Daily Sepsis Research Analysis

IMPORTANCE: Sepsis survivors experience high morbidity and mortality after discharge, but health systems lack effective approaches to improve recovery. OBJECTIVE: To evaluate the effect of a sepsis transition and recovery (STAR) program compared with usual care on postdischarge outcomes. DESIGN, SETTING, AND PARTICIPANTS: The ENCOMPASS (Engagement and Collaborative Management to Proactively Advance Sepsis Survivorship) stepped-wedge cluster randomized clinical trial was conducted among adults hospitalized with sepsis at 7 US hospitals in a single health care system from July 2020 to June 2023. Each hospital was a cluster, with 1 randomly transitioning to STAR every 4 months. Follow-up ended in December 2023. INTERVENTIONS: The STAR program was a navigator-led, telehealth-based strategy to proactively deliver evidence-driven postsepsis care to high-risk patients for 90 days after discharge. MAIN OUTCOMES AND MEASURES: The primary outcome was the composite of all-cause hospital readmission or mortality within 90 days of discharge. RESULTS: Of 3548 patients enrolled, 1843 (52%) were women, and the median (IQR) age was 68 (57-77) years; 1160 (33%) were admitted to the intensive care unit. A total of 1426 patients were randomized to the usual care group and 2122 patients were randomized to the STAR group. In the STAR group, 1393 patients (66%) engaged with the STAR program at least once after discharge. The composite all-cause readmission or mortality at 90 days did not differ between the STAR and usual care groups (1023 [48.2%] vs 684 [48.0%]; adjusted odds ratio, 1.05; 95% CI, 0.90-1.24; P = .53). Analysis of the outcomes separately demonstrated a lower frequency of death among patients in the STAR group compared with those in the usual care group (367 [17.3%] vs 292 [20.5%]; adjusted odds ratio, 0.88; 95% CI, 0.77-0.99; P = .04) and a higher frequency of readmission among patients in the STAR group (763 [35.9%] vs 478 [33.5%]; adjusted odds ratio, 1.13; 95% CI, 0.92-1.38; P = .24). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, a multicomponent, navigator-led STAR program did not reduce the composite of all-cause readmission and mortality at 90 days after discharge. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04495946.

RATIONALE: Sepsis is a leading cause of mortality and involves a dysregulated host response to infection. Host and microbe have historically been considered independently in studies of sepsis, limiting our understanding of key relationships driving mortality. OBJECTIVES: We sought to identify host and microbial factors associated with sepsis mortality and build prognostic classifiers. METHODS: We studied 321 critically ill adults and adjudicated sepsis status. From whole blood collected within 24 hours of admission we performed transcriptional profiling, and from plasma we carried out proteomics and metagenomics. We evaluated associations between in-hospital mortality and gene expression, protein levels and microbial metagenomic data, and built support vector machine-based prognostic classifiers. MEASUREMENTS AND MAIN RESULTS: In patients with sepsis, mortality associated with increased expression of genes related to neutrophil degranulation, lower expression of genes related to T cell signaling, and higher interleukin-8. Mortality also associated with higher microbial mass and greater bacterial relative dominance. Similar findings were observed in a broader group that also included patients with culture-negative sepsis or indeterminate sepsis status. An integrated host-microbe metagenomic classifier predicted sepsis mortality with an area under the curve (AUC) of 0.79, and a host transcriptomic classifier performed comparably with an AUC of 0.75. Both performed better (p<0.05 by paired DeLong tests) that the APACHE-III score (AUC of 0.69). CONCLUSIONS: Taken together, our findings provide a conceptual advance in the understanding of host and microbial factors associated with mortality in critical illness and demonstrate a new approach to mortality prediction in sepsis.

BACKGROUND: Sepsis is the leading cause of Intensive Care Unit (ICU) admissions in kidney transplant recipients (KTRs). However, the optimal immunosuppressive therapy (IST) management in this context is not well-defined. We aimed to evaluate the impact of IST management in the ICU on mortality rates and kidney graft function 6 months after inclusion in KTRs admitted for sepsis. METHODS: We conducted a multicenter, prospective, observational study over 1 year in 11 French ICUs. Inclusion criteria were all KTRs who have been transplanted for at least 3 months, admitted to the ICU for sepsis. All changes of IST (7 days prior to ICU admission or throughout the ICU stay) were collected. The primary outcome was MAKE 180 (Major Adverse Kidney Event), a composite outcome including mortality, kidney graft dysfunction and dialysis requirement at 180 days after inclusion. RESULTS: One hundred and twenty-four patients were included. The main cause of ICU admission was respiratory failure for 78 patients (62.9%). Predominant IST management was mycophenolic acid (MPA) discontinuation for 74 patients (59.7%) and calcineurin inhibitor (CNI) continuation for 63 patients (50.8%). By multivariable analysis, after adjustment for age, non-renal SOFA score at admission, kidney function at admission, sex, and history of cellular rejection we did not find any significant association between MAKE 180 and CNI discontinuation (adjusted OR = 1.05, 95% CI 0.87-1.26, p = 0.6). In contrast, MPA discontinuation was significantly associated with MAKE 180 (adjusted OR = 1.45, 95% CI 1.07-1.96, p = 0.018). No significant association was found between IST discontinuation and ICU-acquired infections (adjusted OR = 1.14, 95% CI 0.95-1.36, p = 0.157). Among ICU survivors, only 2 graft rejections occurred during the year following ICU discharge. CONCLUSION: This study is the first prospective investigation to suggest an association between MPA discontinuation and adverse outcomes during sepsis in critically-ill KTRs. These findings must be interpreted with caution given the potential confounding introduced by SARS-Cov-2-specific treatment protocols. Further interventional trials are necessary to optimize immunosuppressive drug strategies in KTRs during sepsis.