We commend Duan et al. for examining laxative use after cardiac arrest. However, because follow-up began at return of spontaneous circulation, whereas exposure timing was not reported, the observed association may reflect both immortal time and treatment selection: patients who survived and recovered sufficiently may have been more likely to receive laxatives. A time-varying exposure defined by first administration, with landmark analysis as a sensitivity analysis, would better align treatment and risk time. The reported time-varying-effect model does not estimate the effect of initiating treatment on a particular day and, therefore, cannot support a 15-day treatment window. The findings should be framed as observational associations rather than evidence that laxatives improve survival.
Abstract Background Hemoglobin targets are absent from post-cardiac arrest guidelines. New trials suggest that patients with brain and myocardial injury, injuries common post-arrest, may benefit from higher hemoglobin targets. Trends in post-arrest hemoglobin and real-world practices remain poorly characterized. Methods We performed a retrospective cohort study of consecutive adult cardiac arrests at three academic hospitals. We screened in-hospital and out-of-hospital arrests with resuscitation efforts ongoing at hospital arrival for inclusion. Patients who survived the initial resuscitation and had a hemoglobin value measured were included. All post-arrest hemoglobin values and red blood cell transfusions were collected through 30 days; descriptive statistics and graphical visualization were used to present hemoglobin trends and transfusion practices. Exploratory analyses evaluated the association between hemoglobin and in-hospital mortality. Results Of 2,634 cardiac arrests, 958 met inclusion criteria, with 152 (15.9%) out-of-hospital arrests and 806 (84.1%) in-hospital. The mean initial post-arrest hemoglobin was 9.75 g/dL (SD 2.60), with hemoglobin levels declining progressively over the first 20 days post-arrest. Red cell transfusions were delivered for 369 (38.5%) patients in the 30 days post-arrest, with 1,238 total transfusions. The mean pre-transfusion hemoglobin value was 6.96 g/dL (SD 1.06). Pre-transfusion hemoglobin levels were < 7 g/dL for 762 (61.6%) of transfusions, and ≥ 7 g/dL for 476 (38.4%) of transfusions. Over 30 days, the highest proportion of patients transfused was in the first 48 h. Patients with initial post-arrest hemoglobin ≥ 9 g/dL had lower in-hospital mortality (adjusted OR 0.62, 95% CI 0.46–0.84, p <0.01). In time-varying analysis, post-arrest hemoglobin through 30 days demonstrated an L-shaped association with mortality, with 95% of the total reduction in mortality hazard captured below 9.20 g/dL. Conclusions Anemia is common after cardiac arrest, worsening in initial survivors. There is substantial variation in pre-transfusion hemoglobin levels, reflecting clinical equipoise. Clinical trials are needed to disentangle anemia as a driver versus a marker of outcomes, and test whether the risk is modifiable.
Abstract Background Neutrophil extracellular traps (NETs) contribute to organ dysfunction in sepsis, yet clinically accessible biomarkers reflecting NET-associated pathology remain limited. We sought to identify circulating proteins associated with NET formation and evaluate their clinical relevance in sepsis. Methods Unbiased proteomic profiling of stimulated human neutrophil supernatants and serum from murine sepsis was performed to identify proteins released during NET formation and elevated in vivo. Candidate biomarkers were selected through integration of these datasets and filtering based on cell type-specific expression profiles, followed by validation in patients with sepsis and healthy controls. Results Integrative analysis identified five candidate circulating markers associated with NET formation in sepsis: cathelicidin antimicrobial peptide, lactotransferrin, neutrophil gelatinase-associated lipocalin (NGAL), resistin, and histone H4. Among these, resistin, a recently recognized neutrophil-associated protein, and NGAL demonstrated the strongest associations with sepsis-associated complications. Both markers were elevated in patients with sepsis and correlated with circulating cell-free DNA levels. In receiver operating characteristic curve analyses, resistin discriminated multiple organ failure (AUC, 0.83) and disseminated intravascular coagulation (AUC, 0.81), whereas NGAL demonstrated similarly robust performance (AUC, 0.84 and 0.79, respectively). Both markers outperformed conventional clinical parameters for discriminating sepsis-associated complications. Conclusions These findings identify resistin as a circulating marker associated with NET formation that captures key features of sepsis-associated immunothrombosis and organ failure and may improve assessment of disease severity and risk stratification.
Abstract Background Intravenous calcium is frequently administered during sepsis, yet whether early treatment improves 24-h hemodynamic recovery remains uncertain. We compared 24-h hemodynamic recovery between calcium initiation within 2 h of a non-emergency low-ionized calcium (iCa) result and no calcium initiation during the first 6 h after the result. Methods We conducted a retrospective target-trial emulation of 2016–2025 high-resolution electronic health records from Zigong Fourth People's Hospital. Adults with sepsis, final or corrected iCa of 0.90–1.10 mmol/L, and no emergency indication were eligible at result availability. Strategies were executed calcium within 2 h versus no calcium through 6 h; care after 6 h was unrestricted. Clone–censor weighting and overlap tilting addressed grace periods, measured time-varying confounding, and clinical equipoise. The primary outcome was being alive and vasopressor-free at 24 h. Estimates and two-sided 95% percentile intervals came from 2,000 patient-level bootstrap samples with model refitting. Results Of 5,993 patients, 1,538 initiated calcium within 2 h, 147 initiated at 2–6 h, and 4,308 received none through 6 h; none of the latter initiated calcium during 6–24 h. The standardized probability of 24-h hemodynamic recovery was 69.9% with early calcium and 61.1% with deferral, corresponding to a risk difference of + 8.69 percentage points (95% percentile interval, + 4.66 to + 12.84) and a risk ratio of 1.142 (1.074–1.214). The estimated association varied with baseline norepinephrine-equivalent dose (Holm-adjusted P = 2.00 × 10⁻⁶), whereas the iCa interaction did not remain statistically supported after adjustment ( P = 0.097). Early calcium was associated with a 1.29-percentage-point higher observed risk of hypercalcemia (95% percentile interval, + 0.64 to + 2.05). Intervals for severe arrhythmia, new renal replacement therapy, and hospital mortality included the null. Conclusions Early intravenous calcium was associated with a higher probability of 24-h hemodynamic recovery than the deferred strategy, whose observed pathway involved no calcium through 24 h. Estimated effects were larger at higher vasopressor doses. Early calcium was associated with a modestly higher observed risk of hypercalcemia. These findings support randomized evaluation in vasopressor-treated patients. Baseline iCa modification remains exploratory.
Patients considered clinically brain dead undergo neurological assessment and critical care management, along with discussions with their families regarding goals of care and, when appropriate, organ donation. However, how these clinical and organ donation-related practices have evolved over time remains poorly characterized in Japan. We aimed to evaluate temporal changes in neurological assessment, critical care management, and organ donation-related processes among patients considered clinically brain dead. We conducted a retrospective single-center cohort study including consecutive patients considered clinically brain dead in the Emergency ICU of Okayama University Hospital between January 2017 and December 2025. Patients were identified through routine auditory brainstem response testing during evaluation for a brain-death-compatible state. Temporal changes in the determination of a brain-death-compatible state, organ donation discussion, and critical care management were evaluated by calendar year, with three study phases (2017–2019, 2020–2022, and 2023–2025) used for descriptive presentation. Annual trends were assessed using logistic regression and nonparametric trend analyses. Among 128 eligible patients, organ donation was discussed with the families of 110 (85.9
