Marcio Borges-Sa

Inflammatory biomarkers are read at the bedside as one value against one threshold, although serial determinations can be summarized in several ways, and the summary being tested is seldom stated. We measured the extent to which the discrimination attributed to a biomarker depends on the summary is read. We analyzed 53,033 blood cultures from 16,431 patients at one hospital between January 2020 and August 2026, anchoring each culture to its microbiological result and deriving, for eight biomarkers, the first value before the result, the maximum before it, the value nearest it and the amplitude between determinations. The outcomes were pathogen growth, excluding coagulase-negative staphylococci, and bacterial group. In the 35,150 cultures with a procalcitonin determination preceding the result, procalcitonin provided the best discrimination on every metric: area under the curve, 0.766 (95% CI 0.756–0.776) for the maximum before the result, 0.738 (0.728–0.748) for the first value, and 0.773 (0.764–0.784) nearest the result. The advantage of the maximum grew once sampling density and interval length were held constant. The neutrophil-to-lymphocyte ratio performed better before the result than near it, 0.707 versus 0.620, and fell from 0.738 on surgical wards to 0.512 in hematology, whereas procalcitonin varied little between services. Sensitivity at 0.5 ng/mL ranged from 88.0% for Enterobacterales to 55.6% for other Gram-positive organisms. Combining biomarkers improved the area by, at most, 0.015. Which number is read changes the answer as much as which marker is chosen. A procalcitonin level below 0.5 ng/mL argues strongly against Gram-negative bacteremia and far more weakly against enterococcal, other Gram-positive, and fungal bloodstream infection.

Background: Evidence on how hospitals organise sepsis care comes almost entirely from high-income countries, and none is multinational for Ibero-America, where the Pan American Health Organization's sepsis plan runs to 2029.Methods: Cross-sectional survey of hospitals in 21 Ibero-American countries, one response per hospital, fielded from March 2025 to August 2026 through Fundación Código Sepsis and national scientific societies. Responses came through a REDCap instrument and, in Portugal, a parallel questionnaire, deduplicated by georeferencing and centre name. Percentages are over valid responses. Logistic regression adjusted for hospital size and university status, with country-clustered standard errors in the regulatory models. Reporting followed CROSS and CHERRIES.Findings: 703 responses resolved to 544 hospitals. Microbiological studies were available in 90·4% (492/544) of centres and an antimicrobial stewardship programme in 66·2% (360/544), against an institutional sepsis protocol in 37·6% (204/543), 30·8% (118/383) in Latin America and 53·8% (86/160) in Iberia (aOR 2·31, 95% CI 1·49-3·59; p=0·00019). Where stewardship is a legal obligation, stewardship programmes were more frequent (73·8% vs 48·7%; aOR 2·57, 1·06-6·24; p=0·037) and sepsis protocols were not (32·6% vs 33·8%; aOR 0·92, 0·41-2·07). In Portugal, whose norm requires a sepsis team in every emergency service, 97·1% (34/35) of centres reported a rapid response team against 33·5% elsewhere, while none of its 20 centres with a protocol reported a sepsis unit with its own beds.Interpretation: Ibero-American hospitals hold the diagnostic and antimicrobial tools of sepsis care without the organisation that uses them. Regulation was followed by the element it named, and sepsis has been named once.

Antimicrobial resistance claimed an estimated 4.95 million lives in 2019. When clinicians prescribe empiric therapy that follows guidelines, mortality drops by roughly a third; when they de-escalate on the basis of culture results, it drops by more than half. Yet the document that should drive both decisions, the antibiogram, is often read superficially or misinterpreted, particularly by physicians without infectious-disease training. Existing stewardship frameworks address prescribing principles, timing, or ecological impact, but none walks the clinician step by step through an individual susceptibility report and out the other side with a treatment plan. PRECISE is a seven-step mnemonic designed for that purpose. Each letter corresponds to a clinical action: Pathogen assessment, Resistance phenotype interpretation, Evaluate MIC, Curtail spectrum, Individualize PK/PD, Switch route, and Endpoint optimization. Three clinical vignettes (including one in which the steps deliberately collide) illustrate how the framework operates in practice.

Background: Sepsis remains a major global health challenge. International guidelines exist, but their implementation is inconsistent, and supporting evidence largely comes from high‐income settings. The objective of this study was to generate international, multidisciplinary expert consensus on controversial aspects of sepsis management within the framework of sepsis code programs. Methods: A multinational modified Delphi study was conducted with 164 experts from 22 countries, 12 specialties, and 105 scientific societies. Seven domains were evaluated: early diagnosis, biomarkers, diagnostic microbiology, hemodynamic monitoring, source control, antimicrobial therapy, and hemodynamic management. Consensus was defined as ≥70% agreement across three iterative rounds using Likert scales (Rounds 1–2) and binary format (Round 3). Results: Consensus was achieved for 40 statements. Strong endorsement (82%–95%) was reached for structured hospital sepsis programs, NEWS‐2 as the preferred early recognition tool, biomarker use (notably procalcitonin) to complement clinical assessment, urgent source control within 6 h independent of hemodynamic status, rapid molecular diagnostics integrated with antimicrobial stewardship, and norepinephrine as first‐line vasopressor therapy. Experts also supported pharmacokinetic‐ and pharmacodynamic‐guided antibiotic dosing, prolonged infusion of time‐dependent agents, and dynamic rather than fixed fluid strategies. No consensus was reached on routine reliance on Sepsis‐2, Sepsis‐3, or qSOFA; high mean arterial pressure targets; or universal combination antimicrobial therapy. Conclusions: These results provide multidisciplinary guidance for sepsis management, with emphasis on rapid recognition, targeted antimicrobial therapy, timely source control, and hemodynamic management guided by patient physiology. The recommendations are applicable to high‐ and middle‐income healthcare systems.

Background. Sepsis is a leading, time-dependent cause of in-hospital death, and guidelines now prioritize organized care such as code-sepsis protocols. Yet little is known about the long-term activity, organization and outcomes of permanent, hospital-scale programs. We characterized the activity of a hospital-wide multidisciplinary sepsis unit (MSU) over thirteen years and evaluated mortality trends. Methods. Retrospective cohort study using the registry of a hospital-wide MSU (2011–2023). The analysis unit was the sepsis event. Activity, referral pathways, interventions, follow-up and mortality were analyzed; temporal trends used multivariable logistic regression and standardized mortality ratios (SMR). Results. The unit attended 10,874 patients across 15,723 events and 50,925 consultations (median age 67; 59.3% men), referred mainly through the sepsis code (45.0%) and, increasingly, proactive early-warning detection (15.2%). An antibiotic change was recommended in 57.2% of events, and 89.8% of all suggested changes were implemented. Follow-up was sustained (median 3 visits; 61.8%). In-hospital mortality was 7.6%, and 11.8% in protocol-confirmed sepsis. Crude mortality did not fall, but severity rose (organ dysfunctions 1.67 to 2.72; septic shock 8 to 13%; both p < 0.001) with stable age; after adjustment the calendar-year effect disappeared (adjusted OR 1.00/year, p = 0.70) and the SMR stayed near 1.0, including pandemic years. Age, ICU admission (OR 2.65) and organ-dysfunction count (OR 1.37) independently predicted death. Conclusions. Over thirteen years, this hospital-wide MSU delivered large-scale, multi-channel, longitudinal care to an increasingly severe population while maintaining stable risk-adjusted mortality, supporting the long-term feasibility of a model integrating early detection, multidisciplinary decision-making, antimicrobial stewardship and follow-up.

Background/Objectives: Sepsis detection relies on clinical variables and scoring systems assumed to perform uniformly across hospital settings. However, sepsis phenotype distributions shift between clinical environments, suggesting that variable importance may be setting dependent. This study aimed to quantify service-specific variability in the discriminatory capacity of clinical variables for sepsis detection and to evaluate whether this heterogeneity translates into differential performance of machine learning models compared to traditional clinical scoring systems. Methods: This stratified sub-analysis of the BIAlert Sepsis cohort (203,755 patients; 11,864 sepsis episodes, 2014–2018) evaluated 61 structured quantitative variables across nine hospital services (≥90 sepsis episodes each). Within each service, the Mann–Whitney–Wilcoxon test (p < 0.01, Holm-corrected) assessed differences between septic and non-septic episodes. Five machine learning models (Random Forest/BIAlert, XGBoost, CatBoost, SVM, Neural Network) and three clinical rules (NEWS, SIRS, qSOFA) were evaluated globally and stratified across four clinical environments. Results: The proportion of significant variables ranged from 95.1% in the Emergency Department (58/61) to 37.7% in the Intensive Care Unit (23/61). Lactate was the only universally significant variable (9/9 services). Clinical scoring systems collapsed in Critical Care (qSOFA and NEWS AUC 0.459). BIAlert maintained the highest AUC across all environments (0.975–0.857). The Friedman test confirmed significant differences (χ² = 28.00, p < 0.001), with BIAlert achieving a mean rank of 1.0. Conclusions: The discriminatory capacity of clinical variables for sepsis detection is not uniform across hospital services. ML models, particularly BIAlert, maintained robust performance where fixed-rule scoring systems failed.

Objective: To evaluate the diagnostic accuracy of the biomarkers procalcitonin (PCT), interleukin-6 (IL-6), and mid-regional pro-adrenomedullin (MR-ProADM), individually and in combination, for early detection of sepsis and septic shock during emergency department (ED) triage. Materials and methods: A retrospective observational study was conducted in adults presenting to the ED with triage levels 2 and 3 between December 2021 and July 2023. Blood samples were collected at admission, prior to any therapeutic intervention. Plasma concentrations of PCT, IL-6, and MR-ProADM were measured using CMIA or ELISA. Diagnostic accuracy was assessed using ROC curves and AUC analysis. Results: A total of 248 patients were included (214 with sepsis and 34 non-septic controls). Simultaneous elevation of PCT, IL-6, and MR-ProADM was observed in 70% of septic patients compared with 3% of controls. Each biomarker showed high diagnostic accuracy for sepsis (AUROC >0.90). The combined assessment increased specificity and was strongly associated with sepsis and septic shock, with progressively higher odds as the number of elevated biomarkers increased. Higher biomarker burden was also associated with indicators of greater clinical severity, including higher SOFA scores and ICU admission. Conclusions: Combined measurement of PCT, IL-6, and MR-ProADM at ED triage, before therapeutic intervention, improves early identification of patients with sepsis and provides relevant information on initial disease severity. This multiplex platform approach may support clinical prioritization and protocol activation in the ED.

Background/Objective: Coagulopathy is a hallmark of sepsis, associated with poor outcomes. Although platelet count has commonly been used for risk stratification, its prognostic value has remained limited. This study compared the ability of the International Normalized Ratio (INR) and platelet count to predict in-hospital mortality in septic patients; Methods: A retrospective study was conducted including adult patients diagnosed with sepsis and admitted to Hospital Universitario Son Llàtzer (Spain) between 2006 and 2022. The INR and platelet count at diagnosis were categorized using clinical thresholds. The primary outcome was in-hospital mortality. Results: Among 6433 patients (60.6% females), mortality was 8.8%. Mortality increased from 6.3% (INR ≤ 1.2) to 20.2% (INR 2.0–3.0), slightly decreasing at INR > 3.0 (10.8%). The platelet count showed a weaker association, with the highest mortality observed at 3.0 and platelet count < 50 × 10⁹/L). In the full cohort, multivariable analysis confirmed the INR as an independent predictor of mortality (OR 2.183, p = 0.0002), whereas the platelet count was not significant. The model including the INR achieved an AUC 0.746, while adding the platelet count did not improve performance. Conclusions: the INR at diagnosis was a strong and independent predictor of in-hospital mortality, outperforming the platelet count. These findings could support the consideration of the INR in early risk stratification frameworks and highlight the need for prospective validation before integration into sepsis guidelines.