Sepsis-associated encephalopathy (SAE) is a common brain dysfunction, which results in severe cognitive and neurological sequelae and an increased mortality rate in patients with sepsis. Depending on the stimulus, microglia (resident macrophages in the brain that are involved in SAE pathology and physiology) can adopt two polarization states (M1/M2), corresponding to altered microglial morphology, gene expression, and function. We systematically described the pathogenesis, morphology, function, and phenotype of microglial activation in SAE and demonstrated that microglia are closely related to SAE occurrence and development, and concomitant cognitive impairment. Finally, some potential therapeutic approaches that can prime microglia and neuroinflammation toward the beneficial restorative microglial phenotype in SAE were outlined.

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) produces unwanted side-effects that are mainly caused by chemotherapeutic drugs in the treatment of gastrointestinal (GI) cancers, and these effects have not been systematically summarized. The aim of this article was to provide a comprehensive overview of the side-effects of HIPEC for GI cancers and propose practical strategies for adverse event management. Methodology: PubMed, Web of Science, and the Cochrane Library were systematically searched for side-effects of HIPEC in GI cancers prior to October 20, 2022. A total of 79 articles were included in this review. Results: Adverse events, such as enterocutaneous digestive fistulas, GI tract perforation, neutropenia, postoperative bleeding, ventricular tachycardia, hyperglycemia, hypocalcemia, renal impairment, encapsulating peritoneal sclerosis, scrotal ulceration, and sarcopenia were described, and their clinical management was discussed. These side-effects involve the digestive, hematopoietic, circulatory, metabolic, and urinary systems. Effective methods for adverse event management included an expert multidisciplinary team, replacing chemotherapy drugs, using Chinese medicine, and careful preoperative assessments. Conclusion: The side-effects of HIPEC are frequent and can be minimized by several effective methods. This study proposes practical strategies for adverse event management of HIPEC to assist physicians in choosing the optimal treatment method.

Sepsis-associated encephalopathy (SAE) is a common brain dysfunction following sepsis that often results in severe cognitive and neurological sequelae and increases the mortality rate in patients with sepsis. Microglia are resident macrophages in the brain that play essential roles in the pathological and physiological processes of SAE. Depending on the nature of the stimulus, microglia can adopt two polarization states (M1/M2), which correspond to altered microglial morphology, gene expression, and function. Therefore, we systematically described the pathogenesis, morphology, function, and phenotype of microglial activation in SAE. We demonstrated that microglia are closely related to occurrence and development of SAE and concomitant cognitive impairement. Finally, we outlined some potential therapeutic approaches that can prime microglia and neuroinflammation towards the beneficial restorative microglial phenotype in SAE.

Background: Sepsis disrupts intestinal microbiota, and broad‐spectrum antibiotics may worsen dysbiosis. Clostridioides difficile ( C. difficile ) infection (CDI) is a prevalent nosocomial enteric pathogen among critically ill patients, yet its prognostic implications in sepsis remain inadequately studied. Methods: We retrospectively analyzed 13,484 adult sepsis hospitalizations from MIMIC‐IV. The exposure was any laboratory‐detected C. difficile‐positive stool test during the index hospitalization. Cox regression, detailed early‐antibiotic adjustment, stabilized inverse probability weighting, timing‐ and assay‐based sensitivity analyses, and a post hoc nested‐model comparison assessed association and incremental prediction. Archived positive‐subgroup machine‐learning models were retained as exploratory risk‐stratification analyses. Results: Detailed early‐antibiotic adjustment substantially attenuated the association: the 30‐day hazard ratio (HR) was 0.98 (95% CI, 0.87–1.11; p = 0.767) and the 90‐day HR was 1.08 (95% CI, 0.99–1.18; p = 0.103). Early, landmark, PCR‐only, and toxin‐positive analyses were also nonsignificant, whereas the stabilized‐weighted 90‐day estimate remained modest (HR, 1.13; 95% CI, 1.03–1.24; p = 0.010), indicating inconsistency across analyses. Predictive models showed strong performance (C‐index: 0.81 for in‐hospital mortality; 0.68 for 30‐day mortality). Conclusions: While laboratory‐detected C. difficile stool‐test positivity is associated with worse unadjusted outcomes in sepsis, this relationship is substantially attenuated and inconsistent after rigorous adjustment. Accordingly, laboratory positivity may serve as a marker of a complex clinical phenotype. Evidence for its independent prognostic utility remains limited, and its incremental predictive value beyond conventional severity measures is minimal.