Critical Care Medicine

Aim: General ICU severity scores predict hospital mortality across heterogeneous populations, not recovery within one diagnosis. We described favourable discharge across the range of APACHE IVa-predicted hospital mortality after cardiac arrest, and tested whether any bedside subgroup fell below a pre-specified benchmark. Methods: Observational cohort of 3,641 first ICU admissions in 161 eICU hospitals with a cardiac-arrest diagnosis documented within 24 hours. The exposure was APACHE IVa-predicted hospital mortality; the outcome was favourable discharge (home or rehabilitation), a functional-outcome proxy. Fourteen bedside subgroups were pre-specified; the benchmark required an upper 95% bound below 5%. Results: Favourable discharge occurred in 1,039 (28.5%), falling from 78.9% in the lowest predicted-mortality decile to 4.1% in the highest (trend z, -27.2; P < 0.001). Among 2,139 patients with predicted mortality at or above 50%, 301 (14.1%; 95% CI, 12.6 to 15.6) had a favourable discharge; among 281 at or above 90%, 9 (3.2%) did. No subgroup had an upper 95% bound below 5%; the lowest was 8 of 264 (3.0%; 95% CI, 1.3 to 5.9). At a more permissive 10% benchmark, two qualified. Among 1,961 not obeying commands, 263 (13.4%) had a favourable discharge. Discrimination did not differ detectably between unfavourable functional outcome (AUROC 0.789) and in-hospital death (0.774; P = 0.078). Conclusion: Favourable discharge declined as predicted mortality rose but remained observable at the highest risk levels, and no pre-specified subgroup was bounded below 5%. A general ICU mortality estimate is not on its own evidence that a favourable outcome is absent.

Objective We aimed to evaluate the performance of the recently updated Sequential Organ Failure Assessment Score-2 (SOFA-2) on organ dysfunction classification and prognostication compared to SOFA-1 in critically injured trauma patients. Methods Adult trauma patients admitted to critical care at four urban Major Trauma Centres between 2011 and 2024 were included. Daily organ dysfunction scoring was performed using SOFA-1 and SOFA-2 until death or discharge. The primary outcome was MODS, defined as SOFA score [&ge;]6. Results In 2162 severely injured patients (median Injury Severity Score 25 [IQR, 17-34]), SOFA-2 reduced the proportion of patients classified as having MODS compared with SOFA-1 (61.6% vs 68.5%, p<0.001). SOFA-2 scores on the first day after admission were lower than SOFA-1 (median 6 [IQR, 3-8] vs 7 [IQR, 4-10], p<0.001), driven predominantly by lower respiratory and cardiovascular scoring. Critical care mortality in trauma patients was increased in respiratory, cardiovascular and renal components of SOFA-2 at the higher ends of the scores, consistent with the aims of the SOFA-2 reclassification. A group of 159 severely injured patients (7.3%) classified as MODS by SOFA-1 were reclassified to no-MODS by SOFA-2. Despite this reclassification, these patients had substantially higher ICU mortality (7.5% vs 0.7%, p<0.01), greater ventilator and vasopressor requirements, and longer hospital stays than patients classified as no-MODS by both systems. Conclusions SOFA-2 reduces MODS prevalence in severely injured patients and changes organ dysfunction classification, with lower rates of severe respiratory and cardiovascular dysfunction. This represents an important update in trauma MODS measurement and has implications for future trauma trial design. However SOFA-2 reclassification generates a small cohort a small but clinically significant group with occult MODS that warrants further evaluation in severely injured trauma patients.

Purpose To estimate the per-protocol effect of red blood cell (RBC) transfusion strategies on ICU-acquired infection in critically ill adults with sepsis using a target trial emulation framework. We evaluated whether restrictive strategy and liberal strategy, defined by hemoglobin (Hgb) thresholds, differ in their effect on ICU-acquired infection during ICU stay. Methods We conducted a target trial emulation using the MIMIC-IV database and included adults who met Sepsis criteria at ICU admission. Clones were assigned to restrictive or liberal transfusion strategies. Under the restrictive strategy, RBC transfusion was permitted only when Hgb was [&le;]7.0 g/dL, whereas under the liberal strategy, transfusion was permitted when Hgb was >7.0 g/dL. The primary outcome was the first ICU-acquired infection occurring at least 72 hours after ICU admission. Per-protocol effects were estimated using a clone-censor-weight approach with a marginal structural model. A parametric g-formula was used as a complementary analysis that jointly modeled ICU discharge and ICU mortality as competing events to derive strategy-specific 28-day cumulative incidences and risk differences. Results 8 Among 4,013 eligible ICU stays, the liberal-versus-restrictive comparison provided little evidence of a difference in the risk of ICU-acquired infection (adjusted conditional OR, 0.954; 95% CI, 0.797 to 1.142). In the complementary g-formula analysis, the 28-day risk difference for the liberal versus restrictive comparison was -0.02 percentage points (95% CI, -0.15 to 0.11), consistent with the primary analysis. Findings were generally robust across prespecified subgroup and sensitivity analyses. Conclusion In this target trial emulation of adults with sepsis, we observed no clinically meaningful difference in ICU-acquired infection between RBC transfusion strategies defined by hemoglobin thresholds.

Background Despite numerous randomized controlled trials (RCTs) and systematic reviews (SRs), current sepsis guidelines continue to issue only weak recommendations for corticosteroids. We examined the clinical scope, underlying study pools, and mortality conclusions of SRs evaluating corticosteroids for sepsis. Methods We conducted a meta-research study of SRs on corticosteroids in sepsis (2015 to 2025), extracting SR characteristics, mortality results, and included RCTs. Study-pool overlap was assessed using an SRxRCT inclusion matrix, Jaccard similarity (J), and hierarchical clustering. SRs and RCTs were classified according to standardized Population, Intervention, Comparison, Outcome (PICO) profiles. We explored discordance in short-term mortality conclusions among clinically comparable SRs and potential associations with study-pool composition, target populations, and methodological characteristics. Results Forty-two SRs including 121 unique RCTs were identified. More than half of pairwise SR comparisons shared no RCTs, and only three pairs showed high overlap (J>0.8). SRs addressing similar intervention and target population profiles frequently relied on different study pools. Among 38 SRs with short-term mortality meta-analyses, 15 (39%) reported benefit and 23 (61%) no evidence of effect. Discordance occurred exclusively among SRs evaluating broad, non-specific corticosteroid strategies; conclusions were consistent for hydrocortisone plus fludrocortisone (benefit) and hydrocortisone, ascorbic acid, and thiamine (no evidence of effect). SRs including sepsis +/- shock populations more frequently reported benefit than those restricted to septic shock (62% vs 22%), although estimates were imprecise. No single methodological or clinical factor consistently explained discordance. Conclusions SRs addressing apparently similar clinical questions frequently synthesized different underlying evidence bases and reported discordant conclusions. Guideline developers should therefore consider not only methodological quality and reported PICO, but also whether the RCTs included in an SR adequately represent the intended clinical question. Clinically coherent evidence syntheses may improve the interpretability of pooled treatment effects and support more targeted corticosteroid therapy in sepsis.

Background: Capillary refill time (CRT) is an increasingly endorsed bedside perfusion marker in septic shock.Publicly available intensive care unit (ICU) databases such as MIMIC-IV and eICU-CRD enable large-scale multi-database research, but the cross-database comparability of CRT operationalization has not been systematically examined. Methods: We conducted a retrospective, descriptive, cross-database methodological analysis of adult ICU stays in MIMIC-IV v3.1 (2008-2022) and eICU-CRD v2.0 (2014-2015). CRT availability, definitional thresholds, recording patterns and time windows, bilateral measurement consistency, and selection bias in the CRT-documented population were characterized descriptively. Results: Among 94,458 MIMIC-IV and 200,234 eICU-CRD adult ICU stays, CRT availability differed markedly:79.85% of MIMIC-IV stays had at least one CRT record within the first 24 hours, versus 6.35% of eICU-CRD stays across the entire ICU stay, a 73.5-percentage-point gap. The abnormality threshold was 3 seconds in MIMIC-IV and 2 seconds in eICU-CRD. Among CRT-available MIMIC-IV stays, the mean number of CRT records in the first 24 hours was 7.0 (median 6, interquartile range (IQR) 4-10); 99.6% had bilateral records, with 99.4% left-right agreement (Cohen's kappa 0.914). The temporal distribution of CRT records was strikingly similar between databases: only 28.7% of MIMIC-IV and 29.1% of eICU-CRD records occurred within 24 hours of ICU admission (including pre-admission records), with roughly 71% in both databases recorded later in the stay. In eICU-CRD, the CRT-documented population had higher illness severity than the undocumented population (Acute Physiology and Chronic Health Evaluation (APACHE) IV 60.0 versus 54.4; standardized mean difference 0.21), consistent with selection by indication. Structured peripheral perfusion index fields were unavailable in both databases. Conclusions: CRT operationalization differs fundamentally across MIMIC-IV and eICU-CRD in availability, definitional thresholds, recording patterns, bilateral structure, and patient selection. Cross-database CRT research should explicitly declare definitional heterogeneity, avoid pooling across thresholds, and treat sparsely documented subsets as selected populations. Selection bias was evident in both databases, in opposite directions. Severity-score-based comparison was possible only in eICU-CRD. Standardized common data elements for bedside perfusion assessment are needed to make cross-database CRT research valid by design.

Purpose. Prognostic assessments after acute brain injury are largely narrative, and how prognostic language relates to subsequent care has not been measured at scale. We quantified where it is written and its association with a subsequent code-status limitation. Materials and Methods. Multidatabase observational study of adults with acute brain injury or a related neurologic emergency, using MIMIC-IV (2008-2019; discharge summaries and radiology reports) and a timestamped MIMIC-III cohort (notes and code-status orders). The exposure was documented prognostic language; outcomes were its association with a subsequent full-code-to-limitation transition, note-stream location, and completeness of documented command-following relative to structured Glasgow Coma Scale (GCS) motor scores. Results. Among 31,993 admissions (27,054 patients; median age, 69 years; 54.9% male), prognostic language in the timestamped cohort (MIMIC-III) was associated with a subsequent code-status limitation after multivariable adjustment (adjusted hazard ratio, 4.3; 95% CI, 2.9-6.5; unadjusted 14-day cumulative incidence, 40% vs 8.5%), including the comfort-measures component (3.9), a higher-risk subgroup (4.4), and after acute-physiology adjustment (4.1); the association was concentrated in the first 3 days. Non-prognostic severity language showed no comparable association (hazard ratios, 1.1-1.3). Prognostic language localized almost entirely to the narrative (4.9% of discharge summaries vs 0.015% of radiology reports); command-following was undocumented in 55.7% of summaries, and no final-24-hour GCS motor score was charted in 72.8%. Conclusions. Documented prognostic language after acute brain injury was written in the narrative, not structured fields, and was associated with a subsequent code-status limitation after multivariable adjustment. This observational association cannot establish causation but warrants prospective study.

Background: Optimal arterial oxygen targets after return of spontaneous circulation (ROSC) in pediatric out-of-hospital cardiac arrest (OHCA) remain uncertain. We examined whether arterial oxygen tension on the first arterial blood gas after ROSC is associated with neurological or survival outcomes. Methods: Using the Japanese Association for Acute Medicine OHCA Registry, we retrospectively studied pediatric patients (<18 years) with OHCA in whom ROSC was confirmed at or after hospital arrival. Patients were categorized by PaO? on the first arterial blood gas after ROSC as normoxemia (60?200 mmHg) or hyperoxemia (>200 mmHg). Missing covariate data were handled using multiple imputation, and associations were estimated using inverse probability-weighted logistic regression. Outcomes were favorable neurological status at 30 days, defined as a Pediatric Cerebral Performance Category score of 1?3, and 30-day survival. Multiple sensitivity analyses were performed, including analyses using an alternative PaO? threshold, restricting the timing of PaO? measurement, and excluding extracorporeal cardiopulmonary resuscitation cases. Results: A total of 189 patients were included (95 normoxemia, 94 hyperoxemia). A favorable neurological outcome occurred in 21 of 95 (22.1%) normoxemia and 13 of 94 (13.8%) hyperoxemia patients, and 30-day survival in 40 of 95 (42.1%) and 42 of 94 (44.7%), respectively. After weighting, covariate balance was achieved with standardized mean differences below 0.1. Hyperoxemia was not significantly associated with favorable neurological outcome (adjusted odds ratio [aOR] 0.94, 95% confidence interval [CI] 0.49?1.77) or 30-day survival (aOR 1.49, 95% CI 0.88?2.54). Sensitivity analyses yielded consistent results. Conclusions: Early hyperoxemia after ROSC was not significantly associated with neurological or survival outcomes in pediatric out-of-hospital cardiac arrest. These findings suggest that a single early PaO? measurement may be insufficient to characterize the clinical impact of oxygen exposure after resuscitation. Future research should focus on phase-specific and individualized oxygen management incorporating serial physiological assessment.

Artificial intelligence (AI) is increasingly embedded in U.S. emergency department workflows, but no medical specialty has defined what competent use of these tools requires of its physicians. Existing accreditation requirements are silent on AI, and parallel national efforts span the learning continuum but are intentionally specialty-agnostic. As one output of a working group of the 2026 Society for Academic Emergency Medicine (SAEM) Artificial Intelligence Consensus Conference, we developed an emergency medicine-specific framework for AI competency. We employed a multiphase consensus design: a Nominal Group Technique session generated themes from a curated set of clinical AI scenarios, and a two-round modified Delphi process (panel n = 13 across 12 academic medical centers), separated by a consolidation videoconference, evaluated and extended the framework. A priori consensus required [&ge;]70% of panelists rating [&ge;]4 on a 5-point Likert scale ([&ge;]75% for themes) with interquartile range [&le;]1; we followed established Delphi reporting guidance. The framework comprises 5 themes (Communicating about AI, Understanding appropriate use cases, Interacting with AI, AI risk management, Cognitive impacts of AI), 5 derived competencies (one-to-one theme-to-competency mapping endorsed by 12 of 13 panelists), 19 subthemes, and 10 retained clinical scenarios. All themes, derived competencies, and rated subthemes met consensus thresholds; 9 of 10 scenarios reached consensus, with 1 retained as a future-state operational model. Two cross-cutting conceptual frames emerged: pre-emptive versus post-hoc AI integration, and tiered competencies as an articulated need rather than a pre-specified answer. This is, to our knowledge, the first specialty-specific AI competency framework for a United States medical specialty with quantitative content validity evidence from expert consensus. It provides a structural target for emergency medicine curriculum development, assessment design, and faculty development, with downstream priorities including stage-specific competency assignment, assessment instrument development, and periodic re-evaluation as AI deployment evolves.

Background: Molecular markers and mediators of adverse post-hospital outcomes following critical illness remain incompletely characterized. Anemia and red blood cell (RBC) indices integrate inflammation, nutritional status, and hematopoietic function, and may represent biological processes that influence long-term outcomes. We therefore examined whether pre-discharge anemia and hematologic clusters derived from correlated RBC indices were associated with one-year mortality among critical illness survivors. Methods: We conducted an exploratory, retrospective cohort study of adult ICU patients discharged alive using MIMICIV. Pre-hospital discharge RBC indices (hemoglobin, red cell distribution width (RDW), mean corpuscular volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC), and RBC count) were analyzed. Hemoglobin and anemia were first evaluated, followed by Gaussian mixture modeling of standardized RBC indices to identify patient clusters in a derivation cohort (70%) and validated findings in a held-out cohort (30%). Associations with one-year mortality were assessed using multivariable-adjusted Cox models. Results: Among 20,233 ICU survivors with available pre-discharge hemoglobin (median age, 67 years), based on the WHO definition of anemia, 17,247 (85.2%) critical illness survivors were anemic at hospital discharge. Anemia was associated with higher one-year mortality (adjusted HR 1.42, p<0.001). Mortality was 20% overall and decreased across increasing hemoglobin quartiles, from 28.8% to 12.5% (log-rank P<0.005); lower hemoglobin was associated with progressively higher adjusted one-year mortality risk. Six hematologic clusters derived from RBC indices were identified with one-year mortality ranging from 10.1% to 31.4% (log-rank p<0.005). Compared with the lowest-risk group, the cluster characterized by elevated RDW and MCV had a twofold higher adjusted mortality risk (HR 2.14; 95% CI, 1.81-2.53). Conclusion: Both anemia and hematologic clusters derived from standard RBC indices at hospital discharge are associated with one-year mortality following critical illness. These hypothesis-generating findings support further investigation of RBC indices as potential biomarkers for post-discharge risk stratification and of the underlying biological pathways as possible therapeutic targets.

Background: When intravenous insulin is stopped in critically ill patients, the basal insulin dose that balances rebound hyperglycemia against hypoglycemia is uncertain, because randomized trials were small and not designed to quantify this trade-off. We examined how the first glargine dose, relative to the preceding intravenous insulin requirement, was associated with both outcomes. Methods: In this retrospective cohort study of the Medical Information Mart for Intensive Care IV database (2008-2022), we included transitions from intravenous insulin infusions of at least 6 hours to subcutaneous glargine in adults without diabetic ketoacidosis or hyperosmolar hyperglycemic state. The exposure was the ratio of the first glargine dose to 24 times the mean infusion rate over the final 6 hours. The primary outcomes, rebound hyperglycemia (glucose >180 mg/dL within 24 hours) and hypoglycemia (glucose <70 mg/dL within 48 hours) during intensive care unit follow-up, were analyzed with multivariable Cox models after multiple imputation. Results: Among 6,220 transitions in 5,924 patients (87.5% after cardiac surgery), the median ratio was 0.41 (interquartile range 0.30-0.46). Kaplan-Meier cumulative incidences were 44.4% for rebound hyperglycemia (2,109 events) and 6.4% for hypoglycemia (211 events). Each 0.1 increase in the ratio was associated with less rebound hyperglycemia (hazard ratio 0.96, 95% confidence interval 0.93-0.99) and more hypoglycemia (1.11, 1.04-1.18), consistently across 21 sensitivity analyses. Rebound within the first 6 hours (57.6% of events) was not associated with the ratio (0.99, 0.95-1.02), whereas later rebound was (0.91, 0.86-0.96). Standardized to the cohort, a ratio of 0.60 versus 0.40 corresponded to 2.7 (0.6-4.9) fewer rebound and 1.7 (-0.2 to 3.5) more hypoglycemia episodes per 100 transitions. In secondary analyses, rebound was less frequent with glargine given at least 2 hours before discontinuation (0.86, 0.77-0.96) and more frequent with an oral diet (1.49, 1.30-1.71). Conclusions: In critically ill adults, mostly after cardiac surgery, higher glargine doses relative to the preceding intravenous requirement were associated with less rebound hyperglycemia after the first 6 hours and more hypoglycemia, a gradual trade-off. Which basal fraction is preferable depends on the weight given to each outcome; a randomized trial including the guideline-implied fraction of about 0.30 is warranted.

OBJECTIVE: Sepsis-associated encephalopathy (SAE) and sepsis-associated delirium (SAD) lack confirmatory laboratory tests or biomarkers. We evaluated whether the Th17/interleukin (IL)-17 axis or neuroglial-injury biomarkers reflect acute brain dysfunction beyond systemic inflammation and whether biomarker profiles differ between these phenotypes. DATA SOURCES: EMBASE, MEDLINE/PubMed, and the Cochrane Library from inception to August 1, 2026, supplemented by backward and forward citation searching, following PRISMA 2020. STUDY SELECTION: Observational studies of adults with sepsis classified by SAE or SAD status and reporting circulating biomarker concentrations by neurological group or biomarker-outcome associations. Eighteen studies (2,388 participants; 1,863 with sepsis) were included. DATA EXTRACTION: Two reviewers independently extracted study, phenotype, assay, and outcome data. Risk of bias was assessed with the Newcastle-Ottawa Scale and certainty with GRADE. DATA SYNTHESIS: Random-effects models pooled standardized mean differences (SMDs) separately against non-septic and septic controls and odds ratios (ORs) for biomarker-outcome associations. IL-6 was the only mediator elevated in both comparative frameworks and associated with outcomes (non-septic controls: SMD, 0.54 [0.25-0.82]; septic controls: SMD, 1.05 [0.51-1.59]; OR, 1.85 [1.50-2.29]). S100B, neuron-specific enolase, IL-10, tumor necrosis factor; and interferon-gamma; were elevated versus septic controls, whereas IL-17 was modestly elevated only versus non-septic controls (SMD, 0.37 [0.01-0.73]). The IL-6 septic-control effect was concentrated in SAE (p<0.0001) and remained robust in leave-one-out and risk-of-bias sensitivity analyses. Certainty was low to very low, and all 14 computable prediction intervals included the null. CONCLUSIONS: IL-6 emerges as the leading circulating candidate biomarker of sepsis-associated brain dysfunction, while S100B and NSE capture neuroglial injury beyond sepsis. Current evidence does not establish a discriminating role for the Th17 axis. Future studies require standardized neurological phenotyping and appropriately matched septic controls to establish diagnostic value.

Background: While critical care pharmacists (CCPs) are broadly associated with improvements in outcomes for critically ill patients, operationalizing staffing in the intensive care unit (ICU) requires further study. The purpose of this evaluation was to determine the relationship of a CCP on interprofessional rounds for weekday admissions of ICU patients on patient-centered outcomes. Methods: This post-hoc analysis of the Optimizing Pharmacist-Team Integration for ICU Patient Management (OPTIM) study included adults admitted to an ICU on a weekday in the multicenter observational study. The primary outcome was in-hospital mortality. The primary exposure was level of comprehensive medication management (CMM) during the first 24 hours of ICU stay. A secondary exposure was pharmacist-to-patient ratio. Multivariable generalized estimating equations (GEE) were used to estimate associations between mortality and patient, ICU, and institution variables. Fine-Gray sub-distribution hazards regression estimated hazard of discharge alive (HDA) from the ICU and hospital and hazard of extubation alive. Results: 21,835 patients met inclusion criteria, and 76.1% of patients had CMM delivered on interprofessional rounds. Patients who had no CMM on the first ICU day had an increased risk of mortality of 23% (Odds Ratio (OR) 1.23, 95% Confidence Interval (CI) 1.04-1.46, p=0.02) compared to those who received CMM on interprofessional rounds. Patients with no CMM also had decreased HDA from the ICU and hospital and decreased hazard of extubation alive. No difference was seen in any outcomes when comparing other levels of CMM (CMM delivered outside of interprofessional rounds or abbreviated CMM) compared to CMM delivered on rounds. Conclusions: Absence of pharmacist CMM on the first day of ICU stay for patients with weekday admission was associated with an increased risk of in-hospital mortality, but no difference was seen in other levels of CMM: this signal supports further investigation in prospective analysis.

Background Agenda-setting is a fundamental patient-centered communication practice in which a clinician works with a patient to elicit, propose, and organize topics for discussion during a clinical encounter. Various agenda-setting interventions have been developed, including patient-facing tools and clinician training, but their effects have not been systematically evaluated. We aimed to determine the effects of these interventions on encounter, patient, care partner, and clinician outcomes. Methods We searched grey literature and seven databases, including PubMed, from inception through July 2025 for randomized and non-randomized comparative studies of interventions designed to promote or improve clinical visit agenda-setting. Two reviewers independently screened articles and extracted data, with a third reviewer resolving conflicts. We assessed risk of bias using RoB 2 for randomized studies and ROBINS-I for non-randomized studies. We conducted random effects meta-analyses when outcomes were sufficiently comparable, assessed heterogeneity using I2, and rated certainty of evidence using GRADE. Post hoc exploratory subgroup analyses examined study design, adjustment status, and intervention structure. Results Twenty-nine articles describing 22 unique studies met the inclusion criteria, including 13 randomized and nine non-randomized studies. Agenda-setting interventions increased the occurrence of agenda-setting (risk ratio 5.43, 95% confidence interval (CI) 2.06 to 14.28, I2=34.6%) and favored the intervention for concerns addressed when measured as a continuous outcome (standardized mean difference (SMD) 0.37, 95% CI 0.16 to 0.57, I2=65.3%) and overall clinician satisfaction (SMD 0.50, 95% CI 0.23 to 0.78, I2=0.0%). There were no clear differences in the number of concerns raised (mean difference (MD) 0.21, 95% CI -0.19 to 0.61, I2=59.6%), visit duration (MD 0.64 minutes, 95% CI -0.83 to 2.12, I2=51.4%), or overall patient satisfaction (SMD 0.05, 95% CI -0.05 to 0.15, I2=47.0%). Potentially important heterogeneity was present for four of these six outcomes. Post hoc exploratory subgroup analyses did not provide clear evidence that effects varied by study design, adjustment status, or intervention structure. Risk of bias was often high, serious, or critical, and certainty of evidence was low or very low for all pooled outcomes. Conclusions To our knowledge, this is the first comprehensive synthesis of clinical visit agenda-setting interventions. Such interventions may increase the occurrence of agenda-setting and the extent to which patient concerns are addressed without increasing visit length. However, the certainty of evidence was low or very low, and the available evidence does not establish a superior intervention structure.

Background. A primary constraint on the capacity of EMS programs to meet industry demand is psychomotor instruction and verification, requiring direct observation of each student by a qualified evaluator. Whether AI video analysis can relieve it is untested; none has been applied to EMS skill examination or compared with human examiners. Objective. To quantify human EMS evaluator inter-rater reliability and evaluate an AI video-analysis platform against it. Methods. In a prospective, fully crossed study, five certified EMS evaluators and an AI platform independently scored identical video-recorded EMT performances of cervical collar application (n=15), bag-valve-mask (BVM) ventilation (n=14), and medical assessment (n=15) on dichotomous checklists with critical-failure criteria. Agreement was assessed at item, score, and decision levels using Fleiss' kappa, Krippendorff's alpha, Gwet's AC1, and ICC(2,1)/ICC(2,k). Results. Human item agreement was moderate (kappa 0.409 to 0.467), as was single-rater reliability (ICC(2,1) 0.539 to 0.694), against good panel reliability (ICC(2,k) 0.854 to 0.919). Recorded pass/fail agreement was fair (kappa 0.297 to 0.388) and critical-failure agreement near zero for two skills (kappa 0.028, 0.119). AI alignment tracked rubric observability rather than task complexity: r = 0.857 (collar, exceeding every human), -0.173 (BVM), 0.664 (medical), and it was most lenient on two skills. Conclusions. Human evaluators are an imperfect standard, especially on critical failures. The AI was a legitimate additional rater where checklist items were discrete and visually verifiable, but not where credit required judging continuous quantities such as ventilation rate, volume, or suction duration. Defensible uses are formative and archival, not summative. These results reflect an early, non-specialist configuration: a baseline, not a limit.

Background: The condition of a patient with acute stroke often changes within hours of ICU admission. Prognostic work here targets fixed endpoints predicted from admission data, and trajectory phenotyping assigns one label per patient. We used longitudinal ICU data to identify interpretable dynamic clinical states, characterize transitions between them, and relate the current state to later events. Methods: Retrospective cohort study of 6368 adults with acute stroke in MIMIC IV v3.1. The first 72 h were divided into twelve 6-hour windows, and a hidden Markov model was fitted to 21 neurological, physiological and organ support variables. State number was chosen against criteria fixed before fitting: statistical fit, restart stability, state occupancy and clinical interpretability. Generalized estimating equations related the current state to new mechanical ventilation and vasopressor use within 12 h, and to ICU death within 72 h. Eleven sensitivity analyses assessed the robustness of the state solution. Results: Four states were selected: neurologically preserved-low support, neurological impairment low support, impairment renal dysfunction and impairment-respiratory support (63.3%, 7.8%, 11.8% and 17.1% of windows). Within 72 h, 40.3% of patients changed state at least once, and transitions ran in both directions rather than along a single severity gradient. States were identified without outcome data, yet ICU mortality by last state ranged from 2.9% to 43.9%. Adjusted for age, sex, subtype and Charlson index, the current state remained associated with organ-support escalation and death. State prevalence differed by at most 1.1 percentage points between training and test sets, and 10 of 11 sensitivity analyses gave a stable four-state solution (ARI 0.754 0.955). Conclusions: The early ICU course of acute stroke can be represented as movement among a small number of clinically interpretable states. The representation was reproducible in a held out set and across admission eras, but requires validation in an independent database before any clinical use.

Background Mortality in sepsis is often considered a direct consequence of infection and organ dysfunction, although many deaths occur after withdrawal of life sustaining treatment. The clinical factors leading to these decisions and their implications for interpreting sepsis mortality are not well characterized. Methods We performed a secondary analysis of a prospective observational cohort of adults with physician adjudicated sepsis at a tertiary academic medical center. Patients who transitioned to comfort measures only (CMO) during the index hospitalization underwent structured chart review to characterize baseline health and functional status, clinical severity, care preferences, anticipated outcomes following survival, and the primary reason for CMO transition. Results Among 239 patients with adjudicated sepsis, 42 (17.6%) transitioned to CMO. These patients had substantial underlying disease, including malignancy in 76% and immunocompromised status in 62%. However, 88% lived at home before hospitalization, 52% were independent in activities of daily living, an additional 26% were partially independent, and 90% were full code on admission. Progressive multi organ failure (19%), refractory septic shock (19%), and irreversible respiratory failure (12%) accounted for half of CMO transitions, while advanced frailty (5%) and poor baseline functional status (2%) were infrequent primary reasons. Median time from admission to CMO was 16 days (IQR 7 to 33), and median time from admission to death was 18 days (IQR 11 to 35). Anticipated ventilator dependence (62%), dialysis dependence (36%), and cognitive impairment frequently influenced goals of care discussions. Overall, 38 patients died during the index hospitalization, and 35 (92%) of these deaths followed transition to CMO. Conclusions Most CMO transitions in this cohort occurred after an evolving course of severe sepsis and were driven primarily by progressive organ dysfunction and failure to recover rather than advanced frailty or poor baseline function. These findings identify failure to recover after the acute septic insult as an important clinical trajectory and highlight the need to account for treatment limitation when interpreting sepsis mortality. Understanding why some patients recover from sepsis associated organ dysfunction while others progress to irreversible organ failure may help identify patients and mechanisms for future therapeutic intervention.

Abstract Background: In patients with sepsis and pre-existing hypertension, admission findings may not adequately describe the subsequent course of circulatory support and organ dysfunction. We developed and externally validated a model to reassess in-hospital mortality risk after the first 72 hours of intensive care. Methods: This retrospective study used MIMIC-IV for development and eICU-CRD for external validation. Patients had received vasoactive agents and remained in the ICU for at least 72 hours. Static variables were combined with features from six consecutive 12-hour windows. Imputation, feature selection, model fitting, and calibration were performed within training folds during five-fold cross-validation. The final XGBoost model was applied externally without refitting. Evaluation included discrimination, calibration, decision curves, and risk stratification, with an exploratory comparison of static-only and static-plus-dynamic feature sets. Results: The development and external cohorts included 1019 and 1747 patients, with 338 (33.2%) and 516 (29.5%) deaths, respectively. Internal area under the receiver operating characteristic curve (AUC) was 0.752 (95% CI 0.720-0.784). External AUC was 0.713 (95% CI 0.687-0.739), average precision was 0.536, the Brier score was 0.185, and the calibration slope was 0.744. Mortality increased across external risk tertiles from 13.7% to 47.3%. In an exploratory feature-set comparison, the static-plus-dynamic feature set showed a 0.071 higher internal AUC than the static feature set (95% CI 0.042-0.109). Conclusions: Information accumulated during the first 72 hours supported subsequent mortality risk stratification in this selected population. The model retained moderate discrimination externally, supporting further evaluation as an adjunct to clinical reassessment. Local calibration and the clinical consequences of acting on model predictions require evaluation before routine use.

Background: Mortality prediction models often combine early electronic health record data, but the relative prognostic value of baseline vulnerability, physiological severity, treatment exposure, and procedure burden remains unclear. Objective: To compare routinely available first-24-hour clinical domains for visit-level 30-day mortality prediction and assess whether domain-level patterns replicated in MIMIC-IV. Methods: We used CHoRUS, an OMOP-formatted acute-care dataset, with independent domain-level replication in MIMIC-IV. CHoRUS included 22,098 visits among 5,892 unique patients, with 1,004 30-day mortality events and 4.5% mortality prevalence. MIMIC-IV included 23,000 acute-care visits among 10,006 unique patients, with 819 events and 3.6% prevalence. Across both datasets, 45,098 visits and 15,898 unique patients were analyzed. Predictors were restricted to the first 24 hours after visit start. Performance was evaluated using AUPRC, AUROC, Brier score, calibration, sensitivity at 90% specificity, highest-risk 10% analyses, decision-curve analysis, and SHAP summaries. Because 30-day mortality was infrequent, the classification task was class-imbalanced. Accordingly, AUPRC was interpreted relative to the prevalence-based no-skill baseline, rather than as an absolute measure alone. Results and Conclusion: Physiological severity produced the largest improvement beyond baseline in CHoRUS, with median AUPRC 0.38 and median AUROC 0.86, and showed the same primary domain-level pattern in MIMIC-IV. Treatment exposure and procedure burden provided smaller gains. In CHoRUS, the best pairwise model combined baseline, physiological severity, and procedure burden features, with median AUPRC 0.41; the all-domain model was slightly lower, with median AUPRC 0.40 and median AUROC 0.86. In MIMIC-IV, the all-domain model had the highest median AUPRC, 0.25, only modestly above the best pairwise model. First-24-hour physiological severity features therefore provided the most consistent prognostic information across datasets, supporting parsimonious, clinically interpretable acute-care risk models centered on high-quality early physiological data.

Introduction Norepinephrine remains first-line vasopressor therapy for septic shock despite its association at high doses with undesirable cardiovascular, kidney, and immune effects. Angiotensin-II (Ang-II) is a non-catecholamine vasopressor of the renin-angiotensin-aldosterone system (RAAS) now approved to increase blood pressure in vasodilatory shock. RAAS dysregulation is common in septic shock and may represent a treatable trait. However, few prospective investigations evaluate the effect of early Ang-II use in septic shock on dysfunctional RAAS biology, host-response, or clinical outcomes. Therefore, we designed a mechanistic clinical trial to test the hypothesis that early Ang-II therapy in septic shock normalizes systemic RAAS abnormalities and modulates innate immune responses. Methods and Analysis The Mechanistic Assessment of Norepinephrine TheRapy vs. Angiotensin-II in Septic Shock (MANTRA) trial is an investigator-initiated, prospective, multicenter, open-label, randomized mechanistic clinical trial. Adults with septic shock by Sepsis-3 criteria receiving a norepinephrine-equivalent dose (NED) of 0.10-0.50 mcg/kg/min will be randomized 1:1 to primary Ang-II (to a maximum of 40 ng/kg/min) or norepinephrine (to a maximum 35 mcg/min) treatment strategies over a 48-hour period. The primary outcome is the between-group difference in plasma renin trajectory from baseline to 24 hours, analyzed using a linear mixed-effects model with a treatment-by-time interaction term. With n=78, the trial has 90% power (at two-sided =0.05) to detect a 25% between-group difference in 24-hour renin. Secondary clinical outcomes include longitudinal NED, hours alive and vasopressor-free at 72 hours, a 28-day composite outcome (days alive and free of vasopressors, renal replacement therapy, and mechanical ventilation), treatment failure requiring crossover or protocol discontinuation, and thrombotic and arrhythmia events through 28 days. Secondary mechanistic outcomes include serial RAAS biomarkers (prorenin, soluble prorenin receptor, angiotensinogen, ACE, ACE2, Ang-II, angiotensin-(1-7), aldosterone, and DPP3), immune measures (ex vivo monocyte function, monocyte gene expression, plasma cytokines), and organ injury biomarkers. Enrollment is planned from 5/2026-7/2030. Strengths and limitations of this study MANTRA is a randomized trial comparing angiotensin-II against an active standard-of-care norepinephrine strategy rather than placebo, enrolling patients earlier in septic shock than prior trials restricted to catecholamine-resistant shock. Serial sampling profiles RAAS peptides, innate immune function, and organ-injury biomarkers, which will generate rich mechanistic data on how vasopressor strategy shapes the host response. The sample size is adequate for the biomarker primary endpoints and will establish feasibility for a larger trial, but it does not provide sufficient power for hard clinical endpoints, which remain exploratory. MANTRA compares two open-label vasopressor strategies rather than monotherapies; clinician retain discretion over background and rescue vasopressors, steroids, and crossover, which may attenuate differences between-arms. The 48-hour intervention window limit inference about clinician-assessed outcomes and the durability of treatment effect.

Introduction Inappropriate use of echocardiograms and stress tests with nuclear components in the evaluation of cardiopulmonary complaints (chest pain, dyspnea/shortness of breath (SOB), dizziness, and syncope) is common, despite Cardiology society guidelines for appropriate use. Such overuse raises healthcare costs, impairs the availability of resources for other patients, and exposes patients to radiation unnecessarily. Our Emergency Department (ED) runs an observation unit that sees thousands of patients annually with cardiopulmonary complaints. We observed many have echocardiograms and stress tests with nuclear components without indications for either. Working with our Department of Cardiology, we promoted guidelines for appropriate use of echocardiograms and stress tests with nuclear components in the evaluation of such patients. Methods We collected 2024 and 2025 data regarding OU admissions. Patents were included if they were [&ge;]18 years, in the ED OU between 1/1/24 and 12/31/25, aad an OU admission complaint of chest pain, dyspnea/SOB, dizziness, and syncope. We calculated the percent of patients with such presentations who received either an echocardiogram or a stress test with a nuclear component. We then compared the 2024 (pre-implementation) data with full-year data from the first full year of implementation (2025). Results After introducing educational guidelines, there were statistically-significant reductions in nuclear stress tests ordered for dyspnea/SOB (absolute reduction 9.3%; p = 0.0009) and overall usage of nuclear stress tests (absolute reduction 2.4%; p = 0.0095). This was offset by increases in echocardiograms ordered for chest pain (absolute increase 3.7%; p = 0.005) and overall usage of echocardiograms (absolute increase 2.0%; p = 0.0454). There was no net change in the overall use of echocardiograms and nuclear stress tests when considered together: 85.2% of patients had one or the other study in 2024 vs. 84.8% in 2025; p = 0.5768. Discussion Introducing and promoting appropriate-use guidelines for echocardiograms and stress tests with nuclear components in the evaluation of cardiopulmonary complaints was associated with a reduction in unnecessary nuclear stress tests, but not echocardiograms. Success of this program to reduce nuclear stress tests may be attributed to several factors. First, the relevant specialties (emergency medicine, cardiology) were engaged. Second, we relied on guidelines adopted by professional organizations. Third, the initiative corresponds to nationwide efforts to decrease cost of care by providing evidence-based diagnostic and treatment management. Failure to reduce echocardiograms may be due to a well-documented multi-year time lag between changes in medical knowledge and wide-scale adoption; failure to develop the guidelines in collaboration with house staff and mid-level providers and promote them at multiple times and venues in a multi-modal manner; and utilize Department leadership to promote their usage.