Daily Sepsis Research Analysis

Sepsis-induced skeletal muscle atrophy is common in septic patients with the increases risk of mortality and is associated with myocellular mitochondrial dysfunction. Nevertheless, the specific mechanism of sepsis muscle atrophy remains unclear. Here we conducted a clinical retrospective analysis and observed the elevation of skeletal muscle index (ΔSMI) was an independent risk factor for 60-day mortality in septic patients. Moreover, in mouse model of sepsis, the skeletal muscle atrophy was also observed, which was associated with the upregulation of S100a8/a9-mediated mitochondrial dysfunction. Inhibition of S100a8/a9 significantly improved mitochondrial function and alleviated muscle atrophy. Conversely, administration of recombinant S100a8/a9 protein exacerbated mitochondrial energy exhaustion and myocyte atrophy. Mechanistically, S100a8/a9 binding to RAGE induced Drp1 phosphorylation and mitochondrial fragmentation, resulting in muscle atrophy. Additionally, RAGE ablation or administration of Drp1 inhibitor significantly reduced Drp1-mediated mitochondrial fission, improved mitochondrial morphology and function. Our findings indicated the pivotal role of S100a8/a9 in driving the mitochondrial fragmentation in septic muscle atrophy. Targeting S100a8/a9-RAGE-initiated mitochondrial fission might offer a promising therapeutic intervention against septic muscle atrophy.

BACKGROUND: Infections are among the top causes of neonatal mortality, particularly in low-income and middle-income countries. We aimed to describe the clinical characteristics of neonates diagnosed with culture-confirmed bloodstream infections at six lower-tier hospitals in South Africa. METHODS: We did a cross-sectional study of culture-confirmed bloodstream infections among neonates (aged 0-27 days) at six lower-tier hospitals in South Africa. Clinical, demographic, and pathogen data from sick, hospitalised neonates were analysed and bloodstream infections were categorised as early-onset sepsis (EOS; 0-2 days of life) or late-onset sepsis (LOS; 3-27 days of life). Incidence of bloodstream infection and crude in-hospital mortality in neonates with bloodstream infection were calculated and factors associated with death were analysed using multivariable logistic regression models. FINDINGS: From Oct 1, 2019 to Sept 30, 2020, we identified 907 neonatal bloodstream infection episodes. Incidence was 6·4 cases per 1000 patient-days. Most neonates were preterm (median gestation 33 weeks [IQR 29-37]), with 30·5% (n=277) of bloodstream infections classified as EOS and 69·5% (n=630) as LOS. Gram-negative pathogens dominated (63·2% [n=573]), including Klebsiella pneumoniae (25·7% [n=233]) and Acinetobacter baumannii (19·2% [n=174]). Crude in-hospital mortality in neonates with bloodstream infection was 25·5% (n=231), accounting for 21·4% (231 of 1078 cases) of all in-hospital neonatal deaths. Increased all-cause mortality was associated with Gram-negative bloodstream infection (vs Gram-positive pathogens, adjusted odds ratio 3·70 [95% CI 1·46-9·39]; p=0·0059), inborn LOS (vs EOS, 2·42 [1·11-5·29]; p=0·027), preterm birth (5·00 [2·16-11·59]; p=0·0002), and neonatal intensive care unit admission (3·26 [1·51-7·03]; p=0·0026). INTERPRETATION: Hospitalised, preterm neonates who developed Gram-negative bloodstream infections had high in-hospital mortality. Many small vulnerable newborns require prolonged stays in lower-tier hospitals and acquire life-threatening bloodstream infection; appropriate resources are needed at this level of care to prevent infections and save lives. FUNDING: Bill & Melinda Gates Foundation.

INTRODUCTION: Sepsis and septic shock are associated with microcirculatory dysfunction, significantly impacting patient outcomes. This study aimed to evaluate the effects of a 20 % albumin bolus on microcirculation compared to crystalloid resuscitation in fluid-responsive patients (ClinicalTrials.govID:NCT05357339). METHODS: We conducted a single-centre randomised controlled trial, enrolling 103 patients (Albumin n = 52, Control n = 51). Fluid responsiveness was assessed, and fluid was administered in boluses of 100 ml to clinical effect. Microcirculation was measured using the Side stream Dark Field camera and AVA 4.3 software. Baseline characteristics, macrohaemodynamics, and microcirculation parameters were recorded. Three patients were excluded from analysis. RESULTS: The final cohort comprised 100 patients, 35 (35 %) females with a mean age of 58 years (range: 18-86). The mean APACHE score was 28 (range: 7-45), and the mean SOFA score was 9.4 (range: 1-17). No significant differences in APACHE (26.24 vs. 29.4, p = 0.069) or SOFA (9.08 vs. 9.78, p = 0.32) scores were found for albumin and control group respectively. The albumin group had worse microcirculation at baseline but demonstrated significant improvements in microvascular density and activity at 15 min and 60 min (p < 0.005), while the control group exhibited no significant changes. Additionally, both groups were fluid responsive, with a mean pulse pressure variability of 17 % at admission. There were no significant differences in overall fluid balances, vasopressor days, length of ICU stay, or mortality between groups. CONCLUSION: This study demonstrates that a 20 % albumin bolus significantly enhances microcirculation in fluid-responsive patients with septic shock. These findings underscore the potential benefits of targeted microcirculation therapy in critically ill patients.