Sepsis, September 2026 edition

The prospective multicenter PROGRESS randomized trial enrolled 1,373 patients with suspected sepsis and compared droplet digital PCR with standard care. Pathogen-detection positivity was substantially higher with droplet digital PCR than with standard care, at 54.1% versus 21.6%. The study directly evaluated a molecular strategy intended to improve pathogen identification and support more targeted antimicrobial management.

Impact: This is a practice-oriented randomized multicenter study addressing a major diagnostic gap in sepsis. Its large sample and direct standard-care comparator make the findings highly relevant to antimicrobial refinement, although full patient-outcome and implementation results remain necessary.

Clinical Implications: Droplet digital PCR may enable faster and more sensitive pathogen detection, potentially supporting earlier antimicrobial refinement and de-escalation. Routine adoption should await evidence on turnaround time, antibiotic exposure, mortality, cost-effectiveness, pathogen-specific performance, and laboratory feasibility.

This translational study used spatial metabolomics and proteomics to map kidney injury during sepsis and identified increased ARG2 expression in renal tubular cells and macrophages. Pharmacologic ARG2 inhibition and renal tubule-specific knockdown reduced tubular lipid accumulation, improved real-time glomerular filtration rate, and lowered blood urea nitrogen, with restoration of PPARγ signaling implicated as a mechanism. Primary-cell and human kidney organoid experiments provided additional support.

Impact: The paper advances sepsis-associated acute kidney injury research from descriptive injury markers toward a spatially defined metabolic mechanism and a pharmacologically tractable target. Its integration of multi-omics, genetic and pharmacologic intervention, cellular experiments, and human organoids strengthens translational credibility.

Clinical Implications: ARG2 inhibition could eventually help prevent or treat sepsis-associated acute kidney injury, but the therapeutic window, tissue selectivity, effects on systemic arginine metabolism and host defense, and long-term safety remain unknown. Validation in clinically relevant models is required before human trials.

In a prospective cohort of mother-neonate pairs, nearly half of evaluable neonates became colonized with ESBL-producing Klebsiella pneumoniae. Whole-genome sequencing and transmission modeling implicated ward surfaces, particularly sinks and oxygen-delivery equipment, as major reservoirs, with additional contributions from cots, maternal hands, and other neonates. Most invasive isolates clustered genetically with stool or environmental isolates.

Impact: This study directly connected clinical, environmental, and invasive isolates using genomic epidemiology and translated the findings into specific, actionable infection-control targets in a resource-constrained neonatal unit.

Clinical Implications: Neonatal units should prioritize decontamination of sinks and ward surfaces, stool containment, cot cleaning, maternal hand hygiene, and dedicated or single-use oxygen-delivery equipment. Implementation studies are still needed to determine whether these measures reduce invasive infection and mortality.

Using human sepsis samples, murine peritonitis, endothelial heparanase deletion, and human pulmonary endothelial cells, this study identified a cell-free hemoglobin–heparanase pathway that drives endothelial glycocalyx degradation and inflammation. Oxidized cell-free hemoglobin increased heparanase expression and activation, whereas endothelial heparanase deletion or attenuation of hemoglobin oxidation reduced glycocalyx injury and inflammatory effects.

Impact: The study provides convergent human, animal, genetic, and cellular evidence linking hemolysis-related cell-free hemoglobin to endothelial barrier failure and identifies a plausible therapeutic axis.

Clinical Implications: Reducing oxidized cell-free hemoglobin or inhibiting endothelial heparanase could potentially preserve the glycocalyx and reduce organ injury. Translation requires biomarker validation, clinically relevant dosing studies, safety assessment, and testing after sepsis has developed.

Using patient samples, septic mouse models, macrophage-specific depletion, and viral rescue, this study identified LAPTM5 as a regulator of macrophage autophagic homeostasis. LAPTM5 scaffolds PGAM5 and VAMP8, promotes VAMP8 dephosphorylation and autophagosome-lysosome fusion, clears damaged mitochondria, and reduces oxidative stress and inflammatory lung injury.

Impact: The study provides a coherent cell-specific mechanism explaining how defective macrophage autophagy amplifies septic acute lung injury and identifies LAPTM5 as a potentially actionable target.

Clinical Implications: LAPTM5 expression and the associated autophagy pathway may eventually support risk stratification or targeted therapy for septic acute lung injury. The findings remain preclinical and do not currently justify changes to standard sepsis or acute lung injury management.