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14 pages, 580 KB  
Article
A Comparative Analysis of Early Ventilator Mechanics in COVID-19 vs. Non-COVID-19 ARDS: A Single-Center ED-Based Cohort Study
by Murtaza Kaya, Ceyda Nur Irk, Mehmed Ulu, Harun Yildirim, Mehmet Toprak and Sami Eksert
Healthcare 2025, 13(17), 2139; https://doi.org/10.3390/healthcare13172139 (registering DOI) - 27 Aug 2025
Abstract
Background and Aim: Mechanical ventilatory support is often required in patients with acute respiratory distress syndrome (ARDS). However, early differences in ventilatory mechanics and severity scores between COVID-19 and non-COVID-19 ARDS patients remain unclear. This study aimed to compare respiratory parameters and clinical [...] Read more.
Background and Aim: Mechanical ventilatory support is often required in patients with acute respiratory distress syndrome (ARDS). However, early differences in ventilatory mechanics and severity scores between COVID-19 and non-COVID-19 ARDS patients remain unclear. This study aimed to compare respiratory parameters and clinical severity scores in COVID-19 and non-COVID-19 ARDS patients managed in the emergency department (ED) and evaluate their association with in-hospital mortality. Methods: In this retrospective cohort study, adult patients with ARDS (PaO2/FiO2 < 300 mmHg) who received mechanical ventilation in the ED were included. Ventilator parameters and clinical severity scores (SOFA, APACHE II, PSI, and Charlson Comorbidity Index) were recorded at the 120th minute after intubation. Patients were categorized as COVID-19 or non-COVID-19 ARDS, and outcomes were compared between survivors and non-survivors. Logistic regression was used to identify independent predictors of in-hospital mortality. Results: A total of 70 patients were enrolled (32 COVID-19, 38 non-COVID). Plateau pressure, driving pressure, and PEEP were significantly higher in COVID-19 patients, while compliance was without statistical significance. Overall, in-hospital mortality did not differ significantly between the COVID-19 (53.1%) and non-COVID-19 groups (71.1%, p = 0.12). Mechanical power (21.6 vs. 16.8 J/min, p = 0.01) and Charlson Comorbidity Index (6 vs. 5.5, p = 0.02) were significantly higher in non-survivors across the full cohort. Among clinical scores, SOFA was significantly higher in the COVID-19 group (p = 0.02), and APACHE II was significantly higher in non-survivors within the COVID-19 subgroup (p = 0.02). In multivariate analysis, mechanical power and Charlson Comorbidity Index were associated with mortality. Conclusions: COVID-19 patients with ARDS exhibited higher early ventilatory pressures than non-COVID-19 patients, yet early respiratory mechanics were not independently associated with mortality. Mechanical power and Charlson Comorbidity Index were significantly associated with in-hospital mortality. These findings underscore the need to consider both ventilatory load and systemic health status in early outcome assessments of ARDS patients. Full article
(This article belongs to the Section Coronaviruses (CoV) and COVID-19 Pandemic)
40 pages, 30640 KB  
Review
From Data to Diagnosis: A Novel Deep Learning Model for Early and Accurate Diabetes Prediction
by Muhammad Mohsin Zafar, Zahoor Ali Khan, Nadeem Javaid, Muhammad Aslam and Nabil Alrajeh
Healthcare 2025, 13(17), 2138; https://doi.org/10.3390/healthcare13172138 - 27 Aug 2025
Abstract
Background: Diabetes remains a major global health challenge, contributing significantly to premature mortality due to its potential progression to organ failure if not diagnosed early. Traditional diagnostic approaches are subject to human error, highlighting the need for modern computational techniques in clinical decision [...] Read more.
Background: Diabetes remains a major global health challenge, contributing significantly to premature mortality due to its potential progression to organ failure if not diagnosed early. Traditional diagnostic approaches are subject to human error, highlighting the need for modern computational techniques in clinical decision support systems. Although these systems have successfully integrated deep learning (DL) models, they still encounter several challenges, such as a lack of intricate pattern learning, imbalanced datasets, and poor interpretability of predictions. Methods: To address these issues, the temporal inception perceptron network (TIPNet), a novel DL model, is designed to accurately predict diabetes by capturing complex feature relationships and temporal dynamics. An adaptive synthetic oversampling strategy is utilized to reduce severe class imbalance in an extensive diabetes health indicators dataset consisting of 253,680 instances and 22 features, providing a diverse and representative sample for model evaluation. The model’s performance and generalizability are assessed using a 10-fold cross-validation technique. To enhance interpretability, explainable artificial intelligence techniques are integrated, including local interpretable model-agnostic explanations and Shapley additive explanations, providing insights into the model’s decision-making process. Results: Experimental results demonstrate that TIPNet achieves improvement scores of 3.53% in accuracy, 3.49% in F1-score, 1.14% in recall, and 5.95% in the area under the receiver operating characteristic curve. Conclusion: These findings indicate that TIPNet is a promising tool for early diabetes prediction, offering accurate and interpretable results. The integration of advanced DL modeling with oversampling strategies and explainable AI techniques positions TIPNet as a valuable resource for clinical decision support, paving the way for its future application in healthcare settings. Full article
19 pages, 1302 KB  
Review
The Role of Galectin-3 as a Biomarker in the Cardio–Renal–Metabolic Pathology Axis
by Oana Nicoleta Buliga-Finis, Anca Ouatu, Daniela Maria Tanase, Minerva Codruta Badescu, Nicoleta Dima, Evelina Maria Gosav, Diana Popescu and Ciprian Rezus
J. Clin. Med. 2025, 14(17), 6071; https://doi.org/10.3390/jcm14176071 (registering DOI) - 27 Aug 2025
Abstract
Galectin-3 (Gal-3), a multifunctional protein, plays a pivotal role in a wide range of physiological and pathological processes in the human body. Substantial evidence has linked its overexpression and secretion to the pathogenesis of various conditions, including diabetes mellitus, heart failure, fibrosis, atherosclerosis, [...] Read more.
Galectin-3 (Gal-3), a multifunctional protein, plays a pivotal role in a wide range of physiological and pathological processes in the human body. Substantial evidence has linked its overexpression and secretion to the pathogenesis of various conditions, including diabetes mellitus, heart failure, fibrosis, atherosclerosis, and chronic kidney disease. Diabetes mellitus, a persistent metabolic disorder, exerts profound effects on both renal and cardiovascular systems. Contemporary research has investigated a range of various biomarkers aimed at predicting the early onset of renal and cardiac dysfunction in diabetic patients. An early decline in glomerular filtration rate (GFR) may occur even with normal urinary albumin excretion. Given that NT-proBNP concentrations are influenced by GFR, there is a critical need to identify biomarkers capable of detecting early cardio–renal injury in individuals with diabetes. Elevated Gal-3 levels in diabetic patients have been associated with an increased risk of all-cause mortality, cardiovascular disease, and progressive kidney failure and may serve as an indicator of subclinical cardiac and renal dysfunction. Incorporating Gal-3 assessment into clinical practice has the potential to improve diagnostic precision and support personalized management for cardiovascular, renal, and metabolic disorders. This review aims to elucidate the role of Gal-3 as a pivotal biomarker for diagnosis, prognosis, and therapeutic guidance in general in different types of diseases which involve cardio–renal complications. Full article
(This article belongs to the Special Issue New Insights into Cardiorenal Metabolic Syndrome)
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23 pages, 3311 KB  
Article
Association of Serum Cystatin C with Stroke Morbidity and All-Cause and Cardio-Cerebrovascular Mortality: Evidence from the NHANES
by Si Hu, Guoqiang Zhang, Wei Zhou, Yi Hu, Jingwei Zheng, Fei Liu, Zhijie Jiang, Xudan Shi, Kaiyang Shao and Liang Xu
Healthcare 2025, 13(17), 2137; https://doi.org/10.3390/healthcare13172137 - 27 Aug 2025
Abstract
Background: Serum cystatin C is a promising biomarker for vascular risk, yet its nonlinear dose–response relationships and prognostic value in general populations remain unclear, particularly for stroke-specific outcomes. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted [...] Read more.
Background: Serum cystatin C is a promising biomarker for vascular risk, yet its nonlinear dose–response relationships and prognostic value in general populations remain unclear, particularly for stroke-specific outcomes. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted in 1999–2002 cycles. A total of 11,610 participants were included in the primary analysis examining the cross-sectional association between cystatin C and stroke morbidity, using multivariate logistic regression models and odds ratios (ORs). Analyses utilized complete-case data (n = 11,610 for morbidity; n = 11,598 for mortality). Subsequently, 11,598 adults were retained for mortality endpoint analyses, which focused on the longitudinal association between cystatin C and stroke mortality, using cause-specific weighted multivariable Cox models and ratios (HRs). Restricted cubic splines identified nonlinear thresholds, and piecewise regression quantified risk gradients. Models were adjusted for sociodemographic/clinical/behavioral confounders. Results: Serum cystatin C exhibited a nonlinear dose–response relationship with stroke morbidity (p for nonlinear < 0.001), with an inflection point at 1.24 mg/L; below this threshold, each 0.1 mg/L increase conferred 13.84-fold higher odds (95% CI: 7.11–27.03, p < 0.001). For mortality, nonlinear thresholds were identified at 1.24 mg/L for all-cause/cause-specific mortality (HR = 6.73–10.60 per 0.1 mg/L increase, p < 0.001) and 1.81 mg/L for stroke-specific mortality. Conversely, cerebrovascular mortality demonstrated a linear association (HR = 1.43 per 1 mg/L increase, p = 0.008), though cystatin C independently predicted risk (HR = 1.38/continuous, p = 0.034 in fully adjusted models). Conclusions: This study identifies serum cystatin C as an independent predictor after full adjustment of stroke morbidity and all-cause and cardio-cerebrovascular mortality. Consequently, cystatin C emerges as a dual-purpose biomarker for early vascular injury detection in subclinical populations and integrated mortality risk stratification. Future research should validate these thresholds in prospective neuroimaging-confirmed cohorts and investigate interventions targeting cystatin C pathways to optimize preventive strategies. Full article
19 pages, 6232 KB  
Article
Comparison of Open Versus Minimally Invasive Repair of Colovesical Fistula: A Case Report and Propensity-Matched National Database Analysis
by Alexis Volkert, Anmol Nigam, David Stover, Pravin Meshram, Rubeena Naaz, Chidiebere Onongaya, Sean Huu-Tien Nguyen, Jordan Sauve, Wolfgang Gaertner and James V. Harmon Jr.
J. Clin. Med. 2025, 14(17), 6065; https://doi.org/10.3390/jcm14176065 (registering DOI) - 27 Aug 2025
Abstract
Background: Colovesical fistulas are abnormal communications between the colon and urinary bladder, most commonly caused by diverticular disease. Although colovesical fistulas are rare, they should be suspected in patients presenting with recurrent urinary tract infections, pneumaturia, or fecaluria. We integrated two case reports [...] Read more.
Background: Colovesical fistulas are abnormal communications between the colon and urinary bladder, most commonly caused by diverticular disease. Although colovesical fistulas are rare, they should be suspected in patients presenting with recurrent urinary tract infections, pneumaturia, or fecaluria. We integrated two case reports with a retrospective national cohort analysis to assess the surgical treatment of colovesical fistulas. Methods: We report two cases of colovesical fistulas, both secondary to sigmoid diverticulitis, treated surgically via minimally invasive approaches. A retrospective analysis using the National Inpatient Sample database from 2016 to 2022 was conducted to compare outcomes of open surgery with those of minimally invasive surgery. Propensity score matching and multivariable regression analyses were used to evaluate clinical outcomes. Results: The first patient underwent hand-assisted laparoscopic sigmoidectomy with fistula takedown and has remained asymptomatic at 8 months, while the second patient underwent robotic-assisted sigmoidectomy with staged ileostomy reversal and has remained asymptomatic at 1 month. National data analysis showed no significant difference in mortality (<1% versus <1%, p = 0.931), wound complications (1.4% versus 1.0%; p = 0.554), or postoperative sepsis or shock (7.1% versus 5.6%; p = 0.114) between open and minimally invasive surgical approaches. However, the minimally invasive surgery group had significantly shorter length of stay than the open surgery group (6.9 versus 7.3 days, p < 0.001). Conclusions: Minimally invasive repair of colovesical fistulas was associated with shorter hospital stays than open surgery, with no significant differences in major complications. Early identification and timely surgical management are critical for achieving favorable outcomes. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
22 pages, 896 KB  
Review
Epigenetic Alterations in Hepatocellular Carcinoma: Mechanisms, Biomarkers, and Therapeutic Implications
by Adil Farooq Wali, Abid Reza Ansari, Prince Ahad Mir, Mohamed El-Tanani, Rasha Babiker, Md Sadique Hussain, Jasreen Uppal, Asma Ishrat Zargar and Reyaz Hassan Mir
Pharmaceuticals 2025, 18(9), 1281; https://doi.org/10.3390/ph18091281 - 27 Aug 2025
Abstract
Hepatocellular carcinoma (HCC), the most prevalent primary liver cancer, continues to pose a significant global health burden due to its high mortality rate. In addition to genetic alterations, epigenetic aberrations, including DNA methylation, histone modifications, chromatin remodeling, and noncoding RNA (ncRNA) dysregulation, play [...] Read more.
Hepatocellular carcinoma (HCC), the most prevalent primary liver cancer, continues to pose a significant global health burden due to its high mortality rate. In addition to genetic alterations, epigenetic aberrations, including DNA methylation, histone modifications, chromatin remodeling, and noncoding RNA (ncRNA) dysregulation, play critical roles in HCC initiation and progression. Notably, miR-375 and miR-483-5p are among the most dysregulated miRNAs in HCC, with their altered expression levels closely associated with tumor stage and patient survival. These epigenetic modifications offer promising therapeutic avenues due to their reversibility and dynamic nature. Furthermore, specific epigenetic signatures such as CDH1 promoter hypermethylation and HOTAIR overexpression are being explored as potential biomarkers for early detection and treatment response. In this chapter, we review recent advances in the epigenetic landscape of HCC and discuss their diagnostic and therapeutic implications, highlighting their potential to improve patient outcomes through personalized medicine approaches. Full article
(This article belongs to the Section Pharmacology)
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15 pages, 1018 KB  
Article
Development and Validation of a NEWS2-Enhanced Multivariable Prediction Model for Clinical Deterioration and In-Hospital Mortality in Hospitalized Adults
by Sofia Lo Conte, Guido Fruscoloni, Alessandra Cartocci, Martin Vitiello, Maria Francesca De Marco, Gabriele Cevenini and Paolo Barbini
Medicina 2025, 61(9), 1543; https://doi.org/10.3390/medicina61091543 - 27 Aug 2025
Abstract
Background and Objectives: Early identification of patients at risk of clinical deterioration is essential for optimizing therapeutic management and improving outcomes in general medicine wards. The National Early Warning Score 2 (NEWS2) is a validated tool for predicting patient worsening but integrating [...] Read more.
Background and Objectives: Early identification of patients at risk of clinical deterioration is essential for optimizing therapeutic management and improving outcomes in general medicine wards. The National Early Warning Score 2 (NEWS2) is a validated tool for predicting patient worsening but integrating it with additional clinical and demographic data can enhance its predictive accuracy and support timely clinical decisions. Material and methods: In this retrospective cohort study, 2108 patients admitted to the general medicine department of the University Hospital of Siena were analyzed. Logistic regression models incorporating NEWS2 alongside key clinical variables—including age, presence of central venous catheter (CVC), and functional status measured by the Barthel Index—were developed to predict high clinical risk (HCR) and mortality. Model performance was assessed using the area under the ROC curve (AUC). Results: High clinical risk status developed in 29% of patients. Older age, presence of CVC, lower Barthel Index, and higher NEWS2 scores were significantly associated with both HCR and mortality. The integrated predictive model demonstrated good accuracy, with an AUC of 0.798 for HCR and 0.716 for mortality prediction. Conclusions: This study suggests that NEWS2, when combined with additional patient-specific variables from the electronic health record, can become a more sophisticated tool for early risk stratification. Such a tool has the potential to support timely clinical intervention and optimized therapeutic management, potentially contributing to improved patient outcomes. While the model may indirectly support nurse workload balancing by identifying patients requiring intensified care, its ultimate impact on patient outcomes requires confirmation through prospective studies. Full article
(This article belongs to the Section Epidemiology & Public Health)
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20 pages, 1484 KB  
Article
Novel Computed Tomography Perfusion and Laboratory Indices as Predictors of Long-Term Outcome and Survival in Acute Ischemic Stroke
by Eray Halil, Kostadin Kostadinov, Nikoleta Traykova, Neli Atanasova, Kiril Atliev, Elizabet Dzhambazova and Penka Atanassova
Neurol. Int. 2025, 17(9), 136; https://doi.org/10.3390/neurolint17090136 - 27 Aug 2025
Abstract
Background/Objectives: Acute ischemic stroke is a leading cause of mortality and long-term disability globally, with limited reliable early predictors of functional outcomes and survival. This study aimed to assess the prognostic value of two novel predictors: the hypoperfusion intensity ratio calculated from mean [...] Read more.
Background/Objectives: Acute ischemic stroke is a leading cause of mortality and long-term disability globally, with limited reliable early predictors of functional outcomes and survival. This study aimed to assess the prognostic value of two novel predictors: the hypoperfusion intensity ratio calculated from mean transit time and time-to-drain maps (HIR-MTT–TTD), derived from computed tomography perfusion (CTP) imaging parameters, and the Inflammation–Coagulation Index (ICI), which integrates systemic inflammatory (C-reactive protein and white blood cell count) and hemostatic (D-dimer) markers. Methods: This prospective, single-center observational study included 60 patients with acute ischemic stroke treated with intravenous thrombolysis and underwent pre-treatment CTP imaging. HIR-MTT–TTD evaluated collateral status and perfusion deficit severity, while ICI integrated C-reactive protein (CRP), white blood cell (WBC) count, and D-dimer levels. Functional outcomes were assessed using the National Institutes of Health Stroke Scale (NIHSS), Barthel Index, and modified Rankin Scale (mRS) at 24 h, 3 months, and 1 year. Results: Of 60 patients, 53.3% achieved functional independence (mRS 0–2) at 1 year. Unadjusted Cox models showed HIR-MTT–TTD (HR = 6.25, 95% CI: 1.48–26.30, p = 0.013) and ICI (HR = 1.08, 95% CI: 1.00–1.17, p = 0.052) were associated with higher 12-month mortality, worse mRS, and lower Barthel scores. After adjustment for age, BMI, smoking status, and sex, these associations became non-significant (HIR-MTT–TTD: HR = 2.83, 95% CI: 0.37–21.37, p = 0.314; ICI: HR = 1.07, 95% CI: 0.96–1.19, p = 0.211). Receiver operating characteristic (ROC) analysis indicated moderate predictive value, with ICI (AUC = 0.756, 95% CI: 0.600–0.867) outperforming HIR-MTT–TTD (AUC = 0.67, 95% CI: 0.48–0.83) for mortality prediction. Conclusions: The study introduces promising prognostic tools for functional outcomes. Elevated HIR-MTT–TTD and ICI values were independently associated with greater initial stroke severity, poorer functional recovery, and increased 1-year mortality. These findings underscore the prognostic significance of hypoperfusion intensity and systemic thrombo-inflammation in acute ischemic stroke. Combining the use of the presented indices may enhance early risk stratification and guide individualized treatment strategies. Full article
(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)
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19 pages, 2530 KB  
Article
Temporary Passive Shunt for Visceral Protection During Open Thoracoabdominal Aortic Repair Under Intraoperative Advanced Hemodynamic and Perfusion Monitoring: Tertiary Hospital Institutional Bundle and Preliminary Mid-Term Results
by Ottavia Borghese, Marta Minucci, Elena Jacchia, Pierfrancesco Antonio Annuvolo, Lucia Scurto, Antonio Luparelli, Andrea Russo, Paola Aceto, Tommaso Donati and Yamume Tshomba
J. Clin. Med. 2025, 14(17), 6064; https://doi.org/10.3390/jcm14176064 (registering DOI) - 27 Aug 2025
Abstract
Background: The perfusion of viscera, kidney, and spinal cord represents one of the main concerns during open repair (OR) of Thoraco-Abdominal Aortic Aneurisms (TAAAs). Passive shunting (PS) has been historically used for intraoperative distal aortic perfusion but has been progressively replaced almost [...] Read more.
Background: The perfusion of viscera, kidney, and spinal cord represents one of the main concerns during open repair (OR) of Thoraco-Abdominal Aortic Aneurisms (TAAAs). Passive shunting (PS) has been historically used for intraoperative distal aortic perfusion but has been progressively replaced almost entirely by partial left-sided heart or total cardiopulmonary bypass with extra-corporeal circulation (ECC). Despite several advantages of these methods, PS still has potential in mitigating some drawbacks of long extracorporeal circuits connected with centrifugal or roller pumps, such as the need for cardiac and great vessels cannulation, priming and large intravascular fluid volume shifts, high heparin dose, immunosuppressive effects, and systemic inflammatory response syndrome. Methods: This study prospectively analyzed data of a cohort of patients who underwent TAAA OR using a PS in a single institution. Outcomes of interest were mortality, rate of mesenteric, renal and spinal cord ischemia, cardiac complications, and intraoperative hemodynamic stability achieved in this setting. Our institutional bundle and a comprehensive literature review about the different configurations and applicability of PS for TAAA OR is also reported. The search was performed based on three databases (PubMed, EMBASE, and Cochrane Library) by two independent reviewers (LS and AA) from inception to 31 December 2023, and the reported clinical results (visceral, renal, and spinal cord complications and mortality) using PS during TAAAs OR were analyzed. Results: Between March 2021 and December 2023, 51 TAAA repairs were performed and eleven patients (n = 8, 73% male; mean age 67 years, range 63–79) were operated using a PS for a total of one (9%) type I, one (9%) type II, two (18%) type III, five (45%) type IV, and two (18%) type V TAAA. In our early experience, PS was indicated for limited staff resources during the COVID-19 pandemic to treat five non-deferable cases. The sixth and seventh patients were selected for PS as they already had a functioning axillo-bifemoral bypass that was used for this purpose. For the most recent cases, PS was chosen as the primary perfusion method according to a score based on clinical and anatomical factors with ECC as a bailout strategy. Selective renal perfusion with cold (4 °C) Custodiol solution was the method of choice for renal protection in all cases while antegrade perfusion of the coeliac trunk and the superior mesenteric artery was assured by PS through a loop graft (8–10mm) proximally anastomosed to the axillary artery (10 patients, 90.9%) or the descending thoracic aorta (one patient, 9%) and distally anastomosed to the infrarenal aorta (3), common iliac (3), or femoral vessels (5). In-hospital mortality was 9% as one patient died on the 10th postoperative day from mesenteric ischemia following hemodynamic instability; permanent spinal cord ischemia rate was 0% and the rate of AKI stage 3 was 9% (one patient). Bailout shifting to ECC was never required. No cardiac complications, nor a significant increase in serum CK-MB were reported in any patient. No prolonged severe intraoperative hypotension episodes (Mean Arterial Pressure < 50 mmHg) were assessed using the Software Acumen Analytics (Edwards LifeSciences, Irvine CA, USA). No peri-operative coagulopathy nor major bleeding was reported. Conclusions: Our experience showed satisfactory outcomes with the use of PS in specifically selected cases. Current data indicate that PS may represent an alternative to ECC techniques during TAAAs OR in high volume centers where assisted extracorporeal circulation could eventually be applied as a bailout strategy. However, due to the small sample size of this and previously published series, more data are needed to clearly define the potential role of such approach during TAAA OR. Full article
(This article belongs to the Special Issue Vascular Surgery: Current Status and Future Perspectives)
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20 pages, 12477 KB  
Article
Transcriptome Analysis Unravels CD4+ T-Cell and Treg-Cell Differentiation in Ovarian Cancer
by Baoyi Shao, Bo Sun and Zhongdang Xiao
Biomolecules 2025, 15(9), 1241; https://doi.org/10.3390/biom15091241 - 27 Aug 2025
Abstract
Background: Ovarian cancer ranks as the fifth leading cause of cancer-related mortality among women worldwide. Owing to its insidious onset and lack of early symptoms, over 70% of patients are diagnosed at advanced stages. Methods: This study provides a comprehensive transcriptomic analysis of [...] Read more.
Background: Ovarian cancer ranks as the fifth leading cause of cancer-related mortality among women worldwide. Owing to its insidious onset and lack of early symptoms, over 70% of patients are diagnosed at advanced stages. Methods: This study provides a comprehensive transcriptomic analysis of tumor-infiltrating CD4+ T cells in ovarian cancer, highlighting regulatory T cells (Tregs) as the dominant subset. By integrating seven multicenter ovarian cancer single-cell RNA-seq datasets, a robust metadata resource was created for detailed Treg investigation. Using the BayesPrism algorithm, Treg scores from TCGA bulk RNA-seq data enabled patient stratification into high and low Treg groups. These findings were further validated through survival analyses across five independent bulk RNA-seq cohorts. We experimentally validated the inhibitory role of Tregs in modulating CD8+ T-cell activity in ovarian cancer. Results: We conducted an in-depth investigation into the clustering patterns, differentiation trajectories, intercellular interactions, and enrichment profiles of tumor-infiltrating T cells in ovarian cancer. Among the seven functionally defined subclusters (C1–C7), we delineated two distinct “terminal states” of CD4+ T-cell differentiation: FOXP3+ regulatory T cells and STMN1+ proliferative T cells. The OCSCDs dataset comprises seven datasets totaling 137,648 single cells. Using the TCGA dataset, we quantified the proportion of tumor-infiltrating regulatory T cells (Tregs) in OCSCDs through the BayesPrism algorithm and performed survival analyses across five independent bulk RNA-seq datasets from different platforms. Conclusions: Our results establish a framework for studying Treg biology in ovarian cancer and these cells may be become an important point in the field of immunotherapy. Full article
(This article belongs to the Special Issue Advanced Therapeutic Strategies for Hormone-Dependent Cancers)
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16 pages, 660 KB  
Review
The Potential of Artificial Intelligence in the Diagnosis and Prognosis of Sepsis: A Narrative Review
by George Țocu, Elena Lăcrămioara Lisă, Dana Tutunaru, Raul Mihailov, Cristina Șerban, Valerii Luțenco, Florentin Dimofte, Mădălin Guliciuc, Iulia Chiscop, Bogdan Ioan Ștefănescu, Elena Niculeț, Gabriela Gurău, Sorin Ion Berbece, Oana Mariana Mihailov and Loredana Stavăr Matei
Diagnostics 2025, 15(17), 2169; https://doi.org/10.3390/diagnostics15172169 - 27 Aug 2025
Abstract
Background/Objectives: Sepsis is a severe medical condition characterized by a dysregulated host response to infection, with potentially fatal outcomes, requiring early diagnosis and rapid intervention. The limitations of traditional sepsis identification methods, as well as the complexity of clinical data generated in intensive [...] Read more.
Background/Objectives: Sepsis is a severe medical condition characterized by a dysregulated host response to infection, with potentially fatal outcomes, requiring early diagnosis and rapid intervention. The limitations of traditional sepsis identification methods, as well as the complexity of clinical data generated in intensive care, have driven increased interest in applying artificial intelligence in this field. The aim of this narrative review article is to analyze how artificial intelligence is being used in the diagnosis and prognosis of sepsis, to present the most relevant current models and algorithms, and to discuss the challenges and opportunities related to integrating these technologies into clinical practice. Methods: We conducted a structured literature search for this narrative review, covering studies published between 2016 and 2024 in databases such as PubMed/Medline, Scopus, Web of Science, IEEE Xplore, and Google Scholar. The review covered models based on machine learning (ML), deep neural networks (DNNs), Recurrent Neural Networks (RNNs), and clinical alert systems implemented in hospitals. The clinical data sources used, algorithms applied, system architectures, and performance outcomes are presented. Results: Numerous artificial intelligence models demonstrated superior performance compared to conventional clinical scores (qSOFA, SIRS), achieving AUC values above 0.90 in predicting sepsis and mortality. Systems such as Targeted Real-Time Early Warning System (TREWS) and InSight have been clinically validated and have significantly reduced the time to treatment initiation. However, challenges remain, such as a lack of model transparency, algorithmic bias, difficulties integrating into clinical workflows, and the absence of external validation in multicenter settings. Conclusions: Artificial intelligence has the potential to transform sepsis management through early diagnosis, risk stratification, and personalized treatment. A responsible, multidisciplinary approach is necessary, including rigorous clinical validation, enhanced interpretability, and training of healthcare personnel to effectively integrate these technologies into everyday practice. Full article
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26 pages, 643 KB  
Review
The Fibrinolytic System in Bacterial Sepsis: A Comprehensive Review of Current Assessment Methods
by Florin Scarlatescu, Ecaterina Scarlatescu, Jecko Thachil, Dana R. Tomescu and Daniela Bartos
J. Clin. Med. 2025, 14(17), 6055; https://doi.org/10.3390/jcm14176055 - 27 Aug 2025
Abstract
Background: Fibrinolytic impairment is one of the key factors involved in the pathogenesis of hemostasis disturbances in sepsis, significantly contributing to microthrombosis, organ dysfunction, and mortality rates. While hemostatic assessment in sepsis typically focuses on coagulation activation, evaluating fibrinolytic activity remains challenging due [...] Read more.
Background: Fibrinolytic impairment is one of the key factors involved in the pathogenesis of hemostasis disturbances in sepsis, significantly contributing to microthrombosis, organ dysfunction, and mortality rates. While hemostatic assessment in sepsis typically focuses on coagulation activation, evaluating fibrinolytic activity remains challenging due to methodological limitations and a lack of standardization of the currently available methods. Objectives: This comprehensive review examines current methods for assessing fibrinolytic activity in bacterial sepsis, their clinical applications, strengths and limitations, and future perspectives for improved diagnostic approaches. Methods: We conducted a systematic literature search and identified 52 studies that investigated fibrinolysis assessment in adult patients with bacterial sepsis using biomarkers or global tests. Studies included mainly observational cohorts examining various fibrinolytic assessment methods. Results: Fibrinolytic shutdown, primarily mediated by the overproduction of plasminogen activator inhibitor-1 (PAI-1), occurs early in sepsis and correlates with disease severity and mortality. Current assessment methods include plasma biomarker measurements (PAI-1, plasmin-antiplasmin complexes, D-dimer), global plasma-based tests (clot lysis time, plasmin generation assays), and whole-blood viscoelastic testing (rotational thromboelastometry, ROTEM; thromboelastography, TEG). Modified viscoelastic tests incorporating tissue plasminogen activators demonstrate enhanced sensitivity for detecting fibrinolytic resistance. Despite efforts, standardization is still limited, and routine clinical implementation has not been achieved yet. Conclusions: Fibrinolytic assessment provides important prognostic information in sepsis, despite methodological challenges. The integration of point-of-care viscoelastic testing with modified protocols shows promise for real-time evaluation. Future research should focus on developing standardized, automated assays suitable for routine clinical practice, enabling personalized therapeutic interventions that target fibrinolytic dysfunction in sepsis. Full article
(This article belongs to the Special Issue Sepsis: Current Updates and Perspectives)
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14 pages, 248 KB  
Review
A Narrative Review of Treatment Options for Patients with Node-Positive Disease After Radical Prostatectomy: Current Evidence and Controversies
by Paolo Zaurito, Andrea Cosenza, Leonardo Quarta, Pietro Scilipoti, Mattia Longoni, Alfonso Santangelo, Alessandro Viti, Abigail Gettman, Francesco Barletta, Simone Scuderi, Vito Cucchiara, Armando Stabile, Francesco Montorsi, Alberto Briganti and Giorgio Gandaglia
Cancers 2025, 17(17), 2792; https://doi.org/10.3390/cancers17172792 - 27 Aug 2025
Abstract
Purpose of Review: In approximately 10–15% of patients with prostate cancer (PCa), pathological lymph node metastases (pN1) are detected at radical prostatectomy (RP). The aim of this review is to describe the various treatment options for pN1 patients, with a focus on [...] Read more.
Purpose of Review: In approximately 10–15% of patients with prostate cancer (PCa), pathological lymph node metastases (pN1) are detected at radical prostatectomy (RP). The aim of this review is to describe the various treatment options for pN1 patients, with a focus on the most recent evidence reported in the literature. Evidence Synthesis: Due to the lack of prospective studies, several retrospective analyses were conducted according to different types of treatment. Most common strategies are represented by observation plus early salvage radiotherapy (RT) in case of PSA rising, adjuvant androgen deprivation therapy (ADT) alone, or adjuvant RT with or without ADT. Patients with pN1 disease and favorable disease characteristics (lower T stage and ISUP ≤ 2 at RP, <3 metastatic nodes at pathology) have a similar overall mortality risk if observed with PSA testing and eventual use of early salvage RT compared to patients directly treated with adjuvant RT with or without ADT. While conflicting results in terms of survival benefit were reported for the use of adjuvant ADT only, several studies showed an overall survival benefit in patients with pN1 disease treated with adjuvant RT when high-risk features (such as an increasing number of positive nodes, ISUP > 3) were detected at RP. Lastly, few studies analyzed the rate of adverse events following adjuvant ADT or RT, leaving the issue of treatment-related side effects still open. Summary: There is no clearly established standard of care for men with pN1 PCa, and disease characteristics should guide the choice of optimal post-operative management for these patients. Prospective data and clinical trials are clearly needed to define the most effective therapeutic strategy. Full article
14 pages, 596 KB  
Article
Glycocalyx-Shedding and Inflammatory Reactions Occur Yet Do Not Predict Complications Resulting from an Esophagectomy in an Accelerated Recovery After Surgery Program
by Hendrik Drinhaus, Christoph Mallmann, Corvin Cleff, Tobias Neumann, Christina Daniels, Christiane J. Bruns, Andrea U. Steinbicker, Wolfgang Schröder and Thorsten Annecke
J. Clin. Med. 2025, 14(17), 6048; https://doi.org/10.3390/jcm14176048 - 26 Aug 2025
Abstract
Background/Objectives: “Accelerated Recovery after Surgery” (ARAS) programs for esophagectomy aim to shorten the perioperative course without increases in morbidity or mortality. In such programs, the prediction and early detection of perioperative complications is essential, as ICU observation times are limited. We evaluated two [...] Read more.
Background/Objectives: “Accelerated Recovery after Surgery” (ARAS) programs for esophagectomy aim to shorten the perioperative course without increases in morbidity or mortality. In such programs, the prediction and early detection of perioperative complications is essential, as ICU observation times are limited. We evaluated two potential laboratory markers as predictors for postoperative complications: shedding of the endothelial glycocalyx and the veno-arterial CO2-gap as indicators of microcirculatory disturbances. Methods: In total, 26 patients undergoing hybrid Ivor Lewis esophagectomy within an ARAS program were included. Macrocirculatory conditions were kept stable by enhanced hemodynamic monitoring (PiCCO). Glycocalyx shedding parameters (Syndecan-1, heparan sulfate, hyaluronic acid) and a panel of inflammatory mediators were measured preoperatively, upon ICU-admission, and on the first postoperative day. The veno-arterial CO2-gap was calculated at induction of anesthesia, during laparoscopy, and upon admission to the ICU. Results: Complications (Dindo-Clavien ≥3) occurred in n = 16 (62%) patients. From preoperatively to admission to the ICU, Syndecan-1 (29 pre-op to 56 ng/mL at ICU-admission) and Interleukins 1b (1.2 to 1.4 pg/mL), 6 (1.3 to 19.9 pg/mL), 8 (5.2 to 19.9 pg/mL), and 10 (0.50 to 1.33 pg/mL) increased, indicating a temporary increase in inflammation and glycocalyx shedding during surgery. A difference between patients with or without complications could not be detected. There was also no difference in the veno-arterial CO2-gap between the two groups (median of 6.8 mmHg in all patients, 6.7 in patients with complications, 7.8 in patients without complications). Conclusions: Signs of microcirculatory dysfunctions and inflammation occurred during esophagectomy within an ARAS protocol with tightly controlled hemodynamics. Increases in Syndecan-1 and the veno-arterial CO2-gap could not predict perioperative complications. Full article
(This article belongs to the Special Issue Gastrointestinal Cancer: Outcomes and Therapeutic Management)
19 pages, 905 KB  
Review
Failure to Rescue and Lung Resections for Lung Cancer: Measuring Quality from the Operation Room to the Intensive Care Unit
by Prokopis-Andreas Zotos, Vasiliki Androutsopoulou, Marco Scarci, Fabrizio Minervini, Ugo Cioffi, Andrew Xanthopoulos, Thanos Athanasiou and Dimitrios E. Magouliotis
Cancers 2025, 17(17), 2784; https://doi.org/10.3390/cancers17172784 - 26 Aug 2025
Abstract
Failure to rescue (FTR), defined as death following a potentially treatable postoperative complication, has emerged as a critical quality metric in thoracic surgery. In patients undergoing lung cancer resection, who are often at high risk due to comorbidities and limited pulmonary reserve, FTR [...] Read more.
Failure to rescue (FTR), defined as death following a potentially treatable postoperative complication, has emerged as a critical quality metric in thoracic surgery. In patients undergoing lung cancer resection, who are often at high risk due to comorbidities and limited pulmonary reserve, FTR significantly influences morbidity, mortality, recovery, and overall quality of life. This review explores the multifactorial nature of FTR in lung cancer surgery, highlighting key patient-related and system-level risk factors, such as surgical complexity, delayed complication recognition, inadequate escalation of care, and limited critical care resources. Existing models for patient rescue emphasize early detection and timely intervention, but often overlook the institutional and cultural changes required for sustainable improvement. Building on current evidence and integrating Kotter’s eight-step change model, we propose a novel multidimensional roadmap to reduce FTR through proactive monitoring, structured escalation protocols, multidisciplinary coordination, and continuous learning. Finally, reducing FTR in lung cancer resection requires more than clinical responsiveness. This necessitates a systemic transformation that aligns frontline practice with institutional readiness and a culture of safety. Full article
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