Foreground Demo

BACKGROUND: Emergency departments (EDs) are key entry points for many youth experiencing suicidal thoughts and behaviors into mental health care. ED clinicians play a critical role in crisis intervention, prevention, and linking patients to ongoing care, yet many report uncertainty when assessing for and managing suicidal risk. The Collaborative Assessment and Management of suicidal thoughts and behaviors [Collaborative Assessment and Management of Suicidality (CAMS)] is an evidence-based, suicide-focused intervention that has been adapted into a single session [CAMS-Brief Intervention (CAMS-BI)]. OBJECTIVE: This study tested the use of CAMS-BI with youth who are suicidal and presenting to a pediatric ED. METHODS: Participants (aged 12 to 21 y; n = 20) were approached in the ED and completed distress measures before and after CAMS-BI. Following standard discharge timelines was prioritized. RESULTS: Analyses supported CAMS-BI's feasibility for ED youth populations, given the observed low rate of intervention refusal (8.7%) and high completion rate (87%). Participation in the study did not delay ED discharge times. Youth receiving CAMS-BI reported significantly lower distress postintervention, d = 0.45. Three-month follow-up indicated reductions in ED-return rates (0%) compared with youth who did not receive the intervention (15%), and strong patient engagement with outpatient treatment following CAMS-BI was notable (88% attended follow-up appointment). CONCLUSIONS: This pilot study provides evidence for CAMS-BI's feasibility for youth in fast-paced ED settings and its clinical value to quickly decrease distress. Future directions include larger, more rigorous replications to fine-tune CAMS-BI implementation into ED workflows.

BACKGROUND: The lack of consensus on the best pressure injury (PI) risk assessment tools demonstrates the need for further comparative research to identify the most effective options for intensive care unit (ICU) populations. AIM: This study compared the predictive validity and reliability of five PI risk assessment tools in adult ICU patients. STUDY DESIGN: A prospective cohort study was conducted with patients aged ≥ 18 years, admitted to the ICUs for at least 24 h and without pre-existing PI. Five tools (Braden Scale, CALCULATE, Cubbin & Jackson, EVARUCI and Sunderland) were used daily to assess PI risk until either a PI developed or the participant was discharged, died or completed 21 days in the ICUs. The main outcome measures included area under the receiver operating characteristic (ROC) curve, sensitivity, specificity, relative risk and reliability. RESULTS: Of the 150 participants, 40 (26.7%) developed PIs. None of the five tools demonstrated good predictive accuracy. AUC values ranged from 0.605 to 0.692 across the five tools, with none exceeding the predefined threshold of 0.70. Participants classified as high risk by Sunderland, Cubbin & Jackson and EVARUCI had a 3.0, 2.5 and 2.1 times higher risk, respectively, of developing a PI. Cubbin & Jackson was the only tool to achieve acceptable reliability values in Cronbach's alpha, intraclass correlation coefficient (ICC) and Cohen's weighted kappa. CONCLUSIONS: High-risk classification using the Sunderland, Cubbin & Jackson and EVARUCI scales was more strongly associated with subsequent PI development than classification using the other tools. Reliability findings varied across parameters, with Cubbin & Jackson being the only tool to meet acceptable thresholds across all assessed reliability measures. RELEVANCE TO CLINICAL PRACTICE: PI assessment in ICU patients should integrate validated tools with clinical judgement to address patient-specific and device-related risk factors.

BACKGROUND: Guideline-directed medical therapy (GDMT) improves outcomes in heart failure with reduced ejection fraction (HFrEF); however, variations in adherence to guidelines across hospitals and over time remain unknown. We used two Taiwanese national registries to investigate temporal and institutional differences in guideline adherence and outcomes among HFrEF patients. METHODS: We looked at two Taiwanese prospective multicenter cohorts, the TSOC-HFrEF (2013-2014) and TSOC HF 2020 (2019-2022) registries. We looked at adherence to Class I recommended diagnostics and GDMT as well as 1-yr mortality rates. Measured covariates and within-hospital clustering were accounted for using multivariable-adjusted generalized estimating equation models and Cox proportional hazards models, which included marginal models. RESULTS: The study included 3,028 patients with HFrEF from 16 medical centers and four regional hospitals. GDMT prescription and diagnostic testing rates increased significantly between the 2013 and 2020 cohorts (≥2 GDMT classes: 60.4% vs. 86.9%; three GDMT classes: 20.6% vs. 51.6%; both p < 0.001). The adjusted odds ratios for prescribing ≥2 and 3 GDMT classes in 2020 versus 2013 were 4.18 and 3.97, respectively, indicating consistent improvements across hospital types (interaction p-values = 0.721 and 0.467). Patients treated at medical centers had significantly higher prescription rates for angiotensin receptor-neprilysin inhibitors and mineralocorticoid receptor antagonists (39.1% vs. 32.2%, p = 0.011; 62.9% vs. 57.5%, p < 0.001, respectively), while prescription rates for renin-angiotensin system inhibitors were similar across hospital levels (medical center, 71.9% vs. regional hospital, 75.5%, p = 0.179). The 2020 cohort had a significantly lower 1-yr mortality rate (adjusted hazard ratio, 0.75, p = 0.012), with similar survival improvements across medical centers and regional hospitals (interaction, p = 0.106). CONCLUSION: Over time, HFrEF guideline adherence improved significantly at all hospital levels in Taiwan. Improved guideline adherence was associated with a 25% lower risk of all-cause mortality after 1 yr.

CONTEXT: Effective pediatric inpatient discharge relies on clear, responsive communication to support safe transitions from hospital to home. Families who use a language other than English and those with lower health literacy experience disproportionate barriers during discharge, contributing to inequities in postdischarge outcomes. Despite recognition of these disparities, evidence guiding interventions remains fragmented. OBJECTIVE: To identify and evaluate interventions designed to address language and health literacy barriers in pediatric inpatient discharge, assess their impact on patient and caregiver outcomes, and examine methodological quality to inform best practices. METHODS: Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and the World Health Organization International Clinical Trials Registry Platform were searched from inception to June 2025. Eligible studies involved hospitalized pediatric patients and evaluated discharge interventions tailored to families' preferred language, reporting at least 1 discharge-related outcome. Ten studies met criteria. Two reviewers independently extracted data on study characteristics, interventions, and outcomes, and a narrative synthesis was completed because of heterogeneity. Risk of bias analysis was performed. RESULTS: Included studies were heterogeneous in design, interventions, and outcomes, and all were conducted in the United States. Interventions varied substantially and were categorized into health literacy-focused written interventions, language-concordant interventions, multimodal communication strategies, and system-level or workflow-based interventions. Interventions combining language-concordant communication with literacy-informed, multimodal strategies demonstrated more consistent improvements in caregiver understanding. Methodological quality was limited, with substantial risk of bias across studies. CONCLUSIONS: Language concordance alone is insufficient to ensure equitable pediatric discharge. Multimodal, literacy-informed strategies that apply universal precautions principles show greater promise but there is limited-quality evidence. Future research should prioritize rigorous designs, patient-centered outcomes, and meaningful family engagement.

BACKGROUND AND OBJECTIVE: Transient tachypnea of the newborn (TTN) is a common respiratory disorder affecting late-preterm and term infants. Newborns with TTN are typically admitted to the neonatal intensive care unit (NICU) for medical care. Our objective was to reduce NICU length of stay (LOS) for patients with TTN by standardizing care to limit unnecessary intervention. METHODS: We used the Model for Improvement to implement interventions in our level III and IV NICUs and analyzed data using control charts. Interventions included consensus development/data review, clinical practice guideline implementation, case audits, and an electronic medical record (EMR) order set. Infants aged 35 weeks or more with TTN were included. The primary outcome measure was NICU LOS. Secondary outcome measures were time to first feed, time on respiratory support, incidence of peripheral intravenous (PIV) catheter placement, incidence of intravenous fluid (IVF) administration, incidence of hyponatremia, number of blood draws, and percentage of same-day birth parent-baby discharges. Balancing measures included NICU readmissions, percentage of patients with hypoglycemia, and exposure to breast milk during hospitalization. RESULTS: LOS decreased (90 to 51 hours) after study interventions. Time to first feed, time on respiratory support, incidence of hyponatremia, PIV placement, and IVF administration also decreased. Percentage of infants discharged home with their birth parent increased. No changes were noted in any balancing measures. CONCLUSION: By prioritizing clinical guideline development, case audits, and EMR implementations, this quality-improvement initiative resulted in decreased LOS and reduced medical interventions for infants with TTN admitted to a level III and level IV NICU.

BACKGROUND: Delirium is a common neuropsychiatric complication among critically ill patients, particularly those who are mechanically ventilated. Evidence suggests family involvement may improve delirium-related outcomes in adult intensive care units (ICUs). However, limited evidence exists on intensive care nurses' (ICNs) experiences and attitudes towards family involvement in delirium care in South Africa. AIMS: The study aimed to explore intensive care nurses' experiences and attitudes towards family involvement in the care of mechanically ventilated patients with delirium in adult ICUs. STUDY DESIGN: A descriptive qualitative study design was utilised. Four focus group discussions were conducted with 32 ICNs from two adult ICUs at a tertiary academic hospital in Johannesburg between April and August 2022. Participants who had at least 2 years of intensive care experience were purposively sampled. Data were analysed using inductive qualitative content analysis. The study adhered to Consolidated Criteria for Reporting Qualitative Studies guidelines. FINDINGS: Three categories were identified: emotional burden and psychological demands of delirium care, communication and psychosocial support for families in delirium care and barriers to effective family involvement in delirium care. While recognising the therapeutic value of family engagement, the nurses reported experiencing emotional stress related to family expectations and anxiety. They adopted strategies such as structured communication, empathetic listening and technology-assisted contact to support families. However, barriers such as time constraints, limited intensive care space, staffing shortages and restrictive policies limited sustained involvement. CONCLUSIONS: This study provides context-specific insight into how ICNs facilitate family involvement in the care of patients with delirium in a public tertiary ICU. ICNs recognise the therapeutic value of family involvement in the care of patients with delirium and are willing to facilitate engagement. However, systemic and environmental barriers limit consistent implementation. Therefore, strengthening institutional policies and supporting nurses through structured training and team-based approaches may enhance sustainable family-centred delirium care. RELEVANCE TO CLINICAL PRACTICE: This study's findings demonstrate the need for ICNs to adopt

BACKGROUND: Intensive care unit (ICU) delirium is a multifactorial acute brain dysfunction associated with prolonged hospitalization, increased morbidity and mortality, and higher healthcare costs. Despite these substantial negative impacts of delirium, the optimal prevention and treatment strategies are unclear. Olanzapine, an atypical antipsychotic drug, is commonly used for delirium management. We will perform an updated systematic review and meta-analysis to assess the benefits and harms of olanzapine for the prevention and treatment of ICU delirium. METHODS: This protocol is developed in accordance with the recommendations of The Cochrane Collaboration and is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) guidelines. We will include all randomized clinical trials (RCTs) evaluating prophylactic or therapeutic olanzapine versus any comparator, including pharmacological, non-pharmacological, placebo, or routine care/no specific delirium-directed intervention (treated as a single comparator) in ICU patients. Observational studies will be included solely to address potential harms. We will systematically search the following databases: Embase, MEDLINE, The Cochrane Library, Web of Science, CINAHL, Scopus, and PsycINFO, as well as clinical trial registries. We will perform meta-analysis and trial sequential analysis (TSA) to investigate the risk of both Type I and II errors. We will assess the risk of bias using the Cochrane Risk of Bias tool (RoB-2). The quality of trials will be evaluated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. The review is registered in the PROSPERO database (CRD420261474813). OUTCOMES: The primary outcome is days alive and out of the hospital. The secondary outcomes include all-cause mortality at 90 days, number of CAM-ICU (Confusion Assessment Method for the Intensive Care Unit) negative days at 30 days, number of days without pharmacological treatment for delirium other than study drug during the intervention period and serious intervention-related harms. DISCUSSION: This protocol outlines the methodology we will use in a systematic review with meta-analysis designed to evaluate the beneficial and harmful effects of olanzapine for prevention and treatment of delirium in ICU patients. The findings of the systemat

BACKGROUND: The transition from the intensive care unit (ICU) to a general ward is a period of heightened vulnerability, yet the precise timing and modifiable predictors of adverse events remain poorly defined. AIMS: To determine the incidence, timing and types of adverse events following ICU-to-ward transfer, evaluate the predictive accuracy of four early-warning scores and identify independent risk factors. STUDY DESIGN: A prospective cohort study of 207 adult patients transferred from ICUs to general wards at a tertiary university hospital over 20 months (March 2024-October 2025) was enrolled. Four early warning scores (PACS, MEWS, SWIFT, LACE) were calculated daily for 5 days post-transfer. Multivariable logistic regression was used to identify independent risk factors. RESULTS: The total number Adverse events occurred in 52 patients (25.1%), most commonly ICU readmission (n = 46, 22.2%) and healthcare-associated infections (n = 29, 14.0%). Critically, 88% of events occurred within the first 48 h (day 1: 56.0%; day 2: 32.0%). SWIFT demonstrated the highest predictive accuracy at transfer (AUC 0.856). Mechanical ventilation was the strongest independent risk factor (OR 10.11), followed by prolonged ICU stay (OR 6.40), respiratory diagnosis (OR 4.99), > 3 invasive devices (OR 4.41) and comorbidities (OR 3.64). These five factors collectively explained 88.5% of adverse events. CONCLUSION: Adverse events affect one in four patients after ICU-to-ward transfer, with the vast majority occurring within the first 48 h. A simple set of readily identifiable risk factors can guide nursing surveillance and targeted interventions during this critical window. RELEVANCE TO CLINICAL PRACTICE: Bedside nurses should prioritize enhanced monitoring for patients with a history of mechanical ventilation, prolonged ICU stay, multiple invasive devices and significant comorbidities during the first 48 h post-transfer. Daily use of early-warning scores can inform monitoring frequency and rapid response activation.

BACKGROUND: Antimicrobial resistance (AMR), a global public health threat, affects rural communities disproportionately due to their unique regional exposures, including proximity to animal feeding operations (AFOs), a source of AMR genes. OBJECTIVE: We evaluated residential proximity to AFOs and the presence of AMR genes in the home dust resistome, the collection of antimicrobial resistant genes within a microbial community. METHODS: We conducted metagenomic sequencing of 534 bedroom dust samples to characterize the resistome for a subset of homes of Iowa participants in the US Agricultural Health Study. We examined the association between the presence of AMR genes in dust samples and the total number of AFOs and distance-weighted number of livestock animal units (AUs) within 2, 5, and 10 km of participant homes, using data from the Iowa Department of Natural Resources. RESULTS: Homes that were closer to a greater number of AFOs and AUs had increased odds of the presence of AMR genes in the dust, including genes resistant to multiple classes of antimicrobials. SIGNIFICANCE: We found that AFOs were positively related to the composition of the indoor home dust resistome, which may serve as a potential environmental reservoir of antimicrobial resistance with implications for the health of household occupants. IMPACT: This study is the first to detect a positive association between the presence of antimicrobial resistance (AMR) genes in the indoor home dust resistome and residential proximity to animal feeding operations (AFOs), a known reservoir and possible source of AMR in rural communities. Our results indicate that both distance and density were important components of AFO-related AMR risk in rural residential environments. Overall, this suggests that environmental exposures can shape the indoor home dust resistome, which may have implications for the health of inhabitants and increase the risk of AMR infections.

Hypertension involves an impairment of renal sodium excretion along with activation of pro-inflammatory responses in the kidney. Dendritic cells (DCs) are professional antigen-presenting cells that sense disturbances in cell and tissue homeostasis to orchestrate T cell activation and recruitment. Renal DCs distribute as a cellular network throughout the renal interstitium, forming an interface between innate and adaptive immunity. Here, we explore what is known about renal cross-talk following prohypertensive stimuli, which modify renal DCs, T cell polarization, and renal function, leading to hypertension. We also present the phenotypic and functional heterogeneity of DCs, including literature on in vitro and in vivo signaling mechanisms in a variety of hypertensive models. Current studies indicate that renal sodium retention caused by prohypertensive stimuli requires DC function. The prohypertensive action of DCs also requires T cell function. Several cross-talk mechanisms have been proposed, such as signals from the kidney to the DC, including salt activation of DC's via RAAS receptor signaling, and DC-dependent recruitment of T cells to the kidney then promoting increased renal tubular sodium reabsorption. Knowledge gaps include specific functions of renal DC subtypes, sex differences in DC-mediated hypertension, and clinical studies on DC function in hypertension. The identification of mechanisms leading to renal DCs activation in hypertension may offer new strategies for the prevention and treatment of hypertension.

BACKGROUND: Acute myocardial infarction (AMI) remains one of the leading causes of death in Germany, accounting for 41 258 deaths in 2024. The evidence on sex differences in mortality after AMI is mixed, especially for outcomes beyond the acute phase. We used data from a large nationwide database to study sex differences in 12-month mortality after AMI in Germany. METHODS: This retrospective cohort study is based on data from the German Health Data Lab (Forschungsdatenzentrum Gesundheit). Adults who had a principal inpatient discharge diagnosis of incident AMI in 2023 were included in the analysis. The endpoint was all-cause mortality within 12 months. Cox models were fitted with sequential adjustment for age, infarction type, comorbidities, and prior cardiovascular medication. RESULTS: 62 884 women and 113 019 men were included in the analysis. The women were older and had more comorbidities. The crude 12-month mortality was higher in women than in men (21.0% vs 17.8%; 251 vs 207 per 1000 person-years). After adjustment for age, however, the reverse was true: mortality was lower in women than in men (hazard ratio [HR] 0.88; 95% CI 0.86-0.90). This remained the case in the fully adjusted model (HR 0.84; 95% confidence interval [CI] 0.82-0.85). In exploratory stratified analyses, men and women under age 60 did not differ in mortality, while in older age groups and after non-ST-segment elevation myocardial infarction (NSTEMI), mortality was lower in women (but not after ST-segment elevation myocardial infarction [STEMI]). CONCLUSION: Multivariable analysis revealed a slightly lower 12-month mortality among women after the diagnosis of an acute myocardial infarction. Because the adjustment included variables that may act as mediators on the causal pathway between sex and mortality, the adjusted estimates should be interpreted with caution.

Systemic anticoagulation is the standard initial therapy for intermediate-risk pulmonary embolism (PE) but fails to reverse right ventricular (RV) overload rapidly. While full-dose systemic thrombolysis accelerates RV recovery, it carries an unacceptable risk of major hemorrhage. Catheter-directed thrombolysis (CDT) offers a targeted, low-dose alternative to improve hemodynamics safely. A comprehensive search of PubMed, Web of Science, CENTRAL, Scopus, and Embase was conducted up to May 2026. Mean differences (MD) and risk ratios (RR) were pooled using a random-effects model. PROSPERO ID: CRD420261402147. Six RCTs involving 886 patients were included. CDT was associated with a significantly greater reduction in the RV/LV ratio than anticoagulation alone (MD: -0.11, 95% CI: [-0.21, -0.00]; P < 0.05). Also, CDT significantly reduced the risk of early cardiorespiratory deterioration (RR: 0.36, 95% CI [0.19, 0.68]; P < 0.001). There was no significant increase in major bleeding (RR: 1.52, 95% CI [0.71, 3.24]; P = 0.28) or intracranial hemorrhage. However, CDT significantly increased the risk of any bleeding (P = 0.02) and vascular access-site complications/hematomas (P = 0.02). Mortality did not differ between the two groups. Adding CDT to standard systemic anticoagulation led to a statistically significant reduction in the RV/LV ratio compared with anticoagulation alone, with a significantly lower risk of early hemodynamic and cardiorespiratory deterioration, without increasing the risk of major bleeding or intracranial hemorrhage in patients with acute intermediate-risk PE. However, larger RCTs with longer follow-up are required to provide a clearer picture of its sustained effects on hard clinical outcomes.

This correspondence clarifies that DOOR incorporates, rather than causally accounts for, post-randomization treatment modification. In the voriconazole-amphotericin B trial, frequent treatment switching means the reported DOOR probability reflects treatment strategies as implemented, not sustained randomized monotherapy throughout the original trial.

BACKGROUND: Textbook outcome (TO)-simultaneous achievement of all predefined surgical quality criteria-is established in adult oncological surgery but has never been defined for nephroblastoma surgery after Société Internationale d'Oncologie Pédiatrique (SIOP) neoadjuvant chemotherapy. We defined a nine-criterion TO, reported the TO rate, introduced a near-miss TO (NM-TO) category, and identified predictors of failure. PROCEDURE: Single-center retrospective cohort of pediatric patients below the age of 18 years with nephroblastoma treated at King Hussein Cancer Center between 2015 and 2023. Treatment followed SIOP protocols. The nine TO criteria were as follows: no intraoperative tumor spill, lymph node (LN) harvest ≥7, R0 margin, no major vessel injury, no major organ injury, no Clavien-Dindo ≥3 complication, no unplanned return to the theater within 30 days, adjuvant chemotherapy within 14 days, and estimated blood loss (EBL) <10 mL/kg. NM-TO required exactly 8/9 criteria. RESULTS: Seventy-one patients were analyzed. Full TO was achieved in 35/71 (49.3%); NM-TO in 21 (29.6%), giving a combined rate of 78.9%. The most common NM failures were LN harvest <7 (11 patients) and EBL ≥10 mL/kg (9 patients). Tumor dimension was negatively associated with achieving TO in this univariable, uncorrected analysis (Spearman ρ = -0.405; p < 0.001); stage was not (p = 0.853). Systemic relapse occurred in 12 patients (16.9%); there were no postsurgical local recurrences. CONCLUSIONS: This is the first TO analysis in SIOP nephroblastoma surgery. LN harvest is the main modifiable gap; optimizing this single parameter could raise the institutional TO rate to 64.8%. Weight-adjusted EBL adds a pediatric-specific criterion absent from adult TO frameworks. The NM category identifies which single criterion was missed and where to focus quality improvement.

Private psychiatric hospitals provide access to care for the approximately 46% of Australians who pay for private health insurance with hospital coverage. However, although private health insurance coverage has gradually increased, activity in private psychiatric hospitals has stagnated, particularly when measured by separations and Medicare-funded inpatient services. The funding and cost structure of private hospitals may be significant factors in this discrepancy because insurers are making record profits while private hospitals maintain that their costs are not covered. The burden falls on patients who are unable to access private hospital care. An independently determined, cost-based benchmark for private hospitals is recommended. Such independent costing of psychiatric care is already in routine use.

OBJECTIVE: To assess the feasibility of and clinical outcomes after a pan-European training program for robotic pancreatoduodenectomy (RPD). SUMMARY BACKGROUND DATA: The implementation of RPD into clinical practice comes with considerable challenges, leading to concerns about patient safety, oncological outcomes, and costs. To address this, a structured training program was implemented in which 2 surgeons at each of the 20 sites were trained and maintained as a consistent operative team. STUDY DESIGN: A structured training program for RPD was implemented, and outcomes prospectively collected in 20 European high-volume centers, all without previous RPD experience, from 12 countries. The program included a video library, biotissue simulation (pancreaticojejunostomy and hepaticojejunostomy), off-site RPD case observations, and on-site proctoring. Surgeons' simulation anastomoses were assessed using Objective Structured Assessment of Technical Skills (OSATS) and technical errors. The primary endpoint was intra- and postoperative patient outcome. A key secondary analysis assessed safety using OSATS scores and error counts, and major correlated with conversion and postoperative outcomes. RESULTS: Overall, 486 RPD procedures were performed. Median intraoperative blood loss was 200 mL (IQR: 100-400), operative time was 475 minutes (IQR: 414-553.3), and the conversion rate was 18.3% (n=89). The rate of Clavien-Dindo grade ≥III complications was 31.4% (n=153), POPF was 21.2% (n=103), delayed gastric emptying was 15% (n=73), postpancreatectomy hemorrhage was 8.6% (n=42), and in-hospital/30-day mortality was 2.7% (n=13). Median length of stay was 12 days (IQR: 8-20). During simulation training, OSATS scores significantly improved (0.350 points/attempt (ρ), P<0.001) while the duration of reconstruction decreased (P<0.001). Multivariable analysis found no association between error count and major complications. CONCLUSIONS: We report on the first successfully completed international training program for RPD. Simulation established a standardized technical competency, although a learning-curve effect (major complications) remained detectable per center. These data highlight that safe adoption of complex procedures requires structured, team-based, proctored training beyond simulation alone.

OBJECTIVES: Femtosecond photoemulsification cataract surgery requires a higher total laser dose than conventional femtosecond laser-assisted cataract surgery, raising concerns about potential retinal exposure. This study aimed to develop a method for accurately measuring time-averaged fundus optical power and aperture-averaged irradiance during femtosecond photoemulsification and to evaluate retinal safety under the tested conditions. MATERIALS AND METHODS: A biomimetic cataract eye model was constructed using an artificial cornea, a hydrogen peroxide-induced cataractous rabbit lens, and saline to simulate the ocular media. A femtosecond laser system was used to perform lens fragmentation at pulse energies of 5.0, 6.0, 7.0, and 8.0 μJ. Time-averaged optical power reaching the simulated macular region was measured with a power meter and converted to aperture-averaged irradiance over a 5-mm receiving aperture. Post-ablation bubble morphology was observed using optical microscopy. RESULTS: At the effective pulse energy of 7.0 μJ, the maximum measured time-averaged aperture-averaged irradiance in the simulated macular region was 0.249 ± 0.025 W/cm2. Even at the excessive pulse energy of 8.0 μJ, the time-averaged aperture-averaged irradiance remained below the 0.7 W/cm2 retinal thermal limit recommended by the ICNIRP/Sliney guideline. CONCLUSIONS: The measured fundus radiation power during femtosecond photoemulsification remained below the retinal safety threshold, supporting the retinal safety of this surgical mode under the tested conditions.

Following a disaster, each passing hour and day of family separation erodes children's health and wellbeing. Hospital networks must prioritize expeditious reunifications while safeguarding children, yet despite advances in biometric technologies and data protection, healthcare systems and disaster response organizations are unprepared to integrate biometric tools into postdisaster family reunification strategies. Biometric data (eg, fingerprints, facial images, dental records, DNA data) are deployed routinely for postmortem disaster victim identifications; however, deployment for family reunifications, such as in hospital settings, is hindered by access challenges, technological limitations, and perceived risks. Although DNA kinship analysis is particularly valuable for reunification, not only for postmortem identifications but also for reconnecting genetic relatives, especially children who cannot self-identify, varying attitudes towards biometrics may limit its use. Understanding discomfort with biometric technologies among families and healthcare providers is critical to their effective deployment for reunifications. We therefore sought to (1) assess perceived utility of and willingness to use biometric data in varied postdisaster contexts and (2) identify postdisaster family separation scenarios where biometric technologies could be beneficial. Using child separation vignettes featuring varied disaster types, scales, and timelines, we surveyed 364 caregivers and 131 healthcare providers in the Chicago area. The results showed general support for the use of DNA and facial recognition technology in postdisaster family reunifications. In parallel, we documented real-life separation scenarios, capturing key factors influencing the utility of biometric tools. Findings suggest that disaster preparedness that considers the potential for family separation must include strategies to effectively use biometric data to assist reunifications, in accordance with the best interests of the child.

OBJECTIVES: Older adults who identify as lesbian, gay, or bisexual (LGB) may be at increased risk of elder abuse (EA) due to unique risk factors; however, research in healthcare settings has been limited by the lack of data on sexual orientation. Since 2022, the Veterans Health Administration (VHA) has collected self-reported sexual orientation for all patients. The objective of this chart review study was to use newly available electronic health record (EHR) data to explore the documented experiences of older LGB adults identified with EA concerns. METHODS: We randomly sampled 100 of 201 Veterans aged ≥60 years with an outpatient visit between 10/2022-9/2023 who identified as LGB and had a social work visit for possible abuse/neglect. We conducted protocolized chart reviews of clinical notes within ±180 days of the social work visit for 23 LGB patients, with EHR documentation confirming EA, to describe key characteristics and documented EA experiences. RESULTS: Among 23 EA cases in LGB Veterans, 8 (35%) had cognitive impairment, 8 (35%) reported a history of child maltreatment, and 7 (30%) reported military sexual trauma. Veterans' sexual orientation was sometimes noted to contribute to past abuse experiences; however, the relationship between sexual orientation and EA or EA care processes was rarely documented by clinicians. DISCUSSION: Findings highlight important considerations for sexual orientation minority patients experiencing EA, including opportunities to examine both contributors to EA risk among older LGB patients and to address LGB-specific care needs for this population in future research.

OBJECTIVES: To determine whether preoperative [18F]FAPI-42 PET/CT is associated with postoperative pathological phenotypes and tumor budding grade in colorectal cancer. MATERIALS AND METHODS: This retrospective dual-center study included consecutive adults who underwent [18F]FAPI-42 PET/CT before surgery between January 2022 and January 2026. The index test was quantitative primary-tumor PET uptake; the reference standard was surgical pathology including tumor budding grade. PET parameters were compared across postoperative phenotypes and binary budding groups. Logistic regression, receiver operating characteristic analysis, calibration, bootstrap validation, and decision-curve analysis were performed. RESULTS: Sixty-four patients (mean age, 63.8 years ± 9.4; 40 men) with 65 primary lesions were analyzed. Maximum standardized uptake value (SUVmax) differed significantly by tumor budding grade among seven phenotypes (p = 0.012). Intermediate/high-grade budding lesions had higher SUVmax than low-grade lesions (12.66 ± 3.36 versus 10.16 ± 3.86; p = 0.012). A model combining body mass index and SUVmax achieved an area under the curve of 0.841 (95% confidence interval: 0.731, 0.934), with an optimism-corrected area under the curve of 0.830. CONCLUSION: Preoperative [18F]FAPI-42 PET/CT uptake was associated with colorectal cancer tumor budding. A simple body mass index-SUVmax model provides internally validated, interpretable preoperative information on tumor budding grade; however, independent multicenter external validation is required before clinical application. KEY POINTS: Question Can preoperative fibroblast activation protein inhibitor PET/CT identify colorectal cancer tumor budding, a clinically relevant marker of aggressive invasive-front biology? Findings Higher [18F]FAPI-42 uptake was associated with intermediate/high-grade tumor budding; combining body mass index and maximum standardized uptake value improved discrimination. Clinical relevance Fibroblast activation protein inhibitor PET/CT may support noninvasive preoperative risk stratification of colorectal cancer by identifying tumor budding-related aggressive biology without additional procedures.

OBJECTIVE: Austrian correctional facilities face persistent shortages of on-site physicians challenging the principle of equivalence of care. Consequently, the Ministry of Justice launched a telemedicine (TM) pilot to support primary care in correctional facilities without round-the-clock medical cover. The goal of this study was to evaluate TM alongside its implementation in order to investigate key stakeholders' experiences with TM and its integration into routine medical practice and to assess if and how health technologies such as TM can be used to improve quality of care in underserved facilities long-term. DESIGN: We conducted a qualitative evaluation study with semistructured interviews which were analysed using thematic analysis. SETTING AND PARTICIPANTS: Using purposive sampling across 20 correctional facilities, we interviewed a total of 48 participants (35 nurses, 3 physicians, 7 facility directors, 3 correctional officers). RESULTS: TM emerged as a tool to partially mitigate the shortage of physicians. Participants viewed TM as well suited for low-risk prescribing, follow-ups, discussion of test results and administrative tasks, while emergencies and presentations requiring physical examination remained unsuitable for TM according to interviewees' reports. Nurses emerged as central operational actors who scheduled and prepared visits, mediated communication and implemented postconsultation tasks; the resulting workload was experienced as either increased (added coordination work) or reduced (fewer external transfers), depending on context. Overall, TM was valued as a complement rather than a replacement for in-person care. Perceived quality of TM depended on technical reliability, adequate space and-critically-the remote clinician being familiar with facility routines and patients. CONCLUSIONS: Effective scaling should include clear clinical use criteria, stable remote clinician assignment, close collaboration with on-site staff and acknowledgement of nursing workload, while maintaining access to in-person assessment for complex or urgent cases, as well as personalised, in-person care.

BACKGROUND: A particular gap in past research is a lack of understanding of how neurodivergence may impact nurses' workplace well-being. With up to 20% of individuals displaying neurodivergent traits in the workplace, it is important to recognize that those traits could be considered barriers with opportunities for change, or strengths of the individuals in these workplaces. Promoting well-being among neurodivergent nurses is critical for both their health and improving nursing care in general. PURPOSE: The current study sought to investigate the prevalence and well-being of neurodivergent nurses compared to nurses who do not identify as neurodivergent. METHODS: A cross-sectional study of 300 nurses (mean age: 38 years; average experience: 12 years) was conducted wherein participants were asked if they identified as or had been diagnosed as neurodivergent. Participants were then surveyed using various measures of well-being, health, and burnout. Results demonstrated that over a third of nurses identified as neurodivergent, and others reported they had received a diagnosis. Neurodivergent nurses scored higher than their peers on negative factors, such as general and workplace psychological distress, burnout, and pain. DISCUSSION: These findings point to how neurodivergent nurses are more prevalent than previously thought, relative to general population prevalence estimates of up to 20%. This could demonstrate that the occupation of nursing is possibly attractive to neurodivergent individuals, especially those who report attention-deficit hyperactivity traits. CONCLUSION: Findings also demonstrate that nurses have different workplace experiences, which highlights an opportunity to improve well-being for this nursing sub-population.

There are no descriptions of the "ideal candidate" or validated indices to justify admitting respiratory patients to hospital-based rehabilitation. This study aimed to quantify appropriate/inappropriate admissions to in-hospital rehabilitation programs among respiratory patients. We analyzed hospitalization records from the ICS Maugeri repository (01 January 2015 - 31 December 2024) across seven Italian ICS Maugeri centers. Patients were categorized as chronic respiratory failure (CRF; 45.70%), chronic obstructive pulmonary disease (COPD; 22.76%), asthma (0.07%), obstructive sleep apnea (OSAS; 10.89%), and miscellaneous dyspnea not related to COPD (19.84%). Anthropometric, Cumulative Illness Rating Scale, Medical Research Council (MRC) scale, Barthel dyspnea, COPD Assessment Test (CAT), 6-minute walk test (6MWT), and Short Physical Performance Battery (SPPB) were collected. Appropriateness of hospital admission was defined according to literature-based severity cut-offs for all disability items, while inappropriateness was computed on four contemporary items (excluding MRC). The cohort was predominantly male, aged 60-70 years, with CRF (46%) and multiple comorbidities; most (84%) were admitted from home, while >95% of patients returned home. High overall appropriateness in the whole group was 73-87% across items, with the highest % for 6MWT predicted across all TPs (74% OSAS-94% CRF) and lower for SPPB (60% OSAS-78% CRF) and for the MRC dyspnea score (75% OSAS-89% CRF). The CRF group demonstrated very high appropriateness (>78% in all items), COPD presented strong appropriateness for deconditioning (6MWT: 83%) dyspnea (MRC: 84%), asthma patients showed a lower CAT appropriateness (64%). The OSAS subgroup had the lowest entry appropriateness (55-74%). The dyspnea group exhibited high appropriateness for deconditioning (6MWT: 83%) and for dyspnea (MRC: 81%, Barthel dyspnea: 81%). Among 6086 complete cases, only 2.8% were deemed to be inappropriate admissions. The highest inappropriateness was in the dyspnea subgroup (6%), while the lowest was for CRF (0.7%).  Entry appropriateness was high or very high for overall items, showing 6MWT the best rate and CAT and SPPB the worst. CRF patients showed the highest appropriateness, while the rate of inappropriateness was overall low, with dyspnea and OSAS subgroups the worst and CRF the best. Future strategies must foc

PURPOSE: The aim of this study was to estimate the direct health care cost burden of herpes zoster ophthalmicus (HZO) in New Zealand and to evaluate potential implications for shingles vaccination policy. METHODS: This retrospective cohort study analyzed 869 participants with HZO treated at Greenlane Eye Clinic, Auckland, using data from the Auckland Zoster Study. Clinical and demographic data were reviewed and cross-referenced with hospital electronic databases. The total number of hospital visits, medications, and procedures associated with HZO and its complications were recorded. Unit costs were derived from New Zealand pricing data, and cumulative hospital-based direct health care costs were calculated. Factors associated with health care costs were evaluated using a generalized linear model (GLM) with a gamma distribution and log link, with multivariable linear regression performed as a sensitivity analysis. RESULTS: The median follow-up was 6.3 years [IQR 3.7-8.9]. The average hospital-based health care cost captured in this study was New Zealand dollars $3185.95 ± 6791.22 (range $30.49-$85,967.59). Mean inpatient, outpatient, drug, and procedure costs were $278.82 ± 1628.79, $2231.16 ± 3762.62, $113.51 ± 1288.57, and $562.45 ± 2582.89, respectively. In multivariable GLM analysis, higher health care costs were independently associated with older age (P < 0.001), immunosuppression (P = 0.047), uveitis (P < 0.001), optic neuropathy (P < 0.001), and recurrent disease (P < 0.001). CONCLUSIONS: HZO imposes a significant direct health care cost burden on the New Zealand health care system. These findings provide important local cost data for future economic evaluations, including cost-effectiveness analyses of HZ prevention strategies.

INTRODUCTION: Despite improvements in hardware and software availability, and a growing body of research on the use of virtual reality (VR) in intensive care settings, significant barriers to its widespread adoption remain. OBJECTIVES: The aim of this study was to explore intensive care unit healthcare providers' perceptions of the risks, concerns, and opportunities associated with the use of VR in the intensive care setting. METHODS: An online survey (QualtricsXM) focused on perceived relative and absolute contraindications to VR use, as well as perceived risks, safety and privacy concerns, their impact on implementation, and suggested research priorities was undertaken between February and December 2025. RESULTS: Within a cohort of 108 respondents, significant dispersion was observed between responses relating to relative and absolute contraindications. Professional differences were observed relating to the suitability of the use of VR for patients with a history of epilepsy. Similarly, significant dispersion was observed relating to perceived benefits of VR with relaxation, rehabilitation, patient education, and patient cognitive stimulation being perceived as extremely or very useful by more than 50% of respondents. CONCLUSIONS: This survey highlights that intensive care unit healthcare professionals, with little VR experience, lack a cohesive perspective on the risks associated with VR use in this setting. Moving forward, the development of robust implementation strategies should be incorporated into VR research which address healthcare provider concerns and assist in the development of interprofessional clarity on the use of VR between healthcare providers.

BACKGROUND: Stigmatizing language is common in the medical record and can perpetuate bias, which has downstream effects on clinical decision-making and patient care. Internal medicine faculty, residents, and advanced practice providers (APPs) are front-line clinicians for composing documentation, and faculty and APPs are also tasked with providing trainees with feedback and training on best documentation practices. However, resident, APP, and faculty preparedness to address stigmatizing language in documentation is unknown. Furthermore, little is known about clinicians' knowledge, attitudes, and behaviors regarding such language. OBJECTIVE: We sought to understand resident, APP, and faculty experiences, values, and beliefs around stigmatizing language in clinical documentation. DESIGN: We conducted a cross-sectional online survey and knowledge test. PARTICIPANTS: Internal medicine residents, faculty, and APPs within two large academic internal medicine departments. MAIN MEASURES: The knowledge test measured participants' ability to identify stigmatizing language in snippets of documentation and the survey measured attitudes and perceived skills via a series of Likert-style questions. KEY RESULTS: In total, 82 faculty/APPs (72 faculty and 10 APPs; 52% response rate) and 63 residents (21% response rate) responded. Nearly all respondents reported considering how their word choices impact patients (91% of faculty/APPs [n = 74] and 92% of residents [n = 58]) and other clinicians (90% of faculty/APPs [n = 73] and 84% of residents [n = 53]). However, only 10% (n = 8) of faculty/APPs and 24% (n = 15) of residents were confident that their clinical documentation avoided stigmatizing language. Only 4% (n = 3) of faculty/APPs and 3% (n = 2) of residents correctly identified all 11 stigmatizing terms assessed on the knowledge test. CONCLUSIONS: Faculty/APPs and residents at our institutions value the importance of patient-centered language, yet they lack knowledge and skills around this topic, highlighting key opportunities for future targeted educational and systems-level interventions.

BACKGROUND & AIMS: Transcutaneous electrical acupoint stimulation (TEAS) promotes postoperative gastrointestinal recovery. However, existing protocols lack standardization due to unaddressed methodological collinearity between frequency and waveform in previous analyses. We aimed to evaluate the efficacy of TEAS following abdominal surgery and examine whether treatment effects varied across stimulation parameters. METHODS: We searched four major databases from inception to April 2026 for randomized controlled trials (RCTs) comparing TEAS with sham/standard care. Frequency and waveform were systematically reconstructed into a composite "Stimulation Pattern" (Intermittent/Fixed vs. Dilatational/Alternating). Data were pooled using a random-effects model. RESULTS: Twenty RCTs comprising 2,615 patients were included. TEAS significantly accelerated the time to first flatus (MD = -9.08 h, P < 0.0001) and first defecation (MD = -16.48 h, P < 0.0001), and reduced the incidence of strictly defined POI (3 trials; RR = 0.78, 95% CI 0.64-0.96; P = 0.0214). TEAS also shortened hospital stay and mitigated postoperative nausea, vomiting, and pain. The intermittent/fixed stimulation pattern was associated with a greater reduction in time to first flatus than the dilatational/alternating pattern (interaction P = 0.0008). Adverse events were minimal (0%-1.8%). CONCLUSIONS: TEAS safely accelerates gastrointestinal motility recovery. While an optimal protocol remains to be established, the intermittent/fixed stimulation pattern appears to be a promising candidate configuration. Longer or more frequent treatment did not show clear additional benefit, supporting evaluation of a 30-min once-daily regimen as a pragmatic, resource-efficient strategy in future prospective trials.

STUDY OBJECTIVE: To determine whether cloacal complexity, defined by common channel length, is associated with early introital or vaginal stenosis following primary cloacal repair. METHODS: Retrospective analysis of a prospective cohort of patients with persistent cloaca treated at a quaternary-care children's hospital between January 2020 and May 2026. Patients who underwent primary cloacal repair with vaginal reconstruction and post-repair exam under anesthesia were included; those with cloacal exstrophy, cloacal variants, or prior repair at an outside institution were excluded. Complexity was defined by common channel length: moderate (<3 cm) or complex (≥3 cm). The primary outcome was any introital or vaginal stenosis at routine post-repair exam under anesthesia and vaginoscopy. RESULTS: Of 68 primary repairs, 45 patients were included: 27 (60.0%) had moderate cloaca and 18 (40.0%) had complex cloaca. The median age at repair was 0.7 years (range 0.4-10.1 years). Introital or vaginal stenosis occurred in 40.0% (18/45); 5 patients had complete stenosis, all of whom had complex cloaca. Stenosis was far more common following reconstruction of complex cloaca (72.2% vs. 18.5%; p<0.001), with 11-fold higher odds (OR 11.44, 95% CI 2.77-47.17), an association that persisted after adjusting for urethral length (OR 10.08, 95% CI 2.09-48.67; p=0.004). Each 1 cm increase in common channel length was associated with 2.50-fold higher odds of stenosis (95% CI 1.49-4.17; p<0.001), which persisted after adjusting for urethral length (p=0.002). The rate of stenosis was highest following urogenital separation (61.5%), compared with total urogenital mobilization (15.4%) and introitoplasty (0.0%) (p=0.002). Stenosis was also associated with older age at repair (1.0 vs. 0.6 years, p=0.015), uterovaginal anomalies (53.1% vs. 7.7%; p=0.005), longitudinal vaginal septum resection (56.5% vs. 22.7%, p=0.021), and longer operative time (440 vs. 284 minutes, p=0.0001). CONCLUSIONS: Introital or vaginal stenosis was common (40.0%) in the early postoperative period following cloacal repair, and patients with complex cloaca had 11-fold higher odds of stenosis. These findings support anticipatory counseling and longitudinal gynecologic follow-up, particularly for patients with complex anatomy. IRB APPROVAL: Children's National Hospital, IRB Pro00015991.

INTRODUCTION: Targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) have demonstrated promising results in reducing neuroma pain post-amputation. Although the benefits of these techniques have been widely reported, there is limited evidence comparing the postoperative complication profiles of TMR and RPNI. This systematic review evaluates postoperative surgical complications and operative time associated with TMR and RPNI after amputation. METHODS: This systematic review was conducted according to PRISMA guidelines and registered in PROSPERO (CRD42024521608). Seven databases were searched through May 2026 for studies evaluating postoperative surgical complications after upper or lower extremity amputation with TMR or RPNI. Study characteristics, complication outcomes, and operative time data were extracted and synthesized descriptively. RESULTS: Eighteen studies met inclusion criteria, including 8 comparative cohort studies and ten noncomparative studies. Reported complication rates varied substantially across studies. Comparative RPNI studies generally demonstrated lower rates of delayed wound healing, SSI, and revision surgery compared with standard amputation controls. Comparative TMR studies demonstrated mixed findings, with some cohorts reporting higher rates of delayed wound healing and SSI, whereas revision surgery rates were often lower than standard amputation controls. Operative time increased for both TMR and RPNI, ranging from ~20 minutes to more than 2 hours depending on operative approach and institutional experience. CONCLUSIONS: Current evidence suggests that both TMR and RPNI demonstrate broadly comparable postoperative risk profiles relative to standard amputation, although RPNI may be associated with fewer early postoperative complications in limited comparative studies. Further prospective comparative studies with standardized outcome reporting are needed to better define the relative risks and benefits of each technique.

BACKGROUND: The PRODIGE7 trial demonstrated a lack of effectiveness of oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) for colorectal cancer peritoneal metastases (CRC-PM), prompting many centers to transition to mitomycin C (MMC)-based HIPEC. However, the oncologic benefit of MMC-HIPEC remains unclear. METHODS: In 2021, our  center systematically discontinued HIPEC for CRC-PM. We  retrospectively compared consecutive patients who underwent MMC-HIPEC after complete CRS (2009-2021) with those undergoing CRS alone (2021-2024). Outcomes included recurrence-free survival (RFS), peritoneal RFS, and 90-day postoperative outcomes. Propensity score-matching was performed using age, sex, primary tumor location, extraperitoneal disease, completeness of cytoreduction score, peritoneal carcinomatosis index, and preoperative chemotherapy. RESULTS: The study included 107 consecutive patients (median age, 56 years; median peritoneal carcinomatosis index [PCI], 8; 48% male; 45% left-sided primary tumor), 68 (64%) of whom underwent CRS-HIPEC with MMC. Most of the patients (75%) experienced recurrence. After matching, 96 patients remained (32 treated with CRS alone; 64 treated with CRS-HIPEC). Between CRS alone and CRS-HIPEC, RFS was comparable (median, 8.4 months [95% confidence interval {CI}, 5.6-12.7 months] vs. 8.7 months [95% CI, 6.2-11.0 months]; p = 0.527), as was peritoneal RFS (median 12.7 months [95% CI, 8.4-not reached {NR}] vs. 14.2 [95% CI, 8.7-19.8 months]; p = 0.806). The CRS-HIPEC patients had more respiratory complications (0% vs. 13%; p = 0.037) and longer hospital stays (median, 10 vs. 7 days; p < 0.001). Exploratory analyses suggested benefit in node-negative disease. CONCLUSION: Omission of MMC-HIPEC did not compromise oncologic outcomes.

INTRODUCTION: Pediatric readiness is associated with improved quality of care and has known geographic variation. Less is known about disparities in patient access to hospital pediatric capabilities. Our goal was to examine associations between patient race / ethnicity and pediatric capability of the initial hospital presentation. METHODS: We linked state data, combining 2019 National Emergency Department Inventory (NEDI)-USA, 2019 State Emergency Department and State Inpatient Databases (SEDD/SID), 2020 Supplemental NEDI Pediatric Emergency Care Coordinator (PECC) Survey, and the 2021 National Pediatric Readiness Program (NPRP) Survey. Primary exposure was race / ethnicity. We compared pediatric capability definitions and used logistic regressions to examine associations between race / ethnicity and pediatric capability adjusting for select covariates. RESULTS: There were 2,281,885 ED visits in the NPRP cohort, 4,426,520 in the PECC cohort and 4,964,956 in the inpatient capability cohort. In unadjusted analyses, non-Hispanic Black and Hispanic patients had higher odds of presenting to hospitals with high NPRP scores (OR 2.02 [95% CI 1.44, 2.84] and OR 1.94 [95% CI 1.09, 3.46]), with a PECC (OR 2.30 [1.83, 2.88] and OR 3.14 [2.32, 4.26]), and with inpatient capability (2.03 [1.64, 2.51] and 2.08 [1.54, 2.81]). After adjustment, non-Hispanic Black patients had higher odds of presenting to hospitals with inpatient capability (1.47 [1.13-1.92]); in contrast Hispanic patients had higher odds of presenting to hospitals with a PECC (1.48 [1.11-1.98]). CONCLUSION: Non-Hispanic Black and Hispanic children were more likely to present to a hospital with a PECC, suggesting utilization of PECCs may reduce disparities in care.

BACKGROUND: The management of renal cell carcinoma (RCC) long-bone metastases often involves surgery with either resection and reconstruction (R&R) or intralesional (IL) procedures. Some literature suggests that R&R improves survival and reduces the risk of recurrence and reoperation, while IL procedures offer lower surgical morbidity and faster recovery. We compared survival and reoperation outcomes following IL versus R&R procedures for RCC long-bone metastases treated at our institution. METHODS: We retrospectively reviewed patients with histologically confirmed RCC long-bone metastases treated surgically between July 1, 2005, and June 1, 2022. Medical charts were reviewed to collect data on demographics, treatment history, and outcomes. Multivariable Cox proportional-hazards regression and Fine-Gray competing-risks regression were used to evaluate survival and reoperation following IL and R&R procedures. RESULTS: One hundred and five patients (68% male; mean age, 62.6 years; 96% White) with 133 metastases were included. IL surgery was not significantly associated with a greater cumulative incidence of reoperation (subdistribution hazard ratio [sHR] = 1.08, p = 0.87). Reoperations were primarily due to recurrent disease (29%) and pathologic fracture (33%) in the IL group, compared with recurrent disease (29%), pathologic fracture (14%), and wound infection (14%) in the R&R group. IL surgery was associated with a greater hazard of mortality in the overall cohort (HR = 2.03, p = 0.02), although no significant association was observed in the solitary metastasis subgroup (HR = 1.54, p = 0.49). CONCLUSIONS: IL procedures were associated with greater mortality, although this association was not observed among patients with a solitary metastasis. Given no significant difference in the cumulative incidence of reoperation between surgical approaches, IL and R&R procedures are both reasonable treatment options in appropriately selected patients and clinical settings. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

OBJECTIVE: Pain is common among long-term care (LTC) residents, and acetaminophen is often recommended as first-line therapy. We aimed to determine whether regularly scheduled acetaminophen, compared with any comparator, improves pain outcomes in LTC. DESIGN: Systematic review and meta-analysis. SETTING AND PARTICIPANTS: Residents in LTC METHODS: MEDLINE, EMBASE, CINAHL, and Scopus were searched from inception to June 9, 2026. Risk of bias (RoB) was assessed using the Cochrane RoB1 tool. The primary outcome was pain, with secondary outcomes including quality of life and adverse events. Pain outcomes were pooled using standardized mean differences with inverse-variance weighting and a random-effects model. The certainty of evidence was evaluated using GRADE (Grading of Recommendations, Assessment, development and evaluation). RESULTS: Four randomized controlled trials conducted in the United States and Europe met inclusion criteria, enrolling 482 LTC residents with mild-to-moderate pain at baseline and moderate-to-severe dementia. Acetaminophen was administered 3 to 4 times daily at total daily doses of 2500 to 3000 mg, with follow-up ranging from 4 to 13 weeks. Comparators included placebo (n = 3) and usual care (n = 1). Pain was assessed using MOBID-2 (Mobilization-Observation-Behavior-Intensity-Dementia-2 Pain Scale) and DS-DAT (Discomfort Scale-Dementia of the Alzheimer's Type) scales. Overall RoB was low, with the main concerns related to incomplete reporting of study methods and outcomes. There was no statistically significant reduction in pain with regularly scheduled acetaminophen compared with placebo or usual care (standardized mean difference, -0.14; 95% CI, -0.39 to 0.11; I2 = 6%; moderate-certainty evidence). One study evaluated quality of life and found no statistically significant differences between groups. Adverse event reporting was limited and inconsistent among studies. CONCLUSIONS AND IMPLICATIONS: Regularly scheduled acetaminophen probably does not improve pain in LTC residents with moderate-to-severe dementia and mild-to-moderate pain. These findings suggest that regularly scheduled acetaminophen for pain management in LTC may need to be reconsidered.

AimTo evaluate the global impact of the NANDA-I, Nursing Interventions Classification (NIC), and Nursing Outcomes Classification (NOC) (NNN) standardized nursing terminologies on nursing care quality, consistency, and documentation.DesignSystematic review of experimental and quasi-experimental studies conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and registered in PROSPERO (CRD42024564151).Data sourcesPubMed, Web of Science, and Scopus databases were searched for studies published between May 2019 and June 2024 using predefined Population, Intervention/Exposure, Control, and Outcomes-based keywords.Review methodsA total of 783 articles were identified; a total of 32 met inclusion criteria after duplicate removal and full-text screening. Quality was assessed using validated tools, including The National Heart, Lung, and Blood Institute, Joanna Briggs Institute, and Mixed Method Assessment Tool checklists.ResultsThe included studies, mostly from Latin America and Southern Europe, reported positive impacts of the NNN system on clinical reasoning, individualized care planning, documentation quality, and interdisciplinary communication. Barriers included insufficient training, system integration challenges, and limited uptake in regions like North Africa and Asia. Although diverse study designs were used, few evaluated long-term clinical or organizational outcomes.ConclusionNANDA-I, NIC, and NOC classifications enhance nursing practice by supporting structured care processes and measurable outcomes. Their global implementation remains uneven, highlighting the need for institutional support, educational integration, and region-specific implementation research.Relevance to clinical practiceIntegrating standardized nursing languages into clinical, educational, and policy frameworks can strengthen evidence-based care, improve documentation, and elevate the visibility of nursing contributions to patient outcomes.

BACKGROUND: Accurate identification of recent suicide-related risk remains challenging in psychiatric settings. Although clinical assessment is essential, objective physiological indicators such as heart rate variability (HRV) may provide complementary information. This study developed a two-stage machine-learning framework integrating clinical features and HRV to identify recent suicide-related status among psychiatric inpatients. METHODS: This retrospective study included 619 psychiatric inpatients who underwent standardized clinical assessment and 5-min resting HRV recording. Patients were classified as no suicidal ideation or behavior (no SI/SB; n = 416), suicidal ideation without suicidal behavior (SI; n = 137), or suicidal behavior (SB; n = 66) based on suicide-related information within the month before admission. Stage 1 classified patients with any recent SI/SB versus no SI/SB, and Stage 2 further classified recent SB versus SI among patients with suicide-related risk. Demographic-clinical, demographic-HRV, and combined feature sets were evaluated using multiple machine learning algorithms with repeated nested cross-validation. RESULTS: The combined feature set achieved the best overall performance. In Stage 1, the best combined model showed good discrimination (AUC = 0.894; AUPRC = 0.831). In Stage 2, the best combined model showed moderate performance (AUC = 0.778; AUPRC = 0.686). Depressive symptom severity, self-harm, past suicide attempt, younger age, diagnosis, and reduced vagally mediated HRV contributed to identifying any SI/SB, whereas past suicide attempt was the leading predictor of SB. CONCLUSIONS: Integrating clinical and HRV features may support the identification and stratification of recent suicide-related status in psychiatric inpatients. HRV provided modest complementary information, particularly for broad SI/SB identification, but external prospective validation is required.

INTRODUCTION: Robotic pancreatic enucleation (rPE) has emerged as a parenchyma-sparing surgical approach for benign or low-grade malignant pancreatic lesions. However, standardized metrics to assess perioperative quality are lacking. This study aimed to propose an rPE-specific textbook outcome (rPE-TO) reflecting an ideal perioperative pathway and to evaluate its applicability in two independent institutional cohorts. MATERIAL AND METHODS: Patients undergoing completed rPE at University Hospital Heidelberg, Germany, between April 2023 and March 2025 were analyzed, and the proposed rPE-TO was additionally evaluated in an independent institutional cohort from Johns Hopkins University, Maryland, USA. The rPE-TO comprised six components: no conversion to open surgery, no incomplete resection requiring reoperation, no clinically relevant postoperative pancreatic fistula (POPF), no major complications (Clavien-Dindo < IIIa, with POPF assessed separately), no readmission within 30 days, and no mortality within 90 days. RESULTS: The Heidelberg cohort included 31 patients, of whom 20 (64.5%) achieved rPE-TO. Among the individual components, conversion to open surgery occurred in 4 patients (12.9%), incomplete resection requiring reoperation in 1 (3.2%), POPF in 6 (19.4%), major complications in 2 (6.5%), and 30-day readmission in 2 (6.5%); no 90-day mortality occurred. In the Johns Hopkins cohort (n = 48), rPE-TO was achieved in 29 patients (60.4%). Despite comparable overall rPE-TO rates, the distribution of individual failure components differed between institutions. In addition, length of hospital stay was shorter among patients achieving rPE-TO in both cohorts. CONCLUSION: Textbook outcome was achieved in approximately two thirds of patients undergoing rPE in both institutional cohorts. The proposed rPE-TO integrates established perioperative quality measures with procedure-specific outcomes and may provide a composite measure for assessing an ideal perioperative pathway after robotic pancreatic enucleation.

BACKGROUND: Optimal initial management of posterior epistaxis remains controversial. We compared primary endoscopic sphenopalatine artery (SPA) cauterization with double-balloon posterior nasal packing. AIMS/OBJECTIVES: To compare treatment success, hospital stay, and costs between both strategies. MATERIALS AND METHODS: This retrospective cohort included 75 consecutive patients with posterior epistaxis treated at a tertiary referral center (January 2020 and December 2025). Clinical outcomes, hospitalization, and hospital costs were compared by primary treatment strategy (intention-to-treat) and by definitive treatment received, using generalized linear models, and a hospital cost-per-success analysis. RESULTS: Primary treatment success was higher with SPA cauterization than packing (97.0% vs. 69.1%; p = 0.002); 30.9% of packing required rescue surgery. Hospital stay was shorter after SPA cauterization (2.64 ± 1.02 vs. 4.71 ± 1.96 days; p < 0.001). Mean hospital cost per patient did not differ significantly between primary strategies (€4,115.69 vs. €4,193.31), resulting in a lower cost per successfully treated patient with primary cauterization (€4,224 vs. €6,073). Rescue surgery-patients had the longest hospitalization and highest costs. CONCLUSIONS: Primary endoscopy SPA cauterization achieved higher success and shorter hospitalization, without increasing hospital cost per patient at the strategy level. Despite higher adjusted costs, delayed surgery after packing failure was the least efficient strategy.

OBJECTIVES: To compare a combined irrigation-assisted dual-drain suction protocol with single-drain suction alone after surgical drainage of Ludwig's angina. DESIGN: Retrospective comparative cohort study with predefined quasi-randomised alternating allocation. SETTING: A tertiary referral otolaryngology department in Tuscany, Italy. PARTICIPANTS: Sixty adults with odontogenic Ludwig's angina and bilateral submandibular abscesses ≥ 4 cm on contrast-enhanced CT were selected from 118 patients screened between January 2015 and April 2025. Consecutive eligible patients were alternately allocated to the combined protocol (Group A, n = 30) or single-drain suction (Group B, n = 30). MAIN OUTCOME MEASURES: Length of hospital stay and a prespecified major-complication composite of surgical reintervention, imaging-confirmed mediastinitis, or new postoperative tracheostomy. Superficial wound infection was analysed separately. RESULTS: Mean hospital stay was shorter in Group A than Group B (6.1 ± 3.6 vs. 8.2 ± 3.4 days; mean difference, -2.1 days; 95% CI: -3.91 to -0.29; p = 0.024). The major-complication composite occurred in 2 of 30 patients (6.7%) and 7 of 30 (23.3%), respectively (RR: 0.29; 95% CI: 0.06-1.26; Fisher's exact p = 0.145). Superficial wound infection occurred in 2 of 30 and 5 of 30 patients, respectively. Several inflammatory markers declined more rapidly in Group A. CONCLUSIONS: The combined protocol was associated with shorter hospitalisation and a numerical, non-significant reduction in prespecified major complications. Because it combined irrigation with a dual-drain configuration, the independent contribution of irrigation cannot be determined.

BACKGROUND: Early delayed gastric conduit emptying (DGCE) and pneumonia are among the most common complications following oesophagectomy. These issues can be challenging to address during minimally invasive surgery with pyloroplasty or pyloromyotomy. This study evaluated the impact of prophylactic endoscopic pyloric balloon dilatation (PBD) on early postoperative outcomes. METHODS: Consecutive patients undergoing oesophagectomy with gastric conduit reconstruction for cancer at two Australian tertiary centres (2017-2025) were retrospectively analysed. From 2023, intraoperative endoscopic-assisted PBD using a 20 mm balloon inflated for two minutes across the pylorus was adopted as standard practice. Primary endpoints were early DGCE and hospital-acquired pneumonia (HAP) within 30 days; secondary endpoints included nasogastric tube (NGT) output and duration, and hospital length-of-stay. Associations were examined using multivariable logistic regression and inverse-probability-weighted regression adjustment (IPWRA). RESULTS: Of 187 patients, 40 (21.4%) received PBD. Compared with controls, PBD was associated with reduced DGCE (15% vs. 40.1%; odds ratio [OR] 0.26, 95% confidence interval [CI] 0.11-0.65) and HAP (20% vs. 40.8%; OR 0.36, 95% CI 0.17-0.80). Pyloric balloon dilatation independently predicted lower DGCE (OR 0.33, 95% CI 0.12-0.91) and HAP (OR 0.18, 95% CI 0.05-0.67), with absolute risk reductions of 27.4% and 30.8% respectively on IPWRA analysis. Pyloric balloon dilatation was also associated with lower postoperative NGT outputs, earlier NGT removal (median 6 [interquartile range (IQR) 4-11] vs. 4 [IQR 3-7] days; p = 0.032), and shorter hospital length of stay (median 13 [IQR 9-22] vs. 9 [IQR 8-16] days; p = 0.007). CONCLUSIONS: Prophylactic PBD was associated with lower early DGCE and pneumonia. This enabled earlier nasogastric tube removal and shorter hospital stay, supporting its integration into contemporary practice.

PURPOSE: Discharge planning following brain tumor resection is often variable, contributing to delays in care coordination after discharge. While structured discharge prediction tools are widely used in orthopedic and spine surgery, no standardized preoperative framework exists in neurosurgical oncology. We conducted an exploratory analysis of the utility of the Risk Assessment and Prediction Tool (RAPT) for preoperative discharge stratification in supratentorial brain tumor resection patients. METHODS: We performed a retrospective cohort study of adults undergoing supratentorial craniotomy for tumor resection at one institution. Preoperative RAPT scores were recorded, and discharge was categorized as home or non-home. Associations between RAPT score and discharge disposition were assessed using logistic regression. Preliminary discrimination was assessed using receiver operating characteristic (ROC) analysis, and all estimates are apparent. RESULTS: Among 36 patients, higher RAPT scores were associated with increased likelihood of home discharge (OR=1.74; 95% CI: 1.08-2.80). ROC analysis showed preliminary in-sample discriminatory ability (apparent AUC=0.815, 95% CI 0.632-0.999). An optimal RAPT cutoff of 9.5 (operationalized as ≥10 vs ≤9) was associated with an apparent sensitivity of 89.7% and positive predictive value of 92.9% for home discharge. A threshold-based model modestly improved classification accuracy compared to a naïve classifier (86.1% vs 80.6%). CONCLUSION: In this exploratory cohort, preoperative RAPT score was associated with discharge disposition and may help identify patients for earlier discharge planning after supratentorial tumor resection. Preliminary performance was driven principally by the identification of patients destined for home discharge. The modest NPV suggests that the characteristics captured by the tool are necessary but not sufficient determinants of disposition in neurosurgical oncology, where postoperative neurological trajectory, which was not measured in this study, may contribute to the unexplained variation. Low scores may prompt earlier care-coordination rather than definitively predict rehabilitation need. These hypothesis-generating findings warrant prospective, multi-institutional validation to determine a defined role in neurosurgical care pathways.

BACKGROUND: The effect of estrogen-based hormone replacement therapy (HRT) on patient outcomes following posterior lumbar fusion (PLF) is not clear. The purpose of this study is to evaluate the effect of preoperative HRT on older women undergoing PLF. METHODS: A retrospective review of 4596 patients undergoing PLF in the PearlDiver database was performed. Patients prescribed HRT within 1 year preoperatively were matched 1:3 on demographics and pertinent comorbidities with patients not taking HRT; 1149 patients were taking HRT and 3447 were not. Univariate analyses were performed to compare postoperative complications at 90 days and reoperations at 2 years with and without false discovery rate (FDR) adjustment. RESULTS: At 90 days postoperatively, those taking HRT were 41% more likely to experience a urinary tract infection (UTI) within 90 days postoperatively (OR: 1.41, 95% CI: 1.12-1.79; P = 0.005, FDR-adjusted P = 0.090). At 2 years postoperatively, those taking HRT were 65% more likely to have a decompression (OR: 1.65, 95% CI: 1.14-2.38; P = 0.009, FDR-adjusted P = 0.090) and were 35% more likely to have any reoperation (OR: 1.35, 95% CI: 1.04-1.74; P = 0.027, FDR-adjusted P = 0.180). However, these differences were not statistically significant after FDR adjustment. CONCLUSIONS: Patients taking HRT prior to PLF had increased rates of UTI within 90 days of surgery and increased rates of subsequent decompression and any reoperation within 2 years postoperatively, although these trends did not reach statistical significance after FDR adjustment. These results suggest an overall favorable safety profile of HRT use in female PLF patients aged ≥55 years old; however, further surveillance of risk for 90-day UTIs and 2-year reoperations is warranted. CLINICAL RELEVANCE: With the recent removal of most black-box warnings from estrogen-based HRT for menopausal symptoms, it is likely that the number of older female patients taking HRT will increase. It is important to identify the implications of the concurrent use of the medication in patients undergoing spinal fusion surgery.

BACKGROUND: There are no guideline recommendations for antibiotic choice for community-acquired pneumonia (CAP) in children with medical complexity (CMC). We compared broad- vs narrow-spectrum antibiotics in CMC hospitalized with nonsevere CAP. METHODS: This cohort study was conducted using target trial emulation within an academic health system. We included hospitalizations from January 2016 to April 2024 with International Classification of Diseases, 10th Revision (ICD-10) codes for CAP and complex chronic conditions among children aged 3 months to 21 years who received 3 or more days of antibiotics. We excluded children with severe/complicated CAP, chronic pulmonary conditions, sickle cell disease, tracheostomies, immunosuppression, other bacterial infections, or recent CAP admission. The exposure was initial broad-spectrum antibiotics (CAP antibiotics other than aminopenicillins) within 12 hours of presentation. The primary outcome was time to discharge, censored at day 10. Secondary outcomes were progression to severe CAP and 30-day CAP-related revisits. To mitigate confounding, we applied inverse probability of treatment weighting in outcome models, including a Royston-Parmar flexible survival model for time to discharge, and logistic regression for binary outcomes. RESULTS: A total of 847 encounters (749 patients) were included. After weighting and trimming, 742 encounters remained with adequate covariate balance. Compared with the narrow-spectrum group, the broad-spectrum group demonstrated no significant differences in time to discharge (hazard ratio, 0.84; 95% CI, 0.68-1.04), progression to severe CAP (odds ratio [OR], 1.29; 95% CI, 0.7-2.4), or 30-day CAP-related revisits (OR, 0.39; 95% CI, 0.1-1.2). CONCLUSIONS: In CMC hospitalized with nonsevere CAP, initial broad-spectrum antibiotics did not improve clinical outcomes compared with narrow-spectrum antibiotics, supporting the use of aminopenicillins for nonsevere CAP in many CMC.

RATIONALE: Among adults hospitalized with acute infection, a recent randomized trial observed no significant average treatment effect of cefepime versus piperacillin-tazobactam on acute kidney injury or death, but fewer days-alive-and-free-of delirium and coma with cefepime. OBJECTIVES: To determine whether patients' individual characteristics modify the effect of cefepime versus piperacillin-tazobactam on outcomes. METHODS: In this secondary analysis of the Antibiotic Choice On Renal Outcomes (ACORN) trial, an effect model was derived and validated to predict the effect of cefepime versus piperacillin-tazobactam for adults hospitalized with acute infection. The primary outcome was survival without acute kidney injury; the secondary outcome was survival without delirium or coma. MEASUREMENTS AND MAIN RESULTS: The individualized treatment effect predicted in the validation cohort significantly modified the effect of cefepime versus piperacillin-tazobactam on survival without acute kidney injury (Qini 1.68; 95% confidence interval [CI], 0.25-3.18; p-value = 0.01). Among 626 patients predicted to experience ≥5% benefit from cefepime, 81.2% of patients randomized to cefepime survived without acute kidney injury, versus 74.2% randomized to piperacillin-tazobactam (difference, 7.1%; 95%CI, 0.25 to 13.9%). Among 203 patients predicted to experience ≥5% benefit from piperacillin-tazobactam, 56.6% of patients randomized to cefepime survived without acute kidney injury, versus 63.0% randomized to piperacillin-tazobactam (difference, -6.3%; 95%CI, -20.7 to 8.2%). The effect of trial group on survival without delirium or coma was not modified by individual characteristics. CONCLUSIONS: Patients' individual characteristics modified the effect of cefepime versus piperacillin-tazobactam on survival without acute kidney injury but not on survival without delirium or coma.

PURPOSE: The study assessed the effect of a postoperative fluid restriction on the incidence of delayed hyponatremia (DH) following transsphenoidal pituitary surgery (TSS). The incidence of DH in the prospective cohort was compared to that of a published retrospective cohort from our centre managed according to the standard postoperative protocol without fluid restriction. METHODS: This prospective interventional study included patients aged ≥18 years who underwent TSS for pituitary neuroendocrine tumors (PitNETs). A structured postoperative fluid restriction of ≤1.5 L/day was implemented from post-operative day 5 (POD5) to POD14, with daily intake/output monitoring. Serum sodium was measured at defined postoperative intervals. DH incidence in the prospective cohort was compared with a previously published retrospective cohort managed without fluid restriction. Patient adherence and satisfaction were assessed using a study-specific questionnaire. RESULTS: The study included 78 patients with a mean(SD) age of 42.6(11.9) years. Seventy-two (92.3%) patients had macroadenomas and 35.9% of the tumors were invasive. Twelve (15.4%) patients developed early transient AVP deficiency. Eleven (14.1%) patients developed DH between POD 5-14, compared to 36% in the retrospective cohort (p = 0.001). None in the prospective cohort required readmission or prolonged hospitalization for hyponatremia and the hyponatremia resolved with further tighter fluid restriction. Seven patients developed mild asymptomatic hypernatremia/increased serum osmolarity which resolved with relaxation of fluid intake. CONCLUSION: A structured fluid restriction protocol of ≤1.5 L/day in the post-operative period may be safe and effective in reducing the incidence of delayed hyponatremia and readmissions following transsphenoidal pituitary surgery for PitNETs in a tropical setting.

INTRODUCTION: Urinary incontinence (UI) is a prevalent geriatric syndrome that significantly affects the physical, psychological, and social well-being of older adults. Non-pharmacological interventions are recommended as the first-line approach, especially in frail older adults. DESIGN: This was a prospective pre-post observational study. METHODS: The study included sixty-one patients with rehabilitable UI who were admitted to an intermediate care hospital. The nurse-led multidisciplinary program integrated education, hygiene-dietary measures, pelvic floor physiotherapy, behavioral strategies, and transcutaneous electrical nerve stimulation (TENS). The primary outcomes were UI severity (International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF)), voiding awareness, diurnal and nocturnal voids, disposable absorbent product use, functional status (Barthel Index), cognitive status (Pfeiffer test), and quality of life (EQ-5D). Data were collected at baseline and discharge. RESULTS: Data from 61 participants were analyzed. Significant improvements were observed in the ICIQ-SF scores (16.72 ± 3.39 vs. 9.10 ± 5.86; p < 0.001), daytime voiding awareness (83.6% vs. 100%; p = 0.002), nocturnal voiding awareness (66.7% vs. 88.5%; p = 0.002), nocturnal voids (3.46 ± 2.22 vs. 2.35 ± 1.68; p < 0.001), Barthel Index (49.83 ± 23.84 vs. 70.33 ± 19.59; p < 0.001), and EQ-5D scores (0.39 ± 0.28 vs. 0.56 ± 0.26; p < 0.001). The use of disposable absorbent products decreased from 98.36% to 62.30% (p = 0.065). The patient's cognitive status remained stable. The mean satisfaction with the program was 8.53/10. CONCLUSIONS: A nurse-led, multidisciplinary, non-pharmacological intervention effectively reduced UI severity, increased voiding awareness, enhanced functional autonomy, and improved the quality of life in older adults. These findings support the implementation of individualized, evidence-based programs in intermediate care settings. CLINICAL RELEVANCE: Non-pharmacological interventions led by advanced practice nurses provide effective, patient-centered management of urinary incontinence, improving autonomy and quality of life while potentially reducing healthcare costs.

INTRODUCTION: Medication-related readmissions are a significant and preventable cause of patient harm. Patients living in rural and remote areas may face inequitable access to healthcare and fragmented continuity of care, increasing their vulnerability to medication-related harm. Despite this, the burden and drivers of medication-related readmissions in these settings remain poorly understood. Determining the current burden and identifying factors associated with medication-related readmissions is essential to inform targeted strategies to improve medication safety. AIM: To determine the proportion of adult patients with a medication-related readmission within 30 days of discharge from rural and remote hospitals, and to identify factors potentially associated with these readmissions. METHOD: A retrospective cohort study was conducted using medical records of adults admitted to rural and remote hospitals in New South Wales, Australia, between June 1, 2022 and August 31, 2023. Readmissions within 30 days were assessed for medication-related causes using the AT-HARM10, a validated 10-item tool based on admission notes, medication lists, inpatient pathology results, and discharge summaries. Patient demographics, comorbidities and admission details were extracted. Comorbidity burden was calculated using the Charlson Comorbidity Index (CCI). Medication lists were based on medications charted 12 h before discharge. Univariable logistic regression was performed to explore factors associated with 30-day medication-related readmissions, with results reported as unadjusted odds ratios (uOR). RESULTS: Of the 2220 patients admitted during the study period, 6% (n = 133) experienced a 30-day readmission, of which 22.5% (n = 30) were medication-related. Overall, 1.4% of all admitted patients experienced a 30-day medication-related readmission. Older age (uOR 1.04; 95% CI 1.01-1.07), higher CCI (uOR 1.22; 95% CI 1.04-1.44), a greater number of regular medications (uOR 1.07 per additional medication; 95% CI 1.01-1.14), and insulin use (uOR 2.80; 95% CI 1.06-7.42) were associated with medication-related readmission. CONCLUSION: In rural and remote hospitals, a small but clinically important proportion of patients experienced a medication-related readmission within 30 days of discharge. Unadjusted analysis identified that older age, multimorbidity, polypharmacy and insulin

The use of robot-assisted surgery (RAS) has increased markedly in China, but comparative evidence on its perioperative performance in cancer care is dispersed across specialties and study designs. This review synthesized Chinese evidence to examine the safety and effectiveness of da Vinci robot-assisted surgery (dV-RAS) relative to laparoscopic/video-assisted thoracoscopic surgery (LAP/VATS) and open surgery across seven oncologic procedures. We systematically reviewed comparative studies published from 2010 to 2024 and pooled estimates for dV-RAS versus LAP/VATS or open surgery. Prespecified perioperative outcomes were conversion to open surgery, operative time, estimated blood loss, blood transfusion, hospital length of stay, postoperative complications, readmission, reoperation, and 30-day mortality. The review included 116 studies. Relative to LAP/VATS, dV-RAS was associated with lower odds of conversion to open surgery (odds ratio [OR] 0.26; 95% confidence interval [CI] 0.21-0.33; p < 0.01), less blood loss (mean difference [MD] - 32.48 mL; 95% CI - 40.86 to - 24.11; p < 0.01), lower odds of transfusion (OR 0.61; 95% CI 0.51-0.73; p < 0.01), a shorter hospital stay (MD - 1.06 days; 95% CI - 1.30 to - 0.82; p < 0.01), fewer 30-day postoperative complications (OR 0.67; 95% CI 0.61-0.73; p < 0.01), and fewer reoperations (OR 0.62; 95% CI 0.40-0.96; p = 0.03). Comparisons with open surgery likewise favored dV-RAS for blood loss, transfusion, length of stay, and postoperative complications. Operative time, readmission, and 30-day mortality did not differ significantly between approaches. Across seven oncologic procedures, pooled evidence from China indicated that dV-RAS was associated with better outcomes on several perioperative measures than LAP/VATS or open surgery. Because between-study heterogeneity was substantial and most included studies were retrospective, the findings should be interpreted cautiously and confirmed in higher-quality prospective research.

BACKGROUND: Closed-loop oxygen control (CLOC) systems improve accuracy of oxygen delivery compared with standard manual oxygen adjustment. Determination of their efficacy in delivering oxygen noninvasively to adults, using different delivery methods and across different hospital locations, would enhance clinical practice. METHODS: We conducted a systematic review and meta-analysis, searching Medline, Embase, Scopus Basic and Advanced, and Cochrane databases. Randomised controlled trials comparing time spent within a target peripheral oxygen saturation (S pO2 ) range between CLOC and manual oxygen control in hospitalised adults (>18 years) were included. Outpatient studies and studies using mechanical ventilation were excluded. The primary outcome was proportion of time spent within a target S pO2 range. Meta-regression was performed for pre-determined study-level covariates, including oxygen delivery mode and locations of care. RESULTS: The search identified 3777 papers; of these, seven were included, with 635 participants. The mean proportion of time spent within the target S pO2 range was between 81.2 and 94.9% for CLOC and 51.3-84.0% for manual oxygen control. The mean difference was 21.2% (95% CI 18.5-23.8, p<0.0001), favouring CLOC. Evidence of heterogeneity (I2=87.9) was explained by three studies using low-flow oxygen therapy, mean difference 30.9% (95% CI 27.0-34.8, p<0.0001); compared with four studies using high-flow nasal oxygen therapy, mean difference 12.7% (95% CI 9.1-16.4, p<0.001). CONCLUSIONS: CLOC improves adherence to a target S pO2 range compared to manual oxygen control and is an effective approach for achieving a target S pO2 range when delivering oxygen noninvasively in hospitalised adults.

OBJECTIVES: To evaluate whether race and ethnicity are associated with increased odds of physical impairment among post-ICU survivors and to assess how impairment influences healthcare utilization after hospital discharge. DESIGN: This was a retrospective cohort study. SETTING: The study was conducted at an academic medical center. PATIENTS: We included 4370 adult ICU survivors who experienced shock, respiratory failure, or received extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary exposure was self-reported race and ethnicity. The primary outcome was impairment at hospital discharge, defined using the International Classification of Diseases, 10th Revision codes and/or a Johns Hopkins Highest Level of Mobility score of less than or equal to 5. Multivariable logistic regression was used to assess associations with impairment, and Fine-Gray models evaluated post-discharge healthcare utilization. Impairment was identified in 31% of ICU survivors. Non-Hispanic Black race was associated with increased odds of any impairment (adjusted odds ratio [aOR], 1.34; 95% CI, 1.04-1.72), and Hispanic ethnicity was associated with increased odds of new impairment (aOR, 1.42; 95% CI, 1.05-1.91), compared with non-Hispanic White-identifying survivors. Among those with impairment, both non-Hispanic Black and Hispanic individuals had increased risk of healthcare utilization within 1 year. CONCLUSIONS: Non-Hispanic Black race and Hispanic ethnicity are associated with increased odds of post-ICU physical impairment and subsequent healthcare utilization. These findings highlight the need to understand root causes better and explore targeted interventions to reduce disparities among ICU survivors.

BACKGROUND: Whether coded rheumatoid arthritis (RA) among patients undergoing elective total hip arthroplasty (THA) is associated with excess short-term inpatient morbidity in contemporary U.S. practice remains uncertain. METHODS: We performed a retrospective cohort study using the National Inpatient Sample (2016-2021). Adults undergoing elective primary THA were identified using ICD-10-CM/PCS codes. The exposure cohort included admissions with coded RA in any diagnosis position. The comparator cohort included admissions with narrow primary hip osteoarthritis (OA) as the principal diagnosis and no RA. Propensity scores were estimated from demographic, socioeconomic, hospital, and comorbidity variables. Inverse probability of treatment weighting (IPTW) with survey weighting was used for the primary analysis, followed by doubly adjusted regression models that included age and all variables with persistent post-weighting imbalance greater than 0.10 (female sex, osteoporosis, chronic obstructive pulmonary disease, chronic anemia, depression, and race). Additional sensitivity analyses included stricter weight truncation, a restriction analysis, conventional multivariable modeling, and sex-stratified analyses addressing residual sex imbalance. RESULTS: A total of 274,582 admissions met eligibility criteria; 274,539 were included in the final analytic cohort after exclusion of 43 records with missing or invalid propensity-weight inputs. The analytic cohort included 7,264 RA admissions and 267,275 OA admissions. In the primary weighted analysis, RA was associated with higher odds of acute blood loss anemia (OR 1.30, 95% CI 1.23-1.38), red blood cell transfusion (OR 1.40, 95% CI 1.23-1.60), acute kidney injury (OR 1.47, 95% CI 1.26-1.71), non-home discharge (OR 1.27, 95% CI 1.19-1.36), and a composite hematologic/renal in-hospital complication (OR 1.31, 95% CI 1.24-1.39).RA was also associated with slightly longer length of stay (+ 0.14 days, 95% CI + 0.10 to + 0.19) and modestly higher total hospital charges (+$1,018, 95% CI +$89 to +$1,947). Findings were directionally consistent across sensitivity analyses, including stricter weight truncation, restriction to admissions with principal OA plus concomitant RA, and sex-stratified analyses. CONCLUSIONS: In this contemporary national THA cohort, coded RA was associated with a small but consistent increase in in-hosp

RATIONALE: Daily sedation interruption (DSI) aims to limit drug accumulation and promote a more awake state, thereby reducing the duration of mechanical ventilation and its associated complications. This is an update of a Cochrane review first published in 2014. OBJECTIVES: To assess the effects of DSI versus sedation management without DSI on the duration of invasive mechanical ventilation, mortality, intensive care unit (ICU) length of stay, adverse events related to under- or oversedation (including accidental removal of endotracheal tube and tracheostomy), total doses of sedative and analgesic drug administered, and health-related quality of life, for critically ill people requiring intravenous sedation. SEARCH METHODS: We used CENTRAL, MEDLINE All, Embase Classic+Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science Core Collection, and two trial registers, together with reference checking, citation searching, and contact with study authors to identify the studies included in the review. The latest search date was 8 October 2025. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) comparing DSI with sedation strategies that did not include DSI (protocolised sedation, non-protocolised usual care (clinician discretion), or analgesia first/no sedation) in mechanically ventilated, critically ill people (adults and infants or children under 18 years of age). OUTCOMES: Our critical outcomes were duration of mechanical ventilation (from randomisation to successful extubation or death), mortality, and ICU length of stay (LOS). Our important outcomes included hospital LOS, adverse events related to under- or oversedation (e.g. accidental removal of endotracheal tube or other lines or catheters, tracheostomy, new onset of delirium occurrence, use of physical restraint, and cardiac events), total drug doses, and health-related quality of life (HRQoL). RISK OF BIAS: We used the original Cochrane tool, RoB 1, to assess bias in the RCTs. SYNTHESIS METHODS: We synthesised results for each outcome using meta-analysis (random-effects modelling). We conducted subgroup and sensitivity analyses according to pre-defined criteria. We used GRADE to assess the certainty of evidence. INCLUDED STUDIES: This update included 23 trials (one cluster-randomised trial; 18 RCTs in adults, five in children) with 5987 (4910 adj

Human mobility plays a crucial role in the spread of human diseases but is rarely quantified in plant disease epidemics. To address this gap, we integrate a unique, high-resolution network of human movements in New Zealand with a metapopulation model to mechanistically simulate pathogen transmission. We calibrate the model on the nationwide 2010 kiwifruit vine disease (Psa-V) outbreak and show that it reproduces the observed spatio-temporal spread, confirming that the human mobility network is a strong foundation for modelling human-mediated transmission dynamics. By analysing spatial infection trends, we find that most dispersal occurs locally, as often illustrated in the plant-outbreak literature. However, sporadic long-range connections are necessary to model a nationwide outbreak. Using the model as an in silico laboratory, we demonstrate that the severity of human-mediated pathogen transmission is highly sensitive to the timing and location of initial importation. We observe a potential causal link between seasonal labour patterns and epidemic risk in high-traffic seasons. This study showcases a novel data-driven framework for modelling the spatio-temporal spread of agricultural pathogens when human-mediated dispersal is epidemiologically relevant, underscoring the importance of leveraging human mobility networks for building better biosecurity systems.

While culturing the opportunistic pathogen Pseudomonas aeruginosa in standard bacterial culture media has provided fundamental insights into its pathological properties such as virulence and antibiotic resistance, growing evidence suggests that these conditions fail to accurately reflect the in vivo bacterial physiology. In the lungs of people living with cystic fibrosis (pwCF), where P. aeruginosa is a major contributor to the disease process, bacteria reside within a complex physicochemical environment that drives their behaviour. Until recently, efforts to evaluate how well laboratory models mimic these in vivo conditions were hampered by limited data on the physiology of P. aeruginosa during chronic cystic fibrosis (CF) lung infections. However, several omics-based studies have now successfully characterised P. aeruginosa from human CF sputum, revealing unique adaptation patterns associated within this niche. This data enables evaluating the physiological relevance of in vitro and in vivo model systems, hereby highlighting the usefulness (and limitations) of models that mimic aspects of the physicochemical in vivo environment for studying P. aeruginosa infections in CF. In this review, we summarise a range of models of P. aeruginosa infection, including artificial sputum medium, air-liquid interface cell culture, ex vivo pig lung and mouse models, that have been evaluated for their physiological resemblance using omics-based approaches. We also address the current lack of proteomic and metabolomic validation approaches and outline key considerations and future directions to guide the continued refinement of experimental model systems.

Escherichia coli occupies a unique position between commensal colonization and infection. It is a common member of the intestinal microbiota, yet selected pathogenic or opportunistic lineages can persist in mucosal niches, interact with resident microbial communities, and in some cases seed recurrent extraintestinal diseases. The mechanisms enabling long-term colonization, survival under host and antibiotic pressure, and relapse are diverse, depending on pathotype, infection site, host environment, and microbial community structure. Here, we critically examine how T3SS, T5SS, and T6SS may contribute to persistence-associated biology in specific E. coli contexts. T3SS primarily mediates epithelial interaction in enteric pathotypes, T5SS drives adhesion, biofilm formation, mucosal colonization, and immune modulation, and T6SS functions as a microbiota-facing mechanism of interbacterial competition. We distinguish experimentally demonstrated roles from speculative links to chronicity and recurrence, framing these systems as context-dependent interaction modules rather than a unified network, while highlighting evidence gaps relative to established persistence determinants.

SUMMARYBacteria can enter a transient state of reduced metabolic activity to survive temporary unfavorable conditions. This phenomenon, sometimes referred to as dormancy, growth arrest, or quiescence, enables pathogen survival inside and outside of their host, with major clinical consequences for the management of infections. From spores to persister cells, these states associated with bacterial dormancy share molecular mechanisms for controlling cellular activity and for responding to related environmental signals. In this review, we provide a synthesis of the diversity of dormant states in human pathogenic bacteria and their pathophysiology within a unifying framework of a dormant-to-active spectrum. We highlight recent developments in therapeutic strategies targeting growth-arrested bacteria and shed light on the role of dormancy in pathogen dissemination and transmission across compartments under a global health perspective. Finally, we discuss the role of dormancy as a microbial trait that shapes virulence and infection dynamics over the course of evolution. Overall, this work seeks to provide new insights into the links between bacterial dormancy and latency in microbial pathogenesis while alleviating the semantic boundaries of the field.

OBJECTIVE: The Surgical Care Improvement Project (SCIP) was developed and implemented nationally from 2005 to 2015 partly to improve surgical antimicrobial prophylaxis processes. SCIP's manual review process was costly yet led to high compliance rates in the Veterans Administration (VA). Our objective was to develop an electronic compliance algorithm to replicate the SCIP metric for timely discontinuation of antimicrobial prophylaxis (INF-3) in cardiac surgeries. STUDY DESIGN: This retrospective cohort study matched manually adjudicated INF-3 data from the VA External Peer Review Program (EPRP) with 2006-2015 cardiac surgeries in the Corporate Data Warehouse (CDW). Algorithm development used EPRP data as the gold standard, supplemented with manual review, to apply SCIP-defined electronic exclusions and flag cases with appropriate antimicrobial discontinuation. Algorithm validation used manual review of compliant (n = 90) and non-compliant cases (n = 210) among cardiac surgeries not in EPRP. RESULTS: The algorithm utilized CDW prophylactic versus therapeutic antimicrobial drug names and timestamps for drug administration to reliably exclude cases with appropriate antimicrobial use before flagging INF-3 compliance/non-compliance. In the EPRP-CDW development sample (n = 29,431), the algorithm-measured INF-3 compliance rate was 96.2% versus EPRP's rate of 95.9%. In validation (n = 10,131), sensitivity was 92.1% (95%CI: 88.0%, 96.2%) and specificity was 97.0% (95%CI: 93.6%, 100%) compared to manual review. The algorithm exclusion rate in CDW cardiac surgeries was 18.5%-primarily for antimicrobial pharmacy administration indicative of pre-or postoperative infection (7,360/52,310 14.1%). CONCLUSIONS: The SCIP INF-3 cardiac electronic algorithm effectively replicated the EPRP manual review process and has the potential to extend surveillance of appropriate surgical antimicrobial prophylaxis.

INTRODUCTION: This network meta-analysis (NMA) compared the efficacy and safety of antibiotic classes for empirical treatment of suspected intra-abdominal infections (IAIs) and for prophylaxis in at-risk populations. METHODS: PubMed, Embase, SCOPUS, Web of Science, and CENTRAL were searched until 24 January 2026 (PROSPERO-CRD420251106514). Eligible studies assessed empiric antibiotic therapy or prophylaxis for IAI. Outcomes included treatment success, intra-abdominal and wound infection rates, morbidity, mortality, and adverse events. Treatment and prophylaxis data were analyzed as separate networks per outcome using frequentist random-effects NMA, with certainty graded via GRADE. RESULTS: 19 studies (2,910 patients) on treatment and 9 studies (3,014 patients) on prophylaxis, across eight antibiotic classes, were included. In treatment setting, carbapenems were associated with significantly higher treatment success than β-lactam/β-lactamase inhibitor [RR(95%CI)=1.06 (1.01-1.62)], and ranked highest by SUCRA for treatment success and adverse events. In prophylaxis setting, cephalosporin was associated with a lower risk of wound infection than carbapenem [RR(95%CI)=0.79 (0.70-0.88)] and β-lactam/β-lactamase inhibitor [RR(95%CI)=0.38 (0.16-0.91)]. Sensitivity analyses confirmed robustness; certainty ranged from moderate to very low, mainly due to imprecision. CONCLUSION: Carbapenems provide the highest efficacy for empirical IAI treatment but require judicious use given resistance concerns. This benefit does not extend to prophylaxis, where narrower-spectrum agents such as cephalosporins performed well. Further high-quality trials incorporating newer agents and resistance outcomes are needed.

OBJECTIVE: To develop a protocol for a systematic review aimed to evaluate the existing evidence on the use of dalbavancin and oritavancin as suppressive therapy, focusing on their efficacy, effectiveness and safety across different infectious diseases and therapeutic use protocols. METHODS: A systematic review of studies involving patients treated with dalbavancin and/or oritavancin as suppressive therapy will be performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The main outcomes of interest are the efficacy, effectiveness and safety of these treatments as suppressive therapy. Searches will be performed in MEDLINE (PubMed), Embase (Ovid), the Cochrane Central Register of Controlled Trials, and the Latin American and Caribbean Health Sciences Literature database. English- and Spanish-language literature will be included, with no date restrictions. Studies including patients treated with dalbavancin and/or oritavancin as long-term suppressive therapy in adults will be included; studies in which these treatments were used for other purposes will be excluded. Reviews, abstracts, protocols, duplicates, and grey literature will be excluded. Data from the studies will be synthesised in both tabular and narrative form according to the Synthesis Without Meta-analysis reporting guidelines. Extracted data will include study design, patient characteristics, infection type, causative pathogens, dosing regimens, clinical outcomes, adverse events, and therapeutic drug monitoring targets and measurements. Data from these studies will be grouped by the drug(s) reported, infection type, isolated pathogen and used dosing regimens. The methodological quality of included studies will be assessed using the Joanna Briggs Institute critical appraisal tools. The article selection, data extraction, and quality assessment processes will be carried out by two independent reviewers, with a third to resolve discrepancies. This protocol has been reported to follow the recommendations stated by the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. This protocol was registered in the International Prospective Register of Systematic Reviews of the Center for Reviews and Dissemination (registration number: CRD420251054127). DISCUSSION: The current evidence on this topic is mainly limited to small studi

Extraction-string ureteral stents facilitate non-cystoscopic removal after ureteroscopy, but concerns remain regarding postoperative infection and accidental dislodgement. We evaluated whether extraction-string stents were associated with postoperative infection after flexible ureteroscopic lithotripsy (fURSL) in a cohort restricted to procedures with the distal Double-J (D-J) stent portion positioned within the bladder. This retrospective observational study included 102 procedures in 92 unique patients: 58 extraction-string and 44 conventional non-string procedures. Postoperative infection was defined as fever > 38 °C or a positive postoperative urine culture during the stent-indwelling period. Propensity scores incorporated age, sex, positive preoperative urine culture, preoperative pyuria, and procedure laterality. Stabilized inverse probability of treatment weights were truncated at the 1st and 99th percentiles; effective sample size was 85.38. Crude postoperative infection occurred in 8/58 (13.8%) extraction-string and 6/44 (13.6%) non-string procedures. After weighting, estimated infection rates were 13.6% and 8.8%, respectively (OR 1.64, 95% CI 0.50-5.44; P = 0.416). Fever, positive postoperative urine culture, postoperative pyuria, and postoperative day 1 pain did not differ significantly. Sensitivity analyses accounting for repeated procedures and propensity-model specification were consistent with the primary analysis. Extraction-string stent use was not significantly associated with postoperative infection after fURSL; however, the limited number of events and wide confidence intervals preclude exclusion of a clinically meaningful difference.

BACKGROUND: Vancomycin has a narrow therapeutic window requiring careful drug dosing and monitoring to ensure efficacy while avoiding toxicity. Although protocolised prescribing and monitoring are recommended in antibiotic guidelines, adherence in clinical practice is infrequently reported. OBJECTIVES: We sought to describe compliance with a new vancomycin dosing guideline in the intensive care unit (ICU) and to describe its efficacy in reaching serum levels within the therapeutic range. METHODS: In this single-centre retrospective observational study, we assessed compliance with, and efficacy of a newly implemented vancomycin prescribing protocol. All ICU patients prescribed intravenous vancomycin between May and July 2024 were screened for inclusion. Collected data included indication, weight, age, creatinine, urine output, loading dose, maintenance dose, plasma vancomycin concentration, and timing of monitoring. Augmented renal clearance (ARC) was defined as a creatinine level below the reference range and/or an urine output >3 L in 24 h. RESULTS: A total of 148 patients were included. Protocol compliance was 82% for the loading dose (101/123), 49% for maintenance dosing (49/101), and 51% for timing of monitoring (46/91). Compliance across all protocol domains occurred in 27% of instances (17/64). Therapeutic drug levels were achieved in only 20% of prescribing episodes. Central nervous system (CNS) infection vs non-CNS infection (odds ratio [OR]: 9.5, 95% confidence interval [CI]: 2.7-41.3; P < 0.01) and ARC vs no ARC (OR: 15.1, 95% CI: 4.0-80.4; P < 0.01) were independently associated with subtherapeutic levels, while impaired renal function (glomerular filtration rate: <60 mL/min) vs normal renal function (glomerular filtration rate ≥60 mL/min) was associated with supratherapeutic levels (OR: 3.6, 95% CI: 1.1-13.2; P < 0.05). Protocol compliance was not associated with therapeutic levels. CONCLUSIONS: Vancomycin protocol adherence in a mixed medical-surgical ICU was low; however, adherence was not associated with therapeutic levels. Patients with CNS infection, ARC, or renal impairment are at risk of nontherapeutic levels.

UNLABELLED: Optimizing antibiotic duration for pediatric community-acquired pneumonia (CAP) may reduce treatment burden and support antimicrobial stewardship. Although recent randomized trials and evidence syntheses have reported similar clinical outcomes with shorter antibiotic courses, the effect of treatment duration on adherence-an especially relevant consideration in children-has received comparatively limited systematic evaluation. We therefore aimed to compare treatment effectiveness, medication adherence, and antibiotic-related adverse events between short-course and conventional-duration antibiotic therapy for non-severe CAP in immunocompetent children. PubMed, Cochrane Library, Scopus, ClinicalTrials.gov, and WHO Global Index Medicus were sought through April 25, 2025. Only randomized clinical trials that included immunocompetent children < 18 years with non-severe CAP and compared short-course (≤ 5 days) with longer therapy (> 5 days) were considered. Data extraction and risk of bias (ROB 2) assessment were performed by two independent reviewers. Summary data were extracted by published reports. The principal outcomes were treatment effectiveness, assessed through treatment failure and relapse according to the definitions prespecified by each trial, and medication non-adherence to the active (non-placebo) study drug. Antibiotic-related adverse events were assessed as a secondary outcome. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models. Two hundred thirty studies were originally screened, after removal of duplicates and 10 trials (n = 8970) met inclusion criteria. No significant differences were found in treatment failure [RR = 1.07 (95% CI, 0.93-1.24), I2 = 3%] or relapse [RR = 1.04 (95% CI, 0.72-1.49), I2 = 0%]. Shorter regimens markedly reduced non-adherence [RR = 0.35 (95% CI, 0.24-0.50), I2 = 54%], the most consistent and clinically meaningful difference. Adverse events were comparable [RR = 0.71 (95% CI, 0.36-1.40), I2 = 81%]. CONCLUSIONS: Short-course therapy was not associated with significantly different treatment failure or relapse rates compared with longer regimens and was associated with substantially lower non-adherence. These findings support shorter antibiotic courses as a reasonable treatment option for non-severe pediatric CAP, while acknowledging that the present meta-analysis wa

BACKGROUND: Bloodstream infections (BSIs) remain a significant cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT), particularly during the post-transplant neutropenia and immune reconstitution phase. Notably, studies have identified high rates of BSI in the early post-transplant period with PTCy regimens, including single-center cohorts that have highlighted Candida, Enterococcus, and gram-negative rods (GNRs) as predominant pathogens. However, the broader clinical impact of pathogen-specific BSI on post-HCT outcomes in PTCy recipients remains incompletely defined. We aimed to study allo-HCT outcomes in patients who developed BSI in the first 100 days. METHODS: We performed a retrospective, registry-based cohort analysis using dataset P-5242 from the Center for International Blood and Marrow Transplant Research (CIBMTR). Adult patients who underwent allo-HCT with PTCy-based GVHD prophylaxis between 2009 and 2016 were included. Microbiologically confirmed BSIs within the first 100 days post-HCT were categorized by pathogen. Multivariable Cox proportional hazards models were used to evaluate associations between specific pathogens and acute GVHD (grade II-IV), chronic GVHD, time to neutrophil engraftment (ANC ≥ 500), overall survival (OS), and Non-relapse mortality (NRM). Adjusted covariates included patient age, gender, disease type, conditioning intensity, graft source, donor type, Hematopoietic Cell Transplantation-Comorbidity Index, and Karnofsky performance score. RESULTS: A total of 385 patients who developed BSI within the first 100 days post-transplant were included. The mean age was 50.0 years (SD 18.6), and 60.5% were male. 49.1% had acute myeloid leukemia (AML), 15.8% had acute lymphoblastic leukemia (ALL), 26.5% had myelodysplastic syndrome (MDS), and 8.6% had non-malignant diseases. Total body irradiation (TBI) was used in 56.4% patients, and only 5.7% received anti-thymocyte globulin. Graft sources were peripheral blood stem cells (PBSC) in 54.8%, bone marrow in 45.2%, and cord blood in 0.3%. 51.2% had a Karnofsky Performance Score of <90, and 53.8% had an HCT-comorbidity index score>3. In multivariable analysis, Candida infections and Enterococcus were associated with inferior survival (HR 3.369, 95% CI, p < 0.001, and HR 1.497, 95% CI, p = 0.049, respectively). Non-Enterobacteriaceae gram-negat

BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication after total knee arthroplasty (TKA). Intrawound vancomycin powder has been proposed as a local prophylactic measure, but concerns remain regarding systemic absorption and nephrotoxicity. This study evaluated systemic absorption, renal safety, and postoperative infection outcomes after intrawound vancomycin use in primary TKA. METHODS: This prospective comparative cohort study included 260 patients who underwent primary TKA at a single tertiary care center: 130 in the vancomycin cohort and 130 in the control cohort. The vancomycin cohort received one gram of intrawound vancomycin powder before closure. Serum vancomycin levels were measured 12 hours postoperatively. Serial renal function and kidney disease: Improving Global Outcomes (KDIGO)-defined acute kidney injury (AKI) was analyzed in all patients. Infection and wound-complication outcomes were assessed in patients who completed at least six months of follow-up. RESULTS: The 12-hour serum vancomycin levels were below the laboratory reporting threshold (less than 1.00 mg/L) in 104 of 130 patients (80.0%). Among the remaining 26 patients who had numerical values, the median concentration was 0.28 mg/L (interquartile range [IQR], 0.21 to 1.26; range, 0.01 to 2.76 mg/L), which was well below systemic therapeutic levels. Serum vancomycin concentration was not correlated with early changes in serum creatinine or estimated glomerular filtration rate (Spearman ρ range, -0.08 to -0.03; all P ≥ 0.720). AKI occurred in nine patients (6.9%) in the vancomycin group and eight patients (6.2%) in the control group (odds ratio, 1.13; 95% confidence interval [CI], 0.42 to 3.04; P = 1.000). All AKI events in the vancomycin group were stage 1. Surgery-related complication rates were similar between groups, with no statistically significant differences in PJI, superficial infection, or wound dehiscence. CONCLUSION: Intrawound administration of one gram of vancomycin powder in primary TKA resulted in minimal systemic exposure and showed no clinically meaningful nephrotoxicity signal. However, it was not associated with a statistically significant reduction in infection or wound-complication outcomes; therefore, these data do not support its routine prophylactic use in primary TKA.

Salmonella spp. are major foodborne pathogens transmitted through contaminated poultry products. The emergence of antibiotic-resistant strains complicates treatment and increases the risk of multidrug-resistant (MDR). In Morocco, data on antimicrobial resistance (AMR) profiles in poultry-associated Salmonella remain limited. This study aimed to assess the prevalence and AMR patterns of Salmonella spp. isolated from poultry samples collected in Morocco in 2023. A total of 1339 poultry samples (ceca, turkey, and chicken meat) were collected using a representative stratified sampling approach from slaughterhouses, farms, and retail markets across the 10 regional directorates of Morocco. The isolation of Salmonella spp. was performed according to ISO 6579-1:2017, and identification was confirmed via matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Antimicrobial susceptibility to 15 antibiotics was evaluated using Sensititre EUVSEC3 plates. Minimum inhibitory concentrations (MICs) were interpreted according to epidemiological cutoff values established by the European Committee on Antimicrobial Susceptibility Testing. MDR was defined as resistance to at least one antimicrobial agent in three or more antibiotic classes. Salmonella spp. were detected in 155 out of the 1339 samples, with an overall prevalence of 11.6% and regional variation. The category-specific prevalence was 13.8% (48/348) for chicken meat, 12.3% (45/367) for turkey meat, and 10.0% (62/624) for cecal samples. Resistance to nalidixic acid (94.2%), ciprofloxacin (92.3%), tetracycline (63.9%), ampicillin (36.8%), trimethoprim (27.7%), chloramphenicol (16.1%), gentamicin (10.3%), cefotaxime (4.5%), amikacin (3.9%), and ceftazidime (0.6%) was detected, whereas resistance to meropenem was not detected. Overall, 69.7% of the isolates were classified as multidrug-resistant and were mainly resistant to quinolones, tetracyclines, and beta-lactams. These findings highlight the need for strengthened antimicrobial stewardship, improved surveillance, and stricter regulation of antibiotic use in poultry production to reduce public health risks.

AIMS: To reassess the contemporary role of ivabradine in heart failure with reduced ejection fraction and propose a precision-oriented framework for individualized heart rate management in the era of foundational guideline-directed medical therapy. METHODS AND RESULTS: Ivabradine selectively reduces sinus rate without direct negative inotropic effects, with established benefits in selected patients with heart failure with reduced ejection fraction and persistent sinus tachycardia. However, recent meta-analyses differ substantially in study populations, endpoint availability, and background therapy, limiting firm conclusions regarding the incremental effect of ivabradine on major clinical outcomes in the contemporary treatment era. This review integrates established and emerging evidence, with particular emphasis on the conceptual distinction between maladaptive and compensatory tachycardia, candidate individualized and dynamic heart-rate strategies, transmitral filling patterns, atrioventricular timing, and electrophysiological effects beyond the sinoatrial node. Evidence in acute heart failure, atrial fibrillation, and acute myocardial infarction is also considered. Ivabradine should complement rather than replace foundational guideline-directed medical therapy, while physiology-guided titration remains investigational. CONCLUSION: The contemporary role of ivabradine may extend beyond fixed heart rate thresholds toward individualized physiological optimization. The immediate objective of such an approach is to improve filling, hemodynamic tolerance, and treatment response rather than to assume a direct survival benefit. Whether physiology-guided ivabradine therapy improves heart failure hospitalization or survival requires prospective validation before such strategies can be incorporated into routine practice.

18F-fluorodeoxyglucose (18F-FDG) PET is used to diagnose cardiac sarcoidosis (CS) in patients with extracardiac sarcoidosis and suspected cardiac involvement or suspected isolated CS. Rigorous patient preparation suppresses physiological myocardial uptake. 18F-FDG PET is interpreted with myocardial perfusion imaging: abnormal uptake with normal perfusion indicates inflammation without fibrosis, uptake with a perfusion defect indicates inflammation with fibrosis, and a perfusion defect without uptake indicates fibrosis alone. Abnormal uptake, particularly with perfusion defects, predicts major adverse cardiac events, including death and ventricular arrhythmias. Serial 18F-FDG PET monitors response to immunosuppressive therapy and detects reactivation of myocardial inflammation.

This review evaluates the impact of Post-Acute Sequelae of SARS-CoV-2 on adults aged 25 to 55, focusing on the potential for accelerated biological aging and an increased incidence of acute cardiovascular events. By synthesizing evidence from 110 epidemiological and mechanistic studies, we examine the interplay between viral-induced immune dysregulation, endothelial injury, and systemic physiological decline in a demographic previously considered low-risk for severe outcomes. Our analysis indicates that chronic systemic inflammation, potentially maintained by persistent viral reservoirs in immune-privileged sites, may drive aging-associated molecular changes. While accelerated telomere attrition and altered DNA methylation patterns are reported, applying validated epigenetic clocks (e.g., Horvath's, PhenoAge) yields divergent results, ranging from no disparity to slight but significant epigenetic age acceleration. Alongside these evolving metrics, elevated neurofilament light chain and GDF-15 may indicate ongoing neuronal injury and cellular stress. Concurrently, the findings highlight an elevation in cardiovascular relative risks, where sustained endothelial dysfunction and microthrombi formation appear to contribute to a higher frequency of acute events, including myocardial infarction and ischemic stroke, within these younger cohorts. The review concludes that Post-Acute Sequelae of SARS-CoV-2 may represent an emerging driver of premature biological aging and heightened vascular vulnerability. We propose an exploratory clinical framework that prioritizes targeted, symptom-driven care pathways. While early pharmacological interventions remain strictly hypothesis-generating and confined to clinical trials to prevent iatrogenic harm, utilizing advanced biomarkers to evaluate high-risk phenotypes in symptomatic patients may guide future multidisciplinary research to mitigate the long-term societal burden of post-viral decline.

Malignant neurocardiogenic syncope (MNS) is defined as recurrent syncope with minimal prodromes associated with significant prolonged asystole during head-up tilt test (HUTT). Although cardioneuromodulation (CNM) is an emerging therapy for cardioinhibitory reflex syncope and other functional bradyarrhythmias and is increasingly considered an alternative to cardiac pacing in selected adult patients, evidence for its use in children remains limited. This study aims to describe the procedural characteristics and clinical outcomes of CNM in pediatric patients with MNS and to identify the clinical profile of those most likely to benefit from CNM. This is a prospective observational single-arm cohort. All pediatric patients with recurrent traumatic syncope and HUTT-documented asystole (≥ 15 seconds) undergoing CNM were enrolled. Baseline clinical features, HUTT findings, procedural data, acute endpoints, complications, and follow-up outcomes were collected. All patients underwent CNM using a right atrial-only approach, targeting right-sided ganglionated plexi using anatomical and electrogram guidance. Eight patients (50% female; mean age 13 ± 2.5 years) with a high burden of traumatic reflex syncope were enrolled in this study. All procedures were completed without major complications. After ablation, an implantable loop recorder (ILR) was inserted in all patients for continuous rhythm surveillance. During a short-term follow-up (6 ± 3 months), all patients experienced marked reduction in syncope burden with no further traumatic recurrences (from a mean of 2 episodes/month to 0 episodes at 6 ± 3 months); ILR monitoring showed no prolonged asystole. In this small pediatric cohort, CNM was safe, feasible, and associated with favorable short-term clinical and rhythm outcomes. Larger pediatric studies with standardized selection criteria and longer follow-up are needed to define efficacy and durability.

OBJECTIVE: Our objective was to develop age- and height-specific reference ranges for blood pressure, pulse pressure and mean arterial pressure in healthy boys and to compare these to measurements in patients with Klinefelter syndrome followed longitudinally through childhood and adolescence. DESIGN: Cohort study consisting of a population-based reference cohort including 1842 healthy non-obese boys aged 0-20 years and 67 patients with Klinefelter syndrome aged 7-20 years, followed at a single tertiary center. METHODS: Height, weight, and blood pressure were measured, and references were developed as a function of age, height, and their combined effect in healthy boys. In patients with Klinefelter syndrome standard deviation scores were calculated for systolic and diastolic blood pressure, pulse pressure and mean arterial pressure. These were adjusted for age and height independently, as well as combined age and height. A subgroup analysis in patients with Klinefelter syndrome assessed whether testosterone replacement therapy influenced blood pressure. RESULTS: Systolic and diastolic blood pressure increased with increasing age in healthy boys. Patients with Klinefelter syndrome had significantly lower systolic blood pressure compared to the healthy, non-obese reference population, with a mean standard deviation score of -0.65, -0.90, -0.91 when adjusted for age, height, and both, respectively. Diastolic blood pressure did not differ from controls. Pulse pressure showed a mean standard deviation score of -0.74, -0.99, and -0.94 when adjusting for age, height or both, respectively. Mean arterial pressure showed a mean standard deviation score of -0.27, -0.33, and -0.41 adjusted for age, height or both, respectively. Testosterone replacement therapy had no significant effect on blood pressure. CONCLUSIONS: Our study showed that patients with Klinefelter syndrome have lower systolic but similar diastolic blood pressure compared to our new blood pressure reference ranges. Pulse pressure and mean arterial pressure were both significantly lower after any adjustment compared to healthy controls.

Blood pressure is expressed as V (blood pressure) = I (circulating blood volume or cardiac output) × R (peripheral vascular resistance), based on Ohm's law (V (voltage) = I (current) × R (resistance)). Antihypertensive drugs that reduce either I or R are used. On the other hand, the electrical energy consumed per unit time is power (W), which is expressed as W = VI. If we consider the energy consumed by each organ to be W, and assume that an organ consumes a constant amount of functional bioenergy requirement (FBR), then V and I work in a complementary manner. It is conceivable that if a decrease in blood flow occurs first due to conditions such as arteriosclerosis or peripheral circulatory failure, peripheral blood pressure will rise compensatorily; conversely, if systemic blood pressure rises first, tissue blood flow will decrease compensatorily, potentially leading to chronic ischemia. In this medical hypothesis, I would like to consider a shift in perspective from V = IR to W = VI in blood pressure management-a field that has traditionally focused on peripheral vascular resistance (R)-by shifting the focus to blood pressure regulation aimed at maintaining FBR in tissues. Conventional blood pressure regulation is based on Ohm's law (V = IR), where antihypertensive therapy primarily targets cardiac output (I) or peripheral vascular resistance (R) to reduce blood pressure. We propose a complementary framework based on W = VI, in which blood pressure (V) and tissue perfusion (I) are regulated cooperatively to preserve the functional bioenergy requirement (FBR) of tissues. Reduced tissue perfusion may induce a compensatory blood pressure elevation, whereas primary blood pressure elevation may trigger autoregulatory responses that limit the pressure-driven increase in tissue blood flow, potentially resulting in chronic tissue ischemia. This paradigm highlights a shift from lowering visible blood pressure alone toward preserving the invisible FBR of tissues. This figure was created with the assistance of generative AI (GPT-5.6 Thinking) based on the content of this paper. The authors have verified the content.

Developmental dynamics involve the specification of diverse cell types and their spatial organization into multicellular niches1. Here we combine single-cell and spatial multiomics to define 21 distinct tissue niches in the developing heart, which we use to develop a context-aware, resolution-agnostic niche classification tool (TissueTypist). Applying high-resolution spatial profiling to the developing sinoatrial node, we resolve three pacemaker cell subtypes arrayed along a linear axis. First trimester subpopulations, such as pacemaker cells in the sinus horn and sinoatrial node head region, display neuroattractant programs and interact with parasympathetic neurons via interactions that include Eph-ephrin and semaphorin-plexin signalling. Temporal trajectories map the maturation of atrial and ventricular cardiomyocytes and uncover a lipid-metabolic switch and potential key regulators of cell-type identity. In the ventricle, we identify cellular and transcriptional gradients along both pseudotime and transmural axes, which provide molecular insights into myocardial compaction and maturation. Comparative profiling revealed that hearts with trisomy 21 are depleted in compact cardiomyocytes and exhibit increased apoptosis relative to euploid hearts. This finding was validated in isogenic-matched trisomy 21 and euploid cardiomyocytes derived from induced pluripotent stem cells. These early developmental perturbations may contribute to the increased risk of congenital heart disease associated with Down's syndrome. In summary, we present a spatially resolved framework of human cardiac development to enable systematic explorations of developmental niches in health and disease.

BACKGROUND: Chronic activation of the hypothalamic-pituitary-adrenal axis due to long-term stress, reflected by elevated hair cortisol concentration (HCC), has been associated with increased cardiovascular disease risk. However, whether prolonged cortisol exposure is linked to alterations in cardiac structure and function remains unclear. METHODS: In a population-based cohort of 3005 individuals aged 50-64 years in Sweden, HCC was measured and analysed in relation to 19 echocardiographic parameters reflecting cardiac morphology and function. Through linear regression models the association between HCC and echocardiographic parameters was analysed, adjusting for relevant confounders and complemented by sensitivity analyses to assess influence of extreme values and to evaluate potential non-linearity. RESULTS: No significant association between HCC and three broad principal component analysis-derived cardiac phenotypes was observed. Across 19 individual echocardiographic measures, effect estimates were generally small and CIs largely included the null. Left Atrial End-Systolic Volume Index (LAESVI) was the only measure showing a false discovery rate-adjusted significant association with HCC; however the magnitude of this association was modest, with β=0.178 SD per one-unit increase in log10-HCC, corresponding to approximately 0.734 mL/m² higher LAESVI across the IQR of HCC (~2.9% of the cohort median). CONCLUSIONS: Taken together, in this population-based study, these findings provide little evidence that HCC is associated with clinically meaningful differences in cardiac structure or function in generally healthy middle-aged adults.

BACKGROUND: Although the Revised Cardiac Risk Index (RCRI) is widely used to assess major adverse cardiac events (MACE) preoperatively, the impact of risk-factor duration and age stratification on its predictive performance after total knee arthroplasty (TKA) remains unclear. This study evaluated post-TKA MACE incidence and risk according to RCRI score, individual risk factors, their preoperative duration, and age strata. METHODS: This retrospective cohort study used a nationwide claims database, including primary TKA patients (2017 to 2021). The RCRI was modified for claims data by defining renal impairment as chronic kidney disease stage ≥ 3. Following propensity-score matching by RCRI scores (0, 1, ≥ 2), risk factors were categorized by preoperative duration: absent, ≤ one year, or greater than one year. The primary outcomes were 30-day, 90-day, and 1-year MACE. Adjusted hazard ratios (aHRs) were estimated using stratified Cox models. RESULTS: Among 72,672 matched patients, MACE incidence was 0.18, 0.40, and 1.43% at 30 days, 90 days, and one year, respectively. The MACE risk increased with the RCRI category; versus RCRI 0, RCRI 1 raised the postoperative 1-year risk (aHR 1.34, P < 0.001), whereas RCRI ≥ 2 roughly doubled the risk across all periods (aHR 1.86 to 2.15, all P-values ≤ 0.003). Moderate-to-severe renal impairment was the most consistent predictor (all P-values ≤ 0.001), especially when diagnosed ≤ one year preoperatively. Among RCRI ≥ 2 patients, age ≥ 75 years increased 30-day MACE risk (aHR 2.27, P = 0.004), whereas risk in those aged less than 75 years became significant at 90 days (P < 0.001). CONCLUSION: The RCRI provides predictive validity for post-TKA MACE. Beyond static scores, risk-factor duration and age stratification offer incremental prognostic value. Patients who had recent moderate-to-severe renal impairment and older age (≥ 75 years) combined with RCRI ≥ 2 warrant closer perioperative monitoring.

Acute myocarditis (AM) in children and adolescents remains a diagnostic and therapeutic challenge because of its heterogeneous presentation, overlap with dilated cardiomyopathy, and potential for fulminant deterioration, with approximately 5.9% risk of early mortality. We performed a narrative review integrating contemporary guidelines, consensus documents, and weighted analyses from systematically selected large pediatric cohorts to summarize current evidence on epidemiology, diagnosis, risk stratification, and treatment. Pediatric AM shows a male predominance and a bimodal age distribution. Early recognition is often difficult because initial manifestations may be non-specific and the differential diagnosis varies across age groups. Younger children more often present with dilated phenotypes and prominent gastrointestinal symptoms, frequently reflecting low cardiac output and systemic congestion, whereas adolescents may present with an uncomplicated phenotype characterized by chest pain and regional wall motion abnormalities. Severe disease remains a relevant burden, with fulminant myocarditis accounting for approximately one quarter of cases and carrying markedly higher mortality. Initial evaluation should therefore focus on early risk stratification, integrating clinical severity, biomarkers, electrocardiogram, echocardiography, and etiological testing. This approach may help identify high-risk viral phenotypes associated with enteroviruses or parvovirus B19, while also recognizing systemic inflammatory syndromes such as multisystem inflammatory syndrome in children, which may mimic AM but usually responds to timely immunomodulatory treatment. We propose a practical risk-based strategy that classifies patients into low-, intermediate-, and high-risk groups to guide monitoring, referral, cardiac magnetic resonance, endomyocardial biopsy, and therapy. High-risk patients require early referral to tertiary centers with pediatric intensive care, cardiac surgery, and temporary mechanical circulatory support availability. Treatment should be individualized according to risk, ranging from supportive care to mechanical circulatory support, transplant evaluation, and selected immunomodulation. Prospective registries and randomized trials are needed to validate risk-based pathways and define evidence-based therapies.

Atrial fibrillation (AF) affects a greater proportion of cardiac surgery patients than previously appreciated, with pre-operative AF prevalence in Australia and New Zealand recently documented at 14.99%, substantially higher than prior international estimates of 5% to 11%. Both the European Society of Cardiology/European Association of Cardio-Thoracic Surgery (ESC/EACTS) and the Society of Thoracic Surgeons (STS) have now upgraded left atrial appendage occlusion (LAAO) to a Class Ia recommendation for all AF patients undergoing cardiac surgery, based principally on the Left Atrial Appendage Occlusion Study III (LAAOS III); a multicentre randomized trial demonstrating a 33% relative risk reduction in ischemic stroke or systemic embolism with concomitant LAAO (risk ratio 0.66; 95% confidence interval 0.52 to 0.84). Despite these strong guideline endorsements, real-world implementation is critically deficient: in Australia and New Zealand, 77.63% of AF patients undergoing cardiac surgery received no LAA treatment. Critically, ∼21% of all strokes in LAAOS III were fatal, signalling that the stroke reduction LAAO produced, likely prevented fatal stroke. This hidden survival benefit is implied but not explored in the existing data, awaiting only a mortality-powered trial for formal confirmation. The literature to date actively examines stroke prevention and all-cause mortality, yet LAAO fatal stroke prevention is an unreported, and important independent outcome. This review synthesizes the epidemiology, pathophysiology, and trial evidence for LAAO,and appraises the guideline landscape and global implementation gap. In conclusion, LAAO does not merely prevent neurological events; it prevents fatalstrokes.

Alternative splicing is a fundamental post-transcriptional mechanism that contributes to cardiovascular development, homeostasis, and disease. Serine/arginine-rich splicing factors (SRSFs), a conserved family of 12 RNA-binding proteins, regulate splice-site selection and other RNA-processing events through their RNA-recognition motifs and arginine/serine-rich domains. Growing evidence implicates SRSF dysregulation in congenital heart disease, cardiac hypertrophy and heart failure, ischemic injury, vascular remodeling, inflammatory myocardial injury, and cardiovascular aging. In this review, we summarize the structural characteristics, cardiovascular expression patterns, and physiological functions of SRSFs, and discuss their context-dependent roles across cardiovascular diseases. We further examine regulatory mechanisms involving phosphorylation, target-specific RNA processing, interactions with other cardiac splicing regulators, and non-coding RNAs. Finally, we evaluate emerging small-molecule and gene- or RNA-based strategies targeting SRSFs and highlight major barriers to translation, including target specificity, delivery, causal validation, and safety. These advances provide a framework for defining disease-relevant SRSF networks and prioritizing mechanistically supported therapeutic targets in cardiovascular disease.

INTRODUCTION: Ultrathin-strut drug-eluting stents (DES) have been developed to enhance vascular healing and reduce restenosis following percutaneous coronary intervention (PCI). Indigenous biodegradable-polymer ultrathin-strut DES are increasingly used in high-burden settings; however, comparative evidence against internationally established thin-strut DES remains limited. METHODS: This systematic review of randomized controlled trials was conducted according to PRISMA 2020 guidelines. PubMed, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from inception to December 2025. Trials comparing indigenous ultrathin-strut DES with internationally manufactured thin-strut DES in adult PCI populations were included. Primary outcomes were major adverse cardiac events/trial-defined composite endpoints. Secondary outcomes included myocardial infarction, target lesion and vessel revascularization, stent thrombosis, cardiac death, and all-cause mortality. Risk of bias was assessed using the Cochrane RoB-2 tool, and a narrative synthesis was performed. RESULTS: Four randomized trials including 2,793 patients were analyzed. Indigenous stents demonstrated comparable rates of composite endpoints, myocardial infarction, repeat revascularization, and stent thrombosis across studies, with no consistent differences between groups. CONCLUSION: The available RCT evidence shows no consistent signal of superiority or inferiority between indigenous and international thin-strut DES. However, heterogeneity and limited trial numbers warrant larger studies with long-term follow-up and real-world materiovigilance.

Summary: Background: Cardiovascular physiology exhibits circadian rhythms, including a morning surge in platelet reactivity and cardiovascular events. Aligning the timing of antiplatelet therapy with these rhythms may be a simple, cost-effective approach to improve clinical efficacy. This systematic review evaluates the diurnal variability in platelet reactivity among individuals receiving aspirin, clopidogrel, ticagrelor, and prasugrel and explores the potential for timed administration to optimise platelet inhibition and other surrogate cardiovascular markers. Patients and methods: PubMed, Embase, Cochrane Central Register of Controlled Trials, and trial registries (e.g., ClinicalTrials.gov) were searched from 1980 to August 2025 for randomised controlled trials and observational studies in adults investigating morning versus evening dosing or diurnal efficacy. Results: Of 2,340 records, 25 studies were included (17 on aspirin, seven on clopidogrel, one on ticagrelor, and three overlapping with prasugrel). For aspirin, the data showed a tendency that evening administration achieved greater reductions in morning Cyclooxygenase-1 (COX-1)-dependent platelet reactivity in healthy volunteers and cardiovascular disease patients, although there were mixed effects on ambulatory blood pressure. Clopidogrel exhibited diurnal variability, with peaks in Adenosine Diphosphate (ADP)-induced aggregation occurring in the morning, while prasugrel provided more consistent inhibition than clopidogrel or ticagrelor. No studies directly compared evening versus morning dosing for P2Y12-Inhibitors, and clinical outcomes such as major adverse cardiac events were only assessed in one included study. Conclusions: While evening aspirin may enhance chronopharmacological efficacy, the available evidence is limited due to heterogeneity and variable quality. The limited number of studies on agents beyond aspirin highlights a critical research gap, with robust Randomised Controlled Trials needed to evaluate clinical benefits and inform chronotherapeutic strategies.

The concept of left ventricular unloading is deeply embedded in the core principles of cardiac physiology, with ventricular mechanics and energetics serving as its foundation. Modern mechanical circulatory support devices vary in their loading effects. Some actively unload the LV, whereas others primarily support systemic perfusion. Notably, extracorporeal life support systems can paradoxically elevate left ventricular afterload, thereby necessitating supplementary unloading strategies. The recent DanGer-Shock trial revealed a mortality benefit associated with microaxial flow pump support in selected patients experiencing acute myocardial infarction complicated by cardiogenic shock. This finding supports the therapeutic potential of such an approach in selected patients, while highlighting the importance of considering device-specific complications and patient selection. We synthesize the hemodynamic principles and varying unloading efficiencies of different device strategies, proposing a time-dependent repair program: initial acute metabolic cytoprotection via Hippo-YAP, followed by immune reprogramming toward a reparative phenotype, and culminating in chronic structural reverse remodeling. Collectively, these insights offer a mechanism-guided framework for the application of left ventricular unloading, while highlighting emerging opportunities for biomarker-guided monitoring, device-drug synergism, and metabolic phenotyping to refine patient selection, optimize timing, and ultimately translate acute mechanical unloading from a hemodynamic support tool into a precision biological therapy.

Heart failure with preserved ejection fraction (HFpEF) presents a major clinical and therapeutic challenge owing to its complex pathophysiology and pronounced clinical heterogeneity. While traditional empirical strategies targeting comorbidities offered limited success, recent advances in molecular, hemodynamic, and autonomic profiling have catalyzed a fundamental shift toward phenotype-guided, personalized management. Clinical trial insights underscore that precise patient selection is paramount for therapeutic efficacy; for example, interatrial shunt interventions demonstrate clinical benefits primarily in patients without elevated exercise pulmonary vascular resistance, whereas improper application risks right ventricular decompensation. Simultaneously, novel device-based modalities, including transcutaneous vagal nerve stimulation, cardiac contractility modulation, splanchnic nerve ablation, and adjustable interatrial shunts, are emerging as promising avenues to directly address underlying mechanisms such as systemic inflammation, impaired calcium handling, and volume redistribution. Moving forward, the management paradigm of HFpEF will increasingly shift from monotherapy to synergistic multimodal approaches. Combining established foundational pharmacotherapies, such as sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, with continuous pulmonary artery pressure monitoring and targeted interventional devices holds immense potential to establish closed-loop, individualized treatment strategies. In this review, we synthesize current clinical evidence, highlight key anatomical and hemodynamic considerations, evaluate emerging device platforms, and discuss future strategic perspectives aimed at optimizing precision medicine for patients with HFpEF.

BACKGROUND: Five-year survival after continuous-flow left ventricular assist device (LVAD) implantation has improved substantially, resulting in a growing population of ultra-long-term LVAD patients, defined as five years and longer survival on LVAD. Remarkably, determinants of mortality beyond the five-year landmark remain poorly characterized, and ultra-long-term outcomes are rarely investigated. METHODS: We performed a large bicenter observational landmark analysis including patients who survived at least five years on LVAD support. Implanted devices included HeartMate II, HeartWare (HVAD), and HeartMate 3. Clinical, laboratory, echocardiographic, and hemodynamic parameters at the five-year time point were evaluated to represent predictors of mortality. Cox proportional hazards regression was used to identify independent predictors of mortality from the five-year landmark. Model discrimination was assessed using Harrell's C-index and time-dependent area under the curve (AUC). RESULTS: Among 201 patients surviving ≥5 years on LVAD support, 189 had complete data for multivariable analysis. Median age at implantation was 59.9 years (IQR 52.6-65.8), and 86% were male. During post-landmark follow-up, 77 deaths occurred. Age (HR 1.04 per year, 95% CI 1.02-1.07; p=0.002), hemoglobin (HR 0.84 per mmol/L, 95% CI 0.73-0.97; p=0.016), MELD-XI score (HR 1.10 per unit, 95% CI 1.06-1.14; p<0.001), and ICD presence (HR 1.60, 95% CI 1.00-2.54; p=0.049) were independently associated with mortality beyond the five-year landmark. The model showed moderate discrimination (Harrell's C-index approximately 0.74). LVAD model was not independently associated with post-landmark mortality (likelihood-ratio p=0.63). CONCLUSIONS: Among patients who have already survived five years on continuous-flow LVAD support, subsequent mortality was associated with routinely available markers of physiological and end-organ reserve. These findings characterize risk specifically in prevalent long-term LVAD recipients and warrant external validation.

BACKGROUND: The role of guideline-directed medical therapy for heart failure (HF) is unclear in transthyretin amyloid cardiomyopathy (ATTR-CM). Dapagliflozin has demonstrated beneficial effects across HF phenotypes, and retrospective studies suggest potential benefit in ATTR-CM; however, prospective data are lacking. This pilot study evaluated the effect and tolerability of dapagliflozin in patients with ATTR-CM to inform the design of a larger randomized trial. METHODS: Participants were followed for 30 weeks over three study periods: 8 weeks baseline without study medication, 12 weeks intervention with dapagliflozin 10 mg once daily, and 10 weeks withdrawal without study medication. The study was open-label and nonrandomized. Vital signs and NT-proBNP were assessed every second week, while Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) and 6-minute walking test (6MWT) were assessed every 4 weeks. Results were analyzed using linear mixed-effects models. RESULTS: Seven of ten enrolled patients completed the trial. One participant discontinued because of genitourinary adverse effects, and two withdrew for reasons unrelated to the intervention. The estimated intervention-versus-baseline difference was -142 pg/mL (95% CI -324-41) for NT-proBNP, 24.3 m (95% CI -2.8 to 51.5) for 6MWT distance, and 0.4 points (95% CI -4.0 to 4.8) for KCCQ-TSS. Sitting SBP was 8.8 mmHg lower during intervention than during baseline (95% CI -13.2 to -4.4). No increase in hypotensive symptoms or cardiovascular adverse events was detected. CONCLUSIONS: Dapagliflozin was generally well tolerated in this pilot study of patients with ATTR-CM. The estimated differences in NT-proBNP, 6MWT distance, and KCCQ-TSS were imprecise and did not provide conclusive evidence of treatment effects. SBP was lower during treatment, without a detected increase in hypotensive symptoms. These exploratory findings support further evaluation in an adequately powered randomized trial. TRIAL REGISTRATION: This study was registered with clinical trial number EudraCT no 2021-003674-32.

OBJECTIVE: To compare composite inflammatory indices, the Atherogenic Index of Plasma (AIP), and angiographic findings between patients with acute myocardial infarction (MI) aged <55 years and those aged 55-65 years. METHOD: Patients with acute coronary syndrome were retrospectively screened (n=205). Forty patients who died during hospitalization were excluded post hoc, along with 10 patients with normal coronary arteries and 10 with noncritical stenosis not requiring revascularization, leaving 145 patients: Group 1 (<55 years, n=72) and Group 2 (55-65 years, n=73). The Systemic Inflammatory Response Index (SIRI), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), AIP, and C-reactive protein were compared between groups, together with lipid, angiographic, and left ventricular ejection fraction (LVEF) parameters. RESULTS: Younger patients had significantly higher SIRI (1.63 vs. 1.11, P < 0.001), NLR (2.65 vs. 2.26, P = 0.004), MLR (0.261 vs. 0.200, P < 0.001), and AIP (0.440 vs. 0.298, P = 0.039). Because SIRI and MLR were collinear, each index was modeled separately with AIP and ST-segment elevation myocardial infarction (STEMI)/non-ST-segment elevation myocardial infarction (NSTEMI) status; when modeled separately, each was independently associated with younger age after adjustment for MI type (all P ≤ 0.009). LVEF was better preserved (P < 0.001), and among patients with a single identifiable culprit vessel, the right coronary artery was more frequently implicated in younger patients (47.3% vs. 22.2%, P = 0.006). CONCLUSION: Young patients with MI and obstructive coronary disease showed higher inflammatory indices and a more atherogenic lipid profile than middle-aged patients. SIRI, NLR, MLR, and AIP were each independently associated with younger age in the primary multivariable models; however, across exploratory sensitivity analyses using stricter age thresholds, a continuous age model, and a death-inclusive cohort, complete blood count (CBC)-derived inflammatory indices-particularly SIRI and MLR-showed relatively consistent age-associated differences, whereas the association with AIP was more dependent on how age was defined and modeled. These findings support further investigation of CBC-derived inflammatory indices, particularly SIRI and MLR, as candidate markers of age-associated inflammatory and lipid differences among MI

OBJECTIVE: To evaluate the association between tricuspid regurgitation (TR) severity measured near intensive care unit (ICU) admission and 365-day all-cause mortality in echocardiography-selected adult ICU patients. METHODS: This secondary analysis linked Medical Information Mart for Intensive Care-IV (MIMIC-IV) version 3.1 with MIMIC-IV-echocardiogram. Adults with transthoracic echocardiography from 24 hours before to 72 hours after ICU admission and documented TR severity were included. None/trivial and mild TR were combined as the low-grade reference group; moderate and severe TR were compared with this group. Multiple Cox regression analyses evaluated 28-, 90-, and 365-day mortality. Sodium-adjusted and biomarker-availability analyses evaluated additional laboratory information. RESULTS: The cohort included 16 991 patients: 12 417 (73.1%) had low-grade, 3467 (20.4%) moderate, and 1107 (6.5%) severe TR. Crude mortality increased across TR severity at 28 days (15.1%, 24.5%, and 32.7%), 90 days (20.3%, 32.5%, and 42.7%), and 365 days (27.2%, 42.9%, and 53.4%). Compared with low-grade TR, 365-day multiple-adjusted estimates were hazard ratio (HR) = 1.32, P < .001, 95% CI: 1.24-1.41 for moderate TR and HR = 1.67, P < .001, 95% CI: 1.52-1.83 for severe TR; 28- and 90-day estimates were directionally consistent, and sodium-adjusted estimates were similar. CONCLUSION: Moderate and severe TR on early echocardiography were associated with higher 1-year mortality in echocardiography-selected adult ICU patients. This observational association remained consistent after sodium adjustment but should not be interpreted as a treatment effect.

BACKGROUND: The association between transient ischemic attack (TIA) and stroke is well-established but the association with coronary heart disease (CHD) is incompletely characterized. Studying the association between TIA and CHD can also help improve risk stratification and personalized treatment strategies for patients with TIA. We undertook this analysis to determine the incidence, timing and long-term trends of post-TIA CHD and congestive heart failure (CHF) risk. METHODS: Prospective longitudinal cohort study design within the Framingham Heart Study. TIA- and CHD- free participants were matched on age and sex (ratio 3:1) to CHD-free participants with first incident TIA. The main outcomes were: 10-year risk of CHD, major CHD, CHF, and stroke comparing TIA cases with matched controls; and time trends of cardiac outcomes and stroke risk assessed in 3 epochs: 1948-1985, 1986-1999 and 2000-2019. RESULTS: 286 participants with TIA (116 (41%) men, mean age 73.1±10.8 years) were matched to 858 controls without TIA. 54 (19%) participants had CHD, 35 (12%) major CHD, 37 (13%) CHF, 83 (29%) stroke. Participants with TIA had significantly higher risk of CHD (adjusted Hazard Ratio 1.55, 95% CI (1.06-2.28 p=0.03) and stroke (adjusted HR 4.01 (2.73-5.87), p<0.0001), but not of major CHD or CHF. 35 strokes (42%) occurred within 3 months; 44 (81.5%) CHD events occurred >12 months. CHD (HR 0.64, 95% CI (0.52-0.80), p<0.0001) incidence showed a significant decline over time between 1948-2019 driven by controls; it did not decline significantly among TIA cases (HR 0.80 (0.56-1.15), p=0.22. CONCLUSIONS: We found that among patients with TIA CHD events are concentrated beyond the first year, a temporal pattern distinct from the early clustering of post-TIA stroke risk and not well captured in current post-TIA management frameworks. These findings support the need for sustained cardiovascular prevention strategies after TIA that extend beyond current pathways focused on short-term stroke risk reduction.

PURPOSE: Echocardiographic studies have shown that patients with mitral valve prolapse (MVP) exhibit altered regional contraction patterns. With cardiovascular magnetic resonance (CMR) becoming increasingly important in the evaluation of global and regional cardiac function, we aimed to quantify the regional contraction patterns of patients with MVP using CMR feature tracking (FT) strain analysis in comparison to a control group. METHODS: Of all patients who underwent CMR scans from 2013 to 2022 at our institution, 132 patients with MVP were identified and compared to 50 controls without any cardiac condition. CMR scans were performed on 1.5-T and 3-T scanners, and CMR-FT strain analysis was performed on cine images using MEDIS QStrain 4.1. The primary endpoints were regional peak left ventricular (LV) longitudinal strain values. Secondary endpoints included LV global circumferential strain (GCS) and global longitudinal strain (GLS) and left atrial (LA) reservoir strain and right ventricular (RV) free wall longitudinal strain. Differences between groups were assessed using linear regression models, adjusting for age and sex. RESULTS: Patients with MVP showed worse regional peak longitudinal strain compared to controls in the basal and part of the medial LV segments, especially in segments S1, S4, S6, S7, and S12. In contrast, the apical segments S13, S14, S15, and S16 showed better strain values. Additionally, LA reservoir strain was reduced in MVP patients. LV GCS, LV GLS, and RV free wall longitudinal strain were similar between both groups. CONCLUSION: While patients with MVP showed preserved LV GCS and GLS compared to controls, LV regional longitudinal strain analysis showed impaired strain in the basal segments and increased strain in the apical segments.

BACKGROUND: Medication nonadherence after percutaneous coronary intervention (PCI) remains a major barrier to secondary prevention. Prior SMS text messaging interventions have shown inconsistent results, often limited to reminders without addressing behavioral or psychological determinants. OBJECTIVE: This study aimed to evaluate the effectiveness of a theory-informed, WeChat-based messaging intervention for improving medication adherence and patient-reported outcomes after PCI. METHODS: A nonrandomized quasi-experimental parallel-group study was conducted from July 2022 to March 2023 at a tertiary hospital in Hangzhou, China. Patients were allocated by ward admission to the intervention or control group. The intervention comprised 12-week WeChat-based medication reminders and theory-informed messages mapped to capability, opportunity, and motivation-behavior model domains and behavior change techniques. The primary outcome was medication adherence measured using the 8-item Morisky Medication Adherence Scale (MMAS-8); secondary outcomes were medication beliefs, self-efficacy, and disease-specific health status measured using the Beliefs About Medicines Questionnaire (BMQ)-Specific, Self-Efficacy for Appropriate Medication Use Scale, and Seattle Angina Questionnaire (SAQ), respectively. Outcomes were assessed at baseline and 12 weeks by blinded assessors and analyzed using baseline-adjusted analysis of covariance based on the observed outcome data for all 92 participants. Sensitivity analyses included a per-protocol analysis restricted to the 87 participants who completed the full assigned care protocol and a difference-in-differences analysis comparing changes from baseline to 12 weeks between groups. RESULTS: Of 180 patients screened, 92 (51.1%) were enrolled, of whom all completed the 12-week outcome assessment and 87 (94.6%) completed the full assigned care protocol. At 12 weeks, medication adherence was higher in the intervention group than in the control group (adjusted mean MMAS-8 score 7.40, SE 0.05 vs 6.22, SE 0.10; adjusted mean difference 1.18, 95% CI 0.96-1.40; P<.001). Secondary outcomes generally favored the intervention, including the BMQ necessity (adjusted mean difference 1.62, 95% CI 1.06-2.17) and concerns (adjusted mean difference -3.25, 95% CI -3.87 to -2.63) subscales, medication self-efficacy (adjusted mean difference 4.04, 95% CI 3.

BACKGROUND: Atrial fibrillation (AF) prevalence has risen alongside an aging US population and wider adoption of contemporary therapies, yet population-level changes in mechanisms of death among people with AF remain incompletely characterized. We used National Death Certificate Trends in AF Mortality data to assess 25-year trends in AF-related mortality and the contribution of heart failure (HF), stroke, myocardial infarction (MI), and dementia. METHODS: We conducted a retrospective analysis of CDC WONDER records for US decedents aged ≥ 35 years with AF listed as a contributing cause of death from 1999 to 2023, coinciding with the implementation of ICD-10 coding in the CDC database. We quantified all-cause and cause-specific mortality rates per 100 000 and stratified trends by age, sex, and race. The analytic cohort included decedents with AF and at least one of four cardiovascular conditions (stroke, dementia, HF, or MI) listed as a primary or contributing cause of death. Confidence intervals were obtained from CDC WONDER outputs or calculated per CDC guidance. RESULTS: Among 3 273 015 decedents with AF noted on the death certificate, 461 321 had HF, dementia, stroke, or MI listed as a contributing cause. HF emerged as the leading cause/contributor with a steep rise beginning in approximately 2008. Stroke rates were stable or declining, MI-related mortality remained low and stable, while dementia, particularly stroke-free dementia, increased significantly in adults ≥ 85 (outpacing stroke among the oldest White decedents since early 2000s). Non-White groups exhibited higher stroke and HF mortality trends; women ≥ 85 had higher stroke-related mortality than men. CONCLUSIONS: Over 25 years, AF-associated mortality patterns shifted toward HF and stroke-free dementia while ischemic stroke and MI declined or stabilized. Findings highlight the need to expand AF care beyond stroke prevention to prioritize HF prevention/management, cognitive health, equitable AF-care pathways to ensure broad access to therapies, and additional studies of targeted interventions to mitigate disease risks.

OBJECTIVE: Young patients with myocardial infarction (MI) remain at risk for recurrent cardiovascular events despite favorable short-term outcomes. The prognostic significance of the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (non-HDL-C/HDL-C) ratio in this population remains insufficiently studied. We aimed to evaluate its association with 1-year major adverse cardiac and cerebrovascular events (MACCE). METHOD: This retrospective, single-center study included 856 consecutive patients aged ≤50 years who were hospitalized with acute MI between January 2022 and January 2025, including 302 (35.3%) with STEMI and 554 (64.7%) with NSTEMI. The primary outcome was 1-year MACCE, defined as a composite of all-cause mortality, ischemic stroke, recurrent MI, and unplanned repeat coronary revascularization. Patients were categorized into low- and high-ratio groups using a receiver operating characteristic (ROC)-derived cutoff based on the Youden index. Associations were assessed using multivariable Cox proportional hazards models. RESULTS: During follow-up, 129 patients (15.0%) experienced MACCE. The optimal non-HDL-C/HDL-C cutoff was 4.43. The ratio was independently associated with 1-year MACCE (HR=1.568, 95% CI=1.463-1.681; P < 0.001), with consistent effects across the STEMI and NSTEMI subgroups (p for interaction=0.545). The non-HDL-C/HDL-C ratio showed the highest discriminatory performance among the lipid parameters (AUC=0.864), outperforming LDL-C, non-HDL-C, and the atherogenic index of plasma (DeLong P < 0.001). CONCLUSION: In this retrospective observational cohort, a higher non-HDL-C/HDL-C ratio was independently associated with an increased risk of 1-year MACCE in young patients with MI. Prospective multicenter studies are warranted to confirm these findings.

Heat extremes significantly increase morbidity and mortality, particularly among older adults and people with cardiovascular disease (CVD). The year 2024 was the warmest year on record and the first calendar year in which the annual global mean temperature exceeded 1.5°C above pre-industrial levels-exposing people with CVD to a record number of extreme heat days. With the frequency and intensity of heat extremes expected to rise, the health risks for people with CVD will continue to escalate. There is an urgent need to provide scientific evidence to advise patients and healthcare professionals to manage cardiovascular health under these circumstances. This statement builds on a prior European Society of Cardiology document that explored the pathophysiological mechanisms underlying increased risk of cardiovascular events during heat extremes. Here, evidence informed advice guided by experts in thermal physiology and CVD is provided for clinicians and healthcare professionals to help advise their patients and reduce the negative impacts of heat on CVD health. The advice, while novel, relates to best practice for multidisciplinary care before, during, and after heat extremes, ensuring a proactive and comprehensive approach to patient safety. By integrating current evidence with practical strategies, this statement aims to bridge the evidence-to-practice gap and enhance preparedness for the increasing burden of climate-change driven health risks.

BACKGROUND: Despite advances in pharmacologic and device-based treatments, heart failure remains a leading cause of morbidity and mortality in adults. This results in substantial medical costs and significant patient suffering, underscoring the need for complementary interventions that can improve symptom management and well-being beyond conventional treatment. OBJECTIVES: To evaluate the effects of Chan-Chuang Qigong on exercise capacity, quality of life, fatigue, and cardiac function in patients with heart failure. METHODS: This randomized controlled trial recruited 72 patients and randomly assigned them to the qigong group, which received regular care and practiced Chan-Chuang Qigong for 12 weeks, or the control group, which received only regular care. Outcomes were measured using the 6-minute walking test, the Minnesota Living with Heart Failure Questionnaire, the Piper Fatigue Scale, left ventricular ejection fraction, and N-terminal prohormone B-type natriuretic peptide. Data were collected at baseline before the intervention and at Weeks 4, 8, and/or 12 during the intervention. RESULTS: The qigong group demonstrated significant improvements in 6-minute walking test, Minnesota Living with Heart Failure Questionnaire, and Piper Fatigue Scale compared with the control group and baseline at Weeks 4, 8, and 12 (P < .05), but not in left ventricular ejection fraction and N-terminal prohormone B-type natriuretic peptide (P > .05). CONCLUSIONS: Chan-Chuang Qigong effectively improved exercise capacity, quality of life, and fatigue in patients with heart failure. The lack of notable improvement in cardiac function may reflect the effects of ongoing regular medical treatments. Future research should extend the exercise period to detect potential changes in key cardiac metrics and reduce measurement variability.

Contrast-associated acute kidney injury (CA-AKI) is a serious complication associated with increased morbidity and mortality in patients with acute coronary syndrome (ACS) undergoing coronary angiography. The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel biomarker reflecting inflammatory and nutritional status. This retrospective study evaluated the prognostic value of the CALLY index calculated at hospital admission for predicting CA-AKI in 1516 patients with ACS. CA-AKI developed in 267 patients (17.6%). Patients who developed CA-AKI had significantly lower CALLY index values (0.35 ± 0.16 vs 0.84 ± 0.30; P < .001). In separate multivariable logistic regression analyses adjusted for baseline clinical and procedural confounders, the CALLY index emerged as an independent predictor of CA-AKI (Odds ratio [OR] 0.592 per 0.1-unit increase; 95% CI 0.525-0.668; P < .001). Receiver operating characteristic curve analysis demonstrated good discriminatory capacity for the CALLY index (Area Under the Curve [AUC] = 0.822), significantly outperforming conventional clinical scores and other inflammatory indices (DeLong test P < .001). Furthermore, adding the CALLY index to the Mehran risk score significantly improved reclassification metrics (Net Reclassification Improvement [NRI] = 14.2%, Integrated Discrimination Improvement [IDI] = 0.048; P < .001). The CALLY index serves as a simple, practical, and effective score for early CA-AKI risk stratification in ACS.

Dual antiplatelet therapy (DAPT) with low-dose prasugrel (3.75 mg daily) is widely implemented after percutaneous coronary intervention (PCI) in Japan. However, the efficacy compared with clopidogrel-based DAPT has not been fully examined in large-scale research. STOPDAPT-2 Total Cohort enrolled 5,997 patients who underwent PCI without major in-hospital complications. Among them, 2,547 patients received prasugrel-based DAPT and 3,402 patients received clopidogrel-based DAPT at discharge within 30 days after index PCI. After propensity score matching, 2,163 patients in each group were compared with respect to 30-day clinical outcomes. The primary outcome was a composite of cardiovascular events (cardiovascular death, myocardial infarction, stent thrombosis, or any stroke) and bleeding events (Thrombolysis in Myocardial Infarction [TIMI] major or minor). The two major secondary outcomes were these cardiovascular composite events and bleeding events. In the landmark analysis, there was no significant difference in the cumulative incidence of the primary outcome between the prasugrel group and the clopidogrel group at 30 days beyond hospital discharge (0.34% and 0.29%, HR 1.17, 95% CI 0.39-3.48, P=0.78). Similarly, no significant differences were observed in cardiovascular events (0.19% and 0.14%, HR 1.33, 95% CI 0.30-5.96, P=0.71) or bleeding events (0.14% and 0.15%, HR 1.00, 95% CI 0.20-4.97, P=0.99). There was also no significant difference in any clinical outcomes for 30-day incidence from index PCI. In conclusion, no significant differences were detected in short-term cardiovascular or bleeding outcomes between low-dose prasugrel-based and clopidogrel-based DAPT in patients after PCI without major in-hospital complications.

OBJECTIVE: Spontaneous coronary artery dissection (SCAD) is an uncommon but important cause of acute coronary syndrome (ACS) and sudden cardiac death, particularly in women aged 50 years or younger, including those without typical atherosclerotic coronary lesions. This study aimed to evaluate the clinical presentation, angiographic features, management strategies, and outcomes of patients with SCAD. METHOD: This retrospective, single-center study included female patients aged 50 years or younger who underwent coronary angiography for ACS between January 2019 and January 2025. Patients presenting with chest pain, ST-T segment changes, and/or elevated high-sensitivity cardiac troponin levels were evaluated. The diagnosis of SCAD was established according to angiographic criteria and categorized using the Yip-Saw classification system. RESULTS: Among 352 women screened, 40 patients were diagnosed with SCAD, including 18 with ST-segment elevation myocardial infarction and 22 with non-ST-segment elevation myocardial infarction. According to the Yip-Saw classification, Type 3 SCAD was the most frequently observed angiographic pattern. The left anterior descending artery was the most commonly involved vessel. Most patients (n=35) underwent percutaneous coronary intervention, whereas 3 patients were managed conservatively and 2 underwent coronary artery bypass grafting. During follow-up, repeat revascularization was required in only one patient. Two patients died: one from cardiogenic shock during the index event and the other from complications of heart failure. CONCLUSION: SCAD is an important but underdiagnosed cause of ACS in young women. The mortality rate in the study population was 5%. These findings provide real-world observational data and should be confirmed in larger, multicenter, prospective studies.

BACKGROUND: Incidence and recurrence of atrial fibrillation (AF) are associated with several lifestyle risk factors. Lifestyle and risk factor modification (LRFM) clinics could have a role in comprehensively addressing AF from a holistic, patient-centered approach to improve clinical outcomes. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials evaluating the role of LRFM clinics compared with usual care in patients with AF. The primary end point was atrial arrhythmia recurrence. Secondary end points were AF and heart failure-related hospitalization, cardiovascular death, stroke or transient ischemic attack, and quality-of-life. RESULTS: Eleven randomized controlled trials with a total of 3364 patients were included (5 randomized controlled trials performed in the context of AF ablation). Mean age was 58 to 73 years, 30% were female, and 18% had persistent AF. Duration of follow-up ranged from 3 to 24 months. LRFM clinics significantly reduced the primary end point of arrhythmia recurrence compared with usual care after catheter ablation (odds ratio, 0.34 [95% CI, 0.23-0.51]; P<0.001, I2=0%). LRFM clinics also reduced AF-related hospitalization (odds ratio, 0.70 [95% CI, 0.51-0.98]; P=0.04, I2=21%) and improved quality-of-life (mean improvement on Short Form 36 Questionnaire, 8.90 [95% CI, 6.91-10.90]; P<0.001). There was no detected difference between LRFM clinics and usual care for heart failure-related hospitalization (P=0.16), cardiovascular deaths (P=0.79), or stroke/transient ischemic attack (P=0.83). CONCLUSIONS: In this meta-analysis of randomized controlled trials, LRFM clinics reduced AF recurrence after ablation, reduced AF-related hospitalization, and improved quality of life. This study supports a comprehensive multidisciplinary lifestyle risk modification model of care to improve clinical outcomes in patients with AF.

ObjectiveThe main objective of this study was to evaluate the association between eating practices and nutritional status, clinical outcome, intradialytic hypotension, adequate dialysis, and mental health among adults undergoing hemodialysis at An-Najah National University Hospital.MethodsThis study employed an observational and cross-sectional design. Data collection was conducted from July to October 2024. The study enrolled 155 adult patients undergoing hemodialysis at An-Najah University Hospital. Data on sociodemographic characteristics, medical history, dialysis-related information, nutritional status, dietary intake practices, and mental health were collected via face-to-face interviews. The patients' eating practices during dialysis, presence of symptoms, minimum mean arterial pressure, and dialysis adequacy were assessed for three sessions.ResultsThe study included 155 patients undergoing hemodialysis, of whom 66.5% were male and 79.4% reported eating during dialysis. Based on the self-reported data, eating during dialysis was not associated with nutritional status or mental health status. Similarly, observational data revealed no association between eating during dialysis and presence of symptoms, decrease in blood pressure, and adequacy of dialysis.ConclusionsBased on self-reported data, there was no association between eating habits during dialysis and nutrition or mental health status. Observational data additionally revealed no association between eating during dialysis and adequate dialysis, presence of symptoms, or decrease in blood pressure.

INTRODUCTION: Fracture-related, periprosthetic joint, and surgical site infections are difficult to eradicate once biofilm develops. Continuous local antibiotic perfusion (CLAP) delivers sustained high local gentamicin levels with low systemic exposure, but unexpected serum gentamicin elevation has been reported. This study aimed to describe temporal changes in serum gentamicin during CLAP and identify factors associated with levels ≥2 μg/mL. METHODS: We conducted a multicenter study within the Trauma Research Group of Nagoya. Among 205 patients treated with CLAP, 131 met the inclusion criteria after the exclusion of patients with chronic dialysis, short follow-up periods, missing gentamicin data, and baseline aspartate aminotransferase or alanine aminotransferase >80 U/L. CLAP routes, tube configurations, drainage methods, and serum gentamicin levels (baseline, days 3, 1 week, 2 weeks) were recorded. Acute kidney injury (AKI) and hepatotoxicity were defined using standard thresholds. Missing data were handled by multiple imputation. RESULTS: The median serum gentamicin level remained < 2 μg/mL at all time points, with correlations between day 3 and later levels. Drug-related adverse events occurred in 26.0% of patients. AKI developed in 5.3% (N = 7), 6 patients were with hypertension, and 5 were with knee or lower leg infections, and was associated with significantly higher serum gentamicin concentrations at early time points (day 3 and 1 week) compared with those without AKI. Hepatic dysfunction occurred in 4.6% (N = 6), which all used iSAP, but no significant association with serum gentamicin concentrations was observed. All renal and hepatic events resolved after treatment modification. CONCLUSIONS: In our cohort, most patients who developed AKI had hypertension and exhibited higher gentamicin concentrations on day 3 and at 1 week than those without AKI. Early monitoring of serum gentamicin concentrations on day 3 may therefore be warranted in all patients undergoing CLAP, particularly in those with hypertension, to assess AKI risk.

ObjectiveTo evaluate the clinical utility of the admission albumin-to-globulin ratio for assessing disease severity and predicting prognosis in patients with wasp stings.MethodsThis retrospective cohort study enrolled 161 hospitalized patients categorized into mild, moderate, and severe groups according to the 2018 Chinese Expert Consensus Criteria. Baseline characteristics, admission albumin-to-globulin ratio, and inflammatory markers were compared among the severity groups. Spearman correlation analysis was used to assess associations between the albumin-to-globulin ratio and clinical parameters. Multivariable logistic regression was performed to identify independent risk factors for poor prognosis, multiple organ dysfunction syndrome, and acute kidney injury. Receiver operating characteristic curve analysis was used to evaluate the predictive performance of admission albumin-to-globulin ratio and its coefficient of variation.ResultsAdmission albumin-to-globulin ratio was significantly lower in the severe group (p < 0.05) and negatively correlated with white blood cell count, C-reactive protein, procalcitonin, and serum amyloid A. Decreased albumin-to-globulin ratio and elevated coefficient of variation of the albumin-to-globulin ratio were independent risk factors for multiple organ dysfunction syndrome and acute kidney injury. Admission albumin-to-globulin ratio demonstrated strong diagnostic efficacy, with areas under the curve of 0.822 for multiple organ dysfunction syndrome and 0.860 for acute kidney injury. The combination of albumin-to-globulin ratio with coefficient of variation of the albumin-to-globulin ratio significantly improved the areas under the curve for multiple organ dysfunction syndrome prediction to 0.934 (95% confidence interval: 0.854-0.978), yielding 89.29% sensitivity and 82.00% specificity. Admission albumin-to-globulin ratio provides early risk stratification tool, whereas coefficient of variation of the albumin-to-globulin ratio reflects dynamic changes during hospitalization and provides complementary prognostic information. Furthermore, patients with an admission albumin-to-globulin ratio ≤1.1 exhibited significantly higher incidences of acute kidney injury, multiple organ dysfunction syndrome, hepatic dysfunction, and coagulopathy (p < 0.001).ConclusionsAdmission albumin-to-globulin ratio is a simple, effective biomarker for

IgA nephropathy (IgAN) has a heterogeneous clinical course. We retrospectively studied 180 patients with biopsy-proven IgAN and at least 3 years of clinical follow-up. Patient-specific eGFR slopes were estimated from available measurements at biopsy and the 6-, 12-, 18-, 24-, 30-, and 36-month follow-up points. We built a post hoc multivariable model guided by clinical relevance. Oxford T was treated as categorical, with T0 as reference. The median eGFR slope was -1.12 mL/min/1.73 m2/year, and 35 patients (19.4%) met the operational rapid-progression threshold of < -5 mL/min/1.73 m2/year. In the primary model, higher ln(UACR + 1) predicted a steeper decline (β= -0.612, 95%CI -1.073 to -0.150). T2 lesions predicted a 3.87 mL/min/1.73 m2/year faster loss than T0 (β= -3.870, 95%CI -7.087 to -0.654), whereas T1 did not differ from T0. The model R2 was 0.159 (adjusted R2=0.130). UACR and T2 estimates remained negative under HC3 inference and after excluding influential observations, although T2 was less stable in some restricted analyses. Baseline albuminuria was the most consistent adverse marker of eGFR slope. T2 lesions were linked to faster decline as well, but this estimate derived from only 16 patients (8.9%) and lost statistical significance when analysis was restricted to ≥5 measurements, making the finding tentative and strictly hypothesis-generating.

BACKGROUND: Blood pressure (BP) is an important modifiable prognostic factor in maintenance hemodialysis patients. We previously introduced intradialytic time-averaged cumulative blood pressure (TAC-BP), calculated from all BP measurements obtained during each dialysis session using the trapezoidal rule. We hypothesized that the longitudinal slope of session-level TAC-BP values (TAC-BP Slope) is associated with all-cause mortality. METHODS: This single-center retrospective cohort study included 209 maintenance hemodialysis patients followed from August 2018 to March 2025. Four longitudinal BP slope indicators were calculated: TAC-systolic BP (SBP) Slope, TAC-diastolic BP (DBP) Slope, Predialysis SBP Slope, and Predialysis DBP Slope. Multivariable Cox regression was performed. Non-linear associations were examined using tertile analysis. Incremental discrimination was assessed using bootstrap mean C-index comparison. RESULTS: Over a mean follow-up of 2.8 years, 75 patients (35.9%) died. In linear Cox models, all four indicators were significantly associated with mortality, with TAC-DBP Slope showing the strongest linear association (HR 1.767, 95% CI 1.404-2.224). For TAC-DBP Slope, both declining (HR 4.21, 95% CI 2.28-7.75) and increasing (HR 2.81, 95% CI 1.44-5.50) tertiles showed significantly elevated mortality versus stable tertile, indicating a U-shaped association. In sensitivity analyses excluding measurements from the 6 months preceding death or censoring, the association in the declining tertile was attenuated and no longer significant (HR 1.44, 95% CI 0.73-2.84), whereas the increasing tertile remained significant (HR 2.07, 95% CI 1.06-4.06). C-index analysis demonstrated that TAC-DBP Slope deviation provided significantly improved internal discrimination beyond established and predialysis variables (ΔC = +0.048, p=0.010). CONCLUSIONS: Longitudinal TAC-DBP Slope shows a U-shaped association with all-cause mortality, but the two arms differ in origin: the declining arm largely reflects terminal decline preceding death, whereas the increasing arm persists after exclusion of terminal measurements. TAC-DBP Slope may therefore be useful for risk stratification rather than as a validated prediction tool.

Chronic kidney disease (CKD) is a major global health burden, and renal fibrosis is a common pathological correlate of progressive loss of kidney function. Renal tubular epithelial cells (RTECs), particularly proximal tubular epithelial cells (PTECs), contain abundant mitochondria and depend on oxidative metabolism to support solute transport. This metabolic specialization renders them vulnerable to hypoxia, lipotoxicity, uremic toxins, aging, inflammation, and hemodynamic stress. Persistent mitochondrial injury can suppress fatty acid oxidation and oxidative phosphorylation, deplete nicotinamide adenine dinucleotide, increase mitochondrial reactive oxygen species, destabilize mitochondrial DNA, and disrupt biogenesis, dynamics, mitochondria-associated membrane signaling, and mitophagy. These abnormalities promote maladaptive repair, senescence, inflammatory cell death, and paracrine signaling to fibroblasts, macrophages, endothelial cells, and pericytes. Evidence is organized within a tubule-to-niche framework that distinguishes causal perturbation from temporal or transcriptomic association, model-specific findings from cross-model convergence, and experimental efficacy from clinical translation. Single-cell, spatial, and organoid studies are considered alongside evidence from human biopsy specimens and biomarkers. Mitochondrial dysfunction is thus treated as a context-dependent contributor to, and amplifier of, CKD-associated fibrotic remodeling rather than a universal initiating event. Although strategies targeting bioenergetics, redox balance, mitochondrial quality control, and tubular delivery are promising, translation is constrained by disease heterogeneity, intervention timing, target specificity, pharmacokinetics, and the scarcity of validated human antifibrotic endpoints.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most prevalent primary glomerulonephritis worldwide, with 20%-40% of patients progressing to end-stage renal disease. However, the relationship between peripheral immune alterations and local renal injury, particularly with respect to the abundance patterns and post-translational modification signals of secretory proteins, remains incompletely characterized. METHODS: This study included 48 samples, consisting of renal tissue samples from 7 IgAN patients and 10 controls, and peripheral blood mononuclear cells (PBMCs) from 6 patients with IgAN and 25 controls. Renal tissue and PBMC samples were analyzed by proteomic and crotonylation profiling, respectively. These datasets represent cohort-level feature integration rather than paired multi-omics correlation analyses performed within the same individuals. Immune secretory protein annotations from the Human Protein Atlas supported downstream interpretation. Differential abundance analysis, protein-protein interaction (PPI) network analysis, functional enrichment, transcription factor (TF) prediction, and compound enrichment analysis using the DSigDB and Enrichr platforms were performed to explore molecular features and database-derived compounds associated with IgAN. RESULTS: Compared with the corresponding control groups, 92 differentially abundant secreted proteins and 36 secretory proteins with differential protein-abundance-normalized Kcr signals were identified in IgAN patients. PPI network analysis prioritized FGA, FGB, A2M, APOA1, C3, HP, SERPINA1, APOB, FGG, and TF as exploratory hub candidates, while STAT1, PML, STAT5B, and MYH11 were computationally predicted as candidate upstream TFs. Compound enrichment analysis identified thapsigargin as a database-derived, hypothesis-generating compound related to the secretory protein network in IgAN. CONCLUSIONS: This study provides an integrative characterization of secretory protein abundance and crotonylation patterns in IgA nephropathy. The findings suggest candidate hub proteins and upstream TFs potentially associated with immune dysregulation in IgAN. Despite the limited sample size, these results offer exploratory molecular insights and provide a basis for future mechanistic and experimental studies. SIGNIFICANCE: Secretory proteins may contribute to immune dysregulation and renal injury in immunog

BACKGROUND: Patients with chronic kidney disease (CKD) have impaired respiratory function. Although exercise provides several benefits in this population, its effects on respiratory outcomes remain unclear. This study aims to evaluate the effects of different exercise modalities on pulmonary function and respiratory muscle strength in patients with CKD across different stages. METHODS: Systematic review and meta-analysis of experimental studies. Searches were conducted from database inception to May 2026 in MEDLINE/PubMed, CENTRAL, EMBASE, PEDro, Web of Science, LILACS and supplementary searches of grey literature sources, without language or publication-year restrictions. Outcomes included forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC ratio, peak expiratory flow (PEF), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP). Random-effects models were used for meta-analyses. RESULTS: Thirteen studies were included in the meta-nalyses. Exercise significantly improved FVC (MD=0.25 L; 95% CI: 0.01-0.50; I2=51%), MIP (MD=11.47 cmH2O; 95% CI: 7.73-15.22; I2=52%), and MEP (MD=10.42 cmH2O; 95% CI: 5.53-15.31; I2=58%), whereas no significant effects were observed for FEV1, FEV1/FVC, or PEF. In exploratory subgroup analyses, both respiratory interventions and peripheral exercise significantly improved MIP and MEP. However, no significant subgroup differences between exercise modalities were observed for MIP (p=0.67), MEP (p=0.20), or FVC (p=0.70). CONCLUSIONS: Exercise may improve FVC and respiratory muscle strength in patients undergoing haemodialysis. Exploratory analyses did not provide evidence effects between respiratory interventions and peripheral exercise. These findings suggest that exercise may be considered a complementary strategy to improve respiratory function in rehabilitation programmes for these patients.

Multimorbidity is associated with an increased risk of renal function decline in older individuals. In this study, we aimed to evaluate whether multimorbidity patterns differently contributed to this risk in three different hospital settings. We conducted a comparative cohort study of patients aged ≥ 65 years admitted to acute-care hospitals in Italy. Data were drawn from the retrospective SIN-SIGG study (geriatric units, n = 1600; nephrology units, n = 560) and the prospective REPOSI registry (internal medicine units, n = 4595). Quantitative multimorbidity was defined as the number of chronic conditions with prevalence ≥ 5% per cohort; qualitative multimorbidity was derived through latent class analysis of disease combinations. The primary outcome was change in estimated glomerular filtration rate (eGFR) from admission to discharge, calculated using the Berlin Initiative Study 1 (BIS1) equation. A relative decline was defined as ≥ 20% reduction from baseline. Multivariable models were adjusted for age, sex, baseline eGFR, acute diagnoses, and number of medications. Among 6,755 patients (mean age 80.6 years; 47% women), multimorbidity prevalence ranged from 87 to 93%. Quantitative multimorbidity showed modest and inconsistent associations with renal decline. In contrast, qualitative multimorbidity consistently predicted eGFR deterioration. Across all cohorts, the cardiorespiratory and renal cluster was associated with higher odds of in-hospital eGFR decline compared with neurogeriatric and mixed patterns (geriatrics OR 2.24 [95% CI 1.16-4.70]; internal medicine OR 1.72 [95% CI 1.22-2.45]; nephrology OR 2.11 [95% CI 1.01-4.56]). Disease-pattern-based multimorbidity better stratifies short-term renal risk than disease counts, identifying high-risk patients for targeted nephroprotective care during hospitalization.

Reports of survival of infants with serum sodium levels exceeding 200 mmol/L are extremely rare. We describe a 34-day-old, 3.6-kg male infant who developed extreme hypernatremia (serum sodium >200 mmol/L) and multiple organ dysfunction syndrome following accidental salt poisoning. When continuous renal replacement therapy (CRRT) was not feasible because of the patient's low body weight and lack of appropriately sized equipment, peritoneal dialysis (PD) was initiated as rescue therapy. Within 24 hours, serum sodium decreased to 186.7 mmol/L, with parallel improvements in metabolic acidosis, coagulopathy, and other organ functions. PD was discontinued on day 7, and the infant was discharged with normal neurological and organ function. This case supports PD as a life-saving option for extreme hypernatremia in low body weight infants when CRRT is unavailable.

RATIONALE & OBJECTIVE: Despite evidence supporting peritoneal dialysis (PD) as an effective first-line therapy with outcomes comparable to hemodialysis, global PD utilization remains at only approximately 11%. We systematically reviewed qualitative evidence on barriers and facilitators to PD adoption using the Social Ecological Model (SEM) framework to identify multi-level intervention opportunities. STUDY DESIGN: Systematic review of qualitative studies. SETTING & STUDY POPULATIONS: Adults with chronic kidney disease (CKD), caregivers, and healthcare providers involved in dialysis decision-making across 9 countries. SEARCH STRATEGY & SOURCES: Qualitative or mixed-methods studies exploring barriers and/or facilitators to PD adoption published in peer-reviewed journals from database inception through March 2025. DATA EXTRACTION: Two reviewers independently extracted study characteristics, participant demographics, and findings related to PD adoption barriers and facilitators. ANALYTICAL APPROACH: Thematic synthesis with findings mapped to five SEM levels (individual, interpersonal, organizational, community, policy). Quality assessment using the Critical Appraisal Skills Program checklist. RESULTS: From 7,390 records, 13 studies (595 participants) met inclusion criteria. Individual-level barriers included fear of infection (77% of studies), low self-efficacy (62%), and lifestyle disruption (69%). Interpersonal factors included provider influence (69%) and family dynamics (62%). Organizational barriers centered on education quality (85%) and urgent dialysis starts (38%). Community factors included infrastructure limitations (46%) and cultural considerations (31%). Policy barriers included financial constraints (38%) and hemodialysis-centric systems (54%). Facilitators operated synergistically across levels, with autonomy preference and convenience prominent individually, while structured support was prominent organizationally. LIMITATIONS: Heterogeneity of populations and healthcare systems; cross-sectional nature of most studies; potential incomplete capture of all relevant influences on choice of dialysis modality. CONCLUSIONS: PD adoption is influenced by complex, interconnected factors spanning all SEM levels. Effective interventions must address the full ecological context, with particular attention to vulnerable populations facing multiple barrie

INTRODUCTION: Acute kidney injury after cardiac surgery (CSA-AKI) is common and associated with worse outcome. Venous congestion contributes to CSA-AKI and liver dysfunction. We hypothesized that elevated liver enzymes may serve as early markers for CSA-AKI. METHODS: In a single-center cohort study we included adult cardiac surgery patients during a 6-year period. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured at ICU admission, 12 h and 24 h. The primary objective was to assess whether liver enzymes at ICU admission, normalized to their upper limits of normal (ULN), predicted CSA-AKI. Secondary outcomes included prediction of CSA-AKI severity, use of renal replacement therapy (RRT), and the association between central venous pressure (CVP) and liver enzymes. RESULTS: Among 3415 patients, 65.4% developed CSA-AKI, 37.4% had AKI stage ≥2 and 3.8% received RRT. AST/ULN and ALT/ULN at ICU admission predicted CSA-AKI [AUC-ROC (95% CI; resp. 0.587 (0.570-0.604); 0.534 (0.517-0.551); both p < 0.001)], with AST performing better (p < 0.001). The discriminating power of AST/ULN and ALT/ULN at ICU admission for AKI ≥2 were respectively AUC-ROC (95% CI); 0.594 (0.577-0.610) and 0.541 (0.524-0.585) (both p < 0.001). AST/ULN 12 h after ICU admission was the strongest predictor for RRT [AUC-ROC (95% CI; 0.751 (0.733-0.768); p < 0.001)], with a 4-fold increased RRT risk when AST exceeded 1.6 times the ULN. AST and ALT 24 h post ICU admission were weakly associated with CVP (respectively: R2 = 0.007; p = 0.003 and ALT: R2 = 0.006; p = 0.004). CONCLUSION: AST activity may have potential as a predictor of CSA-AKI and use of RRT, although liver enzymes demonstrated a weak association with CSA-AKI.

OBJECTIVES: To assess whether lung ultrasound surface wave elastography (LUSWE), a non-invasive measure of lung stiffness, correlates with pulmonary function and high-resolution CT (HRCT) patterns in suspected interstitial lung disease (ILD). We hypothesised that LUSWE-derived lung stiffness would be associated with functional impairment and radiological ILD patterns. SETTING: Prospective, single-centre pilot study conducted in a tertiary referral ILD unit in Barcelona, Spain. PARTICIPANTS: 68 consecutive patients (41 men and 27 women) with suspected ILD were enrolled between June 2020 and February 2024 and completed LUSWE assessment at diagnosis under clinically stable conditions. Final diagnoses comprised sarcoidosis, idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema, fibrosing ILD, connective tissue disease-related ILD, other ILD and absence of pulmonary disease. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the association between LUSWE velocity and pulmonary function parameters, specifically forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO). Secondary outcomes included associations with HRCT radiological patterns, fibrosing vs non-fibrosing ILD, usual interstitial pneumonia (UIP)/probable UIP vs other HRCT patterns and quantitative HRCT-derived fibrosis extent. RESULTS: LUSWE velocity did not significantly correlate with FVC (r=0.23, 95% CI -0.01 to 0.45; p=0.07) or DLCO (r=0.13, 95% CI -0.12 to 0.36; p=0.31). No significant differences in LUSWE velocity were observed across HRCT patterns (Kruskal-Wallis χ²=1.2018; p=0.8778). Exploratory point-by-point analyses showed one significant association between the R2 point and FVC (r=0.33; p=0.0068), but this did not remain significant after correction for multiple comparisons (adjusted p=0.137). LUSWE distributions were similar between fibrosing and non-fibrosing ILD groups (3.35 (IQR 2.87-4.16) vs 3.55 (IQR 2.98-4.17) m/s; p=0.526) and between UIP/probable UIP and other HRCT patterns (3.36 (IQR 2.89-4.21) vs 3.59 (IQR 2.86-4.15) m/s; p=0.876). Quantitative HRCT analyses also showed weak, non-significant correlations between hemithorax-level fibrosis extent and corresponding LUSWE values. CONCLUSIONS: In this heterogeneous cohort of patients evaluated at diagnosis for suspected ILD, LUSWE was not meaningfully associated with

BACKGROUND: Emotional intelligence (EI) is critical in intensive care unit (ICU) nursing, where nurses face high stress, clinical instability and emotionally demanding situations. EI helps nurses manage emotions, improve communication and support clinical performance. It has also been linked to lower burnout and more adaptive coping among ICU nurses. AIM: This scoping review aimed to map the available evidence on emotional intelligence among nurses working in ICUs, including its key dimensions, associated professional outcomes and current knowledge gaps. STUDY DESIGN: A scoping review was conducted in accordance with the Joanna Briggs Institute (JBI) methodology and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. A structured search was conducted in MEDLINE, CINAHL, PubMed and Scopus for studies published in the past 10 years in Portuguese, English or Spanish. RESULTS: In total, this review included nine studies. The evidence highlights the crucial role of EI in emotional regulation, communication and clinical performance among ICU nurses. Key dimensions of emotional intelligence, including empathy, emotional clarity and self-regulation, were consistently identified as important. Training programmes demonstrated significant improvements in EI and reduced burnout symptoms, and EI was also associated with more adaptive coping strategies and improved professional performance. CONCLUSIONS: Emotional intelligence is an important competency in ICU nursing and has been linked to improved communication, clinical decision-making and lower burnout among nurses. Despite these benefits, research still shows gaps, particularly in standardising EI assessment tools and in the need for longitudinal studies. Targeted emotional intelligence training programmes may strengthen ICU nurses' emotional resilience and enhance care quality. RELEVANCE TO CLINICAL PRACTICE: Integrating EI development into ICU nursing education and institutional policies can help reduce burnout, improve communication with patients and families, and enhance overall clinical performance, thereby supporting a healthier work environment and strengthening nurses' communication and professional performance in intensive care settings.

Research priorities for intensive care nursing have been set internationally but not in Japan. We aimed to identify national priorities and compare them with those reported elsewhere. Focus group interviews with 10 expert intensive care unit (ICU) nurses generated 65 categories, which 50 nurses rated over three modified Delphi rounds (consensus, median ≥ 70, then ≥ 80). Categories were restructured into 20 topics; 16 reached consensus. Five independent nursing researchers who had taken no part in the interviews or the Delphi rounds then appraised every topic for validity, applicability, utility and clarity; all 16 were endorsed, and one was reworded. Symptom management, post-intensive care syndrome prevention and ICU nurse education ranked highest, and education- and system-related topics formed about one-third of the agenda, suggesting workforce regulation shapes national research priorities alongside clinical need. The agenda gives Japanese academic societies, funders and post-graduate programmes an explicit basis for targeting research investment.

BACKGROUND AND OBJECTIVE: Interstitial lung abnormalities (ILAs) are often unreported, and fibrotic ILAs carry a worse prognosis. In this study, we aimed to develop and validate a prediction model for fibrotic ILAs using non-radiological factors. METHODS: Using data from the Kumamoto ILA study (a multicenter prospective cohort in Japan), we developed a four-variable model (age, pack-years, fine crackles, elevated serum surfactant protein-D) in 164 patients (2022-2023, derivation cohort) and temporally validated it in 207 patients (2023-2024, validation cohort), with internal-external cross-validation for between-center heterogeneity. A simplified integer score was similarly assessed against 24-month functional decline and treatment initiation within 3 years. RESULTS: Fibrotic ILAs comprised 82% of cases (approximately 60% subsequently met ATS-defined ILD criteria), consistent across cohorts. The four-variable model achieved an AUC of 0.79 (derivation) and 0.76 (validation; pooled 0.76, 95% CI 0.68-0.82), with good calibration and minimal between-center heterogeneity. The integer score performed similarly (AUC 0.79/0.75) and correlated with functional decline (%FVC ≥ 10% or %DLco ≥ 15%) and treatment initiation. CONCLUSION: Age, smoking exposure, fine crackles, and elevated serum surfactant protein-D are key predictors of progressive fibrotic ILAs, supporting early risk stratification and clinical decision-making. TRIAL REGISTRATION: UMIN000045149/2021.12.1.

Respiratory viral infections constitute a substantial global health challenge, extending their impact beyond acute inflammation to encompass long-term pulmonary sequelae. Recent evidence highlights that respiratory viruses such as influenza, respiratory syncytial virus (RSV), and SARS-CoV-2 reprogram host metabolism to facilitate their replication, with significant alterations in glucose metabolism playing a critical role. This metabolic reprogramming augments glucose metabolism via activation of core signaling pathways including PI3K/Akt/mTOR, HIF-1α, and c-Myc. Beyond facilitating viral proliferation, these metabolic changes crosstalk with oncogenic signaling. By triggering chronic inflammation, oxidative stress and genomic damage, they disrupt the pulmonary immune microenvironment and ultimately promote the pathogenesis of lung cancer and chronic obstructive pulmonary disease (COPD). The pathogenesis of these symptoms is multifactorial and is influenced by genetic susceptibility, environmental exposure, and key interactions between persistent viral infection and the host's immune system. In this review, we synthesize recent advancements on the molecular mechanisms linking virus-induced metabolic alterations to the progression of pulmonary diseases. Furthermore, we discuss novel therapeutic strategies aimed at targeting these metabolic vulnerabilities to mitigate the long-term risks associated with respiratory infections.

OBJECTIVES: Despite evidence of vascular remodeling in emphysematous lungs in chronic obstructive pulmonary disease (COPD), its natural history and clinical course across phenotypes are not fully understood. We aimed to determine the effect of pruning and emphysema co-occurrence on hemodynamics in the Keio COPD Comorbidity Research (K-CCR) and quality of life (QoL), airflow/diffusion decline, and mortality in the Hokkaido COPD Cohort Study. MATERIALS AND METHODS: Pruning was defined as a low blood vessel volume of < 5 mm2 in the lungs relative to total blood vessel volume (BV5/TBV). Within each cohort, participants were classified into four groups using cohort-specific median dichotomization of BV5/TBV and the percentage of low-attenuation volume. Hemodynamics were assessed using echocardiography-derived estimated systolic pulmonary artery pressure (eSPAP). RESULTS: Participants from the K-CCR (N = 115) and Hokkaido COPD Cohort Study (N = 96) were evaluated. In the K-CCR, the pruning/severe-emphysema group was associated with poorer QoL and higher eSPAP. In the Hokkaido COPD Cohort Study, the pruning/severe-emphysema group had worse QoL, faster decline in forced expiratory volume in 1 s, and lower carbon monoxide transfer coefficient than the no-pruning/mild-emphysema group. Ten-year survival rates were 80%, 70%, 61%, and 36% for no-pruning/mild-emphysema, no-pruning/severe-emphysema, pruning/mild-emphysema, and pruning/severe-emphysema groups, respectively. In analyses using continuous variables, the percentage of low-attenuation volume was significantly associated with mortality, whereas BV5/TBV was not. CONCLUSION: Pulmonary vascular pruning may be a CT-derived potential biomarker for subtyping patients with poor outcomes, such as impaired hemodynamics and accelerated airflow/diffusion decline, particularly in patients with severe emphysema, requiring further validation. KEY POINTS: Question Does CT-based pulmonary vascular pruning provide additive prognostic information beyond emphysema severity for predicting pulmonary hemodynamics and longitudinal outcomes in COPD? Findings Categorical analyses suggested that low BV5/TBV was associated with poorer survival, worse hemodynamics, and greater ventilation/diffusion decline in patients with severe emphysema. Clinical relevance CT-derived BV5/TBV may help identify a vascular phenotype associated with wors

OBJECTIVE: Pulmonary function testing is routinely performed before hematopoietic stem cell transplantation (HSCT), but conventional parameters may not capture subtle airway abnormalities. This study evaluated the association of pretransplant forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75) with post-HSCT complications in adults. MATERIAL AND METHODS: This retrospective single-center cohort included 83 adults who underwent HSCT between 2016 and 2023. Reduced FEF25-75 was defined as <75% predicted. The primary outcome was a composite of post-HSCT complications. Multivariable logistic regression models were adjusted for age, sex, ever-smoking status, HSCT type, and reduced forced expiratory volume in 1 second (FEV1). Discrimination was assessed using receiver operating characteristic analysis. RESULTS: Overall, 32 patients (38.6%) experienced post-HSCT complications. Complications occurred in 50.0% of patients with reduced FEF25-75 versus 28.9% of those with FEF25-75 ≥75% predicted (P = 0.049). Reduced FEF25-75 was independently associated with higher odds of complications [odds ratio (OR): 3.58, 95% confidence interval (CI): 1.28-10.04; P = 0.015]. Reduced FEV1 showed an inverse association (OR: 0.12, 95% CI: 0.02-0.71; P = 0.019). FEF25-75 showed poor standalone discrimination (area under the curve: 0.578, 95% CI: 0.450-0.705). CONCLUSION: Reduced pretransplant FEF25-75 was independently associated with post-HSCT complications, but showed poor standalone discrimination. These hypothesis-generating findings suggest that FEF25-75 may provide information complementary to FEV1, but they do not support its use as an independent predictive test. Larger prospective studies are required.

Emerging respiratory infectious diseases increasingly arise at the human-animal-environment interface and challenge clinicians with rapidly evolving diagnostic, therapeutic, and infection-control decisions. This narrative review summarizes clinically relevant viral and bacterial pathogens that may present as severe respiratory disease, but are easily mistaken for common community-acquired infections during early illness. We focus on zoonotic influenza A viruses, including contemporary H5N1, Middle East respiratory syndrome coronavirus (MERS-CoV), hantaviruses, Nipah virus, and inhalational bacterial threats such as anthrax, pneumonic plague, tularemia, and melioidosis. These infections may progress from non-specific symptoms to severe pneumonia, acute respiratory distress syndrome, shock, neurological complications, disseminated infection, or death. Timely recognition depends on careful assessment of travel, occupational and recreational exposures, animal contact, outbreak signals, and pathogen-specific syndromic clues. Multiplex molecular diagnostics can support early triage and exclusion of common pathogens, but targeted PCR, culture, serology, sequencing, and reference laboratory confirmation remain essential. Management requires prompt supportive care, appropriate isolation, public health notification, and pathogen-directed antimicrobial, antiviral, antitoxin, or prophylactic strategies where available. By integrating clinical presentation, diagnostics, treatment, vaccines, and One Health considerations, this review aims to translate knowledge on emerging infections into practical bedside preparedness.

BACKGROUND: Data on health utilities in Alpha-1 antitrypsin deficiency (AATD) are scarce. This study aimed to evaluate health-related quality of life (HRQoL) using the EQ-5D in a cohort of AATD Pi*ZZ individuals from the European AATD Research Collaboration (EARCO) registry and to identify factors associated with impaired health utilities. METHODS: Observational, cross-sectional, multicenter study including AATD patients with Pi*ZZ genotype enrolled up to April 2025. HRQoL was assessed using the EQ-5D questionnaire (index and visual analogue scale (VAS)). Sociodemographic data, smoking history, respiratory symptoms, comorbidities, lung function and exacerbations were collected. Multivariable generalised linear models were used to identify factors independently associated with EQ-5D index scores in the overall population and in patients with AATD-COPD. RESULTS: A total of 1710 Pi*ZZ individuals were analysed with a mean age 55.2 ± 13.8 years, 51% were male and 49.6% had COPD. Mean EQ-5D index and VAS were 0.82 ± 0.22 and 62.9 ± 25.9, respectively. Patients with COPD had significantly worse EQ-5D index (0.75 ± 0.24 vs 0.90 ± 0.16) and VAS scores (56.3 ± 24.4 vs 70.4 ± 26.8; both p < 0.001). In multivariable analyses, higher symptom burden (CAT, mMRC), long-term oxygen therapy, being unemployed, exacerbations, COPD, bronchiectasis and lower educational level were independently associated with worse EQ-5D scores in Pi*ZZ subjects. CONCLUSIONS: HRQoL was substantially impaired in Pi*ZZ individuals, particularly in those with COPD. Symptom burden and exacerbations were stronger determinants of EQ-5D than lung function alone in all Pi*ZZ patients. Patients with AATD-associated COPD exhibited an HRQoL impairment comparable to that observed in usual COPD populations, but at a younger age.

Pulmonary complications are a significant cause of non-relapse mortality in allogeneic hematopoietic cell transplant (HCT) recipients. Pulmonary function tests (PFTs) are recommended to screen for asymptomatic lung function decline that precedes overt disease. HCT clinicians must understand the critical importance of PFTs in the post-HCT context and be able to identify abnormalities for timely intervention. This article provides a concise summary of contemporary PFT interpretation practices, tailored to clinicians caring for this complex patient population. Key principles, including comparison of pre-transplant and routine post-transplant studies, the importance of longitudinal assessments, and consideration of the clinical context of the HCT survivor, are illustrated through case vignettes. We review remaining fundamental questions about the application of PFTs post-transplant and suggest a path towards improved implementation and utilization of PFT data to guide clinical decision-making.

BACKGROUND: Negative-pressure ventilation (NPV) avoids a positive-pressure facial interface, but contemporary multi-center pediatric data comparing NPV with noninvasive positive-pressure ventilation (NIV) are limited. We describe modern NPV epidemiology and compare outcomes with NIV in children younger than 3 years with acute respiratory failure. METHODS: We conducted a multi-center retrospective cohort study using the Virtual Pediatric Systems (VPS) database. Children younger than 3 years who received NPV or NIV during a pediatric ICU (PICU) admission for acute or acute-on-chronic respiratory failure were included; outpatient use of either modality was excluded. Subjects were categorized according to initial respiratory support modality. The primary outcome was endotracheal intubation after initiation of noninvasive respiratory support. The primary analysis used multivariable mixed-effects logistic regression with center included as a random intercept. Propensity-score matching using Pediatric Risk of Mortality III score, age, sex, weight, diagnostic variables, and center was performed as a sensitivity analysis. RESULTS: Crude intubation rates were higher in the NPV group than in the NIV group (27.3% vs 10.4%, P < .001). After adjustment for measured subject-level factors and center-level clustering, ventilation modality was not independently associated with intubation (NIV vs NPV adjusted OR 0.675, 95% CI 0.393-1.158, P = .154). In the propensity-score-matched cohort, intubation remained numerically higher in the NPV group but was not statistically significant (NPV vs NIV OR 1.64, 95% CI 0.92-2.93, P = .12). CONCLUSIONS: In this multi-center retrospective cohort, NPV was used in a small minority of children younger than 3 years with acute respiratory failure. After adjustment for measured confounders and center-level clustering, ventilation modality was not independently associated with intubation. Prospective studies are needed to define optimal patient selection and the role of NPV in pediatric acute respiratory failure.

PURPOSE OF REVIEW: Acute respiratory distress syndrome (ARDS) is associated with profound pulmonary surfactant dysfunction, yet clinical trials of exogenous surfactant have not demonstrated consistent outcome benefits in adults. This review reassesses these failures in light of current understanding of ARDS heterogeneity, surfactant biology and intrapulmonary drug delivery. RECENT FINDINGS: Surfactant dysfunction in ARDS reflects not only quantitative depletion but also inhibition by plasma proteins, altered lipid and protein composition, impaired synthesis and recycling, epithelial injury and heterogeneous alveolar flooding. Previous trials frequently enrolled biologically unselected populations and used variable formulations, doses and delivery strategies. Available evidence provides a rationale for a phenotype-guided approach integrating patient selection, assessment of surfactant dysfunction, formulations capable of maintaining activity under inhibitory conditions and optimized alveolar delivery. Next-generation synthetic surfactants containing surfactant protein B and C analogues, together with surfactant-based delivery of anti-inflammatory or other biologically active compounds, may address limitations of earlier replacement strategies. Future studies should move beyond testing surfactant in unselected ARDS. Clinical translation will require biologically enriched populations, mechanistically appropriate formulations, early treatment and verified delivery to recruitable lung regions.

OBJECTIVE: The transferability of pre-ECMO characteristics and established mortality prediction tools across COVID-19 (C-19) and non-COVID-19 (nC-19) acute respiratory distress syndrome (ARDS) remains uncertain. We compared clinical characteristics, organ dysfunction, respiratory support and outcome in a large cohort of patients treated with veno-venous extracorporeal membrane oxygenation (vvECMO), and explored mortality prediction in C-19 ARDS. METHODS: This retrospective single-center cohort study included n = 600 vvECMO patients (C-19: n = 245, nC-19: n = 355) hospitalized at the Charité ARDS ECMO Center from 01/2007 to 12/2018 (nC-19) and 03/2020-01/2022 (C-19). Pre-ECMO clinical and laboratory variables were compared between cohorts and by ICU survival. RESP score performance was assessed, and an exploratory C-19 ECMO mortality prediction (CEMP) score was derived from pre-ECMO variables using an explainable machine-learning workflow with SHapley Additive exPlanations (SHAP). RESULTS: C-19 patients were older (median 57.0 vs. 51.0 years, p < 0.0001), more often male (74.7% vs. 66.8%, p = 0.0337), and had a higher BMI (29.3 vs. 26.0 kg/m², p < 0.0001). nC-19 patients had a higher CCI (3 vs. 2, p = 0.0137) and SOFA score (12 vs. 11, p = 0.0004). Septic shock before vvECMO initiation was more prevalent in nC-19 patients (65.4% vs. 13.9%, p < 0.0001), and nC-19 patients had higher median baseline bilirubin, creatinine, and lactate levels (all p < 0.0001). nC-19 patients had higher median PEEP, pPeak, and plateau pressure than C-19 patients, whereas their PaO₂/FiO₂ ratio was lower (p < 0.0001). Duration of vvECMO support was longer in C-19 patients (26.0 vs. 12.6 days, p < 0.0001); ICU mortality did not differ significantly (55.1% vs. 47.9%, p = 0.0966). RESP showed limited discrimination in C-19 patients, and the CEMP derivation analysis yielded an apparent AUC of 0.757 (95% CI 0.69-0.82). CONCLUSION: This large single-center comparative vvECMO cohort highlights differences between C-19 and nC-19 ARDS in organ dysfunction burden, respiratory characteristics, and treatment duration. ICU mortality did not differ significantly between groups. RESP showed limited discrimination in C-19; CEMP remains exploratory and requires calibration and independent external validation before clinical application.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a major cause of morbidity and mortality in the ICU and is associated with high antibiotic consumption and increased healthcare resource utilization. OBJECTIVES: This review provides an updated overview of current strategies for VAP prevention. METHODS: A narrative review of the literature was conducted, including randomized controlled trials, systematic reviews, meta-analyses, and recent international guidelines and position papers on VAP prevention. RESULTS: Successful VAP prevention depends on both effective implementation strategies and evidence-based clinical interventions. Current preventive measures target the main mechanisms involved in VAP pathogenesis, including prolonged mechanical ventilation, microaspiration, endotracheal tube biofilm formation, and colonization of the aerodigestive tract. Routine preventive measures with the strongest supporting evidence include minimizing the duration of mechanical ventilation and sedation, avoiding unnecessary intubation and re-intubation, semi-recumbent positioning, oral care with toothbrushing rather than chlorhexidine, early enteral nutrition, and the use of structured prevention bundles. Additional interventions, such as subglottic secretion drainage, selective digestive or oropharyngeal decontamination, inhaled antibiotics, early tracheostomy, and post-pyloric feeding, may be beneficial in appropriately selected patients or specific clinical settings. In contrast, some interventions have inconsistent evidence of clinical benefit and are not recommended for routine use. CONCLUSIONS: Preventing VAP requires a multimodal approach that integrates organizational support with evidence-based preventive measures. As new evidence continues to emerge, prevention bundles should be regularly updated to optimize effectiveness while avoiding interventions that are ineffective or potentially harmful. IMPLICATIONS FOR CLINICAL PRACTICE: Implementation of VAP prevention strategies should focus on interventions supported by the best available evidence, while tailoring selected strategies to local epidemiology, available resources, and individual patient characteristics. Consistent adherence to multidisciplinary prevention bundles remains fundamental for reducing the burden of VAP.

BACKGROUND: Cough syncope (CS) is a rare subtype of syncope that remains underrepresented in evidence-based medicine. We aimed to characterize the clinical features of CS, with the aim of improving recognition and optimizing management strategies. METHODS: We present five cases of CS alongside a systematic review of its clinical characteristics based on published literature to improve recognition and optimize management. Reports of eligible patients were screened, and demographic, clinical, diagnostic, treatment, and outcome data were analyzed. RESULTS: This study included 60 patients with a mean age of 56 ± 15 years, 91% of whom were male. The most common underlying triggers were respiratory diseases, including pulmonary infections (35%) and bronchitis (22%). Common comorbidities included hypertension (26%), bronchial asthma (18%), and diabetes mellitus (15%). CS episodes were directly triggered by severe coughing in 93% (26/28) of patients. Episodes occurred at least twice daily in 20% of patients, and limb convulsions accompanied syncope in 22%. Symptoms improved after treatment in 98% of cases. After a median follow-up of 3.75 months (Interquartile Range: 2-12 months), the recurrence rate of syncope was 11%. CS, predominantly triggered by severe coughing, primarily affected middle-aged and older men. CONCLUSIONS: CS predominantly affects middle-aged and older men and is frequently associated with pulmonary infections. Acute pulmonary infections serve as a common underlying trigger for CS, and patients are at risk of recurrent syncope and falls. Disease management should be focused on treating chronic airway disease, particularly chronic obstructive pulmonary disease.

BackgroundSepsis is a significant public health concern associated with high prevalence and mortality rates. This study aimed to evaluate the prognostic value of platelet count, plateletcrit level, mean platelet volume, and platelet distribution width in patients with sepsis.MethodsThe study cohort included 48 patients diagnosed with sepsis, who were allocated to the sepsis group, and 34 patients admitted with infections who did not meet the diagnostic criteria for sepsis, who were allocated to the infection group. Complete blood count was performed for all patients, which included evaluation of platelet count and other parameters (plateletcrit level, mean platelet volume, and platelet distribution width) as well as C-reactive protein levels within 24 h of admission and again on days 3 and 7. Patients in the sepsis group were monitored until discharge or death and categorized into two subgroups based on outcomes: survivors (39 patients) and nonsurvivors (9 patients).ResultsStatistically significant differences were identified in the platelet count, plateletcrit level, mean platelet volume, and platelet distribution width between the sepsis and infection groups (all p < 0.05). Platelet count and plateletcrit level exhibited negative correlations with the Sequential Organ Failure Assessment score (r = -0.657 and -0.638, all p < 0.05), whereas mean platelet volume and platelet distribution width exhibited positive correlations (r = 0.331 and 0.298, all p < 0.05). Additionally, platelet count and plateletcrit level were inversely associated with C-reactive protein levels (r = -0.346 and -0.327, all p < 0.05). Receiver operating characteristic curve analysis revealed that platelet counts had the highest diagnostic value for sepsis, with an area under the curve of 0.864, sensitivity of 94.12%, and specificity of 73.47%. In the dynamic monitoring of platelet parameters, significant differences in platelet count and plateletcrit level were observed in the prognosis group by day 7.ConclusionAdmission platelet count and related parameters serve as specific diagnostic predictors of sepsis. Dynamic monitoring of platelet count and plateletcrit level on day 7 can guide aggressive management strategies to improve outcomes in patients with sepsis.

Inflammasomes are pivotal for the initiation and control of host inflammatory responses. This is particularly important in the respiratory system due to its direct exposure to noxious environmental and infectious stimuli, which can cause local inflammation, tissue damage and impaired function. Inflammasomes are activated by a variety of processes that result in a loss of cellular homeostasis, leading to the oligomerisation of specific innate immune sensors. Inflammasome complex formation then results in a form of programmed cell death known as pyroptosis and release of cleaved active pro-inflammatory cytokines, interleukin (IL)-1β and IL-18, and the subsequent inflammatory cascade. While acute inflammasome activation can be protective in controlling infection, chronic inflammasome activation is detrimental and can lead to irreversible changes in the lung micro-environment such as chronic inflammation, emphysema, lung fibrosis and impaired gas exchange and lung function. In this review, we describe the role of inflammasomes in the pathogenesis of acute and chronic respiratory diseases, highlight currently available preclinical and clinically available therapies that regulate or inhibit inflammasome activation, and outline the use of multi-omics to identify novel inflammasome biomarkers and therapeutics.

BACKGROUND: The effects of co-existing OSA on the outcomes of ARDS are unclear. OBJECTIVES: This retrospective study aimed to compare the outcomes and resource utilization rates of OSA patients who develop ARDS with a matched control group. MATERIALS AND METHODS: Adult patients hospitalized between 2016 and 2019 with a diagnostic code for ARDS were identified within the Nationwide Inpatient Sample. Patients with acute cardiogenic pulmonary edema were excluded. By utilizing propensity score calculations, patients with OSA were individually matched with and compared to patients without OSA. Primary outcomes were mortality, length of stay and total hospitalization charges. RESULTS: 9405 OSA patients were matched with 9206 controls. OSA was independently associated with 34% lower odds of in-hospital mortality (21.1%vs 24.9%; aOR 0.66, 95% CI 0.61-0.72; p < 0.001), shorter length of stay (B - 2.0 days; p < 0.001), and lower total hospitalization charges (B -$74,601; P < 0.001). OSA patients had lower rates of invasive mechanical ventilation (aOR 0.79; p < 0.001) and tracheostomy (aOR 0.66; p < 0.001) but higher noninvasive ventilation use (aOR 1.40; p < 0.001). In a subgroup analysis of OSA patients, NIV was associated with fewer tracheostomies (aOR 0.61; p < 0.001) and lower charges (B -$26,625; p < 0.001) but was not associated with mortality or length of stay. CONCLUSIONS: In this nationally representative cohort, preexisting OSA was paradoxically associated with lower mortality, shorter hospitalization, and reduced resource utilization in ARDS. These findings suggest possible protective mechanisms warranting further prospective investigation.

OBJECTIVE: While disrupted sleep has long been linked to mental disorders there has been a notable decrease in interest and sleep-wake disorders have received low priority in psychiatric care. The aim of the paper was to present a concise guide for evaluating common sleep-wake disturbances within a psychiatric framework to revitalise the importance of sleep in psychiatry. METHODS: A systematic search strategy was conducted on the importance of sleep-wake assessment in psychiatry (search #1), the typology of sleep-wake disturbances in psychiatric practice (search #2), the guidelines on assessment of sleep-wake disturbances (search#3). Results were summarised and discussed in a narrative way. RESULTS: Evidence suggests that assessing sleep-wake disturbances improves prevention and treatment outcomes in psychiatric patients. Insomnia remains the most common disorder, though other sleep disturbances are highly prevalent. A structured two-step evaluation-combining initial patient clinical interviews with standardised self-report questionnaires-may assist in diagnosis and monitor outcomes. CONCLUSION: A concise guide on how to assess sleep-wake disturbances in psychiatry was summarised for psychiatric clinical practice.

INTRODUCTION: Hospital-acquired pressure injuries remain an important patient-safety burden, yet direct evidence comparing prophylactic sacral dressing technologies is absent. AREAS COVERED: Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched from database inception through 23 January 2026; supplementary searches were completed on 26 January 2026, and one eligible post-search publication was assessed separately. Twenty-five studies were included. Sacral pressure-injury incidence varied widely across settings and study designs. The single-arm SAP study reported no sacral pressure injuries among 50 participants (0.0%; two-sided Clopper-Pearson exact 95% confidence interval, 0.0-7.1%) Two unanchored matching-adjusted indirect comparisons examined population alignment for time to pressure injury and dressing utilization. Adjustment was restricted to available baseline covariates; important differences in pressure-injury risk, setting, follow-up, and prevention protocols remained. EXPERT OPINION: The review supports prophylactic dressings as an adjunct to comprehensive prevention but does not establish the relative effectiveness of superabsorbent polymer and foam technologies. REGISTRATION: : OSF M2ze7.

PURPOSE: To evaluate surgical and visual outcomes in primary rhegmatogenous retinal detachment (RRD) repair with silicone oil, comparing cases with and without adjunctive scleral buckling (SB). METHODS: This retrospective cohort study included eyes that underwent pars plana vitrectomy (PPV) with silicone oil as the initial surgical intervention for primary RRD at Sheba Medical Center (2010-2022). Eyes were grouped based on SB use. Primary outcomes included single-surgery anatomical success (SSAS) and final best-corrected visual acuity. Secondary outcomes included time to reoperation, failure pattern, silicone oil removal, long-term silicone oil retention, and secondary glaucoma. RESULTS: Among 1,900 eyes that underwent vitrectomy for rhegmatogenous retinal detachment during the study period, 107 eyes met inclusion criteria: 28 underwent SB + PPV and 79 underwent PPV alone. The SB + PPV group was younger than the PPV-only group and had a higher prevalence of giant retinal tears and a greater number of retinal tears. Single-surgery anatomical success was similar between groups: 14/28 eyes (50.0%) in the SB + PPV group and 39/79 eyes (49.3%) in the PPV-only group. Among eyes requiring reoperation, the interval to second surgery was numerically longer in the SB + PPV group than in the PPV-only group (6.28 [3.73-9.10] vs. 2.84 [0.85-9.92] months; p = 0.150), while persistent and recurrent RRD patterns were similar between groups. Silicone oil removal was performed more often in the SB + PPV group (92.9% vs. 74.7%), while long-term silicone oil retention was less frequent (7.1% vs. 25.3%), although this difference did not reach conventional statistical significance. Final visual acuity was better in the SB + PPV group than in the PPV-only group (0.70 [0.44-1.30] vs. 1.30 [0.52-2.70] logMAR; p = 0.035), although visual improvement from presentation did not differ significantly between groups. Among PPV-only eyes requiring reoperation, 10/40 (25.0%) underwent secondary scleral buckling. CONCLUSIONS: Despite greater baseline complexity, adjunctive SB was associated with comparable SSAS and better final visual acuity, although visual acuity improvement from presentation did not differ significantly between groups. These findings suggest that adjunctive SB may modify the postoperative course in selected high-risk silicone oil cases, but prospective studies are neede

OBJECTIVE: In a national, multicenter quality improvement (QI) collaborative to reduce subthreshold inpatient phototherapy, the proportion of subthreshold encounters was high at baseline and remained high after the intervention period. This study aimed to assess why clinicians start subthreshold phototherapy and the barriers to reducing its use. METHODS: This convergent mixed methods study used data from the Learning and Implementing Guidelines for Hyperbilirubinemia Treatment QI collaborative. Site leaders were asked 2 open-ended questions on why clinicians start phototherapy below threshold and what the biggest barriers were to changing clinician hyperbilirubinemia practice. Themes from these responses informed the variables selected for the quantitative analysis. For each variable, we used F-tests to assess for associations with changes in mean subthreshold phototherapy from the baseline (2/2022-7/2022) to intervention period (2/2023-1/2024). RESULTS: We identified 6 themes for subthreshold phototherapy use and 6 for barriers of change. Themes identified for both included lack of timely outpatient follow-up, concerns for prolonging birth hospitalizations and/or causing readmissions, and clinician habit and discomfort with change and higher total serum bilirubin levels. Quantitatively, despite the reported challenges with follow-up, access to weekend bilirubin follow-up or home phototherapy were not associated with statistically significant reductions in subthreshold phototherapy, nor was implementation of clinical pathways to standardize care and discourage subthreshold phototherapy. CONCLUSION: Our results suggest that clinician decisions to start subthreshold phototherapy are complex and ineffectively addressed by traditional QI interventions. Deeper exploration of barriers and alternative interventions may be needed in future QI work.

BACKGROUND: Critically ill patients sometimes require insertion of a feeding tube into the small intestine. This study evaluated the ease of placement of a proprietary small intestinal feeding tube incorporating a distal tip camera. METHODS: investigator-initiated, industry-funded, prospective cohort study was conducted at four intensive care units across two countries. Patients were eligible if the treating clinician requested small intestinal feeding tube insertion. Operators were physicians or senior dietitians, and attempts were categorised as "inexperienced" (≤4 attempts) or "experienced" (≥5 attempts). The primary outcome was the overall probability of successful small intestinal placement. Secondary outcomes included procedural time and the posterior probabilities of success according to operator classification and experience, estimated using Bayesian hierarchical regression models incorporating minimally informative priors and random intercepts for clustering within operators. RESULTS: The device was used by 11 operators in 68 patients. Prior 24-h cumulative gastric residual volumes were 454 (standard deviation: 453) millilitres. The overall probability of success was 75% (95% credible interval: 61-86%). Experienced users and inexperienced users were successful in 30 of 38 (79%) and 21 of 30 (70%) attempts, respectively. Overall median (interquartile range) procedural times for successful versus unsuccessful placement were 23 (10-35) and 30 (20-42) minutes, respectively. In a multivariable analysis, the posterior probabilities of improved success (odds ratio >1) were 83% (gastrokinetic drug prescription), 82% (operative versus nonoperative admission), and 65% (device experience). CONCLUSIONS: The probability of successful small intestinal placement of feeding tubes by motivated clinicians in a critical care environment approximated the prespecified threshold of 80%, without the need for extensive specific device experience.

STUDY DESIGN: Retrospective cohort study. PURPOSE: To determine the independent risk factors associated with postoperative shoulder imbalance (PSI) in adolescent idiopathic scoliosis (AIS) patients after posterior spinal fusion. BACKGROUND: Postoperative shoulder imbalance is one of the most frequent complications following surgery in cases of adolescent idiopathic scoliosis (AIS). Quantitative Radiographic parameters that can be used for the preoperative planning of surgery are not clearly identified. The purpose of this study was to determine independent predictors of postoperative shoulder imbalance and to examine the correction PT/MT ratio as a quantitative radiographic predictor. METHODS: For this study, 468 consecutive AIS patients subjected to posterior spinal fusion surgery, during January 2018 through December 2025 have been reviewed retrospectively. Data for this study were collected from the Hakeem electronic medical records system while radiographic measurements were obtained from the Picture Archiving and Communication System (PACS). PT and MT Cobb angles, T1 inclination, clavicle angle, radiographic shoulder height (RSH), and number of fusion segments were some of the radiographic measurements taken. PSI was diagnosed as RSH ≥ 15 mm after at least 24 months of follow up period. Independent predictors of PSI were found using multivariate logistic. RESULTS: Female patients comprised 82%, while the mean age was 14.7 ± 1.9 years. PSI occurred 20.9% (n = 98). In comparison to the non-PSI group, the PSI group had low levels of UIV (below T3, p = 0.003), high preoperative left shoulder elevation, large PT Cobb angles (p < 0.001), and low PT correction rate (p < 0.001). Univariate analysis showed that residual proximal thoracic curvature ≥ 15° (OR 3.1, 95% CI 1.8-5.4, p < 0.001), UIV below T3 (OR 2.8, 95% CI 1.6-4.9, p = 0.001), preoperative left shoulder elevation, and PT/MT correction ratio below 0.59 (r=-0.53, p < 0.001) were independent factors of postoperative shoulder imbalance. The ROC curve analysis revealed an optimal PT/MT correction ratio threshold of 0.59. CONCLUSIONS: Residual proximal thoracic deformity and UIV lower than T3 were significant independent risk factors for shoulder imbalance. A PT/MT correction ratio less than 0.59 was an independent risk factor and might serve as a quantifiable radiographic criterion for surgical plann

BACKGROUND: To compare the clinical and electrophysiological outcomes of subcutaneous ulnar nerve transposition (SCT) alone versus SCT combined with supercharge end-to-side anterior interosseous nerve transfer (SETS) for the treatment of severe cubital tunnel syndrome (CuTS). METHODS: This retrospective cohort study included 48 patients with severe CuTS who underwent surgery between 2016 and 2024. Patients were divided into the SETS group (SCT+SETS, n=24) and the control group (SCT alone, n=24). The primary outcome was the rate of recovery of intrinsic hand muscle strength at 12 months postoperatively. Secondary outcomes included compound muscle action potential (CMAP) amplitude, MCV, Quick-DASH scores, SETS-specific near-nerve stimulation positivity rates, and complication rates. RESULTS: At 12 months postoperatively, 75.0% (18/24) of patients in the SETS group achieved MRC grade 4 first dorsal interosseous (FDI) muscle strength, whereas no control group patient reached grade 4 (P<0.001). SETS group FDI-CMAP amplitude improved from 0.58±0.12 mV preoperatively to 2.45±0.85 mV postoperatively, with a mean improvement of 1.87±0.79 mV, significantly greater than the 0.70±0.78 mV improvement in the control group (P<0.001). The near-nerve stimulation positivity rate in the SETS group was 71.4%. Complication rates did not differ significantly between groups (P>0.05). Multivariate logistic regression identified disease duration <12 months (OR=4.2, 95% CI: 1.6-11.0), preoperative FDI strength ≥MRC grade 2 (OR=3.5, 95% CI: 1.3-9.4), and age <60 years (OR=2.7, 95% CI: 1.0-7.2) as independent predictors of favorable functional recovery after SETS. CONCLUSIONS: In patients with severe CuTS, adding SETS to SCT significantly improves intrinsic hand muscle strength recovery and electrophysiological outcomes without increasing the risk of complications. Patients with disease duration <12 months, age <60 years, and mild-to-moderate preoperative muscle atrophy derive the greatest benefit.

BACKGROUND Pure laparoscopic donor major hepatectomy (PLDMH) offers important advantages for donors but has largely been restricted to expert surgeons. Evidence on fellowship-trained surgeons (FTSs) performing PLDMH after structured training is limited. This study evaluated donor safety and operative efficiency of FTSs using propensity score matching (PSM) and cumulative sum (CUSUM) analysis. MATERIAL AND METHODS We retrospectively reviewed 517 consecutive PLDMHs from 3 centers, including 1 expert surgeon (n = 462) and 3 FTSs (n = 55). FTSs underwent a structured, phase-task-based training program; 2 received short-term on-site proctorship for initial cases. To reduce baseline differences, we applied 1: 3 propensity score matching (PSM) between FTS and expert cases. Donor and recipient characteristics were balanced. Learning curves were assessed using risk-adjusted CUSUM for major donor complications and residual CUSUM for operative time. RESULTS After PSM, 55 FTS cases were matched to 165 expert cases. Major donor complications were comparable (5.5% vs 4.2%, P=0.714) and no case required conversion to open surgery. Donor operative time was longer in the FTS group (338±102 vs 220±44 minutes, P<0.001). Recipient biliary leakage was more frequent in the FTS group (18.2% vs 8.5%, P=0.046), whereas other outcomes were similar after matching. Risk-adjusted CUSUM demonstrated stabilization of donor safety within 8 to 10 cases per FTS, while operative efficiency stabilized after 6 to 15 cases. CONCLUSIONS FTSs demonstrated acceptable donor safety outcomes under structured training conditions, with operative performance showing a trend toward improvement after approximately 10 to 15 cases.

PURPOSE: To evaluate the postoperative healing course and clinical outcomes of high-risk oculoplastic reconstructions requiring graft-based surgery, in which adjunctive hyperbaric oxygen therapy (HBOT) was used to support wound healing. METHODS: This retrospective case series included 11 patients who underwent oculoplastic surgery with graft-based reconstruction and were considered at high risk for delayed healing and/or tissue compromise. Indications for surgery were orbital implant (sphere) exposure repair (n = 5), cicatricial entropion (n = 1), necrotizing scleritis (n = 1), tissue loss following trauma (n = 1), wound dehiscence and infection after lower eyelid blepharoplasty (n = 1), orbital cellulitis following endophthalmitis and evisceration after cataract surgery (n = 1), and delayed wound healing after dermolipoma excision (n = 1). All patients received graft-based surgical management with adjunctive HBOT. Demographic data, culture results, number of HBOT sessions, and recovery time were analyzed. Patients were evaluated according to HBOT exposure (10 vs. 20 sessions). RESULTS: All patients underwent graft-supported surgical repair in the setting of anticipated difficult healing. Culture growth was detected in 5 patients. Clinical stabilization and wound closure were achieved without the need for additional major reconstructive procedures in most cases. Patients receiving 20 HBOT sessions had a longer observed mean recovery time compared with those receiving 10 sessions (82.6 vs. 40.9 days; p = 0.032). CONCLUSION: In a heterogeneous cohort of high-risk oculoplastic reconstructions requiring grafting-including orbital implant exposure repair and complex inflammatory, infectious, or traumatic etiologies-adjunctive HBOT was used as a supportive modality and was associated with acceptable healing outcomes. The longer recovery observed with extended (20-session) HBOT courses likely reflects greater baseline disease severity rather than a reduced treatment effect. Given the retrospective design and clinical heterogeneity, further studies are needed to clarify patient selection criteria and define optimal HBOT protocols in oculoplastic reconstruction.

BACKGROUND: Esophagectomy for esophageal cancer is associated with significant morbidity and can result in financial hardship, yet this aspect of survivorship remains understudied. This study evaluated the prevalence and risk factors of financial toxicity (FT) among patients following esophagectomy. METHODS: Patients who underwent esophagectomy between January 2016 and September 2022 were surveyed about demographic, financial, and employment history. Financial toxicity was measured by using the validated COST survey. Multivariate analyses identified predictors of FT. RESULTS: Of 370 patients contacted, 159 (43%) completed the survey. Median age was 65.3 years; 82.4% were male. Following therapy, 44.7% reported decreased work hours or stopped working entirely. Insurance was employer-based for 50.3%, while 40.6% had Medicare. Financial toxicity was reported by 37.1%. Risk factors included larger household size (odds ratio 2.3), low credit score (odds ratio 13.2), while high income and active retirement were protective. CONCLUSIONS: More than a third of esophagectomy patients were found to have FT. Those with poor baseline financial health or disrupted employment were most vulnerable and may benefit from early financial counseling and support interventions.

INTRODUCTION: Persons with substance use disorders (SUDs) have markedly increased risk for lifestyle-related diseases and reduced life expectancy. Initial findings suggest that high-intensity physical training (HIT) represents an efficient and effective training modality for improving physical and functional capacity for persons with SUDs. However, acheiving such improvements depends not only on the availability of such training modalities but also on adherence, which remains insufficiently understood in this population. Thus, to extend the benefits of HIT to additional persons within this population, there is a need for a broader, deeper, and more patient-centred understanding of their experiences with HIT integrated into specialised treatment, including facilitators and barriers to adherence. METHODS AND ANALYSIS: This protocol article presents an ongoing qualitative collaborative health service study where inpatients with SUDs are interviewed in-depth about their experiences of and adherence to HIT by semi-structured interview guides. Approximately 20 inpatients with SUDs will be purposively recruited based on relevant background variables and inclusion criteria to ensure breadth in experiences: 10 who have adhered to supervised HIT as part of specialised SUD treatment and 10 who have not. Depth will be supported through in-depth interviewing, reflexive field notes, and collaborative thematic analysis with persons with lived experiences. ETHICS AND DISSEMINATION: The study has received ethical approval from Regional Committees for Medical and Health Research Ethics (Reference ID: 2019/501). By strengthening the knowledge base on factors influencing adherence and non-adherence in HIT as part of clinical practice, the findings may support patient's adherence to HIT integrated in SUD treatment in a more person-centred way, ultimately benefiting the physical and functional capacity for additional persons with SUDs. Findings will be disseminated together with persons with lived experiences via conferences, peer-reviewed publications, as well as popular-scientific communication and media. Finally, the findings may generate theoretically informative insights into patients' experiences and mechanisms influencing adherence to HIT, as well as novel concepts and insights needed for new research directions within an increasingly prioritised field in specialised SUD

OBJECTIVES: To identify complications associated with insertion, use, and removal of radial and brachial arterial catheter in two adult ICUs in Bogotá, Colombia, using a comparative cohort design with propensity score matching. METHODS: A retrospective cohort study was conducted in two adult ICUs. Adult patients who underwent ultrasound-guided arterial catheter insertion between January and December 2024 were included. The exposure was catheter insertion site, classified as radial or brachial. The primary outcome was the occurrence of at least one device-related complication during insertion, maintenance, or removal. Secondary outcomes included complications, procedural variables, and ICU length of stay. To reduce confounding, 1:1 propensity score matching was applied; covariate balance was assessed using standardized mean differences. Post-matching binary outcomes were analyzed using generalized estimating equations (GEE) with robust standard errors and matched-pair clustering. RESULTS: A total of 995 patients were included: 496 in the radial group and 499 in the brachial group. After matching, 842 patients were analyzed, with 421 patients in each group and covariate balance (SMD < 0.1). Brachial catheterization was associated with lower odds of at least one catheter-related complication (OR 0.61, 95% CI 0.44-0.86; p = 0.005). Post-insertion hematoma was associated with brachial access after multivariable GEE adjustment (aOR 4.11, 95% CI 1.49-11.31; p = 0.006), whereas brachial access was associated with lower odds of vasospasm (aOR 0.35, 95% CI 0.22-0.55; p < 0.001). No significant differences were observed in other complications or ICU length of stay. CONCLUSIONS: In critically ill adults, brachial arterial catheter insertion was associated with fewer complications, although it showed a higher risk of post-insertion hematoma. Radial insertion was associated with increased vasospasm. IMPLICATIONS FOR CLINICAL PRACTICE: These findings support individualized selection of arterial catheter insertion site according to clinical profile and complication risk.

BACKGROUND: The benefit of additional gastrectomy after eCuraC-2 non-curative endoscopic resection for early gastric cancer in older patients is uncertain because of competing mortality. METHODS: This nationwide retrospective cohort included 1,038 patients aged ≥75 years with eCuraC-2 resection at 22 Korean hospitals (352 additional gastrectomy; 686 surveillance). The primary outcome was overall survival (OS). Secondary outcomes were gastric cancer (GC)-specific mortality and any recurrence. Multivariable Cox and competing-risk analyses were performed. Inverse probability of treatment weighting (IPTW) was used for sensitivity analysis. RESULTS: At 5 years, OS was 76.5% with surveillance versus 83.0% after additional gastrectomy (hazard ratio [HR] 1.37, 95% confidence interval [CI] 1.08-1.74; P=0.01). However, surveillance patients were older (≥80 years: 43.3% vs 24.1%) and more frequently had ECOG-PS 2-4 (11.7% vs. 6.8%), whereas gastrectomy patients had higher-risk pathology, including lymphovascular invasion (60.8% vs 37.0%). Although recurrence was more frequent with surveillance (9.9% vs. 1.8%; adjusted SHR 5.71, 95% CI 2.57-12.69), GC-specific death was rare (17 events; 1.3% vs. 1.1%). The unadjusted SHR for surveillance versus gastrectomy was imprecise (1.62, 95% CI 0.53-4.96; P=0.40), whereas the IPTW-weighted sensitivity estimate was larger (SHR 3.34, 95% CI 1.28-8.72; P=0.014). The derived all-cause/GC-specific mortality-rate ratios were 22.2 with surveillance and 27.3 after gastrectomy. CONCLUSIONS: In elderly patients with non-curative ESD, prognosis is driven more by competing non-GC mortality than by GC-related death. Additional gastrectomy may improve cancer-specific outcomes in selected patients, but its OS benefit appears limited. Management should therefore be individualized rather than based on curability criteria alone, balancing pathological risk against operative risk, postoperative functional consequences, physiological reserve, and patient preferences.

BACKGROUND: Breast reconstruction following oncologic mastectomy is an integral component of comprehensive breast cancer care, with implant-based reconstruction consistently being reported to be the most commonly performed worldwide. Although immediate reconstruction offers the clear benefit of reducing the number of necessary surgical procedures and providing immediate aesthetic results, concerns persist regarding its feasibility in high-risk patient populations. Obesity has been suggested to be a potential contributor to lymphatic dysfunction and impaired lymphatic vasculature; both mechanisms can predispose patients to the development of postmastectomy lymphedema. Postmastectomy lymphedema is a chronic, debilitating condition with significant implications on quality of life, functional capacity, and healthcare utilization. Established risk factors include axillary lymph node dissection, radiation therapy, and the extent of mastectomy resection. Timing of reconstruction, however, especially in obese patients undergoing implant-based reconstruction, has not been clearly delineated. METHODS: Retrospective TriNetX cohort of obese adults undergoing implant-based breast reconstruction compared immediate versus delayed timing using propensity matching, assessing short- and long-term complications, including lymphedema, via risk ratios and survival analyses. RESULTS: Among 6082 obese patients, 1944 matched pairs underwent immediate or delayed implant-based reconstruction. Immediate reconstruction showed higher 90-day complications and a persistently increased risk of lymphedema through 5 years, confirmed by Kaplan-Meier and Cox regression analyses. CONCLUSIONS: Among obese patients undergoing implant-based breast reconstruction, immediate reconstruction is associated with higher rates of early postoperative complications and a persistent increase in postmastectomy lymphedema risk compared with delayed reconstruction.

BACKGROUND: Sleep deprivation and poor sleep quality are critical problems among intensive care unit (ICU) patients, with significant implications for recovery, delirium onset and clinical outcomes. Despite growing scientific interest, no bibliometric study has systematically mapped the intellectual structure and thematic evolution of this field. AIM: To analyse the bibliometric characteristics and thematic structure of publications on sleep deprivation, sleep promotion and sleep quality in ICU patients indexed in the Web of Science (WoS) database between 1983 and 2026. STUDY DESIGN: A descriptive and evaluative bibliometric analysis was conducted. Data were retrieved on April 26, 2026, from the WoS Core Collection using a comprehensive search strategy. Publications were filtered by document type, WoS categories (nursing, critical care medicine, anaesthesiology) and index (SCI-EXPANDED, SSCI, ESCI). Data were analysed using R software with the Biblioshiny interface, and annual publication trends were evaluated using Microsoft Excel. RESULTS: Of 11 418 publications retrieved, 379 met the inclusion criteria, spanning 37 years (1983-2026). Linear regression revealed a statistically significant positive trend in publication output (β = 0.643, R2 = 0.704, r = 0.839, p < 0.001), with mean annual publications of 10.24 ± 8.83 and notable acceleration from the 2000s onwards. Thematic mapping identified 'sleep', 'sleep deprivation' and 'delirium' as motor themes both highly central and well developed. Emerging concepts included circadian rhythm, actigraphy, fatigue, pain and anxiety. CONCLUSIONS: ICU sleep research has grown substantially over four decades, with sleep deprivation and delirium emerging as co-dominant research priorities. Thematic gaps and emerging clusters identified in this analysis highlight important directions for future nursing research and evidence-based practice development in critical care. RELEVANCE TO CLINICAL PRACTICE: This bibliometric analysis identified sleep deprivation and delirium as the co-dominant motor themes of ICU sleep research, and intervention-related concepts such as earplugs, eye masks and melatonin as emerging clusters. These evidence-based trends can guide ICU nurses in prioritizing targeted sleep promotion protocols and support policymakers in directing resources toward the most scientifically mature intervention area

PURPOSE: Inpatient clinical rotations are central to residency training. Studies have examined aspects of the inpatient learning environment, but few have characterized factors that differentiate exemplary from problematic rotations from the resident perspective. This study aimed to understand what distinguishes rotations through analysis of resident-generated evaluations across inpatient and acute-care specialties in a residency program. METHODS: Residents in a large pediatric residency program complete anonymous end-of-rotation evaluations, rating rotations on a 5-point scale with optional free-text commentary. This study analyzed inpatient and acute-care rotation evaluations submitted July 2019-June 2024 with a "very highly" or "very poorly" rating and an associated free-text response. Two investigators inductively coded a subset of evaluations to develop a codebook, which was applied to the remaining evaluations. Codes were organized into subthemes and themes, which aligned with self-determination theory (SDT). SDT was used as a guiding framework, and thematic saturation was confirmed. RESULTS: A total of 712 "very highly" rated and 106 "very poorly" rated rotation evaluations met the inclusion criteria. Subthemes impacted one or more domains of SDT: autonomy, competence, and relatedness. Autonomy was shaped by ownership of patient care, supervisor oversight, and leadership. Competence was fostered by high-quality teaching, educational context, and patient-based learning. Relatedness was enhanced by communication, team culture, and role clarity. Psychological safety and trainee team inclusion impacted all SDT domains. CONCLUSIONS: Autonomy, competence, and relatedness, promoted by psychological safety and trainee integration, are central to the resident experience. Educators should consider these factors when designing inpatient rotations.

Leprosy, also known as Hansen's disease, is a chronic infection caused by Mycobacterium leprae or Mycobacterium lepromatosis. Although global prevalence has decreased, the number of cases each year has plateaued at ∼200,000. In the United States, sporadic cases continue to occur, primarily in the southern states. A retrospective cohort study was conducted from 1992 to 2024 using the TriNetX Research Network (Cambridge, MA, USA), an international electronic health record network, to characterize the clinical features of leprosy and identify factors predicting hospitalization among individuals diagnosed with the disease. Of 215 patients, 30 (14%) required hospitalization. These hospitalized patients were generally older and had other health conditions. Stepwise logistic regression was used to identify a higher absolute neutrophil count and a higher Charlson Comorbidity Index value as predictors of hospitalization. Most patients were from the United States, and the slight majority of cases were clustered in the southern states. These results provide one of the largest recent descriptions of leprosy, highlighting how leprosy reactions and other health issues may influence outcomes, including hospitalization, and emphasizing the importance of ongoing surveillance of leprosy in the southern United States and other regions.

BACKGROUND: Psychosis is a frequent and disabling non-motor complication of Parkinson's disease (PD). Reported prevalence varies widely, and data in Brazilian cohorts remain scarce. OBJECTIVE: To estimate the prevalence of PD-associated psychosis (PDP) in a Brazilian cohort and to describe its sociodemographic and clinical profile. METHODS: We conducted a cross-sectional study in a Brazilian movement disorders outpatient clinic between May and December of 2022. Adult patients with idiopathic PD defined by the United Kingdom's Parkinson's Disease Society Brain Bank criteria were consecutively evaluated. Sociodemographic and clinical variables were collected. Psychosis was assessed using the diagnosis criteria proposed by the National Institute of Neurological Disorders and Stroke and the National Institute of Mental Health (NINDS/NIMH) and graded with the Movement Disorders Society's Unified PD Rating Scale (MDS-UPDRS). Cognitive screening was performed using the Mini-Mental State Examination (MMSE), and disease severity was assessed with the modified Hoehn & Yahr scale (mH&Y). Neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory Questionnaire (NPI-Q). Descriptive analyses and exploratory univariate comparisons were performed. RESULTS: In total, 75 patients were included. The median age was 68 years (IQR: 59.5-74.5), and the mean age at PD onset was 56.0 ±  9.8 years. Median disease duration was 10 years (IQR: 6-14.5). Most patients were male (54.7%) and self-identified as Mixed-race (48.6%) or Black (31.1%). According to the mH&Y scale, 82.7% had mild-to-moderate disease. Furthermore, PDP was diagnosed in 18 patients (24%) according to NINDS/NIMH criteria. Minor phenomena and hallucinations were the most frequent psychotic manifestations, each occurring in 72.2% of PDP cases. CONCLUSION: In this Brazilian cohort, PDP had a prevalence of 24%. These findings reinforce that psychosis is a frequent non-motor manifestation of PD and highlight the importance of systematic clinical screening in routine care.

BACKGROUND: Prophylactic closed-incision negative pressure wound therapy (ciNPWT) may reduce risk of postoperative wound complications, but its use in breast surgery remains uncertain due to lack of breast-specific recommendations in guidelines. This meta-analysis addresses this gap by evaluating the efficacy of ciNPWT versus standard dressings in non-autologous breast surgery. METHODS: A meta-analysis of RCTs and observational studies comparing ciNPWT versus standard dressings in patients undergoing mastectomy, implant-based breast reconstruction, or mammoplasty was conducted following PRISMA (from inception to September 2025). Outcomes were total wound complications, surgical site infection, wound dehiscence, necrosis, seroma, haematoma, re-operation, and implant loss. Risk of bias (RoB2, ROBINS-I) and certainty (GRADE) were assessed, and data pooled (RStudio). Registered with PROSPERO (CRD420251002005). RESULTS: Twenty studies (6 RCTs, 14 observational) involving 2287 patients (3376 breasts) were included. ciNPWT significantly reduced total wound complications (RR 0.56, 95%CI 0.42-0.74; p<0.0001; I²=71.9%; moderate certainty), corresponding to an absolute risk reduction (ARR) of 14% (31.8% to 17.8%). Wound dehiscence (RR 0.48, 95%CI 0.29-0.79; p=0.0037; I²=33.4%) and necrosis (RR 0.67, 95%CI 0.48-0.94; p=0.0187; I²=7.5%) were also significantly reduced. Subgroup analyses suggested stronger effects in BMI ≥30 (RR 0.41 vs 0.61 for BMI <30) and with -125 mmHg settings (RR 0.46 vs 0.65 for -80 mmHg), though differences were not statistically significant (p>0.20). CONCLUSION: Moderate-certainty evidence indicates that ciNPWT reduces postoperative wound complications-particularly dehiscence and necrosis-with a clinically meaningful ARR of 14% for total wound complications. Refining patient selection and device configuration may further enhance its applicability.

BACKGROUND: Gastrointestinal surgery is associated with significant postoperative morbidity. Serum albumin, an inexpensive biomarker that reflects nutritional reserve and systemic inflammation, may help identify at-risk patients. The prognostic value of hypoalbuminaemia in gastrointestinal surgery is not well defined. We aimed to evaluate the association between preoperative hypoalbuminaemia and postoperative outcomes in gastrointestinal surgery. METHODS: We searched MEDLINE, Embase, and two Cochrane databases from inception to July 25, 2025 (PROSPERO: CRD420251130909) for studies comparing adverse outcomes between hypoalbuminaemic and normoalbuminaemic patients. Eligible studies reported at least one postoperative outcome. RESULTS: Across 42 studies, the prevalence of preoperative hypoalbuminaemia was 10.3%, and was lower in bariatric surgery (5.5%) than in non-bariatric surgery populations (17.1%). In hypoalbuminaemic patients, 30-day mortality was more than three-fold higher (RR 3.37, 95% CI 2.59-4.37), all-cause complications were 49% higher (RR 1.49, 1.33-1.68), hospital length of stay was prolonged by 3.02 days (1.63-4.41), and readmission (RR 1.38, 1.22-1.57), reoperation (RR 1.32, 1.22-1.43), and non-home discharge (RR 1.51, 1.28-1.78) were significantly increased. Hypoalbuminaemia was associated with more cardiovascular (RR 1.75, 1.41-2.17), respiratory (RR 2.15, 1.79-2.58), infectious (RR 1.72, 1.47-2.01), and thromboembolic complications (RR 2.00, 1.76-2.27). Between-study heterogeneity was substantial, and prediction intervals were wide. CONCLUSION: Preoperative hypoalbuminaemia is associated with increased mortality, morbidity, and healthcare utilisation in gastrointestinal surgery. As the primary associations derive from unadjusted observational data, preoperative albumin is best interpreted as a marker of perioperative risk rather than a proven modifiable target. Whether interventions that correct hypoalbuminaemia improve postoperative outcomes requires further research.

INTRODUCTION: The optimal ICU sedation strategy to improve patient-reported experience is unknown. In a planned secondary analysis of the A2B randomised trial, we evaluated the effect of sedation strategy (dexmedetomidine, clonidine or propofol) on recalled patient experience at 90 days post-randomisation. Using mediation analyses, we explored plausible mediators of the relationship between sedation strategy and patient experience. METHODS: We analysed data for all patients from A2B who completed the Intensive Care Experience Questionnaire (ICE-Q) at 90 days. The primary outcome was patient-recalled experience, measured by the four ICE-Q domain scores (awareness, frightening memories, recall, satisfaction). Sedation strategy effect was evaluated using linear regression, adjusting for potential confounders. Mediation analyses were conducted for duration of mechanical ventilation; ICU stay; and days with pain behaviour, agitation and coma/delirium. RESULTS: Of 1404 patients included in the primary trial analysis, 1009 (71.9%) were alive at 90 days post-randomisation with ICE-Qs completed by 289/1009 (28.6%). Compared with propofol, dexmedetomidine sedation was associated with higher awareness of surroundings (median score 32 vs. 28, adjusted mean difference 3.6, 95%CI 1.0-6.2, p = 0.01), but clonidine sedation had no association (difference 2.4, 95%CI -0.2-5.0, p = 0.07). No associations were found with other ICE-Q domains. The contribution of the five potential mediators on the dexmedetomidine-awareness relationship was small. DISCUSSION: Dexmedetomidine compared with propofol sedation strategy may be associated with increased recalled awareness of surroundings, which is considered a favourable indicator of ICU experience. Together with the primary A2B trial results, which showed no effect on ventilation duration, these hypothesis-generating findings in a subgroup of the A2B cohort do not support the use of dexmedetomidine over propofol based on patient-reported experience. Based on our findings, we advocate that a personalised approach to sedation strategies should continue to be used.

INTRODUCTION: Respiratory syncytial virus (RSV) causes significant disease in older and comorbid adults. Current UK vaccination recommendations restrict eligibility to adults ≥ 75 years, 65-74 years with chronic respiratory disease or immunosuppression, and those in care homes, but evidence on clinical burden in adults < 75 years with comorbidities is limited. This study assessed patient characteristics, healthcare resource utilization (HCRU), and mortality in adults hospitalized with RSV in England. METHODS: Population-based retrospective cohort study using linked Clinical Practice Research Datalink Aurum and Hospital Episode Statistics. Adults ≥ 60 years hospitalized with RSV between October 2014 and March 2019 were included. We defined RSV episodes as 90 days post-diagnosis. We defined cases using diagnosis codes for confirmed RSV (RSV-specific) or acute lower respiratory tract infection with exclusion of other causative pathogens (RSV-possible). All-cause HCRU (hospitalizations, critical care admissions, outpatient attendance, primary care consultations, and prescriptions) and case fatality rates were assessed. Results were stratified by age (60-74 and ≥ 75 years), case definitions (RSV-specific, RSV-possible), and comorbidity profiles (chronic respiratory disease, immunocompromised, cardiovascular disease). RESULTS: A total of 97,712 hospitalized episodes in those aged ≥ 60 years were included in the analysis, of which 785 (0.8%) were RSV-specific cases (n = 338 aged 60-74 years, n = 447 aged ≥ 75 years). In RSV-specific cases, median (IQR) cumulative length of stay (LoS) for those ≥ 75 years was 10.00 (6.00-22.00) days, which was equivalent to or lower than each comorbidity subgroup in those aged 60-74 years, with the longest LoS in those immunocompromised (11.50 [7.00-26.00] days). Critical care admissions were more often observed across comorbidity stratifications (13.85-22.34%) compared to those ≥ 75 years (5.03%). All-cause and RSV-related case fatality rates for RSV-specific cases were highest among those ≥ 75 years (all-cause: 19.3%; RSV-related: 10.3%). CONCLUSIONS: HCRU within RSV episodes in those aged 60-74 years across comorbidity profiles was equal to or greater than that in those aged ≥ 75 years. These findings highlight the need to prioritize consideration of comorbidity groups that could benefit from RSV vaccination.

BACKGROUND: Minimally invasive surgery (MIS) improves short-term outcomes in elective colectomy, however, the choice of surgical approach in hemodynamically stable patients with obstructing right-sided colon cancer remains unclear in emergency settings. MIS could be considered and the present study aims to evaluate short-term outcomes of MIS in bowel obstructed patients compared with open surgery (OPEN). METHODS: A retrospective nationwide study including patients from the nationwide Swedish Colorectal Cancer Registry (SCRCR) undergoing emergency right-sided colectomy in Sweden (2017-2023) was conducted. Propensity score matching (1:1) was performed based on sex, age, ASA class, hospital size, and operative timing (on-call vs. daytime). Outcomes included length of stay (LOS), postoperative complications, and surgical quality indicators. Analysis was performed according to intention-to-treat. RESULTS: A total of 1147 patients were identified. Of the 1,147 included patients, 99 (8.6%) underwent an initially minimally invasive approach. After matching, 99 patients remained in each group. The conversion rate was 34%. Median LOS was 9 days (IQR 6;14) after OPEN and 6 days (IQR 5;10) after MIS. In quantile regression with bootstrap standard errors, MIS was associated with a 3-day shorter median LOS (median difference - 3.0 days, 95% CI - 4 to - 2, p = 0.002). Postoperative complications (Clavien-Dindo ≥ 2) occurred in 38.8% after OPEN and in 23.2% after MIS. Logistic regression analysis with robust standard errors showed significantly lower odds of postoperative complications after MIS (OR 0.48, 95% CI 0.27-0.83, p = 0.009). No significant differences were observed in re-admission, 90-day mortality, R0 resection, lymph node yield, blood loss or operative time. CONCLUSION: In this nationwide observational cohort, an initially minimally invasive approach was associated with shorter length of stay and fewer postoperative complications. No statistically significant differences were observed in the available short-term surgical and pathological quality indicators. Given the limited number of MIS procedures and potential for residual confounding, these findings support further evaluation of MIS in carefully selected patients.

OBJECTIVES: To develop an Achievable Benchmarks of Care (ABCs) report card for common conditions managed by pediatric hospital medicine (PHM). METHODS: We performed a retrospective cross-sectional study of encounters for 13 common pediatric conditions between January 1, 2023, and December 31, 2024, using the Pediatric Health Information System database. Conditions included bronchiolitis, asthma, pneumonia, urinary tract infection, constipation, gastroenteritis, cervical lymphadenitis, skin and soft tissue infection, orbital cellulitis, osteomyelitis, septic arthritis, neonatal fever, and simple febrile seizure. Overall utilization measures included length of stay (LOS) and readmission rate. Condition-specific measures included imaging, laboratory testing, procedures, and medications ordered. ABCs were calculated using top-performing hospitals (≥10% of each cohort). For each measure, we calculated the median hospital performance, IQR, ABCs, and performance gap (difference between median performance and the ABC). RESULTS: We compiled 115 measures for the 13 conditions, representing 237 283 hospitalizations or 33.5% of nonsurgical discharges among children meeting our overall inclusion/exclusion criteria. For 11 conditions, calculated ABCs for LOS were less than 48 hours. The ABC LOS for the remaining 2 conditions (osteomyelitis and septic arthritis) was less than 74 hours; these 2 conditions experienced the greatest performance gap. ABC readmission rates across all conditions were less than 2.0%. As an example of a condition-specific measure, we assessed chest radiograph performance across respiratory conditions with ABCs ranging from 20.6% to 57.9%, associated with a performance gap of 18.3% to 22.4%. CONCLUSIONS: We developed a core set of PHM-specific ABCs and incorporated them into designed to support local and collaborative multicenter improvement efforts.

PURPOSE: Diabetes mellitus (DM) may affect postoperative recovery, but evidence in pituitary tumor surgery remains limited. We investigated the association between DM and short-term outcomes after transsphenoidal surgery for pituitary tumors. METHODS: We retrospectively analyzed adults in the Taiwan Pituitary Tumor Registry who underwent transsphenoidal surgery for benign pituitary tumors between 2009 and 2019. Patients were categorized into DM and non-DM groups. Associations between DM, prolonged length of hospital stays (LOS), 14-day readmission rate, and complications were determined using regression analyses. Tumor-type stratified analyses and receiver operating characteristic (ROC) analyses of glycated hemoglobin (HbA1c), fasting glucose, and random glucose were also performed. RESULTS: Data of 970 patients were analyzed, of whom 144 (15%) had DM. DM was not significantly associated with prolonged LOS or 14-day readmission, but was significantly associated with higher odds of CSF leak (adjusted odds ratio [aOR] = 3.35, 95% confidence interval [CI]: 1.18-9.51, p = 0.023) and antibiotic use for ≥ 7 days (aOR = 5.41, 95% CI: 1.13-25.87, p = 0.034) in age-adjusted analysis. In the non-functioning tumor subgroup, the association with antibiotic use for ≥ 7 days persisted (aOR 7.37, 95% CI 1.46-37.12), whereas the association with CSF leak was not statistically significant. Among patients with DM and non-functioning tumors, glycemic markers showed apparent discrimination for postoperative infection and CSF leak, with area under the curve values ranging from 0.83 to 0.93. CONCLUSIONS: DM was associated with selected short-term complications after transsphenoidal surgery, particularly CSF leak and prolonged antibiotic use. These exploratory findings require confirmation in larger prospective studies with comprehensive surgical data.

BACKGROUND: Differentiating bacterial from viral infections in acute care is challenging, often leading to inappropriate antibiotic use. MeMed BV (MMBV) is a host-protein test integrating TNF-related apoptosis-inducing ligand, induced protein-10 and C-reactive protein to distinguish infection aetiology. We evaluated whether alignment between MMBV results and antibiotic prescribing is associated with downstream clinical outcomes and costs. METHODS: Data were pooled from two prospective US studies (APOLLO and JUNO). Alignment was defined as: antibiotics prescribed for bacterial MMBV results or no antibiotics for viral results. The primary outcome was unplanned revisits and hospitalisations within 28 days. Exploratory analysis estimated healthcare costs using 2024 Healthcare Cost and Utilisation Project data. RESULTS: The cohort included 297 adults (median age 36.4 years). 20.5% had bacterial, 68.0% viral and 11.4% equivocal MMBV results. In patients with bacterial MMBV results, antibiotic prescription (alignment) was significantly associated with fewer revisits (5.0% vs 33.3%; p=0.003) and hospitalisations (2.5% vs 19.0%; p=0.026). For patients with viral results, outcomes were comparable regardless of antibiotic use. In the exploratory analysis, alignment with MMBV was associated with lower estimated costs (£101 vs £1175/patient; difference £1074), driven mainly by fewer hospital days in the aligned group. CONCLUSION: Misalignment between MMBV bacterial results and antibiotic prescribing in acute care settings was associated with higher revisit and hospitalisation rates. These findings identify a quality gap under diagnostic uncertainty and support a methodology which includes assessment of test versus clinical outcome alignment when evaluating new diagnostic tests.

INTRODUCTION: Across Europe, many people with HIV are diagnosed late despite repeated contact with hospital services for HIV indicator conditions. These conditions flag a possible underlying HIV infection for which HIV testing is recommended. They provide an opportunity to identify people with HIV, yet implementation of indicator condition-based testing remains insufficient in hospital practice. The #aware.hiv Europe study was developed to address this gap by embedding HIV teams into routine care to normalise HIV testing. METHODS AND ANALYSIS: #aware.hiv Europe is a stepped-wedge cluster randomised trial in 30 hospitals across ten European countries. Five clusters of six hospitals each will sequentially transition from control to implementation periods when local HIV teams led by an infectious diseases specialist will be installed. Intervention activities include hospital-wide peer audit and feedback on missed testing opportunities, targeted education, stigma reduction activities and strengthening of linkage to HIV prevention and care. Patients with predefined HIV indicator conditions are identified using International Classification of Diseases, 10th Revision (ICD-10) diagnosis codes, confirmed through manual review.The primary outcome is the change in HIV testing rate among patients with confirmed HIV indicator conditions. Secondary outcomes include HIV case detection, cascades of diagnosis, care and prevention, variation in testing practices, healthcare professional knowledge and stigma, and implementation outcomes. Analyses will use mixed effects regression models accounting for clustering and time within the stepped-wedge design. ETHICS AND DISSEMINATION: The study has ethical approval in all hospitals to use routinely collected clinical data under exemption from informed consent for patient level data. Results will be disseminated through peer reviewed publications, conferences and collaboration with clinical and community partners with the goal to inform HIV testing policies. TRIAL REGISTRATION NUMBER: NCT06900829.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) are common among nursing home residents, notably those with Alzheimer disease and related diseases, impacting both themselves and health care professionals. Nonpharmacological interventions, including virtual reality (VR), have shown promise, but evidence from multicenter ecological studies remains limited. OBJECTIVE: This study aimed to evaluate the effectiveness, in terms of BPSD evolution, immediate well-being, and social interactions, of a VR-based immersion intervention (Lumeen) as a nonpharmacological approach to managing BPSD among nursing home residents. It also aimed to confirm the feasibility of implementing and evaluating group-based immersive VR interventions in nursing homes. METHODS: Fifty-six nursing home residents with BPSD took part in this multicenter randomized controlled trial (ClinicalTrials.gov NCT04769024), receiving either VR-based sessions or an active control condition consisting of nondigital cognitive stimulation. Both interventions consisted of two 45-minute group sessions per week for 6 weeks, resulting in a total of 12 sessions in each intervention group. BPSD severity was assessed preintervention and postintervention using the Neuropsychiatric Inventory (NPI) and the Apathy Interview. Immediate well-being and social interaction were assessed at each session using the Immediate Well-Being Evaluation and the Social Observation Behaviors Residents Index, respectively. RESULTS: No significant between-group differences were found in BPSD reduction or in overall well-being outcomes. However, immediate well-being increased from presession to postsession in both groups when averaged across the 12 sessions, and social interactions were more frequent in the active control group. Only 2 mild adverse events were reported. CONCLUSIONS: VR interventions in nursing home residents with neurocognitive disorders did not demonstrate superiority over an active cognitive stimulation control in reducing BPSD. Both interventions were associated with improvements in immediate well-being, suggesting that nonpharmacological group-based activities may be beneficial in nursing home settings. Additionally, VR interventions were safe and feasible in this population. Immersive VR warrants further investigation in adequately powered pragmatic trials to clarify its specific added value a

In acute heart failure (AHF), non-invasive ventricular-arterial coupling (VAC) surrogates, including right ventricular-pulmonary arterial (RV-PA) and left ventricular-arterial (LV-Ao) coupling, have emerged as practical bedside indices, but their prognostic significance remains largely unknown systematically. We performed a systematic review and meta-analysis to evaluate the prognostic significance of non-invasive VAC assessment, in patients hospitalized with AHF. Outcomes included all-cause mortality, HF hospitalization, length of hospital stay, use of therapies, the composite of all-cause mortality and HF hospitalization, and in-hospital adverse cardiovascular events. Adjusted hazard ratios (aHRs) and odds ratios (aORs) were pooled using random-effects. Subgroup-analyses were performed according to follow-up duration and left ventricular ejection fraction. Thirty-six studies comprising 36,989 patients were analysed. Twenty-eight studies evaluated RV-PA coupling, predominantly the TAPSE/PASP ratio, and eight evaluated LV-Ao coupling, mainly using non-invasive Ea/Ees estimates. RV-PA uncoupling was independently associated with increased all-cause mortality (aHR 1.90; 95% CI 1.42-2.56; I²=49%), with consistent associations at 12 months (aHR 2.03; 95% CI 1.44-2.85) and long-term follow-up (aHR 1.67; 95% CI 1.06-2.64). Associations with HF hospitalization, hospital stay, and the composite endpoint were directionally consistent but not statistically significant. LV-Ao uncoupling was associated with increased in-hospital adverse cardiovascular events (aOR 1.70; 95% CI 1.29-2.24). Sensitivity analyses confirmed robustness of these findings. RV-PA uncoupling predicts mortality, whereas LV-Ao uncoupling identifies patients at increased risk of in-hospital adverse cardiovascular events, supporting VAC-risk-stratification in AHF and future evaluation of VAC-guided therapeutic strategies.

BACKGROUND: Postoperative delirium (POD) is a frequent neuropsychiatric complication after surgery, characterized by acute disturbances in attention, awareness, and cognition. This pilot study assessed the feasibility of a multidimensional assessment protocol and investigated candidate risk factors for POD in older patients undergoing elective surgery. METHODS: This prospective, observational, non-interventional, single-center pilot study enrolled 150 patients aged ≥ 65 years undergoing elective surgery lasting ≥ 60 min. Patients with dementia, neurological disorders (documented diagnoses), or emergency procedures were excluded. After enrollment, 10 patients were excluded due to surgery postponement or unplanned ICU admission, leaving 140 patients for analysis. Data were collected preoperatively, on postoperative days 1-3. Intraoperative and laboratory data were obtained from databases. Handgrip strength was measured by dynamometry. POD was assessed using the CAM-ICU once daily on postoperative days 1-3 by a single trained investigator. Cognitive function and reserve were evaluated using MMSE and MWT-B, frailty with the Clinical Frailty Scale, nutritional status with screening tools, and pain via the Numeric Rating Scale. Descriptive and inferential statistics were applied. RESULTS: POD incidence was 5.0% (n = 7/140; 95% CI: 2.0%-10.0%). Frailty (n = 4/7 [57%] vs. n = 26/133 [20%]) and malnutrition (n = 4/7 [57%] vs. n = 29/133 [22%]) were more common in the delirium group. In an exploratory, unpowered male subgroup analysis, patients with POD had lower preoperative handgrip strength; no statistically meaningful difference was testable in women (n = 3 with POD). During anesthesia induction, patients with POD experienced more hypotensive episodes (MAP<55 mmHg), (n = 3/7 [43%] vs. n = 11/133 [8.0%]). No comparison remained significant after Holm-Bonferroni correction. CONCLUSION: This pilot study demonstrates the feasibility of prospective POD assessment on a general surgical ward and provides an incidence estimate (5.0%) to inform sample-size calculation for confirmatory trials. Frailty, lower preoperative handgrip strength in men, and induction hypotension were more frequent among patients with POD. Given the low event rate and multiple comparisons, these associations are hypothesis-generating and require validation in adequately powered studies. TRIAL R

BACKGROUND: Delirium is the most frequent neurological complication after surgery and is associated with increased postoperative morbidity and mortality. The underlying pathophysiology is not fully understood, but is suggested to be multifactorial, including hypoperfusion and hypoxia; however, the role of deviating vital signs prior to postoperative delirium (POD) remains unclear. This study aimed to examine the association between severe physiological deviations detected by continuous wireless monitoring and the occurrence of POD within the first three postoperative days after major abdominal cancer surgery. METHODS: In this prospective substudy, the primary outcome delirium was assessed daily with the validated 3D-CAM questionnaire during the first three postoperative days following major abdominal cancer surgery, and patients were classified into three groups: POD, neurocognitive decline (NCD), and no cognitive impairment (controls). Vital signs (blood pressure, respiratory rate, heart rate, and peripheral oxygen saturation) were continuously monitored for up to 96 h postoperatively. The primary exposure was the cumulative duration of severely deviating vital signs 24 h before POD diagnosis. Secondary exposures included the frequency of sustained severe vital sign deviation episodes. RESULTS: Of 225 patients with complete 3D-CAM data, 22 (9.8%) developed POD, 73 (32.4%) had NCD, and 130 (57.8%) had no cognitive impairment (controls). The median cumulative duration of vital sign deviations 24 h prior to POD was not significantly different between POD patients and controls (204 min vs. 325 min, p = 0.63). Episodes of sustained tachycardia, bradycardia, and bradypnea in the 24 h prior to POD diagnosis were more frequent in POD patients compared to controls, all p < 0.001. In the 24 h after POD diagnosis, patients with POD also exhibited more frequent episodes of sustained tachypnea, desaturation, tachycardia, and hypertension than controls (all p ≤ 0.005). In NCD patients, deviations were intermediate: bradypnea and bradycardia were more frequent before, and tachycardia, hypotension, hypertension, and desaturation more frequent after the NCD assessment, compared with controls. CONCLUSION: Although the cumulative duration of severe vital sign deviations did not differ between POD patients and controls, episodes of sustained severe vital sign deviations wer

Bacterial infections are serious threats to human life and health and constitute a major global health challenge. Although antibiotics effectively combat bacteria, the emergence of antibiotic resistance severely compromises their efficacy. Therefore, an efficient and practical approach is urgently sought to improve antibacterial efficiency. Porphyrins, as typical photosensitizers (PSs), serve as favorable candidates for constructing porous materials with enhanced properties due to their advantages, including easy modification, strong light-absorbing ability, and good biocompatibility. Typically, porphyrin-based porous materials are categorized into four classic types according to their linkage modes, including porphyrin-based metal-organic frameworks (PMOFs), porphyrin-based covalent organic frameworks (PCOFs), porphyrin-based hydrogen-bonded organic frameworks (PHOFs), and amorphous porphyrin-based porous polymers (APPPs). This review summarizes antimicrobial advances in porphyrin-based porous materials from the perspective of synthetic strategies and structural design in the past 10 years. Key areas include healthcare, food, agriculture, functional textiles, and wastewater treatment. Moreover, the challenges and future development directions in this field are discussed. This review inspires and motivates more researchers to focus on the innovative construction of porphyrin-based porous materials to facilitate the efficient realization of antimicrobial applications.

Quorum sensing (QS) is a cell-to-cell communication system that regulates bacterial behavior, including biofilm formation, virulence, and antibiotic resistance. While QS has been extensively studied in single-species biofilms, emerging evidence highlights the complexity of QS crosstalk in polymicrobial biofilms, where multiple bacterial species coordinate or compete through interspecies signaling molecules. QS-mediated interactions in polymicrobial biofilms significantly influence disease progression by enhancing microbial adaptability, resistance to antimicrobial agents, and immune evasion. Crosstalk between different QS systems can either promote synergistic cooperation, leading to increased virulence, or trigger antagonistic responses that affect microbial dynamics. Understanding QS crosstalk in polymicrobial biofilms is crucial for developing innovative therapeutic interventions. Emerging approaches include quorum quenching strategies, targeting QS signals to disrupt biofilm formation, advanced drug delivery systems, and combination therapies that enhance bacterial susceptibility to antimicrobials. Future research should focus on revealing the intricate molecular mechanisms of QS interactions and identifying novel inhibitors to combat polymicrobial infections. This review provides a comprehensive analysis of QS crosstalk in polymicrobial biofilms, emphasizing its impact on disease progression and therapeutic challenges. Addressing this phenomenon could be used for next-generation antimicrobial strategies, offering new hope for managing chronic infections and antibiotic resistance.

Antimicrobial resistance and the demand for effective food-preservation strategies have increased interest in fatty acids (FAs) and their derivatives as potential antibacterial agents. FAs can affect bacterial membranes, cellular energetics, biofilm-associated phenotypes, and, in some organisms, specific metabolic pathways. However, these effects vary considerably with FA structure, concentration, ionization state, pH, formulation, bacterial species, and assay conditions. Additionally, microbiota-derived short-chain FAs may also contribute to host defense by influencing epithelial integrity, immune signalling, microbiome composition, and colonization resistance. Still, researchers should distinguish these indirect effects from direct bacterial killing. Evidence from laboratory media cannot necessarily predict performance in complex foods, where proteins, lipids, processing conditions, oxidation, and sensory limitations can alter antibacterial activity. Next, monoglycerides, conjugates, and delivery systems may improve stability or availability, although their efficacy, safety, and regulatory status require formulation-specific evaluation. This review critically examines direct antibacterial activity, host- and microbiome-mediated effects, food-matrix applications, resistance-related considerations, and emerging formulation approaches. Current evidence supports the potential of selected FAs in defined applications, while emphasizing the need for standardized assays, appropriate food-matrix validation, and stronger animal and human evidence.

PURPOSE: Urban waste transfer stations serve as critical infrastructure within municipal solid waste management systems, yet they introduce complex, interconnected health, safety, and environmental (HSE) risks. METHOD: This study proposes a novel, integrated framework combining Environmental Failure Mode and Effects Analysis (EFMEA), the Fine-Kinney method, and Partial Least Squares Structural Equation Modeling (PLS-SEM) to systematically identify, prioritize, and validate HSE risks. The framework was demonstrated through a case study of two municipal waste transfer stations in Da Nang, Vietnam, utilizing a comprehensive census survey of 110 personnel and secondary operational data. RESULTS: The risk analysis and structural modeling yielded three distinct sets of findings. First, regarding environmental risks (EFMEA), hazards such as hazardous gas emissions and biological contamination were predominantly categorized as "medium," signaling a critical need for enhanced containment control. Second, regarding occupational safety risks (Fine-Kinney), technical and mechanical hazards were generally maintained at "low" levels, indicating the effective impact of universal safety training at the stations. Third, PLS-SEM modeling analysis demonstrated that External Factors (β = 0.372, t-value = 4.672), Law and Regulation (β = 0.303, t-value = 3.145), and the Working Environment (β = 0.202, t-value = 2.332) exert significant associations with the adherence to and execution of HSE standards. CONCLUSION: These findings suggest that enhancing HSE performance in countries with similar developing contexts necessitates robust regulatory enforcement and external stakeholder pressure alongside improvements in physical working conditions. This research provides a scientific foundation for decision-makers to develop evidence-based roadmaps for sustainable risk management in urban waste infrastructure with comparable operational and regulatory profiles.

Odontogenic infections may progress to deep space infection with systemic complications and require prompt surgical drainage and, when indicated, systemic antibiotics. In patients with a documented penicillin allergy label, empiric therapy is often shifted toward clindamycin, although resistance is increasingly reported. This multicenter retrospective cohort study included 88 hospitalized patients with surgically treated odontogenic infections and a documented penicillin allergy label at two German tertiary oral and maxillofacial surgery centers (Center A, n = 59; Center B, n = 29). Empiric antibiotic therapy was predominantly clindamycin-based (90.9%). Microbiological diagnostics were performed in 58.0% of patients and infections were mostly polymicrobial. Antimicrobial susceptibility testing was available in 43.2%; among cases with clindamycin testing, resistance was 76.7%. Antibiotic regimen changes occurred in 25.0%, most frequently to ampicillin/sulbactam. Median length of stay was 5 days; ICU-level care was required in 5.7%, revision surgery in 15.9%, one intracranial complication and one in-hospital death occurred. These findings suggest a clinically relevant mismatch between label-driven empiric clindamycin use and observed susceptibility patterns. Early structured allergy assessment and delabeling strategies may strengthen antibiotic stewardship and support safe first-line β-lactam use.

BACKGROUND: Prior microbiology results, resistance patterns, and antimicrobial exposure are central to safe and effective antimicrobial prescribing. Digital health fragmentation refers to the dispersal of patient data across multiple electronic systems and the associated challenge of accessing complete information at the point of care. Antimicrobial prescribing for infections represents a critical use case to investigate the impact of digital health fragmentation on patient care. While interoperability has been studied in the context of patient safety, no review has described digital health fragmentation within the United Kingdom and examined its impact on antimicrobial prescribing and antimicrobial stewardship (AMS). OBJECTIVE: This study aimed to (1) characterize the extent of digital health fragmentation in the United Kingdom, (2) summarize the available evidence on its impact on AMS and prescribing practices in high-income countries, and (3) identify potential solutions. METHODS: A rapid review of the peer-reviewed literature was conducted following published guidance for rapid reviews and the PRISMA (Preferred Reporting Items of Systematic Reviews and Meta-Analyses) statement. MEDLINE ALL and PsycInfo were searched on August 19, 2025, using search terms relating to digital health fragmentation or interoperability, patient safety, and antimicrobial use. Searches were limited to English-language publications from 2015 (for characterizing the recent trends or current state of digital health fragmentation in the United Kingdom) or 2010 onward (for AMS-related impacts and solutions). Screening was conducted by 4 researchers following predefined inclusion and exclusion criteria. Extracted data were synthesized narratively through framework analysis. Study quality was appraised using the Mixed Methods Appraisal Tool. RESULTS: Fourteen studies met the inclusion criteria. Ten studies described the extent and nature of digital health fragmentation in the United Kingdom. Digital health fragmentation affects a large number of patients and is linked to clinical care efficiency, quality, and safety risks, including limited access to external clinical records, missing or incomplete information, duplicate investigations, delays in decision‑making, and substantial time spent searching for data. Evidence specific to antimicrobial prescribing was limited (4 studies) bu

STUDY OBJECTIVE: The primary objective of this study was to compare the effectiveness between first-, second-, and third-generation oral cephalosporins for the treatment of pyelonephritis in adult patients discharged from the emergency department (ED). METHODS: This was a multicenter, retrospective, observational cohort study of 11 geographically distributed academic US EDs. Patients aged ≥18 years who were diagnosed with pyelonephritis and discharged home on an oral cephalosporin from the ED between August 1, 2023 and January 1, 2025 were included. The primary outcome was treatment failure at 14 days between the cephalosporin generations. The composite outcome was defined as one of the following: (1) recurrence of symptoms, (2) repeat ED/urgent care visit due to urinary tract infection, (3) receipt of a new antibiotic prescription for urinary symptoms, or (4) hospitalization due to urinary tract infection. Secondary outcomes included the need to modify the patient's initial antimicrobial regimen based on culture and susceptibility. RESULTS: A total of 1,147 patients met inclusion, with 618 (53.9%) receiving a first-generation, 91 (7.9%) a second-generation, and 438 (38.2%) a third-generation cephalosporin. Baseline characteristics were similar across cohorts, with women comprising over 85% of the study population. The most prescribed agents were cephalexin (85% of first generation), cefuroxime (100% of second generation), and cefdinir (79% of third generation). There was no statistically significant difference in 14-day treatment failure rates across generations (first versus second: 19.6% versus 17.6%, difference 2.0%, 95% confidence interval (CI) -7.1 to 11.1; first versus third: 19.6% versus 18.0%, difference 1.6%, 95% CI -3.4 to 6.5). CONCLUSION: First-, second-, and third-generation oral cephalosporins demonstrated comparable 14-day treatment failure rates for the treatment of acute pyelonephritis in patients discharged from the ED.

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INTRODUCTION: Some inpatient antibiotic use metrics have important limitations, including the absence of patient-level risk adjustment. To address this limitation, we previously developed two risk-standardized ratios (RSRs), one based on days of therapy (RSR-DOT) and the other on days of antibiotic spectrum coverage (RSR-DASC). Here, we evaluated the construct validity of these metrics by examining whether hospital performance was associated with the quality of antibiotic selection and duration in patients with either lower respiratory tract infections (LRIs) or urinary tract infections (UTIs). METHODS: Using Veterans Health Administration data from October 2020 through September 2021, we calculated RSR-DOT and RSR-DASC for 121 acute-care hospitals and selected 24 hospitals with relatively low or high values. At each hospital, a blinded infectious diseases physician reviewed 10 admissions each for LRI and UTI. Antibiotic selection at day 3 and total antibiotic duration were adjudicated and summarized as a 6-category ordinal composite outcome. Associations between RSR metrics and antibiotic-prescribing quality were evaluated using ordinal logistic regression; model-fit and bootstrap analyses compared RSR-DOT and RSR-DASC. RESULTS: We reviewed 479 admissions (239 LRI and 240 UTI). In LRI, lower RSR-DASC tended to be associated with a higher quality of antibiotic use (coefficient, 2.906 [P = .053]), whereas RSR-DOT was not (1.418 [P = .374]). In UTI, neither metric was associated with the quality of antibiotic therapy. Model-fit and bootstrap analyses consistently favor RSR-DASC over RSR-DOT for LRI. CONCLUSIONS: RSR-DASC may capture antibiotic-prescribing quality more closely than RSR-DOT for LRI, but not for UTI, potentially supporting the value of spectrum-informed benchmarking metrics.

INTRODUCTION: Infective endocarditis (IE) remains a severe disease with high mortality despite advances in management. Although it predominantly affects male patients, female patients account for about one-quarter of cases. Sex-specific differences in outcomes and prognostic factors remain insufficiently explored. METHODS: We conducted a retrospective study including 519 patients ≥16 years hospitalized for definite or possible IE (ESC 2023 criteria) at La Timone Hospital, Marseille, between March 2019 and October 2023. The primary endpoint was one-year mortality; secondary endpoints included surgical management, valve involvement, and prognostic factors. RESULTS: Of the 519 patients, 26% were female patients. One-year mortality was comparable between sexes (27% in female patients vs. 23% in male patients, p = 0.415). Post-discharge mortality was not significantly different between sexes (p = 0.096). Mitral valve involvement was more frequent in female patients, and aortic involvement predominated in male patients. Independent predictors of mortality included annular complications and lack of surgery. Importantly, sex-specific differences in prognostic factors were observed in this exploratory analysis: in female patients, TAVI and ischemic heart disease were associated with higher mortality; in male patients, right-sided IE and pacemaker presence were predictive. Furthermore, fatal cases in male patients were marked by more in-hospital complications (heart failure, cardiogenic or septic shock, acute renal failure), suggesting distinct mortality pathways. CONCLUSION: Although overall mortality was similar between sexes, male patients and female patients with IE appeared to show different prognostic profiles in this single-center cohort. These preliminary, hypothesis-generating findings suggest that some established risk factors may largely reflect male data, emphasizing the need for larger, multicenter studies to confirm sex-specific determinants and improve individualized management.

Mitochondrial transfer and transplantation (mitoTT) has emerged as an experimental and potentially transformative therapeutic strategy, drawing attention for its ability to modulate cellular bioenergetics, stress responses, and tissue repair. Endogenous mitochondrial transfer can occur through tunneling nanotubes, extracellular vesicles, cell fusion, gap junction-associated communication, and phagocytosis-like internalization. These routes differ substantially in distance, directionality, cargo integrity, regulatory control, and physiological relevance. Preclinical studies indicate that exogenous mitochondria may transiently improve bioenergetic function, attenuate oxidative stress, and support recovery in models of cardiac, skeletal muscle, and nervous system injury, whereas clinical evidence remains limited and heterogeneous. Broad clinical implementation remains constrained by unresolved biological and translational barriers. These include inefficient or poorly controlled uptake of extracellular mitochondria, uncertain long-term persistence, incomplete functional integration, donor-recipient incompatibility, mitochondrial-nuclear mismatch, heteroplasmy-related risks, immunogenicity, and the lack of standardized potency and delivery assays. Here, we critically synthesize the cellular mechanisms enabling mitoTT, emphasizing the checkpoints that determine whether transferred mitochondria are integrated, remodeled, immunologically sensed, or eliminated. We further discuss cristae biology and the mitochondrial contact site and cristae organizing system, mitochondrial nucleoid maintenance, mitochondrial DNA replication, organelle contact sites, and emerging bioengineering strategies required to move mitoTT from experimental rescue toward reproducible therapeutic application.

BACKGROUND: Right ventricular (RV) function is a major determinant of outcomes in heart failure (HF), yet RV systolic performance and venous congestion (VC) are often evaluated separately. We investigated the relationship between tricuspid annular systolic velocity (S'), a tissue Doppler marker of RV systolic function and systemic VC measured by the Venous Excess Ultrasound (VExUS) score in patients with HF. In addition, RV-pulmonary artery (RV-PA) coupling parameters including TAPSE/PASP and S'/PASP were evaluated across VExUS grades. METHODS: In this prospective, single-center observational study, 155 patients admitted with decompensated HF underwent standardized echocardiography, including VExUS assessment and S' measurement. Lung Ultrasound Score (LUS), RV-PA coupling indices, clinical characteristics, in-hospital mortality, and acute kidney injury (AKI) were also recorded. RESULTS: The mean age was 57.5 years, with 68% of the cohort being males. A significant inverse correlation was observed between VExUS grade and S' velocity (p < 0.001). Patients with VExUS Grade 0 had higher S' velocities (median = 11.0 cm/s), while those with Grade 3 had the lowest (8.5 cm/s). Increasing VExUS grades were also associated with progressive worsening of TAPSE, TAPSE/PASP, and S'/PASP ratios, suggesting impaired RV-PA coupling with increasing venous congestion. Both higher VExUS grades and reduced S' were associated with more severe pulmonary congestion on LUS (p < 0.001 and p = 0.003, respectively). Although patients with higher VExUS grades and lower S' values trended towards worse outcomes, neither parameter significantly predicted in-hospital mortality or AKI. CONCLUSION: Systemic VC and RV systolic function are strongly and inversely related in HF. The combined use of VExUS and S' provides an integrated bedside assessment of hemodynamic status that may help guide decongestive therapy. Integration of RV-PA coupling parameters may further enhance bedside evaluation of hemodynamic compromise in HF patients. Additionally, S'/PASP and TAPSE/PASP demonstrated comparable trends across all HF groups, suggesting that S'/PASP may serve as a practical alternative marker of RV-PA coupling in heart failure patients. Larger studies are needed to determine their prognostic utility for predicting mortality and organ injury. TRIAL REGISTRATION: This trial was registered with Cl

BACKGROUND: Individuals across the spectrum of kidney function experience excess risk of acute myocardial infarction (AMI), but whether the plasma proteome's association with this risk is itself modified by the estimated glomerular filtration rate (eGFR) remains uncharacterized. METHODS: Cox proteome-wide association studies of 2,923 Olink proteins in 33,446 UK Biobank participants (fully adjusted model 2: 29,417 complete cases, 1,584 incident AMI events; the full eligible cohort comprised 1,848 events, the complete-case reduction reflecting full covariate adjustment). After fully adjusted screening, protein × eGFR interaction models tested whether each protein association was modified by eGFR (continuous). Incremental prediction was evaluated with a leakage-free elastic-net Cox model. RESULTS: Over a median 13.9-year follow-up, 1,848 AMI events occurred. After multivariable adjustment, 975 proteins were linked to AMI (false discovery rate [FDR]-adjusted p < 0.05). For 176 of these, the AMI association was modified by kidney function (interaction FDR < 0.05)-strengthening as eGFR declined for 154 proteins and at higher eGFR for a smaller set of 22. Exploratory GSEA identified FDR-significant innate immune enrichment in the higher-eGFR direction, whereas lower-eGFR cardiac and matrix signals were nominal. Adding plasma proteins to clinical predictors modestly improved 10-year AMI prediction (Harrell C, 0.748 → 0.780; ΔC = 0.032, 95% confidence interval = 0.021-0.043). CONCLUSION: Kidney function modifies the plasma proteomic signature of incident AMI: most protein-AMI associations intensify as eGFR declines, while a smaller subset strengthens at preserved filtration. This supports kidney function-aware proteomic cardiovascular risk interpretation.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) links to adverse kidney and cardiovascular events. However, current machine learning (ML)-based algorithms do not include comprehensive echocardiographic features or predict adverse kidney outcomes. METHODS: We built ML models to predict 3-year all-cause mortality, major adverse cardiovascular events (MACE), and major adverse kidney events (MAKE) in retrospective HFrEF cohorts. Models were developed from 1,486 patients at Taipei Veterans General Hospital during 2011-2018 and externally validated in 246 patients from the heart-failure-post-acute-care program at Taichung Veterans General Hospital during 2020-2023. Model performance was compared to the traditional Meta-Analysis Global Group in Chronic Heart Failure score (MAGGIC), Logistic Regression (LR), and Kidney-Failure-Risk-Equation (KFRE). RESULTS: For mortality, Ensemble had the highest area under receiver-operating-characteristic curve (AUROC, 0.863; 95% confidence interval [CI], 0.814-0.913; p < 0.001), outperforming MAGGIC (AUROC, 0.741; 95% CI, 0.673-0.810) with net reclassification index (NRI) of 0.294 (95% CI, 0.147-0.440; p = 0.001). For MACE, Ensemble (AUROC, 0.816; 95% CI, 0.769-0.864; p < 0.001) surpassed LR (AUROC, 0.734; 95% CI, 0.677-0.791). For MAKE, Ensemble (AUROC, 0.858; 95% CI, 0.806-0.910; p < 0.001) exceeded KFRE (AUROC, 0.647; 95% CI, 0.560-0.735) with NRI of 0.267 (95% CI, 0.133-0.396; p < 0.001). External validation confirmed good Ensemble discrimination (AUROCs of 0.803, 0.808, and 0.859 for mortality, MACE, and MAKE, respectively). An online tool (https://vghhfrefai.com/) was created for application. CONCLUSION: Ensemble ML models with detailed clinical and echocardiographic features surpassed conventional risk scores, enabling early detection of major adverse cardiorenal events among HFrEF.

PURPOSE OF REVIEW: Catheter ablation (CA) has become a first-line option for rhythm control strategy for atrial fibrillation (AF) and atrial flutter (AFL). We synthesize recent evidence regarding racial and ethnic disparities in CA utilization in the United States and examine the structural mechanism driving them. RECENT FINDINGS: Black patients are 28 to 36% less likely to undergo CA for AF or AFL compared to White patients, with similarly reduced odds (22 - 35%) observed among Hispanic and Asian patients for AF. While subgroup analysis from clinical trials like CABANA demonstrate survival benefits of CA among minority cohorts, real-world data reveal that the very populations that stand to benefit the most are the least likely to receive CA. Public insurance models, upstream referral bottlenecks, geographic specialty deserts, and clinician-level implicit bias serve as primary structural drivers of these disparities. Racial and ethnic gaps persist in CA utilization and outcomes for both AF and AFL. AF/AFL prevalence is influenced by racial and ancestral biology while CA access disparity is driven by race as a social construct. These two phenomena require fundamentally different investigative frameworks and intervention targets.

PURPOSE OF REVIEW: The left atrial appendage (LAA) is nowadays recognized as both an arrhythmogenic substrate and the dominant source of thromboembolism in atrial fibrillation (AF). In this review we tried to summarize recent data on the anatomy, physiology, and imaging of the LAA, and examine how these findings help guide rhythm-control and stroke-prevention strategies. RECENT FINDINGS: High-resolution mapping confirms the LAA as a non-pulmonary-vein trigger source in persistent and post-ablation AF, supporting LAA electrical isolation in selected patients, though isolation may induce mechanical standstill and mandate continued thromboprophylaxis. The 2024 ESC guidelines reframed stroke-risk assessment around the sex-neutral CHA₂DS₂-VA score within the AF-CARE pathway. An important recent study was the OPTION trial, which showed that LAA closure after AF ablation was as effective as oral anticoagulation for preventing death, stroke, or systemic embolism and was associated with less non-procedure-related bleeding. These findings support the use of LAA closure in selected patients after ablation. New imaging and emerging computational tools may also improve patient selection and help guide device sizing. A comprehensive assessment of the anatomy, function, and electrical activity of the LAA can help adapt AF treatment to each patient.

BACKGROUND: Outcomes following catheter ablation for persistent atrial fibrillation (AF) remain suboptimal. Low-voltage areas (LVA), as a surrogate for atrial fibrosis, have been targeted due to their association with arrhythmia recurrence. Ethanol infusion in the vein of Marshall (VoM) has emerged as an adjunctive strategy that may enhance ablation efficacy. We evaluated the effectiveness of a tailored ablation strategy guided by the presence of LVA and incorporating VoM ethanol infusion in patients with persistent AF. METHODS: This prospective, single-center study included patients referred for catheter ablation for persistent AF ablation between August 2022 and August 2024. Patients underwent a tailored ablation strategy guided by the presence of LVA. Procedural endpoints and 1-year outcomes were assessed and compared with those of a propensity score-matched cohort undergoing pulmonary vein isolation (PVI) alone. RESULTS: A total of 118 patients (71% male, mean age of 62 ± 10years) were included in our study: 59 in the tailored approach group and 59 propensity score-matched controls. In the tailored group, VoM ethanol infusion was performed in 60% of patients, while ablation beyond pulmonary veins was not performed in 14% of patients due to LVA absence. Bidirectional block was achieved in all ablation lines except in two patients. At 1-year follow-up, 22% of patients had atrial arrhythmia recurrence. The risk of recurrence was significantly lower in the tailored approach group (13.5% vs. 30.5%, p = 0.02). A tailored approach was independently associated with freedom from atrial arrhythmia recurrence (HR 0.41 [0.17-0.94], p = 0.04). No significant differences in adverse events were observed between groups. CONCLUSIONS: In patients with persistent AF, a tailored ablation guided by LVAs was associated with significantly lower arrhythmia recurrence at 1-year compared with PVI alone.

OBJECTIVE: Congenital cardiac anomalies are a major determinant of morbidity and mortality in Turner syndrome (TS), yet long-term cardiovascular outcome data remain limited. This study assessed cardiovascular morbidity, mortality, valve dysfunction, and aortic outcomes in TS patients with congenital cardiovascular defects. METHODS: In this single-center retrospective cohort study, 84 TS patients with congenital cardiovascular anomalies were analyzed, with follow-up between 01/1980 and 01/2025. Clinical, demographic, electrocardiographic and echocardiographic variables were reviewed; morbidity and mortality were recorded; descriptive statistics applied. RESULTS: Bicuspid aortic valve (BAV) was present in 40 patients (48%) and coarctation of the aorta (CoA) in 29 (35%); 19 patients (23%) had both. At last follow-up (median age 26 years, IQR 31 years), most patients were in NYHA class I (82%) and mean systolic and diastolic blood pressure were 121.7 ± 16.8 mmHg and 76.1 ± 13.1 mmHg, respectively. Sinus rhythm was present in 96% of the patients. In the BAV cohort, aortic regurgitation increased from 6 patients (15%) at first registration to 17 (42.5%) at last follow-up. In the tricuspid aortic valve cohort, aortic regurgitation increased from 1 patient (2.3%) to 12 (27.9%). The last mean ascending aortic diameter indexed to body surface area was 20.4 ± 4.6 mm/m2. Aortic dissection occurred in 2 patients (2.7%). Ten patients died during follow-up; median age at death was 41 years (IQR: 52 years), and cardiac causes accounted for at least 50% of mortality. CONCLUSION: BAV and CoA predominated in this TS cohort. Despite generally favorable functional status among survivors, progressive valve dysfunction, aortic complications and cardiovascular mortality support lifelong structured surveillance.

Pediatric extracorporeal membrane oxygenation (ECMO) saves lives, but its long-term neurodevelopmental cost has been difficult to isolate from the burden of critical illness itself. Le Helleye and colleagues address this with a prospective, matched case-control study comparing ECMO survivors to general PICU survivors matched for age, diagnosis, and admission year. Overall health-related quality of life (HRQoL) was modestly lower in ECMO survivors. Physical functioning, however, showed a clear and robust deficit, persisting even against critically ill comparators. Psychosocial functioning did not differ significantly between groups, suggesting this domain is driven more by contextual and family factors than ECMO-specific injury. Roughly one-third of the entire cohort-ECMO and non-ECMO alike-showed clinically significant executive dysfunction, which proved the strongest independent predictor of poor HRQoL across all domains, outweighing ECMO's own effect. Parental stress emerged as a comparably powerful, and modifiable, mediator of child outcomes. Together these findings argue for reframing post-PICU follow-up: neurodevelopmental monitoring and structured family psychological support as core components of critical care recovery.

BACKGROUND AND AIMS: With improved survival, adults with congenital heart disease (ACHD) increasingly face acquired cardiovascular risk factors; however, their impact on late mortality remains incompletely defined. This study aimed to evaluate the contribution of acquired cardiovascular risk factors to mortality in ACHD. METHODS: A total of 9826 ACHD patients (mean age 39.0 ± 16.4 years; 50.3% male) who attended our tertiary centre between 2000 and 2024 were retrospectively analysed. Clinical and demographic data were obtained from a prospectively maintained database. Cox proportional hazards models were used to assess associations between risk factors and all-cause mortality. RESULTS: During a median follow-up of 10.0 years (98 764 patient-years), 1371 patients died (mortality rate 1.39% per patient-year). In multivariable analysis, older age (hazard ratio [HR] 1.07 per year; P < .001), male sex (HR 1.30; P = .026), greater lesion complexity (HR 2.12; P < .001), coronary artery disease (HR 1.78; P = .005), sleep apnoea (HR 2.22; P < .001), depression (HR 1.45; P = .010), and current smoking (HR 1.67; P < .001) were independently associated with higher mortality, while higher income was associated with lower mortality risk. CONCLUSIONS: Both congenital lesion complexity and acquired comorbidities are associated with late mortality in ACHD. These data support the need for comprehensive, multidisciplinary management that incorporates timely modification of general cardiovascular and other risk factors alongside congenital heart disease-specific care.

BACKGROUND: Pulmonary vein isolation (PVI) is the standard ablation strategy for paroxysmal atrial fibrillation (PAF). Despite guideline recommendations favoring PVI alone in PAF, some operators routinely perform extra pulmonary vein ablation (PVI+) during initial procedures. OBJECTIVE: To determine frequency of PVI+ strategy for treatment of PAF in the real world and examine its impact on arrhythmic recurrence and progression compared to PVI alone. METHODS: Using the TriNetX research network, we identified adults with PAF who underwent catheter ablation between January 2020 and January 2024. Recurrence was defined as repeat ablation, cardioversion, or antiarrhythmic drug (AAD) use beyond a 3-month blanking period. Progression to persistent AF and atypical atrial flutter were also assessed. Kaplan-Meier analysis was performed with 3-year follow-up. RESULTS: Before matching, 5134 of 18,891 patients (27.2%) underwent PVI+. In the propensity matched analysis (n = 5020 per group), recurrence was significantly higher in the PVI+ group (HR 1.28, 95% CI 1.16-1.42; p < 0.001). Repeat ablation, cardioversion and AAD use were more common with PVI+ (HR 1.99, 95% CI 1.60-2.46; p < 0.0001, HR 1.37, 95% CI 1.13-1.66; p = 0.001, and HR 1.41, 95% CI 1.05-1.87; p = 0.020, respectively). Progression to persistent AF was higher with PVI+ (HR 1.37, 95% CI 1.23-1.53, p < 0.001), as was atypical atrial flutter (HR 2.63, 95% CI 1.97-3.50; p < 0.0001). CONCLUSION: Extra-pulmonary vein ablation during first-time PAF ablation remains common in real-world practice but is associated with worse outcomes including repeat ablation, cardioversion, AAD use, atrial flutter, and progression to persistent AF.

BACKGROUND: This study evaluated the prognostic impact of left ventricular (LV) apical aneurysm identified by transthoracic echocardiography (TTE) in a Japanese cohort with hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: We retrospectively enrolled 369 consecutive HCM patients from 2 centers (2016-2023). LV apical aneurysm was defined on TTE as a discrete, thin-walled dyskinetic/akinetic apical outpouching with a wide neck. Primary outcomes were all-cause death and cardiovascular (CV) death. Secondary outcomes were hospitalization for worsening heart failure, systemic embolism, sustained ventricular tachycardia (VT), and sudden cardiac death (SCD)-equivalent events (resuscitated cardiac arrest or appropriate implantable cardioverter defibrillator therapy). LV apical aneurysm was present in 47 of 369 patients (12.7%). There were no significant between-group differences in all-cause death (log-rank P=0.162) or CV death (P=0.103). Patients with LV apical aneurysm more frequently had baseline sustained VT and SCD-equivalent events; however, Kaplan-Meier analyses indicated no significant differences between groups in incident sustained VT and SCD-equivalent events after enrollment. In multivariable Cox models, age, B-type natriuretic peptide (BNP), and SCD-equivalent events were independently associated with all-cause death; BNP and SCD-equivalent events were independently associated with CV death. CONCLUSIONS: In this cohort, echocardiography-identified LV apical aneurysm was associated with a greater burden of baseline arrhythmic events, but not higher mortality. TTE provides a practical means of identifying this phenotype. BNP and SCD-equivalent events were more closely associated with mortality.

BACKGROUND AND AIMS: Randomized evidence comparing conduction system pacing (CSP) and biventricular pacing (BVP) following atrioventricular node ablation in patients with refractory atrial fibrillation (AF) and heart failure (HF) remains limited. This study evaluated whether CSP with left bundle branch area pacing is non-inferior to BVP in patients undergoing atrioventricular node ablation. METHODS: CONDUCT-AF was an investigator-initiated, multicentre, randomized trial conducted across 10 European centres. Patients with refractory AF, HF with left ventricular ejection fraction (LVEF) < 50%, narrow QRS duration (≤120 ms), and N-terminal pro-B-type natriuretic peptide > 600 ng/L were randomized 1:1 to CSP or BVP. The primary endpoint was the change in LVEF after 6 months, assessed by an independent core laboratory. Secondary endpoints included echocardiographic, clinical, and procedural outcomes. Analyses followed the intention-to-treat principle. RESULTS: Eighty-two patients were randomized (mean age 72 ± 7 years, 46% male). At 6 months, LVEF improved similarly in CSP {from 36% [95% confidence interval (CI) 33-39] to 46% [95% CI 44-49]; P < .001} and BVP group [from 34% (95% CI 31-36) to 46% (95% CI 43-49); P < .001]. The between-group difference was .4% (95% CI -3.1-3.8; P = .002 for non-inferiority). Changes in left ventricular volumes, clinical parameters, and composite endpoint of worsening HF or cardiovascular death were comparable between groups. Paced QRS [mean difference -14 ms (95% CI -19 to -9; P < .001)] and procedural and fluoroscopy times were significantly shorter with CSP compared with BVP. CONCLUSIONS: In HF patients with refractory AF undergoing atrioventricular node ablation, CSP with left bundle branch area pacing was non-inferior to BVP for LVEF improvement at 6 months, providing comparable clinical outcomes and a favourable procedural profile.

Initially developed to overcome the limitations of angiography in visualizing plaque morphology, intravascular ultrasound and optical coherence tomography have advanced dramatically in resolution, acquisition speed, and analytical automation. These techniques now provide detailed, real-time assessment of coronary artery structure, enabling precise stent sizing, calcium characterization, and optimization of percutaneous coronary interventions. Clinical trials and meta-analyses demonstrated that intravascular imaging-guided PCI significantly reduces restenosis, thrombosis, target lesion failure, and cardiac mortality compared with angiography-guided approaches. These achievements underpin the current Class I, Level A recommendations for intravascular imaging-guidance of complex PCI in the most recent ESC and ACC/AHA/SCAI guidelines. Intravascular imaging has also become instrumental in studying atherosclerosis regression, plaque vulnerability, and the effects of lipid-lowering therapies such as statins and PCSK9 inhibitors, allowing the implementation of personalized prevention and intervention strategies. Intravascular imaging remains grossly underused in clinical practice but better reimbursement, improved and mandatory training and the integration of artificial intelligence for image interpretation may facilitate a wider application.

A significant population of patients undergoing total knee arthroplasty (TKA) concomitantly have atrial fibrillation (AF). Previous studies have examined acute postoperative complications; however, the long-term impact of pre-existing AF on surgical outcomes after TKA remains underexplored. This study aimed to evaluate 2-, 5-, and 10-year risk and indications for revision among patients with AF undergoing TKA. The TriNetX database was utilized for this retrospective cohort study. The primary outcome was 2-, 5-, and 10-year risk of revision following primary TKA among patients with and without pre-existing AF. The AF and control cohorts were 1:1 propensity matched by age, sex, race, clinical comorbidities, and anticoagulant and aspirin use. Covariate balance after matching was assessed using standardized mean differences (SMDs). Cox proportional hazards models and Kaplan-Meier survival estimates were used to evaluate all-cause revision and specific complications. Results were reported as hazard ratios (HRs) with 95% confidence intervals (CIs), survival probabilities, and p-values. A p-value of < 0.05 was considered statistically significant. Patients with pre-existing AF (n = 24,671) had a significantly higher risk of all-cause revision at 2 years (HR 1.27, 95% CI: 1.13-1.43, p < 0.0001), 5 years (HR 1.23, 95% CI: 1.11-1.37, p < 0.0001), and 10 years (HR 1.23, 95% CI: 1.12-1.35, p < 0.0001) post-TKA compared to matched controls (n = 24,671). The AF cohort demonstrated increased risk of periprosthetic joint infection (PJI) (HR 1.33, 95% CI: 1.22-1.44, p < 0.0001) while showing decreased incidence of arthrofibrosis (HR 0.85, 95% CI: 0.80-0.91, p < 0.0001). No significant difference in periprosthetic fracture, mechanical loosening, osteolysis, or articular wear was observed. Pre-existing AF is associated with increased long-term risk of revision following TKA up to 10 years postoperatively compared to matched controls, even after matching for comorbidity burden and anticoagulant use. These findings should be interpreted cautiously in the context of modest effect sizes and limitations inherent within the TriNetX database. Future studies should examine whether perioperative anticoagulation management strategies influence long-term postoperative complications in patients with AF undergoing TKA.

BACKGROUND: As more adults with atrial septal defect (ASD) survive into older age and undergo atrial fibrillation (AF) ablation, evidence to guide post-ablation risk stratification remains limited. OBJECTIVE: To evaluate long-term outcomes after the first AF ablation across ASD management states compared with an intact interatrial septum. METHODS: This real-world cohort study included 27 675 patients undergoing their first AF ablation, classified by interatrial septal status as intact septum (n = 27 134), unrepaired ASD (n = 232), percutaneous closure (n = 119), or surgical repair (n = 190). Three pairwise comparisons with an intact septum were constructed. Propensity score overlap weighting was used to balance baseline characteristics, and Cox proportional hazards models were used to assess outcomes. The primary outcome was atrial arrhythmia recurrence after the 3-month blanking period; the secondary outcome was a composite cardiovascular outcome. RESULTS: Compared with an intact septum, unrepaired ASD was associated with a higher recurrence risk (hazard ratio [HR], 1.27; 95% CI, 1.07-1.51; p = 0.006), with excess risk mainly observed between 3 months and 1 year after ablation. Surgical repair was also associated with higher recurrence risk (HR, 1.21; 95% CI, 1.01-1.46; p = 0.038), with differences emerging beyond 1 year. Percutaneous closure was not associated with increased recurrence risk (HR, 1.07; 95% CI, 0.83-1.38; p = 0.589). Composite cardiovascular outcomes did not differ significantly across groups. CONCLUSIONS: ASD management status identified distinct temporal patterns of atrial arrhythmia recurrence after AF ablation, suggesting that ASD should not be treated as a single binary condition in post-ablation risk assessment.

BACKGROUND: Preventive percutaneous coronary intervention (PCI) of non-flow-limiting lesions (fractional flow reserve >0.80) that are high-risk plaques has emerged as a potential strategy to reduce cardiac events. However, identifying which lesions derive the greatest benefit from preventive PCI compared with optimal medical therapy alone remains challenging. This post hoc analysis evaluates the role of the near-infrared spectroscopy-derived lipid core burden index in identifying high-risk plaques that may benefit from preventive PCI. METHODS: Among the 1606 patients enrolled in the PREVENT trial (Preventive Coronary Intervention on Stenosis with Functionally Insignificant Vulnerable Plaque) from September 2015 to September 2021, an investigator-initiated, multicenter, open-label, randomized controlled trial, this post hoc analysis included 598 patients (mean age, 64.1±8.8 years; 27.9% women) comprising 632 lesions with a plaque burden >70% and a minimal lumen area <4 mm2 by intravascular ultrasound in whom near-infrared spectroscopy evaluation was also performed. Lipid-rich plaque (LRP) was prespecified as having a maximum lipid core burden index over a 4-mm segment >315. The primary outcome was a composite of death from cardiac causes, target-vessel myocardial infarction, ischemia-driven target-vessel revascularization, or hospitalization for unstable or progressive angina. RESULTS: LRPs were present in 223 patients (37.3%) with 234 lesions. During median follow-up of 5.6 years, primary outcome events occurred more frequently in patients with LRPs than in those with non-LRPs (12.5% versus 4.7%; unadjusted hazard ratio, 2.08; 95% CI, 1.03-4.19; P=0.039) in the overall population. Within the LRP group, preventive PCI was associated with a lower risk of the primary outcome compared with optimal medical therapy alone (7.3% vs. 17.6%; adjusted hazard ratio, 0.23; 95% CI, 0.13-0.41; P<0.001). Conversely, no benefit of preventive PCI was observed in the non-LRP group (5.5% versus 4.2%; adjusted hazard ratio, 1.00; 95% CI, 0.54-1.86; P=0.97). A significant interaction was found between treatment strategy and the presence of LRP (Pinteraction<0.001). CONCLUSIONS: In this post hoc analysis of the PREVENT trial, preventive PCI was associated with a lower risk of the primary composite outcome in patients with near-infrared spectroscopy-defined LRPs, whereas no sign

OBJECTIVE: Early menopause is an established female-specific risk enhancer for incident cardiovascular disease, but its prognostic value after acute coronary syndrome (ACS) remains uncertain. We evaluated whether menopause before age 45 years was associated with long-term ischemic/cardiovascular outcomes after ACS in midlife women. METHODS: We analyzed a multicenter registry of women hospitalized with ACS from February 1, 2020 through February 28, 2025. The primary cohort included women whose menopause preceded or coincided with the index event. Menopausal age was obtained from structured registry/clinical history fields. The primary outcome was a prespecified ischemic/cardiovascular major adverse cardiovascular event. RESULTS: Among 1,039 records, 857 had valid menopausal age data and 728 met temporal criteria. Menopause before age 45 years was present in 124 women; median follow-up was 3.52 years. Crude post-index event rates were higher with early versus later menopause for the primary outcome (21.1% vs. 13.3%), death (8.9% vs. 4.6%), and the composite outcome (25.2% vs. 15.3%). In the primary clinical Cox model, early menopause was associated with the primary outcome (hazard ratio [HR], 1.78; 95% CI, 1.11-2.85), death (HR, 2.57; 95% CI, 1.18-5.57), and the composite outcome (HR, 1.87; 95% CI, 1.21-2.89). Associations attenuated in extended exploratory models including previous vascular disease, surgical menopause, and hormone therapy. CONCLUSIONS: Menopause before age 45 years identified a higher risk post ACS phenotype. Findings extend incident risk evidence into secondary prevention and support routine recording of menopausal age; causality cannot be inferred.

BACKGROUND: Atrial fibrillation (AF) complicates 20-25% of hypertrophic obstructive cardiomyopathy (HOCM) cases and independently predicts heart failure progression, thromboembolism, and mortality. Both surgical myectomy (SM) and alcohol septal ablation (ASA) are associated with new-onset AF through opposing mechanisms; myectomy promoting left atrial reverse remodeling, ASA generating a chronic arrhythmogenic septal scar. Yet no propensity-matched study has directly compared AF incidence between these procedures. OBJECTIVES: To compare the incidence and temporal trajectory of new-onset AF following ASA versus SM at prespecified landmarks of Day 1, Day 7, and Day 30 in a propensity score-matched cohort with 3 years of follow-up. METHODS: Patients with obstructive HOCM who underwent ASA or SM without prior AF were identified in the TriNetX database between Jan. 2010 and Apr. 2023 and were followed for up to 3 years. After 1:1 propensity score matching on demographics, comorbidities, and atrial substrate risk factors, 223 patients remained in each cohort; new-onset AF was ascertained using clinical diagnosis codes applied symmetrically across both groups. RESULTS: Of 1,188 patients (539 ASA, 649 SM), 223 were matched per cohort (mean age 59.5 ± 15.5 years, 37.4% male, 80.3% White); all standardized mean differences were <0.20 after matching. At Day 1, AF occurred in 16.1% vs. 12.1% (ARD 4.0%; HR 1.22, 95% CI 0.74-2.01; p = 0.437). At Day 7, a significant divergence emerged (15.8% vs. 8.4%; ARD 7.4%; RR 1.87, 95% CI 1.10-3.21; p = 0.019). By Day 30, ASA carried a nearly three-fold higher AF risk (15.4% vs. 5.3%; ARD 10.1%; HR 2.75, 95% CI 1.39-5.42; p = 0.039), with AF-free survival of 82.59% vs. 93.83% (log-rank p = 0.002), with progressive Kaplan-Meier separation sustained through 3 years. CONCLUSIONS: In a propensity-matched cohort, ASA was associated with a progressively higher risk of new-onset AF compared with SM, with divergence emerging by Day 7 and widening through Day 30, consistent with substrate reversal after myectomy versus substrate maturation after ASA. These findings support incorporating differential AF risk into procedural selection discussions, extending postprocedural monitoring after ASA, and reassessing early anticoagulation thresholds in ASA patients.

GIM/FP/GP: [Formula: see text] Cardiology: [Formula: see text] Hematology: [Formula: see text].

PURPOSE: Veno-arterial extracorporeal oxygenation (VA-ECMO) provides comprehensive cardiopulmonary support in patients with cardiogenic shock (CS), but may result in complications. While complications rates are known, their impact on risk of death remains largely unknown. METHODS: Using the Extracorporeal Life Support Organization (ELSO) Registry to identify adults with a diagnosis of CS treated with VA-ECMO (2017-2024), we analyzed the association between timing and type of complication and in-hospital mortality using three methodologies: 1) Cox proportional hazards analysis, treating complications as time-dependent covariates; 2) Multi-State Model (MSM) analysis, treating complications as transient states and estimating the differential mortality rate from each of these states; and 3) landmark Kaplan Meier survival analysis, estimating conditional survival curves, given survival to 3 weeks, based on count and timing of complications. RESULTS: Among 22,547 patients (31.7% female), 12,094 (54%) died during index hospitalization. More non-survivors experienced complications than survivors (74% vs 54%), with all sub-types occurring more frequently. Neurologic complications increased the hazard of mortality by 3.6 (95% C.I 3.4 - 3.8). MSM analysis indicated that the absolute 30-day risk of mortality was greater if a patient had a complication, increasing from 48.6% (0 complications) to 93.1% with a neurologic complication. Landmark survival analysis demonstrated that patients without complications within the first 3 weeks had the highest conditional survival. CONCLUSION: Complications on VA-ECMO have a significant and cumulative effect on in-hospital mortality, with a higher number associated with increased risk of death. Neurologic and pulmonary complications were associated with the greatest mortality risk.

STUDY OBJECTIVE: Emergency medical services activate ST-segment elevation myocardial infarction (STEMI) pathways before biomarkers, imaging, or angiography are available. We sought to describe final hospital diagnoses, inhospital care, and outcomes among patients attended by paramedics for suspected STEMI in a statewide ambulance registry. METHODS: We conducted a retrospective statewide registry cohort study using the Victorian Ambulance STEMI Quality Initiative, with hospital follow-up data from January 2020 to June 2025. Principal International Classification of Diseases, 10th Revision, Australian Modification (ICD-10-AM) discharge diagnoses were grouped as STEMI; non-ST-elevation acute coronary syndrome or other coronary syndromes; other cardiac diagnoses; noncardiac diagnoses; and symptom-based diagnoses. Outcomes included out-of-hospital management, coronary angiography, percutaneous coronary intervention, complications, hospital length of stay, inhospital death, 30-day death, and mortality during follow-up. Associations were estimated with multivariable logistic and Cox regression and are reported as odds ratios or hazard ratios with 95% confidence intervals. RESULTS: Among 8,077 suspected STEMI visits with hospital follow-up data, 7,205 (89.2%) had a recorded discharge diagnosis and formed the primary analytic cohort; 872 (10.8%) had no recorded discharge diagnosis. Among the 7,205 with a recorded diagnosis, STEMI was confirmed in 4,330 (60.1%); 824 (11.4%) had non-ST-elevation acute coronary syndrome or other coronary syndromes, 760 (10.5%) other cardiac diagnoses, 613 (8.5%) noncardiac diagnoses, and 678 (9.4%) symptom-based diagnoses. Coronary angiography occurred in 4,836 (67.1%) and percutaneous coronary intervention in 3,200 (44.4%). Inhospital mortality was 8.6%, 30-day mortality 6.5%, and mortality during follow-up 17.5% (median follow-up 2.8 years). Compared with confirmed STEMI, adjusted mortality during follow-up was higher for noncardiac diagnoses (hazard ratio [HR] 1.75, 95% confidence interval [CR], 1.47 to 2.09); other cardiac (HR 1.14, 95% CI, 0.93 to 1.39), NSTE-ACS or other coronary (HR 1.16, 95% CI, 0.98 to 1.38), and symptom-based diagnoses (HR 1.09, 95% CI, 0.89 to 1.34) did not differ materially from STEMI after adjustment. CONCLUSION: Within this statewide pathway population, paramedic-suspected STEMI identified a diagnostica

OBJECTIVES: To evaluate how cross-terminology mapping of International Classification of Diseases (ICD)-coded diagnoses is associated with preservation of diagnostic distinctions and traceability in electronic health record (EHR)-derived phenotypes for genomic research. MATERIALS AND METHODS: We conducted a retrospective, cross-sectional study of real-world ICD code utilization and semantic fidelity among kidney-related diagnoses. Kidney-relevant ICD-9-CM and ICD-10-CM codes were identified using clinician-curated OHDSI ATLAS searches and evaluated in a large academic health system. ICD codes were mapped to Phecodes, SNOMED-CT, the Human Phenotype Ontology (HPO), and Online Mendelian Inheritance in Man (OMIM) using standardized crosswalks. Mapping coverage, richness, and multiplicity were quantified, with multiplicity operationalizing diagnostic aggregation. Three nephrologists independently rated label-level semantic fidelity (0-2 scale). Ordinal logistic regression evaluated associations between mapping multiplicity and semantic fidelity. RESULTS: Among 585 nephrology-relevant ICD codes (571 435 patients), mapping coverage and richness varied across terminologies. Phecodes showed high coverage and mapping multiplicity, whereas SNOMED-CT, HPO, and OMIM mappings were predominantly one-to-one. Among ICD-Phecode mappings, 39% were rated poor, whereas no poor matches were observed among mapped SNOMED-CT, HPO, or OMIM concepts. Greater mapping multiplicity was associated with lower semantic fidelity (OR, 0.33; 95% CI, 0.29-0.37; P < .001). Most ICD-9-CM codes (96%) were represented in at least 1 external cohort. DISCUSSION: Diagnostic aggregation was associated with reduced semantic fidelity and traceability, with potential implications for phenotype construction and interpretation in GWAS, PheWAS, and biobank-scale studies. CONCLUSION: This study provides an empirical framework for evaluating semantic drift in EHR-derived phenotypes and highlights a central tradeoff: abstraction enables scalability, whereas traceability enables translation.

BACKGROUND AND AIMS: Vascular calcification predicts cardiovascular mortality more strongly than traditional risk factors, yet its molecular basis remains poorly understood. The burden is greatest in chronic kidney disease (CKD), where disordered mineral metabolism accelerates arterial mineral deposition. METHODS: Cross-trait genome-wide and phenome-wide association analyses were combined with single-cell RNA-seq and ATAC-seq from human kidneys and coronary arteries to identify upstream regulators. Chromatin immunoprecipitation sequencing and expression profiling were used to assess direct transcriptional control. Functional relevance was evaluated in multiple gene-edited mouse lines and in primary vascular smooth muscle cells (VSMCs) targeting T-box transcription factor 2 (TBX2), Runt-related transcription factor 2 (RUNX2), NLRP3, CASP1, and GSDMD. RESULTS: GWAS followed by expression quantitative trait loci (eQTL) and Bayesian colocalization analysis prioritized TBX2 as a shared genetic locus associated with kidney function and calcification-related cardiometabolic traits. TBX2-deficient mice exhibited increased susceptibility to vascular calcification, hypercalciuria, kidney injury, bone demineralization, and systemic phosphate dysregulation under CKD-like phosphate stress conditions. TBX2 deficiency promoted VSMC calcification and osteochondrogenic differentiation in vitro. Mechanistically, TBX2 acted as a transcriptional repressor by binding the promoter of RUNX2, a key osteogenic transcription factor, and suppressing its expression. Deletion of RUNX2 in TBX2-deficient VSMCs abolished TBX2 loss-induced calcification. TBX2-deficient VSMCs were also more sensitive to activation of the NLRP3 inflammasome by microcrystals generated from osteogenic VSMCs. Genetic deletion of NLRP3, CASP1, or GSDMD in TBX2-deficient mice attenuated vascular calcification and renal injury. In human samples, TBX2 expression inversely correlated with the severity of kidney fibrosis and was reduced in calcified vascular lesions. CONCLUSIONS: Integrative genetic, cellular, and animal studies identify TBX2 as a central transcriptional repressor linking mineral dysregulation, osteogenic signalling, and sterile inflammation in CKD-associated vascular calcification. Therapeutic strategies that restore TBX2 function or target its RUNX2-NLRP3 axis may reduce cardiovascular risk in pa

GIM/FP/GP: [Formula: see text] Nephrology: [Formula: see text].

BACKGROUND: Hyperkalemia is common in chronic kidney disease (CKD) and chronic heart failure (CHF), often leading to treatment dilemmas regarding renin-angiotensin-aldosterone system (RAAS) inhibitors. Although potassium binders and dietary restrictions are central to chronic management, their quality-of-life (QOL) impact remains insufficiently described. This study aimed to characterize real-world treatment patterns and evaluate treatment impact on QOL. METHODS: We analyzed baseline data from a prospective cohort in Japanese nephrology and cardiology outpatient clinics. Participants were adults with CKD (≥ stage G3) or CHF (New York Heart Association class II-IV) who initiated potassium binders within 6 months. Clinical data, serum potassium values, and patient-reported outcomes (generic QOL, disease/treatment-specific QOL, and adherence measures) were obtained at enrollment. RESULTS: Among 347 patients, the median age was 75 years, and 74% were male; 93% had CKD. At enrollment, 59% were prescribed a RAAS inhibitor. Dietary therapy was implemented in 29%. Physical scores of generic QOL were lower than population norms, whereas mental scores were comparable. Treatment-specific QOL scores suggested that potassium binders may have had a relatively small impact on QOL compared with dietary therapy. Adherence to potassium binders was high. CONCLUSIONS: Concurrent use of RAAS inhibitors and potassium binders was common, consistent with a role for binders in supporting RAAS inhibitor continuation. Potassium binders showed little perceived impact, indicating that pharmacologic potassium control may be acceptable to patients managing multiple lifestyle limitations. STUDY REGISTRATION: The study was registered with ClinicalTrials.gov (NCT05297409).

BACKGROUND: Acute kidney injury (AKI) is a frequent and clinically significant complication following cardiac surgery. Doppler-derived renal ultrasound parameters-including the renal resistive index (RRI), semiquantitative power Doppler ultrasound (PDU) scales, and intrarenal venous flow (IRVF)-have been proposed as early, noninvasive predictors of postoperative AKI, but their diagnostic accuracy in this setting remains uncertain. METHODS: We conducted a systematic review of diagnostic test accuracy studies evaluating RRI, PDU, or IRVF for predicting AKI within 7 days after cardiac surgery in adult intensive care unit patients. MEDLINE, Embase, Cochrane CENTRAL, Scopus, Web of Science, and clinical trial registries were searched through June 2025. Sensitivity, specificity, diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC) were extracted or calculated. Meta-analysis was performed for RRI using hierarchical bivariate models; IRVF and PDU were summarized descriptively due to limited studies and heterogeneity. RESULTS: Fourteen studies comprising 1,204 patients were included (12 RRI, 3 IRVF, 1 PDU). RRI thresholds between 0.71 and 0.74 demonstrated the highest diagnostic performance (AUC range 0.72-0.93). IRVF showed modest discrimination (AUC 0.62-0.66). Evidence for PDU was limited to one study. Substantial clinical and methodological heterogeneity was observed and overall certainty of evidence ranged from low to moderate. CONCLUSIONS: Among Doppler-derived renal ultrasound parameters, RRI appears to have the most consistent diagnostic accuracy for predicting AKI after cardiac surgery. However, methodological heterogeneity, the limited number of studies, and the low-to-moderate certainty of the evidence preclude definitive clinical recommendations. Prospective multicenter validation studies with standardized protocols and prespecified thresholds are warranted.

OBJECTIVES: To determine the prevalence of chronic kidney disease (CKD) in internal medicine outpatients in a Central European tertiary care setting, identify associated risk factors and assess use and potential impact of renoprotective therapies. We hypothesised that CKD is common, underdiagnosed and undertreated. DESIGN: Cross-sectional observational study. SETTING: Tertiary care outpatient clinics in Central Europe. PARTICIPANTS: 1933 adult outpatients at risk for CKD were screened; an expanded cohort of 2903 patients with available laboratory data was included for secondary analyses. Inclusion required assessment of estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (uACR) within the study period. Kidney transplant recipients were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was CKD prevalence defined by eGFR and uACR per kidney disease improving global outcomes criteria. Secondary outcomes included detection of previously unrecognised CKD, associations with clinical risk factors and prescription rates of renoprotective therapies. CKD prevalence was also assessed using age-calibrated eGFR thresholds. An exploratory outcome was model-projected gain in dialysis-free time with treatment initiation. RESULTS: CKD prevalence was 32.5% (95% credible interval (CrI) 30.5 to 34.6) and remained high after age-calibrated eGFR adjustment. One new case was revealed for every 5.2 patients screened. CKD odds increased with age (per 25 years: OR 3.81, 95% CrI 3.09 to 4.67), non-renal transplantation (OR 4.38, 95% CrI 3.30 to 5.84), hypertension (OR 2.61, 95% CrI 1.96 to 3.54), heart failure or atrial fibrillation (OR 1.59, 95% CrI 1.29 to 1.96), type 1 (OR 1.97, 95% CrI 1.47 to 2.63) and type 2 diabetes (OR 1.46, 95% CrI 1.21 to 1.77), and atherosclerotic disease (OR 1.49, 95% CrI 1.20 to 1.82). Renoprotective therapy use was suboptimal (sodium-glucose co-transporter-2 inhibitors 42%, glucagon-like peptide-1 receptor agonists 41.7%, nonsteroidal mineralocorticoid receptor antagonists 6.7% of eligible patients). The model-projected gain in dialysis-free time by initiation of renoprotective treatment was estimated to be 11.13 months per CKDe patient on average. CONCLUSIONS: CKD is highly prevalent in tertiary care outpatients and efficiently detected through targeted screening. Suboptimal use of renoprotective ther

OBJECTIVE: To determine the prevalence of chronic kidney disease (CKD) and associated factors among adults with hypertension attending a tertiary cardiac clinic in Tanzania. DESIGN: Hospital-based cross-sectional study. SETTING: Tertiary cardiac outpatient clinic in Dar es Salaam, Tanzania. PARTICIPANTS: A total of 162 adults aged ≥18 years with documented hypertension attending follow-up care from 15 June to 30 July 2024 were recruited using simple random sampling. MAIN OUTCOME MEASURES: The primary outcome was study-defined CKD, classified from available records as estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m² and/or urine dipstick proteinuria ≥1+. Urine albumin-to-creatinine ratio (UACR) and confirmation of persistence for ≥3 months were not available for all participants. Factors associated with CKD were assessed using crude and multivariable logistic regression. RESULTS: Among 162 hypertensive patients, 34 met the study-defined CKD criteria, giving a prevalence of 21.0% (95% CI 15.4% to 27.9%). Median serum creatinine was 94 µmol/L (IQR 77-122; range 48-286) and median eGFR was 77 mL/min/1.73 m² (IQR 62-92; range 19-118); 29 (17.9%) participants had eGFR <60 mL/min/1.73 m². Diabetes was independently associated with CKD (adjusted OR 3.257, 95% CI 1.167 to 9.091, p=0.024). Uncontrolled hypertension was not statistically associated with CKD after adjustment (adjusted OR 1.330, 95% CI 0.546 to 3.236, p=0.531); age, sex and education level were also not significant. CONCLUSIONS: Study-defined CKD was identified in about one-fifth of this tertiary-clinic hypertensive sample, and diabetes was the only independent factor identified. The estimate should be interpreted cautiously because the study was single-centre and full Kidney Disease: Improving Global Outcomes confirmation using chronicity and UACR was not available for all participants. Multicentre studies using repeated eGFR and quantitative albuminuria assessment are needed.

BACKGROUND: Acute kidney injury (AKI) is a global health problem associated with substantial morbidity, mortality, and healthcare costs. Despite advances in prevention and management, in-hospital mortality remains high, particularly among critically ill patients. OBJECTIVES: To determine incidence, risk factors of AKI among patients admitted to Mansoura Nephrology and Dialysis Unit (MNDU), a tertiary nephrology referral center in Dakahlia governorate, Egypt, over one year, and to identify predictors of renal recovery at discharge and in-hospital mortality. METHODS: This prospective observational study was conducted from June 2022 to May 2023 and included adult patients admitted with various kidney disorders. Patients were classified into AKI and non-AKI groups according to KDIGO 2012 criteria. Clinical, laboratory, and outcome data were analyzed, and multivariable regression analyses were used to identify independent predictors of in-hospital mortality and renal recovery after AKI. RESULTS: A total of 839 patients were enrolled, including 330 (39.3%) with AKI and 509 (60.7%) without AKI. The most common pathophysiological causes of AKI were pre-renal (54.2%) followed by intrinsic renal (38.5%) one. In-hospital mortality was significantly higher in AKI than non-AKI group (17.3% vs. 3.8%), with septic shock being the leading cause of death (84.2%). Among patients with AKI, 45.2% achieved complete renal recovery, 21.8% had partial recovery, and 33.0% had no recovery at discharge. On multivariable logistic regression analyses, KDIGO Stage 3 AKI (adjusted OR 0.277, P = 0.046), kidney replacement therapy (adjusted OR 0.409, P = 0.004), and requirement of vasopressor therapy (adjusted OR 0.041, P < 0.001) were independently associated with lower odds of renal recovery, whereas necessity of vasopressor therapy emerged as the only independent predictor of in-hospital mortality (adjusted OR 420.511, 95% CI 97.451-1814.543; P < 0.001). CONCLUSIONS: AKI was common among hospitalized patients and was associated with substantially increased in-hospital mortality. Vasopressor requirement was the strongest independent predictor of mortality, emphasizing the prognostic impact of hemodynamic instability and critical illness severity. Severe AKI (KDIGO Stage 3), kidney replacement therapy, and vasopressor necessity were independently associated with reduced renal recovery

UNLABELLED: Crisponi/Cold-Induced Sweating Syndrome Type 1 (CS/CISS1) is an ultra-rare genetic disorder caused by biallelic variants in the cytokine receptor-like factor-1 (CRLF1) gene and is associated with several comorbidities. Comprehensive data on the respiratory phenotype of this condition are lacking despite being associated with high mortality in infancy, often due to severe respiratory complications like aspiration pneumonia and sudden death related to hyperthermic crises. Our study investigates respiratory complications and lung ultrasound characteristics, enhancing the comprehension of the natural history and pathophysiology of the disease. We enrolled 13 individuals (8 children) carrying a biallelic molecular defect of the CRLF1 gene, either in a homozygous or compound heterozygous state. All were of Italian ancestry, with the majority (77%) being Sardinian. The pathogenic variant c.676dup (p.Thr226fs) in exon 4 was confirmed as the most commonly recurrent variant and was identified in 9 of the 13 patients (69%) of our cohort. Over half of the participants exhibited an ultrasound lung pattern suggestive of sonographic interstitial syndrome findings. Fifteen percent had a documented aspiration pneumonia in infancy, which required hospitalization or ventilatory support. Additionally, one adult patient showed bilateral fibrotic findings, which were validated by a CT scan. CONCLUSIONS: Respiratory involvement appears to be a frequent and under-investigated feature in patients with CS/CISS1. Although lung ultrasound patterns observed in this study were largely nonspecific, LUS may represent a practical, non-invasive screening tool to identify early morphological lung changes potentially related to recurrent or chronic inflammatory processes. WHAT IS KNOWN: • Crisponi/Cold-Induced Sweating Syndrome Type 1 (CS/CISS1) is associated with early-life respiratory complications. • Data on the long-term pulmonary involvement in CS/CISS1 patients are insufficiently documented. WHAT IS NEW: • This is the first study to systematically evaluate lung ultrasound (LUS) findings in a cohort of CS/CISS1 patients, across pediatric and adult ages. • We identified recurrent nonspecific interstitial patterns that suggest chronic inflammatory or fibrotic lung involvement, supporting LUS as a feasible screening tool in disease monitoring.

The airway epithelium serves as a critical barrier against pathogens, allergens, and other environmental insults. Disruption of this barrier contributes to respiratory diseases such as chronic obstructive pulmonary disease, making rapid epithelial repair essential for maintaining lung function. Basal cells (BCs), the primary regenerative cell population of the proximal airway epithelium, drive repair through coordinated collective cell migration rather than isolated cellular behaviors. This process is closely linked to dynamic transitions between jammed and unjammed tissue states that regulate migratory capacity and tissue remodeling. Emerging evidence identifies extracellular matrix (ECM) remodeling, Wnt, and transforming growth factor-β (TGF-β) signaling as key regulators of these multicellular responses. ECM remodeling establishes the mechanical substrate for migration, while non-canonical Wnt signaling promotes cytoskeletal reorganization, cell polarity, and coordinated BC movement. TGF-β signaling acts as a context-dependent regulator of BC migration, differentiation, epithelial jamming, and cytoskeletal remodeling through canonical and non-canonical pathways. ECM-integrin signaling links the extracellular environment to cytoskeletal dynamics and collective migration, while inflammatory and mechanical cues modify these responses. Integrin αvβ5/αvβ6-mediated interactions with the ECM connect mechanical forces to focal adhesion signaling and activation of latent TGF-β, linking tissue mechanics to epithelial repair. Together, integration of inflammatory, biochemical, and biomechanical signals that coordinate collective migration and epithelial restoration. This mini-review highlights recent advances supporting a model where coordinated ECM remodeling, Wnt signaling, and TGF-β signaling regulate BC migration and restore epithelial barrier integrity following injury, and examines how disruption of these processes contributes to abnormal repair in chronic lung disease.

BACKGROUND: Sepsis is a major contributor to maternal morbidity and mortality worldwide and represents one of the leading causes of intensive care unit (ICU) admission among obstetric patients. However, the burden and clinical profile of the most severely affected women remain incompletely defined. This systematic review aimed to estimate the epidemiology, characteristics, and outcomes of sepsis in critically ill obstetric patients. PATIENTS & METHODS: A comprehensive search was conducted for studies published between 2013 and 2025, including studies of women requiring ICU admission for sepsis during pregnancy or the post-partum. Following the screening process, 25 of the 5847 screened studies met the inclusion criteria. All were observational. The overall population included 7,434,710 hospitalised obstetric patients, including 3,593 obstetric ICU admissions for sepsis. The incidence of intensive care unit admissions ranged from 21 to 857 every 10,000 hospitalized obstetric patients and reached incidences of 11.3% among hospitalized obstetric patients with sepsis. Sepsis accounted for 5.7% of obstetric ICU admissions. RESULTS: Half of the patients had one organ dysfunction, while a quarter had three or more, with respiratory and cardiovascular insufficiencies being the most common. The main infection sources were the genital, respiratory, and urinary tracts. Septic shock occurred in 16.6% of the cases. The mean Sequential Organ Failure Assessment (SOFA) score was 6.2 and the Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score was 12.3. ICU and hospital stay were 3 and 8 days. Mortality varied significantly (median 4.6%), with marked disparities between high- and low-income countries. CONCLUSION: Robust epidemiological monitoring is therefore urgently required. REGISTRATION: PROSPERO under ID 2023 CRD42023446466.

OBJECTIVE: To describe the clinical characteristics and outcomes of pediatric patients undergoing palliative extubation (PE) and identify factors associated with in-hospital death. METHODS: This retrospective cohort study included pediatric patients who underwent PE between April 2014 and May 2023. Demographic and clinical variables were assessed, including diagnosis, duration of mechanical ventilation, time between decision-making and extubation, timing and location of extubation, medications used, catecholamine use before extubation, symptoms, treatments instituted, and hospital outcome. Descriptive and comparative analyses were performed according to hospital outcome. Time to outcome was evaluated using Kaplan-Meier survival analysis, with comparisons by the log-rank test. RESULTS: Forty-one patients were included, with a median age of 2.67 years; 51.2% were male, and 90% had neurological impairment secondary to the underlying disease. Most patients underwent PE in the intensive care unit; 73.2% had endotracheal tubes, and 68.3% died in hospital. Median mechanical ventilation duration was 24 days; median time between decision-making and extubation was 1 day; and median time from PE to in-hospital death was 31.2 hours. Symptoms after extubation were less frequent among patients receiving opioids and/or benzodiazepines before extubation (p=0.07). The main symptoms were dyspnea and pain. Dyspnea and opioid use after extubation were associated with in-hospital death. Time to death was shorter among patients receiving catecholamines within 72 hours before PE or morphine and/or benzodiazepines after extubation. CONCLUSIONS: This study provides clinical and epidemiological information on pediatric PE. Findings should be interpreted cautiously given the small sample size.

BACKGROUND: Pulmonary vascular remodelling is a recognised consequence of chronic tobacco exposure and may have prognostic associations even without airway obstruction. The association between the extraparenchymal pulmonary artery (ePA) and all-cause mortality in current and ex-smokers without COPD has not been demonstrated and replicated in large cohort studies. STUDY DESIGN AND METHODS: Retrospective analysis of prospective data from the COPDGene cohort, with validation in the SUMMIT lung cancer screening trial. ePA volume and lung volume were measured on chest CT using automated deep learning-based segmentation. All-cause mortality risk was estimated using Cox proportional hazards models, adjusted for age, gender, body mass index, smoking status, pack-years, emphysema extent, Charlson Comorbidity Index, ILA presence, and FEV1. RESULTS: 4,719 participants without COPD were included in the discovery COPDGene cohort (median age 56 [51-63] years, 50% male) and 3,391 in the SUMMIT validation cohort (median age 64 [59-69] years, 61% male). There were 600 deaths (13%; 39,531 person-years) in COPDGene and 214 deaths (6.3%; 16,629 person-years) in SUMMIT. Each one-standard-deviation (∼25mL) increase in ePA volume was independently associated with all-cause mortality in COPDGene (aHR 1.42 [1.25-1.60], p<0.001) and SUMMIT (aHR 1.23 [1.07-1.42], p=0.003). A parsimonious, ridge-regularised multivariable model developed in COPDGene showed good discrimination (C-index 0.70 [0.65-0.74]) and calibration (integrated calibration index 2.1% [1.3-6.4]) when validated in SUMMIT. INTERPRETATION: Increasing ePA volume in current and ex-smokers without COPD is associated with all-cause mortality and could represent a candidate imaging marker for cohort enrichment in studies of pulmonary vasculopathy, although this requires prospective validation. TRIAL REGISTRATION: N/A.

OBJECTIVES: To determine the prevalence of antiphospholipid syndrome in surgical chronic thromboembolic pulmonary hypertension and its association with late in situ pulmonary artery thrombosis after pulmonary endarterectomy. METHODS: Retrospective cohort of 220 patients undergoing pulmonary endarterectomy at a single centre (2015-2024). Antiphospholipid syndrome was diagnosed per 2006 Sydney criteria with confirmatory antibody testing ≥12 weeks apart. The primary outcome was in situ pulmonary artery thrombosis on follow-up computed tomography pulmonary angiography. Survival and logistic regression analyses were performed. RESULTS: Antiphospholipid syndrome was identified in 36 patients (16.4%), who were younger (40.2 vs 50.2 years; P=.001) and had more prior deep vein thrombosis (69.4% vs 48.9%; P=.038). Over a median 70.5-month follow-up, in situ pulmonary artery thrombosis was more frequent with antiphospholipid syndrome (36.1% vs 15.2%; relative risk 2.37; P=.008). Ten-year recurrence-free survival was 64% versus 82% (log-rank P=.002). Univariate odds ratio was 3.15 (95% confidence interval 1.43-6.94; P=.004); after adjustment for age, sex, and prior deep vein thrombosis, adjusted odds ratio was 2.22 (0.95-5.18; P=.064). Triple-positive patients (n = 6) had 83.3% in situ pulmonary artery thrombosis versus 26.7% in other antiphospholipid syndrome patients (P=.016; absolute risk difference 56.7 percentage points), a hypothesis-generating finding. CONCLUSIONS: Antiphospholipid syndrome is associated with elevated late in situ pulmonary artery thrombosis after pulmonary endarterectomy. The adjusted association was borderline. Triple positivity warrants validation in larger cohorts. Preoperative antibody testing may inform surveillance.

BACKGROUND: While anticoagulation remains the standard of care for acute pulmonary embolism, mechanical thrombectomy (MT) and catheter-directed thrombolysis (CDT) have emerged as effective interventional options for rapid clot removal. However, their comparative outcomes remain incompletely defined. This study aimed to compare the outcomes of MT and CDT for acute PE at a tertiary referral center in the United States. METHODS: We conducted a retrospective cohort study of all patients who underwent MT or CDT for acute PE across a single hospital system between January 2021 and April 2025. Patients were stratified into MT and CDT groups based on the treatment received. Baseline characteristics, procedural data, and clinical outcomes were analyzed. The primary outcome was 30-day mortality. Secondary outcomes included length of hospital stay, major adverse events, reintervention, and PE recurrence. Patients were followed for up to one year or until death. RESULTS: A total of 724 patients were included: 569 (79%) underwent MT and 155 (21%) received CDT. The mean age was 63 ± 16 years, and 49% were female. Most patients (76%) were classified as intermediate-high risk, with a mean right ventricle to left ventricle (RV/LV) ratio of 1.5 ± 0.5. Bilateral or saddle embolism was present in 93% of cases. Patients in the MT group were more likely to have a simplified PE severity index (sPESI) > 0 (73% vs. 60%, p < 0.001). Age, rates of cancer, chronic cardiopulmonary disease, and concurrent deep vein thrombosis were similar between groups. Median procedure duration was longer for MT (66 minutes, IQR 46-89) than CDT (58 minutes, IQR 40-77; p = 0.003). Median postoperative length of stay was 3 days in both groups. MT was associated with a higher incidence of intraoperative adverse cardiac events (2.5% vs. 0%, p = 0.048), while CDT was associated with higher ICU admission rates (83% vs. 36%, p < 0.001). However, thirty-day mortality was similar between groups (CDT: 2.6% vs. MT: 4.6%; p = 0.27). Additionally, the one-year incidences of CTEPH (MT: 4.5% vs. CDT: 3.4%, p=0.69), PE recurrence (MT: 4.4% vs CDT: 2.5%, p=0.31) and all-cause mortality (MT:7.8% vs. CDT: 5.8%, p=0.41) were not statistically significant between MT and CDT respectfully. CONCLUSION: In this retrospective cohort, MT and CDT for acute PE showed statistically comparable mortality, CTEPH, and PE recurrence

BACKGROUND: Treatment of intermediate-high risk pulmonary embolism (PE) with catheter directed therapy remains a topic of controversy. It is unknown if long-term post-hospitalization outcomes of these patients are improved compared to anticoagulation. RESEARCH QUESTION: What is the comparative effectiveness of catheter-directed reperfusion therapy versus conventional anticoagulation on both short- and long-term outcomes among patients with intermediate-high risk PE? STUDY DESIGN AND METHODS: This was a retrospective cohort study of hospitalized patients in the United States with intermediate-high risk pulmonary embolism between 2010 to 2024 from a multi-institutional aggregated electronic health record database. Patients were categorized as receiving catheter-directed intervention (CDI) or conventional anticoagulation and followed for 30-day mortality, bleeding and procedural complications (short-term outcomes) and, among those who survived discharge, for readmission related to heart failure or respiratory failure, oxygen dependence, and pulmonary hypertension related diagnosis (long-term outcomes). Overlap weighting was used to balance characteristics between patients in both groups and calculate adjusted hazard ratios. RESULTS: After application of a specific phenotype definition integrating diagnosis codes, vital signs, and laboratory biomarkers to identify patients with patients with intermediate high-risk PE in a large-scale data set, a total of 50,614 patients were included in the analysis of short-term outcomes and 49,122 were included in the analysis of post-discharge outcomes. CDI was associated with a lower hazard of death in both crude (HR 0.56; 95% CI 0.53-0.59, p<0.001) and adjusted comparisons (aHR 0.70; 95% CI 0.66-0.73, p<0.001). Although there was no increase in CTEPH rates (aHR 1.05; 95% CI 1.00-1.10, p=0.057), long-term outcomes favored CDI including lower rates of readmission for heart failure (aHR 0.79; 95% CI 0.75-0.83, p<0.001), readmission for respiratory failure (aHR 0.85; 95% CI 0.81-0.90, p<0.001), and lower chronic oxygen usage (aHR 0.69; 95% CI 0.65-0.74, p<0.001). INTERPRETATION: Among patients with intermediate-high risk pulmonary embolism, CDI was associated with improved short- and long-term survival compared to anticoagulation alone. These findings suggest a potential benefit of CDI in intermediate-high risk PE and suppo

Current and future clinicians are experiencing a malaise that is at once deeply felt yet difficult to articulate. While "burnout" and "moral injury" have come to dominate many accounts, these terms do not fully capture the experience of clinicians who struggle to name a sense of loss, lament, and love for a beloved profession. Therefore, we propose "heartache" as a more fitting description. While burnout comes from the world of industry and moral injury from the world of war, heartache comes from the world of love. Burnout depends on individuals to cultivate resilience, and moral injury encourages systems-level change. By contrast, heartache moves the healer toward local communities of virtue and friendship where the healer's heartache is most deeply felt and from which creative responses can best emerge. We name several examples of such communities at different academic medical training programs and hospital systems, exploring the "family resemblances" shared among these projects. In these examples, we show how such efforts engage healers not merely as burnt-out workers or morally injured agents, but as friends-through an emphasis on hospitality, a capacity for teaching new ways of speaking and seeing, and deep wells of ethical, spiritual, and practical resources which nourish the heart.

Peer review is widely regarded as the cornerstone of scientific publishing, yet it depends on the voluntary efforts of a limited portion of the academic workforce. For clinician-scientists in academic medicine, peer review represents an essential but largely unrecognized component of faculty workload, competing directly with research, clinical care, teaching, and administrative responsibilities. Despite its central role in ensuring scientific rigor, peer review is rarely formally measured, incentivized, or incorporated into promotion and evaluation processes. This commentary examines the growing burden of peer review from the perspective of a mid-career clinician-scientist and journal editor. As publication productivity increases, so do invitations to review, often concentrating requests among a subset of highly active investigators. At the same time, editors report difficulty recruiting reviewers, sometimes requiring numerous invitations to secure adequate peer review. These dynamics may delay publication, affect dissemination of clinically relevant knowledge, and influence the career progression of authors. This system reflects a misalignment between institutional priorities and the labor required to sustain scholarly publishing. Addressing this imbalance will require greater recognition of peer review as scholarly work, clearer expectations for participation, and broader engagement to ensure sustainability.

BACKGROUND: Physician advocacy is essential to promoting health equity. Despite the Accreditation Council for Graduate Medical Education recognizing advocacy as a core competency, resident training opportunities remain limited. AIM: Develop, implement, and evaluate a legislative advocacy conference for internal medicine residents, in partnership with two community advocacy coalitions. SETTING: Sacramento, CA, in May 2025. PARTICIPANTS: Forty-five internal medicine residents. PROGRAM DESCRIPTION: The first day of the conference involved didactics/workshops in legislative advocacy skills, mock meetings, and a career panel. The second day involved meetings with state legislators. PROGRAM EVALUATION: Sixteen of 45 residents completed a post-conference survey. One hundred percent of residents reported gaining "relevant skills to participate in advocacy" and an "increased likelihood that…(they) will participate in advocacy in the future." A majority of residents reported each session had a major/moderate impact on their advocacy training, and 100% thought meeting with legislators had this level of impact. DISCUSSION: This conference addressed a gap in resident education by providing experiential training in legislative advocacy and increased residents' perceived likelihood that they will engage in advocacy in the future. Challenges include funding, time constraints, and identifying policy priorities. This conference offers a model for future community-engaged, multi-institutional collaborations related to advocacy.

Connected procedural care is increasingly evaluated product by product, although performance emerges from interactions across technologies, organizations, and clinical workflows. This paper proposes System Performance Readiness (SPR) as a capability for understanding system performance across product boundaries. Its defining requirement is that a connected procedural episode be reconstructable, so that any legitimate participant, whether a health system, manufacturer, clinician, or regulator, can understand how the connected system performed. Rather than creating a new regulatory layer or data platform, the framework specifies what a system should be able to know, who is responsible for the relevant evidence, and how learning can occur across platforms and sites. A reconstructable record of the connected episode makes it possible to understand how the system performed, so that learning, not blame, drives improvement.

OBJECTIVES: To examine trends in surgical management of female stress urinary incontinence (SUI) from 2010 to 2025 including the impact of the mesh pause of August 2023 and national credentialing of surgeons. METHODS: This retrospective cohort study used the Health New Zealand National Minimum Dataset (hospital events, NMDS). This includes all publicly funded hospital events from 2010-2025 for female stress urinary incontinence procedures being: mesh slings, fascial slings, Colposuspension and periurethral bulking agents. RESULTS: There was significant and sustained decline in female SUI procedures beginning in 2013 to 2022. There was also a shift in procedural types with mesh slings being the predominant procedure before 2020 and periurethral bulking agents increasing from 2017. Following the mesh pause, there was no change in overall SUI activity prior to and after the pause. However, there was shift in the predominant procedures from mesh slings to periurethral bulking agents. In younger age groups the fall in sling procedures and increase in bulking was more marked. In the context of surgeon credentialing which began in 2022 through till october 2025, we found 64% of Colposuspensions and 22% of fascial slings were performed at a hospital without a New Zealand framework credentialled surgeon. Due to NMDS database being hospital/procedural based, we assigned credentialing at hospital level which may overestimate the availability of credentialled expertise at the hospital level. CONCLUSION: Between 2010 to 2025, there has been a sustained decline in female SUI procedures in New Zealand public hospitals. This decline began in 2013, nine years before the mesh pause of 2023. There has been a significant shift in the predominant SUI procedures following the mesh pause from highly efficacious procedures, mesh slings, to periurethral bulking agents, which are less efficacious. We also found that following credentialing, a significant proportion of procedures were performed in hospitals without a credentialed surgeon.

Demand for recognition of the specialized knowledge and skills required of Infant and Early Childhood Mental Health (IECMH) practitioners, researchers, and policymakers resulted in the establishment of standardized professional credentials that document this expertise. However, to date, research on the influences and impacts of an Infant or Early Childhood Mental Health Endorsement on IECMH professionals is scarce. This descriptive, cross-sectional study aims to fill this gap by reporting quantitative findings from a voluntary online survey, the Perceptions of Endorsement Survey (PES), completed by a diverse group of 911 Endorsed professionals across the United States and Australia. The study by a U.S. research team explores how personal factors, professional supports, and perceived benefits influence the likelihood of continuing to participate in the Endorsement system and of recommending it to others (Attitudes towards Endorsement). Regression analyses revealed three factors that were significant predictors of positive Attitudes towards Endorsement: Confidence and Motivation, Endorsement-related Social Influences, and perceived Opportunities. Moreover, the combination of Endorsement-related Social Influences and Opportunities significantly and uniquely predicted positive Attitudes towards Endorsement above what these factors predicted individually. Discussion focuses on how individual-level demographic characteristics, occupational-level factors, social factors, and perceived benefits relate to Attitudes towards Endorsement.

Psychiatry combines clinical expertise with substantial institutional authority over diagnosis, treatment access, coercion, clinical records and the credibility assigned to people receiving care. This Essay examines how that authority can impede learning from recurrent warnings across professional misconduct, coercive care, diagnostic practices and iatrogenic harm. We propose institutional non-learning as a cross-cutting problem: professional interpretation can shape whose testimony is believed, which harms are measured, how events are recorded and whether reform is evaluated. Drawing on epistemic injustice, psychiatric survivor research, treatment-safety research, publication and outcome-reporting bias, and empirical studies of diagnostic bias, we develop a framework for epistemic reciprocity and accountability. It distinguishes occurrence from prevalence, recognises that treatment risk varies across populations and contexts, separates benefit from safety, applies reflexive scrutiny across clinical, academic and lived experience expertise, and extends representativeness to both research participants and the published evidence base. We use ignorance culture, exclusion culture, defensiveness and diagnostic weaponisation to describe recurring institutional functions. A responsibility culture requires independent scrutiny, prospective harm surveillance, lived experience governance, remedy and redress, and publicly evaluable evidence that practice has changed and safety has improved.

This study reviews the literature on the impacts of Certificate-of-Need (CON) laws on outcomes related to hospitals. CON laws require the approval of states' health planning agencies for health care providers to engage in regulated actions such as opening or expanding facilities or purchasing equipment. Economic theory suggests that barriers to entry should reduce competition, leading to higher prices, greater per-firm quantity but lower market quantity, and larger net revenues for incumbent providers. However, defenders of CON laws argue that they ensure high quality standards for new entrants, while also offsetting distortions that disadvantage hospitals and put some at risk of closure. The preponderance of available evidence points toward CON laws restricting entry of new competitors, which in turn increases the number of procedures per hospital. At the same time, CON laws also appear to inhibit hospital expansion, and there is little evidence of increased prices or higher hospital profitability. Studies on hospital efficiency and quality of care for procedures performed exclusively at hospitals mostly point to null or negative effects, but evidence on quality is more mixed for services that can be provided outside of hospitals. With that said, there is a need for new research that utilizes the latest tools for identifying causal effects and better accounts for the wide variation in CON laws across states.

Delays in accessing clinical genetics services are increasing globally. This systematic review and Synthesis Without Meta-analysis investigated the types and frequency of harms during delayed access to clinical genetics services (PROSPERO CRD42024601622). We searched peer-reviewed literature across multiple databases and included Australian policies, white papers and government documents reporting patient harms. Certainty of evidence was assessed using GRADE. Five studies met inclusion criteria. The clearest signal was non-attendance, which rose with longer waits across two studies (n = 1280). Martinez et al. observed mortality among clinical genetics waiting-list patients. Oncology and other tertiary specialties with higher mortality risk are commonly referred to clinical genetics. A randomised trial (n = 590) of cancer genetics patients found psychological distress during waiting, with high baseline distress persisting despite intervention. A large cohort (n = 48,622) reported family-level harms, including deaths among at-risk relatives. Certainty was moderate for non-attendance and very low for mortality, distress and family harms due to limited studies and imprecision. Direct causal evidence and significant associations linking waiting time delays to harm remain sparse; this represents a significant gap in the evidence base. Better evidence on presentations and factors linked to harm would support more effective waiting-list management. This review characterises the types of harm experienced by patients during the clinical genetics waiting period, providing a foundation for future investigation and demonstrating opportunity for improved services. System-level action is needed, including safety evaluation of emerging models of care, structured prioritisation, improved genetics literacy and transparent waiting-list management to strengthen equity and safety.

OBJECTIVES: Children with medical complexity (CMC) and their caregivers face multifaceted challenges during hospitalization. Pediatric residents are often frontline clinicians for these patients but frequently identify feelings of inadequate preparedness to meet their care needs. We assessed the impact of a multimodal curriculum on common acute and chronic medical devices in CMC on caregiver-reported resident communication. We hypothesized that targeted education would translate to improved caregiver perception of family-centered communication. METHODS: We implemented a novel medical device curriculum for pediatric residents at 2 children's hospitals. Caregivers of hospitalized CMC completed a modified 14-item Communication Assessment Tool pre- and post-curricular intervention. We used generalized estimating equations at the caregiver level and paired t tests at the resident level to evaluate pre-post changes. We compared postintervention scores with those of a cohort of unexposed residents. RESULTS: We collected 253 surveys on 39 pediatric residents. At the resident level, there was a statistical increase in overall mean score following intervention (pre, 4.844/5 [SD = 0.213]; post, 4.934/5 [SD = 0.132]; P = .0328). At the caregiver level, mean survey scores increased, although this was not statistically significant. Four of 14 survey items showed statistical improvement following intervention. Caregiver-level outcomes were consistent in the sensitivity analysis using an unexposed control, indicating robustness of findings. CONCLUSION: Caregivers of CMC reported modest improvements in resident collaborative communication behaviors following intervention. Ongoing deliberate practice, including expanded educational models and the integration of caregiver feedback into physician evaluation tools, may further support skill development for clinicians caring for hospitalized CMC.

We present a novel application of the SCCS method for estimating the effectiveness and waning of the third dose of COVID-19 monovalent vaccine in France. We used data on individuals hospitalised for COVID-19 between September 2021 and February 2022 from the Système National des Données de Santé. Only cases having received a 3rd dose of COVID-19 vaccine prior to or on the day of hospitalisation were included in the analysis. We developed a new SCCS model including only time post-dose 3 vaccination, with reference period 24-65 days post-vaccination to capture maximum vaccine protection. Time was split into short-term and long-term post-vaccination risk periods, including days 4-9 corresponding to minimum protection, and successive 7-day windows from day 66 post vaccination. The model included two exposure variables, representing short-term and long-term effects of vaccination. The analysis confirms the relative effectiveness of the third-dose COVID-19 vaccination, the waning of vaccine immunity though of limited extent, and possible effect modification related to virus strain, vaccine, vaccination history, age, and sex. The strengths and weaknesses of this approach are discussed. Suitably applied, the SCCS method may provide a useful method of analysis of vaccine effectiveness which automatically controls for time-invariant confounders.