Postoperative delirium (POD) is a frequent neuropsychiatric complication after cardiac surgery, yet the biological basis of individual susceptibility remains unclear. In this prospective cohort study, 317 adults undergoing elective on-pump cardiac surgery were enrolled and followed for POD during the first 7 postoperative days. Thirty patients who developed POD were then matched 1:1 with 30 non-POD controls by age, sex, and primary diagnosis for multi-omic analyses. Preoperative fecal samples were collected from the first bowel movement after admission and before prophylactic antibiotic administration, and postoperative fecal samples were collected from the first postoperative bowel movement. Paired fecal samples underwent shotgun metagenomic sequencing, and perioperative serum samples underwent untargeted metabolomic profiling. Preoperatively, α- and β-diversity were comparable between groups, but patients who subsequently developed POD exhibited a less connected and less integrated microbial network structure. Postoperatively, gut microbial composition differed significantly between groups (PERMANOVA R[2] = 0.053, P < 0.001). Metagenomic profiling identified 35 differentially abundant species and 16 differentially enriched KEGG level 3 pathways, with POD-associated features showing inferred functional shifts toward amino-acid catabolism, including branched-chain amino acid (BCAA)-related pathways. Untargeted metabolomics demonstrated marked perioperative remodeling in both groups, but POD was associated with a 27-metabolite panel characterized predominantly by lower postoperative levels or impaired recovery, with pathway enrichment converging on valine, leucine, and isoleucine metabolism. Integrative analyses further linked POD-associated microbial taxa with amino-acid catabolic pathways and lower levels of BCAA-related serum metabolites. These findings suggest that POD is associated with preoperative alterations in microbial network organization and a postoperative microbiome-metabolome disturbance pattern centered on amino-acid metabolism, particularly the BCAA axis.

Background/Objectives: Radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) is associated with high morbidity. Frailty is an important determinant of surgical outcomes; however, its association with the composite outcome Days Alive and Out of Hospital (DAOH) has not been examined following RC. We assessed the impact of preoperative frailty on 90-day DAOH in older patients undergoing RC for MIBC. Methods: We conducted a retrospective cohort study including 408 consecutive patients aged ≥65 years undergoing RC at a tertiary referral center between 2018 and 2023. Frailty was assessed using the record-based Multidimensional Prognostic Index (r-MPI), classifying patients as non-frail (MPI1), moderately frail (MPI2), or severely frail (MPI3). The primary outcome was 90-day DAOH; secondary outcomes included length of stay (LOS), postoperative complications, delirium, and mortality. DAOH was dichotomized at the cohort median. Associations with low DAOH were analyzed using modified Poisson regression with robust variance estimation. Results: Median 90-day DAOH decreased progressively with increasing frailty: MPI1: 81 days (IQR 76-83), MPI2: 73 days (IQR 62-80), MPI3: 67 days (IQR 52-76); p < 0.01. In multivariable analysis, frailty was independently associated with low DAOH (MPI2: RR 2.46, 95% CI 1.94-3.11; MPI3: RR 3.37, 95% CI 2.55-4.46), whereas age and comorbidity were not. Increasing frailty was consistently linked to worse postoperative outcomes, including longer LOS, higher complication burden and severity, and more frequent delirium. Ninety-day postoperative complication-related mortality increased markedly with frailty (MPI1: 1.6%, MPI2: 11.9%, MPI3: 12.1%; p < 0.01). Conclusions: Preoperative frailty is a strong independent predictor of low 90-day DAOH and adverse postoperative outcomes following RC in older patients.

Acute respiratory distress syndrome (ARDS) is characterized by systemic inflammation, immune dysregulation, oxidative stress, and frequent extrapulmonary organ involvement. Neurological complications of ARDS, such as neuroinflammation, cognitive impairment and delirium, are common and worsen outcomes. Early evidence highlights bidirectional communication between the lungs and brain, the lung-brain axis, through which inflammation may amplify both pulmonary and cerebral injury. This narrative review synthesizes recent experimental and clinical data on the immunomodulatory and neuroprotective effects of commonly used sedative agents in ARDS, focusing on their influence on inflammatory mediators (IL-1β, IL-6, IL-8, IL-10, TNF-α) and neuronal injury biomarkers (S100B, neuron-specific enolase). Sedative agents seem to exert effects beyond sedation by modulating systemic and neuroinflammatory responses. Evidence suggests they can influence cytokine profiles and reduce biomarkers associated with neuronal injury, potentially mitigating neuroinflammation and delirium in ARDS patients. Sedatives may modulate lung-brain crosstalk in ARDS through immunoinflammatory pathways, integrating sedative and neuroprotective effects. Mechanistic clarification may enable targeted sedation strategies to improve pulmonary and neurological outcomes.

Bundibugyo virus disease (BVD) remains a high-consequence threat in Eastern and Central Africa, where cross-border mobility, nonspecific early symptoms, and delayed recognition can obscure transmission. In this case report, we describe Uganda's 2026 BVD index case: a male patient who traveled from the Democratic Republic of the Congo to Uganda and was admitted to a private hospital in Kampala on 11 May 2026 after more than two weeks of vomiting and diarrhea, with epigastric pain, weakness, and hiccups. He deteriorated rapidly, developing acute kidney injury, pulmonary edema, hepatic dysfunction, hypoxemia, delirium, atrial flutter, possible disseminated intravascular coagulation, and multiorgan failure, and died on 14 May. A posthumous EDTA whole-blood specimen tested at the Central Emergency Response and Surveillance Laboratory was positive for orthoebolavirus RNA and confirmed as Bundibugyo virus (BDBV) by RT-qPCR. Sequencing achieved 99% genome coverage at ≥100× depth. The 2026 BDBV genome formed a distinct lineage approximately equidistant from the 2007-2008 Butalya and 2012 Isiro variants, differing by 216-227 nucleotides (~1.2% sequence divergence). Here, we demonstrate the value of fatality surveillance, private-sector surveillance, diagnostic optimization through national specimen referral, and rapid molecular-genomic diagnostics for early detection, transmission chain interruption, and public health response coordination.