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Search Results (8,229)

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17 pages, 869 KB  
Systematic Review
Prediction Models for Postoperative Atrial Fibrillation After Cardiac Surgery: A Systematic Review and Critical Appraisal
by Bryam López Tuesta, Yerson Alberca-Naira, Jhair Alexander Leon-Rodriguez, Jonathan Rodriguez-Pratto, Jose D. Andrade-Saavedra, Franck J. Calderon-Chilet, Carlos A. Sarmiento-Maldonado, Oriana Rivera-Lozada, Cesar Bonilla-Asalde and Joshuan J. Barboza
J. Clin. Med. 2026, 15(13), 5255; https://doi.org/10.3390/jcm15135255 (registering DOI) - 5 Jul 2026
Abstract
Background/Objectives: Postoperative atrial fibrillation (POAF) is a frequent complication after cardiac surgery and is associated with increased morbidity, prolonged hospitalization, and higher healthcare costs. Numerous multivariable prediction models have been developed to estimate individual risk; however, their methodological robustness, validation status, and clinical [...] Read more.
Background/Objectives: Postoperative atrial fibrillation (POAF) is a frequent complication after cardiac surgery and is associated with increased morbidity, prolonged hospitalization, and higher healthcare costs. Numerous multivariable prediction models have been developed to estimate individual risk; however, their methodological robustness, validation status, and clinical transportability remain uncertain. This systematic review aimed to critically evaluate the methodological quality, validation strategies, and predictive performance of multivariable prediction models developed to estimate the risk of postoperative atrial fibrillation (POAF) after cardiac surgery. Methods: In accordance with PRISMA 2020 guidelines, we conducted a comprehensive search of PubMed, Scopus, Web of Science, and Embase from inception to July 2025. Studies that developed or externally validated multivariable prediction models for POAF in adult patients undergoing cardiac surgery were eligible. Data extraction was performed using the CHARMS checklist, and methodological quality was assessed with PROBAST. Model performance was summarized descriptively, focusing on discrimination (C-statistic/AUC), calibration reporting, and validation strategies. Results: A total of 39 studies were included. Most models were based on logistic regression, whereas a minority employed Cox regression or machine learning techniques. Reported discrimination ranged from 0.60 to 0.98, demonstrating substantial heterogeneity in predictive performance. Calibration was inconsistently reported. Six studies performed external validation. According to PROBAST, 32 of 39 studies (82%) were rated at high risk of bias, predominantly within the analysis domain due to inadequate handling of overfitting, insufficient events-per-variable ratios, and limited validation procedures. Conclusions: Existing prediction models for POAF show variable discrimination but are frequently limited by high risk of bias, inadequate validation, and incomplete calibration assessment, thereby restricting their clinical applicability. Future research should prioritize rigorous external validation, transparent reporting in accordance with TRIPOD recommendations, and methodological strategies that enhance model generalizability and transportability across diverse surgical populations. Full article
(This article belongs to the Special Issue Coronary Intervention: Current Strategies and Future Directions)
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27 pages, 575 KB  
Review
Nicotine Withdrawal Syndrome in Intensive Care Patients—Preventive and Therapeutic Implications
by Renata Piotrkowska, Aneta Miszewska, Sandra Lange, Wioletta Mędrzycka-Dąbrowska and Sabina Krupa-Nurcek
Med. Sci. 2026, 14(3), 374; https://doi.org/10.3390/medsci14030374 (registering DOI) - 4 Jul 2026
Abstract
Introduction: Nicotine dependence is a chronic disorder with both psychological and somatic components which, in the intensive care unit (ICU) setting, may affect the course of treatment through mechanisms related both to long-term nicotine exposure and to the consequences of its abrupt cessation. [...] Read more.
Introduction: Nicotine dependence is a chronic disorder with both psychological and somatic components which, in the intensive care unit (ICU) setting, may affect the course of treatment through mechanisms related both to long-term nicotine exposure and to the consequences of its abrupt cessation. The aim was to collect and map the current knowledge on smoking-related complications, the prevalence of nicotine withdrawal symptoms in this group, and to identify and describe interventions used to prevent or alleviate nicotine withdrawal symptoms in patients hospitalised in the ICU. Methods: The review included sources retrieved from databases such as PubMed, CINAHL, Scopus, Web of Science, and the Cochrane Library, published in English, that met the PCC criteria, with no time restrictions. Results: Forty-four sources were included. Twenty-nine contributed evidence on smoking-related status as an exposure or associated factor, five explicitly focused on abrupt nicotine cessation or nicotine withdrawal syndrome, and fifteen addressed interventions; categories overlapped. Delirium was the most frequently investigated outcome in smoking-related exposure studies. Withdrawal-focused sources reported or discussed nonspecific manifestations, including agitation, restlessness, anxiety, craving, and delirium-like presentations, but no validated ICU-specific diagnostic approach or robust prevalence estimate was identified. NRT was the only intervention evaluated. Conclusions: Smoking-related status was associated with agitation and delirium in several observational studies; however, heterogeneous exposure definitions and inconsistent evidence syntheses preclude causal or general prognostic conclusions. Evidence specific to nicotine withdrawal syndrome was limited, and the effectiveness and safety of NRT remain uncertain. Implications for clinical practice included routine identification of nicotine dependence at ICU admission, early monitoring of withdrawal symptoms, individualisation of sedation management, careful and selective consideration of nicotine replacement therapy (NRT), education of the therapeutic team, planning of further care, and smoking cessation interventions. Full article
(This article belongs to the Section Nursing Research)
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18 pages, 813 KB  
Review
Use of Natriuretic Peptides in Critically Ill Patients: A Narrative Review
by Ayodeji Olarewaju, Akinade Adebowale, Peter Odutola and Annie Arnold
J. Clin. Med. 2026, 15(13), 5244; https://doi.org/10.3390/jcm15135244 (registering DOI) - 4 Jul 2026
Abstract
Background: Natriuretic peptides, including B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), are established biomarkers of myocardial stress and circulatory overload. Although originally validated for diagnosis and exclusion of heart failure, their diagnostic and prognostic applications have expanded significantly in [...] Read more.
Background: Natriuretic peptides, including B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), are established biomarkers of myocardial stress and circulatory overload. Although originally validated for diagnosis and exclusion of heart failure, their diagnostic and prognostic applications have expanded significantly in the context of critical illness. However, interpretation in critically ill patients is complicated by confounding factors such as systemic inflammation and renal dysfunction. Objective: This review synthesizes current evidence on the diagnostic, monitoring, and prognostic applications of natriuretic peptides in critically ill adults. It further outlines practical considerations, confounding variables, and emerging complementary biomarkers pertinent to clinical decision-making. Methods: A structured search of PubMed, Embase, and the Cochrane Library (January 2000 to October 2025) identified studies evaluating BNP, NT-proBNP, and atrial natriuretic peptide (ANP) in intensive care unit (ICU) patients. Eligible studies and review articles assessed diagnostic utility, volume status, hemodynamic monitoring, and prognostic performance. Narrative synthesis was employed using information obtained from eligible studies. Results: Twenty-four studies met the inclusion criteria. BNP and NT-proBNP facilitate differentiation between cardiogenic and noncardiogenic respiratory failure, identification of mixed shock states, and assessment of volume status when used in association with other modalities such as echocardiography and ultrasonography. Elevated natriuretic peptide concentrations consistently predict mortality, acute kidney injury, prolonged mechanical ventilation, and adverse outcomes in several disease states, including sepsis, acute respiratory distress syndrome [ARDS], postoperative cardiac dysfunction, and COVID-19-related critical illness. However, interpretation remains limited by confounders, including renal impairment, age, systemic inflammation, brain injury, mechanical ventilation, and right-ventricular strain/dysfunction. Conclusions: Natriuretic peptides serve as valuable adjuncts for diagnostic assessment, hemodynamic monitoring, and risk stratification in the ICU. When interpreted with attention to biological kinetics and clinical context, these biomarkers enhance multimodal monitoring and support individualized management. Future research should refine ICU-specific cutoffs and assess natriuretic peptide–guided therapeutic strategies in prospective multicenter trials. Full article
(This article belongs to the Topic Advances in Hemodynamic Monitoring)
11 pages, 867 KB  
Article
Evaluating Outcomes in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease and Vitamin D Deficiency
by Tiana Dodd, Arpit Sharma, Nisar Amin, Veysel Tahan, Ebubekir Daglilar and Nikki Duong
Diseases 2026, 14(7), 243; https://doi.org/10.3390/diseases14070243 (registering DOI) - 4 Jul 2026
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease (CLD) globally and is closely linked to metabolic risk factors and systemic inflammation. Emerging evidence suggests that vitamin D deficiency may influence MASLD severity and outcomes, though limited [...] Read more.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease (CLD) globally and is closely linked to metabolic risk factors and systemic inflammation. Emerging evidence suggests that vitamin D deficiency may influence MASLD severity and outcomes, though limited real-world data often assess long-term clinical outcomes in MASLD patients stratified by vitamin D status. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network (2006–2025). Adult patients with MASLD were stratified into two cohorts based on serum 25-hydroxyvitamin D levels: normal (≥30 ng/mL) and deficient (<20 ng/mL). Patients with other CLD, malignancy, decompensated cirrhosis, and relevant confounding conditions were excluded. Primary outcomes included all-cause mortality, hospital readmissions, and ICU admissions at 1-year and 5-year follow-up. Results: After propensity score matching, 6959 patients were included in each cohort. Compared with patients with normal vitamin D levels, those with vitamin D deficiency had significantly higher rates of hospital readmissions, ICU admissions, and all-cause mortality at both 1-year and 5-year follow-up. A 1 year, readmissions occurred in 10% vs. 6%, ICU admissions 2.6% vs. 1.2%, and mortality 1.5% vs. 0.5% of patients (p = 0.01). Similar findings were observed at 5 years, with higher rates of readmissions 15% vs. 10%, ICU admissions 4.4% vs. 2.4% and mortality 3.2% vs. 1.3% in the vitamin D-deficient cohort (p = 0.01). Conclusions: Vitamin D deficiency was associated with significantly increased mortality, hospital readmissions, and ICU admissions among patients with MASLD. Our findings suggest that vitamin D status may represent a valuable prognostic indicator in this population. Although the observational nature of this study precluded establishing causality, our results support the consideration of routine assessment of vitamin D levels in patients with MASLD. Further prospective and mechanistic studies are needed to determine whether vitamin D supplementation can improve outcomes in this population. Full article
(This article belongs to the Section Gastroenterology)
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24 pages, 1293 KB  
Review
Exercise-Induced Coronary Remodeling and the Atherosclerotic Paradox in Endurance Athletes: Toward a Unified Mechanobiological Framework
by Nardi Tetaj, Andrea Segreti, Michele Pelullo, Camilla Rossi, Alberto Spagnolo, Virginia Ligorio, Aurora Ferro, Antonio Emanuele Lentini, Teresa Trunfio, Martina Ciancio, Chiara Fossati, Fabio Pigozzi and Francesco Grigioni
J. Funct. Morphol. Kinesiol. 2026, 11(3), 265; https://doi.org/10.3390/jfmk11030265 (registering DOI) - 4 Jul 2026
Abstract
Regular endurance exercise is consistently associated with lower cardiovascular mortality, a favorable cardiometabolic profile, and superior cardiorespiratory fitness. However, coronary imaging studies in master endurance athletes have raised a clinically relevant paradox: despite a low burden of conventional risk factors, some athletes—particularly older [...] Read more.
Regular endurance exercise is consistently associated with lower cardiovascular mortality, a favorable cardiometabolic profile, and superior cardiorespiratory fitness. However, coronary imaging studies in master endurance athletes have raised a clinically relevant paradox: despite a low burden of conventional risk factors, some athletes—particularly older men with high lifetime exercise exposure—show a greater prevalence of coronary artery calcium and subclinical coronary plaque than sedentary or less active controls. This observation has challenged the long-standing assumption that high-volume endurance exercise is uniformly protective against coronary artery disease. A binary interpretation of this literature is inadequate. Coronary flow reserve and ischemic threshold may remain adequate in some athletes, although this concept is supported by limited functional and outcome data. Based on experimental vascular biology and indirect human evidence, repetitive high-flow states during endurance exercise generate sustained laminar shear stress, cyclic wall strain, and marked increases in coronary blood flow, thereby activating endothelial mechanotransduction pathways and influencing vascular smooth muscle cell behavior, extracellular matrix remodeling, and calcification biology. These adaptations may culminate in positive arterial remodeling, luminal enlargement, and, in some individuals, a predominantly calcified plaque phenotype. Importantly, structural remodeling does not necessarily equate to functional impairment. In selected athletes, when outward remodeling and endothelial responsiveness are preserved, coronary flow reserve and ischemic threshold may remain adequate, although this concept remains supported by limited functional and outcome data. This narrative review integrates the clinical imaging literature with current concepts in vascular mechanobiology to propose that coronary remodeling in endurance athletes exists along an adaptive–maladaptive continuum shaped by cumulative exercise load, aging, sex, conventional risk factors, and biological susceptibility. This framework may help clinicians interpret CAC/CCTA findings in athletes more appropriately and avoid equating plaque burden with equivalent functional or prognostic significance. Full article
(This article belongs to the Special Issue Exercise Interventions in Cardiovascular Health)
16 pages, 623 KB  
Article
Real-World Treatment Outcomes After Nivolumab Progression in BRAF-Negative Metastatic Melanoma: A Multicenter Cohort Study by the Turkish Oncology Group
by Emine Bihter Eniseler, Atike Pinar Erdogan, Mustafa Şahbazlar, Fatma Keskin Uzundere, Teoman Şakalar, Hasibe Bilge Gür, İlhan Hacıbekiroğlu, Onur Yazdan Balcık, İsmail Beypınar, Mehmet Gürdal Savsar, Gözde Pempe, Sila Oksuz, Tuğba Başoğlu, Özge Demirkıran, Bilgin Demir, Bedriye Açıkgöz Yıldız, Atike Gökçen Demiray, Mehmet Sinan Akarca, İlkay Tuğba Ünek, Mahmut Kara, Muslih Urun, Ahmet Cebeli Gökay, Havva Yeşil and Ferhat Ekinciadd Show full author list remove Hide full author list
J. Clin. Med. 2026, 15(13), 5224; https://doi.org/10.3390/jcm15135224 - 3 Jul 2026
Abstract
Background/Objectives: Despite improved survival with immune checkpoint inhibitors, the optimal treatment after anti-PD-1 progression in metastatic melanoma remains unclear. This study compared survival outcomes and treatment responses between chemotherapy (CT)- and immunotherapy (IO)-based therapies administered after nivolumab progression in patients with BRAF-negative metastatic [...] Read more.
Background/Objectives: Despite improved survival with immune checkpoint inhibitors, the optimal treatment after anti-PD-1 progression in metastatic melanoma remains unclear. This study compared survival outcomes and treatment responses between chemotherapy (CT)- and immunotherapy (IO)-based therapies administered after nivolumab progression in patients with BRAF-negative metastatic melanoma. Methods: This multicenter retrospective study included patients with BRAF-negative metastatic melanoma who developed disease progression during nivolumab treatment. Post-progression systemic therapies were categorized as CT- or IO-based treatments. Treatment responses were assessed according to RECIST version 1.1 criteria. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier method, and prognostic factors were evaluated using Cox regression analyses. Results: A total of 141 patients were included. Following nivolumab progression, 107 (75.9%) received CT and 34 (24.1%) received IO. Based on best response to nivolumab, the objective response rate (ORR; CR + PR) was 55.1% in the CT group and 44.1% in the IO group. After post-nivolumab treatment, ORRs were 29.9% and 32.4% in the CT and IO groups, respectively, whereas complete response rates were higher with IO (21.2% vs. 3.0%). Median PFS was 4.17 months in the CT group and 3.9 months in the IO group (p = 0.403). Median OS was 7.83 and 8.17 months, respectively (p = 0.416). Elevated LDH level was identified as an independent adverse prognostic factor. Conclusions: In this multicenter real-world cohort, no statistically significant differences in survival were observed between patients receiving CT or IO after nivolumab progression. Given the retrospective, non-randomized study design, these findings should not be interpreted as evidence of comparative treatment efficacy. The higher CR rate observed with IO should be interpreted cautiously due to potential selection bias. Prospective studies are warranted to define the optimal treatment strategy after anti-PD-1 failure. Full article
(This article belongs to the Section Oncology)
33 pages, 1148 KB  
Review
The Multifaceted Role of Extracellular Vesicles in Triple Negative Breast Cancer
by Serena El Rayes, Ebaa Ababneh, Varun Nannuri, Manjusha Vaidya, Kiminobu Sugaya and Jihe Zhao
Int. J. Mol. Sci. 2026, 27(13), 5976; https://doi.org/10.3390/ijms27135976 - 3 Jul 2026
Abstract
Triple negative breast cancer (TNBC) is an aggressive and heterogeneous subtype of breast cancer characterized by the absence of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), resulting in limited options for targeted therapy and high [...] Read more.
Triple negative breast cancer (TNBC) is an aggressive and heterogeneous subtype of breast cancer characterized by the absence of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), resulting in limited options for targeted therapy and high rates of metastasis, recurrence and death. Extracellular vesicles (EVs) have emerged as central mediators of TNBC pathophysiology, functioning as key intercellular communication vehicles transporting oncogenic proteins, nucleic acids; lipids, and metabolites. These EV-mediated interactions promote tumor microenvironment (TME) remodeling, immune evasion, metastatic niche formation, and therapeutic resistance. Given their stability, accessibility, and molecular complexity, EVs also represent promising diagnostic and prognostic biomarkers for TNBC. Advances in isolation and molecular profiling technologies have enabled the identification of EV-associated signatures that predict therapeutic response and stratify patient risk. Beyond their utility as biomarkers, EVs are rapidly emerging as therapeutic targets and delivery platforms, demonstrating efficacy in transporting chemotherapeutics, RNA-based therapeutics, immune modulators, and photosensitizers with enhanced targeting specificity and therapeutic efficiency. Collectively, EVs play a multifaceted role in TNBC biology, serving simultaneously as drivers of disease progression, minimally invasive biomarkers, and versatile therapeutic vehicles. The integration of EV-centered diagnostics, multi-omic profiling, and engineered therapeutics holds significant potential to transform TNBC management and advance precision oncology for this challenging breast cancer subtype. Full article
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61 pages, 12517 KB  
Review
A Multilevel Redox-Based Prognostic Model for Asthma Severity: From Genotype to Serum Biomarkers
by Shukur Wasman Smail, Rebaz Hamza Salih, Blnd Azad Ismail, Ivan Sdiq Maghdid, Raya Kh. Yashooa, Taban Kamal Rasheed, Shayma Hassan Hamadamin and Christer Janson
Biomedicines 2026, 14(7), 1509; https://doi.org/10.3390/biomedicines14071509 - 3 Jul 2026
Abstract
Asthma is a heterogeneous chronic airway disease in which oxidative stress (OS) plays a central mechanistic role beyond classical immune-mediated inflammation. Reactive oxygen and nitrogen species (ROS/RNS), generated by recruited inflammatory cells and activated airway structural cells, drive epithelial injury, mucus hypersecretion, airway [...] Read more.
Asthma is a heterogeneous chronic airway disease in which oxidative stress (OS) plays a central mechanistic role beyond classical immune-mediated inflammation. Reactive oxygen and nitrogen species (ROS/RNS), generated by recruited inflammatory cells and activated airway structural cells, drive epithelial injury, mucus hypersecretion, airway remodeling, and modulate key transcription factors including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. This review synthesizes current evidence on the multilevel redox-based determinants of asthma severity, spanning from genetic polymorphisms to circulating biomarkers. We examine serum antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), peroxiredoxins (PRDXs), and the thioredoxin (Trx) system as dynamic indicators of systemic redox status and disease severity, alongside oxidative enzymes including NADPH oxidases and dual oxidases (NOX/DUOX), xanthine oxidase (XO), and myeloperoxidase (MPO) that serve as upstream sources of airway oxidant burden. Functional genetic polymorphisms in antioxidant genes (SOD2, CAT, glutathione S-transferase mu 1/glutathione S-transferase theta 1 (GSTM1/GSTT1), heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/KEAP1)) and oxidative enzyme genes including nitric oxide synthase 1/2/3 (NOS1/2/3), MPO, cytochrome b-245 alpha chain (CYBA), and xanthine dehydrogenase (XDH) are reviewed as modulators of individual redox capacity and asthma susceptibility, with particular attention to gene–environment interactions. We further discuss oxidative damage biomarkers, including malondialdehyde (MDA), 8-isoprostanes, 4-hydroxynonenal, 8-oxo-7, 8-dihydro-2′-deoxyguanosine, protein carbonyls, 3-nitrotyrosine, and advanced oxidation protein products as indicators of lipid, DNA, and protein oxidation that correlate with disease activity and control. The roles of micronutrient cofactors in modulating antioxidant enzyme function and their potential as contextual biomarkers are also addressed. Additionally, emerging evidence on microRNAs (miRNAs) linked to OS biology in asthma is presented. Finally, we critically evaluate the challenges limiting clinical translation, including biomarker non-specificity, analytical variability, gene–environment complexity, and the absence of standardized reference ranges. This integrated framework supports the development of multilevel redox prognostic panels combining genetic, enzymatic, and oxidative damage readouts for improved asthma phenotyping, severity stratification, and personalized therapeutic approaches. Full article
(This article belongs to the Special Issue Biomarker, Phenotyping and Therapeutics for Asthma)
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15 pages, 3675 KB  
Article
Preoperative Platelet-to-Lymphocyte Ratio as a Predictor of Recurrence and Recurrence-Free Survival in Non-Muscle-Invasive Bladder Cancer Across Different Intravesical Therapies
by Muhammet İhsan Öztürk, Musa Ekici, Cemil Aydın, Mustafa Serdar Çağlayan, Mücahit Doğan and Mehmet Murat Baykam
J. Clin. Med. 2026, 15(13), 5199; https://doi.org/10.3390/jcm15135199 - 3 Jul 2026
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Abstract
Background/Objectives: Non-muscle invasive bladder cancer (NMIBC) is characterized by high recurrence rates despite appropriate treatment and surveillance. Identifying inexpensive and readily available biomarkers capable of improving risk stratification remains an important clinical challenge. The platelet-to-lymphocyte ratio (PLR), a marker of systemic inflammation, has [...] Read more.
Background/Objectives: Non-muscle invasive bladder cancer (NMIBC) is characterized by high recurrence rates despite appropriate treatment and surveillance. Identifying inexpensive and readily available biomarkers capable of improving risk stratification remains an important clinical challenge. The platelet-to-lymphocyte ratio (PLR), a marker of systemic inflammation, has emerged as a potential prognostic indicator in several malignancies. This study aimed to evaluate the association between preoperative PLR, tumor recurrence, and recurrence-free survival (RFS) in NMIBC patients treated with intravesical Bacillus Calmette–Guérin (BCG) or thermochemotherapy. Methods: This retrospective study included 153 patients diagnosed with NMIBC between January 2020 and January 2024. All patients underwent transurethral resection of bladder tumor (TURBT) followed by intravesical BCG (n = 123) or thermochemotherapy (n = 30). Preoperative PLR was calculated from complete blood counts obtained before surgery. Receiver operating characteristic (ROC) analysis was used to determine the optimal PLR cut-off value. Recurrence-free survival was evaluated using Kaplan–Meier survival analysis and Cox proportional hazards regression models. Results: During a mean follow-up period of approximately 19 months, recurrence was observed in 35.8% of patients treated with BCG and 30% of those treated with thermochemotherapy. ROC analysis demonstrated good discriminatory ability for recurrence prediction (AUC = 0.831, 95% CI: 0.761–0.901, p < 0.001) and identified an optimal PLR threshold of 120. Patients with elevated PLR values demonstrated higher recurrence rates and shorter recurrence-free survival. Kaplan–Meier analysis revealed a clear separation of survival curves according to PLR status. In multivariable Cox regression analysis, PLR > 120 remained independently associated with recurrence-free survival in the BCG group (HR = 2.703, 95% CI: 1.118–6.534, p = 0.027), whereas only a borderline association was observed in the thermochemotherapy group (HR = 23.265, 95% CI: 0.952–568.336, p = 0.054). Conclusions: Elevated preoperative PLR was associated with recurrence and recurrence-free survival in patients with NMIBC. The prognostic value of PLR appeared to be more pronounced in patients receiving intravesical BCG therapy. Given its low cost, accessibility, and ease of calculation, PLR may serve as a useful adjunctive biomarker for clinical risk stratification when used alongside established clinicopathological prognostic factors. Further prospective multicenter studies are required to validate these findings. Full article
(This article belongs to the Special Issue Bladder Cancer: Clinical Diagnosis and Treatment)
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22 pages, 2339 KB  
Review
Iron Metabolism in the Colorectal Tumor Microenvironment: Current Evidence and Clinical Implications
by Anamaria-Vlăduța Tomoiagă, Angela Cozma, Cezara-Andreea Gerdanovics, Alexandru Gerdanovics, Mircea-Vasile Milaciu, Nicoleta-Valentina Leach, Vasile Negrean, Șoimița-Mihaela Suciu, Simona Valeria Clichici and Olga Hilda Orășan
Diagnostics 2026, 16(13), 2081; https://doi.org/10.3390/diagnostics16132081 (registering DOI) - 2 Jul 2026
Viewed by 172
Abstract
Iron is essential for normal cellular function, but its dysregulation is increasingly recognized as a key factor in colorectal tumorigenesis. This review provides an integrated overview of iron-related biomarkers across the full spectrum of colorectal neoplasia, from preneoplastic lesions to advanced colorectal cancer [...] Read more.
Iron is essential for normal cellular function, but its dysregulation is increasingly recognized as a key factor in colorectal tumorigenesis. This review provides an integrated overview of iron-related biomarkers across the full spectrum of colorectal neoplasia, from preneoplastic lesions to advanced colorectal cancer (CRC). Evidence suggests that alterations in iron metabolism begin early, at the level of colorectal adenomas, where increased iron uptake and impaired export contribute to local iron accumulation and oxidative stress. As lesions progress to carcinoma, this imbalance becomes more pronounced, leading to expansion of the intracellular labile iron pool and supporting tumor growth, metabolic adaptation, and genomic instability. At the systemic level, patients often exhibit reduced circulating iron despite preserved or elevated ferritin levels, reflecting inflammation-driven functional iron deficiency. This pattern is largely mediated by dysregulation of the hepcidin–ferroportin axis. In this context, transferrin saturation and soluble transferrin receptor may provide a more accurate assessment of iron availability than ferritin alone. At the tissue level, increased expression of iron import proteins and impaired iron export promote intracellular iron retention. Excess iron further contributes to reactive oxygen species generation, leading to damage of DNA, lipids, and proteins. Clinically, iron-related biomarkers show variable diagnostic performance but may offer prognostic value. Integrating systemic and tissue biomarkers could improve risk stratification and support personalized approaches across the CRC continuum. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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12 pages, 596 KB  
Article
Glasgow Prognostic Score and Gustave Roussy Immune Score in Hodgkin Lymphoma: Survival Associations and Limited Incremental Prognostic Value Beyond the International Prognostic Score
by Kemal Aygün, Şerife Solmaz, Olgu Aygün, İbrahim Eryılmaz, Tugba Cetintepe, Hatice Demet Kiper Unal, Alev Garip Acar and Eray Arslan
J. Clin. Med. 2026, 15(13), 5159; https://doi.org/10.3390/jcm15135159 (registering DOI) - 2 Jul 2026
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Abstract
Background/Objectives: Although outcomes in Hodgkin lymphoma (HL) have improved substantially, patients with advanced-stage disease, comorbidities, or relapsed/refractory presentations can still fare poorly. Blood-based indices of systemic inflammation and nutrition are derived from routine tests, but their value beyond established prognostic models is uncertain. [...] Read more.
Background/Objectives: Although outcomes in Hodgkin lymphoma (HL) have improved substantially, patients with advanced-stage disease, comorbidities, or relapsed/refractory presentations can still fare poorly. Blood-based indices of systemic inflammation and nutrition are derived from routine tests, but their value beyond established prognostic models is uncertain. We examined the association of the baseline Gustave Roussy Immune Score (GRIm) and Glasgow Prognostic Score (GPS) with treatment response, progression-free survival (PFS), and overall survival (OS) in HL, focusing on their performance relative to the seven-factor International Prognostic Score (IPS-7). Methods: We retrospectively analysed 110 adults with histologically confirmed HL treated at a tertiary haematology centre between January 2015 and December 2025. GPS, GRIm, and IPS-7 were calculated from data recorded at diagnosis. Treatment response was classified as complete versus non-complete. Outcomes were assessed with Kaplan–Meier analysis, log-rank tests, Cox regression, Harrell’s C-index, and likelihood-ratio testing. Results: Most patients had advanced-stage disease (69.1%) and received ABVD-based treatment (94.5%); complete response was achieved in 90 (81.8%). GPS and GRIm were not significantly associated with non-complete response, whereas IPS-7 was. Over a median follow-up of 39.5 months, 28 patients (25.5%) progressed or died and 17 (15.5%) died. In univariable Cox analysis, high GRIm risk (HR = 2.68, 95% CI 1.17–6.14), higher GPS (HR = 2.18 per point, 95% CI 1.23–3.89), and higher IPS-7 (HR = 2.10 per point, 95% CI 1.59–2.77) predicted shorter PFS. For OS, GPS and IPS-7 were significant, whereas GRIm was not. After adjustment for IPS-7, neither GPS nor GRIm remained independently associated with PFS or OS, and adding either score to IPS-7 produced only small, non-significant gains in discrimination. Conclusions: Baseline GPS and GRIm were associated with survival on univariable analysis, particularly for PFS, but their incremental value beyond IPS-7 was limited. These scores may help describe baseline inflammatory and nutritional risk and should not be regarded as alternatives to established HL prognostic models. In particular, GPS and GRIm were not significantly associated with treatment response and should be viewed as supportive markers requiring external validation, rather than as tools that can independently guide treatment decisions. Full article
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42 pages, 3547 KB  
Review
Dual Targeting Strategies in Cancer: Carbonic Anhydrase IX Inhibitors Targeting EGFR or VEGFR-2
by Eleftherios Charissopoulos and Eleni Pontiki
Molecules 2026, 31(13), 2306; https://doi.org/10.3390/molecules31132306 - 1 Jul 2026
Viewed by 232
Abstract
Tumor microenvironment influences the process of tumorigenesis, with hypoxia being a characteristic of many solid tumors and an adverse prognostic factor. Carbonic anhydrases (CAs) are highly efficient zinc-containing enzymes that are overexpressed in many cancers, particularly under acidic and hypoxic conditions. CA IX [...] Read more.
Tumor microenvironment influences the process of tumorigenesis, with hypoxia being a characteristic of many solid tumors and an adverse prognostic factor. Carbonic anhydrases (CAs) are highly efficient zinc-containing enzymes that are overexpressed in many cancers, particularly under acidic and hypoxic conditions. CA IX expression promotes cancer cell proliferation, migration, and invasion. Vascular endothelial growth factor receptor-2 (VEGFR-2) is a tyrosine transmembrane (ΤΜ) protein regulating embryonic development, angiogenesis, tissue homeostasis and cancer. Blocking VEGFR-2 signaling is one of the most promising approaches to hindering angiogenesis and growth of cancer cells. The epidermal growth factor receptor (EGFR) is a member of the ERBB family of receptor tyrosine kinases and plays a key role in cancer progression. EGFR is uniquely found in some brain, lung and other cancers. Development of novel strategies to regulate these factors is important for the treatment of tumors. Multifunctional drugs that act on multiple pathways offer a promising approach, improving therapeutic effectiveness while reducing side effects. The present review focuses on novel compounds that inhibit CA IX and target VEGFR-2 or EGFR. Full article
(This article belongs to the Section Medicinal Chemistry)
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15 pages, 1915 KB  
Article
A Nomogram Model for Early Mortality Risk Stratification in Elderly Patients with Idiopathic Pulmonary Fibrosis: An Integrative Analysis of Serum Biomarkers and Pulmonary Function Parameters
by Yingying Zhu, Zhangyan Ke, Tiantian Zhang, Siyu Sun and Xiaoyun Fan
J. Clin. Med. 2026, 15(13), 5124; https://doi.org/10.3390/jcm15135124 - 1 Jul 2026
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Abstract
Background: Idiopathic pulmonary fibrosis (IPF) has a low incidence but high mortality. Simple prognostic tools for elderly IPF patients in primary care are lacking. This study aimed to develop an accessible nomogram for this population. Methods: A retrospective analysis was conducted on elderly [...] Read more.
Background: Idiopathic pulmonary fibrosis (IPF) has a low incidence but high mortality. Simple prognostic tools for elderly IPF patients in primary care are lacking. This study aimed to develop an accessible nomogram for this population. Methods: A retrospective analysis was conducted on elderly IPF patients from the First Affiliated Hospital of Anhui Medical University (January 2016–February 2023). Early mortality was defined as death within 12 months from diagnosis. A nomogram was developed using predictors identified by univariate and multivariate analyses. To minimize overfitting, we limited the number of predictors to four based on the rule of at least 10 events per variable (39 events). Model performance was assessed using the C-index, calibration curves including the Hosmer–Lemeshow goodness-of-fit test, ROC analysis, and decision curve analysis (DCA). Internal validation was performed using bootstrap resampling (1000 iterations). For missing data, variables with >30% missingness were excluded; for variables with ≤30% missingness, multiple imputation was applied. Risk stratification was performed based on nomogram scores, and survival between groups was compared via Kaplan–Meier analysis. Results: Overall, 83 patients were included. Multivariate analysis identified age, monocyte count, globulin, and DLCO%pre as independent predictors of early mortality. The nomogram incorporating these factors achieved a C-index of 0.846 (optimism-corrected C-index: 0.812 after bootstrap). The AUCs for predicting 1-, 2-, and 3-year overall survival were 0.879, 0.896, and 0.854, respectively. The Hosmer–Lemeshow test showed good calibration (p = 0.42, 0.38, and 0.51 for 1, 2, and 3 years). Kaplan–Meier analysis confirmed significantly worse survival in the high-risk group (p < 0.0001). Conclusions: We developed an accurate and practical nomogram to predict prognosis in elderly IPF patients, offering a useful risk-assessment tool for primary care settings. However, external validation in independent multicenter cohorts is required before clinical implementation. At its current stage, the model should be regarded as hypothesis-generating. Full article
(This article belongs to the Section Respiratory Medicine)
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17 pages, 281 KB  
Article
Prognostic Factors for Adverse Outcomes in Odontogenic Infections Requiring Hospitalization: A Single-Center Retrospective Study in Kraków, Poland
by Michał Gontarz, Agata Wieczorkiewicz, Andrei Hramyka, Jakub Bargiel, Krzysztof Gąsiorowski, Paweł Szczurowski, Kamil Nelke, Barbara Czopik, Ömer Uranbey, Katarzyna Rusek and Grażyna Wyszyńska-Pawelec
J. Clin. Med. 2026, 15(13), 5120; https://doi.org/10.3390/jcm15135120 - 1 Jul 2026
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Abstract
Background/Objectives: Odontogenic infections range from localized abscesses to life-threatening deep neck infections and are a frequent cause of emergency admission. We aimed to identify prognostic factors for postoperative complications after their surgical treatment. Methods: We retrospectively analyzed 194 adults (59.3% male) [...] Read more.
Background/Objectives: Odontogenic infections range from localized abscesses to life-threatening deep neck infections and are a frequent cause of emergency admission. We aimed to identify prognostic factors for postoperative complications after their surgical treatment. Methods: We retrospectively analyzed 194 adults (59.3% male) treated at the Department of Cranio-Maxillofacial Surgery in Cracow between 2020 and 2025. The primary outcome was any postoperative complication, graded by the Clavien–Dindo classification and dichotomized into minor (grade I–II) and major (grade ≥ III). Prolonged hospitalization and prolonged irrigation (>7 days) were secondary outcomes. Pre-specified main factors (advanced age, diffuse phlegmonous spread, diabetes mellitus) and covariates (sex, maxillary location, systemic disease) were tested by uni- and multivariable logistic regression. Results: Comorbidities were present in 69.1%. Complications occurred in 49 patients (25.3%): 19 (9.8%) minor and 30 (15.5%) major, including 12 grade IV intensive-care events and two deaths (grade V). In multivariable analysis, diffuse phlegmonous spread independently predicted any complication (adjusted OR 11.7), major complication (OR 23.4), prolonged hospitalization (OR 5.02) and prolonged irrigation (OR 4.39; all p ≤ 0.004). Advancing age independently predicted major complications (OR 1.03 per year, p = 0.037). Both fatal cases shared phlegmon, maxillary location and diabetes. Conclusions: Diffuse phlegmonous spread was the principal prognostic factor across all adverse outcomes, with advancing age additionally predicting major complications. Because intensive-care admission occurred almost exclusively in phlegmon patients, this association is partly definitional. Early identification of diffuse spread and advanced age may support effective triage. Full article
20 pages, 698 KB  
Article
Emergence and Comparative Analysis of Candidozyma auris Versus Candida spp. Candidemia in a Romanian Tertiary Hospital: A 7-Year Study on Resistance, Mortality and Independent Prognostic Factors
by Sebastian George Smadu, Simona Camelia Tetradov, Corneliu Petru Popescu, Maria Nica, Corina Oprisan, Luminita Ene and Simin Aysel Florescu
J. Fungi 2026, 12(7), 482; https://doi.org/10.3390/jof12070482 - 1 Jul 2026
Viewed by 373
Abstract
Background: Candidemia remains a major cause of morbidity and mortality among hospitalized patients. The emergence of Candidozyma auris has added further complexity due to its persistence in healthcare settings and its high rates of antifungal resistance. Comparative real-world data between Candidozyma auris and [...] Read more.
Background: Candidemia remains a major cause of morbidity and mortality among hospitalized patients. The emergence of Candidozyma auris has added further complexity due to its persistence in healthcare settings and its high rates of antifungal resistance. Comparative real-world data between Candidozyma auris and Candida spp. candidemia remain limited. Methods: We conducted a retrospective cohort study that included adult patients with candidemia, admitted to a tertiary infectious diseases hospital in Romania between August 2018 and August 2025. Risk factors, including medical history, previous hospitalizations, clinical characteristics, laboratory parameters, antifungal susceptibility patterns, treatment, and outcomes, were compared in patients with Candidozyma auris- and Candida spp.-positive blood cultures. Overall survival and prognostic factors were evaluated using univariable and multivariable Cox-proportional hazards models. Results: Sixty-one patients with candidemia were included; out of them, 24 (39.3%) had Candidozyma auris-positive blood cultures. Candidozyma auris infections, which emerged later during the study period, occurred after a significantly longer period of hospitalization compared with Candida spp. candidemia (median 52.5 vs. 20 days, p < 0.001). Azole resistance was almost universal among Candidozyma auris isolates (95.8%), whereas Candida species displayed significantly lower resistance rates and a broader susceptibility spectrum (p < 0.001). Inflammatory markers were comparable between groups; however, Candidozyma auris candidemia was associated with lower neutrophil counts and lower neutrophil-to-lymphocyte ratios at diagnosis (p = 0.020). Persistent candidemia at day 7 occurred more frequently in Candidozyma auris infections (6 vs. 2 patients; p = 0.05) and was universally fatal. Overall, in-hospital mortality was high (70.5%) and did not differ between Candidozyma auris and Candida spp. candidemia. In multivariable analysis, thrombocytopenia < 100,000/μL was independently associated with mortality (HR 2.34, 95% C.I. 1.20–4.56; p = 0.012). Conclusions: In this 7-year study at a Romanian tertiary center, Candidozyma auris emerged as a major healthcare-associated pathogen affecting patients with significantly prolonged hospitalization (median 52.5 days). Despite near-universal azole resistance (95.8%), mortality was exceptionally high (70.5%) and was comparable between groups, with pathogen type not independently associated with outcome after multivariable adjustment. Moderate thrombocytopenia (<100,000/μL) and persistent candidemia identified patients at particularly high risk of death, underscoring the need for early risk stratification, optimized antifungal management, and enhanced diagnostic vigilance, both in intensive care and general wards. Full article
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