Daily Sepsis Research Analysis

Cardiac dysfunction is a serious complication of sepsis-induced multiorgan failure in intensive care units and is characterized by an uncontrolled immune response to overwhelming infection. Type 2 innate lymphoid cells (ILC2s), as a part of the innate immune system, play a crucial role in the inflammatory process of heterogeneous cardiac disorders. However, the role of ILC2 in regulating sepsis-induced cardiac dysfunction and its underlying mechanism remain unknown. The present study demonstrated that autophagic flux blockage exacerbated inflammatory response and cardiac dysfunction, which was associated with mortality of sepsis. Using a cecal ligation and puncture (CLP) mouse sepsis model, we observed an expansion of ILC2s in the septic heart. Furthermore, IL4 derived from ILC2 mitigated cardiac inflammatory responses and improved cardiac function during sepsis. Additionally, IL4 enhanced LAMP2 (lysosomal associated membrane protein 2) expression through STAT3 (signal transducer and activator of transcription 3) activation to stabilize lysosomal homeostasis and rescue the impaired autophagic flux during sepsis. Notably, LAMP2 was preferentially bound to FLOT2 (flotillin 2) after IL4 exposure, and the interaction enhanced autophagosome-lysosome fusion in cardiac endothelial cells. Loss of FLOT2 reversed the regulatory effects of LAMP2 on autophagy mediated by IL4, leading to autophagosome accumulation and suppressed autophagosome clearance. Conclusively, these findings provide novel insights that ILC2 regulates incomplete autophagic flux to protect septic heart and expand our understanding of immunoregulation for sepsis.

BACKGROUND: The incidence of sepsis with identified fungal pathogens is increasing and is associated with higher morbidity and mortality. Co-infection with fungal infections in COVID-19 patients is attracting clinical attention. This study examines the epidemiology, risk factors, and outcomes among sepsis patients with identified fungal pathogens. METHODS: We conducted a nationwide cohort study of adult patients with sepsis from the Korean Sepsis Alliance Database in South Korea between September 2019 and December 2021. We identified 407 patients with documented fungal pathogens, categorized according to the presence of hemato-oncologic malignancies. RESULTS: Of the 11,981 patients with sepsis, fungal pathogens were identified in 3.4% of cases. Among these patients, 38.3% had co-existing hematologic or solid organ cancer. Older age, higher clinical frailty scale scores, and underlying conditions, such as chronic kidney disease, cerebrovascular disease, and dementia, were more prevalent in patients without hemato-oncologic malignancies. The most common fungal pathogens were Candida albicans (47.9%), Candida glabrata (20.6%), and Candida tropicalis (13.5%). Only 6.6% of the patients with confirmed fungal pathogens received antifungal treatment. The presence of hemato-oncologic malignancies did not significantly affect patient outcomes. Factors associated with the presence of identified fungal pathogens included chronic kidney disease (Odds ratio [OR] 1.662; 95% confidence interval [CI] 1.216-2.273; p = 0.001), connective tissue disease (OR 1.885; 95% CI 1.058-3.358; p = 0.032), immunocompromised status (OR 2.284; 95% CI 2.186-3.753; p = 0.001), and invasive mechanical ventilation (OR 2.864; 95% CI 2.186-3.753; p < 0.001). CONCLUSIONS: Sepsis identified fungal pathogen are associated with chronic kidney disease, immunocompromised status and other risk factors, demonstrating the need for early detection, targeted management and improved antifungal strategies to improve patient outcomes.

BACKGROUND: Sepsis is a critical condition associated with high morbidity and mortality, emphasizing the need for reliable biomarkers for its diagnosis and prognosis. This study uses advanced immunological techniques to evaluate monocytic CD39 (mCD39) expression as a potential marker in sepsis. METHODS: This prospective observational cohort study included 206 participants from the First Affiliated Hospital, Zhejiang University School of Medicine between April 2022 and September 2023. Participants were categorized into four groups: healthy donors, patients with mild infections, post-cardiac surgery patients (non-infectious inflammation), and sepsis patients. Peripheral Blood Mononuclear Cells were analyzed using mass cytometry time-of-flight (CyTOF) with a 42-marker immune panel and flow cytometry targeting monocytes. Statistical analyses included ROC curves for diagnostic and prognostic performance and Kaplan-Meier survival analysis for prognostic evaluation. RESULTS: Sepsis patients exhibited significantly lower monocytic CD39 expression than mild infection and post-surgery groups (p < 0.05). The diagnostic performance analysis revealed that mCD39 effectively distinguished sepsis from mild infection (AUC = 0.877) and non-infectious inflammation (AUC = 0.935). Prognostic analysis identified low mCD39 expression as a strong predictor of short-term survival, with a 7-day survival AUC of 0.85 (p = 0.037). Kaplan-Meier analysis showed that sepsis patients with low mCD39 expression had significantly lower 28-day survival rates (56.7% vs. 80.6%, p = 0.016). CONCLUSIONS: Low CD39 expression on monocytes might serve as a potential diagnostic biomarker and a strong predictor of poor prognosis in sepsis patients.