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Sepsis and Organ Dysfunction: New Insights into Diagnosis and Treatment
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Sepsis and Organ Dysfunction: New Insights into Diagnosis and Treatment

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Intensive Care".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 7130

Special Issue Editor

Dr. Barbara Adamik

E-Mail Website
Guest Editor
Clinical Department of Anaesthesiology and Intensive Therapy, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland
Interests: sepsis; septic shock endotoxemia; biomarkers; inflammation; blood purification; adsorption; coagulation disorders; multiorgan dysfunction syndrome
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Knowledge of the pathophysiology of organ dysfunction in sepsis is important for selecting optimal patient treatment, as well as for developing potential new therapies. Dysfunction of one organ in the course of sepsis is rare, and failure of several organs usually develops within a short period of time. Mortality in patients with sepsis correlates with the number of organs involved. Most organ dysfunction in sepsis is reversible.

Current sepsis treatment is aimed at limiting the development of organ dysfunction by (1) infection control, (2) hemodynamic stabilization, and (3) organ support in restoring their function. Understanding the molecular mechanisms of organ damage contributes to the development of novel therapeutic methods and the better utilization of those routinely used, thus improving the prognosis of patients.

In this Special Issue of the Journal of Clinical Medicine, we will discuss the etiology, clinical manifestations, diagnosis, and optimal treatment strategies for organ dysfunction in sepsis. Submissions of clinical studies that include patients are welcome.

Dr. Barbara Adamik
Guest Editor

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Keywords

  • intensive care
  • sepsis
  • septic shock
  • biomarkers
  • multiorgan dysfunction syndrome
  • ex-tracorporeal methods
  • mortality

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Published Papers (6 papers)

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17 pages, 2124 KiB  
Article
Searching for Infectious Foci in Intensive Care Patients: Diagnostic Yield of Computed Tomography and Prognostic Value of Clinical and Laboratory Chemical Parameters
by Ron Martin, Dieter Fedders, Robert Winzer, Jonas Roos, Alexander Isaak, Julian Luetkens, Daniel Thomas and Daniel Kuetting
J. Clin. Med. 2025, 14(7), 2180; https://doi.org/10.3390/jcm14072180 - 22 Mar 2025
Viewed by 260
Abstract
Background/Objectives: Radiological imaging is crucial in intensive care settings, particularly for the differential diagnosis of fever and sepsis. Computed tomography (CT) is the preferred method for detecting infectious foci in critically ill ICU patients. Methods: This study prospectively analyzed non-ECG-gated chest and abdominal [...] Read more.
Background/Objectives: Radiological imaging is crucial in intensive care settings, particularly for the differential diagnosis of fever and sepsis. Computed tomography (CT) is the preferred method for detecting infectious foci in critically ill ICU patients. Methods: This study prospectively analyzed non-ECG-gated chest and abdominal CT scans from ICU patients to assess CT’s diagnostic utility. Data from prior imaging modalities (CT, radiography, MRI, ultrasound), microbiological assays (blood cultures, bronchoalveolar lavage, urinalysis), and enzymatic profiles (transaminases, pancreatic enzymes) were included. The predictive value of clinical and laboratory parameters was evaluated via correlation analysis. Results: A total of 112 patients were evaluated, with 99 exhibiting 147 inflammatory foci (92 thoracic, 55 abdominal). Definitive diagnoses were made in 58.5% of cases, while 41.5% remained classified as possible. Prior diagnostic procedures identified inflammatory origins in 57.1% of cases. Fewer CT-detected foci were observed in patients with bronchial asthma or type 2 diabetes mellitus (p = 0.049 and p = 0.006). Conclusions: CT imaging plays a central role in identifying infectious foci in ICU patients with unexplained syndromes, particularly in the thoracic region. CT scanning is recommended for sepsis management when other diagnostic evidence is lacking. Conditions such as bronchial asthma or diabetes mellitus may prompt earlier suspicion of infectious foci due to elevated inflammatory markers. Full article
(This article belongs to the Special Issue Sepsis and Organ Dysfunction: New Insights into Diagnosis and Treatment)
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13 pages, 1840 KiB  
Article
Association Between Plasma Granzyme B Levels, Organ Failure, and 28-Day Mortality Prediction in Patients with Sepsis
by Min Seo Ki, Ju Hye Shin, Min Dong Sung, Shihwan Chang, Ah Young Leem, Su Hwan Lee, Moo Suk Park, Young Sam Kim and Kyung Soo Chung
J. Clin. Med. 2025, 14(5), 1461; https://doi.org/10.3390/jcm14051461 - 21 Feb 2025
Viewed by 218
Abstract
Background/Objectives: Sepsis is basically an inflammatory disease that involves the host’s immune response. Granzyme B, a cytotoxic protease, has garnered attention for its involvement in modulating immune responses. This study aimed to elucidate the clinical implications of granzyme B in critically ill [...] Read more.
Background/Objectives: Sepsis is basically an inflammatory disease that involves the host’s immune response. Granzyme B, a cytotoxic protease, has garnered attention for its involvement in modulating immune responses. This study aimed to elucidate the clinical implications of granzyme B in critically ill patients with sepsis, focusing on plasma granzyme B levels as a potential prognostic marker. Methods: We conducted a retrospective analysis of sequentially collected blood samples from 57 sepsis patients admitted to the medical intensive care unit at Severance Hospital, a tertiary hospital in Seoul, South Korea. Clinical and laboratory data were comparatively analyzed between 28-day survivors and nonsurvivors. Results: The number of patients in the survivor and nonsurvivor groups was 32 (56.1%) and 25 (43.9%), respectively. Compared to survivors, nonsurvivors had higher APACHE II (23.5 vs. 34, p = 0.007) and SOFA (10 vs. 15, p = 0.001) scores, as well as increased levels of serum lactate (1.8 vs. 9.2 mmol/L, p < 0.001) and plasma granzyme B (28.2 vs. 71 pg/mL, p < 0.001). Granzyme B exhibited a robust area under the receiving operating characteristic (AUROC) for predicting 28-day mortality (AUROC = 0.794), comparable to lactate (0.804), SOFA (0.764), and APACHE II (0.709). The combined index of lactate and granzyme B demonstrated the highest AUROC (0.838) among all investigated predictors. Significant positive correlations were observed between log granzyme B and various inflammatory cytokines, including log IFN-γ (r = 0.780), IL-4 (r = 0.540), IL-10 (r = 0.534), and IL-6 (r = 0.520). Conclusions: Plasma granzyme B demonstrated fair short-term mortality prediction among patients admitted to the ICU, suggesting its potential utility for risk stratification and managing patients with sepsis. Full article
(This article belongs to the Special Issue Sepsis and Organ Dysfunction: New Insights into Diagnosis and Treatment)
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23 pages, 3763 KiB  
Article
Rapid and Robust Identification of Sepsis Using SeptiCyte RAPID in a Heterogeneous Patient Population
by Robert Balk, Annette M. Esper, Greg S. Martin, Russell R. Miller III, Bert K. Lopansri, John P. Burke, Mitchell Levy, Richard E. Rothman, Franco R. D’Alessio, Venkataramana K. Sidhaye, Neil R. Aggarwal, Jared A. Greenberg, Mark Yoder, Gourang Patel, Emily Gilbert, Jorge P. Parada, Majid Afshar, Jordan A. Kempker, Tom van der Poll, Marcus J. Schultz, Brendon P. Scicluna, Peter M. C. Klein Klouwenberg, Janice Liebler, Emily Blodget, Santhi Kumar, Xue W. Mei, Krupa Navalkar, Thomas D. Yager, Dayle Sampson, James T. Kirk, Silvia Cermelli, Roy F. Davis and Richard B. Brandonadd Show full author list remove Hide full author list
J. Clin. Med. 2024, 13(20), 6044; https://doi.org/10.3390/jcm13206044 - 10 Oct 2024
Viewed by 2740
Abstract
Background/Objective: SeptiCyte RAPID is a transcriptional host response assay that discriminates between sepsis and non-infectious systemic inflammation (SIRS) with a one-hour turnaround time. The overall performance of this test in a cohort of 419 patients has recently been described [Balk et al., J [...] Read more.
Background/Objective: SeptiCyte RAPID is a transcriptional host response assay that discriminates between sepsis and non-infectious systemic inflammation (SIRS) with a one-hour turnaround time. The overall performance of this test in a cohort of 419 patients has recently been described [Balk et al., J Clin Med 2024, 13, 1194]. In this study, we present the results from a detailed stratification analysis in which SeptiCyte RAPID performance was evaluated in the same cohort across patient groups and subgroups encompassing different demographics, comorbidities and disease, sources and types of pathogens, interventional treatments, and clinically defined phenotypes. The aims were to identify variables that might affect the ability of SeptiCyte RAPID to discriminate between sepsis and SIRS and to determine if any patient subgroups appeared to present a diagnostic challenge for the test. Methods: (1) Subgroup analysis, with subgroups defined by individual demographic or clinical variables, using conventional statistical comparison tests. (2) Principal component analysis and k-means clustering analysis to investigate phenotypic subgroups defined by unique combinations of demographic and clinical variables. Results: No significant differences in SeptiCyte RAPID performance were observed between most groups and subgroups. One notable exception involved an enhanced SeptiCyte RAPID performance for a phenotypic subgroup defined by a combination of clinical variables suggesting a septic shock response. Conclusions: We conclude that for this patient cohort, SeptiCyte RAPID performance was largely unaffected by key variables associated with heterogeneity in patients suspected of sepsis. Full article
(This article belongs to the Special Issue Sepsis and Organ Dysfunction: New Insights into Diagnosis and Treatment)
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8 pages, 1549 KiB  
Article
Capillary Refill Time as a Part of Routine Physical Examination in Critically Ill Patients Undergoing Vasoactive Therapy: A Prospective Study
by Fabian Wesołek, Zbigniew Putowski, Wiktoria Staniszewska, Robert Latacz and Łukasz J. Krzych
J. Clin. Med. 2024, 13(19), 5782; https://doi.org/10.3390/jcm13195782 - 28 Sep 2024
Viewed by 1390
Abstract
Background/Objectives: In critically ill patients, achieving a mean arterial pressure (MAP) of 65 mmHg is a recommended resuscitation goal to ensure proper tissue oxygenation. Unfortunately, some patients do not benefit from providing such a value, suggesting that other indices are needed for better [...] Read more.
Background/Objectives: In critically ill patients, achieving a mean arterial pressure (MAP) of 65 mmHg is a recommended resuscitation goal to ensure proper tissue oxygenation. Unfortunately, some patients do not benefit from providing such a value, suggesting that other indices are needed for better hemodynamic assessment. Capillary refill time (CRT) has emerged as an established marker for peripheral perfusion and a therapeutic target in critical illness, but its relationship with other exponents of hypoperfusion during vasopressor support after resuscitation period still warrants further research. This study aimed to investigate whether in critically ill patients after initial resuscitation, CRT would provide information independent of other, readily accessible hemodynamic variables. Methods: Critically ill patients who were mechanically ventilated after the resuscitation period and receiving vasopressors were prospectively studied between December 2022 and June 2023. Vasopressor support was measured using norepinephrine equivalent doses (NEDs). CRT, MAP and NED were assessed simultaneously and analyzed using Spearman’s rank correlation. Results: A total of 92 patients were included and 210 combined MAP-CRT-NED-Lactate records were obtained. There was no correlation between CRT and MAP (R = −0.1, p = 0.14) or lactate (R = 0.11, p = 0.13), but there was a positive weak correlation between CRT and NED (R = 0.25, p = 0.0005). In patients with hypotension, in 83% of cases (15/18), CRT was within normal range, despite different doses of catecholamines. When assessing patients with high catecholamine doses, in 58% cases (11/19), CRT was normal and MAP was usually above 65 mmHg. Conclusions: Capillary refill time provides additional hemodynamic information that is not highly related with the values of mean arterial pressure, lactate level and vasopressor doses. It could be incorporated into routine physical examination in critically ill patients who are beyond initial resuscitation. Full article
(This article belongs to the Special Issue Sepsis and Organ Dysfunction: New Insights into Diagnosis and Treatment)
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19 pages, 1470 KiB  
Article
Platelet Metabolites as Candidate Biomarkers in Sepsis Diagnosis and Management Using the Proposed Explainable Artificial Intelligence Approach
by Fatma Hilal Yagin, Umran Aygun, Abdulmohsen Algarni, Cemil Colak, Fahaid Al-Hashem and Luca Paolo Ardigò
J. Clin. Med. 2024, 13(17), 5002; https://doi.org/10.3390/jcm13175002 - 23 Aug 2024
Cited by 1 | Viewed by 1514
Abstract
Background: Sepsis is characterized by an atypical immune response to infection and is a dangerous health problem leading to significant mortality. Current diagnostic methods exhibit insufficient sensitivity and specificity and require the discovery of precise biomarkers for the early diagnosis and treatment [...] Read more.
Background: Sepsis is characterized by an atypical immune response to infection and is a dangerous health problem leading to significant mortality. Current diagnostic methods exhibit insufficient sensitivity and specificity and require the discovery of precise biomarkers for the early diagnosis and treatment of sepsis. Platelets, known for their hemostatic abilities, also play an important role in immunological responses. This study aims to develop a model integrating machine learning and explainable artificial intelligence (XAI) to identify novel platelet metabolomics markers of sepsis. Methods: A total of 39 participants, 25 diagnosed with sepsis and 14 control subjects, were included in the study. The profiles of platelet metabolites were analyzed using quantitative 1H-nuclear magnetic resonance (NMR) technology. Data were processed using the synthetic minority oversampling method (SMOTE)-Tomek to address the issue of class imbalance. In addition, missing data were filled using a technique based on random forests. Three machine learning models, namely extreme gradient boosting (XGBoost), light gradient boosting machine (LightGBM), and kernel tree boosting (KTBoost), were used for sepsis prediction. The models were validated using cross-validation. Clinical annotations of the optimal sepsis prediction model were analyzed using SHapley Additive exPlanations (SHAP), an XAI technique. Results: The results showed that the KTBoost model (0.900 accuracy and 0.943 AUC) achieved better performance than the other models in sepsis diagnosis. SHAP results revealed that metabolites such as carnitine, glutamate, and myo-inositol are important biomarkers in sepsis prediction and intuitively explained the prediction decisions of the model. Conclusion: Platelet metabolites identified by the KTBoost model and XAI have significant potential for the early diagnosis and monitoring of sepsis and improving patient outcomes. Full article
(This article belongs to the Special Issue Sepsis and Organ Dysfunction: New Insights into Diagnosis and Treatment)
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14 pages, 547 KiB  
Case Report
Hemoperfusion Using the Oxiris Membrane in Septic Shock Patients with Preserved Kidney Function: A Case Series
by Darja Smirnova, Rihards Serzans, Mara Klibus, Valdis Liguts, Anna Lece, Andrejs Skesters, Gianluca Villa and Olegs Sabelnikovs
J. Clin. Med. 2025, 14(6), 2113; https://doi.org/10.3390/jcm14062113 - 19 Mar 2025
Viewed by 437
Abstract
Background/Objectives: Sepsis, a life-threatening condition caused by a dysregulated immune response to infection, is associated with high mortality. Endotoxin and cytokine overload play a crucial role in sepsis-induced organ dysfunction. The Oxiris® membrane, traditionally used as a hemofilter for renal replacement [...] Read more.
Background/Objectives: Sepsis, a life-threatening condition caused by a dysregulated immune response to infection, is associated with high mortality. Endotoxin and cytokine overload play a crucial role in sepsis-induced organ dysfunction. The Oxiris® membrane, traditionally used as a hemofilter for renal replacement therapy, has demonstrated the capacity to adsorb endotoxins and cytokines. This study investigates the clinical effect during hemoperfusion with the Oxiris® membrane in patients with septic shock and preserved renal function. Methods: We present three adult patients with septic shock who were admitted to the intensive care unit with high vasopressor requirements and elevated inflammatory markers. As they were refractory to standard therapy and renal function was preserved, a 12-hour hemoperfusion session with an Oxiris® membrane was initiated. Hemodynamic parameters, inflammatory biomarkers, and endotoxin concentrations were evaluated before, during, and after hemoperfusion treatment. Results: All patients demonstrated hemodynamic stabilization, with norepinephrine support reduced by 10.3% to 70.0%. Key inflammatory markers decreased significantly, including interleukin-6 (−41.6% to −94.0%), procalcitonin (−29.3% to −49.5%), and C-reactive protein (4.7% to −37.2%). Endotoxin concentrations decreased by 62.0% and 13.6% in two of the three patients. No adverse effects related to hemoperfusion were observed. Conclusions: Hemoperfusion with the Oxiris® membrane effectively reduced vasopressor support, inflammatory markers, and endotoxin concentrations in patients with refractory septic shock. This approach may offer a novel strategy for early immune modulation in sepsis before renal dysfunction occurs. Further studies with larger cohorts are required to validate these findings and determine optimal treatment protocols. Full article
(This article belongs to the Special Issue Sepsis and Organ Dysfunction: New Insights into Diagnosis and Treatment)
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