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Keywords = sepsis and septic shock management

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13 pages, 469 KiB  
Article
Continuous Hemofiltration During Extracorporeal Membrane Oxygenation in Adult Septic Shock: A Comparative Cohort Analysis
by Nicoleta Barbura, Tamara Mirela Porosnicu, Marius Papurica, Mihail-Alexandru Badea, Ovidiu Bedreag, Felix Bratosin and Voichita Elena Lazureanu
Biomedicines 2025, 13(8), 1829; https://doi.org/10.3390/biomedicines13081829 - 26 Jul 2025
Viewed by 461
Abstract
Background and Objectives: Severe sepsis complicated by refractory shock is associated with high mortality. Adding continuous hemofiltration to venovenous extracorporeal membrane oxygenation (ECMO) may accelerate clearance of inflammatory mediators and improve haemodynamic stability, but evidence remains limited. We analysed 44 consecutive septic-shock [...] Read more.
Background and Objectives: Severe sepsis complicated by refractory shock is associated with high mortality. Adding continuous hemofiltration to venovenous extracorporeal membrane oxygenation (ECMO) may accelerate clearance of inflammatory mediators and improve haemodynamic stability, but evidence remains limited. We analysed 44 consecutive septic-shock patients treated with combined ECMO-hemofiltration (ECMO group) and compared them with 92 septic-shock patients managed without ECMO or renal replacement therapy (non-ECMO group). Methods: This retrospective single-centre study reviewed adults admitted between January 2018 and March 2025. Demographic, haemodynamic, laboratory and outcome data were extracted from electronic records. Primary outcome was 28-day mortality; secondary outcomes included intensive-care-unit (ICU) length-of-stay, vasopressor-free days, and change in Sequential Organ Failure Assessment (SOFA) score at 72 h. Results: Baseline age (49.2 ± 15.3 vs. 52.6 ± 16.1 years; p = 0.28) and APACHE II (27.8 ± 5.7 vs. 26.9 ± 6.0; p = 0.41) were comparable. At 24 h, mean arterial pressure rose from 52.3 ± 7.4 mmHg to 67.8 ± 9.1 mmHg in the ECMO group (mean change [∆] + 15.5 mmHg, p < 0.001). Controls exhibited a modest 4.9 mmHg rise that did not reach statistical significance (p = 0.07). Inflammatory markers decreased more sharply with ECMO (IL-6 ∆ −778 pg mL−1 vs. −248 pg mL−1, p < 0.001). SOFA fell by 3.6 ± 2.2 points with ECMO versus 1.6 ± 2.4 in controls (p = 0.01). Twenty-eight-day mortality did not differ (40.9% vs. 48.9%, p = 0.43), but ICU stay was longer with ECMO (median 12.5 vs. 9.3 days, p = 0.002). ΔIL-6 correlated with ΔSOFA (ρ = 0.46, p = 0.004). Conclusions: ECMO-assisted hemofiltration improved early haemodynamics and organ-failure scores and accelerated cytokine clearance, although crude mortality remained unchanged. Larger prospective trials are warranted to clarify survival benefit and optimal patient selection. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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16 pages, 1261 KiB  
Review
Extracorporeal Cytokine Adsorption in Sepsis: Current Evidence and Future Perspectives
by Matteo Guarino, Anna Costanzini, Francesco Luppi, Martina Maritati, Carlo Contini, Roberto De Giorgio and Michele Domenico Spampinato
Biomedicines 2025, 13(7), 1684; https://doi.org/10.3390/biomedicines13071684 - 9 Jul 2025
Viewed by 724
Abstract
Background: Sepsis and septic shock are major contributors to global morbidity and mortality. The “cytokine storm,” a hyper-inflammatory response, plays a central role in sepsis pathophysiology, leading to multi-organ failure. Extracorporeal cytokine adsorption therapies, such as CytoSorb, Toraymyxin, Oxiris, HA330/380, and Seraph [...] Read more.
Background: Sepsis and septic shock are major contributors to global morbidity and mortality. The “cytokine storm,” a hyper-inflammatory response, plays a central role in sepsis pathophysiology, leading to multi-organ failure. Extracorporeal cytokine adsorption therapies, such as CytoSorb, Toraymyxin, Oxiris, HA330/380, and Seraph 100 Microbind, aim to mitigate the inflammatory response by removing circulating cytokines and other mediators. Methods: A comprehensive search of Scopus and PubMed was conducted for studies published from January 2020 to May 2025. The search terms included “sepsis,” “septic shock,” and “extracorporeal cytokine adsorption.” Relevant studies, including clinical trials and meta-analyses, were included to assess the efficacy and safety of these therapies. Results: Extracorporeal cytokine adsorption has shown promising results in reducing cytokine levels, improving organ function, and decreasing vasopressor requirements. However, evidence regarding mortality reduction remains inconsistent. Studies have demonstrated benefits in sepsis, ARDS, and cardiogenic shock, improving organ recovery and inflammatory markers. Conclusions: Extracorporeal cytokine adsorption is a potential adjunctive therapy in sepsis management, offering improvements in organ function and inflammatory control. While the mortality benefit remains uncertain, ongoing research and large-scale clinical trials are essential to define its clinical role and optimize its application. Full article
(This article belongs to the Section Cell Biology and Pathology)
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15 pages, 239 KiB  
Case Report
Clinical Presentation of Postnatally Acquired Cytomegalovirus Infection in Preterm Infants—A Case Series Report
by Dobrochna Wojciechowska, Dominika Galli, Justyna Kowalczewska, Tomasz Szczapa and Katarzyna Ewa Wróblewska-Seniuk
Children 2025, 12(7), 900; https://doi.org/10.3390/children12070900 - 8 Jul 2025
Viewed by 418
Abstract
Background: Human cytomegalovirus (HCMV) is the leading cause of congenital and acquired viral infections in newborns. While acquired infections are often asymptomatic, premature infants—especially those born before 30 weeks of gestation or with a very low birth weight (<1500 g)—are at an [...] Read more.
Background: Human cytomegalovirus (HCMV) is the leading cause of congenital and acquired viral infections in newborns. While acquired infections are often asymptomatic, premature infants—especially those born before 30 weeks of gestation or with a very low birth weight (<1500 g)—are at an increased risk for severe infections. These can manifest as thrombocytopenia, liver failure, sepsis-like symptoms, and, in rare cases, death. HCMV is transmitted through various human secretions, including breast milk, which is the optimal feeding method for premature infants. Methods: We present five premature neonates, born between 23 and 26 weeks of gestation, each with a distinct clinical presentation of acquired HCMV infection. Results: All infants tested negative for congenital CMV infection via molecular urine testing within the first three weeks of life. Acquired infection was diagnosed between the second and third month of life, with symptoms such as septic shock, persistent thrombocytopenia, and signs of liver failure. Each infant received antiviral treatment along with regular viral load monitoring. Unfortunately, one patient died due to complications of prematurity. The remaining infants were discharged and continue to receive follow-up care in an outpatient clinic. Conclusions: These cases of postnatally acquired CMV infection aim to increase awareness of its highly heterogeneous and nonspecific clinical presentation, which may result in an incorrect, delayed, or concealed diagnosis. Currently, there are no clear guidelines on how to manage the presence of the virus in maternal breast milk, particularly for premature infants. It should be recommended to perform a molecular CMV test in all breast-fed preterm infants who present with sepsis-like symptoms, thrombocytopenia, liver failure, or other organ involvement. In case of a confirmed aCMV diagnosis, appropriate treatment should be introduced. Full article
17 pages, 522 KiB  
Article
Klebsiella pneumoniae Invasive Liver Abscess Syndrome (Klas/Ilas)—Experience of a Single Center and Up-to-Date Review of the Literature
by Octavian Enciu, Elena-Adelina Toma, Valentin Calu, Dumitru Cătălin Pîrîianu, Andrei Ludovic Poroșnicu, Adrian Miron and Mircea Ioan Popa
Diagnostics 2025, 15(12), 1533; https://doi.org/10.3390/diagnostics15121533 - 17 Jun 2025
Viewed by 784
Abstract
Background: Klebsiella pneumoniae liver abscess (KLAS) is a potentially life-threatening condition with variable outcomes. Identifying risk factors for mortality is crucial for improving patient management. We aimed to analyze factors associated with in-hospital mortality in a cohort of patients with KLAS and [...] Read more.
Background: Klebsiella pneumoniae liver abscess (KLAS) is a potentially life-threatening condition with variable outcomes. Identifying risk factors for mortality is crucial for improving patient management. We aimed to analyze factors associated with in-hospital mortality in a cohort of patients with KLAS and review current diagnostic and treatment challenges. Methods: We retrospectively analyzed clinical, laboratory, microbiological, and treatment data from 20 patients admitted with KLAS. Patients were divided into survivor (n = 15) and non-survivor (n = 5) groups. Univariate analyses were performed using appropriate statistical tests to compare groups and identify mortality-related factors. Results: The overall in-hospital mortality rate was 25.0% (5/20). Factors significantly associated with mortality included undergoing laparotomy drainage (60.0% vs. 6.7%, p = 0.018) and developing in-hospital complications (80.0% vs. 6.7%, p = 0.002). Laparoscopic drainage was significantly associated with survival (93.3% vs. 40.0%, p = 0.026). Trends toward increased mortality were observed with diabetes mellitus and higher glucose levels at admission. Despite p-values < 0.05 from prior Fisher’s exact test, and the fact that ESBL positivity (OR = 22, 95% CI 0.86–571.32) and septic shock at admission (OR = 16.08, 95% CI 0.75–343.64) showed a very high point estimate for risk of mortality, the association was not statistically significant in our study. Conclusions: Mortality in this KLAS cohort was considerable. The necessity for open drainage and the development of in-hospital complications emerged as significant predictors of death, while other independent risk factor such as diabetes mellitus, high blood glucose levels at admission, septic shock at admission, and ESBL-positive strains indicated a trend towards unfavorable outcomes. These findings underscore the importance of aggressive sepsis management and addressing antimicrobial resistance. Conflicting results regarding the statistical significance of independent risk factors due to a limited sample size highlight the need for larger studies to confirm these findings. Full article
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8 pages, 480 KiB  
Article
Impact of Prediabetes on In-Hospital Mortality and Clinical Outcomes in Acute Pancreatitis: Insights from a Nationwide Inpatient Sample
by Tahani Dakkak, Nawras Silin, Riaz Mahmood, Shane S. Robinson and Nelson A. Royall
J. Clin. Med. 2025, 14(12), 4271; https://doi.org/10.3390/jcm14124271 - 16 Jun 2025
Viewed by 381
Abstract
Background/Objectives: Prediabetes is characterized by insulin resistance and systemic inflammation, which may increase susceptibility to acute pancreatitis (AP). However, limited data exist on how prediabetes influences in-hospital outcomes in AP patients. This study aimed to evaluate the prevalence and clinical outcomes of [...] Read more.
Background/Objectives: Prediabetes is characterized by insulin resistance and systemic inflammation, which may increase susceptibility to acute pancreatitis (AP). However, limited data exist on how prediabetes influences in-hospital outcomes in AP patients. This study aimed to evaluate the prevalence and clinical outcomes of hospitalized AP patients with prediabetes using the National Inpatient Sample (NIS) database. Methods: We conducted a retrospective cohort study using NIS data from 2016 to 2018, identifying adult patients hospitalized with a primary diagnosis of AP. Patients were stratified based on the presence or absence of prediabetes; those with type 1 or 2 diabetes were excluded. The primary outcome is the association of prediabetes with developing acute pancreatitis and its influence on in-hospital mortality, length of stay, and total hospital cost. Results: Among 193,617 patients hospitalized with AP, 1639 had prediabetes. No statistically significant difference was found in in-hospital mortality, length of stay, or hospitalization costs between patients with or without prediabetes. The in-hospital mortality was 1.22% in prediabetic patients versus 2.01% in non-prediabetic patients (p = 0.0225). The length of stay was shorter in prediabetic patients (4.93 vs. 5.37 days, p = 0.0021), and hospitalization costs were similar (USD55,351.56 vs. USD57,106.83, p = 0.195). Furthermore, prediabetes was not an independent predictor of mortality (OR 0.50, 95% CI 0.31–0.82, p = 0.0063). Significant predictors of mortality included acute kidney injury (OR 12.98, 95% CI 11.96–14.09, p < 0.001) and severe sepsis with shock (OR 5.89, 95% CI 5.27–6.59, p < 0.001). Conclusions: Prediabetes was not associated with an increased in-hospital mortality in AP patients. However, complications such as AKI and septic shock significantly predicted mortality, underscoring the importance of early recognition and management. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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14 pages, 1095 KiB  
Article
Extracorporeal Membrane Oxygenation Modulates the Inflammatory Milieu and Organ Failure Trajectory in Severe COVID-19 and Sepsis
by Nicoleta Barbura, Tamara Mirela Porosnicu, Cristian Oancea, Dorel Sandesc, Marius Papurica, Ovidiu Bedreag, Ciprian Gîndac, Adelina Raluca Marinescu, Ruxandra Laza and Voichita Elena Lazureanu
J. Clin. Med. 2025, 14(12), 4224; https://doi.org/10.3390/jcm14124224 - 13 Jun 2025
Viewed by 510
Abstract
Background and Objectives: Coronavirus disease 2019 (COVID-19) triggers a dysregulated host response that may culminate in refractory hypoxaemic shock. Whether veno-venous ECMO modifies the inflammatory cascade more effectively in COVID-19 than in other septic states, and how it compares with conventional ventilatory support [...] Read more.
Background and Objectives: Coronavirus disease 2019 (COVID-19) triggers a dysregulated host response that may culminate in refractory hypoxaemic shock. Whether veno-venous ECMO modifies the inflammatory cascade more effectively in COVID-19 than in other septic states, and how it compares with conventional ventilatory support for COVID-19, remains uncertain. We compared three groups: COVID-19 patients supported with ECMO (COVID-ECMO, n = 25), non-COVID-19 septic shock patients on ECMO (SEPSIS-ECMO, n = 19) and critically ill COVID-19 patients managed without ECMO (COVID-CONV, n = 74). Methods: This retrospective study (January 2018–January 2025) extracted demographic, laboratory and clinical data at baseline, 48 h and 72 h. The primary end-point was the 72 h change in SOFA score (ΔSOFA). The secondary end-points included the evolution of interleukin-6 (IL-6), C-reactive protein (CRP), D-dimer and ferritin; haemodynamic variables; and 28 day mortality. A post hoc inverse-probability-of-treatment weighting (IPTW) sensitivity analysis adjusted for between-group severity imbalances. Results: Baseline APACHE II differed significantly (29.5 ± 5.8 COVID-ECMO, 27.4 ± 6.1 SEPSIS-ECMO, 18.2 ± 4.9 COVID-CONV; p < 0.001). At 48 h, IL-6 fell by 51.8% in COVID-ECMO (−1 116 ± 473 pg mL−1) versus 32.4% in SEPSIS-ECMO and 18.7% in COVID-CONV (p < 0.001). The ΔSOFA values at 72 h were −4.6 ± 2.2, −3.1 ± 2.5 and −1.4 ± 1.9, respectively (p < 0.001). ECMO groups achieved larger mean arterial pressure rises (+16.8 and +14.2 mmHg) and greater norepinephrine reduction than COVID-CONV. The twenty-eight-day mortality was 36.0% (COVID-ECMO), 42.1% (SEPSIS-ECMO) and 39.2% (COVID-CONV) (p = 0.88). Across all patients, IL-6 clearance correlated with ΔSOFA (ρ = 0.48, p < 0.001) and with vasopressor-free days (ρ = 0.37, p = 0.002). Conclusions: ECMO, regardless of aetiology, accelerates inflammatory-marker decline and organ failure recovery compared with conventional COVID-19 management, but survival advantage remains elusive. COVID-19 appears to display a steeper cytokine-response curve to ECMO than bacterial sepsis, suggesting phenotype-specific benefits that merit confirmation in prospective trials. Full article
(This article belongs to the Section Intensive Care)
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28 pages, 1597 KiB  
Review
Bio-Adrenomedullin and Dipeptidyl Peptidase 3 as Novel Sepsis Biomarkers in the Emergency Department and the Intensive Care Unit: A Narrative Review
by Ioannis Ventoulis, Christos Verras, Dionysis Matsiras, Vasiliki Bistola, Sofia Bezati, John Parissis and Effie Polyzogopoulou
Medicina 2025, 61(6), 1059; https://doi.org/10.3390/medicina61061059 - 9 Jun 2025
Viewed by 645
Abstract
Early recognition and timely treatment of sepsis and septic shock is vital. Despite appropriate management, mortality and morbidity rates remain high. In recent years, many of the research efforts have been directed towards finding novel biomarkers that would rapidly identify, classify and risk-stratify [...] Read more.
Early recognition and timely treatment of sepsis and septic shock is vital. Despite appropriate management, mortality and morbidity rates remain high. In recent years, many of the research efforts have been directed towards finding novel biomarkers that would rapidly identify, classify and risk-stratify the severity of sepsis in order to achieve prompt and targeted treatment of patients with sepsis and septic shock. Among these biomarkers, adrenomedullin (ADM) in the form of the biologically active fragment (bio-ADM) and dipeptidyl peptidase 3 (DPP3) have recently been in the spotlight. The aim of this narrative review is to summarize current evidence on these two novel biomarkers regarding their clinical utility in diagnosis, prognosis, treatment monitoring and therapy guidance of sepsis and septic shock in the emergency department (ED) and in the intensive care unit (ICU) setting. Bio-ADM seems to be a promising biomarker with respect to the overall management of sepsis (diagnosis, severity prediction, prognosis and treatment monitoring and guidance). On the other hand, DPP3 appears to be useful mainly for sepsis prognosis and for predicting sepsis-induced acute kidney injury. Given their potential clinical utility in sepsis management, the use of these two novel biomarkers, in conjunction with established biomarkers and clinical scores, could lead to the application of refined integrated protocols in the ED and the ICU, which could promptly and effectively inform clinical decision-making in patients presenting with sepsis or septic shock. Full article
(This article belongs to the Section Intensive Care/ Anesthesiology)
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15 pages, 1000 KiB  
Systematic Review
Unraveling Pediatric Group A Streptococcus Meningitis: Lessons from Two Case Reports and a Systematic Review
by Lavinia Di Meglio, Maia De Luca, Laura Cursi, Lorenza Romani, Mara Pisani, Anna Maria Musolino, Stefania Mercadante, Venere Cortazzo, Gianluca Vrenna, Paola Bernaschi, Roberto Bianchi and Laura Lancella
Microorganisms 2025, 13(5), 1100; https://doi.org/10.3390/microorganisms13051100 - 9 May 2025
Viewed by 731
Abstract
Streptococcus pyogenes meningitis is a rare invasive disease, accounting for less than 2% of bacterial meningitis. We presented two case reports and conducted a systematic review using PUBMED, covering the database from its inception up to 31 December 2024, of pediatric cases of [...] Read more.
Streptococcus pyogenes meningitis is a rare invasive disease, accounting for less than 2% of bacterial meningitis. We presented two case reports and conducted a systematic review using PUBMED, covering the database from its inception up to 31 December 2024, of pediatric cases of Streptococcus pyogenes meningitis. Only case reports and case series were included. Differences in clinical and laboratory parameters were compared between uneventful course and complicated admissions. A total of 57 cases were included. The median age at diagnosis was 4 years. A primary infection focus outside the brain was identified in 61.39% of cases. S. pyogenes was identified from cerebrospinal fluid in 66.66% of cases and from blood in 15.79%. Septic shock occurred in 24.56% of cases, and 36.84% had brain anatomical anomalies. All patients received broad-spectrum empiric antibiotics, while protein-synthesis inhibitors were administered in 26.31% of cases. A total of 17% of patients died, and 28.07% experienced sequelae. The identification of S. pyogenes from blood and a Phoenix Sepsis Score ≥ 2 were significantly associated with a complicated clinical course. Our findings may offer useful insights for the clinical management of Streptococcus pyogenes meningitis. Full article
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12 pages, 893 KiB  
Article
A Retrospective Single-Center Analysis from Southern Italy on the Use of T2 Magnetic Resonance Assays as a Point-of-Care Method for Patients with Sepsis
by Mariarita Margherita Bona, Vincenza Maria Carelli, Nicola Serra, Salvatore Amico, Roberta Bartolini, Anna Giammanco, Paola Di Carlo, Teresa Fasciana and Maria Andriolo
Biomedicines 2025, 13(4), 999; https://doi.org/10.3390/biomedicines13040999 - 20 Apr 2025
Viewed by 514
Abstract
Background: The rapid and accurate identification of the pathogens responsible for sepsis is essential for prompt and effective antimicrobial therapy. The T2Bacteria® Panel (T2B) and T2Candida® Panel (T2C) are rapid molecular tests performed on whole blood that exploit T2 Magnetic [...] Read more.
Background: The rapid and accurate identification of the pathogens responsible for sepsis is essential for prompt and effective antimicrobial therapy. The T2Bacteria® Panel (T2B) and T2Candida® Panel (T2C) are rapid molecular tests performed on whole blood that exploit T2 Magnetic Resonance (T2MRsup®) technology. Objectives: This study evaluates the impact of the T2MR system as a point-of-care device for managing sepsis and septic shock patients. Methods: This single-center retrospective study was conducted at the Sant’ Elia Hospital of Caltanissetta from 1 January 2023 to 31 July 2023. The study population was composed of patients with suspected sepsis and septic shock according to the Sepsis-3 criteria and for whom concurrent T2MR and BC samples were requested for diagnosis. Results: A total of 81 consecutive patients were enrolled in this study. Concordant T2/BC results were obtained in 69/81 (85.2%) patients; 58/81 (71.6%) were concordant-negative and 11/81 (13.6%) were concordant-positive. Discordant T2MR+/BC− results were observed in 9/81 patients (11.1%), while T2MR−/BC+ results were detected in 3/81 patients (3.7%). Furthermore, the median time for reporting positive T2MR test results (5.2 h) was significantly shorter than that for BC (122 h). Conclusions: Due to its high reliability, faster detection time, and simple workflow, T2MR in combination with BC improved the etiological diagnosis of sepsis in the enrolled patients. Full article
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14 pages, 2291 KiB  
Systematic Review
Hemoadsorption in the Management of Septic Shock: A Systematic Review and Meta-Analysis
by David Steindl, Tim Schroeder, Alexander Krannich and Jens Nee
J. Clin. Med. 2025, 14(7), 2285; https://doi.org/10.3390/jcm14072285 - 27 Mar 2025
Cited by 4 | Viewed by 2067
Abstract
Background/Objectives: Septic shock remains a significant clinical challenge with consistently high mortality rates. Recent investigations have focused on the efficacy of CytoSorb® (CytoSorbents Corporation, Monmouth Junction, NJ, USA), an extracorporeal cytokine adsorber, and how it impacts outcomes in sepsis. The current [...] Read more.
Background/Objectives: Septic shock remains a significant clinical challenge with consistently high mortality rates. Recent investigations have focused on the efficacy of CytoSorb® (CytoSorbents Corporation, Monmouth Junction, NJ, USA), an extracorporeal cytokine adsorber, and how it impacts outcomes in sepsis. The current meta-analysis reports on the impact of CytoSorb® on survival, specifically in septic shock patients. Methods: We conducted a comprehensive systematic search across the PubMed and COCHRANE databases for studies published up to 10 June 2024. The analysis prioritized randomized controlled trials and observational studies with control groups involving septic shock patients while excluding case reports and case series. Nine studies were finally included in our meta-analysis following the initial screening of 115 articles after excluding duplicates and irrelevant entries. Results: The meta-analysis was performed on 744 critically ill patients with septic shock from one RCT and eight observational studies. Of these, 449 patients received treatment with CytoSorb® in addition to standard care. Our data indicate that CytoSorb® use is associated with reduced in-hospital mortality, evidenced by an odds ratio (OR) of 0.64 [0.42; 0.97] and a p-value of 0.036. For 28–30-day mortality, the findings were more pronounced with an OR of 0.46 [0.28; 0.78] and a p-value of 0.003. The analysis of the longest observed mortality showed a trend for improved survival within the CytoSorb group; however, it did not reach statistical significance. Additionally, there was a significant improvement in hemodynamic stability as a secondary endpoint, as evidenced by notable reductions in vasopressor requirements in the hemoadsorption group. Conclusions: The current meta-analysis suggests that the use of CytoSorb® alongside standard of care management may be linked to improved short-term survival in patients with septic shock; however, these findings should be interpreted with caution in light of the heterogeneity and the modest quality of the studies included. Prospective studies are needed to better determine the impact of hemoadsorption on shock reversal and survival in these critically ill patients. Full article
(This article belongs to the Special Issue Sepsis: Current Updates and Perspectives)
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37 pages, 2637 KiB  
Review
Septic Cardiomyopathy: Difficult Definition, Challenging Diagnosis, Unclear Treatment
by George E. Zakynthinos, Grigorios Giamouzis, Andrew Xanthopoulos, Evangelos Oikonomou, Konstantinos Kalogeras, Nikitas Karavidas, Ilias E. Dimeas, Ioannis Gialamas, Maria Ioanna Gounaridi, Gerasimos Siasos, Manolis Vavuranakis, Epaminondas Zakynthinos and Vasiliki Tsolaki
J. Clin. Med. 2025, 14(3), 986; https://doi.org/10.3390/jcm14030986 - 4 Feb 2025
Cited by 3 | Viewed by 7149
Abstract
Sepsis is a systemic inflammatory response syndrome of suspected or confirmed infectious origin, which frequently culminates in multiorgan failure, including cardiac involvement. Septic cardiomyopathy (SCM) remains a poorly defined clinical entity, lacking a formal or consensus definition and representing a significant knowledge gap [...] Read more.
Sepsis is a systemic inflammatory response syndrome of suspected or confirmed infectious origin, which frequently culminates in multiorgan failure, including cardiac involvement. Septic cardiomyopathy (SCM) remains a poorly defined clinical entity, lacking a formal or consensus definition and representing a significant knowledge gap in critical care medicine. It is an often-underdiagnosed complication of sepsis. The only widely accepted aspect of its definition is that SCM is a transient myocardial dysfunction occurring in patients with sepsis, which cannot be attributed to ischemia or pre-existing cardiac disease. The pathogenesis of SCM appears to be multifactorial, involving inflammatory cytokines, overproduction of nitric oxide, mitochondrial dysfunction, calcium homeostasis dysregulation, autonomic imbalance, and myocardial edema. Diagnosis primarily relies on echocardiography, with advanced tools such as tissue Doppler imaging (TDI) and global longitudinal strain (GLS) providing greater sensitivity for detecting subclinical dysfunction and guiding therapeutic decisions. Traditional echocardiographic findings, such as left ventricular ejection fraction measured by 2D echocardiography, often reflect systemic vasoplegia rather than intrinsic myocardial dysfunction, complicating accurate diagnosis. Right ventricular (RV) dysfunction, identified as a critical component of SCM in many studies, has multifactorial pathophysiology. Factors including septic cardiomyopathy itself, mechanical ventilation, hypoxemia, and hypercapnia—particularly in cases complicated by acute respiratory distress syndrome (ARDS)—increase RV afterload and exacerbate RV dysfunction. The prognostic value of cardiac biomarkers, such as troponins and natriuretic peptides, remains uncertain, as these markers primarily reflect illness severity rather than being specific to SCM. Treatment focuses on the early recognition of sepsis, hemodynamic optimization, and etiological interventions, as no targeted therapies currently exist. Emerging therapies, such as levosimendan and VA-ECMO, show potential in severe SCM cases, though further validation is needed. The lack of standardized diagnostic criteria, combined with the heterogeneity of sepsis presentations, poses significant challenges to the effective management of SCM. Future research should focus on developing cluster-based classification systems for septic shock patients by integrating biomarkers, echocardiographic findings, and clinical parameters. These advancements could clarify the underlying pathophysiology and enable tailored therapeutic strategies to improve outcomes for SCM patients. Full article
(This article belongs to the Section Cardiology)
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14 pages, 451 KiB  
Article
Unlocking the Predictive Power of Nutritional Scores in Septic Patients
by Arianna Toscano, Federica Bellone, Noemi Maggio, Maria Cinquegrani, Francesca Spadaro, Francesca Maria Bueti, Giuseppe Lorello, Herbert Ryan Marini, Alberto Lo Gullo, Giorgio Basile, Giovanni Squadrito, Giuseppe Mandraffino and Carmela Morace
Nutrients 2025, 17(3), 545; https://doi.org/10.3390/nu17030545 - 31 Jan 2025
Cited by 2 | Viewed by 1335
Abstract
Background: Sepsis is a critical condition characterized by severe immune dysregulation, ranking among the leading causes of morbidity and mortality in intensive care and internal medicine units. Nutritional status plays a pivotal role in modulating these responses, as when inadequate it can [...] Read more.
Background: Sepsis is a critical condition characterized by severe immune dysregulation, ranking among the leading causes of morbidity and mortality in intensive care and internal medicine units. Nutritional status plays a pivotal role in modulating these responses, as when inadequate it can compromise immune defenses, the body’s ability to handle stress and inflammation, and the clinical course. Malnutrition is frequently observed in septic patients and is strongly associated with worse clinical outcomes, including increased mortality, prolonged hospital stays, and greater complication rates. In this context, nutritional scoring systems have emerged as valuable tools to evaluate patients’ nutritional status and predict clinical trajectories. Objectives: Given the absence of a direct comparison of their performance in an internal medicine setting, this study aimed to assess the effectiveness of various nutritional scores as predictive tools for clinical outcomes in septic patients, emphasizing their application within the field of internal medicine. Methods and Results: A retrospective analysis was conducted on 143 patients diagnosed with sepsis or septic shock who were admitted to an internal medicine unit. Key variables included clinical and laboratory parameters, comorbidities, and nutritional scores at the time of diagnosis. The modified Glasgow Prognostic Score (mGPS), the Prognostic Nutritional Index (PNI), the Controlling Nutritional Status (CONUT) score, the modified Nutrition Risk in Critically Ill (mNUTRIC) score, and the blood urea nitrogen-to-albumin ratio (BAR) were evaluated in forecasting mortality and clinical outcomes in patients with sepsis. Among them, the mNUTRIC score emerged as the strongest independent predictor of in-hospital mortality, with a good performance and a reasonable threshold for risk stratification. Conclusions: The study highlights the mNUTRIC score’s practicality and reliability in assessing nutritional and inflammatory risks in septic patients, particularly in non-ICU settings. These findings suggest its potential utility in guiding nutritional interventions and improving clinical outcomes, emphasizing the importance of integrating nutritional assessment into sepsis management. Full article
(This article belongs to the Section Clinical Nutrition)
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14 pages, 1853 KiB  
Article
Healthcare Professionals’ Perspectives on Sepsis Care Pathways—Qualitative Pilot Expert Interviews
by Lea Draeger, Carolin Fleischmann-Struzek, Jutta Bleidorn, Lena Kannengiesser, Konrad Schmidt, Christian Apfelbacher and Claudia Matthaeus-Kraemer
J. Clin. Med. 2025, 14(2), 619; https://doi.org/10.3390/jcm14020619 - 18 Jan 2025
Viewed by 1487
Abstract
Background/Objectives: Despite recent decades’ rapid advances in the management of patients with sepsis and septic shock, global sepsis mortality and post-acute sepsis morbidity rates remain high. Our aim was, therefore, to provide a first overview of sepsis care pathways as well as [...] Read more.
Background/Objectives: Despite recent decades’ rapid advances in the management of patients with sepsis and septic shock, global sepsis mortality and post-acute sepsis morbidity rates remain high. Our aim was, therefore, to provide a first overview of sepsis care pathways as well as barriers and supportive conditions for optimal pre-clinical, clinical, and post-acute sepsis care in Germany. Methods: Between May and September 2023, we conducted semi-structured, video-based, one-to-one pilot expert interviews with healthcare professionals representing pre-hospital, clinical, and post-acute care settings. The interviews were audio-recorded, transcribed verbatim, and analyzed according to the principles of Mayring’s content analysis. Results: The eight interviewed professionals identified perceived critical success factors along the entire care pathway with regard to early detection (e.g., disease awareness), early acute treatment (e.g., unknown origin of infection), rehabilitation/aftercare (e.g., availability of primary care actors), and patient transitions within and between sectors (e.g., advance notice of patient arrival). These critical factors comprised: (1) the characteristics of the staff providing care (e.g., available experience), (2) the aids/utilities used (e.g., SOPs), (3) the presentation of the disease (e.g., clear symptoms), (4) the workplace (e.g., high workload), and (5) the cooperation between the staff caring for the patient (e.g., announced and standardized handovers). Conclusions: Apart from the specific recommendations that can be derived from the individual factors presented, it can be summarized that all levels of care seem only to be purposeful if providers collaborate and communicate efficiently (i.e., correct triage, multiple-eye principle, transfer management, provision of content-rich medical/discharge letters). Full article
(This article belongs to the Section Emergency Medicine)
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17 pages, 960 KiB  
Review
The Need for Standardized Guidelines for the Use of Monocyte Distribution Width (MDW) in the Early Diagnosis of Sepsis
by Andrea Piccioni, Fabio Spagnuolo, Silvia Baroni, Gabriele Savioli, Federico Valletta, Maria Chiara Bungaro, Gianluca Tullo, Marcello Candelli, Antonio Gasbarrini and Francesco Franceschi
J. Pers. Med. 2025, 15(1), 5; https://doi.org/10.3390/jpm15010005 - 27 Dec 2024
Viewed by 1845
Abstract
Sepsis is a complex and potentially life-threatening syndrome characterized by an abnormal immune response to an infection, which can lead to organ dysfunction, septic shock, and death. Early diagnosis is crucial to improving prognosis and reducing hospital management costs. This narrative review aims [...] Read more.
Sepsis is a complex and potentially life-threatening syndrome characterized by an abnormal immune response to an infection, which can lead to organ dysfunction, septic shock, and death. Early diagnosis is crucial to improving prognosis and reducing hospital management costs. This narrative review aims to summarize and evaluate the current literature on the role of monocyte distribution width (MDW) as a diagnostic biomarker for sepsis, highlighting its advantages, limitations, and potential clinical applications. MDW measures the volumetric distribution width of monocytes, reflecting monocytic anisocytosis, and is detected using advanced hematological analyzers. In 2019, it was approved by the FDA as a biomarker for sepsis due to its ability to identify systemic inflammatory response at an early stage. Thirty-one studies analyzed by us have shown that an increased MDW value is associated with a higher risk of sepsis and that its combination with clinical parameters (such as qSOFA) and other biomarkers (CRP, PCT) can enhance diagnostic sensitivity and risk stratification capacity. Despite its high sensitivity, MDW has lower specificity compared to more established biomarkers such as procalcitonin, thus requiring a multimodal integration for an accurate diagnosis. The use of MDW in emergency and intensive care settings represents an opportunity to improve early sepsis diagnosis and critical patient management, particularly when combined with other markers and clinical tools. However, further studies are needed to define a universal cut-off and confirm its validity in different clinical contexts and pathological scenarios. Full article
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10 pages, 965 KiB  
Article
Evaluating the Accuracy of the SIL Score for Predicting the Sepsis Mortality in Emergency Department Triages: A Comparative Analysis with NEWS and SOFA
by German Devia Jaramillo, Lilia Erazo Guerrero, Natalia Florez Zuñiga and Ronal Mauricio Martin Cuesta
J. Clin. Med. 2024, 13(24), 7787; https://doi.org/10.3390/jcm13247787 - 20 Dec 2024
Viewed by 769
Abstract
Background/Objective: Sepsis is a disease with a high mortality rate, which emphasizes the importance of developing tools for the early identification of high-risk patients and to initiate timely treatments to reduce mortality. The SIL score is a scale that uses the shock index [...] Read more.
Background/Objective: Sepsis is a disease with a high mortality rate, which emphasizes the importance of developing tools for the early identification of high-risk patients and to initiate timely treatments to reduce mortality. The SIL score is a scale that uses the shock index and arterial lactate level to identify early on the patients that are at a high risk of in-hospital mortality due to sepsis. The purpose of this study was to validate the SIL score as a tool for estimating the probability of sepsis in-hospital mortality from the triage room in emergency departments. Additionally, the advantages of the SIL score were evaluated in comparison with NEWS and SOFA. Methods: All of the patients with suspected sepsis were prospectively recruited from the triage room in an emergency department. The SIL score, as well as other evaluation scales, were calculated for these patients. The sensitivity, specificity, predictive values, and areas under the curve (AUC) of each scale were assessed to predict mortality. Results: This study included 315 patients. The total mortality of the cohort was 20.4%. Of the total population, 35.5% were in septic shock. The SIL, NEWS, and SOFA scores had similar sensitivities, approximately 60%; however, a higher specificity was documented in the SIL score over the other scales (67%). The SIL score demonstrated superior discriminatory ability compared to the NEWS and SOFA scores (AUC = 0.754, p = 0.01). Conclusions: The SIL score proved to be a useful tool for predicting in-hospital mortality due to sepsis. Its discriminatory ability surpasses that of other evaluated scales. Therefore, the SIL score can be successfully implemented in the triage room of emergency departments to improve the identification and early management of patients with sepsis. Full article
(This article belongs to the Section Intensive Care)
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