decedents' homes (34.14%), long-term care facilities (16.30%), hospice (6.65%), and other settings (3.67%). The AAMR increased markedly from 1.68 in 1999 to 20.7 in 2023 (AAPC of 12.09, 95% confidence interval [CI]: 10.97-14.26). A substantial increase was observed from 1999 to 2005 (APC: 38.5%, 95% CI: 29.1-55.8), followed by a slower increase until 2020 (APC: 5.68%, 95% CI: 5.02-14.8). Men showed consistently higher AAMRs than females (18.8 vs. 8.65). By age group, mortality was highest among individuals aged 65 years and older. CONCLUSION: Using CDC WONDER data (1999-2023), we found a sharp rise in HF mortality linked to psychoactive substance abuse, from 1.68 to 20.7 per 100 000. Mortality burden was highest among males, older adults, non-Hispanic White individuals, and rural populations, highlighting widening demographic and geographic disparities.

INTRODUCTION: Recreational drug use is rising globally, with significant cardiovascular implications. Sympathomimetic substances such as cocaine, amfetamine(amphetamine)-type stimulants and synthetic cathinones are increasingly associated with emergency department presentations and acute cardiac events. Despite this growing burden, standardized guidance for diagnosing and managing acute sympathomimetic recreational drug-related cardiovascular complications remains limited. METHODS: A narrative review of the literature was conducted to identify acute cardiovascular complications associated with commonly used recreational drugs. A PubMed search was performed from database inception to 1 March 2024 using combinations of cardiovascular symptoms and cardiovascular complications with terms related to sympathomimetic recreational drug use. RESULTS: These substances exert potent sympathomimetic effects through catecholamine excess, and cause receptor activation, ion channel interference, and direct myocardial toxicity. Cocaine additionally induces vasospasm and thrombosis via endothelin-1 and causes sodium channel and potassium channel blockade. Amfetamine-type stimulants and synthetic cathinones amplify catecholamine release, contributing to arrhythmia, ischemia, and myocardial injury. Acute cardiovascular manifestations include chest pain, acute coronary syndrome, arrhythmias, cardiomyopathy, and sudden cardiac death. Presentations often mimic classical cardiac syndromes but may be more severe, especially in younger patients without traditional risk factors. Diagnosis begins with detailed history-taking, although self-reported drug use is frequently unreliable. Depending on symptoms, electrocardiography, cardiac biomarkers and echocardiography may be essential for risk stratification and identifying the underlying pathology. Toxicological testing may be considered when clinically indicated and should be interpreted in conjunction with clinical findings. For cocaine associated chest pain patients, risk stratification with the HEART pathway may guide safe discharge in low-risk cases. Management should be individualized based on the specific recreational drug involved and the presenting symptoms. Sedation, antihypertensives, and dual antiplatelet therapy are foundational, with vasodilators when indicated. Beta-blockers with alpha-blocking properties may be benefici

BACKGROUND: Angina with no obstructive coronary artery disease (ANOCA) is associated with persistent symptoms and impaired quality of life. Although guidelines advocate a patient-centered, multidisciplinary approach, randomized evidence is lacking. OBJECTIVES: The aim of this study was to determine whether a multidomain lifestyle intervention improves patient-reported health status and quality of life in patients with ANOCA. METHODS: SAMCRO was a prospective, multicenter, randomized trial with blinded endpoint assessment. Patients with angina and invasive evidence of coronary microvascular dysfunction and/or coronary vasomotor disorder were randomized 1:1 to endotype-guided therapy plus a structured multidomain lifestyle intervention (intervention group) or endotype-guided therapy alone (control group). The intervention integrated exercise training, Mediterranean dietary counseling, and psychological support. The primary endpoint was the change in Seattle Angina Questionnaire summary score. RESULTS: A total of 123 patients were randomized (62 to intervention and 61 to control), with follow-up completed at 12 months for the primary endpoint. The mean age was 65.8 ± 9 years, and 46% were women. The adjusted mean improvement in Seattle Angina Questionnaire summary score was significantly greater in the intervention group (between-group difference: 13.12 points; 95% CI: 9.68-16.56; P < 0.001). A clinically meaningful improvement (≥10-point increase) was achieved in 48 (77%) versus 23 (38%) of patients, respectively (adjusted risk ratio: 1.98; 95% CI: 1.20-3.26; P < 0.001). Significant improvements were also observed in the EuroQol 5-Dimension 5-Level index and Beck Depression Inventory scores. CONCLUSIONS: In patients with invasively confirmed ANOCA, a structured multidomain lifestyle intervention provided clinically meaningful improvements in patient-reported health status on top of endotype-guided medical therapy. REGISTRATION: (Standardizing the Management of Patients With Coronary Microvascular Dysfunction [SAMCRO]; NCT06025994).

BACKGROUND: Ischemic heart disease and cardiac arrhythmias are major contributors to cardiovascular mortality in the United States. Understanding long-term national trends and demographic disparities is essential for guiding prevention strategies and public health policies. METHODS: A retrospective cross-sectional analysis was conducted using mortality data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database from 1999 to 2024. Deaths in which IHD and a cardiac arrhythmia were both recorded were identified using ICD-10 codes. Crude mortality rates and age-adjusted mortality rates per 100,000 population were calculated. Temporal trends were assessed using Joinpoint regression to estimate annual percent change (APC) and average annual percent change (AAPC). Mortality patterns were further stratified by sex, race/ethnicity, age group, geographic region, and urbanization status. RESULTS: A total of 1 885 917 deaths were attributed to IHD and cardiac arrhythmias between 1999 and 2024. The overall AAMR declined from 41.97 in 1999 to 31.75 in 2024. Mortality decreased substantially from 1999 to 2009, stabilized through 2018, and increased sharply during 2018-2021 before declining again through 2024. The cumulative AAMR was 45.09 among males and 23.33 among females. Mortality varied across racial and ethnic groups, geographic regions, urbanization levels, and age groups. CONCLUSION: Although overall mortality related to IHD and cardiac arrhythmias has declined over the past two decades, demographic and geographic differences persist. The temporary rise during 2018-2021 coincided with the COVID-19 pandemic period and underscores the need for sustained prevention strategies and equitable healthcare access.

BACKGROUND: Cardiac damage (CD) is prevalent across the spectrum of aortic stenosis (AS) and is a strong predictor of adverse outcomes. The natural history of CD in early AS and drivers of its progression, are poorly defined. We aimed to identify predictors and the prognostic significance of CD progression in patients with non-severe AS. METHODS: This was a single centre cohort study with longitudinal follow-up. Patients with mild or moderate AS at baseline and over serial echocardiographic follow-up were evaluated for the presence and progression of CD over time. RESULTS: 1751 patients were included. At baseline, CD was present in 1320 (75%), categorized as stage 1 in 231 (13%), stage 2 in 672 (38%), stage 3 in 109 (6%) and stage 4 in 308 (18%). Over a median follow-up of 2.1 [Q1-Q3 1.1-3.6] years, the prevalence of advanced-stage (stages 3 and 4) CD increased from 24% to 30%. Factors associated with progression to advanced-stage CD included comorbidity burden (adjusted OR [aOR] 1.23 per additional comorbidity; 95% CI: 1.10-1.38; p < 0.001) and the presence of atrial fibrillation (aOR 3.23; 95% CI: 1.15-9.07, p = 0.024) or left atrial dilation (aOR 1.55; 95% CI: 1.11-2.16, p = 0.010)], but not AS severity. Progression of CD was independently associated with all-cause mortality (adjusted HR [aHR] 1.35; 95% CI: 1.07-170; p = 0.012). CONCLUSIONS: In non-severe AS, CD is common and frequently progresses over time. CD progression appears to be driven by comorbidities and pre-existing myocardial remodelling and is an independent predictor of all-cause mortality.

BACKGROUND: Although recent large-scale randomized trials have demonstrated that sodium-glucose cotransporter 2 (SGLT2) inhibitors following acute myocardial infarction (AMI) are safe, the mechanisms underlying their potential cardioprotective effects remain poorly understood. OBJECTIVES: The aim of this study was to evaluate the effects of SGLT2 inhibitor therapy on myocardial injury and left ventricular (LV) remodeling in AMI patients undergoing percutaneous coronary intervention (PCI), using cardiac magnetic resonance imaging (CMR). METHODS: In this prospective, open-label, randomized controlled trial, patients ≥18 years of age at high risk for heart failure after successful PCI for AMI were randomly assigned to receive empagliflozin 10 mg once daily or not. The primary endpoint was infarct size (% LV mass) assessed by CMR at 6-month follow-up. The coprimary endpoint was a difference in LV end-systolic volume measured by CMR between baseline and 6 months (ΔLV end-systolic volume). RESULTS: A total of 200 patients underwent randomization, with 100 assigned to the SGLT2 inhibitor group and 100 assigned to the control group. CMR assessments for 6 months were available for 169 patients (84.0%) of the total study population (89 patients in the SGLT2 inhibitor group and 80 patients in the control group). Compared with control, SGLT2 inhibition did not reduce infarct size (% LV mass) at 6-month follow-up (SGLT2 inhibitor vs control, 12.5% [8.5%-20.9%] vs 12.9% [5.0%-20.7%]; P = 0.92). There was no significant difference in ΔLV end-systolic volume between the 2 groups (SGLT2 inhibitor vs control, -3.3% [-19.7% to 13.6%] vs -6.8% [-23.4% to 10.6%]; P = 0.40). CONCLUSIONS: Among patients with AMI undergoing PCI who were at high risk for heart failure, SGLT2 inhibitor use did not reduce infarct size or facilitate reverse LV remodeling at 6 months as assessed by CMR. (Peri-Treatment of SGLT-2 Inhibitor on Myocardial Infarct Size and Remodeling Index in Patients With Acute Myocardial Infarction and High Risk of Heart Failure Undergoing Percutaneous Coronary Intervention [PRESTIGE-AMI]; NCT04899479).

A 55-year-old woman with chronic respiratory failure due to diffuse panbronchiolitis, on a lung transplant waitlist, developed acute left ventricular failure with an ejection fraction of 18%. Although cardiac reversibility was uncertain, it was considered potentially reversible and transplant eligibility was judged to be maintainable; therefore, veno-arterial extracorporeal membrane oxygenation with Impella was initiated as extracorporeal life support (ECLS), with combined support selected to prevent left ventricular distension and provide circulatory stabilization. Cardiac function improved, and she was successfully weaned from ECLS, subsequently undergoing bilateral lung transplantation. In this case, the decision to initiate ECLS was determined not only by the need for life-saving circulatory support but also by the simultaneous assessment of cardiac reversibility and the feasibility of maintaining transplant eligibility. This case highlights the importance of integrating these considerations in selecting appropriate candidates for ECLS as a bridge-to-decision.

PURPOSE: To evaluate the efficacy and safety of early aspirin discontinuation followed by P2Y12 inhibitor monotherapy versus standard dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). METHODS: This systematic review and meta-analysis followed PRISMA 2020 guidelines and a prespecified protocol registered in PROSPERO (CRD420261293472). MEDLINE, Embase, Scopus, and CENTRAL were searched through December 2025 for randomized controlled trials comparing early aspirin discontinuation (≤ 3 months) with standard DAPT in ACS patients undergoing PCI with drug-eluting stents. Two reviewers independently conducted study selection, data extraction, and risk of bias assessment (Cochrane RoB 2.0). Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using a random-effects model. RESULTS: Seven trials including 20,501 patients (10,246 early discontinuation; 10,255 standard DAPT) were analyzed. Early aspirin discontinuation significantly reduced bleeding (RR, 0.46; 95% CI, 0.36-0.60; p < 0.001; I²=21.9%). There was no significant difference in major adverse cardiovascular events (RR, 0.98; 95% CI, 0.77-1.26) or in myocardial infarction, stroke, repeat revascularization, or all-cause mortality. However, early aspirin discontinuation was associated with an increased risk of stent thrombosis (RR, 1.72; 95% CI, 1.07-2.78). In trials with aspirin discontinuation within 1 month, bleeding reduction remained substantial, with numerically higher but nonsignificant ischemic outcomes. CONCLUSION: In ACS patients undergoing PCI, early aspirin discontinuation reduces bleeding without a statistically significant increase in overall ischemic events; however, a significant increase in stent thrombosis was observed. These results support individualized decision-making, particularly favoring patients at high bleeding risk and low thrombotic risk treated with potent P2Y12 inhibitors. Further adequately powered studies focused on rare ischemic outcomes, including stent thrombosis, are warranted.

Human kidney potassium (K+) handling evolved to clear massive Paleolithic loads, functioning as a high-capacity survival mechanism to prevent lethal hyperkalemia. This review elucidates the molecular machinery underlying this adaptation, identifying the WNK-SPAK-OSR1 kinase network as the central regulator. We detail how the distal convoluted tubule functions as a sensory organ, utilizing an "NCC switch" driven by intracellular chloride to resolve the "aldosterone paradox". This adaptation ensures K+ secretion is prioritized over Na+ reabsorption during high intake. Furthermore, we examine the roles of the gut-kidney axis and the molecular circadian clock as anticipatory feed-forward mechanisms that prime the kidney for excretion prior to absorption. This framework integrates the flow-dependent gating of BK channels, the acid-base sensitivity of ROMK, and the electroneutral pendrin/KCC3a pathway as redundant "fail-safe" valves necessary to clear massive Paleolithic K+ loads. Finally, we conclude that while the modern diet rarely challenges this massive excretory potential, the machinery remains biologically wired to prioritize the purging of K+, ensuring survival by preserving resting membrane potential above all else.

BACKGROUND: Chronic kidney disease (CKD) progresses via complex mechanisms, including oxidative stress and impaired antioxidant defenses. We aimed to investigate longitudinal changes in serum and urinary levels of superoxide dismutase (SOD), catalase, and glutathione in children with CKD, and to assess their relationship with heat shock proteins (HSPs), which we have previously reported to be altered in this population. METHODS: A total of 117 children with CKD and 56 healthy children were enrolled in the study. The CKD group was followed prospectively for 24 months. Serum and urinary levels of SOD, catalase, and glutathione were measured using ELISA at baseline, 12 months, and 24 months. Longitudinal changes and associations with kidney outcomes and CKD progression were analyzed using mixed-effects and logistic regression models. RESULTS: Serum SOD and catalase levels, as well as urinary SOD, catalase, and glutathione levels were higher in the CKD group than in the control group. Serum and urinary SOD and catalase levels steadily decreased over time, similarly to urinary HSP levels. Most antioxidant biomarkers were not significantly associated with longitudinal kidney outcomes. However, higher longitudinal urinary catalase levels were modestly associated with better kidney function over time, and higher baseline urinary catalase was independently associated with a lower risk of CKD progression. In contrast, higher baseline serum SOD levels were associated with an increased risk of progression. Antioxidant biomarkers showed strong correlations with serum and urinary HSP levels. CONCLUSION: Although urinary catalase consistently associates with kidney function and CKD progression, most antioxidant biomarkers alone have limited predictive value. Children with CKD show altered antioxidant defenses that decline over time, and their correlations with HSPs suggest that they may act together in response to oxidative stress.

BACKGROUND: The global burden of chronic kidney disease (CKD) is rising, disproportionately impacting on low- and middle-income countries. In African populations, use of serum creatinine to estimate glomerular filtration rate (GFR) significantly underestimates CKD prevalence, contributing to its under-recognition as a health problem. Serum cystatin C provides more accurate estimates of Iohexol measured GFR than creatinine. Early diagnosis and treatment of CKD is essential to reduce premature morbidity and mortality. However, little is known about risk factors for CKD development and progression in Africa owing to limited longitudinal data. This study aims to determine risk factors for progressive kidney function decline among adults living in rural, northern Malawi. METHODS: This protocol describes a prospective study being conducted in a general population Health and Demographic Surveillance Site in rural Karonga, Malawi (2024-2025). Eligible participants are adults aged 18 years and over who participated in two population-based surveys of long-term health conditions (2013-2016 and 2021-2025), with availability of baseline measures. New household-level data is being prospectively collected on CKD risk factors, alongside blood and urine samples. Cystatin C and creatinine will be tested on individual-level paired, stored serum samples collected at three longitudinal time points. Urine will undergo dipstick urinalysis, microscopy and testing for albumin and creatinine to quantify proteinuria. The primary outcome will be sustained 25% reduction in estimated GFR (eGFR) from baseline and change in eGFR category, determined using serum cystatin C. Multivariable logistic regression will be used to determine effect size estimates of key risk factors for kidney function decline. DISCUSSION: This study will provide important data on risk factors for eGFR decline and CKD progression amongst Malawian adults. The findings will inform future research into important context-specific risk factors, and could directly inform health policies in Malawi for targeting CKD screening, prevention and treatment strategies to high-risk patient groups.

Pulmonary hypertension (PH), defined as a mean pulmonary artery pressure >20 mmHg, is a common comorbidity in patients with chronic kidney disease (CKD). The prevalence of PH increases as kidney function declines, and PH is associated with a higher risk of cardiovascular complications and mortality. The pathophysiology of PH in CKD has not been studied in detail primarily because studies incorporating right heart catheterization, the gold-standard test for diagnosing and phenotyping PH, are rare and therefore data regarding the hemodynamic phenotypes of PH in CKD patients are sparse. Factors such as left-sided heart failure, anemia, and the presence of arteriovenous fistulas all likely play a role in the development of PH in CKD patients. As pressures in the pulmonary arteries increase, maladaptive changes such as hypertrophy and dilation occur in the right ventricle to maintain cardiac output, eventually leading to clinical heart failure and death. While this pathologic cycle is well characterized in PH patients, there are few data on longitudinal changes in the right ventricle in patients with PH and CKD. There are no specific treatments that have been evaluated for PH in the CKD population although there are several strategies which may mitigate the effects of PH including improved volume management, reduction in flow of high-flow arteriovenous fistulas, and potentially kidney transplantation. The role of medications used for pulmonary arterial hypertension in patients with CKD is unclear as they were excluded from most clinical trials of these therapies. More research is needed including the characterization of longitudinal right ventricular changes in CKD patients, refinement of the molecular pathways implicated in the pathogenesis of PH, fistula flow rates which put patients at risk for the development of PH and clinical trials of PH therapies in patients with CKD.

BACKGROUND: Airway diseases, including asthma and chronic obstructive pulmonary disease (COPD) are global public health burden due to their high prevalence, morbidity, and mortality. Although these conditions are clinically distinct, they share key pathogenic mechanisms, including chronic inflammation, oxidative stress, and airway remodeling. Continuous exposure of the lungs to environmental agents and pathogens increases their susceptibility to injury and dysregulated immune responses, thereby promoting chronic disease progression. Environmental factors, including cigarette smoke and air pollution, can induce epigenetic changes that act as intermediaries between external insults and disease phenotypes. These epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs, regulate gene expression without altering the DNA sequence. By modulating chromatin structure and transcriptional activity, they influence immune function, lung homeostasis, and disease susceptibility, thereby contributing to persistent inflammation, airway remodeling, and variability in therapeutic responses. MAIN BODY: Advances in epigenetics have led to the identification of novel biomarkers and potential therapeutic targets, offering new perspectives for diagnosis and treatment. We provide a comprehensive overview of the most recent advances in this field. REMARKS: Current evidence and emerging insightsh discussed in this review might facilitate the understanding of how epigenetic alterations contribute to the biological mechanisms of respiratory diseases and help future research priorities.

PURPOSE: To evaluate the use of mechanical thrombectomy (MT) in patients who require veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for the management of acute high-risk pulmonary embolism. MATERIALS AND METHODS: This retrospective case series included patients who underwent VA-ECMO followed by MT for the treatment of pulmonary embolism between January 2017 and December 2025. Clinical, laboratory, and imaging data were collected from the electronic medical record. Outcomes included 30-day mortality and procedural complications. Potential risk factors for mortality were evaluated. Exploratory analyses between survivors and non-survivors were performed using the Mann-Whitney U test for continuous variables and Fisher's exact test for categorical variables. RESULTS: A total of 20 patients met inclusion criteria. The mortality rate was 15% (n=3) at 48 hours, 35% (n=7) at 30 days, and 45% (n=9) at six months. Procedure-related complications were present in 45% (n=9) of patients. Acute bleeding events occurred in 30% (n=6) of patients, and neurologic events occurred in 15% (n=3) of patients following ECMO cannulation and MT. No variables evaluated were significantly associated with mortality. CONCLUSION: In this single-center retrospective cohort, patients undergoing MT while supported with VA-ECMO for high-risk pulmonary embolism demonstrated a 30-day mortality of 35%. Further studies including matched controls and larger cohorts are needed to better define the role of MT in this critically ill population.

BACKGROUND: Cystic Fibrosis (CF) and primary ciliary dyskinesia (PCD) are congenital disorders characterized by impaired mucociliary clearance, resulting in chronic airway infection, inflammation, and progressive lung damage. CF lung disease involves defective CFTR function throughout the entire airway epithelium, whereas PCD originates from dysfunction of motile respiratory cilia located predominantly in proximal airways. Diagnostic tools such as FEV1 lack sensitivity to detect early peripheral lung damage. Lung clearance index (LCI), obtained via multiple breath washout (MBW), has emerged as a promising marker for early detection of lung abnormalities. OBJECTIVES: To compare LCI between age and FEV1-matched people with (pw) CF and PCD (without highly effective CFTR modulator treatment), hypothesizing more abnormal LCI in CF due to more peripheral airway involvement. Secondary objectives included comparing phase III slope parameters (Scond x VT, Sacin x VT) to explore ventilation inhomogeneity and localization of lung disease. METHODS: This retrospective cross-sectional study included pwCF and pwPCD aged 6-20 years with available MBW and spirometry data (2011-2024). RESULTS: PwCF (n23, median age 14.4 y) had similar FEV1 z-scores compared to 23 pwPCD (median age 14.4 y) (-0.1 vs. -1.1, p: 0.33). LCI values were more abnormal in the CF group compared to the PCD group (7.8 vs. 7.1; p: 0.04). FEF25-75%pred and phase III slope parameters were not significantly different, though a trend toward higher Scond x VT in CF was noted (0.08 vs. 0.06; p: 0.11). CONCLUSION: Despite similar FEV1 abnormalities, reflecting proximal airway impairment, pwCF exhibit greater peripheral airway involvement than pwPCD, as indicated by higher LCI values.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD) with poor prognosis. Radiological pleuroparenchymal fibroelastosis (PPFE)-like findings, characterised by upper-lobe subpleural fibrosis, have been associated with worse outcome in IPF. While short leukocyte telomere length (LTL) is a recognised prognostic factor, its relationship with PPFE-like findings remains unclear. METHODS: We conducted a secondary analysis of an ongoing ILD cohort. IPF patients who underwent LTL measurement by quantitative PCR were classified into those with PPFE-like findings on high-resolution computed tomography (IPF/PPFE group) and those without such findings (IPF/usual interstitial pneumonia (UIP) group). Clinical characteristics, pulmonary function, telomere length and outcomes were compared. Age-adjusted LTL was evaluated using healthy controls. Prognostic factors were analysed using Cox regression. RESULTS: Among 179 IPF patients, 29 (16%) were assigned to the IPF/PPFE group. Compared to the IPF/UIP group (n=150), the IPF/PPFE group had lower body mass index and forced vital capacity, and significantly shorter LTL (p=0.002), with more patients below the 10th percentile of healthy controls (37.9% versus 12.0%). The IPF/PPFE group showed greater respiratory functional decline and higher mortality (65.5% versus 25.3%, p<0.001). In survival analysis, both PPFE-like findings and shortened LTL predicted worse outcomes; however, only PPFE-like findings remained independently associated with mortality in multivariate analysis. CONCLUSIONS: IPF patients with PPFE-like findings constitute a distinct high-risk phenotype with shorter telomeres, accelerated progression, and poor prognosis. These findings highlight the clinical importance of recognising PPFE-like changes and telomere biology in IPF for risk stratification and emphasise the need for close monitoring and early intervention.

Chemotherapy remains a cornerstone in cancer treatment, yet its associated toxic effects, particularly pulmonary complications, pose significant clinical challenges. Chemotherapeutic agents, either alone or in combination, can induce severe pulmonary toxicity through mechanisms involving direct cytotoxicity, oxidative stress, and inflammatory responses. Drug-induced lung injuries, including interstitial pneumonitis, acute respiratory distress syndrome, and fibrosis, are commonly observed, with agents such as bleomycin, cyclophosphamide, and busulfan. Approximately 10% of patients undergoing chemotherapy experience pulmonary complications, necessitating effective management strategies. Emerging evidence suggests that natural products, particularly antioxidants and plant-derived compounds like ellagic acid, can mitigate chemotherapy-induced pulmonary toxicity by counteracting oxidative stress and inflammation. We aim to summarize the toxic implications of chemotherapeutic drugs on the respiratory system, elucidating the underlying pathophysiological mechanisms. It also explores potential therapeutic interventions, including natural products, to reduce pulmonary toxicity. A thorough understanding of overall mechanisms will aid in the advancement of targeted strategies to improve the efficacy of cancer treatment while minimizing adverse effects.

PURPOSE: To identify risk factors for prolonged mechanical ventilation (PMV) after liver transplantation (LT) and to develop and internally validate a predictive nomogram. METHODS: A multicenter retrospective cohort of 746 LT recipients (January 2015-June 2023) was randomly split 7:3 into training (n = 522) and validation (n = 224) sets. We conducted univariate and multivariate logistic regression to identify factors linked to PMV. A risk nomogram was created based on the multivariate analysis, and its performance was evaluated for calibration, discrimination, and clinical utility, with internal validation using the Validation Set data. RESULTS: The incidence of PMV was 21.6%. Multivariate analysis identified five independent predictors of PMV: ASA scores ≥ 3, mechanical ventilation before LT, MELD score, albumin levels, and anhepatic phase. The nomogram developed from these predictors showed a concordance index (C-index) of 0.780 (95% CI, 0.734-0.827) and demonstrated good calibration. After internal validation, the model maintained a C-index of 0.731 (95% CI, 0.653-0.810). Decision curve analysis and clinical impact curve confirmed the nomogram's effectiveness. CONCLUSION: The nomogram enables individualized PMV risk estimation in LT recipients and may guide early intervention and resource allocation.

OBJECTIVE: To compare the total direct healthcare costs of nasal high flow (NHF) therapy and standard oxygen therapy (SOT) as first-line treatments for paediatric acute hypoxaemic respiratory failure (AHRF) and to identify what factors explain variations in these costs. DESIGN: Cost analysis following a randomised controlled trial. SETTING: 14 hospitals across Australia and New Zealand. PATIENTS: 1517 children aged 1-4 years admitted with AHRF between 18 December 2017 and 18 March 2020, enrolled in the Paediatric Acute Respiratory Intervention Study 2(PARIS-2) trial. INTERVENTIONS: Patients were randomised to receive either NHF or SOT. MAIN OUTCOME MEASURES: Total and average cost per patient admission for the two first-line treatments of AHRF. RESULTS: The total cost of treating the trial cohort was $A10 788 793 (US$7 660 143; €6 689 052; £6 041 724), corresponding to an average of $A7112 (US$5050; €4409; £3983) per patient. Average cost per patient admission was significantly higher in the NHF group at $A7815 (US$5549; €4845; £4376) compared with the SOT group at $A6419 (US$4557; €3980; £3595), with a mean difference of $A1396 (US$991; €866; £782, 95% CI $A419 to $A2372). Subgroup analyses showed that NHF non-responders, particularly those presenting with wheeze, incurred greater costs due to higher likelihood of intensive care admission and longer hospital stays. CONCLUSION: NHF costs more than SOT and does not lead to better clinical outcomes. Although NHF remains an important respiratory support modality for paediatric AHRF, its higher costs, particularly among those not responding to NHF, emphasise the need for more targeted use. TRIAL REGISTRATION NUMBER: ACTRN12618000210279.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of lung cancer, and type 2 diabetes mellitus (T2DM) is a common comorbidity in COPD patients. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have pleiotropic effects beyond glucose lowering. However, their association with lung cancer risk in patients with COPD and T2DM remains uncertain. RESEARCH QUESTION: Is SGLT2 inhibitor initiation associated with a lower risk of incident lung cancer in patients with COPD and T2DM? STUDY DESIGN AND METHODS: We conducted a nationwide population-based cohort study using the National Health Insurance Database, including adults aged ≥40 years with COPD and T2DM who initiated SGLT2 inhibitors or sulfonylureas between September 2014 and December 2023. The primary outcome was incident lung cancer. Secondary outcomes included severe COPD exacerbation and all-cause mortality. RESULTS: Among 14,927 patients (5,651 SGLT2 inhibitor initiators and 9,276 sulfonylurea initiators), 234 incident lung cancer events occurred during a median follow-up of 2.97 years. The 4-year cumulative incidence of lung cancer was 1.6% in the SGLT2 inhibitor group and 2.7% in the sulfonylurea group. Initiation of SGLT2 inhibitors was associated with a lower risk of incident lung cancer compared with sulfonylureas (IPTW HR 0.73; 95% CI, 0.60-0.90). SGLT2 inhibitor use was also associated with reduced risks of severe COPD exacerbation (IPTW HR 0.77; 95% CI, 0.71-0.83) and all-cause mortality (IPTW HR 0.81; 95% CI, 0.75-0.88). INTERPRETATION: In this nationwide cohort of patients with COPD and T2DM, initiation of SGLT2 inhibitors was associated with lower risks of lung cancer, COPD exacerbation, and all-cause mortality compared with sulfonylureas.

Study DesignPropensity score-matched retrospective cohort study.ObjectivesTo determine whether early cervical decompression is associated with in-hospital pulmonary embolism (PE) after traumatic cervical spinal cord injury (SCI).MethodsAdults with traumatic cervical SCI undergoing coded cervical decompression after direct admission were identified in the National Trauma Data Bank, 2019 to 2024. Early decompression was within 24 hours; delayed decompression was after 24 hours. Patients were matched 1:1 using 30 covariates. The primary outcome was detected in-hospital PE. Robustness analyses included sensitivity, subgroup, landmark, negative-control, competing-risk, clustered-error, bootstrap, and McNemar analyses.ResultsAmong 11,530 decompression-coded patients, matching yielded 4,480 balanced pairs. Early decompression was not associated with detected PE (OR 0.97, 95% CI 0.70 to 1.35; p = 0.868; absolute risk difference -0.04%, 95% CI -0.58% to 0.49%). Robustness analyses supported this null finding, including a null negative-control outcome (OR 1.10, 95% CI 0.75 to 1.62). No subgroup interaction was significant after multiplicity correction. In patients with Injury Severity Score ≥25, PE risk was similar (OR 0.88, 95% CI 0.56 to 1.39). Early decompression was associated with higher in-hospital mortality overall (OR 1.54, 95% CI 1.30 to 1.82), creating potential competing-risk bias.ConclusionsEarly cervical decompression after traumatic cervical SCI was not associated with increased detected in-hospital PE. PE risk alone should not justify delaying otherwise indicated decompression, but differential mortality and residual confounding require cautious interpretation and prospective confirmation.

INTRODUCTION: Invasive fungal infections (IFI) are becoming more and more frequent in the intensive care unit (ICU), affecting not only immunocompromised patients. Invasive pulmonary aspergillosis, invasive candidiasis, and mucormycosis are associated with substantial mortality. Management of these patients remains challenging because the histopathological confirmation is often unfeasible. Consequently, clinicians must rely on a probabilistic approach integrating host factors, clinical and radiological features, and mycological evidence. AREAS COVERED: This narrative review summarizes current evidence on the epidemiology, risk factors, definitions, diagnostic strategies, and management of critically ill patients with IFI. We discuss adaptations of diagnostic criteria for critically ill patients, with a special focus on performance and limitations of non-culture-based tools. Diagnostic work-up and therapeutic strategies are discussed with a focus on ICU-specific considerations. EXPERT OPINION: Management of IFI in the ICU requires an individualized approach combining early clinical suspicion based on clinical risk stratification, targeted use of culture and non-culture-based tests, and timely initiation of antifungal therapy. Refining risk stratification, validation of molecular diagnostics in large ICU cohorts, and multidisciplinary collaboration are warranted to improve outcomes in this highly vulnerable population.

BACKGROUND: Pulmonary function tests (PFTs), particularly spirometry, are the reference standard for assessing airflow limitation in respiratory diseases such as chronic obstructive pulmonary disease (COPD) and interstitial pulmonary disease. However, spirometry requires substantial patient cooperation and may be unreliable in children, the elderly, and patients with cognitive impairment, and its use was further limited during the COVID-19 pandemic. Dynamic chest radiography (DCR), which captures sequential thoracic images during respiration at low radiation dose, has emerged as a promising modality for evaluating respiratory dynamics, but its potential to quantitatively estimate pulmonary function through radiomic analysis remains insufficiently explored. PURPOSE: This study aimed to determine the potential of radiomic features of the lung on DCR to predict pulmonary function (FEV1, forced expiratory volume in the first second; FVC, forced vital capacity) and to classify patients at high risk (FEV1/FVC). METHODS: We retrospectively analysed data from 151 patients. The DCRs at end-inspiration (EI), end-expiration (EE), and the respiratory phase of maximum variation in the lung area from EI to EE (insp2expvmax) or from EE to EI (exp2inspvmax) were defined based on the lung area. A respiratory motion map was also calculated. To combine the defined DCR and respiratory motion map, feature extraction was performed, followed by the least absolute shrinkage and selection operator (LASSO). Predictive regression and classification models with various radiomic feature combinations (nos. 1-6) were constructed for pulmonary function. Pearson's correlation coefficients (R) were calculated for FEV1 and FVC, and the area under the curve (AUC) was calculated for FEV1/FVC. Our predictive models were compared using the conventional formula. RESULTS: We constructed a predictive regression and classification model for FEV1, FVC, and FEV1/FVC ratio using DCR images and a respiratory motion map. The model accuracy with DCR at each respiratory phase and the respiratory motion map-based radiomic features was better than that of the conventional method. CONCLUSIONS: In this single-center retrospective study, radiomic features extracted from DCR at multiple respiratory phases combined with respiratory motion maps showed promise for estimating pulmonary function, outperforming con

Chronic obstructive pulmonary disease (COPD) is optimally managed through a comprehensive, individualized, and adaptable treatment approach. This review summarizes current and emerging strategies in COPD care, emphasizing both pharmacologic and non-pharmacologic interventions aimed at relieving symptoms, reducing exacerbations, and improving quality of life. Long-acting bronchodilators remain the cornerstone of pharmacologic therapy, with combination long-acting β-agonists (LABA) and long-acting muscarinic antagonist (LAMA) therapy preferred as initial treatment for most patients with persistent dyspnea or exercise intolerance. Inhaled corticosteroids (ICS) are recommended for select patient phenotypes, particularly individuals with frequent exacerbations or elevated blood eosinophil levels. Triple therapy (LABA+LAMA+ICS) demonstrates significant benefits in reducing exacerbations and may provide mortality benefits in appropriately selected patients. Personalized treatment strategies guided by exacerbation history, blood eosinophil counts, and symptom burden have become central to contemporary COPD management. Novel biologic therapies targeting type 2 inflammation, including dupilumab and mepolizumab, have demonstrated efficacy in reducing exacerbations in patients with eosinophilic phenotypes who remain symptomatic despite optimized triple inhaler therapy. Bronchoscopic interventions, particularly endobronchial valve placement for lung volume reduction, offer meaningful improvements in lung function and quality of life for carefully selected patients. Despite these advances, significant challenges persist, especially in resource-limited settings. Barriers include limited access to guideline-recommended therapies, difficulties in managing comorbidities, inadequate implementation of pulmonary rehabilitation programs, and broader health system constraints continue to impact optimal disease management.

Recommended performance validity test (PVT) cutoffs may vary across examinee characteristics. This study evaluated Word Choice (WC) and Test of Memory Malingering Trial 1 (TOMM T1) cutoffs in a diverse clinical sample (41% Hispanic/Latino, 26% English/Spanish bilingual, education: 5-20 years). Logistic regressions examined predictors of performance using established cutoffs. Older age predicted reduced odds of WC valid performance. Higher education predicted increased odds of WC and TOMM T1 valid performance. Ethnicity and language were not statistically significant predictors. WC false positive rates were low (4.8%-6.5%) and did not differ by ethnicity or language. TOMM T1 false positives were higher in Hispanic/Latino and bilingual participants (13.5%-14.3%) compared to Non-Hispanic/Latino and monolingual participants (9%-10%); differences were nonsignificant. WC and TOMM T1 cutoffs appear appropriate for Hispanic/Latino and bilingual examinees, though caution is warranted given elevated TOMM T1 false positives and risk of misclassification in examinees with less education.

AIMS/BACKGROUND: Perinatal Mood and Anxiety Disorders (PMADs) are among the most common complications of childbirth. Intensive Outpatient Programming (IOP) treats the most acute/severe PMADs while fostering birthing patient-infant relationships. As perinatal psychiatric treatments expand, non-birthing partners are critical to include and serve, both for their own PMADs risk and to support birthing patients. DESIGN/METHODS: This quality improvement study describes the development and early implementation of a 1-3 session program, termed Partner Project, serving patients in a perinatal IOP and their partners. Treatment goals were to: improve partner understanding of PMADs/treatment, promote partner well-being and contact with services, cultivate partner skills for patient support, and foster intimate relationship functioning. Couples (n = 17) participated, with measures of anxiety, depression, bonding, and program feedback. RESULTS: The final protocol involves two sessions with both partners beginning during early/middle IOP treatment and ending around graduation. Patient anxiety, depression, and bonding symptoms began in clinical ranges and significantly decreased after treatment. On average, no partner questionnaires (baseline only) were in clinical ranges, though prompted important discussions about thoughts of self-harm, coping, and partner mental health. Referrals were requested/provided to individual, couples, and fathering group therapies. Feedback forms were not required (patient n = 6, partner n = 4), though indicated high levels of satisfaction and provided qualitative information on treatment experiences. CONCLUSIONS: Partner Project sessions adapted evidence-based couple-based interventions to the perinatal IOP context, and demonstrated treatment interest and satisfaction. Patients, partners, and infants stand to benefit from including and addressing partner PMADs and relational functioning within perinatal mental health treatment.

AIMS: This meta-synthesis of qualitative studies aimed to explore the experiences and perspectives of healthcare providers in the Intensive Care Unit (ICU) setting regarding the implementation of early mobilization. DESIGN: A qualitative systematic review and meta-synthesis was conducted. The review protocol was registered with PROSPERO (CRD420251057721). DATA SOURCES: Six databases (PubMed, EMBASE, Web of Science, CINAHL, CNKI and Wanfang Data) were searched from inception to March 5, 2025. A total of 759 records were identified, and 34 studies met the eligibility criteria and were included in the final meta-synthesis. REVIEW METHODS: We evaluated the quality of the included studies using the Critical Appraisal Skills Programme-Qualitative Research Checklist. RESULTS: Thirty-four studies conducted in 13 countries and involving 699 ICU healthcare providers were included. Four analytical themes were generated: characteristics of early mobilization, the inner setting of implementation, the key role system and core determinants of successful implementation. CONCLUSION: Early mobilization in ICUs should be understood as a multidimensional implementation process rather than a single rehabilitation task. Sustainable practice depends on the characteristics of the intervention, organizational readiness, clearly defined interprofessional roles, patient engagement and process-level strategies such as preplanning, real-time monitoring, debriefing and feedback. The findings support the development of context-sensitive implementation strategies to translate early mobilization evidence into routine ICU care. IMPACT: This review underscores the critical importance of organizational support, team collaboration mechanisms and the professional capacity building of healthcare providers in advancing early mobilization within ICU settings. Frontline clinicians should be equipped with targeted training and structured planning tools, while leadership is encouraged to foster a culture of shared responsibility and continuous improvement. PATIENT OR PUBLIC CONTRIBUTION: This qualitative systematic review did not involve original patients or the public. Therefore, this is not applicable.

BackgroundAdolescent psychiatric hospitalisation is often organised as if one patient had entered the ward while the family remained outside. This may stabilise acute symptoms but can intensify relational rupture, institutional dependency and weakened parental agency.ObjectiveThis paper presents the Admitted Family Model, hereafter referred to as the AFM, as a clinical-conceptual framework for adolescent inpatient care.ApproachThe AFM is developed from sustained clinical observation, multidisciplinary reflection, supervision, teaching and iterative comparison with family systems, mentalisation, psychoanalytic, dialogic, child- and family-centred and service literatures; the clinical vignettes are composite and substantially disguised.Clinical contributionThe framework identifies five linked functions: the family within the admission field; restoration of parental function; calmamiento, a deliberate slowing of the ward's relational tempo through which urgency, shame and overpressure are reduced, allowing reflective, regulatory and relational capacities to emerge, return or be restored; team vitality; and discharge as sustainable reorganisation, with auxiliary family space and attractor-informed discharge planning specified as additional mechanisms.ConclusionsAcute admission can be understood not only as symptom stabilisation but as a relational intervention that may lessen institutional dependency, blame and shame, and create conditions for adolescents, families and teams to think and relate more safely.

AIM: As survival after gastric and esophageal cancer continues to improve, sustained work participation has become an important survivorship outcome. We aimed to evaluate return-to-work (RTW) rates 18 months after curative-intent surgery for gastric and esophageal cancers and to identify clinical and socioeconomic factors associated with delayed or failed RTW. METHODS: This multicenter, longitudinal, prospective cohort study evaluated working-age Japanese patients undergoing curative-intent surgery for gastric or esophageal cancer. Working status was assessed preoperatively and at 6, 12, and 18 months postoperatively. The primary outcome was working status at 18 months. Secondary outcomes included time to first RTW, and factors associated with non-working and delayed RTW. Exploratory analyses evaluated 6-month patient-reported outcomes (QLQ-C30) and postoperative weight loss. RESULTS: Among 158 eligible patients, 124 (78.5%) were working at 18 months. Older age (≥ 65 years) and pathological stage≥ III were associated with non-working at 18 months, whereas sedentary work and self-employment were associated with a lower risk of non-working. Postoperative appetite loss, financial difficulties (QLQ-C30), and ≥ 10% body weight loss at 6 months were associated with non-working status. Median time to first RTW was 30 and 70 days for gastric and esophageal cancers, respectively. Esophageal cancer and advanced stage were consistently associated with delayed RTW, with weaker evidence for associations with female sex and preoperative retirement. CONCLUSIONS: Approximately 80% of patients were working at 18 months after surgery. Postoperative nutritional impairment and symptom burden were associated with long-term work participation and may help identify patients at risk of not working after surgery.

BACKGROUND: To compare the transvaginal natural orifice transluminal endoscopic surgery (vNOTES) approach versus conventional laparoscopy in bilateral tubal ligation for interval sterilization regarding perioperative outcomes, postoperative pain, and sexual function. METHODS: This retrospective cohort study at a tertiary center included 88 women who underwent elective tubal ligation between February 2024 and October 2025 (vNOTES: n = 39; laparoscopy: n = 49). Women aged 18-45 years seeking permanent contraception with American Society of Anesthesiologists (ASA) physical status classification ≤ 3 were included. Primary outcomes included operative time and estimated blood loss (assessed by hemoglobin/hematocrit changes). Secondary outcomes included length of hospital stay, postoperative pain assessed using a visual analog scale (VAS) at 6 and 24 h postoperatively, total amount of analgesic requirements and sexual function evaluated using the Female Sexual Function Index (FSFI) preoperatively and at 1 and 6 months postoperatively. Statistical analysis used t-test/Mann-Whitney U test and chi-square/Fisher's exact test (α = 0.05). RESULTS: Baseline characteristics were comparable between groups (vNOTES: n = 39; laparoscopy: n = 49). No significant differences were found in hemoglobin changes or operative time. vNOTES demonstrated significantly shorter hospital stay (14.90 ± 7.27 vs. 20.10 ± 3.96 h, p < 0.001), lower postoperative total amount of analgesic requirements (1.72 ± 0.76 vs. 4.88 ± 1.63 doses, p < 0.001), and reduced VAS pain scores at 6 and 24 h. No intraoperative conversions occurred. Complication rates were similar between groups (p > 0.999). FSFI scores showed no significant differences at baseline, 1, or 6 months postoperatively. CONCLUSION: vNOTES for tubal ligation offers significant advantages in postoperative pain reduction, decreased analgesic requirements, and shorter hospital stay while maintaining comparable operative times, safety, and sexual function outcomes.

BACKGROUND: Obesity poses significant technical challenges during rectal cancer surgery (RCS). Robotic surgery may improve operative performance in this setting. We therefore performed a systematic review and meta-analysis comparing robotic and laparoscopic approaches in obese patients. METHODS: A systematic search was conducted across PubMed, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials up to May 2026. Pooled odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated using random-effects models. Bayesian analyses were additionally performed for overall morbidity and conversion to open surgery. RESULTS: Five observational studies involving 531 patients were included, of whom 280 underwent robotic RCS, and 251 underwent laparoscopic RCS. Robotic surgery was associated with a significantly shorter hospital stay (MD = -1.8 days; 95% CI: -2.5 to -1.0; P < .01; I2 = 67.8%) but a longer operative time (MD = 48.5 minutes; 95% CI: 1.8-95.3; P = .04; I2 = 81.7%). No significant differences were observed regarding conversion to open surgery, overall morbidity, anastomotic leakage, blood loss, lymph node yield, circumferential resection margin positivity, quality of total mesorectal excision, urinary retention, urinary tract infection, or surgical site infection. Bayesian analyses yielded posterior probabilities of benefit of 89.0% for conversion to open surgery and 95.0% for overall morbidity. CONCLUSION: Robotic RCS in obese patients was associated with shorter hospitalization but longer operative time compared with laparoscopy. Perioperative morbidity and pathological outcomes were comparable between approaches in conventional analyses, although Bayesian analyses suggested higher posterior probabilities of benefit for conversion to open surgery and overall morbidity; however, these findings should be interpreted cautiously given the wide credible intervals and very low certainty of evidence. Further high-quality prospective studies are needed to confirm these findings.

OBJECTIVE: The aim of this study was to compare the epidemiology and mortality of hospital-acquired versus non-hospital-acquired COVID-19 infections among hospitalised patients. METHODS: We conducted a retrospective cohort study of COVID‑19 hospitalisations in Victoria, Australia (January 2021-June 2024), using linked state surveillance systems. Episodes were classified as hospital acquired if the first positive test occurred ≥8 days post admission. Age, sex, intensive care unit admission and 30‑day mortality were compared between hospital-acquired and non‑hospital-acquired cases across pre‑Omicron and Omicron periods. RESULTS: Of 6,485 hospital-acquired and 62,670 non-hospital-acquired episodes, median age for hospital-acquired versus non-hospital-acquired cases was 77.8 versus 77.6 years before Omicron and 52.6 versus 73.1 years during Omicron. Monthly proportion of hospital-acquired cases increased during Omicron (range: 1% to 21%). Case fatality rates were higher in hospital-acquired than in non-hospital-acquired cases, with a larger difference before the Omicron (incidence rate ratio: 4.49, 95% confidence interval: 2.02, 9.99) than during the Omicron period (incidence rate ratio: 1.62, 95% confidence interval: 1.44, 1.82). Intensive care unit admission was associated with 30-day mortality for hospital-acquired (adjusted odds ratio: 4.4, 95% confidence interval: 2.3-8.4) and non‑hospital-acquired cases (adjusted odds ratio: 4.0, 95% confidence interval: 3.5-4.7). CONCLUSIONS: Hospital-acquired COVID-19 infections remain significant, associated with higher mortality rates than non-hospital-acquired infection and disproportionately affecting older patients. IMPLICATIONS FOR PUBLIC HEALTH: Our findings underscore the need for robust hospital COVID-19 infection prevention strategies.

BACKGROUND: Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) carry substantial short-term mortality. While liver transplantation is the definitive therapy, access is often delayed in settings reliant on living-donor transplantation, such as Egypt. Therapeutic plasma exchange (TPE) has emerged as a potential bridging strategy, but evidence from resource-limited health systems remains scarce. METHODS: We conducted a prospective randomized pilot study including 46 adults with ALF or ACLF at a tertiary center in Egypt. Participants were assigned to standard medical therapy (SMT; n = 15), standard-volume plasma exchange (SVPE; n = 16), or high-volume plasma exchange (HVPE; n = 15). SVPE involved exchange of 1.5-2.0 plasma volumes per session, whereas HVPE delivered 8-12 L/day for 3 consecutive days. All patients received guideline-based SMT. Changes in alanine aminotransferase (ALT), total bilirubin, international normalized ratio (INR), and MELD-Na score were evaluated alongside procedure-related complications and 90-day mortality. RESULTS: Both TPE strategies produced greater improvements in ALT, total bilirubin, INR, and MELD-Na compared with SMT alone. HVPE achieved the largest reduction in MELD-Na but was associated with higher rates of catheter-related infection and neurological complications. SVPE demonstrated a more favorable safety-effectiveness profile. Ninety-day mortality was highest with SMT and lower in both TPE groups. CONCLUSIONS: In a resource-limited tertiary setting, protocolized TPE is feasible and may improve short-term outcomes in ALF and ACLF. SVPE may represent a safer and more scalable bridging strategy when immediate access to liver transplantation is limited.

The San Diego/Tijuana (US/Mexico) coastal region has immense water quality issues due to untreated wastewater sources. Regular ddPCR Enterococcus sampling provides same-day water quality information for beachgoers but does not provide forecasts for decision making. We describe the Pathogen Forecast Model (PFM) V1.0, providing daily 5 day forecasts of swimmer illness risk along 30 km of shoreline on a web dashboard. PFM is based upon a hydrodynamic model using forecasted waves, winds, offshore currents, and Tijuana River flow as inputs. PFM accurately forecasts tides and waves and forecasts depth-averaged shelf currents moderately well. Modeled untreated wastewater concentration tracer C evolves with a constant decay rate representing Norovirus. Over 13 km of shoreline, forecasted C and observed Enterococcus E are moderately log-correlated (≈0.5) for day-1 and -5 forecasts. The C and E power-law relationship has an exponent of ≈0.5, possibly suggesting the tracer decays 2× slower than Enterococcus DNA, among other potential explanations. Using the cutoff C = 10-5, PFM classified advisory exceedances with nearly 80% raw accuracy, high sensitivity, and lower specificity. This is the first forecast model that resolves estuarine, surfzone, and shelf regions. PFM is a useful public health tool and is constantly being improved.

Store-operated calcium entry (SOCE) mediated by STIM and Orai proteins is a fundamental Ca2+ influx mechanism that critically regulates intracellular calcium homeostasis and participates in cardiovascular pathophysiology. Upon endoplasmic reticulum Ca2+ store depletion, STIM1/2 activate plasma membrane Orai1/3 channels, initiating Ca2+ entry that drives vasoconstriction, smooth muscle proliferation, platelet activation, and cardiac hypertrophy. Dysregulated SOCE is closely associated with hypertension, atherosclerosis, pulmonary hypertension, and thromboembolic disorders. However, SOCE is not a simple binary pathway but operates within a complex regulatory network. Beyond the core STIM-Orai axis, auxiliary proteins including transient receptor potential canonical 1 (TRPC1), tetraspanin 18 (Tspan18), tropomyosin 3 (TPM3), SOCE-associated regulatory factor (SARAF), and A-kinase anchoring protein 79/150 (AKAP79/150) modulate SOCE amplitude, kinetics, and downstream signaling in a cell- and context-dependent manner. Moreover, the functional consequences of SOCE are highly heterogeneous: Orai1 protects adult cardiomyocytes but promotes pathological hypertrophy in neonatal cells, posing a therapeutic dilemma. Although preclinical studies have shown efficacy of SOCE inhibitors, clinical translation remains hindered by poor isoform selectivity, suboptimal pharmacokinetics, lack of tissue-specific delivery, disease-stage-dependent effects, and absence of validated biomarkers. Importantly, recent evidence has definitively ruled out amlodipine-induced CRAC channel activation at therapeutic concentrations, confirming it as an experimental artifact. This review systematically summarizes the molecular complexity, functional diversity, and translational barriers of STIM/Orai-mediated SOCE, aiming to inform precision therapeutic strategies for cardiovascular diseases.

BACKGROUND: Inability to decrease pulmonary vascular resistance (PVR) with exercise may lead to right ventricular failure. In this two-step study, we define an unfavorable exercise PVR response among a broad cohort and then determine its high-risk correlates in HFpEF. METHODS: 164 participants (80 HFpEF, 57 pre-capillary PH, 27 non-cardiac dyspnea) underwent invasive cardiopulmonary exercise test. Dichotomous groups were created with a stepwise approach: "unfavorable exercise PVR" (n = 85, HFpEF = 46) defined as exercise PVR > 1.74Woods unit (WU) and ∆PVR decrease with exercise of < 22%, the remainder of the cohort was labeled as "favorable exercise PVR" (n = 79, HFpEF = 34). Stepwise approach included: physiological groups (tertiles) using exercise PVR cutoff = 1.74 WU and median approach with ∆PVR decrease with exercise. RESULTS: In unfavorable (vs. favorable) PVR HFpEF subgroups, rest PVR = 3.4 ± 2.0 vs. 2.9 ± 2.0WU, exercise PVR = 3.7 ± 2.6 vs. 2.0 ± 1.3WU, and ∆PVR = +11% ± 39% vs. -26% ± 22%. Correlates of unfavorable exercise PVR with univariate regression were: atrial fibrillation, COPD, increased LAVI, lower TAPSE, and lower TAPSE/PASP. Multivariate model (including clinical data: age, sex, BMI) revealed that atrial fibrillation (β-estimate = 1.93, p = 0.003) and COPD (β-estimate = 1.74, p = 0.03) were significant. However, with multivariate model (including LAVI and TAPSE), COPD remained significant (β-estimate = 3.26, p = 0.02), while atrial fibrillation (β-estimate = 1.60, p = 0.06) and LAVI (β-estimate = 0.05, p = 0.09) approached significance. The unfavorable versus favorable exercise PVR HFpEF subgroups had similar biventricular morphology by cardiac MRI (p < 0.30). CONCLUSIONS: Compared to traditional cardiometabolic comorbidities, COPD and atrial fibrillation are uniquely linked to pulmonary vascular remodeling in HFpEF. The impact of these two comorbidities on pulmonary vascular-left atrial axis is highlighted by the shared biventricular morphology among HFpEF subgroups.

Oxidative stress is a well-established driver in the pathogenesis and progression of various kidney diseases. The peroxiredoxin (PRDXs) family, comprising typical 2-Cys, atypical 2-Cys, and 1-Cys members, serves as essential thiol-dependent peroxidases that maintain cellular redox balance. Unlike classical antioxidant enzymes that solely scavenge reactive oxygen species, PRDXs are unique in their ability to undergo redox-sensitive structural transitions, functioning as molecular chaperones and intracellular signaling hubs. In the kidney, PRDXs exert multifaceted protective roles by preserving mitochondrial integrity and attenuating inflammatory and fibrotic signaling. Interestingly, beyond these canonical functions, several PRDX members exhibit context-dependent detrimental effects that paradoxically aggravate renal injury. Such dual functionality is regulated through sophisticated mechanisms, including specific post-translational modifications, molecular chaperone switching, and extracellular release as damage-associated molecular patterns. Although PRDXs represent promising therapeutic targets and biomarkers, their functional duality poses considerable challenges for drug development. Future efforts must focus on spatiotemporally precise regulation to selectively augment PRDXs-mediated defense while mitigating their injury-promoting effects.

BACKGROUND: Hyperkalaemia is a life-threatening electrolyte abnormality commonly managed with intravenous insulin-dextrose therapy (IDT). Although effective, IDT frequently causes hypoglycaemia, particularly in patients without diabetes. Glucose-only therapy, which leverages endogenous insulin production, may offer comparable potassium-lowering effects with reduced hypoglycaemia risk. However, evidence remains limited. METHODS: The HIGH-K Trial is a single-centre, double-blind, randomised controlled trial in adult, non-diabetic patients presenting to an Australian Emergency Department with hyperkalaemia (>5.5 mmol/L [99 mg/dL]). Ninety-five participants are randomised 1:1 to receive either glucose-only therapy (100 mL 50% dextrose bolus followed by 250 mL 10% dextrose infusion over 2 h) or standard IDT (10 units IV insulin with 25 g dextrose followed by 250 mL saline infusion). The primary safety outcome is the incidence of hypoglycaemia (<3.9 mmol/L [70 mg/dL]) within six hours. The primary non-inferiority outcome is the mean change in serum potassium from baseline to two hours, using a non-inferiority margin of -0.5 mmol/L (-9 mg/dL). Secondary outcomes include severity of hypoglycaemia, rescue insulin requirements, and serum insulin/C-peptide levels. DISCUSSION: This is the first double-blind, randomised controlled trial to directly compare the safety and biochemical non-inferiority of glucose-only therapy versus standard insulin-dextrose therapy in the emergency department. By utilising a continuous glucose infusion following a bolus, the protocol aims to sustain endogenous insulin release and optimise intracellular potassium shift while preventing hypoglycaemia. If non-inferiority is demonstrated, this approach could provide a safer alternative in high-acuity or resource-limited clinical settings. CONCLUSION: Results will be disseminated in peer-reviewed journals and at national and international conferences. Findings may inform future research and clinical practice guidelines regarding glucose-only therapy for hyperkalaemia.

BACKGROUND: The EuroQol EQ-5D-5L is recommended to assess health-related quality of life (HRQoL) in intensive care unit (ICU) survivors and included in many national ICU registries at the time of follow-up. While establishing baseline HRQoL in elderly ICU survivors is important for informing follow-up services, it is rarely performed in clinical practice. We aimed to compare pre-critical illness EQ-5D-5L scores with Norwegian general population norms in elderly adults. METHODS: We conducted a prospective multicenter observational study across five ICUs to assess pre-critical illness HRQoL in mechanically ventilated patients ≥ 65 years old using EQ-5D-5L. Data assessing HRQoL before critical illness were collected during the ICU stay, obtained primarily from proxies or via patient self-report where feasible. Response frequencies for the EQ-5D-5L dimensions, EQ-5D-5L index, and EQ VAS scores were compared with those for general population norms after random exact matching for age and sex. The five dimensions were dichotomized into the presence of health problems or not. RESULTS: Based on responses from 345 participants, the ICU population had a baseline mean EQ-5D-5L index of 0.78 (±0.24), an EQ VAS of 61 (±23), and 60 ICU patients reported no problems in any of the five domains. The norm population had a mean EQ-5D-5L index of 0.88 (±0.17), an EQ VAS of 79 (±20), and 107 had no problems in any of the five dimensions. Pearson chi-square or two-tailed t-tests showed significantly (p < 0.05) poorer scores for all EQ-5D-5L scores for the ICU population compared to the norm data. The greatest differences were found in the younger age group 65-72 years. Comorbidity was a strong independent predictor of baseline health status, whereas chronological age showed no significant association. CONCLUSION: Compared to the age- and sex-matched general population, the elderly ICU population had poorer HRQoL before critical illness occurred. To improve the interpretation of post-ICU assessments, baseline EQ-5D-5L should be assessed at ICU admission. The results highlight the need for studies in ICU patients that include HRQoL as part of a prospective study design. EDITORIAL COMMENT: This study presents pre-ICU quality of life scoring for older cases requiring mechanical ventilation. Compared to a matched non-ICU cohort, significant lower reported quality of life scoring wa

INTRODUCTION: This narrative review examines endovascular treatments for acute pulmonary embolism (PE), focusing on percutaneous mechanical thrombectomy (MT). METHODS: PubMed (Medline) and Google Scholar were searched from January 1990 up to November 2024 (updated Feb 2026). Studies were included if they discussed PE and the use of thrombectomy devices. Full-text randomised controlled trial studies, observational studies, case series, and case reports were included. Opinion articles, letters to the editor, animal studies, and non-English studies were excluded. RESULTS: A total of 116 articles were reviewed. Current guidelines recommend systemic thrombolysis as first-line reperfusion for high-risk PE, whereas intermediate-high-risk PE is managed with anticoagulation and monitoring, with reperfusion reserved for deterioration. MT is currently an alternative, mainly when thrombolysis is contraindicated or has failed. However, the last two decades have seen a surge in thrombectomy devices including the FlowTriever, Indigo, and AngioVac. Numerous studies, most notably the PEERLESS trial, have reported rapid haemodynamic improvement with MT, including reduced pulmonary artery pressure, low major bleeding rates, and fewer intensive care admissions [1]. CONCLUSION: MT has shown early promise in the management of PE. Much of the current evidence derives from single-arm trials, registries, and industry-sponsored observational studies, with randomised comparative data still limited. Nonetheless, randomised evidence suggests MT may reduce clinical deterioration, intensive care use, and hospital length of stay compared with catheter-directed thrombolysis, though without a demonstrated difference in mortality, intracranial haemorrhage, or major bleeding. Further trial evidence is required before MT is recommended as first-line in PE.

UNLABELLED: Early identification of high-risk children at pediatric intensive care unit (PICU) admission is essential. This study evaluated the association of admission combined acidosis-hyperlactatemia risk classification and lactate-to-bicarbonate ratio (LBR) with PICU mortality and organ support requirements. This retrospective cohort study included children aged 1 month to 18 years admitted to a tertiary PICU between January 2022 and May 2025 who had lactate and bicarbonate values available from blood gas analysis within the first 24 h. Metabolic acidosis was defined as pH ≤ 7.30 and/or base excess ≤  - 7 mmol/L, and hyperlactatemia as lactate > 2.3 mmol/L. Patients were classified as low risk, intermediate risk, or high risk according to the presence of neither, either, or both abnormalities. The primary outcome was PICU mortality. A total of 1,636 patients were included, and PICU mortality was 7.3%. The low-, intermediate-, and high-risk groups included 874 (53.4%), 569 (34.8%), and 193 (11.8%) patients, respectively. Mortality increased progressively across risk groups from 3.4% to 7.0% and 25.9% (p < 0.001). Similar increases were observed for invasive mechanical ventilation, inotrope/vasopressor use, continuous renal replacement therapy, acute kidney injury, and plasma exchange (all p < 0.001). The combined metabolic risk model showed moderate discrimination for PICU mortality (AUC 0.710), comparable to lactate (AUC 0.707) and LBR (AUC 0.700), while PRISM showed the highest discrimination (AUC 0.820). After PRISM adjustment, high-risk status remained independently associated with mortality (adjusted OR 3.31, 95% CI 1.86-5.88; p < 0.001), whereas LBR showed borderline significance (adjusted OR 2.48, 95% CI 0.96-6.44; p = 0.062). CONCLUSION: The coexistence of admission hyperlactatemia and metabolic acidosis identified a high-risk phenotype associated with higher mortality and greater organ support requirements. The combined metabolic risk classification may support early bedside risk assessment, whereas LBR should be interpreted as a complementary marker rather than a prognostic measure superior to lactate or validated severity scores. WHAT IS KNOWN: • Lactate and acid-base parameters are associated with illness severity and adverse outcomes in critically ill children. • Validated severity scores remain the standard approach for mortality risk asse

OBJECTIVE: To describe the clinical characteristics of patients diagnosed with vesico-vaginal fistula in a urology service in Cali, Colombia, between 2016 and 2025. METHODS: A retrospective cross-sectional study was conducted using medical records from the Urology service at a high-complexity public referral hospital in Cali, Colombia, between June 2016 and June 2025. Patients with confirmed vesico-vaginal fistula were identified through ICD-10 codes. Sociodemographic, clinical, and treatment data were extracted and analyzed descriptively. RESULTS: We found 25 patients with vesicovaginal fistula; the median age was 45 years. A history of cervical cancer and prior radiotherapy was present in 32% and 48% of patients, respectively, and 68% had undergone previous pelvic surgery, most commonly hysterectomy (48%). Cystoscopy was the main diagnostic modality (84%), with a mean fistula size of 14.6 mm and predominantly retrotrigonal or trigonal locations. Conservative management was unsuccessful in all cases, while surgical repair-mostly laparoscopic-achieved a success rate of 72.2%, with postoperative complications occurring in 16.7% of patients. CONCLUSION: Vesicovaginal fistula in this cohort was mainly associated with prior pelvic surgery and radiotherapy. Conservative management was ineffective, while surgical repair-especially laparoscopic-achieved acceptable success with low complication rates.

OBJECTIVE: To evaluate the safety and efficacy of ultrasound (US)-guided percutaneous needle biopsy combined with FAL tissue adhesive needle tract sealing in pediatric hypervascular malignant solid tumors. METHODS: A retrospective analysis was conducted on 149 pediatric patients with Adler grade ≥2 malignant solid tumors who underwent US-guided percutaneous needle biopsy between January 2021 and October 2025. Based on the application of FAL sealing, patients were divided into the FAL group (n=57) and control group (n=92). Using 1:1 propensity score matching (PSM) for baseline covariates (e.g., age, tumor size, Adler grade, biopsy needle size, and hematological metrics), we generated 39 matched pairs. The number of needle passes, postoperative changes in laboratory values, complication rates, and follow-up outcomes were compared between the two cohorts. RESULTS: Before matching, the FAL group presented with larger tumors, lower preoperative hemoglobin levels, a different pathological distribution, and imbalance in biopsy needle size than the control group. After PSM, baseline characteristics were balanced between the two groups. Patients in the FAL group more frequently underwent ≥4 needle passes than those in the control group [84.6% (33/39) vs. 60.5% (23/38), P=0.034]. Furthermore, there were no significant differences in postoperative laboratory changes, complication rates, or diagnostic accuracy among surgically validated cases between the two groups. No FAL-related adverse events or needle tract seeding were observed during a median follow-up of 140 days in the matched FAL group. CONCLUSION: In pediatric hypervascular malignant solid tumors, US-guided PNB combined with FAL tract sealing was associated with a higher number of biopsy passes without an observed increase in procedure-related complications, while diagnostic accuracy remained comparable. Further prospective multicenter and large-sample studies are needed for validation.

This article examines the political abuse of psychiatry in Romania during the Ceaușescu era (1965-1989), analyzing how psychiatric institutions were systematically transformed into instruments of ideological control. Drawing on Securitate archives, victim testimonies, legal documents, and medical reports, this study demonstrates three interconnected dimensions of psychiatric repression: the operational mechanics through which political dissent was pathologized into psychiatric diagnosis; the deployment of medical authority to disguise political persecution as therapeutic intervention; and Romania's distinctive post-1989 failure of accountability, through which perpetrator structures survived regime change intact. The analysis reveals how complicit psychiatrists wielded diagnostic categories such as "paranoia" and "discordant syndrome" as political code, while institutions inflicted systematic violence masked as treatment. Unlike other post-communist transitions where lustration laws dismantled collaborator networks, Romania's psychiatric nomenclatura maintained uninterrupted control over professional structures, investigative commissions, and institutional memory. This article contributes to scholarship on medical ethics, state violence, and the weaponization of health care under authoritarian regimes, integrating operational, institutional, and transitional justice perspectives. In doing so, it demonstrates how the fusion of medical authority with security power produced a form of repression uniquely resistant to external scrutiny and post-communist accountability.

OBJECTIVE: To describe the work-related psychosocial risk factors and the level of clinical and cultural competence among healthcare professionals in the Ceuta Health District (Spain), and to provide a descriptive analysis of both dimensions within this population. METHOD: An observational, descriptive, cross-sectional study was conducted in four public health centres in the city of Ceuta and in the 061 Primary Care facility (October 2020-March 2021). All healthcare professionals (doctors, nurses, nursing assistants, and physiotherapists) who met the inclusion criteria were invited to participate. With regard to the calculated sample size, 278 participants were initially. A self-administered questionnaire with 146 items was used, including questions on sociodemographic and occupational factors, health habits and psychosomatic symptoms, as well as instruments validated in Spanish to assess psychosocial risks and clinical-cultural competence. The data were analysed using descriptive statistics. RESULTS: A response rate of 38.2% was obtained (134 questionnaires). Most participants were women (82.1%), predominantly nurses (56.7%) with more than 10 years' service, mostly working full-time. Relatively favourable health habits were observed (low consumption of alcohol and tobacco and perception of good health), although there was a significant presence of psychosomatic symptoms. In the psychosocial sphere, unfavourable levels of exposure were identified in areas such as conflict, perceived leadership and working conditions. In terms of clinical-cultural competence, more than half of the professionals showed intermediate levels of knowledge and skills to care for a culturally diverse population, coexisting with areas for improvement in awareness and specific training. CONCLUSIONS: Healthcare professionals are highly exposed to certain psychosocial risks linked to the organisation of work and the healthcare context, along with intermediate levels of clinical-cultural competence. This highlights the need to develop organisational strategies to reduce psychosocial risks and implement structured training programmes in cultural competence adapted to the uniqueness of Ceuta as a border and multicultural enclave.

INTRODUCTION: Posterior fossa tumours present substantial clinical challenges due to their deep anatomical location and proximity to vital neurovascular structures. Limited awareness and diagnostic delays remain major obstacles to early detection of paediatric brain tumours. For the last two decades, the 5-year overall and event-free survival of children with posterior fossa tumours has been doubled due to the improvement in the diagnostic tools and the advances in the surgical techniques approaching total or near-total resection. MATERIALS AND METHODS: This retrospective comparative cohort study was conducted at a tertiary care cancer hospital in Pakistan, following approval from the Institutional Review Board (IRB). The study included paediatric patients with posterior fossa tumours treated between January 2021 and February 2025 and compared two cohorts: the Regular Pathway and the Rapid Assessment Pathway (RAPT). Collected variables included demographic characteristics, duration of symptoms, time interval from initial symptom onset to acceptance for treatment (from walk-in clinic), surgical intervention, frequency of shunt or external ventricular drain insertion and initiation of adjuvant therapy. Data were analysed using SPSS version 27. RESULTS: A total of 59 patients were included, 30 patients in the Regular Pathway (January 2021-December 2023) and 29 patients in RAPT (January 2024-February 25).  In the Regular Pathway, the mean duration of acceptance after initial presentation was 15 days, as compared to RAPT, which was 5 days (p ≤ 0.001). The frequency of shunt insertion was reduced significantly in RAPT compared to Regular Pathways. A total of 83% of patients in RAPT were operated within 72 h of acceptance as compared to Regular Pathway cohorts, in which 55% patients had surgery within 4 weeks (p ≤ 0.001). The average duration of the start of adjuvant therapy in the RAPT cohort was within 6 weeks, while in the Regular Pathway cohort, it was 7 weeks. CONCLUSION: RapidRAPT has demonstrated a significant improvement in the timeliness of care for paediatric patients diagnosed with posterior fossa tumours. Early intervention facilitated by RAPT contributes to better outcomes and reduced treatment delays.

BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD) significantly impairs quality of life. Although proton pump inhibitors are first-line therapy, a subset of patients remains refractory to medical treatment. Laparoscopic Nissen fundoplication (LNF) is considered the gold-standard surgical option; however, high-quality prospective outcome data from Southeast Asia, particularly Vietnam, remain limited. This study aimed to evaluate clinical outcomes and symptom control following LNF in patients with refractory GERD. METHODS: This prospective cohort study included 61 consecutive patients with refractory GERD who underwent LNF at Can Tho General Hospital between March 2022 and September 2025. Gastroesophageal reflux disease questionnaire (GERD-Q) scores and symptom control were assessed at 1 month, 6 months, 12 months, and at the end of follow-up. RESULTS: The mean age was 38.9±14.3 years, and 54.1% of patients were male. All procedures were completed laparoscopically, with a mean operative time of 102.3±17.4 minutes. Postoperative recovery was rapid, with early resumption of oral intake and ambulation. Postoperative complications occurred in 19.7% of patients and were limited to Clavien-Dindo grades I-II, with no mortality. GERD-Q scores decreased significantly from 14.26±1.69 preoperatively to 7.00±0.99 at 1 month and continued to decline during follow-up, reaching 5.41±1.18 at the end of the study (p<0.001). Good symptom control was maintained in 83.6-90.2% of patients across follow-up time points. CONCLUSIONS: LNF is a safe and effective treatment for refractory GERD, providing rapid recovery and durable symptom control in appropriately selected patients.

BACKGROUND: Trends in functional recovery after ischemic stroke within inpatient rehabilitation settings are not well-described. This study evaluated 18-year trends in functional motor improvement among adults receiving inpatient rehabilitation for ischemic stroke. METHODS: We conducted a retrospective cohort study of adults with ischemic stroke admitted to a large rehabilitation system from December 2001 to September 2019. The primary outcome was the attainment of a minimal clinically important difference (MCID) in the Functional Independence Measure Motor score, defined as a ≥20-point increase in Functional Independence Measure Motor score. Multivariable logistic regression was used to evaluate temporal trends and their interaction with insurance. Sensitivity analyses evaluated changes in case-mix index, Charlson Comorbidity Index, and length of stay. RESULTS: Among 9809 ischemic stroke rehabilitation admissions representing 9126 unique patients, 4445 (45.3%) admissions attained MCID. The adjusted odds of MCID attainment increased annually (odds ratio, 1.085 [95% CI, 1.067-1.104]). Model-based predicted probabilities for MCID attainment increased from 0.239 (95% CI, 0.192-0.286) in 2001 to 0.555 (95% CI, 0.509-0.601) in 2019 for Medicare Fee-for-Service and from 0.345 (95% CI, 0.307-0.383) to 0.564 (95% CI, 0.530-0.598) for non-Medicare patients. The year-by-insurance interaction was significant, indicating smaller annual gains for non-Medicare patients (odds ratio, 0.973 [95% CI, 0.953-0.993]; P=0.007). The case-mix index showed no temporal change, while the Charlson Comorbidity Index increased and length of stay declined over time. However, neither the Charlson Comorbidity Index, case-mix index, nor rehabilitation duration explains the temporal improvement in MCID attainment. CONCLUSIONS: Functional motor recovery improved substantially over 18 years, independent of patient complexity and comorbidity burden, establishing contemporary benchmarks for inpatient stroke rehabilitation outcomes.

BACKGROUND: Hospitalized children with chronic and complex conditions are particularly vulnerable to nutritional deterioration, which has been associated with adverse clinical outcomes. Early identification of nutritional risk (NR) and nutritional status (NS) may support timely nutritional interventions; however, evidence on the combined use of STRONGkids and mid-upper arm circumference-for-age z-scores (zMUAC/A) in tertiary pediatric wards remains limited. AIM: To evaluate the association of NR, NS, energy-protein adequacy, nutritional evolution, length of hospital stay (LOS), infection, and 30-day hospital readmission in children admitted to a tertiary pediatric ward. METHODS: This prospective observational cohort included 216 children and adolescents (1 month to 18 years) admitted to a tertiary teaching hospital in a low- and middle-income country. NR was assessed using STRONGkids, and NS was assessed using zMUAC/A. Associations between nutritional variables and clinical outcomes were evaluated using regression models and complementary statistical analyses. RESULTS: The median age was 5.2 years, with a predominance of infants (34.7%) and males (55%). Undernutrition was more frequently identified by zMUAC/A than by zBMI/A (49.5% vs. 17.6%), and 31.5% of patients presented low height-for-age z-scores. STRONGkids demonstrated good performance for identifying undernutrition at admission (AUC = 0.858). Higher NR was associated with longer LOS and infection occurrence, whereas impaired NS was associated with infection occurrence and 30-day hospital readmission. Energy-protein adequacy and short-term nutritional evolution were not associated with the evaluated clinical outcomes. Overweight/obesity showed a descriptive trend toward shorter LOS than undernutrition; however, this finding should be interpreted cautiously because of the small subgroup size. CONCLUSIONS: Hospitalized pediatric patients in this tertiary care setting presented a high burden of undernutrition and nutritional risk, both of which were associated with clinically relevant outcomes. The combined use of STRONGkids and MUAC-based nutritional assessment may improve the early identification of nutritionally vulnerable patients and support targeted nutritional interventions in children with complex clinical conditions.

Elderly patients with post-operative complications following neurosurgical procedures represent a high-risk population. The combined effects of frailty, poor nutritional status, and anemia on morbidity and mortality in such patients remains poorly defined. This study aimed to assess the interplay of revised Risk Analysis Index (RAI-rev), Geriatric Nutritional Risk Index (GNRI), and anemia in this prognostication of this population. A retrospective cohort study was performed using the 2011-2023 National Surgical Quality Improvement Program (NSQIP) database. Patients aged 65 and older with Clavien-Dindo (CD) grade complications ≥ 3 following neurosurgical procedures were identified using Current Procedural Terminology (CPT) and International Classification Of Disease (ICD) codes. The study population was divided based on RAI-rev frailty status, with frail patients further subdivided based on anemia and GNRI status. Using receiver operating characteristic (ROC) and multivariable analyses, we compared the discriminative thresholds and independent predictors of extended hospital length of stay (LOS), non-routine discharge (NRD), and 30-day mortality. Of the 9,862 patients, 2,468 (25.0%) were frail alone (F), 1,534 (15.6%) frail and anemic (FA), 1,430 (14.5%) frail and malnourished (FM), 2,976 (30.2%) frail, anemic, and malnourished (FAM), and 1,454 (14.7%) not frail (NF). On multivariable analysis, extended LOS was independently associated with a lower GNRI score (p < 0.001), higher RAI-rev (p < 0.001), and anemia (p < 0.001). NRD was independently associated with a lower GNRI score (p < 0.001) and anemia (p = 0.027). 30-day mortality was independently associated with a lower GNRI score (p < 0.001) and higher RAI-rev (p < 0.001). Relative to RAI-rev alone, the RAI-rev + anemic (p < 0.001), RAI-rev + GNRI (p < 0.001), and RAI-rev + anemic + GNRI (p < 0.001) models were superior predictors for extended LOS. For NRD, the RAI-rev + GNRI (p = 0.025) and RAI-rev + anemic + GNRI (p = 0.029) models were superior. For 30-day mortality, the RAI-rev + GNRI (p < 0.001) and RAI-rev + anemic + GNRI (p < 0.001) models were superior. Our findings demonstrate the superior predictive capacity of RAI-rev, anemia, and GNRI for LOS, NRD, and 30-day mortality in elderly neurosurgery patients with CD grade III/IV complications. A comprehensive preoperative assessment including RAI-rev,

BACKGROUND AND AIMS: Cancer patients, especially those with hematologic malignancies (HMs), are considered among the most vulnerable groups at risk for severe outcomes from influenza infection. This study aimed to investigate influenza infection in patients with HMs and identify the risk factors associated with mortality. METHODS: This cross-sectional descriptive observational study included 90 patients with confirmed influenza infection and HMs. The data collected included demographic information, cancer type and status, influenza type, symptoms, laboratory and radiologic findings, length of hospital stay, ICU admissions, and mortality rate. The primary outcome was analysis endpoints included mortality risk factors based on ICU admission, death and type of malignancies. RESULTS: The mean age of patients was 34.3 ± 26.7 years (median 34, range 2-91). Most had acute lymphoblastic leukemia (ALL, 45.6%), followed by acute myeloid leukemia (AML, 22.2%), lymphomas (14.4%), multiple myeloma (MM, 6.7%), chronic myelogenous leukemia (CML, 2.2%), and other malignancies (8.9%). Nearly half (49.3%) were in the maintenance phase of treatment, and 80% were infected with influenza A. Pleural effusion (22.2%) and ground-glass opacities (17.8%) were the most common radiologic findings. ICU admission was significantly linked to older age (p = 0.002), comorbidity (p = 0.003), lower respiratory tract infection (LRTI) (p = 0.02), muscle ache (p = 0.03), and malignancies including MM, CML, and AML (p = 0.02). Higher mortality was observed in patients with MM or AML (p = 0.01), comorbidities (p = 0.02), and LRTIs (p = 0.04). Age-adjusted analysis confirmed MM, LRTI, and comorbidity as potential strong predictors of mortality. CONCLUSION: ICU admission was significantly associated with older age, the presence of at least one comorbidity, LRTI, and body muscle aches. MM, CML, and AML were notably more associated with ICU admission. Patients diagnosed with MM and AML, those with at least one comorbidity, and those with LRTIs had a higher risk of mortality. The age-adjusted analysis identified MM, LRTIs, and comorbidities as potential strong predictors of mortality in this cohort, requiring validation in larger studies.

BACKGROUND: Distal cholangiocarcinoma (dCCA) is a rare but aggressive biliary malignancy arising from the distal bile duct with significant clinical burden. Pancreaticoduodenectomy (minimally invasive or open) remains the only potentially curative treatment for dCCA. However, the comparative safety and oncologic adequacy of minimally invasive versus open pancreaticoduodenectomy remains unclear, creating an evidence gap that this systematic review addresses. OBJECTIVE: This systematic review and meta-analysis aimed to compare perioperative outcomes and oncologic effectiveness of MIPD versus OPD in patients undergoing surgery for distal cholangiocarcinoma. METHODS: A systematic literature search of PubMed, Embase, Cochrane Library, and Science Direct was conducted through April 2025 in accordance with PRISMA guidelines. Eligible studies included cohort studies, randomized controlled trials, and case-control studies comparing MIPD (laparoscopic or robotic) with OPD in dCCA. Data regarding operative parameters, oncologic outcomes, perioperative morbidity, and mortality were extracted. Meta-analysis was performed using Review Manager 5.4, applying fixed- or random-effects models based on heterogeneity. RESULTS: Seven retrospective cohort studies comprising 1,803 patients (775 MIPD vs. 1,028 OPD) were included. MIPD was associated with significantly lower blood loss (WMD - 100.86 mL, 95% CI - 107.27 to - 94.46; I² = 90%; p < 0.001) and shorter hospital stay (WMD - 2.46 days, 95% CI - 4.08 to - 0.84; I² = 89%; p = 0.003), but longer operative time (WMD 52.60 min, 95% CI 16.82 to 88.39; I² = 99%; p = 0.004). There was no significant difference in major complications (Clavien-Dindo ≥ III) (OR 0.97, 95% CI 0.74-1.28; p = 0.85) or postoperative mortality (OR 0.46, 95% CI 0.16-1.33; I² = 56%; p = 0.15) between groups. Importantly, long-term oncologic outcomes were also comparable between groups, with no significant differences observed in overall survival (HR 0.90, 95% CI 0.77-1.05; p = 0.19) or disease-free survival (HR 0.98, 95% CI 0.83-1.16; p = 0.83). No survival disadvantage was demonstrated for MIPD compared with OPD. CONCLUSION: MIPD appears to be a safe and feasible alternative to OPD for selected patients with distal cholangiocarcinoma, offering perioperative benefits without compromising oncologic outcomes. Importantly, available evidence also demonstrates

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, fatal disease associated with a substantial health care system burden. The aim of this study was to compare health care resource utilization and associated costs among individuals with ATTR-CM, with non-amyloid heart failure (HF), and without HF in the United States. METHODS: Optum's de-identified Clinformatics Data Mart Database (January 2016 to September 2023) was used to identify patients with ATTR-CM based on HF and/or cardiomyopathy claims within 2 years of the first ATTR diagnosis. Patients with ATTR-CM were matched to patients with non-amyloid HF (HF/cardiomyopathy without ATTR) and non-HF controls using 1:1 propensity score matching. All-cause and cardiovascular-related hospitalizations and costs were compared during follow-up. RESULTS: Each matched cohort included 4571 patients (mean age, 75.3-75.5 years; 56.0%-56.6% male; mean follow-up: 2.9-3.2 years). The ATTR-CM, non-amyloid HF, and non-HF cohorts had 3.3, 2.7, and 1.5 all-cause hospitalizations per patient during follow-up, respectively. Compared with non-amyloid HF, patients with ATTR-CM had a longer mean length of stay per hospitalization (all-cause and cardiovascular-related: 8.0 versus 7.5 days; P<0.001), more mean days hospitalized annually per patient (all-cause: 10.6 versus 8.4; cardiovascular-related: 10.5 versus 8.3 [both P<0.001]), and higher mean annual inpatient hospitalization costs per patient (all-cause: $42 868 versus $36 061; cardiovascular-related: $42 841 versus $36 027 [both P<0.001]). In ATTR-CM subgroups, mean cardiovascular-related length of stay and days hospitalized were higher among patients aged 46 to 64 years and 65 to 80 years (versus >80 years), Black patients (versus White patients), and patients in the Northeast or South US regions (versus West regions). CONCLUSIONS: ATTR-CM is associated with a higher health care resource utilization/cost burden than non-amyloid HF and the general population.

BACKGROUND: Terlipressin is a synthetic vasopressin analogue that is indicated for the treatment of hepatorenal syndrome-acute kidney injury (HRS-AKI) to improve kidney function and haemodynamics. Despite its previous approval in Europe, terlipressin was Food and Drug Administration (FDA)-approved in 2022 in the United States. Historical standards of care, such as midodrine and octreotide (MO), are still used alternatively to terlipressin, and mortality benefit among treatments is unknown. OBJECTIVE: To examine the effects of terlipressin vs MO in hospitalized patients with HRS-AKI. METHODS: This single-centre, retrospective, cohort study was conducted at a large, tertiary academic medical centre. Data were collected from the electronic health record for patients admitted from July 2018 to July 2024. Patients ≥18 years of age admitted with International Classification of Diseases codes for cirrhosis, AKI, and clinical diagnosis of HRS were included. The primary outcome was the incidence of in-hospital mortality between patients receiving terlipressin vs MO. Descriptive statistics and parametric and non-parametric tests were utilized as appropriate. RESULTS: A total of 49 terlipressin patients and 30 MO patients were identified. The rate of in-hospital mortality was lower with terlipressin (n = 12, 24.5%) vs MO (n = 21, 70%) (P < .001). The mean hospital length of stay (days) was greater with terlipressin than MO (21.4 ± 14 vs 15.5 ± 8.4, P = .081) as was baseline serum creatinine (SCr) (2.94 ± 1.1 vs 1.89 ± 1.2 mg/dL, P < .05). Numerically more patients receiving terlipressin had a response to therapy (21/49 vs 12/30, P = .1033) with a similar decrease in SCr (-34.8 ± 21% vs -36.1 ± 21%, P = .86). The number of days from therapy initiation until the lowest SCr was less with terlipressin vs MO (4.97 ± 3.5 vs 7.92 ± 3.7, P = .02). CONCLUSION AND RELEVANCE: Terlipressin appears to effectively improve renal function and in-hospital mortality in patients with HRS-AKI compared with MO. Terlipressin may be used as a first-line treatment for HRS-AKI or after a trial of MO based on the study's results.

BACKGROUND AND AIMS: In the ambulatory setting, mildly low hemoglobin (Hb), < 13 g/dL in men or < 12 g/dL in women, is associated with reduced cognition. However, in hospitalized patients, clinicians tolerate much lower Hb levels due to restrictive transfusion policies. Older adults who are at higher risk for cognitive impairment may also be particularly susceptible to impaired cognition from lower Hb levels. The purpose of this study was to test for an association between restrictive Hb levels during hospitalization and patient's cognitive function, particularly in older adults. METHODS: The data for this study came from an ongoing prospective observational study of hospitalized general medicine patients at the University of Chicago Medical Center (UCMC). Any adult with a Hb < 10 g/dL between March 2017 and February 2020 was eligible. Cognition was measured using the Short Portable Mental Status Questionnaire (SPMSQ), which ranges from 0 to 10. Higher scores indicate worse cognition. Zero-inflated Poisson (ZIP) and logistic regression were used to test the association between cognition as the dependent variable, measured by the SPMSQ, and patients' nadir Hb and age as predictor variables, controlling for race, sex, Charlson Comorbidity Index, transfusion, and a diagnosis of dementia. RESULTS: The SPMSQ questionnaire was completed by 5112 patients who had Hb < 10 g/dL. Lower nadir Hb levels were associated with decreased cognition (higher SPMSQ). Across all ages, a 1 g/dL decrease in Hb was associated with a 7.2% increase in SPMSQ score (95% confidence interval (CI) = 2.9%-11.7%). The effect of decreasing Hb on cognition was greater in older populations, where a 1 g/dL decrease in Hb was associated with an 8.8% (3.1%-14.8%) and 20.8% (9.7%-33.0%) increase in SPMSQ score for patients above 50 and 65, respectively. CONCLUSIONS: Lower Hb levels during hospitalization are associated with decreased cognition, especially in older adults.

Bacterial immune systems encompass the multi-layered defense mechanisms that bacteria develop against bacteriophages and mobile genetic elements, such as plasmids. This review covers bacterial innate defense systems (surface defenses, superinfection exclusion, restriction-modification, abortive infection, and toxin-antitoxin systems), CRISPR-Cas-mediated adaptive immunity, and the escape strategies used by phages to overcome these defenses (genome modifications, anti-restriction proteins, and anti-CRISPR factors). Emerging evidence also highlights the role of outer membrane vesicles (OMVs) in anti-phage defense and their translational potential as vaccine and delivery platforms. In this context, a better understanding of bacterial defense systems contributes to the development of biotechnology and medical applications such as CRISPR technologies, diagnostic approaches, and phage therapy.

INTRODUCTION: Bovine tuberculosis (bTB) is a zoonotic disease of major public health concern, particularly in developing countries such as Cameroon, where control measures are poorly implemented and there is a high risk of human infection. This study aimed to estimate the prevalence of bTB lesions in slaughtered cattle and identify the associated risk factors in slaughterhouses in the city of Ngaoundéré. METHODOLOGY: A cross-sectional study was conducted to investigate the prevalence of tuberculosis lesions in two slaughterhouses between April and October 2024. Tuberculosis lesions were identified during postmortem inspections performed by veterinary inspectors on slaughtered animals, and the presence of acid-fast bacilli (AFB) in these lesions was detected using Ziehl-Neelsen (ZN) staining. In addition, a structured questionnaire was administered to assess potential risk factors, and their associations with the prevalence of tuberculosis were analyzed using univariate and multivariate logistic regression models. RESULTS: Among the 1,256 cattle examined, the overall prevalence of bTB was 5.1% (95% CI: 3.88-6.22). Suspicious lesions were detected in 64 carcasses, of which 17.14% were positive for AFB, suggestive of Mycobacterium spp. Regarding the multivariable analysis, only cattle origin remained significantly associated with the outcome, particularly for animals from Touboro (OR = 18.9; 95% CI: 3.3-367.1) and Mbaiboum (OR = 14.9; 95% CI: 2.5-292.2). During the study period, financial losses were estimated based on 302.5 kg of organs condemned due to tuberculosis infection, using prevailing market prices. The total losses were estimated at 541,200 CFA francs. The organs contributing to the highest financial losses were the lungs and carcasses during the study period in the surveyed abattoirs. CONCLUSION: This study confirmed the presence of tuberculosis in slaughterhouses in Ngaoundéré, with infected cattle originating from various border areas of the town. It also highlighted that the lungs and carcasses were the most frequently affected, resulting in significant financial losses for butchers. These findings raise food safety concerns in Ngaoundéré and indicate a potential risk of zoonotic transmission of the pathogen.

BACKGROUND: Non-typeable Streptococcus pneumoniae (NT-Sp) strains lack detectable capsules and are often missed by traditional serotyping. While associated primarily with asymptomatic carriage, NT-Sp has emerged as a key player in antimicrobial resistance (AMR) gene dissemination and serotype replacement in the post-vaccine era. This systematic review and meta-analysis synthesize global evidence on NT-Sp carriage, its prevalence, antimicrobial resistance patterns, and genetic diversity. METHODS: A systematic search of PubMed, Scopus, Web of Science, Google Scholar, and ScienceDirect was conducted up to May 2025. Eligible studies reporting NT-Sp carriage, molecular typing, or AMR profiles were included. Data extraction and quality assessment followed PRISMA guidelines. A meta-analysis was performed to estimate pooled prevalence of NT-Sp carriage and resistance, with subgroup and meta-regression analyses exploring heterogeneity. Methodological quality was assessed using the Newcastle-Ottawa Scale adapted for cross-sectional studies. Only open-access and free full-text articles were included, which may have introduced selection bias. RESULTS: Forty studies from 23 countries were included. The pooled NT-Sp carriage prevalence was 4.64% (95% CI: 2.78%-6.92%), with substantial heterogeneity (I 2 = 97.1%, 95% CI: 96.6%-97.5%). Subgroup analyses revealed geographic variation, with Oceania showing the highest prevalence (7.24%, 95% CI: 1.39%-17.04%) and North America the lowest (0.44%, 95% CI: 0.05%-1.11%). Age-stratified analysis showed that studies, including all ages had the highest estimate (29.88%, 95% CI: 0.00%-100.00%), while children had a pooled prevalence of 4.05% (95% CI: 0.00%-15.80%). Vaccination era did not significantly influence NT-Sp carriage (p = 0.312). Resistance was highest for co-trimoxazole (67.21%, 95% CI: 49.92%-82.73%), penicillin (44.57%, 95% CI: 24.45%-65.50%), and erythromycin (39.85%, 95% CI: 19.58%-61.77%). Meta-regression identified the "all ages" participant category as a significant predictor of lower NT-Sp prevalence (p = 0.034). Molecular tools revealed substantial genomic diversity, with dominant clonal complexes varying by region. CONCLUSION: NT-Sp is a globally distributed and genetically diverse pneumococcal subset with considerable AMR potential. Its persistence post-PCV introduction and resistance gene carriage highlights

PURPOSE: To systematically review the microbiological spectrum, antimicrobial resistance (AMR) patterns, management strategies, and outcomes in culture-positive endophthalmitis, a rare vision-threatening complication of cataract surgery increasingly challenged by resistance. METHODS: A comprehensive literature search was conducted in PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials from 1 January 1990 to 30 June 2025. Eligible studies included culture-positive cases of acute Post-Cataract Endophthalmitis reporting antimicrobial susceptibility and outcomes. Data were extracted on organisms, resistance profiles, treatment strategies and visual acuity. Risk of bias was assessed using the ROBINS-I tool. RESULTS: Six studies (five retrospective, one prospective) from Europe, Asia, and North America met inclusion criteria. Coagulase-negative staphylococci predominated, with frequent methicillin and fluoroquinolone resistance; Staphylococcus, Streptococcus, and Pseudomonas were less common. An Indian cohort described multidrug-resistant Pseudomonas with near-universal resistance to fluoroquinolones, aminoglycosides, and cephalosporins but susceptibility to colistin, piperacillin, and imipenem. While vancomycin remained active against Gram-positive organisms, emerging resistance was reported in the United Kingdom. Visual outcomes varied: tap-and-inject was comparable to early pars plana vitrectomy (PPV), except in Gram-negative infections where PPV conferred benefit. Amikacin resistance correlated with poorer outcomes, whereas vancomycin or moxifloxacin resistance did not. Systemic antibiotics and intravitreal corticosteroids showed no consistent benefit. CONCLUSION: AMR in Post-Cataract Endophthalmitis is an escalating concern with marked geographic variation. Prompt intravitreal therapy remains the key determinant of prognosis, but empiric regimens must reflect local resistance trends, particularly for Gram-negative coverage. Current evidence is limited by retrospective design and regional variability; multicentre prospective studies are needed to refine prophylaxis and treatment protocols, reducing visual and economic burden.

BACKGROUND/AIM: Dentists are responsible for a substantial proportion of antibiotic prescriptions, and antibiotic use contributes to selection pressure for antimicrobial resistance, while inappropriate use increases this burden without corresponding patient benefit. Adequate knowledge of antibiotic indications, prophylaxis and selection is therefore essential in dental education. This study aimed to evaluate the knowledge and awareness of final-year dental students and dental interns in Poland regarding systemic antibiotic therapy and antibiotic prophylaxis in dentistry. MATERIAL AND METHODS: A nationwide, multi-institutional cross-sectional survey was conducted among final-year dental students and dental interns from all 10 dental universities in Poland. A validated questionnaire assessed knowledge of indications for antibiotic prophylaxis in systemic conditions, indications for systemic antibiotic therapy in dental diseases, use of prophylaxis during dental procedures in immunocompromised patients, antibiotic selection in clinical scenarios and self-reported prescribing experiences. RESULTS: A total of 1144 respondents participated, including 801 students and 343 interns. Interns demonstrated significantly better adherence to guideline-based recommendations across most domains. Students more frequently indicated antibiotic use in conditions where it is not recommended, such as localised dental infections without systemic involvement and selected systemic diseases. Differences were also observed in antibiotic selection, with interns more often choosing guideline-recommended first-line agents. Interns reported more frequent antibiotic prescribing due to concerns about postoperative complications and diagnostic uncertainty. CONCLUSIONS: Although dental interns exhibited greater knowledge and selected guideline-concordant responses more frequently than final-year students, important gaps in understanding of evidence-based antibiotic use persist in both groups. These findings highlight the need for enhanced education and antimicrobial stewardship training in undergraduate and postgraduate dental curricula to promote rational antibiotic prescribing and combat antimicrobial resistance.

Decellularized extracellular matrix (dECM) materials derived from cardiac tissues have emerged as multifunctional biomaterials that recapitulate native microenvironmental cues while serving as controlled-release reservoirs of therapeutic agents and cells for cardiac repair. Recent advances have demonstrated that decellularized cardiac ECM (dcECM) hydrogels and patches can localize the release of angiogenic peptides, growth factors, or genes to promote neovascularization and mitigate adverse remodeling. Simultaneously, dcECM platforms have been applied to improve the survival and engraftment of stem cells, cardiomyocytes (CMs), and cardiac progenitor cells (CPCs) in infarcted myocardium, facilitating paracrine signaling and immune modulation. This review summarizes recent progress in the design and translational development of dcECM-based drug and cell delivery strategies for cardiac repair. We emphasized the interactions between matrix composition, its capacity to protect therapeutic factors and enhance cell retention, and therapeutic release profiles that collectively regulate cardiac tissue repair outcomes and highlighted emerging clinical applications and regulatory challenges for next-generation dcECM-based therapeutics.

Despite the availability of medications and advocacy for lifestyle interventions, over half of individuals with hypertension do not achieve recommended treatment goals owing to limitations with medications, such as high cost, side effects, and poor adherence. Renal denervation (RDN), a minimally invasive endovascular procedure targeting sympathetic nerves near the renal arteries, is gaining recognition as a safe and effective adjunctive therapy for blood pressure control in resistant hypertension, supported by several clinical trials and meta-analyses. Recognising the clinical complexity of resistant hypertension, a group of hypertension experts from India convened to develop an "RDN triage tool" to guide clinicians in selecting appropriate candidates for RDN therapy based on demographics, blood pressure, renal function, and cardiac status. This approach is supported by clinical evidence and expert recommendations and aims to optimise patient selection for RDN therapy, aid clinical decision-making, minimise risks, and enhance patient outcomes.

BACKGROUND: Coronary microvascular disease (CMVD) is an important contributor to ischemic heart disease. Symptomatic patients without obstructive coronary lesions may still have microvascular ischemia, which is associated with an increased risk of major adverse cardiovascular events. The diagnosis of CMVD relies on coronary function testing or noninvasive imaging techniques, which are not universally available and may limit routine clinical implementation. OBJECTIVES: Growing evidence supports the notion that biological processes such as inflammation and oxidative stress drive vascular aging and contribute to microvascular dysfunction. The systemic immune-inflammation index (SII) is a marker used to assess immune-inflammatory and thrombotic status and has shown prognostic value in chronic heart failure, and acute myocardial infarction. However, its role in CMVD remains underexplored. DESIGN: To address this gap, we retrospectively analyzed 180 patients with angina who underwent myocardial contrast stress echocardiography between January and November 2022 at the First Affiliated Hospital of Harbin Medical University. METHODS: Based on coronary microcirculatory function, patients were divided into two groups: 91 with normal function and 89 with microcirculatory disorders. Clinical data and lab indicators were compared. RESULTS: SII was significantly higher in the CMVD group (722.96 ± 354.10 vs 618.51 ± 324.50; p < 0.05). Logistic regression identified SII, LDL cholesterol as independent CMVD predictors. Pearson correlation demonstrated an inverse relationship between SII and coronary flow reserve, supporting its link with impaired microvascular function. Receiver operating characteristic analysis further showed that the combined SII and LDL model provided improved discriminatory performance compared with either marker alone, achieving an area under the curve of 0.76 with a sensitivity of 77.5% and specificity of 69.2%. CONCLUSION: SII is independently associated with CMVD and improved discriminatory performance when combined with LDL.

INTRODUCTION: We aimed to assess whether Paget's disease of bone (PD) increases the risk of major adverse cardiovascular events (MACE) and arterial stiffness in middle-aged men and women. METHODS: We analyzed data from the CARTaGENE cohort, including individuals aged 40-69 years, recruited in the province of Quebec, Canada in 2009/2010, linked to healthcare administrative databases to identify PD and MACE (both before and after recruitment, 1997-2021). Comorbidities and arterial stiffness parameters (augmentation index, estimated pulse wave velocity) were measured at recruitment. Cardiovascular risk factors were compared in an age-standardized population. MACE was defined as 3-component (myocardial infarction, stroke, cardiovascular death) or 5- component (3-point + heart failure, unstable angina) variables. Time-to-event analyses (from birth) used Cox and Fine-Gray models in a 1:3 propensity-score matched population, and associations with arterial stiffness were tested with linear and logistic regressions. RESULTS: Among 19,990 participants, 101 (0.5%) had PD. PD participants were older (57.5 ± 7.7 vs 54.2 ± 7.9 years) and had a higher prevalence of diabetes (22.4% vs 9.9%) than participants without PD. Ten (10%) MACE-3 and 15 (15%) MACE-5 occurred in the PD group versus 18 (6%) and 24 (8%) in the matched sample (n = 303). Hazard ratios were 1.86 (95%CI 0.80-4.34) for MACE-3 and 2.06 (95%CI 1.06-4.04) for MACE-5. Competing risk models yielded similar results. No significant associations were observed with arterial stiffness parameters. CONCLUSION: PD was associated with an independently increased risk of MACE, but not with arterial stiffness.

Hypertrophic cardiomyopathy (HCM) is the most common myocardial disease in domestic cats and breed-associated variants in MYBPC3 have been reported in Maine Coon and Ragdoll cats. This study developed and analytically evaluated two polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays for detecting the MYBPC3 c.91G>C (A31P) variant in Maine Coon cats and the c.2453C>T (R820W) variant in Ragdoll cats, and applied the assays to a small Vietnamese cohort with concurrent echocardiographic phenotyping. Twenty-five Maine Coon and 34 Ragdoll client-owned cats were examined and classified using echocardiographic criteria based primarily on left ventricular wall thickness after exclusion of secondary causes of hypertrophy. The A31P assay generated a 128-bp amplicon digested with HaeIII, whereas the R820W assay generated a 319-bp amplicon digested with BccI. Restriction profiles were concordant with in silico predictions and representative Sanger sequencing results. Heterozygous carriers were detected in 3/25 Maine Coons (12.0%; mutant allele frequency 0.06) and 3/34 Ragdolls (8.8%; mutant allele frequency 0.044); no homozygous mutant cats were identified. Clinical HCM was observed in one heterozygous cat of each breed, but Fisher's exact tests did not provide evidence of genotype-HCM associations. Heterozygous cats showed exploratory differences in selected echocardiographic variables. These findings support the technical feasibility of PCR-RFLP for targeted MYBPC3 genotyping in resource-limited laboratory settings, but this cohort is underpowered for penetrance estimation, clinical risk prediction, or population-level allele-frequency inference.

The growing celebration of "skin-to-skin" time in atrial fibrillation (AF) ablation reflects a concerning shift from physiology to optics. Procedural brevity, while operationally attractive, is increasingly highlighted as a visible marker of efficiency and may at times be interpreted as a marker of excellence despite lacking mechanistic or clinical validation as a quality surrogate. AF ablation is not defined by how rapidly lesions are delivered, but by how completely arrhythmogenic substrates are interrogated, challenged, and durably eliminated. Overemphasis on speed may unintentionally de-emphasize critical electrophysiological steps, including electrophysiologic testing, inducibility assessment, mapping, and rigorous post-ablation validation. In doing so, they promote a reductionist model of AF ablation-one that values efficiency over durability and appearance over outcome. Contemporary technologies, including pulsed field ablation, have undoubtedly improved procedural workflows, but they have not altered the biological determinants of success. Durable pulmonary vein isolation, identification of non-pulmonary vein triggers, and mechanistic completeness remain central. The field must therefore resist the conflation of speed with quality. In AF ablation, excellence is not measured in minutes, but in outcomes that endure.

BACKGROUND: Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) is well established, but data on differences between men and women in real-world use, tolerability, and outcomes are limited. We examined these differences in contemporary HFrEF patients. METHODS AND RESULTS: TITRATE-HF is a prospective registry across 48 Dutch hospitals (inclusion June 2022-February 2024), enrolling patients with de novo, chronic, and worsening heart failure (HF). This analysis studied 3,367 HFrEF patients and compared men and women regarding GDMT implementation, side effects, change in left ventricular ejection fraction (LVEF), and clinical outcomes (composite endpoint: first HF hospitalization or all-cause death). The cohort included 2,408 men (71.5%; 71 years [IQR 63-77]) and 959 women (28.5%; 72 years [IQR 64-79]). At 12-month follow-up, 59.0% of men and 59.7% of women received quadruple therapy (p=0.729). Men more often achieved quadruple therapy at ≥50% of target doses (16.2% versus 11.9%, p=0.004). Compared to men, women experienced more downgrades of ARB (11.6% versus 6.9%, p=0.040) and MRA (13.2% versus 10.4%, p=0.038) due to side effects. In de novo HFrEF, women showed greater LVEF improvement than men (15% versus 13%, p=0.005). In chronic HFrEF, women had lower risk of the composite endpoint compared to men (aHR 0.64, 95% CI 0.45-0.91; p=0.015). CONCLUSIONS: GDMT initiation and sequencing were comparable between men and women, but differences were observed in dose achievement, treatment tolerability, and clinical outcomes. These findings underscore the need for implementation and dosing strategies that account for differences between men and women.

BACKGROUND: Intramyocardial injection of human pluripotent stem cell-derived cardiomyocytes after myocardial infarction improves cardiac function in large animal models, but associated ventricular arrhythmias are a major safety concern. We hypothesized that transendocardial injection of human induced pluripotent stem cell-derived committed cardiac progenitor cells (CCPs), combined with cardiac fibroblast-derived extracellular matrix (cECM) to enhance cell retention, will generate cardiac tissue grafts improving contractility without triggering ventricular arrhythmias. METHODS: Human induced pluripotent stem cells were differentiated using a bioreactor and small molecules to produce CCPs. Myocardial infarction was created using a coronary artery balloon occlusion and reperfusion model in Yucatan mini pigs. Four weeks later, transendocardial injections of CCPs+cECM (n=14), CCPs alone (n=14), cECM alone (n=4) or vehicle control (n=13) into the peri-infarct region in a randomized cohort. Arrhythmias were evaluated using implanted event recorders. Cardiac magnetic resonance imaging, invasive pressure-volume assessment, and immunohistology were performed. RESULTS: A scalable biomanufacturing protocol was developed generating CCPs. Intramyocardial delivery of CCPs to post-myocardial infarction porcine hearts resulted in engraftment and differentiation of CCPs, forming ventricular cardiomyocyte-rich grafts. There was no significant difference in cardiac magnetic resonance imaging-based measured cardiac volumes or function between control, CCP and CCP + cECM groups; however, pressure-volume analysis showed the greatest dobutamine-stimulated functional reserve in the CCP group. Delivery of CCPs did not result in tumors or ventricular arrhythmias. CONCLUSIONS: Transendocardial delivery of CCPs with or without cECM into postmyocardial infarction porcine hearts resulted in comparable human cardiomyocyte grafts that did not improve resting left ventricular function but CCPs did improve stress-induced contractile reserve without triggering ventricular arrhythmias.

The designation "not an advanced heart failure candidate" is applied to patients deemed ineligible for heart transplantation or durable left ventricular assist device (LVAD) therapy at a specific point in time. While this designation accurately captures a therapeutic boundary, it is increasingly conflated with broader notions of futility, diminished prognosis, and reduced appropriateness for cardiac intensive care unit (CICU) admission. This conflation is both clinically inaccurate and potentially harmful. Transplant and LVAD candidacy are determined by a narrow, time-sensitive, and often modifiable set of criteria that do not necessarily reflect whether a patient can benefit from invasive hemodynamic monitoring, decongestion, guideline-directed medical therapy initiation, rhythm or conduction interventions, or coronary or peripheral revascularization. Contemporary data demonstrate that acute decompensated heart failure now accounts for most cardiogenic shock cases encountered in contemporary CICUs, a population in which advanced therapy ineligibility is common yet in whom thoughtful critical care may yield meaningful hemodynamic improvement, end-organ recovery, and reassessment of candidacy. This perspective argues for a triage framework that evaluates CICU appropriateness across three independent domains: acute physiologic need, reversibility of the index derangement, and longitudinal prognosis aligned with patient preferences. Advanced therapy ineligibility should close one door, not determine how many remain open.

TOPIC IMPORTANCE: Unique features of extracorporeal membrane oxygenation (ECMO) contribute to ethical dilemmas and decisional complexity. Initiation of ECMO is a growing challenge for providers, families, and centers. OVERVIEW: We offer four practical recommendations for ethically supported, informed decision-making regarding starting ECMO. Recommendations draw on clinical experience, existing literature, and ethical frameworks, and they distinguish between offering ECMO and initiating ECMO within the broader concept of 'starting ECMO'. 1) To offer ECMO, clinicians should first determine that support is technically feasible and medically indicated, offering plausible therapeutic benefit by allowing time for recovery or effects of disease-directed therapies. Clinicians have an ethical imperative to make comprehensively reasoned, individualized, and fair decisions. As a result, ECMO decision-making should follow a robust, structured process aligned with principles of procedural fairness to mitigate barriers to high-quality deliberation. If ECMO is offered, clinicians should incorporate patient and family values into the decision to initiate ECMO, providing clinical recommendations within shared decision-making. 2) Clinicians must expand consideration of informed consent beyond a single time-point. Clinicians should engage in frequent, iterative conversations to achieve informed consent-grounded in the principle of respect for persons-throughout the ECMO course. Clinicians should emphasize ECMO as a temporary, goal-directed intervention during consent discussions to set clear expectations. 3) When ECMO is not offered, the team should document and as appropriate, communicate the rationale to patients, surrogate decision-makers, and families. 4) Institutions should establish processes including a forum to resolve disagreements, measures to capture and share organizational experience, and promote institutional accountability.

BACKGROUND AND AIM: Individuals without stenotic large-artery atherosclerosis (LAA) are an important subgroup of the patients who suffer transient ischemic attack (TIA) or ischemic stroke (IS), and they are commonly treated with dual antiplatelet therapy (DAPT). Stenotic LAA is a marker of higher vascular risk, and current guideline-defining trials did not prospectively evaluate if negative LAA status modifies the effect of DAPT. Moreover, platelet activation may not contribute as much towards future stroke risk after excluding stenotic LAA, leaving uncertainty regarding the applicability of this treatment amongst populations without this marker. We aimed to evaluate the efficacy and safety of DAPT compared with monotherapy for patients who suffered a TIA or IS without stenosis of 50% or more on vessel imaging. METHODS: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to November 2025 for publications in English. We included randomized controlled trials comparing short-term (up to 90 days) DAPT to single antiplatelet therapy after a TIA or IS with outcome data available for the groups without 50% or more stenosis on vessel imaging. Data was pooled using random-effects for non-rare outcomes and Bayesian models for rare outcomes. The primary outcome was a new ischemic or hemorrhagic stroke. We also analyzed ischemic and hemorrhagic stroke individually, moderate and severe bleeding, any bleeding, all-cause death, functionality and a composite vascular outcome. RESULTS: 8 publications met the eligibility criteria. DAPT was associated with a reduction in new stroke, with a relative risk of 0.80 (95% CI 0.65 to 0.98; p = 0.04, I² = 25.5%). Trial sequential analysis showed a substantial risk of type I error, and a sensitivity analysis restricted to studies that included only high-risk TIA or mild IS found no significant benefit. There was an increase in moderate and severe bleeding (odds ratio of 2.70, 95% Bayesian Credible Interval 1.28 to 4.85) and no differences in functionality and mortality. Heterogeneity in trial methodology and populations may limit interpretation of our findings, but sensitivity analyses evaluating the impacts of DAPT duration and region of trial conduction on new stroke did not show significant effects, although they are hindered by the small number of studies. CONCLUSION: In patients with T

BACKGROUND AND AIMS: Recent advancements in gene expression studies have shed light on the role of non-coding RNAs in negatively regulating mRNA and inhibiting mRNA translation. Given the significant impact of miRNAs on cardiovascular function, our review aims to comprehensively explore their contribution to mitigating heart injury and their protective effects during cardioplegic-induced cardiac arrest. METHODS: A systematic search conducted in December 2023 across PubMed, Web of Science, Scopus, and Google Scholar yielded valuable insights. RESULTS: Our findings indicate that cardioplegia leads to the upregulation of several miRNAs, including miR-208b, miR-499-5p, miR-10b, miR-96, miR-339-5p, and miR-483-3p, alongside the downregulation of miR-139-5p, and miR-194-5p. Many of these miRNAs are implicated in cardiac pathophysiology, particularly in myocardial injury following cardioplegia in on-pump cardiac surgery. CONCLUSION: While current applications of discovered miRNAs primarily focus on early diagnosis and prognosis of cardiac conditions, their therapeutic potential holds promise for revolutionizing the management of various heart diseases in the future. By elucidating the intricate roles of miRNAs in cardiac health and disease, this review underscores the importance of harnessing their therapeutic potential for improved patient outcomes.

BACKGROUND: Acute myocardial infarction is associated with substantial mortality risk that persists beyond the acute phase. Many existing post-acute myocardial infarction risk models were developed before contemporary advances in treatment, potentially limiting their relevance in current practice. We aimed to develop simplified machine learning-based models to predict short- and long-term mortality after acute myocardial infarction in a contemporary therapeutic context. METHODS: The Korean Artificial Intelligence-Based Risk Model for Acute Myocardial Infarction (KARMA) was developed to predict 3-month and 3-year mortality using a boosted decision tree algorithm. Model development and internal validation were performed using the KAMIR (Korea Acute Myocardial Infarction Registry)-National Institutes of Health registry (2011-2015), with external validation in the KAMIR-V registry (2016-2020). Seven routinely available clinical variables were included. RESULTS: The KARMA models demonstrated excellent discrimination for both early and late mortality. Areas under the receiver operating characteristic curves for 3-month KARMA and 3-year KARMA were 0.91 (95% CI, 0.88-0.94) and 0.85 (95% CI, 0.82-0.87), respectively, significantly outperforming the GRACE (Global Registry of Acute Coronary Events) score (3-month score: 0.79; 3-year score: 0.80) and the KAMIR score (3-month score: 0.84; 3-year score: 0.82). Kaplan-Meier curves showed clear and sustained separation across KARMA risk groups. Predictive performance was consistent across subgroups defined by age, sex, MI type, left ventricular dysfunction, and renal dysfunction. External validation in the KAMIR-V cohort confirmed robust performance (area under the receiver operating characteristic curve, 0.92 for 3-month and 0.86 for 3-year mortality). CONCLUSIONS: The KARMA scores provide a reliable and readily accessible tool for predicting short- and long-term post-acute myocardial infarction mortality. Identification of high-risk individuals would enable providers to optimize management strategies that could improve outcomes.

ST-segment elevation myocardial infarction (STEMI) remains a major cause of cardiovascular mortality and morbidity worldwide. Despite advances in reperfusion therapy, many patients still develop irreversible myocardial injury and adverse ventricular remodeling. Intracoronary mesenchymal stem cell (MSC) administration has been investigated as a potential therapeutic approach, but clinical evidence remains inconsistent. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing intracoronary MSC administration with standard care in STEMI patients. Databases were searched from inception through February 2026. Eight RCTs involving 796 patients were identified, and seven trials with 400 patients were included in the quantitative analysis after excluding one study under Expression of Concern. MSC administration significantly improved ΔLVEF (I2 = 44.6%, p = 0.108; WMD = 3.18, 95% CI: 1.52-4.83, p < 0.001). No significant differences were detected in rehospitalization for heart failure (I2 = 0.0%, p = 0.592; RR = 1.14, 95% CI: 0.36-3.61, p = 0.831), all-cause mortality (I2 = 0.0%, p = 0.525; RR = 1.51, 95% CI: 0.24-9.31, p = 0.659), or MACE (I2 = 0.0%, p = 0.887; RR = 2.47, 95% CI: 0.55-11.05, p = 0.236). Intracoronary MSC administration after STEMI is associated with a modest improvement in left ventricular function, while no reduction in clinical events was found. No major safety signal was identified, although available safety data remain limited. Larger and well-designed trials with longer follow-up are still needed. Trial Registration: PROSPERO: CRD420261286620.

TOPIC: Chronic kidney disease (CKD) and age-related macular degeneration (AMD) share vascular and inflammatory pathways. Clarifying their association could inform risk stratification across nephrology and ophthalmology. CLINICAL RELEVANCE: In adults with renal impairment, especially those with more advanced kidney dysfunction, closer AMD risk surveillance may be warranted, supporting integrated care between ophthalmology and nephrology even though causality cannot be fully confirmed from observational evidence alone. METHODS: We systematically searched MEDLINE, Embase, Scopus, and Web of Science from inception to 11 August 2025. Eligible human observational studies and Mendelian randomization (MR) analyses assessed CKD/renal metrics (eGFR, albuminuria/proteinuria, dialysis) in relation to AMD. Random-effects meta-analyses used REML with Hartung-Knapp adjustments, and pooled evidence using odds ratios (ORs) and 95% confidence intervals (95%CI). Heterogeneity was quantified using I², subgroup analyses explored design, phenotype, and CKD severity, and small-study effects were assessed using funnel plots and Egger's test when appropriate. Certainty of evidence was rated using the GRADE prognostic-factor framework. RESULTS: Nineteen studies contributed to the primary meta-analysis. CKD was associated with higher odds of AMD (OR = 1.27, 95% CI 1.07-1.50; I² = 95.1%). Effects were similar by design (P for subgroup difference = 0.84): cohorts OR = 1.29 (0.98-1.69) and cross-sectional studies OR = 1.25 (0.96-1.62). By phenotype, associations were significant for non-exudative AMD (OR = 1.46, 1.06-1.99), while exudative AMD showed an imprecise increase (OR = 1.71, 0.72-4.08), and early AMD was not statistically significant (OR = 1.32, 0.90-1.93). CKD severity analyses suggested significantly higher odds with eGFR <60 mL/min/1.73 m² (OR = 1.40, 1.15-1.72), and a stronger association in dialysis ≥90 days (OR = 1.74, 1.52-2.00). Continuous renal markers aligned with a biological gradient (per SD decrease in eGFR OR = 1.30, 1.11-1.52). Two Mendelian randomization studies supported a causal association between lower eGFR and AMD (pooled OR = 1.65, 1.54-1.76). Overall certainty ranged from moderate (any AMD overall, non-exudative AMD, dialysis exposure, MR) to low/very low for most subgroups due to heterogeneity and imprecision. CONCLUSIONS: Renal impairment, particular

BACKGROUND: Chronic kidney disease-mineral bone disorder (CKD-MBD) concerns more than 50% of patients with moderate/severe CKD, increasing their risk for fractures and cardiovascular events. PURPOSE: To present its pathogenesis, clinical presentation and management. METHODS: A Pubmed search for CKD-MBD until December 2025 was conducted using combinations of relevant terms. RESULTS: Total-body positive phosphate balance, increased levels of fibroblast-growth factor 23 (FGF-23) and sclerostin, and bone resistance to parathyroid hormone (PTH) are the earliest detected abnormalities, followed by calcitriol deficiency, secondary hyperparathyroidism, and bone minerals derangement. High bone turnover and adynamic bone disease stem from PTH excess and deficiency/resistance respectively, with the latter being prevalent in early CKD, peritoneal dialysis and post-kidney transplantation. Osteomalacia is rare, while mixed uremic osteodystrophy is rather common. Fracture risk assessment is based on fracture risk assessment tool, bone mineral density testing and vertebral morphometry, while bone biopsy remains the gold standard for renal osteodystrophy evaluation. Cardiovascular manifestations include vascular calcifications and left ventricular hypertrophy induced by mineral stress in the setting of disrupted buffering system, osteoblastic differentiation of vascular smooth cells and direct FGF-23 effects in myocardium. In severe secondary hyperparathyroidism, active vitamin D and analogues, calcimimetics, and, in refractory cases, parathyroidectomy effectively lower PTH. In mild/moderate CKD, the efficacy of all anti-osteoporotic agents is mainly proven in post-menopausal women without biochemical evidence of CKD-MBD. In dialysis patients, denosumab is the best-studied agent, while recent data highlight pronounced therapeutic benefit of romosozumab. Finally, teriparatide has demonstrated utility in treating adynamic bone disease. CONCLUSIONS: Fracture risk prevention in CKD-MBD should be prioritized. Dedicated research and validation of CKD-specific bone turnover markers may assist towards this direction.

BACKGROUND: In South and Southeast Asia, chronic diseases (CD) are a major public health concern and have a considerable impact on people's quality of life (QoL). CD and their ailments place a dual burden of sickness and socioeconomic difficulties on afflicted people and healthcare systems. AIM: This review aims to provide a comprehensive synthesis of evidence on the relationship between chronic diseases and HRQoL in the region, focusing on study populations, disease types, methodologies, sample sizes, and assessment tools used. METHODS: A systematic search was conducted to identify studies published between 2014 and 2024 that assessed HRQoL among patients with CD in South and Southeast Asia. Eligible studies included cross-sectional, observational, prospective cohort, and economic evaluation designs involving conditions such as chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), diabetes mellitus, sarcopenia, cardiovascular diseases, breast cancer, and hepatitis C. Data extracted included study design, sample size, participant characteristics, and validated HRQoL measurement instruments. RESULTS: Twenty-five studies conducted across multiple South and Southeast Asian countries were included. Sample sizes ranged from 99 to 816 participants. A variety of validated instruments were used to assess HRQoL, including the St. George's Respiratory Questionnaire (SGRQ), Kidney Disease Quality of Life (KDQOL), WHOQOL-BREF, and Short Form-36 (SF-36). Overall, CD were consistently associated with reduced HRQoL, with variations influenced by disease severity, comorbidities, and socioeconomic status. Specific challenges included reduced functional capacity among patients with sarcopenia and significant decisional conflict among patients with CKD. In addition, economic evaluations, particularly for hepatitis C treatments using direct-acting antivirals, highlighted important cost-effectiveness considerations. CONCLUSION: CD negatively affect HRQoL, which is influenced by disease severity, sociocultural factors, and barriers to healthcare access. Community-based disease management, telemedicine, culturally tailored health education, and financial protection policies may improve outcomes. Future studies should assess the effectiveness and scalability of these interventions across diverse regional settings.

BACKGROUND: In this study, we compared established equations for estimating the glomerular filtration rate (GFR) in a cohort of apparently healthy children and adolescents and aimed to evaluate the equations' validity. METHODS: Blood samples and anthropometric data from 4,776 apparently healthy participants (0.25-21 years) were analyzed. The glomerular filtration rate was estimated (eGFR) using the revised Schwartz Bedside (2009), the Cystatin C- and Serum Creatinine- based Schwartz equation, the Chronic Kidney Disease in Children (CKiD) equation, the 3 versions of the U25 (U25cys, U25scr, U25ave), the Serum Creatinine version, as well as the Cystatin-C based equation from the European Kidney Function Consortium (EKFCcr, EKFCcys), the CAPA equation, and the Cystatin C-Creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). The resulting eGFR distributions were compared, and the percentages of eGFR values within the expected physiological eGFR range (90-120 ml/min/1.73 m²) were calculated stratified by age and sex. Subsequently, age ranges with implausible distributions were identified. RESULTS: EKFCcr, CKiD, Schwartz, and U25scr yielded the highest proportion of eGFRs within the expected range and showed consistent values across age groups without large jumps. Bland-Altman analysis indicated extremely low biases between Schwartz and EKFCcr and very high biases especially between CKD-EPI, CAPA and Bedside in reference to the other equations. Males showed higher eGFRs than females. CONCLUSIONS: We found that the EKFC equations, Schwartz, and U25 resulted in eGFR distributions within the expected physiological range for an apparently healthy pediatric cohort. Estimates from simpler equations such as Bedside and CAPA were more prone to implausible results. TRIAL REGISTRATION: Clinical trial number NCT02550236 (clinicaltrials.gov, date of registration: 2014-12-15).

OBJECTIVES: Low haematocrit during cardiopulmonary bypass is a known risk factor for acute kidney injury, but it is unclear whether high haematocrit also increases acute kidney injury risk. We examined if a haematocrit range associated with a reduced risk for acute kidney injury could be identified. METHODS: This observational study included cardiac surgery patients operated on between 2016 and 2020, using prospectively collected data from the SWEDEHEART registry and a local cardiopulmonary bypass database. Acute kidney injury was defined by registry available data as a postoperative serum‑creatinine increase >1.5 times baseline or postoperative initiation of renal replacement therapy. For each predefined haematocrit threshold, weighted exposure was calculated as the accumulated time‑and‑magnitude by which haematocrit rose above or fell below the thresholds. Associations between weighted exposure and acute kidney injury were analysed using multivariable logistic regression adjusted for established acute kidney injury risk factors. RESULTS: A total of 3798 patients were included. Postoperative acute kidney injury occurred in 598 of 3798 patients (15.7%). After adjustment, a non‑linear association between haematocrit weighted exposure during aortic cross‑clamp and acute kidney injury was observed. AKI risk increased with haematocrit below 25% (adjusted odds ratio [aOR] 1.006 per 1 [%×min]; 95% confidence interval [CI] 1.002-1.009; p < 0.001) and above 38% (aOR 1.006 per 1 [%×min]; 95% CI 1.001-1.011; p = 0.019). CONCLUSIONS: In this cohort, haematocrit exposure below 25% and above 38% during aortic cross-clamp was associated with higher postoperative acute kidney injury risk. Further studies are needed to confirm these findings.

BackgroundFollowing Hurricane Helene, our rural level 1 trauma center in Eastern Tennessee managed a sharp rise in tree-related injuries. We sought to determine whether post-disaster patients required greater inpatient resources than patients injured under baseline conditions, independent of presenting injury severity.MethodsThis IRB-approved (#0125.12) retrospective study identified adult patients with tree-related injuries from our trauma registry using ICD-10 E codes. We compared a pre-Helene cohort (January 2018-September 26, 2024; n = 176) to a post-Helene cohort (September 27-December 2024; n = 25). Outcomes included ICU admission, ICU length of stay, mechanical ventilation, operative intervention, and discharge disposition.ResultsPost-Helene patients required significantly more intensive care despite presenting with similar injury severity scores and initial physiologic parameters. Mechanical ventilation was needed in 24% of post-Helene patients vs 9.1% pre-Helene (OR 3.16, 95% CI: 1.10-9.04, P = 0.025). ICU length of stay was longer post-Helene (6 days [IQR 3-16] vs 3 days [IQR 2-7], P = 0.036). Discharge to extended care facilities was more frequent (36% vs 15.9%, OR 2.97, 95% CI: 1.20-7.39, P = 0.015). Post-Helene patients also carried a substantially higher burden of cardiopulmonary and renal comorbidities.ConclusionIn a rural disaster setting, tree-related trauma patients placed greater demands on critical care, ventilator, and post-acute resources than their initial presentations predicted. Hospital preparedness plans for rural level 1 trauma centers must account for this gap between triage acuity and downstream resource utilization.

The 2026 AHA/ACC guideline on acute pulmonary embolism introduces normotensive shock as a clinically relevant pre-cardiopulmonary failure state with implications for treatment escalation. Evidence from cardiogenic shock indicates that tissue hypoperfusion despite preserved arterial blood pressure is associated with substantial mortality, underscoring the need for early recognition. This requires reliable, rapidly obtainable, and broadly applicable criteria. As several proposed indicators are limited by delayed availability or restricted bedside use, shock assessment should integrate concordant clinical signs of tissue hypoperfusion rather than rely on a single marker. Prolonged capillary refill time and skin mottling may complement lactate as bedside markers of abnormal skin perfusion. Critical care echocardiography further supports this multimodal approach by confirming acute right ventricular pressure overload, excluding alternative causes of circulatory failure, and assessing right ventricular adaptation and right ventricular-pulmonary arterial coupling. Early recognition may identify patients at imminent risk of deterioration who could benefit from timely treatment escalation, including consideration of reperfusion therapy.

BACKGROUND: Acute pulmonary embolism remains a major cause of cardiovascular mortality, and static D-dimer measurements may not fully capture short-term mortality risk. METHODS: We conducted a retrospective cohort study of adult intensive care unit patients with acute pulmonary embolism. Latent class growth modeling (LCGM) identified D-dimer trajectories during the first 10 days following acute pulmonary embolism diagnosis. Associations with 30-day all-cause mortality were assessed using Cox proportional hazards models and Kaplan-Meier analysis. Incremental prognostic value beyond the baseline prediction model was evaluated using area under the curve (AUC), integrated discrimination improvement (IDI), net reclassification improvement (NRI), and the median improvement in risk score. Sensitivity analyses included landmark analyses and an alternative five-class Trajectory Model. RESULTS: Among 303 patients, four D-dimer trajectories were identified: low and stable, mildly elevated and stable, highly elevated and decreasing, and persistently elevated. Compared with the "low and stable" trajectory, the "persistently elevated" trajectory was associated with the highest 30-day all-cause mortality in both unadjusted (HR, 15.06; 95% CI: 7.61-29.80; p < 0.001) and the fully adjusted model (HR, 5.08; 95% CI: 2.32-11.09; p < 0.001). Survival curves differed significantly across trajectory classes. Adding D-dimer trajectory membership to the Baseline Model improved discrimination (increased the AUC from 0.90 to 0.93; p = 0.04) and reclassification (IDI: 0.07; NRI: 0.28). The findings remained robust in subgroup analyses, landmark analyses, and the alternative five-class model. CONCLUSION: Distinct D-dimer trajectories were associated with 30-day all-cause mortality. The persistently elevated trajectory identified a high-risk subgroup and improved mortality prediction.

BACKGROUND: Up to 40% of patients with chronic obstructive pulmonary disease (COPD) have evidence of elevated eosinophil counts ≥ 300 cells/μL at some point during their disease. Blood eosinophil counts (BECs) are a biomarker that can identify patients with COPD and type 2 inflammation who are candidates for add-on inhaled corticosteroids (ICS) or biologic therapy. Evidence from real-world and clinical trial data shows variation in BECs over time in patients with COPD and type 2 inflammation. OBJECTIVE: In this article, we discuss factors that can influence eosinophil counts, how the use of historical eosinophil counts can inform treatment decisions, and practical considerations for identifying underlying type 2 inflammation in patients with COPD in the clinic. EXPERT OPINION AND CONCLUSIONS: Currently, there is no consensus on what constitutes "low" or "high" BEC in COPD or the frequency or number of eosinophil measurements needed to effectively guide disease management. Based on our experience from the clinic and available literature, we propose four broad phenotypic groups of patients with COPD: those with BEC predominantly ≥ 300 cells/μL, intermittently ≥ 300 cells/μL, within an intermediate range of 100 to 300 cells/μL, and those with BEC predominantly < 100 cells/μL. Identifying these patterns can help with more precise stratification for pharmacological interventions, such as adding ICS or biologic therapies. While single BEC measurements are easy to obtain and often sufficient to identify patients with COPD and high levels of type 2 inflammation, when interpreted alongside clinical characteristics, repeated BECs may be able to support a more personalized approach to COPD care.

BACKGROUND: Pulmonary embolism (PE) remains a complex clinical challenge with significant morbidity and mortality. Despite significant advancements in diagnosis and management, as well as the availability of recent guidelines, disparities in their implementation persist due to socioeconomic factors and other barriers. The study aims to assess the degree of implementation of guidelines in the diagnosis and management of PE. RESULTS: Among 8,648 patients presenting to the National Heart Institute emergency department, 200 were diagnosed with acute PE, accounting for 2.3% of ED visits during the study period. The mean age was 56.7 ± 9.8 years, with 58% being female. Dyspnea was the most common symptom, occurring in 64% of cases, while bed rest for > 3 days was the most frequent risk factor (32%). Computed tomography pulmonary angiography (CTPA) confirmed PE in 95.5% of cases. Risk stratification classified 80% as low to intermediate-low risk, 13% as intermediate-high risk, and 6% as high-risk. Unfractionated heparin monotherapy was initiated in 63% of patients, while only 8.5% were discharged on direct oral anticoagulants (DOACs). Mortality was 3%, including 1% due to life-threatening bleeding. There was notable overuse of D-dimer testing, underutilization of ventilation-perfusion (V/Q) scans, limited prescription of DOACs, and absence of interventional therapies in eligible patients. CONCLUSIONS: This study highlights critical gaps in adherence to PE management guidelines, influenced by physician discretion, socioeconomic constraints, and diagnostic inconsistencies. Strengthening outpatient care pathways, refining risk stratification practices, and ensuring consistent guideline implementation are key priorities to optimize outcomes.

RATIONALE: Supplemental oxygen use in COPD is a readily usable signal for progression to advanced disease and limited prognosis, but it is unclear whether this is reflected in different patterns of end-of-life (EOL) healthcare use or advance care planning (ACP). OBJECTIVE: To determine whether older adults with COPD using supplemental oxygen have different EOL healthcare use and ACP engagement compared to those without oxygen. METHODS: We analyzed nationally-representative Health and Retirement Survey data (2012-2018), including decedents aged ≥50 with COPD and self-reported oxygen use. Proxies completed post-death interviews about healthcare use (hospitalization, intensive care, life support equipment [e.g., mechanical ventilation], hospice, palliative care use) and ACP (durable power of attorney, advance directives, care preferences) within the last two years of life. We report adjusted probabilities derived from logistic and linear regression models adjusted for sociodemographics and comorbidities for the associations between oxygen use and EOL healthcare and ACP outcomes. RESULTS: Among 848 decedents (mean age 81, 53% female, 82% White), 47% used supplemental oxygen for a median of 2 years (IQR: 1-4) before death. Compared to those without oxygen, those using oxygen had higher mean hospital days (12.4 vs 9.8 days, p = 0.03), intensive care (54% vs 40%, p = 0.001) and life support use (42% vs 27%, p < 0.001) in the last two years of life. In contrast, rates were similar for use of palliative care (26% vs 24%), hospice (48% vs 48%), and ACP, including completion of durable power of attorney (74% vs 74%) and advance directives (56% vs 56%). Among those who completed advanced directives (n = 464), decedents with and without oxygen use expressed similarly high preferences to limit care (88% vs 88%) and focus on comfort (91% vs 87%). CONCLUSIONS: Supplemental oxygen use in older adults with COPD was associated with substantially higher hospital, ICU, and life support use at EOL. Yet, overall ACP engagement and palliative care use was low and those who completed advance directives had strong preferences to limit care. Supplemental oxygen may be an important and under-utilized indicator for integration of timely palliative care among older adults with COPD.

The primary purpose of this review is to compare the implementation of Balint groups (mandatory versus voluntary participation) in medical training, particularly for medical students and psychiatry trainees, and the accreditation pathways for Balint leaders across the United Kingdom (UK), the United States (USA), Ireland, Canada, and Germany. The review aims to highlight the rationales and implications of each model. A comparative literature review was conducted to evaluate existing approaches in the specified countries, drawing on national guidelines, society requirements, and relevant studies. The methods focused on identifying specific requirements set by governing bodies such as the Royal College of Psychiatrists (UK), the American Balint Society (ABS), the College of Psychiatrists of Ireland, and the German Medical Association. Data were handled by summarizing the variations in implementation and accreditation. Implementation varies significantly; the UK, Ireland, Canada, and Germany typically mandate some form of reflective group work for psychiatry trainees, linking it to progression or certification. Ireland and Germany have explicit session requirements, while the USA largely maintains a voluntary model. Accreditation pathways share core philosophies but differ in specific hour requirements, with European pathways being more rigorous than the portfolio-based models in the USA and Canada. The global trend recognizes a clinician's emotional awareness as crucial for effective patient care, pushing toward mandatory exposure to reflective group work in psychiatry training. To ensure consistency across diverse national Balint societies, the International Balint Federation could develop global minimum standards for participation and co-leadership to eliminate ambiguity.

Financial toxicity (FT) is increasingly recognized as an important patient-centered burden in cancer care. However, the heterogeneity of FT and its associations with healthcare utilization and catastrophic health expenditure (CHE) among patients with primary liver cancer (PLC) remain insufficiently understood. This study aimed to identify latent profiles of FT among patients with PLC and to examine their associations with healthcare utilization and CHE. We conducted a retrospective cohort study of consecutive adult patients with PLC who received inpatient and/or outpatient care between December 2024 and December 2025 (N = 720). FT was assessed using the COmprehensive Score for FT and multidimensional hardship indicators, including material hardship, financial worry, and coping behaviors. Latent profile analysis was used to identify FT profiles. Healthcare utilization outcomes included annual counts of outpatient visits, inpatient admissions, and emergency department visits. CHE was defined as annual out-of-pocket spending exceeding 40% of household capacity to pay, with a 25% threshold used in sensitivity analyses. Associations between FT profiles and utilization were estimated using covariate-adjusted negative binomial regression, and associations with CHE were estimated using covariate-adjusted logistic regression. A 3-profile solution was identified, comprising low FT (45.0%, n = 324), moderate FT (37.5%, n = 270), and high FT (17.5%, n = 126). Overall, the mean COmprehensive Score for FT score was 25.0 (standard deviation 10.9), and CHE occurred in 27.0% of participants. Compared with the low FT profile, the moderate and high FT profiles were associated with lower outpatient visit rates but higher inpatient admission and emergency department visit rates. CHE prevalence increased stepwise across the low, moderate, and high FT profiles. In adjusted models, moderate FT and high FT were associated with higher odds of CHE compared with low FT. Findings were robust using the 25% capacity-to-pay threshold. Patients with PLC exhibit distinct FT profiles that are strongly associated with healthcare utilization patterns and CHE risk. Routine FT screening and profile-informed interventions may help improve care continuity and strengthen financial protection in PLC management.

Robotic-assisted surgery has transformed minimally invasive surgery worldwide, offering improved precision, visualization, and dexterity. However, evidence describing program implementation and perioperative outcomes in low- and middle-income countries remains limited. This study describes the initial institutional experience of a multidisciplinary robotic-assisted surgery program in Peru. A retrospective cohort study included consecutive adult patients undergoing robotic-assisted surgery during the early implementation phase (December 1, 2024 to March 31, 2026) at a national referral center in Peru. Demographic, clinical, procedural, and perioperative outcomes were collected. Multivariable linear regression identified independent predictors of operative time. A total of 398 robotic-assisted procedures were analyzed. Mean age was 49.8 ± 17.2 years, and 68.2% of patients were female. Most procedures were performed for benign disease (64.8%), followed by malignancy (29.4%) and complex/reconstructive indications (3.8%). Cholecystectomy (18.1%) and hysterectomy (17.6%) were the most common procedures. Mean operative time was 236.8 ± 152.1 min. The conversion rate was 7.5%, postoperative complications occurred in 10.3% of patients, mean length of stay was 7.68 ± 8.17 days, 30-day readmission was 2.5%, and no postoperative mortality occurred. Increasing age (β = 0.85 min/year; p = 0.032), male sex (β = 52.3 min; p = 0.011), and higher ASA classification (β = 8.7 min/category; p < 0.001) independently predicted longer operative time. The model explained 54% of operative-time variability (R²=0.54). Early implementation of a multidisciplinary robotic-assisted surgery program in a Peruvian public referral hospital demonstrated broad procedural adoption, acceptable perioperative outcomes, and predictable variation in operative duration. These findings provide an implementation benchmark for robotic-assisted surgery in resource-limited healthcare systems.

BACKGROUND: Sarcoidosis is a heterogeneous granulomatous disease with an unpredictable course. Population-level evidence describing its long-term trajectories and their prognostic implications remains limited. METHODS: We identified individuals newly diagnosed with sarcoidosis in the Swedish National Patient Register (≥ 2 ICD-coded visits; 2006-2018). Sarcoidosis-related visits over five years were modeled using zero-inflated Poisson finite mixture models to identify trajectories. Baseline demographic and clinical predictors of trajectory membership were assessed with Poisson regression. Associations between trajectories and long-term outcomes were estimated using multivariable Cox regression. Supplementary analyses incorporated clinical, genetic, and physiological data from the Karolinska cohort. RESULTS: Among 9665 patients, two distinct trajectories were identified: a resolving trajectory (71.5%) with near-complete remission of sarcoidosis-related visits within two years, and a chronic trajectory (28.5%) with persistently elevated visit rates over five years. Older age modestly increased the risk of chronic disease. The strongest predictor of chronic disease was immunosuppressive treatment around diagnosis (risk ratio 2.18 [95% CI 2.04, 2.33]). Diagnosis in neurology, ophthalmology, or cardiology, uveitis, and hospitalization at diagnosis were also associated with chronicity, whereas diagnosis in rheumatology and dispensation of non-steroidal anti-inflammatory drugs were protective. In the Karolinska cohort, Löfgren's syndrome and HLA-DRB1*03 were strongly associated to a resolving course. Chronic sarcoidosis was associated with higher risks of infection, heart failure, diabetes, depression, anxiety, and early death. CONCLUSIONS: Sarcoidosis follows two long-term trajectories. Clinical phenotype and need of early treatment predict chronicity, which is associated with substantial long-term morbidity and mortality. Early prognostication may support personalized sarcoidosis management.

BACKGROUND: Characterizing the incidence and determinants of corneal abrasions in burn patients and evaluating the roles of burn severity, comorbidities, and social determinants of health (SDOH) in shaping risk can inform screening and care. METHODS: We conducted a retrospective cohort study of patients admitted to a regional burn center between January 1, 2019, and January 1, 2024. Eligible patients had documented burns and a complete ophthalmologic examination at admission. Demographics, burn severity, comorbidities, SDOH indices (Social Vulnerability Index [SVI], Area Deprivation Index [ADI]), geographic access, and outcomes were abstracted from the medical record. Group comparisons were performed using standard statistical tests. RESULTS: Among 2023 patients, 90 (4.4%) had corneal abrasions. They had greater total body surface area burned (17.5% vs 6.2%, P < 0.001) and longer hospitalizations, intensive care unit stays, and ventilation durations (all P < 0.001). Abrasions were associated with inhalation injury (58% vs 19%, P < 0.001) and in-hospital mortality (18.9% vs 4.9%, P < 0.001). Patients with abrasions traveled farther (151 vs 121 miles, P = 0.02) and were more often from out of state (8.2% vs 3.6%). No significant differences were found in SVI, ADI, or most comorbidities, though diabetes was less common (7.8% vs 16.4%, P = 0.04). CONCLUSION: Corneal abrasions occur in about 1 in 20 burn admissions and are strongly associated with burn severity and critical illness. Geographic distance and incomplete race documentation were additional risk factors, while SDOH indices and diabetes were not. These findings identify corneal abrasions as markers of systemic severity and health system disparities, supporting standardized eye-care protocols for high-risk burn patients.

BACKGROUND: Pelvic mesh implants are commonly used in female urology for the treatment of stress urinary incontinence and pelvic organ prolapse. However complications can be substantial and a number of the patients in this cohort proceed to mesh explantation. We evaluated urinary morbidity after pelvic mesh removal within New Zealand's National Mesh Service. METHODS: Retrospective review of women undergoing pelvic mesh removal between March 2009 and December 2024 by the National Mesh Service. Primary outcomes were patient-reported urinary symptoms using validated instruments: Pelvic Floor Distress Inventory [PFDI] and International Consultation on Incontinence Questionnaire-Short Form [ICIQ-SF]. Secondary outcomes included clinician-reported symptoms at last follow-up, reintervention for incontinence, and complications (Clavien-Dindo). RESULTS: Of 345 patients (median age 58 years; median 105.3 months from insertion to removal), pain was the commonest indication for explantation, followed by bladder outlet obstruction/lower urinary tract symptoms. Among 184 with urodynamics, 32% met criteria for likely/definite outlet obstruction. Robotic assistance was used in 97 cases. Eight patients (2.3%) developed Grade III complications. Mean follow-up was 27.2 months. Post-removal, clinician-reported persistence of SUI, pain, and overactive bladder was seen in 30-40%, dyspareunia in 20%, recurrent urinary tract infection in 9%, and obstructive voiding in 12%. Overall, 25% needed concurrent procedure during pelvic mesh removal and 48% required ≥ 1 subsequent incontinence procedure. 6 patients ultimately underwent cystectomy. In 83 patients with paired PFDI, mean total scores improved from 168.4 to 149.6 (p < 0.05) with concordant subscale improvements. ICIQ-SF severity categories showed minimal overall shift. CONCLUSIONS: Urinary morbidity after pelvic mesh removal is common and frequently persists despite explantation, with high reintervention rates indicating chronicity. Findings support robust pre-operative counselling, multidisciplinary care, and prospective studies to define predictors and optimise surgical pathways.

BACKGROUND: Functional abdominal pain syndrome (FAPS) is a relatively uncommon functional gastrointestinal disorder. Recent years have witnessed substantial advancements in the study of FAPS; however, no bibliometric analyses have been conducted to date. OBJECTIVE: This study systematically reviews current research and emerging issues in the field of FAPS using bibliometric methods to understand research trends and future development prospects. METHODS: The foundational literature in the field of FAPS was sourced from the Web of Science database. Visual analysis was performed using CiteSpace and VOSviewer software, focusing on factors such as the number of published papers, countries (regions), research institutions, journals, authors, highly cited papers, and keywords. RESULTS: From 1996 to 2025, 996 publications were analyzed, showing a phased growth in annual publication volume peaking in 2021. The United States led in publications and centrality. The "Journal of Pediatric Gastroenterology and Nutrition" had the highest publication count. Marc A. Benninga authored the most articles, notably "Functional Disorders: Children and Adolescents." The prevalent keyword was "children." Research on FAPS focuses on evolving disease definitions, the "brain-gut interaction disorder" paradigm, the microbiota-gut-brain axis, children with irritable bowel syndrome, functional abdominal pain, and nonpharmaceutical therapies like probiotics, dietary interventions, and cognitive behavioral therapy. Pediatric populations and non-pharmacological interventions were the most prominent themes, whereas adult-specific research and biomarker-related studies appeared less frequently. CONCLUSION: This bibliometric study identified key research areas including the microbiota-gut-brain axis, pediatric populations, and non-pharmacological interventions, alongside emerging topics such as gut-brain interaction disorders. These findings suggest that future research should prioritize large-scale trials validating non-pharmacological therapies and biomarkers for central sensitization. Clinically, the development of age-specific diagnostic protocols and interdisciplinary management teams integrating gastroenterology, neurology, and psychology is warranted to improve patient outcomes.

Free flap failure secondary to microvascular thrombosis remains a significant complication in reconstructive surgery, and timely detection of vascular compromise is critical to maximize salvage. This retrospective cohort study evaluated 932 free flaps performed over a four-year period at a tertiary center, of which 302 were monitored postoperatively using Masimo's O3® Regional Oximetry system's near-infrared spectroscopy (NIRS) device in addition to standard clinical assessment. Primary outcomes included re-exploration, complete flap failure, and salvage following take-back. The overall re-exploration rate was 7.9%. Flaps monitored with NIRS demonstrated higher salvage rates following re-exploration and lower complete flap failure rates compared with clinical monitoring alone. Use of NIRS during the index reconstruction was independently associated with improved flap survival. Receiver operating characteristic analysis demonstrated good discriminative performance of NIRS trend changes for predicting flap compromise, and a 22.5% reduction in regional oxygen saturation was identified as the optimal threshold for detecting early vascular compromise. These findings support the use of adjunctive NIRS surveillance as a reliable modality for postoperative free flap monitoring and provide an objective threshold to assist clinical decision-making.

BACKGROUND: Hospital-based violence intervention programs (HVIPs) provide victims of violence with case management services to promote healing and reduce violent reinjury. Life Outside Violence (LOV), the St. Louis region-wide HVIP, is the first multisystem HVIP in the country. The objective of this study was to describe rates of individualized treatment plan (ITP) goal completion among adolescent and young adult LOV participants and explore differences across ITP goal categories. METHODS: This is a retrospective observational cohort study of patients aged 8-30 who presented to a LOV partner hospital for a violent injury between August 15, 2018 and December 31, 2024 and participated in LOV. The LOV REDCap database was queried for patient demographics, injury type, ITP goal category, and goal completion. Analysis included descriptive statistics of participant characteristics and goal categories set and completed. RESULTS: This cohort included 263 LOV participants who were primarily black (96%), male (63%) young adults (51%) and injured by a firearm (63%). A majority of LOV participants (85%) identified an ITP goal; of these 139 (62%) completed at least one goal. The most common goal category identified was Health and healthcare (34%), within which the subcategory of Mental health was prominent (58%). Social and community goals were completed at the highest rate (70%). CONCLUSIONS: HVIPs are highly individualized programs that address the unique needs of violent injury survivors. Overall, LOV participants set and completed ITP goals at a high rate. Findings indicated robust support for social and community related goals. These findings can inform patient-centered service provision and evaluation methods among other HVIPs and violence intervention programs.

BACKGROUND: Migration is a well-established risk factor for psychosis, yet limited research has examined long-term clinical trajectories following first-episode psychosis (FEP) in migrant populations within Southern European settings. This study investigates how country of origin and time since migration influence psychiatric outcomes in a naturalistic FEP cohort. METHODS: A 5-year longitudinal study was conducted on 184 patients with FEP attending the Early Intervention Service from Hospital Universitari de Mataró. Patients were grouped by geographic origin (Spanish, Latin American, Maghrebi, Sub-Saharan) and migration recency (≤5 years vs. >5 years). Primary outcomes included treatment adherence, use of long-acting injectable (LAI) antipsychotics, relapse, and service disengagement. Logistic regression and survival analyses were used to identify associations. RESULTS: Maghrebi origin was associated with lower treatment adherence (OR = 0.32, 95% CI [0.12-0.89], p = 0.030). In time-to-event analyses, Maghrebi patients showed a higher hazard of service disengagement compared with Spanish-born patients (HR = 2.42, 95% CI [1.10-5.34], p = 0. 028). Recent migrants (≤5 years in Spain) also had a significantly increased hazard of disengagement (HR = 2.89, 95% CI [1.30-6.40], p = 0.009). Sub-Saharan origin was strongly associated with earlier initiation of long-acting injectable antipsychotics (HR = 3.40, 95% CI [1.58-7.32], p = 0.002), alongside higher overall odds of LAI use. No significant differences were observed in relapse rates across groups. CONCLUSIONS: Both migrant origin and recent arrival were associated with differences in psychiatric care trajectories following FEP. These findings highlight the need to consider adaptation of treatment approaches for migrant populations according to their origin and migration context in order to improve long-term outcomes.

INTRODUCTION: The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) is recommended by peri-operative core outcome sets as a measure of disability. Despite its growing use, the effect of different surgical procedures on disability measured by WHODAS 2.0 remains poorly understood and heterogeneous reporting across studies limits direct comparison. METHODS: We conducted a systematic review to assess the effect of different surgical procedures on disability measured by WHODAS 2.0, and the reporting of disability endpoints in peri-operative medicine. The primary outcome was the difference in WHODAS 2.0 summary score before and after surgery. Disability scores were calculated as a metric between 0% (no disability) and 100% (complete disability). RESULTS: Thirty-nine studies were included. Pre-operative disability ranged from 2% to 61%. In 21 studies, disability increased by 1% to 17% within 3 months of surgery, with little change between 6 and 12 months (0% to -2%). Studies of orthopaedic surgery generally reported high pre-operative disability (> 35%) but also reductions in disability (10-37% reduction) within 3 months of surgery. In contrast, studies evaluating cancer surgery (n = 12) generally reported lower pre-operative disability (< 20%) but small increases (1-8%) within 3 months of surgery. Cardiovascular surgical studies displayed pre-operative disability between 4% and 17% with a difference in disability of -8% to +3% 3 months after surgery. Three different thresholds to define disability and 13 different WHODAS 2.0 endpoints were used, measured at eight different time-points after surgery. DISCUSSION: The effect of surgical procedures on postoperative disability as measured by WHODAS 2.0 is influenced by the type of surgery. Orthopaedic surgery may decrease disability, whereas cancer surgery may be associated with persistent increases. Standardised reporting of disability endpoints is needed to enhance the quality and comparability of future studies using WHODAS 2.0.

PURPOSE: The incidence of invasive fungal infection (IFI) in pediatric liver transplant (LT) recipients in Korea has not been characterized; consequently, antifungal prophylaxis is not covered by the national health insurance. We aimed to determine the incidence and epidemiology of IFI. MATERIALS AND METHODS: We conducted a single-center, retrospective study of children (age ≤19 years) who underwent LT at Severance Children's Hospital, Republic of Korea (2012-2023). IFI was defined as fungal isolation from a sterile site (fluid/blood/tissue) with compatible clinical features. RESULTS: Of the 126 LT cases involving 115 children, 69.0% (n=87) were performed due to biliary atresia. Twenty-four IFI episodes in 20 recipients yielded a 90-day post-LT crude incidence of 19.0% and an incidence rate of 0.14 per 1000 patient-days. Invasive candidiasis predominated (95.4%) with Candida albicans (40.9%), C. parapsilosis (31.8%), and C. auris (9.1%). The most common clinical manifestations were peritonitis (54.2%) and fungemia (16.7%). Emergency LT [subdistribution hazard ratio (sHR), 3.97; 95% confidence interval (CI), 1.39-11.3; p=0.010] and reoperation or interventional procedures (sHR, 4.05; 95% CI, 1.53-10.7; p=0.005) were independently associated with IFI. One-year overall survival was significantly lower in the IFI group than in the non-IFI group (58.4% vs. 82.8%, p=0.037). CONCLUSION: IFIs impose a burden on pediatric LT recipients in Korea and are associated with poorer survival. These data support the consideration of universal antifungal prophylaxis. However, multicenter studies are warranted to validate these findings and define the prophylaxis regimen.

BACKGROUND: Pediatric care is becoming increasingly regionalized. A rise in pediatric admissions following transfer may indicate increasing pressure on health systems to accommodate pediatric care. We evaluated nationwide trends in children admitted following transfer. METHODS: We performed a retrospective repeated cross-sectional study of the Kids' Inpatient Database in 2009, 2012, 2016, 2019, and 2022. Using logistic regression, we evaluated longitudinal changes of children admitted to the hospital following transfer overall. We stratified by hospital type, medical complexity, presence of trauma, and diagnosis. We evaluated changes in costs attributed to transferred-in patients. RESULTS: Over the 13-year study period, overall admissions decreased by 61 344 per year (95% CI, -74,013 to -48,675). Admissions following transfer increased by 7714 per year (95% CI, 5339-10 090), and the likelihood of a transferred-in admission rose by 5.7% annually (95% CI, 4.7%-6.7%). The increase in transferred-in admissions was noted in all hospital types and with or without trauma. The likelihood of transferred-in admissions for children without medical complexity was greater than in children with medical complexity (6.4% per year [95% CI, 5.3%-7.6%] vs 4.2% per year [95% CI, 3.2%-5.2%]). Most diagnoses demonstrated an increase in transferred-in admissions. The share of costs for transferred-in patients increased from 17.2% in 2009 to 29.5% in 2022. CONCLUSION: Transferred-in admissions and costs increased, with greatest relative increases in rural hospitals, non-medically complex children, and select admission diagnoses. These findings highlight a growing reliance on interfacility transfer and suggest a need to bolster local pediatric capacity and regional care coordination.

BackgroundPostoperative pain remains a major concern after anorectal surgery, contributing to delayed discharge and increased opioid use. Although perioperative gabapentin has been evaluated in multiple surgical settings, its clinical value in anorectal surgery remains uncertain.MethodsA systematic search of PubMed, Scopus, and the Cochrane Central Register of Controlled Trials identified studies published through May 2025. Randomized clinical trials and observational cohorts comparing preoperative gabapentin with placebo or standard analgesia in patients undergoing anorectal surgery were included. The primary outcome was 24-hour postoperative pain measured on the Visual Analogue Scale (VAS). Mean differences (MDs) were pooled using a random-effects model with 95% confidence intervals (CIs), and heterogeneity was quantified using the I2 statistic. To assess robustness and clinical probability, a complementary Bayesian random-effects meta-analysis was performed. Analyses were conducted in R (version 4.4.2).Results6 studies, including 504 patients (242 gabapentin and 262 control), were included. Among these, postoperative pain at 24 hours (VAS) was available in four studies comprising 415 patients. Pooled results demonstrated significantly lower 24-hour VAS scores with gabapentin (MD = -2.10 cm; 95% CI -3.98 to -0.22; P = 0.029; I2 = 99.2%). The Bayesian model favored gabapentin, with a posterior probability of benefit of 99.8%.ConclusionGabapentin shows a statistically detectable reduction in postoperative pain after anorectal surgery, but the effect is heterogeneous and supported by very low certainty evidence, making its clinical relevance uncertain and limiting its role in routine practice.

PURPOSE: To identify pre/perioperative factors that predict graft failure after Descemet membrane endothelial keratoplasty (DMEK). METHODS: This retrospective cohort study included consecutive eyes that underwent DMEK in 2015-2023 in a regional referral hospital and were followed for at least 12 months. DMEK-graft failure was defined as need for regrafting during follow-up. Univariable analysis of graft-failure associations with 20 covariates was performed. Hierarchical multivariable analysis was conducted for DMEK-graft failure with covariates whose univariable-analysis p-values were ≤0.15. Posthoc univariable analyses were performed to elucidate the mechanisms by which covariates promoted DMEK-graft failure. RESULTS: 171 eyes (129 patients) with mostly Fuchs endothelial corneal dystrophy (94%) were included. Median (range) follow-up was 24 (12-29) months, during which 15 grafts (9%) failed. On univariable analyses, graft failure associated with eight variables, including long (≥25 mm) preoperative axial length (AXL): 40% of graft-failure eyes had AXL ≥ 25 mm vs. 13% for graft-success eyes (p = 0.01). On multivariable analysis, graft failure was predicted by AXL ≥ 25 mm (OR=5.70; 95%CI = 1.27-25.68; p = 0.02), younger graft-donor age (OR=0.93; 95%CI = 0.88-0.99; p = 0.02), graft-unscrolling/positioning difficulties (OR=6.93; 95%CI = 1.58-30.48; p = 0.01), and major graft detachment (OR=6.28; 95%CI = 1.36-28.96; p = 0.02). The model accounted for 14% of total graft-failure variance. Posthoc univariable analysis showed that eyes with AXL ≥ 25 experienced graft-unscrolling/positioning difficulties more often than shorter eyes (27% vs. 10%, p = 0.0497). CONCLUSIONS: Eyes with long AXL (≥25 mm) may be more prone to DMEK-graft failure than shorter eyes. This may reflect the deep anterior chamber, which can complicate graft unscrolling and/or graft positioning. The additional graft handling may induce endothelial-cell loss and subsequent graft failure. Younger donor age weakly predicted DMEK-graft failure, possibly due to tighter scrolling of younger grafts. Major graft detachment strongly predicted DMEK-graft failure. This could reflect surgical and/or rebubbling-induced endothelial damage and/or pre-existing graft weakness.

BACKGROUND: This multicenter retrospective study aimed to develop and validate a prognostic nomogram incorporating preoperative immunonutritional indices and postoperative pathological factors to predict overall survival (OS) in patients with ampullary adenocarcinoma (AAC) undergoing pancreaticoduodenectomy. METHODS: We analyzed 102 AAC patients treated at the National Cancer Center Hospital, randomly divided into a pilot (n = 71) and an internal validation cohort (n = 31). Candidate variables were screened using univariate Cox regression (P < .20) and variance inflation factor analysis. A multivariable Cox model was constructed using age, platelet-to-lymphocyte ratio, prognostic nutritional index, lymphatic invasion, and nodal status. The model was visualized as a nomogram to estimate 3- and 5-year OS. Performance was evaluated using the concordance index (C-index), time-dependent receiver operating characteristic curves, and Kaplan-Meier analysis. An independent cohort from Hamamatsu University School of Medicine (n = 25) was used for exploratory external validation. RESULTS: The nomogram showed higher area under the curves (AUCs) than tumor-node-metastasis (TNM) classification, with AUCs of 0.742 and 0.792 for 3- and 5-year OS (vs. 0.615 and 0.648 for TNM). The mean C-index was 0.713 in internal validation. Kaplan-Meier analysis demonstrated risk stratification, with a trend toward worse OS in the high-risk group (P = .090). A similar separation was observed in the external cohort. T stage was not a significant predictor. CONCLUSIONS: This nomogram integrating immunonutritional and pathological factors may improve OS prediction beyond TNM staging in AAC and provide a practical tool for perioperative risk stratification.

The objective of this study was to determine whether protocolized triage using the Rib Injury Guidelines (RIG) can safely reduce intensive care unit (ICU) admissions and improve institutional resource utilization in a rural, Appalachian, level 1 trauma center. This was a single-center retrospective cohort study that included a total of 1148 adult patients who presented to the institution with radiographically confirmed rib fracture(s) over the course of 2 years (557 pre-RIG, 591 post-RIG). Prior to RIG implementation, triage decisions were made at the discretion of the attending provider using a protocol based on three factors: ≥3 rib fractures, age >65, and incentive spirometry (IS) <1L or <15 mL/kg ideal body weight (IBW). Patients in the post-RIG group were of higher acuity with a significantly higher percentage having ≥3 rib fractures (53.3% vs 45.2%, P = 0.006) and thoracic injuries as their highest Abbreviated Injury Scale (AIS) score (56.0% vs 24.6%, P < 0.001). Despite this higher acuity, implementation of RIG was associated with a 28.9% decrease in ICU admissions from the ED (OR 0.711, 95% CI: 0.563-0.899, P = 0.004) without a corresponding increase in floor-to-ICU transfers (P = 0.166), unplanned intubations (P = 0.803), morbidity, or mortality (P = 0.364). Additionally, it reduced the hospital charges incurred by each patient. These findings suggest that protocolized triage using RIG is feasible and safe in rural settings, improving resource utilization without compromising patient outcomes.

BACKGROUND: Fluid accumulation (FA) and fluid depletion (FD) are associated with worse outcomes in critically ill patients. However, it is not known at what threshold a positive or negative fluid balance leads to impaired organ function and impacts outcomes. The aim of this study was to investigate the association between the degree of weight-adjusted fluid balance (wFB) and the days alive without life support (DAWOLS) and to identify proposed wFB thresholds. METHODS: Retrospective, single-centre cohort study including adult ICU patients. The association between wFB three days after ICU admission and DAWOLS was examined. The lowest positive / highest negative wFB with a statistically significant and relevant association with DAWOLS was determined as threshold for a significant FA and FD, respectively. In addition, we analysed the association between FA / FD and mortality, organ support, length of stay, and delirium. RESULTS: In the 17'956 patients included in this analysis, we identified a wFB cut-off of +7% and -4% to be significantly associated with DAWOLS (p < 0.001). Using these cut-offs, FA (regression coefficient β -3.92 (95%-CI -4.37; -3.46), p < 0.001) as well as FD (-0.95 (-1.35; -0.54), p < 0.001) were significantly associated with DAWOLS. Furthermore, FA and FD were significantly associated with mortality, the need for organ support, a longer length of ICU and hospital stay, and delirium. CONCLUSIONS: When assessing the relationship between wFB and DAWOLS, the threshold for FA was a wFB ≥+7%, while FD could be defined with a wFB cut-off of ≤-4%. Both FA and FD were significantly associated with reduced DAWOLS, with a less robust association for FD.

ObjectiveTo identify pneumonia-specific lactate trajectory phenotypes and evaluate their association with 28-day mortality in ICU patients with pneumonia.MethodsA retrospective cohort study was performed using the MIMIC-IV database. Adult ICU patients with pneumonia were identified via ICD-9/10 codes. Exclusions were non-index ICU admissions, age <18 or >100 years, ICU stay <3 days, and incomplete lactate data in the first 72 hours. Demographics, vital signs, laboratory results, comorbidities, severity scores, and treatments were extracted. Group-based trajectory modeling (GBTM) was applied to lactate values over 72 hours. Model selection considered BIC, AIC, average posterior probability (AvePP), odds of correct classification (OCC), class size, and clinical interpretability. Outcomes included 28-day all-cause mortality (primary) and secondary endpoints. Kaplan-Meier analysis and Cox regression were used to examine associations, with subgroup analyses across demographic and clinical strata.ResultsA total of 2,091 patients were included. Four distinct lactate trajectories were identified: low-stable (n=1161), moderate with gradual decline (n=721), initial rise then decline (n=89), and very high with rapid decline (n=120). Unfavorable trajectory classes were associated with greater illness severity, metabolic derangements, resource use, and higher mortality. As a continuous variable, lactate showed a borderline association with 28-day mortality in unadjusted analysis (HR 1.03, 95% CI 1.00-1.05, p=0.082), but lost significance after adjustment. In contrast, trajectory-based groups remained independently associated with outcomes: fully adjusted HRs were 1.30 (95% CI 1.08-1.56, p=0.004) for class 2, 1.49 (95% CI 1.03-2.15, p=0.034) for class 3, and 1.71 (95% CI 1.20-2.45, p=0.003) for class 4. Subgroup analyses showed consistent associations, with a stronger effect in patients <65 years (p for interaction=0.033).ConclusionsIn ICU patients with pneumonia, 72-hour lactate trajectory phenotypes were independently associated with 28-day mortality and may help characterize prognostic heterogeneity, including delayed lactate elevation patterns not captured by admission lactate alone.

BACKGROUND: The glycemic ratio (GR), defined as the ratio of mean intensive care unit (ICU) blood glucose (BG) to estimated preadmission BG (EPBG), may provide superior prognostic insight compared with the single admission snapshot represented by the stress hyperglycemia ratio (SHR, the ratio of ICU admission BG to EPAG). METHODS: This retrospective study included 4148 patients treated in a university-affiliated medical-surgical ICU from 2019 to 2023 who had >4 ICU BG measurements and a glycated hemoglobin (HbA1c) measured at admission. We compared SHR and GR prognostic ability for mortality, analyzed across prespecified GR and SHR bands, and calculated observed:expected mortality ratios (OEMRs). RESULTS: We observed a more sharply defined J-shaped relationship between GR and mortality compared with that generated by SHR. Mortality in the reference band of 0.8 to <1.0 for GR and SHR mortality was 7.5% vs 10.9%, respectively (P = .0087), and for the strata ≥1.4, mortality was 25.6% vs 20.5% (P = .0376). Compared with the reference band, GR < 0.8 and GR > 1.0 had higher OEMR (P < .0001 for each), but the OEMR for SHR <0.8 and >1.0 compared with the reference band was not significantly different. CONCLUSIONS: Glycemic ratio was superior to SHR as a predictor of mortality. This study demonstrates that a mean ICU BG level representing 80% to 100% of the patient's EPBG was associated with the lowest mortality rate in a heterogeneous cohort of critically ill patients. These results may inform current BG management strategies and should be considered when designing future interventional trials in the critically ill.

OBJECTIVES: To quantify and characterize aggression and violence against nurses, identify associated clinical characteristics, evaluate measures in response, and explore predictors of recurrent incidents in the ICU. DESIGN: Retrospective single-center study. Incidence and characteristics of aggression and violence against ICU nurses were the primary outcomes. Aggression was defined as hostile behavior or resistance to care without intent to harm. Violence comprised verbal, physical, or sexual acts to threaten or inflict harm. Secondary outcomes included risk factors for recurrent incidents, defined as multiple episodes of aggression/violence separated by greater than or equal to 24 hours. Multivariable analyses were performed to identify potential independent associations. SETTING: Data were collected from 2023 to 2024 at the tertiary medical-surgical ICU with up to 35 beds at the University Hospital Basel. Nursing operations followed a three-shift system: day (07:00-15:00), late (15:00-23:00), and night (23:30-07:00). SUBJECTS: Clinical reports from ICU nurses were screened. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During 2190 shifts, 308 aggressive or violence incidents (14% of shifts) were reported. Most occurred during late (37%) or night (34%) shifts; 75% involved violence. Violent incidents were combined in nature (79% physical, 43% verbal, and 3% sexual). Patients were mainly involved (97%) and predominantly male (71%; median age 67; 90% emergency admissions). Psychiatric comorbidities, drug, and alcohol abuse were found in 20-33%. Recurrent aggression/violence occurred in 27%, predicted by longer ICU stay (adjusted odds ratio [OR] = 1.05/every additional hour), aggression as the first incident (adjusted OR = 6.9), and verbal violence as the first incident (adjusted OR = 4.3). Nurses (89%, two-thirds female, median 7 yr' experience) rarely documented harm (1.3%), but patients were reported to suffer complications in 60% of incidents, mainly from oversedation and physical harm from restraints. CONCLUSIONS: Violence in the ICU is frequent and almost always caused by patients. Recurring violence was independently associated with longer ICU stay, initial aggression, and verbal violence. Staff harm was rare, but incidents were frequently associated with complications in patients.

INTRODUCTION: Healthcare systems increasingly screen for social needs, yet referrals often fail to connect patients with services-particularly in emergency department (ED) settings where unmet social needs are common. Our research highlights critical barriers to service connection, including unstable access to cellphones, limited internet and low digital literacy. These challenges disproportionately affect socio-economically disadvantaged groups and are associated with poorer health outcomes and more frequent ED visits. With the recognition of information and communication technology (ICT) access as a 'super social determinant of health', we have a timely opportunity to test solutions that address these disparities. METHODS AND ANALYSIS: We will conduct a three-arm randomised controlled trial enrolling 600 ED patients across three ED sites. Participants are eligible if they self-report at least one unmet social need using the validated Screener for Intensifying Community Referrals for Health (SINCERE) screening instrument, identify barriers to ICT access and want to be referred to community services. Arm 1 will receive community service referrals using email or alternate phone numbers (211 service navigator outreach, usual care). Arm 2 will receive stable cellphone access and community service referrals (cellphone with data+211 service navigator outreach). Arm 3 will receive cellphone access, community service referrals and tailored digital navigation support (Cellphone with data+211 service navigator outreach+digital navigation). Primary outcomes will include community service use and health-related outcomes such as depression, anxiety, social support, loneliness, self-reported global health and healthcare utilisation over 6 months. Using a mixed methods design, we will explore contextual and individual factors influencing engagement and outcomes. ETHICS AND DISSEMINATION: This study has been approved by the University of Utah Institutional Review Board (IRB). Findings will be shared with clinical and policy stakeholders, community organisations and published in open-access journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT07174466, start of enrolment 3 November 2025.**The start date for this trial is listed as 8 August 2025 on ClinicalTrials.gov. This date marks the pilot procedures conducted with five patients under IRB approval. These patient

OBJECTIVE: This study aimed to estimate the incidence and predictors of loss to follow-up (LTFU) among adults after antiretroviral therapy (ART) initiation at five provincial referral hospitals in Sierra Leone. DESIGN: A facility-based retrospective cohort study. SETTING: This study was conducted at five provincial government referral hospitals in Sierra Leone from January 2020 to December 2024. PARTICIPANT: HIV patients aged 15 and above who initiated ART between 1 January 2020, and 31 December 2020, and attended at least one follow-up visit at the five national referral hospitals. PRIMARY OUTCOME MEASURE: The primary outcome in this study was LTFU. LTFU was defined as absence from care, operationalised as no documented clinical encounter and/or ART refill for ≥90 days after the last expected clinical contact among patients not recorded as dead or transferred out. RESULTS: Of the 1544 patients (67.7% female), the median follow-up was 4.25 years (IQR not stated), totalling 5748.6 PY. Outcomes were 550 LTFU (35.6%), 853 in care (55.2%), 64 (4.1%) transferred and 77 (5.0%) died. The LTFU incidence was 9.57 per 100 PY (95% CI 8.78 to 10.37). Multivariable analyses revealed several factors significantly associated with higher LTFU: lack of tuberculosis (TB) screening (HR=4.47; 95% CI 3.66 to 5.46), WHO stage III/IV (HR=1.51; 95% CI 1.20 to 1.89), no regimen change (HR=5.12; 95% CI 2.39 to 11.00), non-disclosure of HIV status (HR=1.63; 95% CI 1.19 to 2.25), underweight body mass index (BMI) at follow-up (HR=1.37; 95% CI 1.05 to 1.78) and residence in the Southern (HR=1.97; 95% CI 1.57 to 2.48) or Eastern region (HR=2.13; 95% CI 1.49 to 3.03). Conversely, rural residence was associated with lower LTFU (HR=0.58; 95% CI 0.43 to 0.79). CONCLUSION: The study found a substantial incidence of LTFU. Risk factors of LTFU were gaps in TB screening, advanced clinical stage, absence of timely regimen adjustments, non-disclosure, low BMI and regional disparities. Strengthening integrated TB/HIV services, nutritional support, disclosure-enabling counselling and region-specific retention strategies, especially in urban, Southern and Eastern areas, may improve retention.

PURPOSE: Postoperative infectious complications (POI) after gastrectomy remain a major concern. While bioelectrical impedance analysis (BIA) is used for nutritional assessment, the clinical relevance of the preoperative extracellular water-to-total body water ratio (ECW/TBW) remains unclear. We investigated the association between preoperative ECW/TBW and POI. METHODS: This single-center retrospective cohort study included 181 patients who underwent curative gastrectomy between November 2020 and October 2025. Preoperative ECW/TBW was measured using multifrequency BIA. The primary outcome was POI, defined as surgical site infection (SSI) and/or remote infection (RI) within 30 days. Multivariable logistic regression and receiver operating characteristic (ROC) analyses were performed. RESULTS: POI developed in 44 patients (24.3%), as SSI in 30 (16.6%) and as RI in 16 (8.8%). Multivariable analysis identified that a higher ECW/TBW was associated with POI (odds ratio [OR] per 0.01 increase, 1.68; 95% confidence interval [CI], 1.02-2.77; P = 0.040) and RI (OR 1.79; 95% CI, 1.00-3.21; P = 0.048), but not with SSI. ROC analysis showed a numerically higher AUC of ECW/TBW for predicting RI (area under the curve, 0.833) than phase angle (0.761). CONCLUSIONS: Elevated ECW/TBW may reflect systemic physiological vulnerability associated with RI, particularly postoperative respiratory infection.

This study aimed to investigate the risk factors associated with 1-year postoperative mortality in patients with lumbar compression fractures and to construct and validate a predictive nomogram model. Clinical data of patients admitted between January 2021 and December 2024 were retrospectively analyzed. Independent predictors of 1-year mortality were identified using univariate and multivariate logistic regression analyses. A nomogram was constructed based on the final model. Model discrimination was evaluated using the receiver operating characteristic curve and the area under the curve. Calibration, Bootstrap resampling, and 10-fold cross-validation were used for internal validation. A total of 378 patients were included, of whom 21 (5.56%) died within 1 year postoperatively. Five independent predictors were identified: bone mineral density ≤ -2.5, multiple segmental fractures, age > 70 years, albumin ≤ 40 g/L, and neutrophil-to-lymphocyte ratio > 4. The nomogram showed good discriminative performance, with an area under the curve of 0.826 in the training cohort and 0.813 in the validation cohort. Calibration curves demonstrated good agreement between predicted and observed outcomes. One-year postoperative mortality in lumbar compression fracture patients is influenced by multiple clinical and inflammatory factors. The proposed nomogram demonstrates good discriminative ability and may help clinicians identify high-risk patients for early intervention.

OBJECTIVES: Falls remain a significant public health concern given both the person-level and system-level effects of experiencing a fall, namely decreased function, decreased intrinsic capacity, social isolation, and increased health care utilization. The World Health Organization has prioritized falls as a health outcome indicator in evaluating the impact of policy, strategy, and programming. The objective was to establish cross-sectoral fall rates across health care sectors in Canada and identify key risk factors as candidate risk adjustment variables for a falls quality indicator. DESIGN: A retrospective, cross-sectional study. SETTING AND PARTICIPANTS: Seven hundred thousand two hundred four Canadian health care recipients, across multiple health care sectors, aged 60 years and older, were included. METHODS: This study analyzed data from interRAI assessments. Frequencies and χ2 analyses were used in descriptive analysis. Multivariable logistic regression analyses were used to establish key fall risk adjustors for a quality indicator. The independent variables considered in development included measures, such as function, cognition, health instability, balance impairment, and demographic variables. This model was then applied to a cohort with no serious mobility impairment. Mobility impairment included being completely dependent with ambulation, using a wheelchair or a scooter, or being bedbound. RESULTS: A higher prevalence of falls was observed in community settings. Regression analysis showed a protective effect of those receiving care in a designated care facility (odds ratio range across facilities with mandated assessments, 0.36-0.55). Those with balance impairment, bladder incontinence, health instability, cognitive impairment, and activities of daily living impairment were more likely to fall. Similar trends were observed in the subgroup with no mobility impairment. CONCLUSIONS AND IMPLICATIONS: These findings provide a national cross-sectoral landscape of falls in settings not generally considered in population surveys. The rates of falls are highly variable across settings, and key fall risk factors identified in this study provide a foundation for risk adjustment in global comparisons of falls in older adults.

SUMMARY: In April 2024, the possession and cultivation of non-medical cannabis for adults were legalized in Germany, and the regulation of cannabis for medical purposes was liberalized. We studied whether the rate of hospital admissions with cannabis-specific diagnoses has risen since then. METHODS: The number of inpatient admissions each week from January 2022 to September 2025 was ascertained from DRG and PEPP statistics. The primary endpoint was the rate of admissions with a cannabis-specific ICD-10 main diagnosis (F12.0-F12.9; T40.7) as a proportion of all admissions, determined separately for minors and adults. Secondary endpoints for adults were the admission rates for acute intoxication and poisoning (F12.0; T40.7) and for cannabis-induced psychosis (F12.5) as a percentage of all admissions. Immediate and gradual changes after the modification in the law were examined with time-series analyses. RESULTS: After 1 April 2024, the rate of hospital admissions with a cannabis-specific diagnosis initially rose by 5.6% (risk ratio (RR) = 1.056) and remained stable thereafter (RR = 1.000). Among minors, an initial immediate rise of 14.9% (RR = 1.149) was followed by a decline of 0.4% (RR = 0.996) per week. Among adults, cases of acute cannabis poisoning saw an immediate rise of 37.1% (RR = 1.371), followed by a slight, non-significant, gradual decline (RR = 0.998). The hospitalization rate of cannabis-induced psychosis among adults rose immediately by 16.4% (RR = 1.164) and remained stable thereafter (RR = 1.000). CONCLUSION: The change in cannabis laws in Germany was followed by a rise in cannabis-specific hospital admissions, particularly among adults, mainly because of acute intoxication and cannabis-induced psychosis. The reason may be increased consumption of highly potent medical cannabis.

BACKGROUND: Many autistic adolescents receive in-patient psychiatric care from services that are ill-equipped to meet neurodivergent needs. However, the outcomes for autistic adolescents accessing in-patient care remain poorly understood. AIMS: To document the demographics and clinical outcomes of autistic adolescents referred to in-patient psychiatric services over a 5-year period and compare these with those of their allistic peers accessing the same services. METHOD: We conducted a retrospective cohort study involving all adolescents (aged 12-17 years inclusive) referred for in-patient psychiatric care through the Thames Valley Provider Collaborative between 1 April 2019 and 31 March 2024. Clinical characteristics and outcomes of referrals for autistic and allistic adolescents were collected and summarised from routine service data. Inferential statistics (including t-tests and chi-squared tests) were used to compare characteristics between the autistic and allistic groups. RESULTS: Autistic adolescents were more likely than their allistic peers to be referred in an emergency (24.6 v. 16.6%) and for risk management (53.7 v. 33.5%). Autistic adolescents without an eating disorder had longer average length of stay than their peers (146.1 v. 97.5 days) and were more likely to be discharged to more secure settings following admission (12.9 v. 7.7%). Emerging evidence from routine outcome measures suggests less positive progress during in-patient care and greater impairment among autistic adolescents at both admission and discharge. CONCLUSIONS: There are important differences in outcomes from psychiatric in-patient admissions between autistic and allistic adolescents. Greater work is needed to understand these differences and the factors influencing treatment success for autistic adolescents.

Pelvic drains have traditionally been utilized following radical cystectomy to facilitate early identification of urinary leaks and postoperative complications. However, evidence supporting routine drain placement following robot-assisted radical cystectomy (RARC) remains limited. This study evaluated the association between intraoperative pelvic drain placement and postoperative outcomes following RARC. Patients undergoing RARC were identified from the American College of Surgeons National Surgical Quality Improvement Program database. Patients were stratified according to intraoperative pelvic drain placement. Baseline characteristics, perioperative variables, and 30-day postoperative outcomes were compared between cohorts. Multivariable logistic and linear regression analyses adjusting for demographic characteristics, comorbidities, American Society of Anesthesiologists classification, and operative time were performed. A total of 5,256 patients undergoing RARC were identified, including 4,946 (94.1%) managed with pelvic drains and 310 (5.9%) without drains. Drain placement was associated with longer operative duration (363.3 ± 124.8 vs. 294.6 ± 117.6 min, p < 0.001), while no significant difference hospital length of stay was found between cohorts (p = 0.294). On unadjusted analysis, urinary tract infection was more common in patients managed without drains (9.4% vs. 5.2%, p = 0.002), whereas ureteral obstruction was more frequent in the drain cohort (5.6% vs. 2.3%, p = 0.012). Rates of mortality, readmission, reoperation, overall complications, urinary leak, sepsis, and surgical site infection were otherwise similar between groups. Following multivariable adjustment, drain placement was independently associated with lower odds of urinary tract infection (adjusted odds ratio [aOR] 0.55, 95% confidence interval [CI] 0.37-0.84, p = 0.005) and higher odds of ureteral obstruction (aOR 2.85, 95% CI 1.31-6.19, p = 0.009), without significant associations with most other major postoperative outcomes. Routine pelvic drain placement following RARC was not independently associated with reductions in most major postoperative complications. These findings suggest that routine prophylactic drain utilization may provide limited overall benefit following contemporary robotic cystectomy and support a more individualized approach to drain placement.

OBJECTIVE: Endoscopic transsphenoidal surgery (eTSS) is a common neurosurgical procedure used to treat pituitary adenomas (PAs). The authors evaluated the incidence of complications, early readmission, and early reoperation following eTSS for PAs and identified clinical, surgical, and tumor characteristics predictive of these outcomes. METHODS: The data of all patients with histologically confirmed PAs who underwent eTSS at the authors' institution between May 2011 and September 2024 were retrospectively reviewed. Thirty-day postoperative complications were grouped into surgical and medical categories. Early readmission and early reoperation were defined as occurring within 90 days of discharge and surgery, respectively. RESULTS: A total of 709 endoscopic transsphenoidal operations (655 direct and 54 extended approaches) were performed in 693 patients. The median tumor diameter (IQR) was 24 (17-32) mm, and 656 cases (93%) were macroadenomas. Cavernous sinus invasion on MRI was noted in 32.2% of cases. Fifteen percent were reoperations. Gross-total resection was achieved in 63.5% of patients, and the median length of stay was 3 days. Surgical complications included postoperative CSF leakage (4.2%), epistaxis (2.7%), cranial nerve palsy (1.0%), worsened vision (1.0%), meningitis (1.0%), stroke (0.8%), hydrocephalus (0.7%), hematoma (0.6%), sinusitis (0.6%), abdominal hematoma or infection (0.4%), carotid artery injury (0.1%), and death (0.3%). Medical complications included transient diabetes insipidus (8.7%), permanent diabetes insipidus (2.4%), bacteremia/sepsis (0.7%), pneumonia (0.3%), and deep venous thrombosis/pulmonary embolism (0.1%). Early readmission and early reoperation were observed in 10.2% and 4.8% of cases, respectively. The most common reasons for early readmission were delayed hyponatremia (4.2%), CSF leakage (1.8%), infection (1.1%), epistaxis (0.7%), and hypocortisolemia (0.1%), while the most common reasons for early reoperation were CSF leakage (2.5%), residual tumor (1.3%), worsened vision (0.6%), infection (0.6%), and hematoma (0.3%). Predictors of complications included increasing tumor diameter, firm tumor consistency, the presence of an intraoperative CSF leak, and use of an extended approach. While not statistically significant, rates of postoperative CSF leakage (5.1% vs 3.4%), early readmission (11.4% vs 9.1%), and early reopera

This study holds the primary objective of confirming the risk factors for cerebrospinal fluid leakage (CSFL) following posterior lumbar interbody fusion for lumbar degenerative disease. The 684 patients who received posterior lumbar interbody fusion for lumbar degenerative disease at our hospital from 2017 to 2023 fell into the CSFL group (n = 115) or the control group (n = 569). We retrospectively recorded demographic, surgical, and radiographic data for the examination of the independent risk factors related to CSFL. Univariate and multivariate logistic regression analyses were conducted to more thoroughly measure their significance. The incidence of CSFL was 16.8% (115/684 patients). According to multivariate analysis, elderly individuals (age ≥ 60 years; odds ratio [OR], 1.601; 95% confidence interval [CI], 1.004-2.554; P = .048), patients with fusion levels ≥ 4 (OR, 3.665; 95% CI, 1.523-8.818; P = .004), patients with scoliosis (OR, 5.213; 95% CI, 1.380-19.698; P = .015), patients with spondylolisthesis (OR, 2.229; 95% CI, 1.382-3.595; P = .001), and patients with a duration of operation ≥ 250 minutes (OR, 8.586; 95% CI, 1.114-66.172; P = .039) could independently indicate the risk of CSFL. For patients with CSFL, obvious increases in postoperative drainage, lengths of stay, hospitalization costs, and frequency of blood transfusions, all with P < .001, were detected. Elderly age (≥60 years), fusion level ≥ 4, scoliosis, spondylolisthesis, and operative duration ≥ 250 minutes were identified as independent predictive factors for the risk of CSFL. CSFL patients had significantly more postoperative drainage, longer lengths of stay, higher hospitalization costs, and more frequent blood transfusions.

RATIONALE: Solid organ transplantation is the optimal treatment for patients living with end-stage organ failure. Globally, the majority of organ donors are deceased, most commonly following brainstem death. The process of brain death is known to cause significant injury to organs. Therefore, efforts to optimise the pre-donation care of these donors should be maximised to achieve improved recipient outcomes. OBJECTIVES: To assess the benefits and harms of therapeutic donor hypothermia in recipients of organs donated from brain-dead donors. SEARCH METHODS: We searched Cochrane Kidney and Transplant's Specialised Register, CENTRAL, MEDLINE, Embase and two trials registers up to 03 September 2025. ELIGIBILITY CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) investigating therapeutic donor hypothermia compared with donor normothermia following brainstem death to improve the quality of transplanted organs. OUTCOMES: Critical outcomes were post-transplant outcomes (delayed graft function (DGF), graft survival), utilisation and donor adverse events. Important outcomes were patient survival, primary nonfunction, acute rejection, quality of life and cardiovascular disease. RISK OF BIAS: We used Cochrane's risk of bias 1 tool. SYNTHESIS METHODS: Two review authors independently selected trials for inclusion, assessed methodological quality and risk of bias, and extracted data. We used random-effects models for the meta-analysis. We assessed the certainty of evidence using the GRADE approach. INCLUDED STUDIES: We included four studies, enrolling 2096 donors. Two studies compared donor hypothermia versus normothermia in kidney transplantation. Two studies investigated kidney, heart, lung, liver and pancreas transplantations. SYNTHESIS OF RESULTS: Four studies assessed the impact of donor hypothermia compared with normothermia on kidney outcomes. Donor hypothermia may not reduce the rate of kidney DGF compared to donor normothermia (RR 0.87, 95% CI 0.71 to 1.08; I² = 57%; 4 studies, 3015 participants; low-certainty evidence). Donor hypothermia may not be associated with one-year kidney graft survival (HR 0.77, 95% CI 0.51 to 1.14; I² = 0%; 3 studies, 2075 participants; low-certainty evidence) or one-year

BACKGROUND: The cytokine profile may provide clinically relevant information for assessing the inflammatory response in infectious diseases, including SARS-CoV-2. However, the threshold concentrations of cytokines associated with severe pediatric COVID-19 and cytokine patterns related to multisystem inflammatory syndrome in children (MIS-C), remain insufficiently characterized. OBJECTIVES: This study aimed to evaluate serum levels and exploratory threshold concentrations of IL-1β, IL-6, IL-8, IL-12, TNF-α, and IFN-α associated with severe pediatric COVID-19 and MIS-C, and to characterize cytokine patterns across different clinical forms of SARS-CoV-2 infection in children. DESIGN: The cohort study included 200 children with laboratory-confirmed SARS-CoV-2 infection, including mild COVID-19 (n=106), moderate COVID-19 (n=72), and severe COVID-19 (n= 22), 40 children diagnosed with MIS-C, and 45 children with negative PCR and ELISA results for SARS-CoV-2. Participants were aged 1 month to 17 years (6.47±5.53 years), and none had received a COVID-19 vaccine at the time of inclusion. METHODS: Serum concentrations of IL-1β, IL-6, IL-8, IL-12, TNF-α, and IFN-α were measured within the first 24 hours of hospitalization, before treatment initiation, using immunoenzymatic assays. RESULTS: Cytokines associated with severe COVID-19 included IL-1β (cut-off 6.96 pg/mL), IL-6 (cut-off 68.37 pg/mL), IL-12 (cut-off 34.53 pg/mL), TNF-α (cut-off 60.63 pg/mL), and IFN-α (cut-off 26.96 pg/mL). All measured cytokines demonstrated adequate discriminatory performance for identifying MIS-C: IL-1β (cut-off 7.28 pg/mL), IL-6 (cut-off 100.64 pg/mL), IL-8 (cut-off 16.93 pg/mL), IL-12 (cut-off 34.91 pg/mL), TNF-α (cut-off 80.19 pg/mL), and IFN-α (cut-off 30.56 pg/mL). Random Forest analysis identified IL-1β and IL-8 as variables with the highest model-derived importance for COVID-19 severity classification, whereas age and sex showed lower model-derived importance than cytokine biomarkers. CONCLUSION: Cytokine profiling may support a more nuanced evaluation of hyperinflammatory immune responses in pediatric SARS-CoV-2-associated disease. However, its additional clinical value beyond routine clinical and laboratory markers requires validation in larger independent pediatric cohorts.

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumour in adults, characterized by diffuse infiltration and poor prognosis despite multimodal therapy. Maximal safe surgical resection remains the cornerstone of management, as greater extent of resection (EOR) correlates with improved survival. However, conventional white-light microscopy often fails to distinguish tumour margins from surrounding functional brain tissue. 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery enhances intraoperative visualization by selectively accumulating protoporphyrin IX in tumour cells, allowing real-time delineation of malignant tissue. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of 5-ALA-guided resection compared with conventional white-light microsurgery in adults with newly diagnosed GBM. The review was conducted in accordance with PRISMA and Cochrane guidelines, and prospectively registered on PROSPERO (CRD420251160699). Comprehensive searches of PubMed, Embase, Scopus, Cochrane Library, and Google Scholar were performed from inception to July 2025. Randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) comparing 5-ALA-guided and white-light surgery were included. Two reviewers independently screened studies, extracted data, and assessed risk of bias using RoB 2.0 for RCTs and the Newcastle-Ottawa Scale for NRCTs. Meta-analyses were performed using random-effects models (RevMan 5.4), and outcomes were summarized as risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs). Certainty of evidence was graded using GRADE methodology. Seven studies involving 790 patients (three RCTs, four NRCTs) were included. Pooled analysis demonstrated that 5-ALA-guided surgery significantly improved gross total resection (GTR) compared with white-light microsurgery (RR = 1.54; 95% CI: 1.16-2.04; p = 0.003). Although 12-month overall survival (OS) did not differ significantly (RR = 1.31; 95% CI: 0.81-2.13; p = 0.27), mean OS was significantly prolonged with 5-ALA (MD = 2.89 months; 95% CI: 0.73-5.04; p = 0.009). Neurological morbidity was comparable between groups (RR = 1.31; 95% CI: 0.81-2.13; p = 0.27). Systematic evidence further supported higher EOR and lower subtotal resection rates with 5-ALA. Functional outcomes and progression-free survival (PFS) were generally

Clinical practice guidelines (CPGs) are essential tools to support evidence-based nutritional care in critically ill patients; however, the methodological quality and credibility of recommendations for nutritional risk screening remain unclear. This study aimed to evaluate the methodological quality of CPGs addressing nutritional risk screening in critically ill adults and to critically appraise the evidence supporting these recommendations. A systematic search was conducted between January and April 2026 in Embase, PubMed, SciELO, Scopus, LILACS, Google Scholar, and guideline repositories. CPGs, consensus statements, and position papers, including nutritional risk screening recommendations for critically ill adults were eligible. Guideline quality was assessed using the AGREE II and AGREE-REX instruments. Original studies and systematic reviews supporting nutritional risk screening recommendations were critically appraised using ROBINS-E and AMSTAR 2, respectively. Four CPGs were included. AGREE II assessment demonstrated satisfactory methodological quality overall, particularly in Scope and Purpose (84.4%) and Clarity of Presentation (92.0%), whereas Applicability showed the lowest performance (50.0%). AGREE-REX evaluation demonstrated moderate overall recommendation quality (64.8%), with the Chinese Society of Critical Care Medicine guideline presenting the highest score (77.8%). Most original studies supporting recommendations were classified as having high or very high risk of bias, and one systematic review was classified as critically low confidence. Although the included guidelines demonstrated satisfactory methodological quality, important limitations were identified regarding recommendation credibility, applicability, and evidence quality. These findings highlight the need for higher-quality evidence synthesis, transparent risk-of-bias assessment, and improved implementation strategies in future guideline development.

BACKGROUND: Postoperative delirium (POD) is a common complication in older adults after hip fracture surgery. Although cognitive impairment is a key risk factor, accurately assessing baseline cognition in acute settings remains challenging. Informant-based tools may better reflect premorbid cognitive status; however, their utility in hip fracture populations is unclear. METHODS: This retrospective analysis used data from a prospective cohort of patients aged ≥ 80 years who underwent hip fracture surgery at two acute hospitals in Japan. Pre-fracture cognitive status was assessed using the Dementia Assessment Sheet for Community-based Integrated Care System (DASC-21), primarily based on reports from informants. For selected patients without available informants and with Mini-Mental State Examination (MMSE) scores ≥ 21, structured patient interviews and clinical observations were used. The DASC-21 categories were classified as normal cognition, mild impairment and moderate-to-severe impairment. Cognitive function at admission was evaluated using the MMSE. POD was assessed using the Confusion Assessment Method within the first three postoperative days. Multivariable logistic regression analyses were performed. RESULTS: Among 368 patients, 137 (37.2%) developed POD. POD incidence increased with worsening pre-fracture cognitive impairment (5.6%, 44.3% and 48.7% for normal, mild and moderate-to-severe impairment, respectively; p < 0.001). Each 1-point increase in the MMSE score was associated with lower odds of POD (OR 0.91, 95% CI 0.88-0.94). Compared with normal cognition, the adjusted ORs for POD were 14.11 (95% CI 5.08-39.24) for mild impairment and 15.39 (95% CI 5.56-42.61) for moderate-to-severe impairment. Discrimination was similar between MMSE and DASC-21 (area under the receiver operating characteristic curve 0.75 vs. 0.74). CONCLUSIONS: Pre-fracture cognitive impairment, including DASC-21-defined mild impairment, was associated with POD. The DASC-21 categories showed comparable discriminative performance to the MMSE and may help estimate baseline cognitive vulnerability in acute clinical settings.

BACKGROUND: Acute to postacute care continuum for individuals with stroke significantly influences functional recovery, quality of life, and healthcare utilization. Prior studies have focused largely on older adults with stroke, limiting generalizability for the younger population. OBJECTIVE: This study is aimed at identifying patient- and hospital-level factors associated with postacute discharge destination following acute stroke hospitalization. DESIGN: This study is a retrospective cohort study. SETTING: This study was set in acute care hospitals in Virginia (2017-2021). PARTICIPANTS: Participants are adults ≥ 18 years hospitalized with a primary diagnosis of ischemic or hemorrhagic stroke identified in the Virginia All-Payer Claims Database. INTERVENTIONS: There were no interventions applicable. MAIN OUTCOMES: Postacute care discharge destination was categorized as home, home health, skilled nursing facility (SNF), inpatient rehabilitation facility (IRF), or other. Patient-level variables included age, sex, race, insurance, comorbidity burden, stroke type, length of stay, and hospital-acquired complications. Facility-level variables included hospital size, ownership, stroke center status, and county-level clinical care rankings. Multivariable logistic regression models estimated associations between patient and hospital factors and postacute care discharge destination. RESULTS: Older age, higher comorbidity burden, presence of hospital-acquired complications, and longer length of stay were associated with increased likelihood of discharge to post-acute care, particularly IRF and SNF. Male patients were less likely than females to be discharged to home health (OR = 0.90, 95%CI = 0.85-0.95) or to SNF (OR = 0.91, 95%CI = 0.87-0.96). Black patients had higher odds of discharge to home health (OR = 1.13, 95%CI = 1.05-1.22), IRF (OR = 1.10, 95%CI = 1.02-1.19), and SNF (OR = 1.13, 95%CI = 1.05-1.21) compared with White patients. Medicaid beneficiaries had higher odds of discharge to post-acute care settings compared with commercially insured patients, including home health (OR = 1.34, 95%CI = 1.17-1.54), IRF (OR = 1.20, 95%CI = 1.05-1.38), and SNF (OR = 1.17, 95%CI = 1.02-1.34). CONCLUSIONS: Postacute care after stroke is associated with both clinical complexity and sociodemographic factors. These findings highlight potential differences and variations

BACKGROUND: Early warning and severity scores are widely used to support triage and predict clinical deterioration. Their diagnostic performance in low- and middle-income countries (LMICs) however remains uncertain due to differences in patient populations and healthcare resources compared with high-income settings. OBJECTIVES: This study aimed to evaluate and compare the diagnostic accuracy of commonly used scoring systems for predicting intensive care unit (ICU) admission and in-hospital mortality among adults presenting to emergency departments in LMICs. METHODS: We conducted a systematic review and meta-analysis of PubMed, Science Direct, Web of Science and the Cochrane Library. Observational studies assessing the accuracy of early warning or severity scores for ICU admission or in-hospital mortality of patient admitted to the emergency department were included. Data were pooled using a bivariate random-effects model to estimate sensitivity, specificity and area under the curve (AUC). Study quality was appraised using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2). RESULTS: Twenty-six studies comprising over 45 000 patients from LMICs were analysed. For in-hospital mortality, quick Sequential Organ Failure Assessment (qSOFA) showed sensitivity of 0.61 and specificity of 0.73 (AUC=0.67); National Early Warning Score (NEWS)-family had higher sensitivity (0.80) but lower specificity (0.56, AUC=0.68); Modified Early Warning Score (MEWS) provided high specificity (0.83) but lower sensitivity (0.53, AUC=0.68). For ICU admission, NEWS demonstrated balanced performance (sensitivity 0.74, specificity 0.77, AUC=0.76), while Rapid Emergency Medicine Score (REMS) achieved the highest overall accuracy (sensitivity 0.79, specificity 0.85, AUC=0.81). Considerable heterogeneity was observed across studies. CONCLUSIONS: Early warning scores show moderate accuracy in predicting ICU admission and in-hospital mortality in LMIC emergency departments. qSOFA and MEWS may be most useful when high specificity is required, while NEWS and REMS provide more balanced performance, with REMS showing the best overall accuracy. No single score was optimal across settings, underscoring the need for local validation and adaptation in resource-limited environments.

BACKGROUND: Cardiac surgery-associated acute kidney injury (CSA-AKI) following cardiopulmonary bypass (CPB) remains a high-risk complication with limited effective management. Hemoadsorption is increasingly used as an adjunctive therapy due to its potent cytokines clearance in experimental settings, yet its clinical efficacy is debated. This study aimed to evaluate the effect of hemoadsorption versus standard care on CSA-AKI and other major outcomes in adult cardiac surgery patients. METHODS: An updated systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted following PRISMA guidelines. PubMed, Medline, Embase, Web of Science, and the Cochrane Library were systematically searched from inception to 8 February 2025. Eligible RCTs enrolled adult patients undergoing cardiac surgery and compared intraoperative hemoadsorption with standard care, with reported outcomes including CSA-AKI and other major endpoints. Pooled estimates were synthesized using inverse-variance random-effects models, with heterogeneity quantified by I² statistics. Subgroup, sensitivity and trial sequential analyses (TSA) were further performed. RESULTS: Fifteen RCTs were included, of which nine reported CSA-AKI (947 patients). Hemoadsorption was not associated with a statistically significant reduction in CSA-AKI (RR 0.80, 95% CI 0.63-1.03, P = 0.08, I2 = 40%, GRADE: very low). The finding was sensitive to model choice and the inclusion of two studies (Diab 2022 and Abou-Arab 2025). Subgroup analyses revealed no significant interaction by device type. TSA indicated that the required information size was not reached. No significant differences were observed for CSA-AKI Stage 1 (RR 0.72, 95% CI 0.49-1.05, P = 0.09, I2 = 16%), Stage 2 (RR 0.66, 95% CI 0.30-1.43, P = 0.29, I2 = 11%), Stage 3 (RR 0.43, 95% CI 0.17-1.05, P = 0.06, I2 = 0%), or renal replacement therapy (RR 0.52, 95% CI 0.22-1.25, P = 0.15, I2 = 0%). Mortality and other clinical endpoints were comparable between groups. Among exploratory outcomes, only an overall reduction in IL-8 was noted (MD -18.23, 95% CI -31.90 to -4.56, P = 0.009, I2 = 40%). CONCLUSIONS: Intraoperative hemoadsorption did not significantly reduce CSA-AKI or improve clinical outcomes in adult cardiac surgery. Although trends favored severe AKI, very low certainty evidence and insufficient information preclude definitive conc

BackgroundOutpatient total and completion thyroidectomy is increasingly feasible, but long-term institutional data describing simultaneous expansion of same-day discharge and maintenance of low readmission are limited. We describe 14-year outcomes using a PACU parathyroid hormone (PTH)-guided calcium and calcitriol supplementation pathway.MethodsRetrospective single-institution cohort of total and completion thyroidectomies (2010-2023) analyzed across three complementary data sources: an NSQIP case-level cohort (N = 1111) for readmission, length of stay, and discharge timing; institutional NSQIP Semiannual Report (SAR) data (N = 1393) for hypocalcemia-related readmission; and the NSQIP thyroidectomy-targeted module (N = 766) for postoperative hypocalcemia. Institutional NSQIP observed-to-expected (O/E) ratios were reviewed as contextual benchmarking.ResultsSame-day discharge (LOS = 0 days) rose from <5% before 2017 to 60.0% in 2022 and 70.9% in 2023, and short-stay discharge (LOS ≤1 day) exceeded 90% annually from 2019 onward. Across the full period, 30-day all-cause readmission was 1.71% (95% CI: 1.10-2.66%). Hypocalcemia requiring readmission occurred in 1.4% of the SAR cohort and accounted for 67.9% of readmissions. Postoperative hypocalcemia was documented in 7.4% of the module subset (95% CI: 5.8%-9.5%), with clinically significant events in 4.0%. The mean institutional NSQIP O/E ratio was 0.93 (range 0.74-1.24).DiscussionAcross a 14-year cohort, same-day discharge after total and completion thyroidectomy expanded while 30-day readmission and clinically significant hypocalcemia remained low. These findings support the feasibility of outpatient thyroidectomy within a standardized PACU PTH-guided supplementation pathway; because PACU PTH values were unavailable, prospective studies are needed to determine whether the pathway independently influenced these outcomes.

OBJECTIVES: Ventilator-associated pneumonia (VAP) is a frequent and serious infection among mechanically ventilated children in pediatric intensive care units (PICUs), with oral colonization playing a key role in its pathogenesis. Effective oral hygiene measures are therefore crucial to reduce VAP incidence and improve clinical outcomes. This study aimed to compare the incidence of VAP in PICU patients receiving routine oral care versus toothbrushing with chlorhexidine, and to evaluate the impact on mechanical ventilation duration, PICU stay, and mortality with secondary outcomes including microbiological colonization, inflammatory markers, and inotropic support requirements. DESIGN: A parallel-group superiority randomized controlled trial. METHODS: A randomized controlled trial was conducted on 118 children aged 18 months to 16 years, including PICU patients requiring invasive mechanical ventilation for ≥ 48 h. On admission, patients were randomly allocated into two groups: the intervention group received oral care with toothbrushing plus 0.12% chlorhexidine mouth rinse, while the control group received routine care with 0.12% chlorhexidine rinse only. Both procedures were performed three times daily. VAP was diagnosed according to CDC criteria. Quantitative and qualitative analyses assessed variables distinguishing VAP cases from controls, and multivariate logistic regression identified independent predictors of disease severity. RESULTS: The results of our study revealed that VAP occurred in 31 patients (52.5%) in the control group and 25 patients (42.3%) in the intervention group, indicating a lower incidence with toothbrushing plus chlorhexidine, although this difference was not statistically significant (p = 0.36). Among all participants, 45.8% died and 54.2% were discharged. Mortality was higher in the control group (53.7%) compared with the intervention group (46.3%), while discharge rates favored the intervention group (53.1% vs. 46.9%); however, these differences did not reach statistical significance (p = 0.46). Positive sputum cultures were more frequent in the control group (55.6%) than in the intervention group (44.4%), whereas negative cultures were more common among intervention patients (54.7% vs. 45.3%), with no significant difference between groups (p = 0.268). CONCLUSION: Although adding toothbrushing to routine chlorhexidine oral car

As ureteroscopy (URS) is increasingly utilized, preventing and managing severe postoperative infections-such as urosepsis-has become a clinical priority. Elevated intrarenal pressure (IRP) and irrigation fluid absorption (IFA) represent two core pathophysiological steps in the translocation of bacteria and endotoxins into the bloodstream. This review compares the clinical utility and technological maturity of IRP and IFA monitoring during URS. The analysis indicates that IRP is the instantaneous physical driving force for pyelovenous backflow, whereas IFA is the integrated outcome of multidimensional variables, including the pressure gradient, operative time and tissue permeability. Consequently, monitoring a single dimension may be insufficient to comprehensively assess infection risk. IRP monitoring (e.g., using a ureteral access sheath with a pressure-sensing channel or a flexible URS with an integrated pressure sensor) offers the advantage of real-time feedback, potentially playing a key role in maintaining low IRP and proactively preventing intrarenal backflow. However, it cannot account for the cumulative effect of time or changes in tissue permeability. IFA monitoring, despite its inherent lag, may provide a more comprehensive quantitative measure of the pathogenic load absorbed by the patient, suggesting potential predictive and warning value for the occurrence of infection; however, clinically validated thresholds and prospective evidence are currently lacking. In the future, with advancements in monitoring technology, the development of automated closed-loop systems integrating high-precision IRP monitoring, real-time IFA monitoring, intelligent irrigation and negative pressure suction holds promise for maximizing the balance between surgical efficacy and patient safety, provided that future studies can establish evidence-based intervention triggers.

The aquaculture sector faces increasing challenges from bacterial diseases and growing restrictions on antibiotic use due to concerns regarding antimicrobial resistance (AMR). Phage therapy, the therapeutic application of bacteriophages to selectively infect and lyse pathogenic bacteria, offers a targeted strategy to combat AMR pathogens while minimizing ecological disruption. This review synthesizes current evidence on major bacterial pathogens in aquaculture, with particular emphasis on infections caused by Aeromonas, Vibrio, Edwardsiella, Flavobacterium and Streptococcus species. Available in vivo studies indicate that phage-based interventions, particularly phage cocktails, can significantly improve survival rates in aquaculture species, including catfish, salmonids, and shrimp. However, the current evidence base is dominated by laboratory challenge studies, and substantial heterogeneity in experimental designs, outcome measures, dosing strategies, and host-pathogen systems limits direct cross-study comparisons and broader translational interpretation. Additional challenges include large-scale field implementation, the emergence of phage-resistant bacterial variants, formulation and delivery constraints, and the absence of standardized regulatory frameworks. This review critically evaluates the translational readiness of phage therapy in aquaculture, examines advances in phage isolation, formulation and delivery strategies, and discusses key practical, regulatory and scientific barriers to commercial adoption. Finally, it identifies priority research areas and strategic investments required to facilitate the transition of phage therapy from experimental proof-of-concept to routine practice.

INTRODUCTION: Community-acquired pneumonia (CAP) remains a significant cause of adult morbidity and mortality. Respiratory syncytial virus (RSV) contributes meaningfully to adult CAP, particularly in older adults and those with chronic cardiopulmonary disease, yet is frequently underdiagnosed because clinical features overlap with other respiratory infections and routine testing is limited. AREAS COVERED: This review summarizes key virological and immunological characteristics of RSV, highlights diagnostic challenges in adults, and discusses clinical consequences beyond respiratory illness, including cardiovascular complications, severe in-hospital outcomes, and secondary bacterial infection with antibiotic exposure. Using Korean and international data, we emphasize the value of multi-specimen molecular testing to improve detection and discuss the implications for antimicrobial stewardship in CAP management. We also provide an overview of vaccine efficacy in phase 3 trials and early real-world effectiveness in older adults. EXPERT OPINION: Reducing the adult RSV burden will require a feasible diagnostic pathway during periods of RSV circulation, strengthened surveillance that captures clinically meaningful outcomes, and targeted vaccination of high-risk populations. Ongoing post-authorization evaluation and research in immunocompromised and other high-risk groups are needed to optimize vaccination strategies and inform next-generation prevention.

BACKGROUND: Candida spp. infections are an increasing challenge in high-complexity hospitals, yet epidemiological data remain scarce in underrepresented in Colombian regions such as Tolima. METHODS: We conducted a retrospective observational study in a high-complexity hospital in Ibagué (Tolima, Colombia) from 2014 to 2024, integrating two institutional data sources: administrative/clinical records and the microbiology laboratory database (WHONET). Species identification relied on culture and VITEK, and antifungal susceptibility was interpreted using criteria from the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST). We summarized data using frequencies/proportions and medians (IQR), explored patterns with multiple correspondence analysis (MCA), and estimated associations with candidemia using penalized multivariable logistic regression due to low event frequency. RESULTS: We identified 987 candidiasis episodes and 776 fungal isolates, of which 314 were Candida (40.46%). Mucocutaneous disease predominated (vulvovaginal 50.7%; oropharyngeal 24.3%), while candidemia represented 2.0% of episodes. Among isolates, Candida albicans was most frequent (58.9%), followed by C. parapsilosis (16.6%), C. tropicalis (12.1%), and Nakaseomyces glabratus (6.4%); Candida auris was detected once. In exploratory clinical/administrative models, clinically recorded candidemia showed associations with invasive devices (OR 5.54, 95% CI 2.01-15.64), recent surgery (OR 7.11, 95% CI 1.20-30.88) and tumor (OR 19.88, 95% CI 3.14-97.51). Susceptibility data were available for 196/314 isolates (62.4%); echinocandin activity was high, whereas azole susceptibility was more variable. CONCLUSIONS: Candidiasis showed a sustained recorded burden and substantial non-albicans diversity, supporting local surveillance, species-level identification, and isolate-level susceptibility testing.

The pursuit of sustainable and efficient animal production systems has intensified global interest in microbiota-targeted nutritional strategies. This review synthesizes current research on prebiotics and probiotics, selectively utilized microbial substrates and beneficial live microorganisms, respectively, that confer health benefits, across major livestock and aquaculture sectors, including poultry, swine, ruminants, fish, and shrimp. It examines the fundamental role of host-specific gut microbiomes in regulating health and productivity and elucidates how prebiotics, alone or in synergistic formulations with probiotics, modulate these microbial communities. Mechanisms of action involve enhanced nutrient digestibility, improved intestinal morphology and barrier integrity, selective stimulation of beneficial bacteria (e.g., Lactobacillus, Bifidobacterium), suppression of pathogens (e.g., Escherichia coli, Salmonella, Vibrio), and potentiation of innate and humoral immune responses. Consistent evidence demonstrates that microbiota-targeted interventions improve key zootechnical indicators, including weight gain, feed conversion ratio, and carcass quality, while enhancing animal welfare and resilience to environmental and physiological stressors. A pivotal finding is their ability to reduce reliance on antimicrobial agents, addressing antibiotic resistance and aligning with consumer demand for ethical and natural production systems. Furthermore, this review highlights the valorisation of agro-industrial by-products (e.g., fruit pomace, cereal brans) and novel substrates such as Hermetia illucens (black soldier fly) as functional, cost-effective sources that embed animal nutrition within a circular bioeconomy framework. By integrating multidisciplinary findings from terrestrial and aquatic species, this review concludes that microbiota-based functional nutrition is indispensable for advancing next-generation sustainable animal production, uniting productivity, environmental stewardship, and animal welfare while supporting safe, ethical, and climate-resilient food systems worldwide.

The persistence and dissemination of antibiotic resistance genes (ARGs) in aquatic ecosystems pose increasing risks to public health and ecological stability. The limited capacity of conventional wastewater treatment plants (WWTPs) to reduce ARG abundance and transferability highlights the need for advanced mitigation technologies. Electrochemical technologies exhibit significant potential for ARG elimination due to their in situ generation of potent oxidants, mild reaction conditions, operational flexibility, and environmental compatibility. This review systematically summarizes recent advancements in electrochemical technologies for removing ARGs from wastewater, critically evaluating the technical characteristics and efficiencies of diverse processes such as anodic oxidation, electro-Fenton, three-dimensional electrodes, and hybrid systems. The fundamental mechanisms governing direct and indirect oxidation pathways are comprehensively examined by elucidating the distinct roles of reactive oxygen species (ROS) and reactive chlorine species (RCS) in inactivating host bacteria versus degrading intracellular and extracellular ARGs. Furthermore, the influence of critical factors such as electrode material properties, operational parameters, and water matrix complexity on ARG removal efficacy is analyzed in depth. Current technical and environmental challenges regarding energy consumption, long-term electrode stability, toxic byproduct generation, and limitations in functional assessment frameworks are also identified. Finally, future research perspectives are proposed, emphasizing the development of novel low-energy and highly selective electrode materials, investigation of micro-interface reaction mechanisms in complex environments, establishment of standardized risk assessment protocols, and application of multi-omics analyses to characterize microbial responses. This review aims to provide theoretical guidance and technical support for advancing electrochemical technologies in ARG pollution control.

A central Texas resident found an engorged Ornithodoros turicata tick attached to their ankle while at home. The tick tested positive for Borrelia turicatae, an agent for soft tick-borne relapsing fever. Three weeks earlier, the patient started experiencing febrile episodes, rash, and nausea, yet the etiological agent went undiagnosed.

INTRODUCTION: Inappropriate antibiotic prescribing in primary care remains a major driver of antimicrobial resistance, despite national guidelines and audit-and-feedback systems. Digital antimicrobial stewardship tools may support clinicians in making evidence-based prescribing decisions. The Prescription Search Support (PSS) tool translates guideline recommendations into an interactive decision tree integrated into electronic health records (EHR). This project aims to evaluate the impact of implementing the tool on antibiotic prescribing behaviour in Belgian general practice and to understand the contextual factors influencing its adoption. METHODS AND ANALYSIS: This stepped-wedge cluster randomised trial includes four steps over 12 months. Belgian general practices were randomised in a 1:3:3:3 ratio using stratified block randomisation. All practices start in the control condition, where physicians are expected to provide usual care. At each step, one cluster transitions to the intervention, where PSS becomes accessible through the EHR. The primary objective is to assess whether the implementation of the tool reduces practice-level antibiotic prescribing rates. The primary analysis will use generalised linear mixed models with a logit link, accounting for clustering, time effects and relevant covariates. Secondary analyses include subgroup analyses by region, EHR vendor and intensity of tool use. A nested process evaluation, combining user log file analysis and semistructured interviews, will assess usability, acceptability, fidelity and mechanisms of impact. Sample size calculations indicate that at least 36-48 practices are required to detect a 5% absolute reduction in prescribing with 80% power. All quantitative analyses will be performed in R, and qualitative data will be analysed using reflexive thematic analysis. ETHICS AND DISSEMINATION: The study will be conducted in compliance with the principles of the Declaration of Helsinki (current version) and the principles of Good Clinical Practice and in accordance with all applicable regulatory requirements. Ethics approval for this study was obtained on 10 October 2025 from the Ethical Committee Research UZ/KU Leuven under reference MP037810. We will ensure that the findings of the study will be disseminated to relevant stakeholders beyond the scientific world including the public, healthcare providers

BACKGROUND: Linezolid-resistant Enterococcus faecalis (LREfs) is emerging globally. We investigated the temporal trends and genomic architecture of LREfs through the nationwide surveillance and evaluated the predictors for LREfs bloodstream infections (BSI) in an independent clinical cohort. METHODS: Clinical isolates were collected via the Taiwan Surveillance of Antimicrobial Resistance programs (2014-2020). De novo assemblies were completed using hybrid (MinION/Illumina) or PacBio HiFi sequencing. A matched case-control BSI cohort assessed the association between prior antibiotic exposure and resistance acquisition. RESULTS: LREfs prevalence rose significantly from 2014-2016 to 2018-2020 (1.5% vs. 8.9%, P<0.001). Among 54 LREfs isolates, clonal complex CC480 (37.0%) and CC16 (29.6%) predominated. The optrA gene was present in 96.3% of isolates, with 86.8% of copies chromosomally integrated within the Tn6674 transposon among two prevalent CCs and other sequence types. Conversely, plasmid-mediated resistance driven by IS1216E or other insertion sequences was sporadic. Multi-gene co-carriage (optrA, poxtA, and cfr) was rare and exclusively plasmid-borne. In the clinical cohort, prior linezolid exposure was not associated with LREfs acquisition. CONCLUSIONS: E. faecalis has emerged as a primary linezolid resistance reservoir. The chromosomal fixation of Tn6674-encoded optrA facilitates the widespread distribution of these major lineages, allowing resistance to persist even in absence of recent direct linezolid exposure.

INTRODUCTION: Antibiotic prescribing in simple hand trauma is variable, and poor documentation may undermine antimicrobial stewardship. This study combined a closed-loop audit with a literature review to evaluate prescribing practices and current evidence regarding prophylactic antibiotic use in hand trauma. METHODS: A retrospective closed-loop audit of adult patients presenting with simple hand trauma to a tertiary plastic surgery trauma clinic was performed over two 2-week cycles. Uncomplicated lacerations and nail bed injuries were included, while bite wounds, crush injuries, and open fractures were excluded. Data collected included wound characteristics, antibiotic prescribing practices, and documentation quality. Following cycle one, a departmental teaching session on antimicrobial stewardship and a revised trauma clinic proforma with mandatory prescribing prompts were introduced prior to re-audit. A literature review of PubMed, Scopus, and Google Scholar was also conducted. RESULTS: Twenty-two patients were included in cycle one and 15 in cycle two. In cycle one, antibiotics were prescribed in 72% (15/22) of cases, with poor documentation of indication (6.7%), wound status (6.7%), antibiotic choice and route (40%), and duration (20%). Following intervention, prescribing reduced to 60% (9/15; p=0.099). Documentation of indication, wound status, duration, and appropriate antibiotic choice improved to 100%. The literature review demonstrated substantial variation in prescribing practices and limited evidence supporting routine prophylactic antibiotics in uncomplicated hand trauma. CONCLUSION: Antibiotic prescribing and documentation in simple hand trauma were suboptimal at baseline. Targeted education and redesign of the trauma proforma improved documentation quality and adherence to antimicrobial stewardship principles, highlighting the value of simple, low-cost interventions in supporting evidence-based prescribing.

BACKGROUND: Inappropriate antibiotic use in surgical wards is a major driver of antimicrobial resistance (AMR), especially in low- and middle-income countries, where empirical prescribing is common. This study assessed inpatient antibiotic use and AMR patterns, integrating these findings with qualitative in-depth interviews (IDIs) which explored determinants of prescribing practices. METHODS: A convergent mixed methods study design was employed on the surgical wards of Mulago National Referral Hospital (MNRH) in Uganda. Quantitative data was collected through Point Prevalence Surveys (PPS) of antibiotic use and retrospective analysis of routine laboratory AMR data. Qualitative data was obtained through IDIs with healthcare workers (HCWs). Quantitative data was analysed using R version 4.2.2 and STATA 19. In-depth interviews were recorded and transcribed verbatim, open coded and then analysed using NVivo 12. RESULTS: Of 303 total surgical inpatients, 193/303 (63.7%) (95% CI: 58.0-69.12) were receiving at least one of the 281 antibiotic prescriptions and were included in this study. Surgical antibiotic prophylaxis (SAP) accounted for 256/281 (91.1%) of all antibiotic prescriptions, with 239/256 (93.4%) SAP extending beyond the first 24 hours. Ceftriaxone 89/281 (31.7%) (95% CI: 26.27-37.46), metronidazole 66/281 (23.5%) (95% CI: 18.66-28.89) and levofloxacin 24/281 (8.5%) (95% CI: 11.61-20.44) were most prescribed antibiotic agents. Watch category antibiotics were most used 152/281 (54.1%) (95%: 48.08-60.08), followed by Access category 129/281 (45.9%) (95% CI: 39.9-51.9). Although HCWs demonstrated awareness of AMS principles, formal stewardship systems were fragmented, and prescribing behaviour was strongly influenced by laboratory constraints, infection prevention and control (IPC) gaps and systemic challenges. CONCLUSION: Prolonged SAP and Watch category predominant prescribing occur within a context of high AMR prevalence and constrained AMS infrastructure. Integrated AMS interventions combining institutional antibiograms and their reinforcement, audit and feedback mechanisms, establishment of clear AMS structures and laboratory capacity strengthening are urgently needed to mitigate AMR and optimize surgical antibiotic use.

Myocardial autoimmune responses result in distinctive cardiac diseases and are associated with poor clinical outcomes. Autoantibodies (AAbs) play a crucial role in myocardial humoral autoimmunity by targeting endogenous tissue, or "self-antigens." Myocardial tissue injury or myocyte disarray caused by AAbs triggers a cascade of defensive immunological responses that may lead to worsening biventricular remodeling. However, over the past decade, the concept of AAbs in myocardial diseases has shifted from viewing AAbs as uniformly deleterious to a more nuanced explanation of AAbs influencing downstream intracellular pathways with multiple possible outcomes. This paradigm shift arose from technological advances such as large language models for accelerated epitope screening and high-throughput protein assays that uncover complex autoimmune cross-reactivity and downstream intracellular signaling pathways. In this contemporary review article, we critically appraise the latest translational data on the role of AAbs in myocardial disease and provide a framework to encourage scientific endeavors in the development of new therapeutics for cardiomyopathies.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare but life-threatening condition occurring during late pregnancy or the postpartum period. Although late gadolinium enhancement (LGE) has prognostic value in other cardiomyopathies, its role in PPCM remains unclear. This study aimed to evaluate the prognostic significance of LGE in PPCM. METHODS: Three electronic databases were systematically searched to identify studies assessing the association between LGE and clinical outcomes in PPCM. Outcomes included reduced left ventricular ejection fraction (LVEF), arrhythmia, heart failure decompensation, device implantation, transplantation, and mortality. Pooled hazard ratios were calculated using the generic inverse variance method. RESULTS: Eight cohort studies involving 227 patients were included. The mean age was 32.2 ± 6.6 years and mean LVEF was 30.5%. The pooled hazard ratio analysis revealed that LGE was significantly associated with poor outcomes (HR 1.34, CI 1.04-1.73 I2 = 52%, p = 0.02). Further analysis demonstrated that LGE was strongly linked to adverse clinical outcomes (HR 2.95, CI 1.62-5.37, I2 = 0%, p = 0.004), whereas no significant association was observed with persistently reduced LVEF (HR 1.11, CI 0.85-1.45, I2 = 14%, p = 0.45). CONCLUSION: LGE is associated with poor outcomes in PPCM and may provide complementary prognostic value for risk stratification. PROTOCOL REGISTRATION: www.crd.york.ac.uk/prospero identifier is CRD42024568502.

Wellens syndrome was initially described in the early 1980s and is characterized by 2 high-risk electrocardiographic (ECG) patterns associated with critical stenosis of the left anterior descending artery (LAD). A prevailing theory suggests that Wellens' pattern A is underdiagnosed due to delays in clinical presentation; therefore, the most common finding upon arrival at the Emergency Department is pattern B, accounting for nearly 80% of cases. This suggests that pattern A often evolves prior to medical assessment. Alternatively, aligning with our study, we propose a dynamic model characterized by a distinct electrocardiographic transition between pattern A and B, electrophysiologically explained by ischemic vectoring shifting and supported by clinical observations where some patients do not complete the classic transition. We enrolled 51 patients with Wellens syndrome to assess serial electrographic changes and transitions, alongside analyzing demographics, cardiovascular risk factors, clinical past history, left ventricular ejection fraction, and revascularization outcomes. All cases underwent coronary angiography, which confirmed LAD involvement, consistent with Wellens' original description. Notably, an ECG transition from patterns A to B was documented within 6 to 12 hours in 18 patients (36%). All patients in our cohort achieved favorable clinical outcomes.

BACKGROUND: Decision to perform a fenestrated Fontan remains difficult to standardize, and criteria vary widely across centres. AIM: To evaluate, in a cohort of pediatric patients undergoing total cavo-pulmonary connection (TCPC), the prognostic implications of fenestration at baseline and medium-term follow-up. METHODS: This retrospective study included children who underwent extracardiac TCPC between 2012 and 2024. Patients were stratified by fenestration status at last follow-up. Primary endpoint was a composite of cardiovascular death, heart failure hospitalization, functional limitation, symptomatic desaturation, listing for heart transplantation, or Fontan failure. Predictors of adverse outcomes were analysed using Cox proportional hazards models and Random Survival Forest (RSF). RESULTS: Among 109 patients, 61 (55.9%) underwent fenestrated TCPC. Of these, 29 (48%) had persistently patent fenestration, 16 (26%) had spontaneous closure, and 16 (26%) underwent transcatheter closure. Percutaneous closures occurred at a median of 3.8 years after TCPC (IQR 2.2-5.1), whereas spontaneous closure occurred earlier (0.3 years; IQR 0.2-0.9). Patients with persistent fenestration had worse pre-Fontan haemodynamical profile. Over a median follow-up of 7.54 years, 10 patients reached the primary outcome. At univariate time-dependent Cox analysis, HLHS, >moderate AV regurgitation, and persistent fenestration were associated with the primary outcome. In exploratory multivariable analysis, HLHS remained independently associated, while persistent fenestration showed borderline association. RSF analysis confirmed fenestration status as a major predictor, followed by HLHS, TPG, and AV valve regurgitation. CONCLUSION: A persistently patent fenestration may be a marker of high risk in the Fontan population. Pre-Fontan haemodynamic characteristics influence the likelihood of fenestration closure.

Cardiovascular imaging plays a central role in the diagnosis, risk stratification, and longitudinal management of cardiovascular disease during pregnancy. Physiological adaptations-including increased blood volume, cardiac output, and chamber remodeling-pose important challenges for image acquisition and interpretation, necessitating a nuanced understanding of normal versus pathological findings. This review provides a practical, cardiology-focused framework for the use of imaging in pregnant patients with suspected or established cardiovascular disease. We emphasize key aspects relevant to cardiac imagers, including appropriate modality selection, pregnancy-adapted imaging protocols, and interpretation of findings in the context of dynamic physiological changes. Transthoracic echocardiography remains the first-line modality, while cardiovascular magnetic resonance offers complementary, radiation-free evaluation in selected cases. Imaging techniques involving ionizing radiation, such as computed tomography and invasive angiography, should be reserved for acute or high-risk scenarios and carefully optimized to minimize fetal exposure. We further discuss common diagnostic pitfalls, limitations of each modality, and areas of uncertainty, including the use of contrast agents and thresholds for advanced imaging. The importance of integrating imaging findings into multidisciplinary decision-making within Pregnancy Heart Teams is highlighted. By providing a structured, clinically oriented approach, this review aims to support cardiac imagers in delivering safe, accurate, and evidence-informed care to this complex patient population.

Dyspnea is a key symptom of heart failure (HF), particularly in its acute form, where it represents the most common cause of hospitalization. Although traditionally attributed to pulmonary congestion, dyspnea in HF is a multidimensional phenomenon resulting from complex interactions among elevated cardiac filling pressures, hemodynamic alterations, fluid redistribution, impaired gas exchange, activation of mechano- and chemoreceptors, and maladaptive neurohormonal activation. Comorbidities, including chronic lung disease, obesity, cachexia, renal dysfunction, anemia, and chronic inflammation, further modulate symptom perception and lower the threshold for its occurrence. In this review, we synthesize current knowledge on the pathophysiological mechanisms underlying dyspnea in HF, emphasizing its heterogeneity and the complex interplay between hemodynamics, ventilatory regulation, and peripheral factors. We discuss available dyspnea assessment tools, highlighting their strengths and methodological limitations in clinical practice and randomized trials. Despite the use of standardized scales, dyspnea remains a subjective and dynamically evolving symptom. Data from large clinical trials in acute HF indicate that early improvement in dyspnea is common but does not translate into reduced mortality or rehospitalization, whereas residual dyspnea identifies patients at higher risk of adverse events. A better understanding of its multidimensional pathophysiology, measurement limitations, and prognostic significance has important implications for the interpretation of clinical trial results and for optimizing the assessment and management of this fundamental symptom.

Heart failure with preserved ejection fraction (HFpEF) is the most prevalent form of heart failure and is characterized by high morbidity, limited therapeutic options, and marked biological heterogeneity. Coronary microvascular dysfunction (CMD) has emerged as a central pathophysiological mechanism linking cardiometabolic comorbidities to myocardial remodeling and clinical HFpEF phenotypes. Impaired coronary flow reserve, endothelial dysfunction, reduced nitric oxide bioavailability, and microvascular rarefaction contribute to myocardial stiffening, energetic inefficiency, and ultimately diastolic dysfunction, often preceding overt structural heart disease in the setting of HFpEF. Notably, HFpEF disproportionately affects females, yet the biological mechanisms underlying this sex difference remain incompletely understood. Accumulating evidence suggests that sex-specific differences in vascular biology, immune-metabolic signaling, hormonal regulation, and myocardial-vascular coupling modulate susceptibility to CMD and influence the progression from vascular dysfunction to myocardial disease. Females exhibit a higher prevalence of CMD in the absence of obstructive coronary artery disease, distinct inflammatory and metabolic profiles, and accelerated vascular and ventricular stiffening, particularly after menopause. In contrast, males more frequently display eccentric remodeling and obstructive epicardial coronary disease. This narrative review synthesizes current evidence on the mechanistic role of CMD in HFpEF, with a specific focus on sex-specific biological pathways that shape disease trajectory. Understanding how sex modifies CMD may inform improved diagnostic strategies, risk stratification, and the development of precision-based therapeutic approaches in HFpEF.

Atrial fibrillation (AF) can be sustained by intramural reentrant circuits within three-dimensional arrhythmogenic hubs formed by fibrotically-insulated myobundles. However, the efficacy of different multi-electrode mapping (MEM) to identify the micro-reentrant pathways sustaining AF remains undefined. An anisotropic atrial tissue structure (30 × 30 × 4 mm), incorporating a sub-endocardial laterally-insulated myobundle (15 × 2.5 × 1.5 mm) was simulated reflecting persistent AF conditions. Simulations included endocardial unipolar, bipolar, and omnipolar electrograms, with local activation time maps calculated for reentry visualization. N = 656 MEM configurations were evaluated, varying inter-electrode distances (1, 3, 6 and 9 mm), orientations (parallel and perpendicular), contact distances to the wall (0.25 and 1.0 mm), and electrode positions (in 1-mm increments) relative to the reentrant circuit. Conduction along the reentrant pathway was identified by electrograms within <3 mm of the micro-reentrant circuit, and confirmed by their comparison to action potential traces. However, detection on electrogram (EGM) traces was highly dependent on catheter configuration and distance to the atrial wall. Dense unipolar MEM configurations (1-6 mm spacing) facilitated pathway identification, while bipolar MEM required electrode pairs to align with the myobundle for effective detection. Omnipolar configurations offered no significant advantages over unipolar for modest inter-electrode spacings (1-6 mm) but improved detection accuracy at larger spacings (9 mm). Mapping was affected by micro-reentrant track width, though reentrant mapping still detected tracks thinner than electrode spacing. Track thickness and conduction velocity did not impair detection and sometimes improved it. Unipolar MEM configurations (1-6 mm spacing) with optimal contact enabled the detection of sub-endocardial reentry pathways sustaining AF in 50-100% of simulated cases. Combining unipolar and omnipolar mapping approaches (3 mm spacing) may enhance the detection rates of AF micro-reentry. These findings provide critical insights into optimizing MEM techniques for human AF reentrant circuit detection and may improve the efficacy of AF ablation procedures.

BACKGROUND: Peripartum cardiomyopathy disproportionately affects women experiencing socioeconomic disadvantage, yet the prognostic impact of deprivation within contemporary U.S. health systems remains uncertain. OBJECTIVE: To evaluate whether socioeconomic deprivation independently influences 1-year clinical outcomes in patients with peripartum cardiomyopathy. STUDY DESIGN: This retrospective cohort study used the TriNetX U.S. research network (2015-2024) to identify adults with peripartum cardiomyopathy. Socioeconomic deprivation was defined using validated ICD-10/HCPCS social risk codes. Patients were propensity score-matched (1:1) for demographics, comorbidities, medications, and laboratory values. Cox proportional hazards models estimated 12-month outcomes. RESULTS: After 1:1 propensity score matching, 1,298 women were included in each cohort, with balanced baseline characteristics. At 12 months, socioeconomic deprivation was not associated with the primary composite outcome of all-cause mortality or hospitalization (HR 1.03; 95% CI 0.89-1.19; P=0.728), nor with either component individually. Socioeconomically deprived women had lower hazards of heart failure events (HR 0.82; 95% CI 0.73-0.93; P=0.001) and arrhythmia (HR 0.83; 95% CI 0.70-0.99; P=0.039). No significant differences were observed in thromboembolic events, new-onset thromboembolism, cardiogenic shock, or procedural outcomes. CONCLUSIONS: In this large real-world U.S. cohort, socioeconomic deprivation did not worsen 1-year outcomes in peripartum cardiomyopathy, suggesting that access to high-quality, equitable care may attenuate socioeconomic disparities.

Electrical storm (ES) refers to a life-threatening state of cardiac electrical instability, and occurrence of three or more episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF) within 24-hour period. Contemporary management extends beyond antiarrhythmic therapy and catheter ablation to include autonomic modulation, rehabilitation, and longitudinal patient engagement. We present two illustrative cases: one with non-ischemic cardiomyopathy with refractory VT storm, and the other with post-myocardial infarction VF storm, to demonstrate a practical stepwise management framework from acute stabilization to long-term surveillance. These cases highlight the importance of early sedation, optimized pharmacologic therapy, neuromodulation, tailored ablation strategies, rehabilitation, and structured continuity of care.

OBJECTIVE: Pacing artifacts in electrocardiogram (ECG) signals can interfere with waveform analysis and downstream quantitative interpretation. This study presents an algorithm for detecting and removing pacing artifacts from routine ECG recordings. METHODS: The algorithm applies high pass filtering and Shannon energy computation to suppress cardiac components and enhance pacing artifacts. Principal component analysis (PCA) is then applied to the 12-lead ECGs to identify artifact start and end points from the first principal component. At each candidate location, slopes are calculated across leads, and artifacts are removed by linear interpolation only when the slope magnitude exceeds a predefined threshold. The algorithm was developed using 493 12-lead ECGs from the Chronic Renal Insufficiency Cohort and validated using 203 Cleveland Clinic 12-lead ECGs, 80 Cardiac Memory with ICD 12 lead ECGs, and 200 10-second two-lead Holter ECG epochs from the MIT-BIH Arrhythmia Database. A graphical user interface was developed for review and refinement. RESULTS: The algorithm automatically detected and removed pacing artifacts in 84% of validation ECG files; the remaining files required user-guided refinement. Overall sensitivity and specificity for pacing artifact detection were 98.4% and 76.2%, respectively. CONCLUSION: The proposed algorithm detects and removes pacing artifacts with substantial automation while allowing guided refinement in challenging recordings. SIGNIFICANCE: The framework combines multilead PCA-based localization, lead-specific slope confirmation, and adaptive artifact-width removal directly on routine ECG, enabling morphology-preserving preprocessing for quantitative and AI-enabled ECG analysis.

INTRODUCTION: SGLT2 inhibitors (SGLT2i) reduce heart failure events across the ejection fraction spectrum, but their association with device-adjudicated ventricular arrhythmias in real-world primary-prevention ICD recipients remains poorly characterized. METHODS AND RESULTS: In a prospectively maintained primary-prevention ICD registry (n = 62; January 2021 onward), 36 patients (58%) were receiving SGLT2i at implantation. The primary endpoint was first appropriate ICD shock for sustained ventricular tachyarrhythmia; death without prior shock was the pre-specified competing event. Cumulative incidence functions were estimated by the Aalen-Johansen method. Over a median follow-up of 752 days, 22 first appropriate shocks occurred. SGLT2i-treated patients had more advanced structural disease (median LVEF 31% vs. 51%) and lower baseline arrhythmic burden (NSVT 36% vs. 69%) than untreated patients. Cumulative incidence of appropriate shock differed significantly between groups (Gray test p = 0.008). In a cause-specific Cox model adjusted for LVEF and amiodarone use, SGLT2i was associated with a lower hazard of appropriate shock (HR 0.34; 95% CI 0.13-0.91; p = 0.031), confirmed by Fine-Gray subdistribution analysis (sHR 0.36; 95% CI 0.13-0.99; p = 0.047). Results were consistent in an HFrEF sub-cohort (LVEF 35% or less; HR 0.24; 95% CI 0.06-0.92; p = 0.037). Adjustment for baseline NSVT attenuated the association to non-significance (HR 0.43; p = 0.12), reflecting confounding by arrhythmic substrate. CONCLUSION: In this single-center competing-risk analysis, SGLT2i use at ICD implantation was associated with fewer device-adjudicated arrhythmic events. Whether this reflects direct electrophysiological modification or favorable patient selection requires confirmation in larger cohorts.

BACKGROUND: Anthracycline use is associated with cardiotoxicity. Dexrazoxane may prevent anthracycline-associated cardiotoxicity, yet its adoption remains inconsistent due to concerns about oncological interference and myelosuppression. METHODS: A systematic review was conducted following PRISMA guidelines (PROSPERO: CRD420251039900). MEDLINE, EMBASE, CENTRAL, Web of Science, and Scopus were searched from inception to 12/2025. Both randomized and observational studies reporting on the effects of dexrazoxane on risk of clinical heart failure (HF) and left ventricular ejection fraction (LVEF) decline, oncological outcomes (objective response, overall survival, progression-free survival), and hematological toxicities (anemia, neutropenia, thrombocytopenia) in adults receiving anthracycline-based chemotherapy were included. Random-effects meta-analyses were performed, stratified by study design. Certainty of evidence was assessed using GRADE. RESULTS: Sixteen studies (N=3996) were included. Based on moderate certainty randomized trial evidence, dexrazoxane likely reduces clinical HF (RR 0.23, 95% CI 0.10-0.51) with no difference in neutropenia (RR 1.04, 95% CI 0.98-1.11). Based on low certainty randomized trial evidence, dexrazoxane may reduce LVEF decline (RR 0.38, 95% CI 0.26-0.54) with little to no difference in objective response (RR 0.91, 95% CI 0.80-1.04), anemia (RR 1.44, 95% CI 1.19-1.75), and thrombocytopenia (RR 0.89, 95% CI 0.65-1.24). Evidence was uncertain regarding the effect on overall and progression-free survival. CONCLUSIONS: Dexrazoxane was associated with a lower risk of clinical HF and LVEF decline without significant differences in cytopenias or oncologic response. However, the certainty of evidence was limited. Further research in contemporary cardio-oncology should focus on non-breast cancer populations, standardize outcome definitions, and evaluate alternative dosing regimens.

OBJECTIVE: Sex hormones is linked to the inflammatory and diastolic dysfunction. The testosterone-to-estradiol ratio (T/E2) may better capture the relative androgenic-to-estrogenic balance more comprehensively. We investigated whether T/E2 is associated with systemic inflammation, diastolic dysfunction, and short-term outcomes in postmenopausal women with HFpEF. METHODS: This single-center prospective cohort included 184 postmenopausal women with HFpEF and followed up for 12 months. Sex hormones were measured by chemiluminescent immunoassays. Associations of T/E2 with inflammatory biomarkers, echocardiographic indices, 12-month NT-proBNP and clinical outcomes were evaluated using correlation, multivariable linear regression, and logistic regression analyses. RESULTS: Median testosterone and estradiol concentrations were 14.61 ng/dL and 18.60 pg/mL, respectively. Higher T/E2 was independently associated with lower hs-CRP (β = -0.353, P < 0.001), NLR (β = -0.162, P = 0.015), IL-6 (β = -0.166, P = 0.005), and E/e' (β = -0.073, P = 0.032), but not with D-dimer, LAD or 12-month NT-proBNP (β = 0.065, 95% CI -0.115 to 0.245; P = 0.481). The 12-month composite clinical endpoint occurred in 54 participants (29.3%). Higher T/E2 was associated with lower odds of the composite endpoint (OR = 0.653, 95% CI 0.450-0.949; P = 0.025), mainly reflecting heart failure hospitalization (OR = 0.618, 95% CI 0.417-0.915; P = 0.016). CONCLUSIONS: In postmenopausal women with HFpEF, lower T/E2 is associated with greater systemic inflammation, worse diastolic hemodynamics, and higher odds of short-term clinical event. These findings suggest that T/E2 may serve as a candidate endocrine-inflammatory marker for HFpEF phenotyping in postmenopausal women.

Intracardiac echocardiography (ICE) is an alternative to transesophageal echocardiography for imaging guidance during left atrial appendage occlusion (LAAO) in patients with atrial fibrillation with intolerance to long-term oral anticoagulation. This narrative review synthesizes contemporary evidence on ICE-guided LAAO. Across observational studies, ICE provides real-time high-resolution imaging enabling accurate trans-septal puncture, device sizing, and deployment under conscious sedation. Procedural success, peri-device leak, and device-related thrombus rates appear comparable between ICE- and TEE-guided LAAO, while ICE may also shorten fluoroscopy time and avoid general anesthesia. Challenges with ICE include operator learning curve, need for additional venous access and intracardiac catheter manipulation, that may add to risks like pericardial effusions, vascular complications and higher costs. Emerging 3D/4D ICE and artificial-intelligence-integrated computed tomographic planning may improve efficiency and allow for combined ablation and LAAO procedures. Further randomized controlled trials and cost-effectiveness studies are needed to define the role of ICE-first approach.

BACKGROUND: Long-term garment-type wearable Holter electrocardiographic (ECG) monitoring is frequently affected by noise contamination, which complicates automated atrial fibrillation (AF) detection in real-world recordings. Although deep learning has shown high performance for AF detection, relatively few studies have evaluated explicit strategies for handling noise-included wearable ECG data. An alternative representation using the R-R interval (RRI) time series may reduce the dependence on waveform morphology and provide an alternative pathway for AF screening in noisy recordings. OBJECTIVE: This study aimed to develop and evaluate a 3-class, noise-aware RRI-based AF screening framework that explicitly separated AF, non-AF, and uninterpretable noise windows, and to assess the impact of analysis window length on model performance. METHODS: Single-lead garment-type wearable Holter ECG data from 117 patients at the University of Osaka Hospital were analyzed after exclusion of patients with documented atrial tachycardia, flutter, or paced rhythm according to the predefined task definition. R-peaks were automatically detected, and the resulting RRI segments were converted into 2D histogram images, with time on the x-axis and RRI-derived heart rate on the y-axis, for 1.5-, 3-, and 6-minute windows. A ResNet-34-based 2D convolutional neural network was trained for 3-class classification. Model performance was evaluated using 5-fold interpatient cross-validation on the institutional dataset and independent external testing on the MIT-BIH (Massachusetts Institute of Technology-Beth Israel Hospital) AF Database (AFDB). In the external validation, atrial flutter-annotated intervals were excluded to match the training task definition. Patient-level AF burden was evaluated by comparing reference AF burden with model-estimated AF burden using Pearson and Spearman correlation coefficients, and linear regression. RESULTS: Of 129 monitored patients between March 1, 2023, and November 20, 2025, 117 were analyzed. In the internal validation, the 3-class model (non-AF, AF, and noise) showed similarly high performance for the 1.5- and 3-minute windows, both with an accuracy of 96.6%. In independent external validation, the 3-minute window showed numerically the highest overall performance (accuracy: 97.3%; AF sensitivity: 96.9%; and AF specificity: 97.7%), although the dif

BACKGROUND: Longitudinal metabolomic studies can refine understanding of heart failure (HF) progression and enable precision prevention. This study aims to identify serum metabolites associated with HF risk via longitudinal metabolomic analysis, delineate their dynamic trajectories, and explore metabolite profiles in populations with different metabolic disorders. METHODS: This study analyzed longitudinal serum metabolomic data from 4774 serum samples from 1728 HF-free participants in the Chinese Multi-Provincial Cohort Study Metabolomics Project at 4 time points over a 20-year follow-up. Intensity models and Cox proportional-hazards models identified metabolites associated with HF risk. Latent variable mixed-effects models evaluated metabolite trajectories. RESULTS: Of the 784 detected metabolites, 23 were associated with HF risk at a false discovery rate-adjusted P<0.05, including 9 not previously reported in relation to HF. The HF risk-associated metabolites exhibited 4 distinct trajectory clusters and corresponding biological trends. Most metabolites that showed positive associations with HF risk remained relatively stable throughout the 20-year follow-up period, whereas metabolites that were negatively associated with HF risk generally exhibited a declining trend. The levels of these 23 metabolites in the group who developed HF began to diverge from the levels in the non-HF group >5 years before clinical HF diagnosis, with most changes initiating 15 to 20 years before clinical manifestation. Populations with different metabolic disorders exhibited distinct metabolite profiles related to HF. The HF-associated metabolites were primarily involved in energy metabolism and the vasodilatory response among individuals with hypertension, lipotoxic effects and oxidative stress among those with obesity, and inflammatory processes and glucotoxic mechanisms among individuals with dysglycemia. CONCLUSIONS: This longitudinal metabolomic study identifies HF-associated metabolite profiles, characterizes their changes during the 20 years preceding clinical diagnosis, and reveals heterogeneity across individuals with different metabolic disorders, thereby informing future biomarker and intervention research.

BACKGROUND: The platelet-to-albumin ratio (PAR) has shown to be linked with cardiovascular disorders. However, the specific association between the admission PAR and one-year outcomes in patients with acute coronary syndrome (ACS) remains to be fully characterized. This study investigated the linkage between PAR levels and the occurrence of one-year all-cause mortality and major adverse cardiovascular and cerebrovascular events (MACCEs) in the ACS population. PATIENTS AND METHODS: This retrospective cohort study enrolled patients diagnosed with ACS between January 2022 and December 2023. The primary endpoint was one-year all-cause mortality, and the secondary endpoint was MACCE, defined as a composite of all-cause mortality, non-fatal myocardial infarction, ischemic stroke, heart failure rehospitalization, target vessel revascularization or in-stent thrombosis, and malignant arrhythmia. To evaluate the relationship between PAR and these clinical events, we employed multivariate Cox proportional hazards models, restricted cubic splines (RCSs) and two-piecewise linear regression to identify potential non-linear associations and specific inflection points. RESULTS: A total of 1326 participants (median age: 67 years) were followed for one year, during which 137 (10.3%) deaths and 280 (21.1%) MACCE events occurred. The one-year all-cause mortality rates across the PAR quartiles (Q1-Q4) were 11.6%, 6.1%, 7.0% and 16.7%, respectively, with a similar trend observed for MACCE (22.1%, 15.2%, 18.7% and 28.5%). RCS analysis revealed significant nonlinear associations between the PAR and both clinical endpoints (all p for nonlinear < 0.05). Two-piecewise linear regression analysis identified specific inflection points at 5.28 (95% confidence interval [CI]: 4.86-9.86) for one-year all-cause mortality and 5.29 (95% CI: 4.37-6.58) for MACCE. CONCLUSIONS: The PAR demonstrates a significant nonlinear relationship with one-year all-cause mortality and MACCE in patients with ACS.

BACKGROUND: While the pro-inflammatory M4 macrophage phenotype contributes to cardiovascular pathogenesis, its specific involvement in chronic post myocardial infarction (MI) remodeling and responsiveness to different exercise modalities remain unexplored. We hypothesized that high-intensity interval training (HIIT) confers enhanced cardioprotection compared to moderate-intensity continuous training (MICT) by mitigating M4 macrophage polarization. METHODS: A murine MI model was randomized to 4-week HIIT, MICT, or sedentary groups. Cardiac function, structural remodeling, and macrophage phenotypes were evaluated, followed by transcriptomic profiling of the myocardium. For clinical translation, plasma samples from a human coronary artery disease (CAD) cohort (with/without prior MI) were analyzed. Causality was investigated in vitro using PF4-stimulated human macrophages with targeted genetic knockdown, co-cultured with AC16 ventricular cardiomyocytes. RESULTS: Both exercise modalities improved functional capacity and attenuated adverse remodeling post-MI, with HIIT demonstrating enhanced efficacy over MICT. HIIT significantly attenuated MI-induced M4 macrophage polarization, evidenced by diminished expression of MMP7, S100A8, and downstream pro-inflammatory cytokines. Additionally, plasma S100A8 levels significantly elevated in post-MI patients. Transcriptomic profiling identified integrin subunit alpha M (Itgam) as a critical upstream target; while significantly upregulated post-MI, its expression was effectively suppressed by HIIT. In vitro, targeted ITGAM knockdown effectively suppressed PF4-induced M4 polarization and mitigated macrophage-mediated cardiomyocyte apoptosis. CONCLUSIONS: Compared to MICT, HIIT demonstrates superior efficacy in attenuating post-MI adverse remodeling, accompanied by significant suppression of pro-inflammatory M4 macrophage polarization. In vitro validations link this protective phenotype to ITGAM downregulation. These findings inform post-MI exercise regimens and highlight potential molecular targets for developing exercise mimetics.

Chrysin (5,7-dihydroxyflavone), a naturally occurring flavonoid abundant in various fruits, plants, vegetables and other dietary sources, which has shown cardioprotective potential in the management of cardiovascular disorders like myocardial infarction, atherosclerosis, hypertension, cardiotoxicity and diabetic associated cardiovascular complications. Chrysin exerts cardio protection through decreasing oxidative stress by increasing endogenous antioxidant enzymes like SOD, catalase and glutathione. It shows anti-inflammatory response via suppression of pro-inflammatory mediators such as interleukins, NF-κB, TNF-α and COX-2. Chrysin treatment treatment improves endothelial function by regulating lipid metabolism and blood lipid profile. It increases endothelial nitric oxide levels and decreases apoptosis by downregulating pro-apoptotic markers. In myocardial ischemia and cardiac hypertrophy, it has been associated with reduced infarct size, vascular proliferation and enhance cardiac function. Chrysin treatment is modulated key pathways like PI3K/Akt/Nrf2, MAPK, NOX4 and TGF-β/Smad Signalling pathway. In this review we summarize the available research literature of chrysin in different cardiovascular disorders, highlighting the cellular and molecular mechanisms underlying its therapeutic potential.

PURPOSE: There are few national studies of waiting-list mortality for heart transplantation (HT) in Korea. Our multicenter study examined mortality on the HT waiting list and its associated risk factors. MATERIALS AND METHODS: We retrospectively analyzed 1101 consecutive patients who were wait-listed for HT between 2012 and 2017 in four centers. Time on the HT waiting list was defined as the time from initial wait-listing to delisting due to HT, death, or recovery. Subjects were censored at the time of transplantation or recovery. RESULTS: Of the whole cohort, 327 (29.7%) patients needed mechanical circulatory support (MCS) while on the waiting list, 314 (28.5%) were treated with extracorporeal membrane oxygenation (ECMO) as a bridge, and 13 (1.2%) were treated with a ventricular assist device (VAD) as a bridge. The waiting-list survival rate for ECMO-bridged patients was significantly lower than that for VAD-bridged or non-MCS-bridged patients. The waiting-list survival rate for patients with a status of 0 or 1 was significantly lower than for patients with a status of 2 or 3. Multivariate analysis revealed that the independent risk factors for waiting-list mortality were congenital heart disease and restrictive cardiomyopathy compared with dilated cardiomyopathy, status 0 compared with status 2 and 3, low hemoglobin, history of ventricular arrhythmia, high MELD-XI score, and ECMO bridging during the waiting period. CONCLUSION: This study showed that ECMO as a bridge to transplantation and status 0 were associated with significantly higher waiting-list mortality. Advanced end-organ damage at the time of listing was also found to be an independent risk factor for waiting-list mortality.

OBJECTIVES: To determine the time to major adverse cardiovascular events (MACE) and identify its predictors among patients with acute coronary syndrome (ACS) discharged on secondary prevention medications in Ethiopia. DESIGN: Institution-based retrospective cohort study. SETTING: University of Gondar Comprehensive Specialized Hospital, Northwest, Ethiopia. PARTICIPANTS: A total of 400 adult patients diagnosed with ACS and discharged with secondary prevention medications between January 2020 and December 2024. OUTCOME MEASURES: The primary outcome was time to first MACE, defined as reinfarction, stroke or heart failure, measured in years from hospital discharge. A Cox proportional hazards regression model was fitted to identify predictors of time to develop MACE. Data collected from patient medical charts were exported to STATA V.17 for analysis. The log-rank test was used to determine the survival difference between subgroups of participants. RESULTS: During follow-up, 33.8% of patients experienced at least one MACE. The median time to MACE was 1.5 years. Female sex (adjusted HR (AHR)=2.08; 95% CI 1.24 to 3.49), presence of chronic comorbidities (AHR=2.09; 95% CI 1.42 to 4.41) and higher Killip class (IV vs I: AHR=1.57; 95% CI 1.22 to 1.78) were independently associated with a shorter time to MACE. Patients aged ≤55 years had a lower risk of MACE compared with those aged ≥66 years (AHR=0.77; 95% CI 0.54 to 0.98). CONCLUSIONS: Among patients with ACS discharged on secondary prevention medications, one-third experienced MACE within a median of 1.5 years. Older age, female sex, presence of comorbidities and higher Killip class were significant predictors of shorter time to MACE. These findings highlight the need for targeted postdischarge monitoring and secondary prevention strategies, particularly in resource-limited settings.

The optimal timing for venoarterial extracorporeal membrane oxygenation (VA-ECMO) initiation in patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) remains unclear. This study evaluated whether initiating VA-ECMO before primary percutaneous coronary intervention (PCI) improves survival compared with post-PCI initiation in patients with AMICS. We performed a single-center retrospective cohort study using registry data from 113 patients with AMICS who received VA-ECMO. The patients were classified into ECMO pre-PCI (n = 72) and ECMO post-PCI (n = 41) groups. The 30-day mortality rate in the ECMO pre-PCI group (29.2%) was lower than that in the ECMO post-PCI group (61.0%) (adjusted hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.17-0.60; p < 0.001) and remained consistent across most subgroups. The ECMO pre-PCI group was also associated with lower in-hospital (27.8% vs. 61.0%; adjusted odds ratio, 0.20; 95% CI, 0.08-0.48; p < 0.001), 180-day (36.1% vs. 63.4%; adjusted HR, 0.36; 95% CI, 0.20-0.65; p < 0.001), and 360-day (40.3% vs. 65.9%; adjusted HR, 0.37; 95% CI, 0.21-0.66; p <0.001) mortality. In selected patients with AMICS, initiating VA-ECMO support before primary PCI may reduce short- and long-term mortality compared with initiating support after primary PCI. These findings highlight the potential significance of early hemodynamic stabilization and warrant further prospective studies.

BACKGROUND: Frequent premature ventricular complexes (PVC) can lead to a reversible form of left ventricular (LV) dysfunction termed PVC-induced cardiomyopathy (PIC). Catheter ablation is increasingly recognized as the most effective treatment; however, outcomes may differ by the anatomical site-of-PVC origin. METHODS: We conducted a systematic review and meta-analysis of studies published from 2000 to 2025 evaluating catheter ablation in patients with PIC. Eligible studies reported outcomes stratified by PVC origin, including right ventricular outflow tract (RVOT), LV outflow tract (LVOT), papillary muscle, and epicardial/para-His regions. Primary outcomes were change in LV ejection fraction (LVEF) and normalization (≥ 50%). Secondary outcomes included PVC recurrence, repeat ablation, and major complications. Pooled estimates were calculated using random-effects models. RESULTS: Twelve studies (n = 718) met inclusion. Overall, ablation improved LVEF by a mean of 11.0% (95% confidence interval 9.5-12.5; P < .001), with normalization in ~65% of patients. Outcomes varied by PVC origin: RVOT (ΔLVEF ~12.5%, normalization ~70%), LVOT (ΔLVEF ~11.0%, normalization ~65%), papillary muscle (ΔLVEF ~8.0%, normalization ~55%), and epicardial/para-His (ΔLVEF ~6.5-7.0%, normalization ~50%). Recurrence rates were lowest for RVOT/LVOT (~12-20%) and highest for papillary and epicardial sites (~28-30%). Major complications were infrequent (~3-5%), but more common with epicardial or para-His ablations. CONCLUSION: Catheter ablation provides substantial and often reversible improvement in LVEF for patients with PIC, with generally low complication rates. However, outcomes are strongly site-dependent, favoring RVOT and LVOT origins.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Antazoline, a first-generation antihistamine with antiarrhythmic properties, has shown efficacy in the rapid conversion of recent-onset AF to sinus rhythm; however, direct comparative evidence against standard antiarrhythmic agents remains limited. This study aims to systematically evaluate the efficacy and safety of antazoline for pharmacological cardioversion of AF, in comparison with standard antiarrhythmic agents such as amiodarone and propafenone. METHODS: The methodology of this systematic review and meta-analysis adhered to the preferred reporting items for systematic reviews and meta-analyses guidelines. A systematic search was conducted in ScienceDirect, Embase, PubMed, and Cochrane Library from inception to April 2025, including citation and reference screening. Statistical analyses were performed using R version 2025.05.0 + 496. RESULTS: From 172 records, 5 studies comparing antazoline with propafenone (n = 5) or amiodarone (n = 3) for AF were included. For antazoline vs propafenone, conversion to sinus rhythm favored antazoline (risk ratio [RR] 1.13 [95% confidence interval (CI): 1.04-1.23], P = .017). No significant difference was observed in time to conversion (mean difference -10.98 [95% CI: -124.93-102.98], P = .436), bradycardia (RR 0.84 [95% CI: 0.35-2.03], P = .478), hypotension (RR 0.40 [95% CI: 0.14-1.12], P = .056), or other adverse events (RR 1.24 [95% CI: 0.01-247.13], P = .694). For antazoline vs amiodarone, conversion to sinus rhythm favored antazoline (RR 1.22 [95% CI: 1.08-1.36], P = .018, I2 = 0%), with no significant differences in bradycardia (RR 1.36 [95% CI: 0-1072357.09], P = .823) or hypotension (RR 1.05 [95% CI: 0.04-26.16], P = .877). CONCLUSION: Antazoline might be more effective than propafenone and amiodarone in achieving sinus rhythm in AF, with no significant differences in safety outcomes.

BACKGROUND: Myocardial injury activates the complement lectin pathway (LP) in acute coronary syndrome (ACS) and LP inhibition improved cardiac function in experimental studies, suggesting a direct pathogenic role. The clinical consequences of LP activation are insufficiently defined. We investigated how plasma levels of the LP activators mannose-binding lectin (MBL) and ficolin-2 (FCN2) relate to cardiac recovery and prognosis in ACS patients. METHODS: MBL and FCN2 were measured at baseline in a cohort of 546 ACS patients and at 6-weeks in 124 patients with available samples. Prospective associations with heart failure (HF), stroke, and major adverse cardiovascular events (MACE) during a median follow-up of 2.2 years were assessed by multivariable Cox regression. Spearman correlation was used to assess relationships between MBL and FCN2 levels, inflammatory and fibrotic mediators in plasma, and echocardiographic parameters of left ventricular (LV) remodelling and dysfunction. RESULTS: Baseline MBL was associated with incident HF (HR 1.50, 95% CI 1.04-2.16, p = 0.029), independently of clinical risk factors, revascularization, baseline troponin and renal function. Patients with persistently elevated MBL at baseline and follow-up had increased pro-inflammatory and pro-fibrotic mediators in plasma, dilated LV and reduced LV systolic function at 1-year post-ACS. FCN2 showed no association with the outcomes. CONCLUSIONS: ACS patients with persistently high plasma MBL levels suffer cardiac remodelling and dysfunction, and have an increased risk for HF. Our findings provide clinical support to experimental data suggesting that the complement LP might be a potential therapeutic target to prevent post-ACS HF.

BACKGROUND: Heart failure (HF) is a major public health problem associated with frequent hospitalizations, high mortality, and substantial health care costs. Self-care is fundamental to improving health outcomes; yet, self-care is commonly poor among patients with HF. SMS text messaging interventions may provide a simple, scalable, and accessible strategy to support HF self-care, particularly among older adults who may face barriers to using more complex digital health technologies. However, the efficacy of text messaging as a standalone intervention for patients with HF remains underexplored. OBJECTIVE: This protocol paper describes the rationale and design of a pilot randomized controlled trial examining the feasibility, acceptability, and preliminary efficacy of an individually Tailored Text Messaging Intervention to Improve Self-Care in Adults with HF (Text4HF). METHODS: This study is a single-site, stage I, parallel-group randomized controlled trial. Participants (n=30) are community-dwelling adults aged 50 years or older with stage C HF and suboptimal self-care, defined as a score of 3 or less on at least 2 items of the Self-Care of Heart Failure Index (SCHFI v7.2). Participants are randomized (1:1) to either a 12-week tailored text messaging intervention (Text4HF) plus usual care or usual care alone. Text messages are triggered based on patient responses to validated instruments assessing evidence-based, modifiable behavioral factors of HF self-care. Feasibility (recruitment and retention) and acceptability of the intervention are assessed as key process outcomes. The main exploratory patient-reported outcome is HF self-care (SCHFI v7.2). Other patient-reported outcomes include medication adherence, adherence to a heart-healthy diet, HF knowledge, health-related quality of life, self-efficacy, and health beliefs. RESULTS: This study was funded in June 2022, and participant recruitment began in September 2024. A total of 26 participants have been enrolled and randomized to the intervention (n=13) and control (n=13) groups. Participants have a mean age of 60 (SD 6.6) years, 46% (12/26) are female, and 73% (19/26) identify as non-Hispanic Black. Half of the participants are individuals with reduced ejection fraction. Study completion is anticipated in June 2026. CONCLUSIONS: This protocol describes an important step toward evaluating a scalable, low-

INTRODUCTION: Functional assessment is essential to quantify kidney graft quality early after kidney transplantation. Kidney transplantation is inherently associated with ischemia-reperfusion-injury, a noxious insult for proximal tubule cells that may not be captured by glomerular function markers. The urine ammonium-pH index (uAPI) is a functional measure of the tubulointerstitial capacity for ammonium excretion. Here, we aimed to investigate the association between the uAPI and graft function in kidney transplant recipients. METHODS: In this post-hoc observational analysis of the CONTEXT trial (NCT01395719), kidney transplant recipients with available urine samples were divided into an exploration cohort (n = 112) and a validation cohort (n = 88). The uAPI was assessed at baseline, 90 min after reperfusion, day 1, 2 and 3 posttransplant. Day 6 kidney graft biopsies were stained for VCAM1 as a marker of tubular injury. Outcomes were delayed graft function, estimated time to 50% reduction in plasma creatinine, and measured GFR on day 5 and 12 months posttransplant. Results were adjusted for age, sex, plasma creatinine and albuminuria. RESULTS: In the exploration cohort, a higher uAPI on day 2 and day 3 was associated with lower VCAM1 expression (p < 0.001 and p = 0.002, respectively), lower risk of delayed graft function, and shorter estimated time to 50% reduction in plasma creatinine (p < 0.001). A higher uAPI on day 3 was associated with higher measured GFR on day 5 (p < 0.001) and at 12 months (p < 0.001) posttransplant. These findings were confirmed in the validation cohort and robust to adjustments. Associations between day 3 uAPI and long-term graft function were consistent in subgroup analyses, including in patients with vs. without delayed graft function. Inclusion of day 3 uAPI improved prediction of measured GFR > 60 at 12 months posttransplant. CONCLUSIONS: A higher uAPI likely informs about better tubulointerstitial function posttransplant and is associated with better early and 12-month kidney graft function.