Daily Sepsis Research Analysis

OBJECTIVES: We evaluated the Phoenix criteria and the Phoenix Sepsis Score in a multicenter retrospective cohort of critically ill children with a clinical diagnosis of sepsis or septic shock in Bolivia. In addition, we aimed to assess whether management in a PICU at high altitude in the Bolivian Andes was associated with the performance of the respiratory dysfunction component in the Phoenix Sepsis Score. DESIGN: Multicenter retrospective cohort study. SETTING: Fourteen PICUs in Bolivia. PATIENTS: Children admitted to the PICU with a clinical diagnosis of sepsis or septic shock from January 2023 to December 2023. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 273 patients with a diagnosis of sepsis in 2023, of which 257 (94.1%) met the 2024 Phoenix criteria for sepsis, and 166 (60.8%) met the systemic inflammatory response syndrome (SIRS)-based criteria for sepsis. Among the 257 patients meeting Phoenix sepsis criteria, 86 died (33.5%). Of the patients with Phoenix-based sepsis, there were 100 of 257 (38.9%) who were SIRS-negative, and 27 of 100 died (27.0%). After correcting the oxygenation indices for altitude, 149 of 273 patients (54.6%) had a lower Phoenix respiratory score and an associated mortality more consistent with the expected mortality of the newly derived subscore. Patients at higher altitudes had higher hemoglobin levels and higher estimated oxygen carrying capacity, and these data were independently associated with lower odds of mortality after controlling for altitude-corrected Phoenix score. CONCLUSIONS: In this 2023, retrospective cohort of PICU patients with sepsis in Bolivia, we have found that the majority met the 2024 Phoenix sepsis criteria, but less than two-thirds met the SIRS-based criteria for diagnosis. However, the respiratory score in the Phoenix criteria overestimated the severity of respiratory dysfunction in more than half of the cohort, likely because the score does not take account of the Andean adaptation to high altitude, with higher oxygen carrying capacity.

BACKGROUND: Sepsis is a systemic inflammatory response syndrome triggered by infection, often accompanied by severe coagulopathy, leading to high mortality. Tissue factor (TF) plays a pivotal role in sepsis by promoting both coagulation and inflammation. Recently, TREM2 (Triggering Receptor Expressed on Myeloid cells 2) has emerged as a key regulator of macrophage function, but its specific role in sepsis remains unclear. METHODS: An in vitro sepsis model was established by stimulating RAW264.7 cells with 10 μg/mL lipopolysaccharide (LPS) for 6 h, with four groups: Negative Control (NC), NC + LPS, TREM2, and TREM2 + LPS. Inflammatory cytokines and coagulation factors were measured in each group. Cells in the TREM2 and TREM2 + LPS groups were pretreated with TREM2 overexpression plasmid for 48 h. In vivo, mice were assigned to Sham, TREM2, Cecal Ligation and Puncture (CLP), CLP + NC, and CLP + TREM2 groups. Mice in the NC group received macrophages via tail vein injection, while those in the TREM2 and CLP + TREM2 groups received TREM2-overexpressing macrophages. Lung tissue and plasma samples were collected to assess inflammatory cytokines, coagulation factors, and signaling pathway activity. RESULTS: TREM2 overexpression significantly improved survival, reduced lung inflammation, and alleviated coagulopathy in mice. It increased platelet counts and reduced fibrin deposition. Furthermore, TREM2 inhibited TF release from macrophages by suppressing aberrant activation of the AKT-mTOR signaling pathway, thereby modulating the macrophage inflammatory response. CONCLUSIONS: TREM2 plays a crucial protective role in sepsis-associated coagulopathy, suggesting that it could serve as a potential therapeutic target, providing novel strategies to improve clinical outcomes in sepsis patients.

INTRODUCTION: Despite global surveillance efforts, antibiotic resistance (ABR) is difficult to address in low- and middle-income countries (LMICs). In the absence of country-wide ABR surveillance data, peer-reviewed literature is the next most significant source of publicly available ABR data. Médecins Sans Frontières conducted this review in hopes of using the pooled findings to inform treatment choices in the studied countries where sufficient local ABR data are unavailable. METHODS: A systematic literature review reporting ABR rates for six infection sites in nine countries in the Middle East and Southern Asia was conducted. PubMed was used to identify literature published between January 2012 and August 2022. A meta-analysis of the included studies ( RESULTS: This paper focuses on sepsis, burns and wound infections, specifically, with the largest number of papers describing data from Iran, Türkiye and Pakistan. High (>30%) resistance to recommended first-line antibiotics was found. Gram-negative resistance to ceftriaxone, aminoglycosides and carbapenems was high in burn-related infections; colistin resistance among CONCLUSIONS: High-quality data on ABR in LMIC settings remain difficult to obtain. While peer-reviewed literature is a source of publicly available ABR data, it is of inconsistent quality; the field also lacks agreed reporting standards, limiting the capacity to pool findings. Nonetheless, high resistance to first-line antibiotics underscores the need for improved localized surveillance and stewardship.