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Search Results (252)

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Keywords = sequential organ failure assessment score

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17 pages, 989 KB  
Systematic Review
Neonatal Sepsis as Organ Dysfunction: Prognostic Accuracy and Clinical Utility of the nSOFA in the NICU—A Systematic Review
by Bogdan Cerbu, Marioara Boia, Manuela Pantea, Teodora Ignat, Mirabela Dima, Ileana Enatescu, Bogdan Rotea, Andra Rotea, Vlad David and Daniela Iacob
Diagnostics 2026, 16(2), 349; https://doi.org/10.3390/diagnostics16020349 - 21 Jan 2026
Viewed by 231
Abstract
Background and Objectives: Early recognition of life-threatening organ dysfunction is central to modern sepsis frameworks. We systematically reviewed the prognostic performance and clinical utility of the Neonatal Sequential Organ Failure Assessment (nSOFA) for mortality and major morbidity in NICU populations. The search identified [...] Read more.
Background and Objectives: Early recognition of life-threatening organ dysfunction is central to modern sepsis frameworks. We systematically reviewed the prognostic performance and clinical utility of the Neonatal Sequential Organ Failure Assessment (nSOFA) for mortality and major morbidity in NICU populations. The search identified 939 records across databases; after screening and full-text assessment, 16 studies met the inclusion criteria. Methods: Following PRISMA guidance, we searched major databases (2019–2025) for observational or interventional studies reporting discrimination or risk stratification using nSOFA in neonates. Populations included suspected/proven infection and condition-specific cohorts. Heterogeneity in timing, thresholds, and outcomes precluded meta-analysis. Results: A cumulative sample exceeding 25,000 neonates was identified across late- and early-onset infection, all-NICU admissions, necrotizing enterocolitis, respiratory distress, and very preterm screening cohorts. Across settings and timepoints, nSOFA demonstrated consistent, good-to-excellent mortality discrimination, with reported AUROCs ≥ 0.80 and upper ranges near 0.90–0.92; serial scoring within the first 6–12 h generally improved risk classification. Disease-specific applications (NEC, early-onset infection) showed similar discrimination for death or composite adverse outcomes. Conclusions: Evidence from diverse NICU contexts indicates that nSOFA is a pragmatic, EHR-ready organ dysfunction score with robust discrimination for mortality and serious morbidity, supporting routine, serial use for risk stratification and standardized endpoints in neonatal sepsis pathways, aligned with contemporary organ dysfunction–based pediatric criteria. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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12 pages, 703 KB  
Article
Early Identification of Sepsis by Emergency Medical Services: Diagnostic Accuracy of Scoring Systems in a Retrospective Cohort
by Andrea Kornfehl, David Mickerts, Mario Krammel, David Hauer and Sebastian Schnaubelt
J. Clin. Med. 2026, 15(2), 827; https://doi.org/10.3390/jcm15020827 - 20 Jan 2026
Viewed by 192
Abstract
Background/Objectives: Emergency Medical Services (EMSs) frequently provide the first medical contact for sepsis patients, but recognition is challenging. This study thus aimed to determine how often EMSs suspect sepsis and to evaluate the diagnostic accuracy of the quick Sequential Organ Failure Assessment (qSOFA), [...] Read more.
Background/Objectives: Emergency Medical Services (EMSs) frequently provide the first medical contact for sepsis patients, but recognition is challenging. This study thus aimed to determine how often EMSs suspect sepsis and to evaluate the diagnostic accuracy of the quick Sequential Organ Failure Assessment (qSOFA), the Prehospital Early Sepsis Detection (PRESEP) score, and the Modified Early Warning Score (MEWS). Methods: A retrospective observational study of all EMS transports to one emergency department during a one-month period in 2023 was conducted. Prehospital vital signs, EMS working diagnoses, and final in-hospital diagnoses were abstracted. Scores were calculated post hoc. The primary outcome was the diagnostic accuracy of the EMSs’ working diagnosis of “suspected sepsis.” Secondary outcomes included the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of qSOFA, PRESEP, and MEWS. Results: Among 786 EMS encounters, 597 met the inclusion criteria. Twelve patients (2.0%) were ultimately diagnosed with sepsis. EMSs explicitly suspected sepsis in three of them (25.0%; sensitivity 16.7%, specificity 99.8%). Retrospective application of scores yielded markedly higher sensitivity: qSOFA 83.3%, PRESEP 91.7%, and MEWS 83.3%. Specificities were 74.2% for qSOFA, 41.2% for PRESEP, and 77.6% for MEWS. The AUCs were 0.838 for qSOFA, 0.695 for PRESEP, and 0.863 for MEWS, with MEWS significantly outperforming PRESEP (p = 0.0215). Conclusions: EMS personnel rarely labeled patients with sepsis, recognizing 3 of 12 cases (25%). Retrospective use of scoring systems based on routine vital signs substantially improved diagnostic accuracy, with MEWS performing best overall. Structured screening tools should be prospectively validated and potentially implemented in EMS. Full article
(This article belongs to the Special Issue Sepsis: Current Updates and Perspectives)
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15 pages, 947 KB  
Article
Multi-Marker Approach in Sepsis: A Clinical Role Beyond SOFA Score
by Gun Hyuk Lee, Hanah Kim, Hee-Won Moon, Yeo-Min Yun, Seungho Lee and Mina Hur
Medicina 2026, 62(1), 201; https://doi.org/10.3390/medicina62010201 - 18 Jan 2026
Viewed by 211
Abstract
Background and Objectives: Procalcitonin (PCT), presepsin (PSEP), interferon-λ3 (IFN-λ3), and bioactive adrenomedullin (bio-ADM) are promising sepsis biomarkers. We explored the clinical utility of a multi-marker approach using these four biomarkers in patients with suspected sepsis. Materials and Methods: In a total [...] Read more.
Background and Objectives: Procalcitonin (PCT), presepsin (PSEP), interferon-λ3 (IFN-λ3), and bioactive adrenomedullin (bio-ADM) are promising sepsis biomarkers. We explored the clinical utility of a multi-marker approach using these four biomarkers in patients with suspected sepsis. Materials and Methods: In a total of 248 patients, the biomarkers were evaluated with the sequential organ failure assessment (SOFA) score. Receiver operating characteristic curves with area under the curve (AUC) were analyzed to diagnose sepsis and predict in-hospital mortality. Survival and reclassification analyses were also used to predict in-hospital mortality. Results: The four biomarkers showed comparable diagnostic performance (AUC = 0.61–0.95, p < 0.001–0.003), and sepsis proportion increased significantly as the number of biomarkers used in the multi-marker approach increased (7.7–91.7%, p < 0.001). The proportion of biomarker quartiles (Q1–Q4) differed significantly according to SOFA score (p < 0.001). The four biomarkers predicted in-hospital mortality (AUC = 0.63–0.84, p < 0.001–0.004). The multi-marker approach performed better than the SOFA score (mortality rate, 58.3% vs. 31.3%; adjusted hazard ratio [HR], 14.7 vs. 4.6), and the addition of biomarkers to the SOFA score increased the performance. The multi-marker approach resulted in a higher HR in patients aged ≥75 years than in the overall population (9.2 vs. 4.2). Conclusions: Each biomarker showed clinical utility in patients with suspected sepsis. The multi-marker approach showed complementary clinical utility in addition to the SOFA score and better prognostic performance in patients aged ≥75 years. The use of biomarkers, alone or in combination, would be a valuable tool in combination with the SOFA score. Full article
(This article belongs to the Collection The Utility of Biomarkers in Disease Management Approach)
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15 pages, 901 KB  
Article
Survival Prediction in Septic ICU Patients: Integrating Lactate and Vasopressor Use with Established Severity Scores
by Celia María Curieses Andrés, Maria del Pilar Rodriguez del Tio, Ana María Bueno Gonzalez, Mercedes Artola Blanco, Silvia Medina Díez, Amanda Francisco Amador, Elena Bustamante Munguira and José M. Pérez de la Lastra
Diseases 2026, 14(1), 11; https://doi.org/10.3390/diseases14010011 - 29 Dec 2025
Viewed by 439
Abstract
Background: Accurate prediction of survival in septic patients remains a major challenge in intensive care medicine. Established severity scores such as the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) are widely used to estimate [...] Read more.
Background: Accurate prediction of survival in septic patients remains a major challenge in intensive care medicine. Established severity scores such as the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) are widely used to estimate prognosis, while biochemical markers such as serum lactate may provide complementary information. However, the prognostic interplay between these scores, lactate dynamics, vasopressor requirement, and infection focus has not been fully elucidated in septic populations. Methods: We conducted a retrospective observational study of 146 adult patients with sepsis admitted to the intensive care unit (ICU) of the Hospital Clínico Universitario de Valladolid (HCUV), Spain, between 2022 and 2024. Demographic data, APACHE II and SOFA scores at admission, lactate levels at admission and 24 h, albumin, and procalcitonin were recorded. Vasopressor use (categorized by intensity) and infection focus (urinary vs. non-urinary) were documented. The primary outcome was ICU mortality. Correlation analyses (Pearson or Spearman as appropriate) were performed separately for urinary and non-urinary subgroups. Multivariable logistic regression models were constructed using APACHE II, SOFA, log-transformed lactate at 24 h, vasopressor use, and urinary focus as predictors. Model performance was assessed using Nagelkerke R2, area under the ROC curve (AUC), and classification accuracy. Results: ICU mortality was 23.3%. APACHE II (OR 1.092; p = 0.004) and SOFA (OR 1.185; p = 0.023) were independent predictors of ICU mortality, while log-transformed lactate at 24 h showed a positive trend (OR 1.920; p = 0.066). The addition of urinary focus (protective effect, OR 0.19; p = 0.035) and vasopressor requirement (OR 2.20; p = 0.04) modestly improved model discrimination (Nagelkerke R2 = 0.395). ROC analyses showed AUCs of 0.800 for APACHE + SOFA + log-lactate, 0.824 for the vasopressor model, and 0.833 for the urinary focus model. The best-performing models achieved >85% overall accuracy, with specificity consistently above 95%. Conclusions: In septic ICU patients, APACHE II and SOFA scores remain independent predictors of ICU mortality, and lactate at 24 h adds prognostic value—particularly in non-urinary infections. Vasopressor requirement and infection focus modestly improved model discrimination, underscoring their clinical relevance. These findings suggest that integrating severity scores with selected metabolic and clinical variables may modestly refine survival prediction in septic patients. Full article
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18 pages, 753 KB  
Article
Therapeutic Plasma Exchange in COVID-19-Associated Sepsis: IL-6 Dynamics, Inflammatory Phenotypes, and Short-Term Organ-Failure Trajectories in a Real-World Cohort
by Nicoleta Sgavardea, Dorel Sandesc, Tamara Mirela Porosnicu, Ovidiu Bedreag, Ciprian Gîndac, Marius Papurica, Elena Hogea, Patricia Hogea, Iulia Georgiana Bogdan and Voichita Elena Lazureanu
J. Clin. Med. 2026, 15(1), 10; https://doi.org/10.3390/jcm15010010 - 19 Dec 2025
Viewed by 351
Abstract
Background and Objectives: In severe COVID-19-associated sepsis, therapeutic plasma exchange (TPE) is used as a rescue strategy to modulate cytokine and coagulation derangements, but its biomarker and organ-failure effects remain incompletely characterised. We evaluated peri-procedural changes in interleukin-6 (IL-6), other inflammatory markers, and [...] Read more.
Background and Objectives: In severe COVID-19-associated sepsis, therapeutic plasma exchange (TPE) is used as a rescue strategy to modulate cytokine and coagulation derangements, but its biomarker and organ-failure effects remain incompletely characterised. We evaluated peri-procedural changes in interleukin-6 (IL-6), other inflammatory markers, and Sequential Organ Failure Assessment (SOFA) scores according to TPE intensity, timing, and inflammatory phenotypes. Methods: We conducted a single-centre retrospective cohort study including 102 mechanically ventilated adults with COVID-19-associated sepsis who received ≥1 TPE session. Patients were grouped by number of sessions (1, 2, ≥3), timing (≤14 vs. >14 days from symptom onset), IL-6 responder status (≥50% reduction), and two unsupervised inflammatory–thrombotic clusters. Peri-procedural changes (Δ) in biomarkers and SOFA were compared using non-parametric tests, with multivariable logistic and linear regression exploring predictors of IL-6 response and ΔSOFA. Results: Baseline severity was similar across TPE-intensity groups, with median APACHE II scores of 11–12 and SOFA scores around 7 in all strata. Median IL-6 concentrations declined after TPE in each group (e.g., Δ −59.4 pg/mL after 1 session and Δ −65.1 pg/mL after ≥3 sessions), but between-group differences in ΔIL-6 were not statistically significant (p = 0.276). By contrast, D-dimer exhibited a marked decline only in the 1-session group (median Δ −1.7 mg/L vs. ~0.0 mg/L in the 2- and ≥3-session groups; p < 0.001). Timing (early vs. late TPE) did not materially affect ΔIL-6, ΔCRP, ΔSOFA (median 0.0 in both), or ΔD-dimer. Overall, 50% of patients were IL-6 responders; baseline IL-6 was the only independent predictor (adjusted OR 1.9 per doubling, 95% CI 1.3–2.8). A hyperinflammatory–thrombotic cluster (n = 44) exhibited higher baseline IL-6 (612.3 vs. 92.4 pg/mL), more ≥3-session TPE (65.9% vs. 29.3%), and higher IL-6 responder rates (75.0% vs. 31.0%), but similar 28-day mortality (40.9% vs. 29.3%). Conclusions: In this real-world TPE programme, biochemical improvements—particularly IL-6 and D-dimer reductions in hyperinflammatory–thrombotic patients—were not consistently accompanied by short-term SOFA or survival benefits, underscoring the need for phenotype-guided and trial-based use. Full article
(This article belongs to the Section Hematology)
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12 pages, 401 KB  
Article
Association of oXiris® Therapy with Lower Vasopressor Requirements and Modulation of Hemodynamic, Inflammatory, and Perfusion Markers in Septic Shock: A Retrospective Cohort Study
by Nazrin Bakhshaliyeva, Fernando Ramasco Rueda, Ana Estiragués Barreiro and Miguel Ángel Olmos Alonso
J. Pers. Med. 2025, 15(12), 626; https://doi.org/10.3390/jpm15120626 - 14 Dec 2025
Viewed by 539
Abstract
Background: Septic shock remains a critical challenge with high mortality, particularly in refractory cases requiring high doses of vasopressors. Hemoadsorption with the oXiris® membrane, capable of simultaneously removing endotoxins, cytokines, and damage-associated molecular patterns (DAMPs), represents a personalized therapeutic strategy targeting [...] Read more.
Background: Septic shock remains a critical challenge with high mortality, particularly in refractory cases requiring high doses of vasopressors. Hemoadsorption with the oXiris® membrane, capable of simultaneously removing endotoxins, cytokines, and damage-associated molecular patterns (DAMPs), represents a personalized therapeutic strategy targeting the underlying pathophysiology. However, clinical evidence on its impact remains limited and lacks consensus. This study aims to analyze the effects of oXiris® therapy on hemodynamic, inflammatory, and perfusion parameters in a real-world cohort of patients with septic shock. Methods: We conducted a retrospective cohort study in a surgical Intensive Care Unit (ICU) at a tertiary hospital, including 45 adult patients with septic shock treated with continuous renal replacement therapy using the oXiris® membrane for at least 48 h. The institutional protocol involved filter changes at least every 24 h during the first 48 h of therapy. Hemodynamic variables, vasopressor doses, and biochemical markers were collected at baseline (T0), 24 h (T1), and 48 h (T2). The primary objective was to describe the evolution of these parameters. Secondary objectives included analysis of 30-day mortality and identification of prognostic factors. Results: The cohort consisted of 45 patients (80.0% male, median age 71 years), with a predominance of abdominal infectious focus (71.1%). A significant reduction in median norepinephrine requirements was observed from T0 to T2 (p < 0.00001), along with a significant increase in mean arterial pressure (MAP) (p < 0.00001). Key markers of perfusion and inflammation also improved, with a significant decrease in arterial lactate (p < 0.00001) and procalcitonin (p = 0.00082) at 48 h. No significant changes were observed in the Sequential Organ Failure Assessment (SOFA) score. The observed mortality rate in the ICU was 31.1%, lower than the median predicted mortality by Simplified Acute Physiology Score II (SAPS II) (37%). Baseline Charlson Comorbidity Index (CCI), creatinine, arterial lactate, and SOFA score were independent predictors of mortality. Conclusions: In this cohort of septic shock patients, therapy with oXiris®, applied with a frequent filter exchange protocol, was associated with a significant reduction in vasopressor requirements and an improvement in key hemodynamic, perfusion, and inflammatory markers. The observed ICU mortality was lower than predicted by severity scores. These findings support the role of oXiris® as a personalized adjuvant therapy in specific septic shock phenotypes and underscore the need for prospective randomized trials to confirm these benefits. Full article
(This article belongs to the Special Issue Emergency and Critical Care in the Context of Personalized Medicine)
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10 pages, 469 KB  
Article
Treatment Options for Critically Ill Patients with Infections Caused by Metallo-Beta-Lactamase-Producing Klebsiella pneumoniae
by Konstantinos Mantzarlis, Vassilios Vazgiourakis, Dimitrios Papadopoulos, Asimina Valsamaki, Stelios Xitsas, Masumi Tanaka, Achilleas Chovas and Efstratios Manoulakas
Antibiotics 2025, 14(11), 1156; https://doi.org/10.3390/antibiotics14111156 - 14 Nov 2025
Viewed by 851
Abstract
Background/Objectives: Antimicrobial resistance (AMR) has increased significantly over the years, contributing to a real challenge in the intensive care unit (ICU). The emergence of metallo-beta-lactamases (MBLs) has contributed to the protection of pathogens against all current beta-lactam/beta-lactamase inhibitors (BL/BLIs), including the newer [...] Read more.
Background/Objectives: Antimicrobial resistance (AMR) has increased significantly over the years, contributing to a real challenge in the intensive care unit (ICU). The emergence of metallo-beta-lactamases (MBLs) has contributed to the protection of pathogens against all current beta-lactam/beta-lactamase inhibitors (BL/BLIs), including the newer ceftazidime–avibactam (CAZ-AVI), meropenem–vaborbactam, and imipenem–relebactam. Treatment of such infections is challenging. In vitro and clinical data suggest that combinations of CAZ-AVI with aztreonam (ATM) and the use of two different carbapenems (double carbapenem therapy, DCT) may be an option for MBL-producing pathogens. The aim of our study was to evaluate the effectiveness of the combination CAZ-AVI + ATM and the effectiveness of DCT against MBL-producing K. pneumoniae infections in the critically ill, mechanically ventilated patients. Methods: This is a retrospective study conducted in the two ICUs of hospitals in central Greece. Mechanically ventilated patients admitted to the ICU were included in the study if they developed an infection by MBL-producing K. pneumoniae. Patients were divided into three groups: the first one consisted of patients who were treated with CAZ-AVI plus ATM (CAZ-AVI + ATM group), and the second group consisted of patients who received DCT (DCT group). The third group included patients who received appropriate antibiotic therapy other than CAZ-AVI + ATM and DCT (control group). The primary outcome of the study was the evolution of the sequential organ failure assessment (SOFA) score, and secondary outcomes were duration of mechanical ventilation (MV), ICU length of stay (LOS), and, finally, ICU mortality. Results: 108 patients were included in the study. 35 (32%) in the CAZ-AVI + ATM group, 31 (29%) in the DCT group, and the remaining 42 (39%) patients in the control group. The SOFA score was not statistically different on day 1, day 4, and day 7 of the infection among the three groups (p > 0.05). Duration of MV and ICU LOS were also similar. Finally, mortality did not differ between the groups [20 patients (57.1%) vs. 18 (58.1%) vs. 25 (59.5%) for CAZ-AVI + ATM, DCT and control group, respectively, p = 0.98]. Comparison between survivors and non-survivors revealed that independent risk factors for mortality were SOFA score at day 1 of infection and medical cause of admission (p < 0.05). Conclusions: Treatment with CAZ-AVI + ATM or DCT presented similar efficacy with appropriate antibiotic therapy for infections caused by MBL-producing K. pneumoniae strains. Larger studies are required to confirm the findings. Full article
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13 pages, 375 KB  
Article
Predicting Outcome and Duration of Mechanical Ventilation in Acute Hypoxemic Respiratory Failure: The PREMIER Study
by Jesús Villar, Jesús M. González-Martín, Cristina Fernández, Juan A. Soler, Marta Rey-Abalo, Juan M. Mora-Ordóñez, Ramón Ortiz-Díaz-Miguel, Lorena Fernández, Isabel Murcia, Denis Robaglia, José M. Añón, Carlos Ferrando, Dácil Parrilla, Ana M. Dominguez-Berrot, Pilar Cobeta, Domingo Martínez, Ana Amaro-Harpigny, David Andaluz-Ojeda, M. Mar Fernández, Estrella Gómez-Bentolila, Ewout W. Steyerberg, Luigi Camporota and Tamas Szakmanyadd Show full author list remove Hide full author list
J. Clin. Med. 2025, 14(22), 7903; https://doi.org/10.3390/jcm14227903 - 7 Nov 2025
Viewed by 1045
Abstract
Objectives: The ability of clinicians to predict prolonged mechanical ventilation (MV) in patients with acute hypoxemic respiratory failure (AHRF) is inaccurate, mainly because of the competitive risk of mortality. We aimed to assess the performance of machine learning (ML) models for the early [...] Read more.
Objectives: The ability of clinicians to predict prolonged mechanical ventilation (MV) in patients with acute hypoxemic respiratory failure (AHRF) is inaccurate, mainly because of the competitive risk of mortality. We aimed to assess the performance of machine learning (ML) models for the early prediction of prolonged MV in a large cohort of patients with AHRF. Methods: We analyzed 996 ventilated AHRF patients with complete data at 48 h after diagnosis of AHRF from 1241 patients enrolled in a prospective, national epidemiological study, after excluding 245 patients ventilated for <2 days. To account for competing mortality, we used multinomial regression analysis (MNR) to model prolonged MV in three categories: (i) ICU survivors (regardless of MV duration), (ii) non-survivors ventilated for 2–7 days, (iii) non-survivors ventilated for >7 days. We performed 4 × 10-fold cross-validation to validate the performance of potent ML techniques [Multilayer Perceptron (MLP), Support Vector Machine (SVM), Random Forest (RF)] for predicting patient assignment. Results: All-cause ICU mortality was 32.8% (327/996). We identified 12 key predictors at 48 h of AHRF diagnosis: age, specific comorbidities, sequential organ failure assessment score, tidal volume, PEEP, plateau pressure, PaO2, pH, and number of organ failures. MLP showed the best predictive performance [AUC 0.86 (95%CI: 0.80–0.92) and 0.87 (0.80–0.93)], followed by MNR [AUC 0.83 (0.76–0.90) and 0.84 (0.77–0.91)], in distinguishing ICU survivors, with non-survivors ventilated 2–7 days and >7 days, respectively. Conclusions: Accounting for ICU mortality, MLP and MNR offered accurate patient-level predictions. Further work should integrate clinical and organizational factors to improve timely management and optimize outcomes. This study was initially registered on 3 February 2025 at ClinicalTrials.gov (NCT06815523). Full article
(This article belongs to the Special Issue Acute Hypoxemic Respiratory Failure: Progress, Challenges and Future)
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17 pages, 1178 KB  
Article
Hemodynamic Heterogeneity in Community-Acquired Sepsis at Intermediate Care Admission: A Prospective Pilot Study Using Impedance Cardiography
by Gianni Turcato, Arian Zaboli, Lucia Filippi, Fabrizio Lucente, Michael Maggi, Alessandro Cipriano, Massimo Marchetti, Daniela Milazzo, Christian J. Wiedermann and Lorenzo Ghiadoni
Healthcare 2025, 13(21), 2686; https://doi.org/10.3390/healthcare13212686 - 23 Oct 2025
Cited by 1 | Viewed by 574
Abstract
Background: Sepsis is a heterogeneous syndrome in which patients with similar clinical presentations at admission may exhibit markedly different treatment responses and outcomes, suggesting that comparable macroscopic features can conceal profoundly distinct perfusion and hemodynamic states. Aim: This study aimed to [...] Read more.
Background: Sepsis is a heterogeneous syndrome in which patients with similar clinical presentations at admission may exhibit markedly different treatment responses and outcomes, suggesting that comparable macroscopic features can conceal profoundly distinct perfusion and hemodynamic states. Aim: This study aimed to characterize the hemodynamic profile of patients with community-acquired sepsis, assess its correlation with macro-hemodynamic indices, compare fluid responders with non-responders, and explore the prognostic value of early identification of a feature consistent with distributive shock. Methods: A prospective observational pilot study was conducted in the Intermediate Medical Care Unit (IMCU) of Ospedale Alto Vicentino (Santorso, Italy), September 2024–May 2025. 115 consecutive adults with community-acquired sepsis underwent NICaS® bioimpedance assessment at IMCU admission. Sepsis was diagnosed at IMCU admission as suspected/confirmed infection plus an acute increase in total Sequential Organ Failure Assessment (SOFA) ≥ 2 points. Hemodynamic indices were analyzed in relation to the Sequential Organ Failure Assessment (SOFA) score and mean arterial pressure (MAP), fluid responsiveness, and 30-day mortality. Results: Hemodynamics were heterogeneous across patients and within SOFA strata. SOFA showed no correlation with SV, SI, CO, or CI; weak inverse associations for TPR (r = −0.198, p = 0.034) and TPRI (r = −0.241, p = 0.009) were observed. MAP did not correlate with SV, SI, CO, or CI, but correlated positively with TPR (r = 0.461) and TPRI (r = 0.547) and with CPI (ρ = 0.550), all p < 0.001. A distributive profile was present in 21.7% (25/115), increasing with higher SOFA (p = 0.033); only 20% of those with this profile had MAP < 65 mmHg at admission. Fluid non-responders (27.8%) had lower resistance and higher CI (4.1 vs. 3.4 L/min/m2; p = 0.015). The distributive profile was not associated with 30-day mortality (log-rank p = 0.808). Conclusions: In IMCU patients with community-acquired sepsis, macro-indices (SOFA, MAP) correlate poorly with the underlying hemodynamic state. Early noninvasive profiling reveals within-SOFA circulatory heterogeneity and may support operational, individualized resuscitation strategies; these pilot findings are hypothesis-generating and warrant prospective interventional testing. Full article
(This article belongs to the Special Issue New Tools and Technologies in Emergency Medicine and Critical Care)
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16 pages, 1468 KB  
Article
Prognostic Value of Tryptophanyl-tRNA Synthetase in Sepsis Combined with Kidney Dysfunction or Urinary Tract Infection: A Prospective Observational Study
by Uihwan Kim, Sijin Lee, Kap Su Han, Su Jin Kim, Sungwoo Lee, Dae Won Park and Juhyun Song
Diagnostics 2025, 15(20), 2634; https://doi.org/10.3390/diagnostics15202634 - 19 Oct 2025
Viewed by 875
Abstract
Background: Although tryptophanyl-tRNA synthetase (WRS) is a novel biomarker released during bacterial and viral infections, its prognostic value in sepsis has rarely been reported. This study aimed to evaluate the prognostic performance of WRS in patients with sepsis in the emergency department (ED). [...] Read more.
Background: Although tryptophanyl-tRNA synthetase (WRS) is a novel biomarker released during bacterial and viral infections, its prognostic value in sepsis has rarely been reported. This study aimed to evaluate the prognostic performance of WRS in patients with sepsis in the emergency department (ED). Methods: This prospective, observational study included 243 patients with sepsis. Blood samples were collected to measure full-length WRS levels. The prognostic value of WRS was evaluated using the area under the receiver operating characteristic curve, Kaplan–Meier survival curve analysis, and the Cox proportional hazards model. Results: The WRS levels were higher in patients with septic shock than in those without shock (p = 0.018). WRS could predict 30-day mortality (area under the curve, 0.648; 95% confidence interval [CI], 0.569–0.726; sensitivity, 56.7%; specificity, 73.3%; cut-off value, 84.15 µg/L; p < 0.001). Patients with WRS levels of ≥84.15 µg/L showed higher 30-day mortality than those with WRS levels of <84.15 µg/L. Among patients with WRS levels of ≥84.15 µg/L, those with positive urine culture results had higher 30-day mortality than those with negative urine culture. Patients with renal Sequential Organ Failure Assessment (SOFA) score of ≥1 had higher 30-day mortality than those with renal SOFA score of 0. WRS was an independent risk factor of 30-day mortality (hazard ratio = 1.003; 95% CI, 1.001–1.005; p = 0.014). Conclusions: WRS effectively predicted clinical outcome in patients with sepsis and could be more useful in those with kidney dysfunction or urinary tract infection. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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30 pages, 955 KB  
Review
The Involvement of Endothelin-1 in Sepsis and Organ Dysfunction—A Novel Biomarker in Patient Assessment
by Cristian Sorin Prepeliuc, Maria Antoanela Pasăre, Maria Gabriela Grigoriu, Ionela Larisa Miftode, Radu Ștefan Miftode, Andrei Vâță, Irina Iuliana Costache-Enache and Egidia Gabriela Miftode
Biomedicines 2025, 13(10), 2480; https://doi.org/10.3390/biomedicines13102480 - 11 Oct 2025
Cited by 1 | Viewed by 844
Abstract
Sepsis represents a life-threatening organ dysfunction caused by a dysregulated host response to infection, and is considered a medical emergency. Therefore, quick diagnosis and treatment are required in order to improve survivability. Currently, patient evaluation in sepsis is based on the Sequential Organ [...] Read more.
Sepsis represents a life-threatening organ dysfunction caused by a dysregulated host response to infection, and is considered a medical emergency. Therefore, quick diagnosis and treatment are required in order to improve survivability. Currently, patient evaluation in sepsis is based on the Sequential Organ Failure Assessment (SOFA) score to determine the severity of the disease; however, novel biomarkers are also actively researched with the aim to develop quicker diagnostic tools and better therapy. Endothelin-1 is one of the most potent vasoconstrictors found in the human body and is involved in the pathophysiology of both sepsis and other conditions involving organs that make up the SOFA score. In this narrative review, we aimed to gather information of this peptide’s multiple effects and to help determine whether or not it could prove a valuable biomarker in the evaluation of patients with multi-organ dysfunction in sepsis. Full article
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12 pages, 1060 KB  
Article
ICU Admission-Related Factors Affecting the Duration of Mechanical Ventilation After Elective Cardiac Surgery—Retrospective Cohort Study from a Tertiary Center in Croatia
by Darko Kristović, Verica Mikecin, Ivana Presečki, Zrinka Šafarić Oremuš, Nataša Sojčić, Ivan Gospić, Hrvoje Lasić, Sanja Sakan, Danijela Kralj Husajna, Nikola Bradić, Jasminka Peršec and Andrej Šribar
Medicina 2025, 61(10), 1778; https://doi.org/10.3390/medicina61101778 - 1 Oct 2025
Viewed by 796
Abstract
Background and Objectives: Enhancing recovery after cardiac surgery involves minimally invasive procedures, early extubation/mobilization, and swift discharge. While mechanical ventilation is often essential post-operation, prolonged invasive ventilation (IMV) increases mortality risk. Duration is influenced by patient factors (age and comorbidities), surgical complexity, [...] Read more.
Background and Objectives: Enhancing recovery after cardiac surgery involves minimally invasive procedures, early extubation/mobilization, and swift discharge. While mechanical ventilation is often essential post-operation, prolonged invasive ventilation (IMV) increases mortality risk. Duration is influenced by patient factors (age and comorbidities), surgical complexity, and complications. Prognostic scores like EuroSCORE II, sequential organ failure assessment (SOFA), the Charlson Comorbidity Index (CCI), and the vasoactive–inotropic score (VIS) help to predict ventilation needs. The aim of this study is to analyze the effect of pre-/post-operation factors and procedure type as predictors of ventilation time. Materials and Methods: This is a retrospective cohort observational study analyzing factors affecting the duration of postoperative mechanical ventilation in elective cardiac surgical patients treated between 1 January and 31 December 2024 in a tertiary center in continental Croatia. Patients were stratified into two groups according to the duration of IMV: normal (first three quartiles) and prolonged (upper quartile). In total, 493 elective cardiac surgical patients operated on under general endotracheal anesthesia with sternotomy or mini-sternotomy were admitted postoperatively to the cardiovascular ICU and mechanically ventilated during the observed period, and 463 patients were included in the final analysis after the exclusion criteria had been applied. Results: The mean age was 64.7 ± 9.8 years, and 28.7% of the cohort were females while 71.3% were males. The median Charlton Comorbidity Index was 4 (IQR 3–5), the VIS was 2 (IQR 0–3), the SOFA score at ICU admission was 5 (IQR 3–6), and the adjusted SOFA score was 3 (IQR 2–4). In the multivariate logistic regression model, a significant effect of female sex (OR 1.98), age (OR 1.05), VIS (OR 1.05), and history of previous cardiac surgery (OR 6.67) on the duration of mechanical ventilation was observed. In the time-to-extubation multivariate analysis, there was a significant effect of re-do surgery (HR 3.70), corrected SOFA score (HR 1.14), and VIS (HR 1.05) on the duration of mechanical ventilation. There was no significant effect of the type of surgery (CABG, aorta, aortic valve, mitral/tricuspid valve, or other) or the amount of chest tube drainage on the duration of mechanical ventilation. Conclusions: A history of previous cardiac surgery and the vasoactive–inotropic score during the first 24 postoperative hours in the ICU are the strongest predictors of the duration of mechanical ventilation after elective cardiac surgery, with a statistically significant effect present in both the logistic regression model and hazard ratio analysis. Further analyses with more variables are warranted in the future to refine the prognostic model. Full article
(This article belongs to the Special Issue Approaches to Ventilation in Intensive Care Medicine)
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16 pages, 538 KB  
Review
Heparin Binding Protein in Sepsis—A Comprehensive Overview of Pathophysiology, Clinical Usage and Utility as Biomarker
by Foteini Tasouli, Eleni Georgopoulou, Christodoulos Chatzigrigoriadis, Dimitrios Velissaris and Christos Michailides
Biomedicines 2025, 13(9), 2315; https://doi.org/10.3390/biomedicines13092315 - 22 Sep 2025
Viewed by 2094
Abstract
The heparin-binding protein (HBP) is an enzymatically inactive protein of the serine protease family that plays an important role in host response to stress, especially infection and sepsis. It is produced by activated neutrophils due to a variety of stimuli and is part [...] Read more.
The heparin-binding protein (HBP) is an enzymatically inactive protein of the serine protease family that plays an important role in host response to stress, especially infection and sepsis. It is produced by activated neutrophils due to a variety of stimuli and is part of the immune response that leads to macrophage, lymphocyte, and neutrophil activation and monocyte adhesion. Its most common repository is the azurophilic granules of the neutrophils. HBP has been studied as a biomarker for several infections, including central nervous system infection, respiratory tract infection, and urinary tract infection, and in several settings, including the Emergency Department and Intensive Care Unit, with promising results. As a biomarker for infection and sepsis, HBP has been compared to other commonly used biomarkers such as Neutrophil to Lymphocyte Ratio, White Blood Count, C-reactive protein, and Procalcitonin, with at least comparable performance. Its sharp increase is promising for the early detection of sepsis. The ability to differentiate inflammatory conditions from infections and bacterial from non-bacterial causes of infection has also been demonstrated. The sepsis-related organ damage, as it is represented by the Sequential Organ Failure Assessment score, can also be reflected by the proportional increase in HBP. Consequently, HBP could be a helpful and promising biomarker for sepsis and infection. Full article
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17 pages, 1310 KB  
Article
The Diagnostic and Prognostic Value of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Urosepsis
by Petru Octavian Drăgoescu, Bianca Liana Grigorescu, Andreea Doriana Stănculescu, Andrei Pănuș, Nicolae Dan Florescu, Monica Cara, Maria Andrei, Mihai Radu, George Mitroi and Alice Nicoleta Drăgoescu
Medicina 2025, 61(9), 1713; https://doi.org/10.3390/medicina61091713 - 19 Sep 2025
Viewed by 1519
Abstract
Background and Objectives: The severe systemic response to urinary tract infections known as urosepsis is associated with significant morbidity and mortality rates. The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) are simple blood tests that could be useful in predicting the outcome [...] Read more.
Background and Objectives: The severe systemic response to urinary tract infections known as urosepsis is associated with significant morbidity and mortality rates. The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) are simple blood tests that could be useful in predicting the outcome of sepsis. Materials and Methods: A prospective observational study was conducted at a tertiary care hospital, where our team studied 223 patients with urosepsis. The patients underwent Sepsis-3 criteria-based urosepsis and septic shock stratification followed by survivor and non-survivor classification. Clinical scores (Sequential Organ Failure Assessment-SOFA, National Early Warning Score-NEWS), laboratory markers (NLR, PLR, PCT-procalcitonin), and patient outcomes were then analysed. Results: An admission NLR ≥ 13 was a strong predictor of septic shock (adjusted Odds Ratio (OR) 2.10, 95% Confidence Interval (CI) 1.25–3.54) and in-hospital mortality (adjusted OR 2.45, 95% CI 1.40–4.28). While the prognostic value of the PLR remained moderate, the NLR demonstrated superior predictive power. As easily measurable biomarkers, the NLR and PLR provide valuable information to help clinicians identify at-risk patients during the early stages of urosepsis. Conclusions: The NLR is an independent predictor with high predictive value for both septic shock and mortality, performing as well as established clinical scores. The combination of these parameters with clinical assessments could lead to better early decisions and improved outcomes for patients with urosepsis. Full article
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14 pages, 673 KB  
Article
SOFA Score Trends in Predicting Mortality in Critically Ill COVID-19 Patients
by Fadhilah Abdul Munim, Aliza Mohamad Yusof, Saw Kian Cheah, Mohd Khazrul Nizar Abd Kader, Wan Rahiza Wan Mat, Normahaini Abdul Hamid and Muhammad Maaya
COVID 2025, 5(9), 154; https://doi.org/10.3390/covid5090154 - 12 Sep 2025
Viewed by 1770
Abstract
The COVID-19 pandemic increased demand for intensive care unit (ICU) beds, requiring reliable disease severity scoring tools to optimise patient management and resource allocation. This retrospective study investigated the accuracy of the Sequential Organ Failure Assessment (SOFA) score in predicting mortality among critically [...] Read more.
The COVID-19 pandemic increased demand for intensive care unit (ICU) beds, requiring reliable disease severity scoring tools to optimise patient management and resource allocation. This retrospective study investigated the accuracy of the Sequential Organ Failure Assessment (SOFA) score in predicting mortality among critically ill COVID-19 patients. Data from 357 patients aged 18 years and above admitted to the ICU with COVID-19 category 5a and above, requiring ventilatory support throughout 2021, were analysed. The SOFA scores were calculated on days 1, 3 and 5 of ICU admission. The highest score and trends were noted; whether scores increased, were maintained or decreased was also determined. Patient outcomes were classified as survivors and non-survivors. There were significant differences in SOFA score trends between survivors and non-survivors. The high sensitivity (83.95%) and positive predictive value (PPV) (86.08%) in those with increased SOFA score trends showed that a SOFA score of ≥9 strongly predicted mortality, albeit with moderate specificity (65.63%). High sensitivity (81.85%) with low PPV (49.45%) was seen in those with decreased SOFA score trends. A high negative predictive value (87.50%) was observed for survivors. The SOFA score trend is effective in prognosticating survival in critically ill patients with COVID-19 infection, making it useful for critical care resource management. Full article
(This article belongs to the Section COVID Clinical Manifestations and Management)
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