Daily ReportSep 8, 2026
Sepsis, September 8 edition
We read 32 papers and selected 3.
Summary
Today’s most impactful sepsis-related research spans high-precision mortality surveillance, dynamic characterization of organ dysfunction, and rigorous reassessment of bedside perfusion monitoring. The findings emphasize that sepsis risk is heterogeneous and time-dependent, while standardized laboratory confirmation and longitudinal physiological measurements can improve prevention, prognostication, and clinical decision-making.
Research Themes
- Laboratory-confirmed causes and preventability of child mortality
- Dynamic heterogeneity of organ dysfunction in neonatal sepsis
- Physiological validation of capillary refill time during acute inflammation
Selected Articles
1. Causes of Death Among Stillbirths and Children Aged <5 Years in Africa and South Asia - Child Health and Mortality Prevention Surveillance, Seven Countries, 2016-2024.
This large, multicountry Child Health and Mortality Prevention Surveillance study integrated minimally invasive tissue sampling, molecular and conventional microbiology, histopathology, verbal autopsy, and clinical record review to determine causes and preventability of deaths. Among 8,500 deaths with multidisciplinary cause-of-death determinations, sepsis contributed to 36.5% of neonatal deaths and 36.9% of infant and child deaths; 80.7% of deaths with a preventability assessment were preventable or potentially preventable.
Impact: The study provides unusually precise, laboratory-confirmed mortality data from high-burden regions and directly links causes of death to actionable prevention opportunities. Its findings support improvements in antenatal care, intrapartum management, infection prevention, vaccination, and child health policy.
Clinical Implications: Clinical and public health programs should prioritize antenatal and intrapartum care, neonatal infection prevention, laboratory-supported surveillance, antimicrobial and infection-control capacity, and targeted prevention of gram-negative and polymicrobial infections. The findings also support incorporating minimally invasive postmortem investigation into mortality review systems where feasible.
Key Findings
- Among 8,500 deaths with completed multidisciplinary cause-of-death determinations, 36.5% of neonatal deaths and 36.9% of infant and child deaths involved sepsis.
- Gram-negative bacteria predominated, and 44.5% of deaths with identified pathogens had polymicrobial involvement.
- Of 7,558 deaths assessed for preventability, 6,103 (80.7%) were considered preventable or possibly preventable through improvements in existing maternal, newborn, and child health interventions.
Methodological Strengths
- Standardized, population-defined surveillance was conducted across seven countries and included laboratory-confirmed postmortem investigations.
- Multidisciplinary cause-of-death panels integrated microbiology, histopathology, clinical records, maternal factors, and verbal autopsy data.
Limitations
- The surveillance catchment areas were not nationally representative of all countries or regions.
- Enrollment and minimally invasive tissue sampling required family consent, and only 8,500 deaths had completed multidisciplinary cause-of-death determinations.
Future Directions: Future work should evaluate how CHAMPS-derived findings can be integrated into routine vital registration, maternal and neonatal mortality reviews, infection-control programs, and vaccine development. Implementation studies are needed to determine which surveillance components are feasible and cost-effective in different resource settings.
PROBLEM/CONDITION: Sub-Saharan Africa and South Asia have the highest rates of stillbirths and rates of death among children aged <5 years, with many countries in those regions unlikely to meet the 2030 goal of ending preventable deaths among newborns and children aged <5 years. Conventional mortality surveillance (determining cause of death through interviews with family members or caregivers [i.e., verbal autopsy] and vital registration) in areas with high mortality often lacks laboratory confirmation of causes and incompletely identifies maternal contributors and comorbid conditions, providing information that is insufficiently specific to guide prevention efforts.
2. Physiological limits of capillary refill time: a human endotoxemia study.
In a double-blind, randomized, crossover human endotoxemia study, quantitative finger capillary refill time (qCRT) was measured in 25 healthy volunteers after intravenous lipopolysaccharide or placebo. qCRT increased markedly early in inflammation and then shortened below the conventional threshold later in the same inflammatory episode, showing that a single 3-second cutoff can be misleading and that serial within-person changes may be more informative.
Impact: The study rigorously tests a widely used bedside perfusion sign and demonstrates that its conventional threshold behaves nonlinearly during acute inflammation. This challenges simplistic interpretation of capillary refill time and provides a mechanistic basis for serial, context-aware assessment.
Clinical Implications: Clinicians should avoid interpreting a single capillary refill time value against the fixed 3-second threshold without considering skin temperature, hemodynamics, and the direction of change. The findings support serial measurements but do not yet justify changing septic shock protocols because the participants were healthy volunteers rather than patients with sepsis.
Key Findings
- After lipopolysaccharide administration, mean estimated qCRT increased to 8.31 seconds at 1.5 hours, with 14 of 25 participants reaching the 10-second measurement ceiling.
- By 5 hours, qCRT shortened to 1.27 seconds despite ongoing systemic inflammation; contrasts with placebo were significant at both early and late time points.
- Skin temperature was the strongest physiological covariate, and between-subject differences explained only a minority of total qCRT variance.
Methodological Strengths
- The double-blind, randomized, crossover design reduced between-person confounding and provided a controlled inflammatory challenge.
- Quantitative polarized-reflectance imaging minimized observer variability, and mixed-effects models accounted for repeated measurements and physiological covariates.
Limitations
- The study used a controlled lipopolysaccharide challenge in 25 healthy volunteers rather than patients with sepsis or septic shock.
- The follow-up covered only 5 hours, and no formal mediation analysis was performed for the relationship between skin temperature, hemodynamics, and qCRT.
Future Directions: Prospective studies in patients with sepsis and septic shock should test whether serial quantitative capillary refill measurements improve resuscitation decisions or outcomes. Future work should also establish context-specific reference ranges and evaluate integration with lactate, peripheral temperature, echocardiography, and other perfusion markers.
BACKGROUND: The capillary refill test is a widely used bedside marker of tissue perfusion, but its reliability during acute inflammation is not well characterised. The guiding 3-s threshold rests on limited physiological validation and on visual assessment with high observer variability. How finger capillary refill time (CRT) behaves during acute inflammation remains unclear. Using quantitative capillary refill time (qCRT), which removes observer variability, we determined how finger qCRT behaves over an acute inflammatory episode in a controlled human endotoxemia model.
3. Heterogeneity of Critical Organ Dysfunction During Late-Onset Bacteremia in Preterm Infants.
This multicenter cohort study analyzed hourly neonatal Sequential Organ Failure Assessment (nSOFA) scores in 221 preterm infants with first episodes of late-onset single-pathogen bacteremia. Although organ dysfunction was often minimal at initial evaluation among survivors, peak severity, cumulative burden, trajectory, and timing varied markedly—even among infections caused by the same pathogen—supporting dynamic organ dysfunction phenotyping rather than binary microbiologic classification alone.
Impact: The study reframes neonatal sepsis severity as a dynamic and heterogeneous process rather than a binary bacteremia diagnosis. This approach may improve risk stratification, endpoint selection, clinical trial design, and individualized neonatal intensive care.
Clinical Implications: A single nSOFA measurement or pathogen category may inadequately represent an infant’s illness burden. Serial organ dysfunction trajectories could support earlier recognition of deterioration, more precise prognostication, and better selection of infants for intervention or clinical trials, although prospective clinical validation is needed.
Key Findings
- The cohort included 221 preterm infants with a median gestational age of 27 weeks and median birth weight of 840 g.
- Organ dysfunction trajectories varied widely, with broad dispersion in nSOFA change, maximum severity, cumulative burden, and temporal pattern even among episodes caused by the same pathogen.
- Substantial differences in cumulative organ dysfunction burden could emerge within 24 hours, despite minimal dysfunction at initial evaluation among many survivors.
Methodological Strengths
- The multicenter cohort included longitudinal hourly organ dysfunction data from 48 hours before culture through 14 days after onset or death.
- The study quantified multiple dimensions of illness burden, including trajectory, peak severity, cumulative burden, onset timing, and temporal dispersion.
Limitations
- The study was observational and limited to first episodes of single-pathogen bacteremia in preterm infants from four academic neonatal intensive care units.
- The findings describe associations and organ dysfunction patterns but do not establish that trajectory-based monitoring improves treatment or survival.
Future Directions: Future studies should externally validate trajectory-based nSOFA phenotypes across diverse neonatal intensive care units and pathogens. Interventional research should determine whether real-time trajectory monitoring can guide antibiotic, hemodynamic, respiratory, or organ-support decisions and improve outcomes.
IMPORTANCE: Late-onset sepsis in preterm infants is predominantly defined by bacteremia. Although binary classifications are critical for pathogen epidemiology and antibiotic stewardship efforts, they limit more granular understanding of the severity or organ dysfunction trajectory as experienced by individual infants. OBJECTIVE: To quantify the heterogeneity of illness severity and organ dysfunction during late-onset sepsis episodes in preterm infants. DESIGN, SETTING, AND PARTICIPANTS: Multicenter cohort study of first episodes of late-onset single-pathogen bacteremia in infants at 33 weeks' gestation or less at 4 academic neonatal intensive care units (January 2012 to February 2025).