Daily Sepsis Research Analysis

Neonates primarily rely on innate immune defense, yet their inflammatory responses are usually restricted compared to adults. This is controversially interpreted as a sign of immaturity or essential programming, increasing or decreasing the risk of sepsis, respectively. Here, combined transcriptomic, metabolic, and immunological studies in monocytes of healthy individuals reveal an inverse ontogenetic shift in metabolic pathway activities with increasing age. Neonatal monocytes are characterized by enhanced oxidative phosphorylation supporting ongoing myeloid differentiation. This phenotype is gradually replaced during early childhood by increasing glycolytic activity fueling the inflammatory responsiveness. Microbial stimulation shifts neonatal monocytes to an adult-like metabolism, whereas ketogenic diet in adults mimicking neonatal ketosis cannot revive a neonate-like metabolism. Our findings disclose hallmarks of innate immunometabolism during healthy postnatal immune adaptation and suggest that premature activation of glycolysis in neonates might increase their risk of sepsis by impairing myeloid differentiation and promoting hyperinflammation.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a frequent and life-threatening complication of cirrhosis, contributing to considerable morbidity and mortality. METHODS: A cross-sectional derivation study was conducted to assess the diagnostic accuracy of two sepsis-related calcitonin peptide family biomarkers, mid-regional pro-adrenomedullin (MR-pro-ADM) and procalcitonin, in ascitic fluid for identifying bacteriologically confirmed SBP (BC-SBP). In a subsequent validation study, the diagnostic performance of the 'SBP score' was evaluated in an independent patient cohort using an absolute polymorphonuclear (PMN) leukocyte count threshold of ≥250 cells/mm RESULTS: In the derivation study, the concentration of MR-pro-ADM in ascitic fluid was significantly higher in patients with BC-SBP compared to those without BC-SBP (3.14 nmol/L [IQR, 2.39-6.74] vs. 1.91 nmol/L [IQR, 1.33-2.80]; p = .0002). Bayesian ANOVA indicated that MR-pro-ADM was highly discriminative for diagnosing BC-SBP, with a substantial Bayes factor (BFM = 2505), whereas procalcitonin exhibited poor discriminatory performance. Receiver-operating characteristic (ROC) analysis identified an optimal MR-pro-ADM cut-off of ≥2.50 nmol/L for diagnosing BC-SBP, with an area under the ROC curve (AUROC) of 0.746 (95% CI, 0.685-0.801; p < .0001). Multivariable logistic regression identified three independent predictors of BC-SBP, which were subsequently incorporated into the 'SBP score' (MR-pro-ADM ≥2.5 nmol/L, absolute PMN count ≥250 cells/mm CONCLUSION: MR-pro-ADM in ascitic fluid emerges as a promising biomarker for SBP diagnosis. Combining MR-pro-ADM with absolute PMN count and Child-Pugh score in the 'SBP score' greatly improves the diagnostic accuracy of SBP.

BACKGROUND: Ultrasound-guided fluid management is increasingly used in the intensive care unit, yet it's benefits in septic shock remains unknown. OBJECTIVE: To evaluate the use of critical care ultrasound for individualized volume management in septic shock patients. METHODS: A single-center, randomized controlled, prospective study was conducted on patients with septic shock admitted to the intensive care unit in Xi'an Daxing Hospital, Xi'an City, China, from September 2022 to December 2023. Upon intensive care unit admission, the patients were resuscitated according to the latest sepsis and septic shock guidelines and early goal-directed therapy. The study group additionally underwent critical care ultrasound examination to monitor and guide the adjustment of fluid resuscitation in real-time. The two groups' physiological and biochemical indexes and prognoses were compared before (T0) and 6 hours after (T6) fluid resuscitation. RESULTS: A total of 113 patients with septic shock were selected and randomly allocated into study (n = 57) and control (n = 56) groups. The central venous oxygen saturation, heart rate, mean arterial pressure, blood lactate, and lactate clearance rate of the two groups at T6 were significantly improved compared to T0 (P < .05). At T6, the study group's blood lactate was significantly lower and the lactate clearance was significantly higher than the control group (P < .05). At T6, the incidence of pulmonary edema, incidence of left heart failure, Sequential Organ Failure Assessment (SOFA) score and length of the intensive care unit hospitalization in the study group were significantly lower than the control group (P < .05). CONCLUSION: The application of critical care ultrasound improved the outcome and helped guide individualized management of patients with septic shock.