BACKGROUND: Preclinical studies suggest that initiating activity-based therapy (ABT) within days of an acute spinal cord injury (SCI) best enhances recovery, but may also increase the risk of inducing spinal cord damage....BACKGROUND: Preclinical studies suggest that initiating activity-based therapy (ABT) within days of an acute spinal cord injury (SCI) best enhances recovery, but may also increase the risk of inducing spinal cord damage. This study assesses the effects of early ABT initiated within 48 h of spinal surgery (or 3 days of the SCI), while patients are in the intensive care unit (ICU) for hemodynamic management. METHODS: This single-arm proof-of-concept trial included 45 adults with a severe traumatic SCI receiving daily 30-minute sessions of in-bed leg cycling for 14 consecutive days, in comparison to a matched historical control cohort that did not undergo ABT. Cycling was initiated in the ICU within 48 h of spinal surgery. The main patient outcome was the recovery of independent walking 6 months post-SCI. Secondary outcomes included the rates of complications and other neurofunctional assessments. RESULTS: Recovery of independent walking occurred in 31% of PROMPT-SCI participants and 36% of controls (p = 0.3). Neurological recovery was similar between the two cohorts. The PROMPT-SCI cohort had decreased spontaneous spams (9% vs. 40%, p<10− 3) and co-occurrence of pneumonia, pressure injury and urinary tract infection (P/UTI/PI) (2% vs. 13%, p = 0.03). Readiness for rehabilitation transfer was decreased by 7 days in the PROMPT-SCI cohort, approaching statistical significance (p = 0.051). When adjusting for baseline motor score, spontaneous spasms remained decreased with ABT (p = 0.001; odds ratio = 0.14 [95%CI: 0.04–0.45]), and rehabilitation transfer readiness was shorter (p = 0.03; β=-0.22 [95%CI: -0.41 – -0.04]). However, there was no significant association between concomitant P/UTI/PI and ABT (p = 0.08; Odds ratio = 0.14 [95%CI: 0.02–1.24]). CONCLUSIONS: Early acute ABT did not increase the risk for neurological deterioration when initiated in the ICU for patients requiring hemodynamic management. It can decrease the early occurrence of spontaneous spasms, and may potentially reduce the co-occurrence of P/UTI/PI and accelerate rehabilitation transfer readiness. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04699474 (Registration Date: January 5th 2021).
BACKGROUND: Obtaining intraosseous (IO) access is an established procedure within the critical care setting. Mechanisms for routinely confirming IO placement and sustained IO efficacy lack objectivity, fail to incorporat...BACKGROUND: Obtaining intraosseous (IO) access is an established procedure within the critical care setting. Mechanisms for routinely confirming IO placement and sustained IO efficacy lack objectivity, fail to incorporate modern technology, and lack protocol advancement that improves patient treatment, safety, and provider confidence. In this study, we investigate the novel use of color and doppler point-of-care ultrasound (POCUS), in combination with an IO fluid bolus, as a potential means to confirm IO placement. METHODS: Design: randomized single-blinded comparison using doppler and color flow to confirm proximal central venous flow during IO infusion. Study model: fresh, never frozen, unembalmed, and consented cadavers. Standard arm: intentionally correct IO placement randomized across the proximal humerus, distal femur, and proximal tibia. Comparison arm: intentionally incorrect IO placement. Protocol: Following access confirmation, an IO fluid bolus was initiated. An operator, blinded to the correct versus the intentionally incorrect IO placement, applied POCUS to the central vein proximal to the established IO catheter. POCUS, in concert with a fluid bolus, was then used to assess for color flow and the generation of a doppler waveform at the associated proximal central vein. The operator additionally applied POCUS to assess the IO insertion site and extremity for the presence of extravasation. RESULTS: The unblinded operators identified proximal venous color flow and doppler waveform in 100% of intentionally placed IOs, while the blinded POCUS operator identified them in 86% and 88% of cases with correctly placed IOs. 7% intentionally misplaced IOs generated doppler waveform and color flow, ultimately determined on post-procedure dissection to be secondary to an inadvertent cannulation of a deep peripheral vein adjacent to the bone. On average, correctly placed tibial IOs required more volume to produce color and doppler flow than humoral IOs. CONCLUSION: The ability to accurately confirm and reassess IO catheter placement and patency is of vital importance throughout the entire critical care continuum. Awareness of procedural POCUS specific to the use of color flow and doppler waveform to confirm IO placement may provide additional assurance that an IO catheter has been successfully placed, remains in position, and is functioning safely.
Submarine emergencies represent one of the most extreme and logistically challenging scenarios in disaster and military medicine, where isolated, high-pressure environments create a perfect storm of medical, psychologica...Submarine emergencies represent one of the most extreme and logistically challenging scenarios in disaster and military medicine, where isolated, high-pressure environments create a perfect storm of medical, psychological, and operational challenges. This perspective examines the unique challenges of providing medical care in submarine accidents, drawing on historical cases such as the Russian Kursk (2000), the Canadian Chicoutimi (2004), the USS San Francisco (2005), and the Argentine Navy’s San Juan (2017) or the Indonesian KRI Nanggala (2021) which illustrate operational constraints and rescue feasibility issues inherent to these types of incidents. The onboard survival phase is marked by rapidly deteriorating conditions, especially on non-nuclear submarines, including hypoxia, hypercapnia, hypo- or hyperthermia, toxic fumes, possible ionizing radiation and psychological stress, as life support systems fail and emergency resources, such as oxygen candles and carbon dioxide scrubbers are finite. Distress signaling is severely limited by the lack of reliable underwater communication, forcing crews to rely on surface beacons without confirmation of receipt, thereby inducing additional mental stress, prolonging isolation and self-sustainment efforts. Rescue operations, for instance coordinated through networks like International Submarine Escape and Rescue Liaison Office (ISMERLO), originally founded by NATO but now a worldwide collaboration, face significant logistical hurdles, including delays in localization, limited Deep Submarine Rescue Vehicle (DSRV) availability, and the complexities of mass-casualty triage, particularly when decompression illness (DCI) complicates trauma management. The dual threat of trauma and DCI necessitates a modified triage approach, where traditional trauma classifications must be integrated with decompression risk assessments to prioritize treatment effectively. Ethical dilemmas further arise in conflict zones, where resource scarcity, security risks, and adherence to humanitarian law introduce profound moral distress for decision-makers and rescue personnel.
BACKGROUND: The clinical prognosis of severe acute pancreatitis (SAP) varies significantly, and traditional scoring systems fail to reveal its intrinsic heterogeneity. METHODS: This multicenter retrospective cohort stu...BACKGROUND: The clinical prognosis of severe acute pancreatitis (SAP) varies significantly, and traditional scoring systems fail to reveal its intrinsic heterogeneity. METHODS: This multicenter retrospective cohort study enrolled SAP patients from a Chinese Jiangxi cohort (n = 3,022) and the US MIMIC-IV cohort (n = 840). Consensus K-means clustering was applied to the derivation cohort to identify clinical subphenotypes, which were externally validated in the independent cohort. An XGBoost classifier was constructed based on selected variables and its performance was evaluated. Multivariable Cox regression models were used to analyze the association of each subphenotype with mortality and to assess heterogeneous associations with three key early interventions: early fluid intake, low molecular weight heparin (LMWH) anticoagulation, and early enteral nutrition. RESULTS: Cluster analysis consistently identified three stable and reproducible SAP clinical subphenotypes: K1 (Stable type, n = 1,446), characterized by younger age, stable hemodynamics and renal function, and good nutritional status; K2 (Renal impairment-dominant type, n = 317), defined by severe renal insufficiency, hypoalbuminemia, and lower mean arterial pressure; and K3 (Elderly/Hepatic impairment type, n = 1,259), featuring the oldest age and significantly elevated liver injury markers. The K2 subphenotype had the highest in-hospital mortality (44.8%), significantly greater than that of K1 (8.3%) and K3 (14.9%) (p < 0.001). Multivariable Cox regression showed that, using K1 as reference, the K2 subphenotype was independently associated with an increased risk of 28-day mortality (adjusted hazard ratio [aHR] = 6.70, 95% CI 4.94-9.08). The constructed XGBoost subphenotype classifier demonstrated excellent discriminative performance in the training, test, and external validation sets (macro-average AUCs: 0.997, 0.994, and 0.958, respectively). Analysis of heterogeneous associations revealed that fluid overload (total intake ≥ 2.5 L within the first days) was significantly associated with increased mortality specifically in the K3 subphenotype. LMWH therapy showed a clear survival benefit only in the K2 subphenotype (aHR = 0.66, 95% CI 0.45-0.96, p = 0.031). CONCLUSION: This study identified three SAP subphenotypes with significantly heterogeneous clinical features and prognoses based on early routine indicators and developed a high‑performance classifier for bedside use. The distinct associations with fluid administration and anticoagulation across subphenotypes suggest that phenotype‑based strategies may optimize the clinical management of SAP, although these findings are hypothesis‑generating and require prospective validation.
Heylen J, Lopuhaä B, Vanderbeke L
… +21 more, Feys S, Maessen L, Jacobs C, Lauwers HM, Beuselinck K, De Vlieger G, De Sadeleer L, Hermans G, Lagrou K, Meersseman P, Meersseman W, Peetermans M, Van Wijngaerden E, Wilmer A, Verjans GM, van den Bosch TPP, von der Thüsen JH, De Hertogh G, van Kampen JJA, Wauters J, OPPORTUNE consortium
BACKGROUND: Herpes simplex virus type 1 (HSV-1) and cytomegalovirus (CMV) are frequently detected in respiratory samples from patients with acute respiratory distress syndrome (ARDS), yet whether PCR positivity reflects...BACKGROUND: Herpes simplex virus type 1 (HSV-1) and cytomegalovirus (CMV) are frequently detected in respiratory samples from patients with acute respiratory distress syndrome (ARDS), yet whether PCR positivity reflects histologically confirmed pulmonary infection and contributes to lung injury remains unclear. We aimed to characterize the histopathological features of pulmonary HSV-1 and CMV using PCR and immunohistochemistry on lung tissue specimens of critically ill patients with influenza- or COVID-19-related ARDS obtained at autopsy. In addition, we sought to correlate pulmonary herpesvirus loads in antemortem bronchoalveolar lavage fluid (BALF) samples with postmortem histological findings. METHODS: In this retrospective autopsy cohort, we included patients with COVID-19- or influenza-related ARDS who died in the intensive care unit and underwent autopsy between 2009 and 2021. Lung tissue blocks were systematically screened for HSV-1 and CMV using PCR and immunohistochemistry. Performance of HSV-1 PCR on BALF for diagnosing proven HSV-1 infection was evaluated with receiver operating characteristic analysis. RESULTS: We included 22 patients with COVID-19- and 20 with influenza-related ARDS. Proven HSV-1-associated necrotizing tracheobronchitis was identified in 6/42 patients (14%). Proven CMV infection was identified in only one patient, displaying focal presence of a few CMV-infected cells. An optimal cutoff of 4.11 log₁₀ copies/mL for HSV-1 in BALF yielded 100% sensitivity and 69% specificity for diagnosis of proven HSV-1 infection. CONCLUSIONS: Pulmonary HSV-1 was associated with tracheobronchitis in a subset of patients in a viral load dependent manner. Pulmonary CMV presence appeared histologically insignificant and likely represents a bystander phenomenon of critical illness.
Chen S, Liu S, Ren B
… +32 more, Zhang Y, Dai J, Ye Z, Xu L, Fan Y, Li C, Jiang Z, Liu Q, Zou K, Zhang Z, Lian W, Li S, Wang P, Ke L, Pan W, Mao W, Guo F, Xu YM, Lin T, Tan W, Wei W, Yang Q, Duan J, Ren D, Duan Z, Xing L, Xu H, Dou L, Su W, Zhan L, Zhu F, Chang Z
BACKGROUND: Current guidelines make no recommendation regarding appropriate fibrinogen replacement thresholds for non-traumatic massive bleeding. We aimed to determine the optimal post-treatment fibrinogen level associat...BACKGROUND: Current guidelines make no recommendation regarding appropriate fibrinogen replacement thresholds for non-traumatic massive bleeding. We aimed to determine the optimal post-treatment fibrinogen level associated with survival in critically ill patients with non-traumatic massive bleeding. METHODS: This multicenter retrospective cohort study enrolled adult ICU patients with non-traumatic massive bleeding and hypofibrinogenemia (fibrinogen <2.0 g/L) from 12 centers in China (2018–2025). Maximum fibrinogen level (FIBmax) achieved during treatment within 3 Days of hemorrhage onset was the primary predictor. We used the Boruta algorithm for variable selection, multivariable logistic regression to assess the independent association between FIBmax and hospital mortality, restricted cubic splines to examine dose-response relationships, and pairwise group comparisons with Bonferroni correction to identify the optimal threshold. RESULTS: Among 358 patients (median age 59 years; 62.6% male), 74 (20.7%) died during hospitalization. FIBmax was independently associated with hospital mortality after adjustment for confounders (OR 0.37 per g/L increase; 95% CI 0.25–0.57; P < 0.001). Adding FIBmax to the base model significantly improved discrimination (AUC 0.899 vs. 0.868; P = 0.017), calibration (Hosmer-Lemeshow P = 0.096 vs. 0.031), and reclassification (NRI 0.814; IDI 0.076). Restricted cubic spline analysis revealed a non-linear dose-response relationship (P for non-linearity = 0.026), with an inflection point at 2.03 g/L. Pairwise comparisons identified a significant hospital mortality transition at 2.0 g/L: patients with FIBmax of 1.5–2.0 g/L had 3.23-fold higher hospital mortality compared to those achieving 2.0–2.5 g/L (P = 0.004), representing the only significant transition point across all adjacent group comparisons. Hospital mortality plateaued at higher levels, with no additional benefit observed above 2.5 g/L. Patients achieving FIBmax ≥ 2.0 g/L had hospital mortality of 10.1% versus 48.0% for those below this threshold (P < 0.001). CONCLUSIONS: In critically ill patients with non-traumatic massive bleeding, a post-treatment fibrinogen level of 2.0–2.5 g/L appears optimal, and 2.0 g/L may represent a potential therapeutic threshold.
Targeted next-generation sequencing (tNGS) has demonstrated higher analytical detection of respiratory pathogens than conventional microbiological tests (CMTs), yet its real-world clinical value in intensive care units (...Targeted next-generation sequencing (tNGS) has demonstrated higher analytical detection of respiratory pathogens than conventional microbiological tests (CMTs), yet its real-world clinical value in intensive care units (ICUs) remains uncertain. We conducted an interim analysis of a prospective study including 51 adult ICU patients with severe pneumonia at a tertiary medical center in Taiwan and examined the challenges to its routine implementation in the ICU. Bronchoalveolar lavage samples were analyzed using a hybrid capture–based Respiratory Pathogen ID/AMR Enrichment Panel (RPIP) and compared with standard testing (CMT combined with the FilmArray Pneumonia Panel [FAPP]). Causative pathogens were determined through multidisciplinary expert adjudication. RPIP showed a higher analytical detection rate than standard testing (90.2% vs. 82.4%). However, the proportion of adjudicated causative pathogens was similar between RPIP and standard testing (47.1% vs. 49.0%), with no significant difference (McNemar’s exact test, p = 1.00). After expert adjudication, RPIP provided additional clinically actionable yield in 23.5% of patients compared with CMT + FAPP, mainly related to antimicrobial resistance determinants, while 17.6% showed concordant results, 13.7% demonstrated lower yield with RPIP, and 45.1% of cases had no adjudicated causative pathogen after comprehensive review. Although tNGS broadens pathogen and resistance detection, its routine implementation in the ICU requires clearly defined indications, validated genotype–phenotype correlations, optimized turnaround time, strict contamination control, and structured multidisciplinary integration.
BACKGROUND: Amikacin nebulization may be used in mechanically ventilated patients for pneumonia prevention and treatment. Available drug delivery and pharmacokinetic knowledge mainly rely on in vitro data and studies of...BACKGROUND: Amikacin nebulization may be used in mechanically ventilated patients for pneumonia prevention and treatment. Available drug delivery and pharmacokinetic knowledge mainly rely on in vitro data and studies of a limited number of patients. METHODS: To evaluate pulmonary and systemic pharmacokinetics of nebulized amikacin in mechanically ventilated patients and assess the influence of ventilation and nebulization conditions on drug concentrations in the tracheal aspirate and plasma, this ancillary study of a published randomized trial performed population pharmacokinetic modelling on 498 tracheal aspirates and 602 plasma concentrations following 20 mg/kg amikacin vibrating mesh nebulization among 261 patients. RESULTS: Tracheal aspirate amikacin concentrations were very high but variable between patients (median peak concentration 7269 µg/g, interquartile range 4935–9846 µg/g). The tracheal aspirate concentration declined with a median terminal half-life of 7.6 h (interquartile range 5.3–44.2 h), and no accumulation was observed over three doses. Systemic absorption was marginal (median peak plasma concentration 1.9 mg/L, interquartile range 1.3-3.0 mg/L). Despite differences in ventilation mode, circuit type, humidification, inspiratory flow rate, respiratory rate, and tidal volume, no significant impact on tracheal aspirate and plasma amikacin concentrations was observed. CONCLUSIONS: Nebulized amikacin achieved high pulmonary concentrations with minimal systemic exposure. Tracheal aspirate and plasma drug concentration were not significantly influenced by ventilation or nebulization conditions. These findings suggest that strict optimization of nebulization parameters may not be necessary when aiming for tracheobronchial antibiotic inhaled delivery such as to prevent ventilator associated pneumonia.
Contemporary mechanical ventilation strategies in ARDS rely on lung-protective ventilation approaches that typically utilize separate static variables/settings (e.g., tidal volumes, plateau pressure) and cut-off values....Contemporary mechanical ventilation strategies in ARDS rely on lung-protective ventilation approaches that typically utilize separate static variables/settings (e.g., tidal volumes, plateau pressure) and cut-off values. This approach fails to capture complex patient dynamics. Increasing efforts have focused on the interactions between different parameters (e.g. mechanical power, driving pressure); however, these only accommodate a limited number of interactions and do not integrate the complexity of patient-specific, severity-dependent and time-varying thresholds for “safe” mechanical ventilation. In aviation, the “flight envelope” concept revolutionized flight safety by defining flexible, context-dependent boundaries as a function of multiple dimensions (e.g. flight speed, altitude, (dynamic) loads on the aircraft) within which an aircraft can operate. When a new aircraft is developed, its operational safety envelope is determined analytically. Calculations are quickly followed by flight simulations and flight testing, beginning from a known safe point within the envelope and gradually carefully exploring its boundaries to characterize its limits. Inspired by this aviation approach, we propose the “respiratory envelope” framework for mechanical ventilation: a conceptual framework that allows for the incorporation of multiple (time-dependent) dimensions and integrates interactions between ventilator variables/settings and patient characteristics. Just as flight envelopes informed the development of automated envelope protection algorithms and autopilot systems, a similar framework could be applied in clinical settings to simulate real-time “safety zones” based on continuously monitored, yet underutilized, physiological data, such as in digital twins.
BACKGROUND: Critically ill patients experience rapid skeletal muscle wasting due to immobility and systemic inflammation. Traditional imaging modalities—including computed tomography, magnetic resonance imaging, and dual...BACKGROUND: Critically ill patients experience rapid skeletal muscle wasting due to immobility and systemic inflammation. Traditional imaging modalities—including computed tomography, magnetic resonance imaging, and dual-energy X-ray absorptiometry—can accurately quantify muscle mass but are impractical for monitoring critically ill patients because of cost, radiation, and logistical constraints. Ultrasound offers a bedside, radiation-free, and repeatable alternative capable of assessing both quantitative (cross-sectional area, muscle thickness) and qualitative (echointensity, pennation angle) muscle changes. This systematic review and meta-analysis synthesizes existing evidence regarding ultrasound-derived measures of muscle atrophy monitoring in critically ill adults. MAIN BODY: A systematic search identified 69 eligible studies evaluating lower-limb muscle ultrasound in the ICU. Meta-analysis demonstrated substantial, progressive atrophy. By Day 7 of ICU admission, the rectus femoris cross-sectional area showed a decline of 15.76% (95% CI − 18.06 to − 13.47, I2 = 88.72%), while quadriceps muscle thickness exhibited a parallel, yet smaller, reduction of 11.00% (95%CI − 14.38 to − 7.62, I2 = 90.63%). Echointensity tended to increase, while pennation angle decreased, reflecting compositional and architectural deterioration. Considerable heterogeneity may reflect differences in patient characteristics, anatomical landmarks, and ultrasound technical factors. Limited data linked early ultrasound changes with ICU-acquired weakness. However, after excluding an outlier, pooled analysis of Day 1–3 rectus femoris cross-sectional area changes showed a statistically significant greater muscle loss in patients who developed ICU-acquired weakness to those who did not (mean difference: − 3.58%; 95% CI − 5.95 to − 1.22, I2 = 0%). CONCLUSIONS: Ultrasound detects early, rapid muscle wasting and concurrent quality degradation in critically ill adults. However, very low certainty of evidence due to heterogeneity and methodological limitations hinders clinical translation. Standardized protocols and prospective validation studies are needed to clarify ultrasound’s potential clinical utility in ICU muscle monitoring.
Granton D, Hajjaj OI, Ishaq L
… +12 more, Ahimsadasan R, Paleczny SG, Ahimsadasan N, Ying E, Jabri G, Mansuri A, Warfield N, Pettenuzzo T, Honarmand K, Gandhi P, Englesakis M, Fan E
BACKGROUND: Acute respiratory distress syndrome (ARDS) carries substantial morbidity and mortality. Supportive care with invasive mechanical ventilation (IMV) remains a cornerstone of management. The breadth and prevalen...BACKGROUND: Acute respiratory distress syndrome (ARDS) carries substantial morbidity and mortality. Supportive care with invasive mechanical ventilation (IMV) remains a cornerstone of management. The breadth and prevalence of complications experienced by patients with ARDS undergoing IMV is unclear. METHODS: We performed a systematic review and meta-analysis to quantify complications reported by studies featuring patients with ARDS undergoing IMV. We searched MEDLINE, MEDLINE In-Process/ePubs, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and ClinicalTrials.gov from database inception until November 28, 2025. We included randomized controlled trials (RCTs) and cohort studies featuring adults with ARDS undergoing IMV that reported at least one complication. We excluded studies of COVID-19, studies with 25% or more patients on extracorporeal life support, and studies with under 200 participants. We extracted data on any reported clinical complication, based on author definitions. For complications reported by three or more studies we performed a random effects meta-analysis of logit-transformed complication proportions using inverse-variance weighting. RESULTS: Of 25,421 citations, we reviewed 2620 full texts and included 53 studies (25 RCTs and 28 cohort studies). Complications were variably and infrequently reported. Only barotrauma, ventilator associated pneumonia (VAP), hypotension, arrhythmia, stroke, myopathy and cardiac arrest were reported by three or more RCTs. In cohort studies, barotrauma, VAP, acute renal failure, sepsis and bacteremia were reported by three or more studies. All estimates featured considerable heterogeneity. CONCLUSIONS: In this systematic review of studies including patients with ARDS receiving IMV, reporting of complications was variable and infrequent. Our synthesis was descriptive and did not investigate causality. Future studies should establish consensus on the spectrum of complications to improve reporting and help evaluate the risks and benefits of novel therapies. We propose a process to develop a core outcome set for complications experienced by patients with ARDS undergoing IMV. Preliminary results of this work were presented at the ESICM LIVES conference in October 2021
BACKGROUND: The role of vitamin D on the risk and clinical outcomes of sepsis remains incompletely elucidated. OBJECTIVES: This study aims to investigate the association between serum 25-hydroxyvitamin D [25(OH)D] concen...BACKGROUND: The role of vitamin D on the risk and clinical outcomes of sepsis remains incompletely elucidated. OBJECTIVES: This study aims to investigate the association between serum 25-hydroxyvitamin D [25(OH)D] concentrations and the risk of incident sepsis, and to evaluate its relationship with 28-day, 60-day, and 1-year mortality. METHODS: In this prospective cohort study, we analyzed data from the UK Biobank. The association between serum 25(OH)D concentrations and sepsis incidence was evaluated using Cox proportional hazards models, Kaplan–Meier survival curves, and restricted cubic spline analyses. RESULTS: Over a mean follow-up of 14 years, 15,452 incident sepsis cases were documented. A negative and nonlinear association was observed between serum 25(OH)D levels and sepsis risk. Compared with participants whose 25(OH)D levels were > 20 ng/mL, those with levels < 10 ng/mL exhibited an adjusted hazard ratio (HR) of 1.28 (1.22–1.34) for sepsis. This association was stronger among women and participants with a BMI < 25 kg/m2. Furthermore, participants with 25(OH)D < 10 ng/mL had significantly higher mortality than those with 25(OH)D > 20 ng/mL, with adjusted HRs of 1.14 (1.02–1.27) for 28-day mortality, 1.11 (1.01–1.23) for 60-day mortality, and 1.10 (1.02–1.19) for 1-year mortality. CONCLUSION: Lower serum 25(OH)D concentrations were associated with an increased incidence of sepsis and higher mortality.