Daily Sepsis Research Analysis

Septic cardiomyopathy (SC) is a severe complication of sepsis that significantly increases patient mortality. The onset of SC is associated with excessive reactive oxygen species (ROS), leading to increased oxidative stress and iron accumulation. Herein, we develop a library of conductive polypyrrole-polythiophene copolymer (PPy-co-PTh)-stabilized nanozymes by coordinating different metal ions within the copolymer framework. From this library, we identify a PPy-co-PTh stabilized ruthenium-based nanozyme (Ruzyme), which exhibits significant catalase- and superoxide dismutase-like activity, as well as nitrogen radical scavenging capability. Modifying the conductive interface significantly improves the catalytic activity and stability of the Ruzyme by lowering the catalytic energy barrier, reducing excessive oxidation caused by ROS, and facilitating the continuous decomposition of ROS. To achieve precise targeted delivery to myocardial mitochondria, (5-carboxypentyl) triphenyl phosphonium bromide  (TPP-COOH) and a cardiac-targeting peptide (CTP) are conjugated onto the surface of the Ruzyme. In vitro, the stabilized nanozymes effectively scavenge ROS, reduce iron accumulation, and inhibit iron-dependent cell death, thereby lowering lipid peroxidation. In male SC mice, they improve cardiac function, demonstrating therapeutic benefits. Given the growing interest in nanozymes for cardiovascular diseases, this study provides a potential foundation for the development of therapeutic agents for severe cardiomyopathy and related conditions.

BACKGROUND: In the ICU, distinguishing immune-mediated thrombotic thrombocytopenic purpura (iTTP) from sepsis-associated thrombotic microangiopathy (TMA) is time-critical. We tested whether serial ADAMTS-13 combined with targeted coagulation and inflammation markers improves iTTP risk stratification in a Sepsis-3 ICU cohort and whether a pragmatic rule-out is feasible. METHODS: Prospective single-center study of adults meeting Sepsis-3 with thrombocytopenia and schistocytes ≥ 1% or LDH > 2× ULN within 24 h of ICU admission. ADAMTS-13 activity and VWF: Ag were assayed at 0/24/48/72 h alongside a thrombo-inflammatory panel. We derived a Dynamic ADAMTS-13 Index (DAI), a Coagulation Consumption Index (CCI) anchored to ISTH DIC and fibrinogen/antithrombin III, and an Inflammation Index (IL-6/HBP). The prespecified main rule-out required a ≥ 15% ADAMTS-13 rise by 48 h plus low CCI. A prespecified RCV-anchored sensitivity analysis required ≥ 35% relative rise or ≥ 10 absolute % points plus low consumption. For decision-making, pre-treatment (pre-plasma exchange, PEx) analyses are emphasized. Intent-to-diagnose (care-embedded) analyses are exploratory, and internal validation used a bootstrap optimism correction. RESULTS: Of 1,274 screened, 330 were included (iTTP = 34). Discrimination improved from baseline ADAMTS-13 (AUROC 0.78) to DAI (0.93), with smaller gains after adding CCI (0.95) and the Inflammation Index (0.96). With the main rule-out (≥ 15% + low CCI) in the intent-to-diagnose analysis, sensitivity was 97.1%, specificity was 86.1%, and NPV was 99.6%. The RCV-anchored sensitivity analysis preserved 100.0% sensitivity and NPV with 76.0% specificity. A 72-h phenotype (ADAMTS-13 < 10% with high IL-6/HBP) was associated with higher 28-day mortality (adjusted HR 2.6). CONCLUSIONS: In Sepsis-3 ICU patients with TMA features, serial ADAMTS-13 testing, along with targeted coagulation/inflammation markers, enhances early iTTP risk stratification and supports a pragmatic rule-out framework. External validation and implementation studies remain essential. These findings also support investment in rapid/automated ADAMTS-13 activity assays and decision-support workflows to enable timely adoption beyond tertiary centers.

BACKGROUND: Bloodstream infection (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) is a serious and urgent threat for hospitalized patients. This study aims to describe the clinical and molecular characteristics of CRKP causing BSI in a tertiary care hospital in Chengdu, China. METHODS: In total, 123 nonconsecutive CRKP strains were collected in the hospital from 2020 to 2022 and sent for whole genome sequencing. String tests were performed of all CRKP strains, and clinical information of relevant cases was collected. RESULTS: Among the 123 CRKP strains collected, the median age of the patients was 53 years, 77.2% of patients with CRKP BSI were elderly men, 62.6% were admitted to the intensive care unit, 80.5% underwent intravascular catheters procedures, and 86.7% had underlying lung diseases. The rate of 30-day mortality was 21.1%. Microbiological characteristics showed that carbapenem resistance was primarily mediated by carbapenemase acquisition, predominantly blaKPC-2 (93.5%). The 123 CRKP isolates comprised 9 sequence types (STs) and 10 serotypes, with ST11 being dominant (84.6%). The serotype KL64 accounted for 73.2%, followed by KL47 at 7.3%. The positive rate of the string test was 13.8%, and virulence genes (rmpA2, iuc-iutA) were detected in 48.8% of ST11-KL64 strains. Phylogenetic analysis indicated that most ST11 strains were closely related. Genomic transmission analyses revealed that 6.7% of pairs had ≤20 pairwise single-nucleotide polymorphisms and were thus designated as "highly likely" transmission. CONCLUSIONS: This study poses an urgent need for enhancing infection control measures in the hospital, especially CRKP strains with hypervirulent genes.