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Diagnostics
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Diagnosis and Prognosis of Sepsis
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Diagnosis and Prognosis of Sepsis

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Clinical Diagnosis and Prognosis".

Deadline for manuscript submissions: 30 April 2026 | Viewed by 28299

Special Issue Editor

Dr. Zhongheng Zhang

E-Mail Website
Guest Editor
Department of Emergency Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
Interests: emergency and critical care medicine; AI
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Sepsis, characterized by an uncontrolled inflammatory response in the presence of an infection, remains one of the most extensively studied diseases in the critical care setting. This Special Issue is dedicated to advancing the diagnosis and prognosis of sepsis. We welcome a diverse range of contributions, including reviews, original research articles, case reports, interesting images and guidelines, all aiming to advance our understanding of sepsis.

Dr. Zhongheng Zhang
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (7 papers)

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Research

Jump to: Review

13 pages, 714 KB  
Article
Free Thyroxine as a Predictor of Mortality in Critically Ill Septic Patients—A Retrospective Study
by Matei Florin Negruț, Vlad Pastor, Robert Bolcaș, Oana Antal, Robert Szabo and Cristina Petrișor
Diagnostics 2026, 16(5), 680; https://doi.org/10.3390/diagnostics16050680 - 26 Feb 2026
Viewed by 91
Abstract
Background/Objectives: Euthyroid sick syndrome (ESS), and particularly low T3, have been associated with increased mortality in septic patients, yet the prognostic value of free thyroxine (fT4) remains controversial. This study aims to evaluate the association between fT4 on ICU admission and mortality in [...] Read more.
Background/Objectives: Euthyroid sick syndrome (ESS), and particularly low T3, have been associated with increased mortality in septic patients, yet the prognostic value of free thyroxine (fT4) remains controversial. This study aims to evaluate the association between fT4 on ICU admission and mortality in septic patients. Methods: We conducted a single-center, retrospective observational study including 149 adult patients with sepsis or septic shock admitted to the Anesthesia and Intensive Care I Department of the Cluj County Emergency Hospital, Cluj-Napoca, Romania, between January 2019 and September 2025. Free T4 and thyroid-stimulating hormone (TSH) levels were measured within 24 h of ICU admission. The primary outcome was 28-day mortality, and the secondary outcome was in-hospital mortality. Demographic data, comorbidities, severity scores (SOFA, APACHE II), laboratory parameters, and outcomes were analyzed. Univariate and multivariate logistic regression analyses were performed, and predictive performance was assessed using area under the receiver operating characteristic curve (AUROC). Results: A total of 149 patients were included. Twenty-eight-day mortality was 29.73%, and 53.57% in patients with sepsis and septic shock, respectively. Serum fT4 was significantly lower in non-survivors, for both primary and secondary outcome (p = 0.01 and p = 0.014, respectively), whereas TSH levels were similar between groups. In the univariate analysis, fT4 showed moderate predictive ability for mortality (AUROC 0.615 and 0.632). Multivariate models, including age, hemoglobin, SOFA score, and fT4, showed a greater discriminative performance (AUROC 0.805 and 0.799). Conclusions: Lower fT4 levels on ICU admission seem to be independently associated with increased mortality in septic patients. Incorporating fT4 into multiparametric prognostic models might improve early risk stratification in sepsis, particularly in settings where other thyroid parameters are not routinely available. Full article
(This article belongs to the Special Issue Diagnosis and Prognosis of Sepsis)
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13 pages, 889 KB  
Article
Evaluation of the Course of Acute-Phase Reactants in the Postoperative Period of Newborns and Their Diagnostic Utility in Identifying Postoperative Sepsis
by Erkan Deniz, Leyla Sero, Duygu Tuncel and Nilufer Okur
Diagnostics 2026, 16(4), 545; https://doi.org/10.3390/diagnostics16040545 - 12 Feb 2026
Viewed by 201
Abstract
Background/Objectives: Neonatal sepsis remains a major diagnostic challenge, particularly in postoperative infants where systemic inflammatory responses may mimic infection; therefore, reliable biomarkers are urgently needed to distinguish sepsis from normal post-surgical changes. Methods: This prospective cohort study included 135 neonates who [...] Read more.
Background/Objectives: Neonatal sepsis remains a major diagnostic challenge, particularly in postoperative infants where systemic inflammatory responses may mimic infection; therefore, reliable biomarkers are urgently needed to distinguish sepsis from normal post-surgical changes. Methods: This prospective cohort study included 135 neonates who underwent surgery without preoperative signs of infection. Serum levels of C-reactive protein (CRP) and procalcitonin (PCT) were measured preoperatively and at 24, 72 and 120 h postoperatively. Patients were classified as having proven sepsis based on positive blood cultures or clinical sepsis using European Medicines Agency (EMA) neonatal sepsis scoring. Biomarker levels were compared between septic and non-septic infants, and diagnostic performance was evaluated using receiver operating characteristic analysis. Results: Sixteen infants had proven sepsis and twenty-five had clinical sepsis. Both CRP and PCT levels showed a significant rise in septic infants at 72 h postoperatively (p < 0.01) and remained elevated at 120 h. PCT demonstrated the highest diagnostic accuracy at 72 h (AUC 0.911; threshold 1.2 µg/L; sensitivity 83%; specificity 84%), while CRP also showed good performance (AUC 0.802–0.838). Conclusions: CRP, PCT and albumin are valuable postoperative sepsis markers; however, single-parameter interpretation is insufficient, and a multiparametric, time-dependent approach provides superior diagnostic reliability in neonatal sepsis. Full article
(This article belongs to the Special Issue Diagnosis and Prognosis of Sepsis)
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12 pages, 3524 KB  
Article
Is GDF15 a Feasible Biomarker in Sepsis?
by Ertugrul Yigit, Mehmet Akif Simsek, Merve Huner Yigit, Gorkem Akca, Berat Sonmez and Hakki Uzun
Diagnostics 2025, 15(17), 2224; https://doi.org/10.3390/diagnostics15172224 - 2 Sep 2025
Cited by 1 | Viewed by 1059
Abstract
Background/Objectives: Sepsis is a high-mortality syndrome characterized by organ dysfunction resulting from a dysregulated host response to infection. This study aimed to evaluate the potential of growth differentiation factor 15 (GDF15), a stress-inducible cytokine, as a biomarker in patients diagnosed with urosepsis. [...] Read more.
Background/Objectives: Sepsis is a high-mortality syndrome characterized by organ dysfunction resulting from a dysregulated host response to infection. This study aimed to evaluate the potential of growth differentiation factor 15 (GDF15), a stress-inducible cytokine, as a biomarker in patients diagnosed with urosepsis. Methods: A total of 13 patients diagnosed with urosepsis, based on an increase of ≥2 points in the Sequential Organ Failure Assessment (SOFA) score and positive urine culture, were included in the study. Daily blood samples were collected from patients for 10 days, and serum levels of GDF15, procalcitonin (PCT), and presepsin (P-SEP) were measured by ELISA. C-reactive protein (CRP), blood urea nitrogen (BUN), serum creatinine, estimated glomerular filtration rate (eGFR), hemoglobin, and neutrophil, lymphocyte, and platelet counts were determined using autoanalyzers. Temporal changes were analyzed using the Friedman test, and correlations were analyzed using Spearman’s test. Results: GDF15 levels began to decrease from Day 3, with a significant decline observed from Day 7 compared to Day 1 (p < 0.001). Similar decreasing trends were observed in CRP and PCT levels, whereas presepsin levels did not exhibit significant changes. Significant positive correlations were identified between GDF15 and CRP (r = 0.65, p = 0.015), BUN (r = 0.57, p = 0.041), and creatinine (r = 0.62, p = 0.024), and a significant negative correlation was observed with eGFR (r = −0.62, p = 0.024). No significant correlation was found between GDF15 and presepsin (p > 0.05). Conclusions: GDF15 is a biomarker sensitive to the resolution phase of inflammation and organ dysfunction in sepsis, demonstrating significant temporal changes. It holds potential as an indicator for monitoring clinical progression and assessing prognosis. Full article
(This article belongs to the Special Issue Diagnosis and Prognosis of Sepsis)
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14 pages, 1243 KB  
Article
The Prognostic Value of the CALLY Index in Sepsis: A Composite Biomarker Reflecting Inflammation, Nutrition, and Immunity
by Ali Sarıdaş and Remzi Çetinkaya
Diagnostics 2025, 15(8), 1026; https://doi.org/10.3390/diagnostics15081026 - 17 Apr 2025
Cited by 21 | Viewed by 2345
Abstract
Background/Objectives: Sepsis remains a leading cause of mortality worldwide, necessitating the development of effective prognostic markers for early risk stratification. The C-reactive protein–albumin–lymphocyte (CALLY) index is a novel biomarker that integrates inflammatory, nutritional, and immunological parameters. This study aimed to evaluate the [...] Read more.
Background/Objectives: Sepsis remains a leading cause of mortality worldwide, necessitating the development of effective prognostic markers for early risk stratification. The C-reactive protein–albumin–lymphocyte (CALLY) index is a novel biomarker that integrates inflammatory, nutritional, and immunological parameters. This study aimed to evaluate the association between the CALLY index and 30-day all-cause mortality in sepsis patients. Methods: This retrospective cohort study included adult patients diagnosed with sepsis in the emergency department between 1 January 2022, and 1 January 2025. The CALLY index was calculated as (CRP × absolute lymphocyte count)/albumin. The primary outcome was 30-day all-cause mortality. Five machine learning models—extreme gradient boosting (XGBoost), multilayer perceptron, random forest, support vector machine, and generalized linear model—were developed for mortality prediction. Four feature selection strategies (gain score, SHAP values, Boruta, and LASSO regression) were used to evaluate predictor consistency. The clinical utility of the CALLY index was assessed using decision curve analysis (DCA). Results: A total of 1644 patients were included, of whom 345 (21.0%) died within 30 days. Among the five machine learning models, the XGBoost model achieved the highest performance (AUC: 0.995, R2: 0.867, MAE: 0.063, RMSE: 0.145). In gain-based feature selection, the CALLY index emerged as the top predictor (gain: 0.187), followed by serum lactate (0.185) and white blood cell count (0.117). The CALLY index also ranked second in SHAP analysis (mean value: 0.317) and first in Boruta importance (mean importance: 37.54). DCA showed the highest net clinical benefit of the CALLY index within the 0.10–0.15 risk threshold range. Conclusions: This study demonstrates that the CALLY index is a significant predictor of 30-day mortality in sepsis patients. Machine learning analysis further reinforced the prognostic value of the CALLY index. Full article
(This article belongs to the Special Issue Diagnosis and Prognosis of Sepsis)
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13 pages, 1372 KB  
Article
The Association of Body Mass Index and Waist Circumference with Sepsis-Related Mortality in South Korea
by Tak-Kyu Oh and In-Ae Song
Diagnostics 2024, 14(6), 574; https://doi.org/10.3390/diagnostics14060574 - 7 Mar 2024
Cited by 5 | Viewed by 2072
Abstract
Obesity is a major public health problem worldwide and is associated with increased morbidity and mortality. However, studies have shown that obesity has sepsis-related mortality benefits. We aimed to determine whether there is an improved sepsis-related survival rate in patients with obesity in [...] Read more.
Obesity is a major public health problem worldwide and is associated with increased morbidity and mortality. However, studies have shown that obesity has sepsis-related mortality benefits. We aimed to determine whether there is an improved sepsis-related survival rate in patients with obesity in South Korea. We included data from 77,810 adults with sepsis between 1 January 2013 and 31 December 2020, extracted from the National Health Insurance Service database in South Korea. The patients underwent standard health examinations within a year before sepsis, and body mass index (BMI) and waist circumference (WC) were used to reflect obesity. Lower 30-day and 1-year mortality rates were observed in the overweight and obesity groups after adjusting for confounders, including WC. However, there was no difference in mortality between the patients with severe obesity and those with normal BMI. Underweight was associated with higher 30-day and 1-year mortality. Higher 30-day and 1-year mortality was found in the high and very high WC groups. In conclusion, patients with abdominal obesity and overweight and obesity and with sepsis showed reduced mortality, whereas underweight patients with sepsis showed increased mortality in South Korea. Full article
(This article belongs to the Special Issue Diagnosis and Prognosis of Sepsis)
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Review

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16 pages, 1869 KB  
Review
Sepsis-Associated Acute Kidney Injury: What’s New Regarding Its Diagnostics and Therapeutics?
by Dimitris Kounatidis, Ilektra Tzivaki, Stavroula Daskalopoulou, Anna Daskou, Andreas Adamou, Anastasia Rigatou, Evangelos Sdogkos, Irene Karampela, Maria Dalamaga and Natalia G. Vallianou
Diagnostics 2024, 14(24), 2845; https://doi.org/10.3390/diagnostics14242845 - 17 Dec 2024
Cited by 10 | Viewed by 8750
Abstract
Sepsis-associated acute kidney injury (SA-AKI) is defined as the development of AKI in the context of a potentially life-threatening organ dysfunction attributed to an abnormal immune response to infection. SA-AKI has been associated with increased mortality when compared to sepsis or AKI alone. [...] Read more.
Sepsis-associated acute kidney injury (SA-AKI) is defined as the development of AKI in the context of a potentially life-threatening organ dysfunction attributed to an abnormal immune response to infection. SA-AKI has been associated with increased mortality when compared to sepsis or AKI alone. Therefore, its early recognition is of the utmost importance in terms of its morbidity and mortality rates. The aim of this review is to shed light on the pathophysiological pathways implicated in SA-AKI as well as its diagnostics and therapeutics. In this review, we will elucidate upon serum and urinary biomarkers, such as creatinine, cystatin, neutrophil gelatinase-associated lipocalin (NGAL), proenkephalin A 119–159, interleukin-6, interleukin-8 and interleukin-18, soluble toll-like receptor 2 (sTLR2), chemokine ligand 2 (CCL2) and chemokine C-C-motif 14 (CCL14). In addition, the role of RNA omics as well as machine learning programs for the timely diagnosis of SA-AKI will be further discussed. Moreover, regarding SA-AKI treatment, we will elaborate upon potential therapeutic agents that are being studied, based on the pathophysiology of SA-AKI, in humans and in animal models. Full article
(This article belongs to the Special Issue Diagnosis and Prognosis of Sepsis)
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18 pages, 679 KB  
Review
Advancing Pathogen Identification: The Role of Digital PCR in Enhancing Diagnostic Power in Different Settings
by Alessia Mirabile, Giuseppe Sangiorgio, Paolo Giuseppe Bonacci, Dalida Bivona, Emanuele Nicitra, Carmelo Bonomo, Dafne Bongiorno, Stefania Stefani and Nicolò Musso
Diagnostics 2024, 14(15), 1598; https://doi.org/10.3390/diagnostics14151598 - 25 Jul 2024
Cited by 38 | Viewed by 12466
Abstract
Digital polymerase chain reaction (dPCR) has emerged as a groundbreaking technology in molecular biology and diagnostics, offering exceptional precision and sensitivity in nucleic acid detection and quantification. This review highlights the core principles and transformative potential of dPCR, particularly in infectious disease diagnostics [...] Read more.
Digital polymerase chain reaction (dPCR) has emerged as a groundbreaking technology in molecular biology and diagnostics, offering exceptional precision and sensitivity in nucleic acid detection and quantification. This review highlights the core principles and transformative potential of dPCR, particularly in infectious disease diagnostics and environmental surveillance. Emphasizing its evolution from traditional PCR, dPCR provides accurate absolute quantification of target nucleic acids through advanced partitioning techniques. The review addresses the significant impact of dPCR in sepsis diagnosis and management, showcasing its superior sensitivity and specificity in early pathogen detection and identification of drug-resistant genes. Despite its advantages, challenges such as optimization of experimental conditions, standardization of data analysis workflows, and high costs are discussed. Furthermore, we compare various commercially available dPCR platforms, detailing their features and applications in clinical and research settings. Additionally, the review explores dPCR’s role in water microbiology, particularly in wastewater surveillance and monitoring of waterborne pathogens, underscoring its importance in public health protection. In conclusion, future prospects of dPCR, including methodological optimization, integration with innovative technologies, and expansion into new sectors like metagenomics, are explored. Full article
(This article belongs to the Special Issue Diagnosis and Prognosis of Sepsis)
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