Daily Sepsis Research Analysis

We propose a selective prediction framework for clinical triage that combines calibrated probabilistic modeling, conformal prediction, and cost-aware deferral to prioritize patient safety. The system produces set-valued predictions with finite-sample coverage control and defers low-confidence cases to clinicians when doing so reduces an explicit expected clinical cost. We construct prediction sets using split conformal prediction, a group-conditional Mondrian variant for gender-stratified coverage, and an importance-weighted variant to improve robustness under distribution shift, and we select a single deferral threshold by minimizing expected cost on a held-out calibration set. On temporally separated in-distribution and out-of-distribution test splits for early sepsis prediction, selective deferral yields a favorable risk-coverage trade-off, reducing error on retained cases by 49.6% on the in-distribution (ID) test split and 46.7% on the out-of-distribution (OOD) test split, both at 80% coverage, while achieving low expected cost on both splits with only a moderate increase under shift. Calibration remains strong with low expected calibration error on both test sets, and rule-out performance is conservative, attaining near-perfect negative predictive value at a 95% sensitivity target. Coverage stays close to the nominal 90% target in-distribution and degrades only slightly out-of-distribution, with the weighted method most robust, and the Mondrian method reduces the gender coverage gap to 1.4 percentage points. These results indicate that conformal uncertainty quantification combined with cost-aware deferral can provide transparent and safer clinical decision support that degrades gracefully under temporal distribution shift.

Group B Streptococcus (GBS) remains a leading cause of neonatal sepsis, meningitis, stillbirth, and long-term neurodevelopmental impairment worldwide. Although intrapartum antibiotic prophylaxis (IAP) has substantially reduced early-onset GBS disease in high-income settings and remains an effective and evidence-based intervention, it does not prevent late-onset disease, maternal colonization, or GBS-associated stillbirths, and its implementation is challenging in many low- and middle-income countries (LMICs). Maternal vaccination has therefore emerged as a promising complementary strategy to achieve broader, more equitable prevention of GBS disease. This review critically examines current progress in maternal GBS vaccine development by integrating three interrelated dimensions that will shape future vaccine impact: immune correlates of protection, microbiome-related trade-offs of existing antibiotic-based prevention strategies, and global implementation challenges. We highlight recent advances and remaining uncertainties in defining serological and functional immune correlates required for regulatory decision-making, discuss emerging evidence on microbiome perturbations associated with peripartum antibiotic exposure while emphasizing their currently uncertain clinical significance, and analyze operational and policy considerations relevant to vaccine introduction in LMICs. By moving beyond descriptive summaries of the vaccine development pipeline, this review provides an integrated immunological, biological, and implementation-focused framework to inform vaccine evaluation, regulatory pathways, and policy decisions as maternal GBS vaccines approach licensure and global deployment.

BACKGROUND: Coagulopathy is a key driver of organ dysfunction during sepsis/septic shock, yet its relationship with microcirculatory autoregulation is not fully characterized. This study aimed to evaluate the association between sepsis-induced coagulopathy (SIC) and alterations in tissue oxygenation, oxygen extraction capacity and microvascular reactivity. METHODS: Prospective observational study on 23 adult septic patients. Coagulation status was evaluated with standard laboratory parameters and thromboelastography (TEG). A SIC score ≥ 4 was used to identify the presence of coagulopathy. The peripheral (skeletal muscle) tissue oxygen saturation (StO2) was assessed using thenar near infrared spectroscopy (NIRS). By combining a vascular occlusion test, the desaturation rate during ischemia was assessed as an index of oxygen extraction capacity: this was measured separately for the first (StO2 downslope-1) and last part (StO2 downslope-2) of the desaturation curve, and the difference between the two was calculated (delta-downslope). The reoxygenation rate (StO2 upslope) and the area of the hyperemic phase were calculated to evaluate microvascular reactivity. RESULTS: In patients with SIC, the delta-downslope was higher (1.7 ± 2.5 versus -0.8 ± 3.2, p = 0.049) and the StO2 upslope was reduced (96 ± 74 versus 185 ± 91, p = 0.017), suggesting altered tissue oxygen extraction capacity and microvascular reactivity. Both parameters were able to discriminate the presence of SIC in the receiver operating characteristics curve analysis. Negative correlations were found between StO2 downslope-1 and TEG maximum amplitude (r = -0.470, p = 0.023), and Delta-Downslope and platelet count (r = -0.527, p = 0.01). CONCLUSIONS: SIC is associated with alterations in peripheral tissue oxygen extraction capacity and microvascular reactivity.