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Critical Care Medicine

Ovid Technologies (Wolters Kluwer Health)

Preprints posted in the last 7 days, ranked by how well they match Critical Care Medicine's content profile, based on 12 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit.

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Protocol for Implementation and Evaluation of a Reserve-Stress-Rescue Pathway for High-Risk Preoperative Triage.

Sohn, I.; Singh, T.; Carr, Z. J.

2026-07-13 surgery 10.64898/2026.07.09.26357629 medRxiv
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Background High-risk preoperative triage remains fragmented: existing tools often estimate risk without identifying modifiable mechanisms or linking classification to postoperative monitoring, destination planning, and rescue resources. This protocol describes implementation and evaluation of a Reserve-Stress-Rescue (RSR Framework), pathway that operationalizes perioperative high risk as a mismatch among patient physiologic reserve, procedural stress, and system rescue capacity. Approach RSR is a proposed clinician-facing, modular scoring framework for adults undergoing major surgery, especially patients with frailty, multimorbidity, poor functional capacity, anemia or malnutrition, cardiopulmonary disease, or limited postoperative support. Each domain, Reserve, Stress, and Rescue, is scored from 0 to 4 and recorded as both a three-part profile and a total score from 0 to 12. Scores map to Green, Amber, Red, and Crimson triage bands that trigger escalating actions, including targeted optimization, multidisciplinary review, anesthesia and surgical planning, postoperative destination selection, monitoring intensity, and predefined escalation criteria. Validation Plan The initial phase of this study received an exemption determination from the Yale University Institutional Review Board on June 3, 2026, under IRB Protocol ID 2000042729, with exempt categories 2(ii) and 4(iii), including a waiver of HIPAA authorization for access to and use of protected health information as described in the approved protocol. Evaluation will proceed in stages, assessing feasibility, interrater reliability, completeness, acceptability, discrimination, calibration, and clinical utility. Key outcomes include postoperative complications, unplanned escalation of care, intensive care utilization, failure to rescue, mortality, length of stay, triage burden, low-yield testing cascades, and management-changing pathway activation. Conclusion The RSR pathway reframes high-risk status as a modifiable interaction between vulnerability, operative insult, and rescue capacity rather than a fixed patient label. If feasible and valid, RSR may standardize high-risk identification, align perioperative resources with anticipated physiology, improve communication, and support safer, actionable shared decision-making.

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Institutional Standing and Trainee Outcomes in the 2025 US Residency Match

Turner, J. I.; Arias, A.; Burk-Rafel, J.; Oermann, E. K.

2026-07-13 medical education 10.64898/2026.07.09.26357696 medRxiv
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Importance: The transition from medical school to residency forms a national training network, yet its large-scale structure and implications for trainee outcomes remain poorly characterized. Objective: To evaluate the US residency match as a network and assess how institutional position relates to residency placement, educational debt, and specialty choice. Design: Cross-sectional analysis of publicly reported 2025 residency match outcomes. Setting: 107 US MD-granting medical schools and 301 residency institutions with available match data. Participants: 14,616 US MD students matching into residency in 2025 (convenience sample). Exposure: Institutional position within the residency match network, quantified using PageRank network centrality. The relative strength of each school's graduating class was defined as the median centrality of residency destinations across graduates (placement score). Main Outcomes and Measures: Residency placement outcomes, mean medical school debt at graduation, and specialty choice (primary care vs surgical specialties) in relation to institutional position within the residency match network. Network-derived measures were also compared with NIH funding, residency reputation, and student selectivity. Results: Among 14,616 US MD students matched across 107 medical schools and 301 residency institutions (approximately 73.5% of total US MD cohort), network-derived measures of institutional influence closely aligned with benchmarks of institutional standing such as NIH funding, residency reputation, and student selectivity (Spearman's Rho; = 0.72-0.86; all p < .001). Graduate outcomes varied systematically across institutions. Graduates of highly connected medical schools were more likely to match into highly connected residency programs (87.3% for top-quintile vs 41.0% for bottom-quintile schools). Schools with higher placement scores had graduates with lower educational debt, reduced entry into primary care, and increased entry into surgical or competitive specialties. Compared with bottom-decile schools, top-decile schools (stratified by placement score) had 37% lower mean graduate debt, 24% lower primary care entry, and 75% higher surgical specialty entry. Higher educational debt was not associated with entry into higher-compensated specialties. Conclusions and Relevance: The residency match network reflects a hierarchical structure of institutional standing. Graduates of higher- and lower-positioned medical schools experience systematically different residency placement outcomes. These findings provide a population-level, behavior-based perspective on institutional influence and its relationship to training pathways.

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Sociodemographic Predictors of Consent: A Protocol and Statistical Analysis Plan for a Nested Observational Study of Canadian Sites in the REVISE Trial

Bauer, N.; Binnie, A.; Lad, V.; Marticorena, M.; Tsang, J.; Poirier Zytaruk, N.; Heels-Ansdell, D.; Cook, D. J.

2026-07-09 intensive care and critical care medicine 10.64898/2026.07.06.26357216 medRxiv
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Background: In Canada, there is a lack of data relating sociodemographic characteristics to the likelihood of consent and clinical trial participation. Objective: The overall objective of this study is to examine the association of hospital-level sociodemographic variables with a priori informed consent rates for participation in the REVISE trial. Design: This study is a retrospective observational analysis of Canadian sites participating in the international REVISE trial. Methods: Sociodemographic characteristics for 42 hospitals participating in the REVISE trial will be supplemented by national data from the 2021 Canadian Census of Population Profile at the census tract level corresponding to the hospital's location. Hospital level information for Ontario sites will be derived from the Institute for Clinical Evaluate Sciences (ICES) database. Site clustering will be performed using latent class analysis, a flexible clustering technique that identifies meaningful subgroups based on sociodemographic variables purposively selected from data available through the Statistics Canada 2021 census profile, ICES, and hospital-reported data. Clustering analysis will be performed for all Ontario hospitals with available ICES data, followed by a separate analysis for all Canadian REVISE sites using Statistics Canada data. Concordance in the clustering of REVISE sites will be examined by comparing the assignment of hospitals to the latent classes separately identified using ICES and Statistics Canada data. If there is a high degree of agreement between the two datasets, sociodemographic predictors will be analyzed using the clusters identified through ICES for Ontario sites with the concordant classes based on Statistics Canada data for Canadian sites outsite Ontario. If there is disagreement in cluster assignment between the two datasets, separate analyses of sociodemographic factors will be conducted for Ontario sites using ICES data and for all Canadian sites using the 2021 Census Profile. Multivariate linear regression models will be used to analyze the association between hospital-level characteristics and the likelihood of a priori and deferred consent. Results: Results of this study will generate information about the relationship between informed consent to participate in a low-risk critical care clinical trial using different consent models, and socioeconomic patient characteristics at the hospital site level (e.g., educational attainment, knowledge of official languages, citizenship rates, family income, poverty, rurality and immigration patterns). Conclusions: This study will fill an evidence gap by generating information on the relationship between sociodemographic variables and the likelihood of informed consent to participate in a critical care clinical trial in Canada.

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Comparative Evaluation of Central Venous Oxygen Saturation, Carbon Dioxide Venous Arterial Gradient, and Lactate Levels as Markers of Tissue Perfusion After Cardiac Surgery: A Prospective Exploratory Observational Study

Neves, J. K.; Venturini, V.; Zeferino, S.; Galas, F. R. B. G.; Auler Junior, J.

2026-07-10 intensive care and critical care medicine 10.64898/2026.07.04.26357161 medRxiv
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Objective: This study aims to identify which markers of tissue hypoperfusion - specifically lactate levels, central venous oxygen saturation (ScvO2), and venous arterial carbon dioxide gradient (CO2 gradient) - have the highest sensitivity and specificity in predicting the discharge of postoperative cardiac surgical patients from the ICU within 48 hours. This is an exploratory, hypothesis-generating investigation. Methods: Prospective observational study involving 100 patients in the Surgical ICU at InCor-HCFMUSP undergoing cardiac surgery with cardiopulmonary bypass. Perfusion markers were assessed at ICU admission and 24 hours post-admission. Results: ScvO2 at 24 hours was the only marker significantly associated with ICU discharge (OR=1.096; 95% CI=1.020-1.180; p=0.012). Formal DeLong's test confirmed ScvO2 had significantly superior discriminatory performance compared to lactate (AUC 0.661 vs. 0.428; p=0.004). Lactato and CO2 gap showed no significant associations. Conclusions: In this exploratory cohort, ScvO2 at 24 hours post-admission showed a statistically significant association with early ICU discharge and superior discriminatory performance compared to lactate. These findings are hypothesis-generating and require prospective validation before clinical recommendations can be made.

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The Causal Artificial Intelligence Clinician for early haemodynamic management of septic shock in ICU

Angelotti, G.; Azzimonti, L.; Cecconi, M.; Zaffalon, M.

2026-07-09 health informatics 10.64898/2026.07.06.26357375 medRxiv
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Introduction: Standardizing fluid and vasopressor resuscitation in sep- tic shock is challenging due to patient heterogeneity. We trained a causal model to identify optimal dosing during the first six hours of intensive care unit (ICU) admission. Methods: Graphical causal inference models were applied to estimate het- erogeneous treatment effects. Grounding models in expert clinical knowl- edge minimizes bias from spurious correlations to generate robust, contextu- ally meaningful recommendations. Our model was trained on 1,702 MIMIC database admissions and externally validated on 1,434 eICU admissions. Pri- mary outcomes were in-hospital survival and 24-hour clinical improvement (SOFA score reduction of two points or more). Findings: The cohort comprised 3,136 participants (median age 65 years [IQR 53-75]; 42.7% female). Deviation from vasopressor recommendations was associated with increased in-hospital mortality (median OR 5.61, 95% CI 5.44-5.78) and failed clinical improvement (median OR 6.33, 95% CI 6.17-6.50). Fluid deviations yielded corresponding median ORs of 1.02 (95% CI 1.02-1.02) and 1.14 (95% CI 1.14-1.14). In external validation, the model achieved a median survival AUROC of 0.73 (95% CI 0.69-0.77) and clini- cal improvement AUROC of 0.69 (95% CI 0.66-0.72), matching predictive baselines. Treatment effects were heterogeneous: optimal fluids increased survival by up to 4% in low-severity subgroups, while vasopressor responses varied from 0.5% to 17% across acute severity levels. Sensitivity analyses across 36 scenarios confirmed primary associations in 33 cases (91.7%). Interpretation: Recommendations from expert-grounded causal models correlate with improved septic shock outcomes in external validation, cap- turing significant heterogeneity in patient response.

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The Patients' Voice in Clostridioides difficile Infection: Large Language Model-Assisted Thematic Analysis of Patient Testimonials

Villafuerte-Galvez, J. A.; Noriega, M. A.; Cakir Colak, S.; Crawford, C. V.

2026-07-09 infectious diseases 10.64898/2026.07.08.26357545 medRxiv
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Background. Clostridioides difficile infection (CDI) imposes a burden that extends well beyond the gastrointestinal tract, yet existing outcome measures only partially capture the patient experience. We used frontier large language models (LLMs) on patient and caregiver narratives at scale to describe how burden shifts with disease course. Methods. We analyzed 189 testimonials from the Peggy Lillis Foundation corpus, sorted into four cohorts with recurrence (r) and fulminant (f) severity as axes (rfCDI, fCDI, rCDI, non-rfCDI). Two independent LLMs coded eight thematic domains, four fulminant flags, thirteen emerging semantic fields, the dominant dimension, and narrative arcs. Two clinicians independently coded a subset for inter-rater reliability (PABAK, Gwet's AC1). Results. Treatment trajectory was the dominant theme in recurrent disease, whereas death and near-death dominated non-recurrent fulminant narratives. Psychological burden was near-universal in fulminant disease (98.0% in rfCDI, 97.2% in fCDI). Caregiver and bereavement content concentrated in fCDI (66.7%). Diagnostic failure was frequent across recurrent cohorts (47.6 - 56.1%). Bacteriotherapy tracked recurrence (60.2% rfCDI versus 5.6% fCDI). Financial, mental-health, and caregiver burdens were prominent and are currently unaddressed by guidelines. Human-human reliability was substantial (PABAK 0.79 for semantic fields, 0.76 for domains); arc coding was least reliable. Conclusions. Patient narratives reveal a course-dependent, multidimensional burden in CDI. Concrete gaps exist between what patients prioritize, what guidelines recommend, and what therapy access provides. Frontier-LLM coding, validated against clinicians, offers a reproducible route to translate these priorities into research, care, and policy.

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Is simple better? Comparing Computational Cost and Carbon Impact of Machine Learning Models for Traumatic Brain Injury Prediction; A Case Study for Sustainable Digital Health Implementation

Gauss, T.; Delude, T. F.; Kalimouttou, A.; Seddiki, O.; Sanchez, C.; Greze, J.; Brossard, C.; Moyer, J.-D.; Brelurut, G.; Medjkoune, S.; Krainik, A.; Boulier, T.; Lagarde, K.; Lazard, A.; Bouzat, P.; Lemasson, B.

2026-07-08 intensive care and critical care medicine 10.64898/2026.07.05.26357337 medRxiv
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Background Machine learning (ML) models for traumatic brain injury (TBI) prediction increasingly demand extensive data, computational resources, and energy consumption, yet simpler models may offer comparable clinical benefit with lower barriers to deployment. This study compares predictive performance, computational efficiency, carbon footprint, and real-world feasibility of resource-efficient ("pauci-parameter") versus data-intensive ("multiparameter") ML models for predicting TBI patient care pathways and outcomes. Methods External validation study in a level 1 trauma center (n=534 adult TBI patients with GCS<9 and/or intracranial injuries). Seven models tested: two pauci-parameter models using only routine prehospital variables (PREHOSP, 15 variables) or CT image analysis (CT-TIQUA), and five multiparameter models integrating clinical and imaging data. Primary outcome: positive likelihood ratio for predicting neurocritical care intensity, mortality (7/30-day, 6-month), and functional outcome (Glasgow Outcome Scale Extended). Secondary outcomes: computation time, carbon footprint, clinical implementability. Results Multiparameter models showed superior performance but did not consistently translate to better clinical utility. PREHOSP (pauci-parameter) showed comparable performance to complex models for most outcomes. The best-performing multiparameter model (MULTI-PRE) required 100-fold longer inference time and 10-fold higher carbon emissions per prediction versus simple models, while net clinical benefit was nearly identical (0.06 vs 0.05). Models using only prehospital data demonstrated greater generalizability and lower deployment barriers. Interpretation Computational complexity and resource intensity should factor equally with predictive performance in clinical AI deployment decisions. For sustainable digital health implementation--especially in resource-limited settings--simpler models with comparable clinical benefit may enable broader access while reducing environmental and financial costs.

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Assessment of Perioperative Biomedical Equipment Availability, Functionality, and Management Practices Across Rwanda: A Cross-sectional Observational Study.

Fofanah, T.; Temesgen, W. B.; Berhe, D. F.; Mukundwa, P. N.; Belachew, A. G.; Gemechu, N. B.; Murithi, G.; Mukanahayo, E.; Bitew, A. A.; Ndizeye, A.; Turc, R.; Alemu, S. B.; Ntihumbya, J. B.; Bekele, A.; Rice, H. E.; Alayande, B.

2026-07-10 health systems and quality improvement 10.64898/2026.07.07.26357184 medRxiv
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Effective management of biomedical equipment prevents breakdowns, extends equipment lifespan, ensures perioperative safety and cost-efficiency. There are major challenges in managing biomedical equipment, particularly in low- and middle-income countries. This study aimed to assess the availability, functionality, and adherence to maintenance practices of biomedical equipment in operating rooms (ORs) and post-anaesthesia care units (PACUs) across Rwanda. A cross-sectional observational study was conducted at one Level 2 district hospital in each of Rwanda's five provinces (n=5 sites). Data were collected using three main tools: 1) a medical equipment checklist, 2) a checklist for hospital biomedical management, and 3) direct inspections of selected biomedical equipment. All tools underwent pretesting and face validation with support from biomedical experts prior to data collection in May 2024. Key measures, including the availability and functionality of biomedical equipment, and adherence to maintenance and management practices, were summarised using descriptive statistics. The five hospitals had a total of 16 ORs, 4 PACUs, and 226 pieces of equipment. The overall availability of biomedical equipment was 45%, and the functionality of the available equipment was 96%. The mean adherence rate to national management practices was 66%. The Rwandan government, non-governmental organisations, and hospitals were identified as direct funders of the equipment, accounting for 42%, 12%, and 4%, respectively. However, 42% of the equipment surveyed could not be linked to any of the above sources of acquisition. Among non-functional equipment, 75% was due to a lack of spare parts, while 25% was due to a lack of skills to maintain the equipment. In summary, we found low availability of perioperative biomedical equipment across Rwanda, although the available equipment was highly functional. Adherence to national management practice guidelines was relatively low, threatening the sustainability of functional equipment. We recommend that the government and hospital administrators implement robust, regular auditing systems to ensure proper management of biomedical equipment.

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Multi-omics and network propagation reveal latent innate immune programmes stratifying high-risk thrombotic primary antiphospholipid syndrome

Sasikumar, S.; Baltsiotis, M.; Verrou, K.-M.; Rouni, G.; Sfikakis, P. P.; Samiotaki, M.; Petsalaki, E.; Tektonidou, M. G.

2026-07-09 rheumatology 10.64898/2026.06.26.26356680 medRxiv
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Thrombotic primary antiphospholipid syndrome (thrPAPS) outcomes are associated with thrombosis type (arterial versus venous), recurrence, and antiphospholipid antibody (aPL) profile (single versus triple-aPL). We investigated molecular signatures underlying disease status and high-risk phenotypes. We performed whole-blood transcriptomics and mass spectrometry-based plasma proteomics in patients with thrPAPS and age/sex-matched healthy controls. Analyses included differential expression, pathway enrichment, weighted gene co-expression network analysis (WGCNA) and machine learning. Multi-Omics Factor Analysis (MOFA2) and network propagation were applied to identify latent molecular programmes associated with high-risk phenotypes. Transcriptomic and WGCNA analyses revealed an interferon-associated module associated with high-risk phenotypes. Plasma proteomics distinguished thrPAPS from healthy controls through a coordinated thromboinflammatory signature encompassing complement, acute-phase, platelet, and coagulation-associated pathways. Complement factor D, a rate-limiting enzyme of the alternative complement pathway, discriminated recurrent from single-event thrPAPS (AUC = 0.79) and correlated with thrombotic event count (Spearman's correlation = 0.62, p < 0.001). Mixed arterial/venous phenotype showed the greatest degree of subgroup-specific dysregulation, including complement and coagulation/fibrinolysis-related proteins. MOFA2 identified a proteome-dominant latent factor that increased with aPL burden (Spearman's correlation = 0.33, p = 0.017) and was enriched for complement cascade proteins. Network propagation embedded this signature within immune-cell signalling (STAT-1, PI3K-AKT, MAPK8, SRC), N-linked glycosylation, and mitochondrial oxidative phosphorylation. Longitudinal profiling identified reactive oxygen species-associated proteins during active disease. ThrPAPS is characterised by a complement-, interferon- and platelet-driven thromboinflammatory programme that scales with aPL and thrombosis burden, converging on innate immune activation as a central feature of high-risk disease.

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Study protocol: Empowering Singaporeans to better manage chronic heart failure

Bairavee, B.; Wang, Y.; Kanna Ravi, D.; Lee Shan Yin, A.; Ching Chiew Wong, R.; Loh, S. Y.; Graves, N.; Sung, S.; Yoon, S.; Hausenloy, D. J.; Low, L. L.; Yeo, K.-K.; Sim, K. L. D.; Zhang, Y.; Kularatna, S.; Senanayake, S.

2026-07-13 health systems and quality improvement 10.64898/2026.07.09.26357623 medRxiv
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Background The prevalence of chronic heart failure is increasing in Singapore and is associated with frequent hospitalisations, high costs, and impaired quality of life. Patient empowerment interventions for chronic diseases, which are structured approaches that enable patients to actively engage in and influence their care, have demonstrated promising effects on health-related outcomes. In chronic heart failure, however, many interventions focus on selected aspects of empowerment, and there remains limited synthesis of which approaches are most acceptable, preferred, and effective as comprehensive intervention packages. This protocol describes the methods for a study to identify an empowerment-based intervention for adults with chronic heart failure that is both contextually suitable and cost-effective in Singapore. Methods We will use a staged, sequential design comprising three objectives. Objective one is to conduct a systematic review (PROSPERO registration number CRD420251249957) and meta-analysis to synthesise international evidence of the effectiveness of empowerment-based interventions for adults with chronic heart failure. Objective two is to complete a mixed-methods study, including semi-structured interviews with chronic heart failure patients, as well as their caregivers, to identify empowerment-related needs, barriers and facilitators in local chronic heart failure care. This will be followed by a discrete choice experiment to elicit patients preferences for features of an empowerment-based intervention. Objective three is to conduct a cost-effectiveness analysis of the proposed intervention from the perspective of the Singapore health system. Discussion This series of studies integrates international evidence with local stakeholder perspectives and patient preferences to inform a feasible, patient-centred empowerment intervention for chronic heart failure in Singapore. The findings will inform intervention design and provide policy-relevant evidence on costs, health outcomes, and implementation decisions for empowerment-based chronic heart failure care in Singapore.

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Efficacy and Safety of Whartons Jelly-Derived Mesenchymal Stem Cells in Patients with Ischemic Cardiomyopathy: A Randomized Pilot Trial

Atehortua, L.; Estrada-Mira, S.; Torres-Alzate, S.; Velazquez, O.; Florez, J. P.; Villegas, F.; Atehortua, M.; Villada, O.; Ortiz, J. C.; Jaimes, F.

2026-07-07 intensive care and critical care medicine 10.64898/2026.07.03.26357234 medRxiv
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Introduction Whartons jelly-derived mesenchymal stem cells (WJ-MSCs) have emerged as a promising regenerative strategy for ischemic heart disease because of their immunomodulatory, angiogenic, and antifibrotic properties. This pilot randomized trial evaluated the safety, feasibility, and exploratory efficacy of intramyocardial WJ-MSC administration combined with an extracellular matrix (ECM) patch in patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting (CABG). Methods In this randomized, controlled pilot trial, 28 patients with ischemic cardiomyopathy, left ventricular ejection fraction (LVEF) <40%, and viable myocardium on cardiac magnetic resonance imaging (MRI) were assigned to receive intramyocardial WJ-MSC injections plus an extracellular matrix (ECM) patch or a placebo patch. Patients were followed for 12 months with echocardiography, cardiac MRI, Holter monitoring, functional assessment, and quality-of-life evaluation. Results Among 44 screened patients, 28 were randomized (16 to WJ-MSC and 12 to control). At 12 months, echocardiography showed a greater improvement in LVEF in the WJ-MSC group than in the control group (8% vs. 0%, p=0.045). Myocardial fibrosis decreased by 32% in both groups. Cardiac MRI demonstrated improvement in both groups, with numerically greater gains in LVEF and larger reductions in fibrosis in the WJ-MSC arm, although between-group differences were not statistically significant. No significant between-group differences were observed in ventricular arrhythmias or serious adverse events. Two non-cardiac postoperative deaths occurred in the WJ-MSC group. Conclusions Intramyocardial WJ-MSC administration combined with an ECM patch during CABG appears feasible and safe, with signals of functional improvement. Larger, adequately powered trials are needed to confirm efficacy and long-term safety.

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Sociodemographic inequalities in onset, mortality and prognosis among patients developing diabetic foot ulcers: a flexible parametric analysis

Farr, I.; James, J.; Howcroft, T.; Yap, M. H.; Reeves, N. D.; Pappachan, J. M.; Chandrabalan, V. V.

2026-07-09 endocrinology 10.64898/2026.07.06.26355671 medRxiv
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Aim: Inequalities in diabetic foot ulcer (DFU) outcomes are driven by several factors including sociodemographic factors. This study examined the intersectional risks of ethnicity, sex, and deprivation on DFU progression, which prior research often evaluated in isolation. Methods: A retrospective cohort study (2009 - 2024) of 2,125 patients at Lancashire Teaching Hospitals Trust utilized flexible parametric survival modelling. Models assessed DFU onset, overall mortality, and post-clinic prognostic survival, adjusting for demographics and comorbidities. Results: The most deprived patients presented significantly younger (median 64 vs. 73 years). Male sex accelerated DFU onset (HR: 1.24) and increased overall mortality risk (HR: 1.14). Black patients presented older with higher comorbidity burdens but paradoxically exhibited lower overall mortality risk (HR: 0.49). Deprivation heavily impacted life expectancy as the most deprived group showed higher mortality rates (HR: 0.73) and reduced 5-year prognostic survival (48.7% vs. 59.1%). Presence of comorbidities linearly increased overall mortality risk. Furthermore, severe deprivation caused greater overall life-years lost in men (4.0) than women (2.5). Conclusions: Patient outcomes with DFU are heavily influenced by cumulative demographic and socioeconomic factors. Effective management requires accessible, holistic care that actively accommodates these complex biosocial-economic realities.

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Resistive Load During CPAP and Automatic Tube Compensation (ATC): A Bench Comparison of ICU Ventilators

Fabry, B.; Kuster, C.; Francis, R.

2026-07-13 intensive care and critical care medicine 10.64898/2026.07.08.26357537 medRxiv
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Background: Automatic tube compensation (ATC) was designed to compensate for the additional resistive load imposed by the endotracheal tube during spontaneous breathing. In ATC mode, the ventilator adds or subtracts the flow-dependent pressure drop across the tube during both inspiration and expiration so that tracheal pressure remains close to PEEP. Early prototype ventilators achieved true tracheal-pressure control and showed physiological and clinical benefits, but clinical studies with commercial systems have failed to confirm these earlier findings. A 2003 bench study found that commercial ventilators provided, at best, only partial tube compensation, unlikely to result in meaningful clinical benefit. We therefore tested whether this limitation has been remedied in contemporary ICU ventilators. Methods: We performed a bench comparison of five commercial ICU ventilators and an ATC prototype ventilator designed to accurately compensate for the flow-dependent resistance over a wide range of flow rates. An active lung simulator generated spontaneous breathing patterns with weak, moderate, and strong inspiratory efforts at different PEEP levels. We tested each breathing pattern through endotracheal tubes with inner diameters of 7 and 8 mm, and measured airway pressure, tracheal pressure, and flow during CPAP with and without ATC. Breathing through the tube against open atmosphere served as a zero-PEEP/T-piece reference. Results: In CPAP mode, the commercial ventilators showed flow-dependent airway-pressure deviations, amounting to a substantial added resistance of 1.5 - 6.5 mbar/(L/s), whereas the ATC prototype ventilator imposed an added resistance of only 0.6 mbar/(L/s). In ATC mode, the commercial ventilators reduced the resistive load by no more than by 25%, and large tracheal-pressure deviations remained, especially at higher inspiratory effort and during expiration. In some cases, the residual load during ATC was even greater than the load during unsupported breathing through the tube. By contrast, the ATC prototype ventilator maintained tracheal pressure close to PEEP throughout the breathing cycle and eliminated on average 79% of the tube-related resistive load. Conclusions: In the commercial ventilators evaluated in this study, the defining physiological objective of ATC was only partially achieved. Therefore, clinical benefits previously reported for tracheal-pressure control support should be interpreted with caution when applied to commercial ATC implementations, unless effective tube compensation has been demonstrated under relevant conditions. These findings suggest that more advanced control approaches, such as those implemented in the ATC prototype ventilator, may be required to achieve consistent and physiologically accurate tube compensation.

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Hosting Displaced Medical Students in Times of Crisis: A Multi-National Qualitative Study Advancing the Consolidated Framework for Implementation Research (CFIR)

Rezaei Zadeh, M.; Hamam, Y.; Sayeed, S.; Gay, S.; AbuZarifa, M.; Zaqout, k.; AbuOlwan, O.; Massri, L.; Alhennawi, L.; Miqdad, F.; Zughbur, M.

2026-07-13 medical education 10.64898/2026.07.09.26357620 medRxiv
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Catastrophic geopolitical conflicts increasingly disrupt the continuity of global medical education, placing immense pressure on clinical training pipelines and forced-migration student groups. While short-term, reactive, remote learning models exist, there are a profound lack of evidence-based implementation templates for medical schools within stable host nations to systematically host and integrate displaced clinical student cohorts mid-stream. This study explores the multi-level barriers and facilitators to hosting displaced medical students across diverse international environments, seeking to establish a rigorous, scalable model of educational sanctuary while advancing implementation science theory in crisis contexts. Employing a qualitative multi-site case study design guided by a critical realist ontology, this study analysed 66 semi-structured interviews with displaced Gazan medical students, hosting lecturers, clinical coordinators, and support staff across the United Kingdom, Malaysia, Pakistan, Turkey, and South Africa, mapping reflexive thematic analysis findings onto the Consolidated Framework for Implementation Research (CFIR). The analysis revealed that while rigid immigration policies, clinical placement caps, and severe cultural distance represent substantial barriers, key facilitators include assessment considerations, flexible placement models, sanctuary institutional cultures, peer networks, and decentralised administrative trust. Strategic administrative approaches, such as classifying displaced students as extended clinical elective visitors rather than full-time matriculants, enabled institutions to accommodate them within existing frameworks. This study demonstrates that public sector higher education institutions can act as vital global sanctuary networks to preserve clinical training pipelines. Crucially, the findings advance implementation science by proposing three novel constructs for the updated CFIR in crisis environments: Agile Implementation Over Perfection within the Implementation Process domain, Protective Leadership Shielding within the Inner Setting domain, and Bidirectional Boundary Subversion at the Inner/Outer Setting interface. This theoretical refinement transforms CFIR from a determinant model for stable, clinical interventions into an active, equity-driven framework for rapid humanitarian response in politically contested environments.

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Delay discounting and low-value care decision-making by primary care clinicians in a survey-based vignette experiment

Epling, J. W.; King, M. J.; Rockwell, M.; Tegge, A. N.; Hester, C. M.; Clay, T. L.; Callen, E. F.; Turner, J. K.; Stein, J.

2026-07-13 health systems and quality improvement 10.64898/2026.07.09.26357617 medRxiv
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Introduction: Primary care clinicians (PCC) commonly make decisions in the context of time delay and uncertainty. Delay discounting (DD) and probability discounting (PD) are cognitive biases related to delay and uncertainty that are minimally explored in PCC. We assessed DD and PD in PCC and evaluated their association with low-value care (LVC) decision-making. Methods: We administered a survey to PCC in a Southeastern U.S health system and within the American Academy of Family Physicians networks. The survey comprised standardized psychometric assessments of DD and PD and four LVC clinical vignettes. Outcomes included DD and PD discounting rates for two monetary rewards ($100 and $10,000) and ratings of LVC likelihood (0-100). We used regression analysis with model selection to evaluate the relationship between variables. Results: 225 PCC (89% physicians, 11% advanced practice providers) participated. Heterogeneity in DD and PD rates was observed. For the $10,000 reward, ln k(DD)= -6.80, IQR:-7.60--6.10) and ln h(PD)= 1.75, IQR:1.75-2.36). The reward amount impacted DD and PD in opposing directions (i.e., lower DD/higher PD rates for $10,000 vs. $100). LVC likelihood was highest for low-value antibiotics and lowest for low-value cervical cancer screening (median 20, IQR:10-40 and 0, IQR:0-10, respectively). Model selection revealed demographic associations with LVC likelihood, but no association with DD or PD. Conclusions: Consistent with effects previously reported in non-clinicians, PCC exhibited a range of DD and PD, which ranged by reward magnitude. Neither DD nor PD predicted vignette-based LVC likelihood. Further research should investigate actual clinical practice patterns and other LVC scenarios.

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Serum potassium elevation and acute respiratory acidosis during thoracoscopic esophagectomy with intrathoracic carbon dioxide insufflation: a multicenter retrospective observational study

Okamoto, S.; Tochii, T.; Hotta, R.; Nakamura, K.; Nakada, J.; Note, H.

2026-07-08 anesthesia 10.64898/2026.07.04.26357266 medRxiv
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Background Thoracoscopic esophagectomy with intrathoracic carbon dioxide insufflation and lung collapse, usually performed in the prone position, can markedly alter respiratory physiology and acid-base balance. Serum potassium elevation is often observed during acute respiratory acidosis in these procedures, despite the conventional view that respiratory acidosis has little effect on potassium. We quantified the intraoperative potassium change and explored associated factors. Methods This multicenter retrospective study included adults undergoing thoracoscopic esophagectomy with carbon dioxide insufflation in the prone or lateral decubitus position during 2022-2024. Arterial blood gas variables were evaluated after anesthesia induction and at the time of the lowest arterial pH during carbon dioxide insufflation. The primary outcome was the paired difference in serum potassium. Sensitivity, subgroup, and regression analyses were performed. Results All 131 patients were included: 117 in the prone position and 14 in the lateral decubitus position. Serum potassium increased from 3.96 {+/-} 0.38 to 4.59 {+/-} 0.63 mEq/L (mean increase, 0.64 mEq/L; 95% confidence interval, 0.55-0.73; p < 0.001). During the same period, pH decreased from 7.387 to 7.247 and arterial carbon dioxide tension increased from 41.48 to 58.60 mmHg. After excluding marked metabolic acidosis, the increase remained significant and similar in magnitude (0.618 mEq/L). In the centered multivariable model, lactate change was independently associated with potassium change ({beta} = 0.303; p = 0.004), whereas arterial carbon dioxide change and preoperative renal function were not. The intercept remained significantly positive. Conclusions A clinically meaningful potassium increase was observed during thoracoscopic esophagectomy with carbon dioxide insufflation, while acute respiratory acidosis developed during the same period. The increase persisted after excluding marked metabolic acidosis and may not be explained solely by metabolic stress. Arterial blood gas assessment, including potassium measurement, is warranted during significant hypercapnia, and potential electrolyte consequences should be considered when permissive hypercapnia is accepted.

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General-Purpose vs. Domain-Specific Large Language Models in Antibiotic Clinical Decision-Making: A Double-Blind Evaluation with a 2X2 Factorial Design

Liu, Y.; Zhang, C.; Wang, F.; Xu, W.; Zhang, Y.; Ma, S.; zhang, H.

2026-07-13 intensive care and critical care medicine 10.64898/2026.07.11.26357814 medRxiv
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Background: Antimicrobial resistance poses a major threat to global public health. Large language models (LLMs) offer new possibilities for optimizing antibiotic prescribing decisions, but the capabilities of general-purpose versus domain-specific medical LLMs under different prompting strategies remain to be clarified. Methods: This double-blind, randomized-sequence evaluation used a 2X2 factorial design comparing four AI conditions-the domain-specific model MedGo and the general-purpose model DeepSeek V3.5, each under standard direct prompting and chain-of-thought (CoT) prompting-alongside real physician prescriptions across 59 complex inpatient infection cases. Five parallel regimens were generated per case and independently evaluated by three senior clinicians (1-5 comprehensive score and five domain sub-scores). ChatGPT 5.2 was additionally assessed as an automated evaluation tool. Results: Score ranking: real physicians > MedGo-CoT > DeepSeek-CoT > MedGo> DeepSeek (Friedman test, p<0.001). In base mode, MedGo significantly outperformed DeepSeek (Holm-adjusted p=0.040). CoT improved both models (Holm-adjusted p<0.001 for DeepSeek; p=0.024 for MedGo) and reduced score dispersion. MedGo-CoT significantly outperformed DeepSeek-CoT in individualized adjustment (adjusted p<0.001) and dosing precision (adjusted p=0.005). ChatGPT-expert correlation was negligible (overall Kendall {tau}=0.153, p=0.003; subgroup {tau}=0.06-0.20, all p>0.05). Conclusions: Domain-specific medical LLMs enhanced by CoT approach the antibiotic decision-making level of real physicians, with advantages in individualization and dosing precision. However, notable deficiencies persist in antimicrobial stewardship ecological awareness and automated evaluation reliability, underscoring the continued indispensability of senior clinical expertise.

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Navigating Care in Crisis: A Qualitative Study of Healthcare Access Among Ethnically Diverse COVID-19 Patients in The Netherlands

Hensen, N.; Muru, G. N.; Prins, M.; Stronks, K.

2026-07-13 health systems and quality improvement 10.64898/2026.07.10.26357237 medRxiv
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Ethnic minority and migrant populations experienced disproportionately severe COVID-19 outcomes across Europe, yet the mechanisms underlying these disparities, particularly inequities in healthcare access, remain insufficiently understood at the patient level. This qualitative study examines healthcare-seeking behaviours and access to care among ethnically diverse patients hospitalised with COVID-19 in Amsterdam between 2020 and 2022, and the contextual factors shaping their pathways to care. Twenty adults of Turkish, Moroccan, Surinamese, Ghanaian, and Dutch ethnic backgrounds, all hospitalised with COVID-19, were interviewed using a semi-structured retrospective approach to reconstruct individual care pathways from symptom onset to hospitalisation. Data were analysed thematically, guided by the Candidacy Framework and the Health Belief Model. Pandemic-induced structural disruptions, including healthcare system strain, capacity shortages, absent care protocols, and fragmented referral pathways, constituted the primary barriers to care across all ethnic groups. Participants with longer hospital stays tended to be older, less educated, and with more comorbidities, yet reported fewer barriers once hospitalised, as disease severity triggered prioritisation. Those with shorter stays or emergency department visits without admission encountered greater difficulties, including repeated discharge despite worsening symptoms. Language barriers and prior negative experiences with healthcare services compounded access challenges for some participants with migrant backgrounds, though pandemic phase and disease severity were the dominant determinants across the sample. Inequities in access to care were driven primarily by pandemic-induced structural factors rather than ethnic background. Pre-existing vulnerabilities among migrant groups, including reduced institutional trust and language barriers, intensified these structural barriers for some. These findings are directly relevant for equity-sensitive pandemic preparedness: crisis response frameworks must explicitly address structural accessibility alongside targeted support for groups facing compounding disadvantage.

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Association of Insurance Payor with Time to Discharge to Inpatient Rehabilitation After Ischemic Stroke

Shah, R. J.; King, B.; Strobel, S.; Feyisetan, R.

2026-07-13 health policy 10.64898/2026.07.08.26357596 medRxiv
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Background: Transition timing to post-acute rehabilitation after ischemic stroke is heavily influenced by non-clinical factors, introducing potential systemic disparities in care access. We evaluated the association between insurance payor status and acute hospital length of stay (LOS) prior to inpatient rehabilitation discharge among critically ill stroke patients. Methods: Using the MIMIC-IV database, we identified ICU-admitted adults with ischemic stroke discharged to inpatient rehabilitation (n=1,285). The primary outcome was hospital LOS prior to rehab transfer. Multivariable log-transformed linear regression evaluated the association with insurance payor (Medicare, private, other/unknown; reference: Medicaid), adjusting for demographics, diagnostic-code counts (medical complexity), and ICU LOS (acute illness severity). Results: Median hospital LOS before rehab discharge was longest for Medicaid patients (13.2 days) compared with private insurance (11.0 days) and Medicare (9.5 days). In the adjusted model, Medicare insurance was associated with a significantly shorter transition time to inpatient rehabilitation, corresponding to a 13.5% shorter acute hospital stay (adjusted LOS ratio 0.87; 95% CI: 0.79-0.96; p=0.005) relative to Medicaid. Private insurance demonstrated a descriptive trend toward shorter LOS that did not achieve statistical significance (adjusted LOS ratio 0.93; 95% CI: 0.84-1.02; p=0.122). Other and unknown payor categories showed no significant differences. Conclusions: Insurance payor status serves as an independent predictor of acute care transition timing for stroke patients requiring inpatient rehabilitation. The prolonged acute stays observed among Medicaid beneficiaries suggest significant non-clinical, administrative bottlenecks in post-acute placement, underscoring the critical need for standardized, streamlined insurance approval pathways to ensure equitable neurological recovery.

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Pre-Operative Single 150 Mg Dose of Pregabalin for Postoperative Pain Management in Laparoscopic Cholecystectomy: A Systematic Review and Meta-Analysis

Dewasi, G.; Nagda, P.; Jain, S.

2026-07-13 pharmacology and therapeutics 10.64898/2026.07.11.26357848 medRxiv
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Effective postoperative pain control is essential following laparoscopic cholecystectomy, yet the analgesic value of a standardised 150 mg preoperative dose of pregabalin has not been clearly established. This systematic review and meta-analysis synthesised evidence from seven randomised controlled trials published between 2008 and 2025 to evaluate the efficacy and safety of pregabalin when administered before surgery. Four trials reported 24-hour postoperative pain scores, and pooled analysis demonstrated that pregabalin significantly reduced pain compared with control (SMD = 0.80 lower; 95% CI, 1.42 to 0.18 lower; p = 0.01), although statistical heterogeneity was high (I-squared = 81%). Pregabalin also produced notable reductions in opioid consumption, including fentanyl (SMD = 1.24 lower; p = 0.002) and tramadol (SMD = 4.21 lower; p = 0.002), again with considerable variability across studies. Sedation was slightly increased but did not reach statistical significance, and there were no significant differences in postoperative nausea, vomiting, or headache. Sensitivity analyses supported the stability of these findings. Overall, the results indicate that a single 150 mg preoperative dose of pregabalin meaningfully reduces postoperative pain and opioid requirements following laparoscopic cholecystectomy while maintaining an acceptable safety profile, supporting its use as part of a multimodal analgesic strategy.