Daily Sepsis Research Analysis

To evaluate the interchangeability of cardiac output (CO) monitoring devices compared to reference methods in adult ICU patients with septic shock, we systematically searched electronic databases through January 2025 for prospective studies comparing CO monitors with pulmonary artery catheter (PAC), transpulmonary thermodilution (TPTD), or echocardiography. Eligible studies included Bland-Altman analysis and, when available, trending assessment via polar or 4-quadrant plots, precision, and time response.  Agreement was defined as percentage error (PE) < 30%, and acceptable trending as concordance ≥ 90%. Pooled bias, limits of agreement (LoA), and PE were calculated using the Sidik-Jonkman random-effects model. Twenty-six studies were included, yielding 37 unique device-reference datasets and encompassing 1,323 patients. PAC was the most common reference (18 datasets), followed by TPTD (16) and echocardiography (3). The pooled bias was 0.15 L min⁻¹ with LoA of ± 3.45 L min⁻¹ and pooled PE of 49%. Calibrated pulse contour analysis (PCA) showed the best agreement (PE 25%), whereas uncalibrated PCA, thoracic electrical bioimpedance, and bioreactance demonstrated poor agreement (PE ≥ 52%). Heterogeneity for mean bias was high across all subgroups (I² >80%). Of 15 datasets reporting trending, only three achieved concordance ≥ 90%. Most CO monitors demonstrate poor agreement with reference methods in septic shock. However, their true clinical utility remains unclear, as usual validation frameworks-centered on Bland-Altman analysis-overlook metrics that matter most to intensivists. Precision, time response, and trending ability are critical for real-time decision-making but were rarely assessed. Future studies must incorporate these parameters to meaningfully evaluate device performance at the bedside. PROSPERO registration: CRD42024509384.

Cationic polymers have emerged as promising next-generation antimicrobial agents, albeit with inherent limitations such as low potency and limited biocompatibility. Classical cationic polymers kill bacteria via physical membrane disruption. We propose a non-classical mechanism of crossing the bacterial plasma membrane barrier, a step required for subsequent inhibition of intracellular targets, by cationic polymers which are carbon acids. Oligoimidazolium (OIM) carbon acids, instead of lysing bacteria, transiently deprotonate in water to form hydrophobic N-heterocyclic carbenes (NHCs) and exhibit efficient plasma membrane translocation. Only OIMs that are carbon acids have potent antibacterial activities against even colistin- and multidrug-resistant bacteria. OIM amide derivatives exhibit excellent antibacterial efficacy in murine sepsis and thigh infection models, while a polymeric version acts as a prophylactic agent against bovine mastitis, which is a global agricultural problem. This study unveils a promising path for the development of an alternative class of potent antimicrobial agents.

Elevated circulating lactate serves as a critical biomarker in sepsis, yet the epigenetic mechanisms by which lactate influences disease progression remain unclear. This study aims to identify lactate-associated genes in sepsis, decode their regulatory roles, and assess their potential as therapeutic targets. We performed transcriptome-wide bioinformatic analyses to identify lactylation-related differentially expressed genes (DEGs) between sepsis patients and healthy controls. Pathway enrichment highlighted immune signaling circuits. Five DEGs (ZC3H4, RBM10, PCBP2, RBM25, HNRNPM) were prioritized via ROC analysis, and their combined expression formed a prognostic signature with strong predictive power (AUC > 0.85). Validation in murine sepsis-induced acute lung injury (ALI) models (cecal ligation-puncture and LPS challenge) confirmed significant upregulation of these five genes by qRT-PCR. RBM25 was selected for deeper functional study. Mechanistic assays implicate an RBM25-Acly axis that couples altered metabolism to histone lactylation and transcriptional reprogramming. Notably, we propose the RBM25-Acly axis that couples altered metabolism to histone lactylation and transcriptional reprogramming. Our work uncovers a novel metabolic-epigenetic circuit in sepsis driven by lactylation, with RBM25 and its regulation of ACLY as a key node. The lactylation-based gene signature offers a high-fidelity prognostic tool, and targeting the RBM25-Acly pathway may open new therapeutic avenues. These findings lay a foundation for precision interventions that integrate metabolic and epigenetic strategies in sepsis care.