Daily Sepsis Research Analysis
Across three studies spanning epidemiology, therapeutics, and diagnostics in sepsis-related care, initiating SGLT2 inhibitors was associated with markedly lower sepsis-related hospitalizations versus DPP4 inhibitors, while increasing foot and genital infections. A meta-analysis suggests angiotensin II reliably raises blood pressure in distributive shock and may reduce mortality in select subgroups. In acute-on-chronic liver failure, early procalcitonin measurement helped identify SIRS and sepsis
Summary
Across three studies spanning epidemiology, therapeutics, and diagnostics in sepsis-related care, initiating SGLT2 inhibitors was associated with markedly lower sepsis-related hospitalizations versus DPP4 inhibitors, while increasing foot and genital infections. A meta-analysis suggests angiotensin II reliably raises blood pressure in distributive shock and may reduce mortality in select subgroups. In acute-on-chronic liver failure, early procalcitonin measurement helped identify SIRS and sepsis, supporting timely intervention.
Research Themes
- Antidiabetic therapy shaping infection and sepsis risk
- Precision vasopressor use in distributive shock
- Biomarker-enabled early recognition in high-risk liver disease
Selected Articles
1. Initiation of sodium-glucose cotransporter-2 inhibitors and the risk of infection-related hospitalisations: A population-based cohort study.
In a statewide, active comparator new-user cohort, initiating SGLT2 inhibitors was linked to lower overall infection-related hospitalizations versus DPP4 inhibitors, including significantly fewer admissions for sepsis (wIRR 0.60). Increased hospitalizations were observed for osteomyelitis, foot, and genital mycotic infections, highlighting differential infection risks by type.
Impact: This large, real-world analysis indicates antidiabetic drug choice can materially alter sepsis and infection-related hospitalization risks post-discharge. It provides actionable evidence for therapy selection in type 2 diabetes with implications for antimicrobial stewardship and preventive care.
Clinical Implications: For adults with type 2 diabetes, SGLT2 inhibitors may reduce hospitalizations for sepsis and several infection types compared with DPP4 inhibitors, but clinicians should intensify foot care, skin inspection, and counseling on genital hygiene to mitigate increased foot and mycotic infection risks.
Key Findings
- Overall infection-related hospitalizations were lower with SGLT2 inhibitors versus DPP4 inhibitors (wIRR 0.74, 95% CI 0.71-0.77).
- Sepsis hospitalizations were markedly reduced (wIRR 0.60, 95% CI 0.54-0.66), with similar reductions for pneumonia (0.61), UTI (0.38), and influenza (0.63).
- Higher hospitalization rates occurred for osteomyelitis (wIRR 1.14), foot infections (1.25), and genital mycotic infections (1.48).
Methodological Strengths
- Active comparator, new-user cohort design minimizing immortal time and prevalent user bias
- Inverse probability of treatment weighting with negative binomial regression for rate comparisons across all statewide hospitals
Limitations
- Observational design with potential for residual confounding and confounding by indication
- Lack of microbiological data and infection severity details; adherence and outpatient treatment not captured
Future Directions: Prospective comparative effectiveness and mechanistic studies are warranted to clarify causal pathways, identify high-risk subgroups for adverse infections, and test preventive bundles (e.g., foot care programs) alongside SGLT2 initiation.
AIMS: To assess the association between initiating sodium-glucose cotransporter-2 (SGLT2) inhibitors compared to dipeptidyl peptidase-4 (DPP4) inhibitors and the rate of infection-related hospitalisations among individuals with type 2 diabetes following hospital discharge. MATERIALS AND METHODS: In this active comparator, new user cohort study, we compared rates of infection-related hospitalisations among new users of SGLT2 inhibitors to new users of DPP4 inhibitors over 2 years post-discharge. We analysed data from all public and private hospitals in Victoria, Australia. Weighted incidence rate ratios (wIRRs) and 95% CIs were estimated using negative binomial regression with inverse probability of treatment weighting. RESULTS: New users of SGLT2 inhibitors had a lower rate of overall infection-related hospitalisations (wIRR 0.74, 95% CI 0.71-0.77), and specifically for sepsis (wIRR 0.60, 95% CI 0.54-0.66), pneumonia (wIRR 0.61, 95% CI 0.55-0.66), gastrointestinal infections (wIRR 0.77, 95% CI 0.70-0.85), urinary tract infections (wIRR 0.38, 95% CI 0.34-0.43), respiratory tract infections (wIRR 0.68, 95% CI 0.63-0.74), influenza (wIRR 0.63, 95% CI 0.48-0.83) and kidney infections (wIRR 0.49, 95% CI 0.34-0.71). No significant differences were observed for rates of hospitalisation for cellulitis (wIRR 1.04, 95% CI 0.98-1.10). In contrast, hospitalisations for osteomyelitis (wIRR 1.14, 95% CI 1.02-1.27), foot infections (wIRR 1.25, 95% CI 1.19-1.31), and genital mycotic infections (wIRR 1.48, 95% CI 1.24-1.76) were higher in new users of SGLT2 inhibitors. CONCLUSIONS: Initiating SGLT2 inhibitors is associated with lower overall rates of infection-related hospitalisations over 2 years. However, the association between SGLT2 inhibitors and infection-related hospitalisations is dependent on the type of infection.
2. Analysis of clinical experience with angiotensin II: A meta-analysis and 4 AI.
Across 10 studies, angiotensin II substantially increased mean arterial pressure without a clear overall mortality benefit, yet mortality reduction was significant in patients with high renin or on renal replacement therapy. Safety signals were not increased, and AI-based evidence syntheses converged on similar conclusions.
Impact: This synthesis supports targeted use of angiotensin II in distributive shock, suggesting renin-guided or RRT-specific strategies may yield survival gains while maintaining safety.
Clinical Implications: Consider angiotensin II for refractory distributive shock, especially in high-renin states or during renal replacement therapy, with careful hemodynamic monitoring and standardized adverse event surveillance.
Key Findings
- Overall mortality reduction with ATII did not reach significance (OR 0.86, 95% CI 0.60-1.23).
- Significant mortality reduction in high renin (OR 0.45) and renal replacement therapy subgroups (OR 0.38).
- ATII markedly increased mean arterial pressure (OR 3.25) without increasing adverse events (OR 0.77).
Methodological Strengths
- Systematic evidence synthesis across RCTs, non-randomized trials, and observational studies
- Predefined subgroup analyses identifying populations with potential survival benefit
Limitations
- Heterogeneity across included study designs and populations may bias pooled estimates
- Overall mortality effect was nonsignificant; publication bias and risk-of-bias assessments were not detailed
Future Directions: Prospective, renin-guided RCTs and IPD meta-analyses should validate subgroup effects, optimize dosing, and assess long-term outcomes and safety in septic/distributive shock.
OBJECTIVE: Angiotensin II (ATII) was approved for distributive shock in Spain (2023). The objective is to assess the experience with ATII by comparing a meta-analysis (MTA) and 4 Artificial Intelligence (AI) tools. DESIGN: A search was conducted in Pubmed®, Central®, Embase®, and Scopus®. Randomized clinical trials, non-randomized trials, and observational studies were included. The primary outcome was all-cause mortality. Odds ratios (OR) with 95% confidence intervals (CI) were pooled. Four AI tools were used: Consensus, Perplexity, Elicit, and Scite. SETTING: Intensive care medicine. PATIENTS OR PARTICIPANTS: One thousand six hundred and thirty-six studies were identified, with 10 studies included in the MTA. INTERVENTIONS: No interventions. MAIN VARIABLES OF INTEREST: Mortality, efficacy, and safety. RESULTS: ATII shows a trend towards mortality reduction when compared with controls, OR 0.86 (95% CI: 0.60-1.23); this reduction reaches significance in patient subgroups: High Renin Levels, OR 0.45 (95% CI: 0.22-0.93); shock with renal replacement therapy, OR 0.38 (95% CI: 0.17-0.84). ATII is very effective in increasing mean arterial pressure, OR 3.25 (95% CI: 2.24-4.73), without increasing events, OR 0.77 (95% CI: 0.51-1.14). The AI reached the same conclusions, but only 25%-30% of the studies were included in the MTA. CONCLUSIONS: ATII effectively increases blood pressure without side effects and without altering mortality. AI can assist in evaluating clinical evidence.
3. Role of procalcitonin in identifying systemic inflammatory response syndrome and sepsis in acute-on-chronic liver failure and its impact on survival.
In a prospective ACLF cohort (n=135), SIRS and sepsis were frequent and associated with higher severity scores and worse short-term outcomes. Procalcitonin measurement supported early identification of SIRS and sepsis, informing timely management during the high-risk early phase.
Impact: PCT-guided early recognition of SIRS/sepsis in ACLF addresses a critical diagnostic gap, with potential to improve timing of antimicrobials and organ support in a population with high short-term mortality.
Clinical Implications: Implement early PCT testing in ACLF to aid differentiation of inflammatory decompensation versus sepsis, triage patients for escalation, and guide early antibiotics and supportive care pending cultures.
Key Findings
- SIRS and sepsis were present in 59.2% and 42.2% of ACLF patients, respectively.
- Patients with SIRS/sepsis had higher MELD-Na, AARC, and CLIF-SOFA severity scores than those without.
- Early PCT measurement supported identification of SIRS/sepsis and was proposed to guide timely interventions and improve outcomes.
Methodological Strengths
- Prospective design with standardized timepoints through day 7 and 28-day outcome assessment
- Use of multiple validated severity scores (MELD-Na, AARC, CLIF-SOFA)
Limitations
- Single-country, single tertiary-center setting may limit generalizability
- Sample size modest; PCT thresholds and diagnostic accuracy metrics were not fully detailed in the abstract
Future Directions: Define PCT cutoffs and kinetics for ACLF-specific sepsis diagnosis, integrate with clinical scores into decision algorithms, and test PCT-guided strategies in randomized trials.
BACKGROUND: Systemic inflammatory response syndrome (SIRS) and sepsis are commonly observed in patients with acute-on-chronic liver failure (ACLF). This study aimed to identify the presence of SIRS and sepsis in ACLF patients to assess their impact on patient survival and the role of procalcitonin (PCT) in identifying SIRS and sepsis. METHODOLOGY: This prospective study was performed at a tertiary hospital in India from August 2023 to August 2024. Patients with ACLF according to the APASL classification were included in the study. These patients were assessed for the presence or absence of SIRS or sepsis at baseline and monitored until day 7, and clinical outcome was evaluated on day 28. RESULTS: A total of 135 patients with a median age of 44 years (IQR: 38–51) and a male predominance (98.5%, 133/135) were included in the study. Alcohol was the primary cause of ACLF in 88.1% of patients. Among these patients, SIRS was present in 59.2% of patients, while sepsis was present in 42.2%. Patients with SIRS and sepsis had significantly higher median MELD-Na, AARC, and CLIF-SOFA scores than those without SIRS and sepsis ( CONCLUSION: Sepsis and SIRS are common in ACLF patients and carry a high mortality risk. PCT measurement may be used to detect SIRS and sepsis in these patients early and can be used to guide prompt intervention to improve the outcome of these patients.