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Volume 14
Issue 4
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Diseases, Volume 14, Issue 4 (April 2026) – 35 articles

Cover Story (view full-size image): Intestinal strictures are a major complication of Crohn’s disease, affecting about 20% of patients at diagnosis. While medical therapy controls inflammation, it is often ineffective for fibrotic strictures, which may require intervention. Endoscopic balloon dilation (EBD) is first-line but has high recurrence rates and frequent need for repeat procedures. New techniques such as endoscopic stricturotomy (ESt) and strictureplasty (ESTx) have emerged as alternatives. This meta-analysis of 15 studies (1500 patients) shows high technical success (93%), yet variable clinical success (50–96%). Complications are uncommon, with rare perforation (<2%). These techniques may delay or avoid surgery and support a step-up endoscopic approach in fibrostenotic CD. View this paper
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15 pages, 522 KB  
Review
Post-Psychotic Depression: A Comprehensive Narrative Review
by Karol Piotr Mirkowski, Kalina Aleksandra Hac, Zuzanna Kryś and Jerzy Leszek
Diseases 2026, 14(4), 150; https://doi.org/10.3390/diseases14040150 - 20 Apr 2026
Viewed by 613
Abstract
Background: Post-psychotic depression (PPD) is an underestimated but clinically significant affective syndrome that occurs during remission from psychosis, particularly in schizophrenia. Material and Methods: This comprehensive review traces the evolution of this concept over five decades of research, starting from its initial differentiation [...] Read more.
Background: Post-psychotic depression (PPD) is an underestimated but clinically significant affective syndrome that occurs during remission from psychosis, particularly in schizophrenia. Material and Methods: This comprehensive review traces the evolution of this concept over five decades of research, starting from its initial differentiation from primary depression and schizoaffective disorders in the 1970s. Relying on more than thirty studies, we analyze historical definitions, biological and psychosocial mechanisms, diagnostic controversies, and therapeutic implications. Results: Research indicates that PPD develops from multiple contributing factors, including psychological insight, autobiographical disturbances, pharmacological influences, and social losses, rather than simply as a byproduct of psychosis or pharmacological treatment. We discuss the persistence of depressive symptoms after acute remission, their role in suicidal tendencies, and the diagnostic challenges arising from the overlap of negative symptoms and demoralization. Despite its exclusion from current diagnostic standards, PPD continues to affect a significant fraction of patients, particularly those with high insight and early onset. Conclusions: Effective treatment requires a multidimensional, phase-specific approach combining antidepressants, atypical antipsychotics such as lurasidone, and psychological interventions targeting identity, self-esteem, and narrative processing. We argue that PPD should be reintroduced as a distinct clinical unit and incorporated into psychiatric guidelines to reduce diagnostic oversights and improve patient outcomes. Full article
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16 pages, 1409 KB  
Article
Predictors of Response to Induction Therapy with Ustekinumab in Patients with Ulcerative Colitis: Results from a National Study in Greece
by Konstantina Chalakatevaki, Georgios Kokkotis, Maria Gazouli, Stratigoula Sakellariou, Ioannis Vamvakaris, Alexandros Chatzidakis, Gerasimos Gerasimatos, Maria Kalogirou, Kanellos Koustenis, Dimitra Lazou, Afroditi Orfanidou, Maria Palatianou, Evgenia Papathanasiou, Andreas Psistakis, Christos Sotiropoulos, Evaggelia Anagnostopoulou, Konstantinos Argyriou, Matina-Lydia Chatzinikolaou, Kalliopi Foteinogiannopoulou, Olga Giouleme, Andreas Kapsoritakis, Pantelis Karatzas, Konstantinos Karmiris, Nikolaos Kiriakos, Ioannis Koutroubakis, Christos Liatsos, Aikaterini Mantaka, Gerasimos Mantzaris, Panagiotis Markopoulos, Georgios Michalopoulos, Spiros Michopoulos, Dimitrios Polymeros, Konstantinos Soufleris, Georgios Theocharis, Angeliki Theodoropoulou, Eftychia Tsironi, Maria Tzouvala, Nikos Viazis, Eirini Zacharopoulou, Evanthia Zampeli and Giorgos Bamiasadd Show full author list remove Hide full author list
Diseases 2026, 14(4), 149; https://doi.org/10.3390/diseases14040149 - 19 Apr 2026
Viewed by 566
Abstract
Background/Objectives: Ustekinumab has been approved for the treatment of moderate to severe ulcerative colitis. Real-world data regarding its efficacy and the discovery of predictive factors of response need to be studied further. We aimed to evaluate the efficacy and identify predictors of response [...] Read more.
Background/Objectives: Ustekinumab has been approved for the treatment of moderate to severe ulcerative colitis. Real-world data regarding its efficacy and the discovery of predictive factors of response need to be studied further. We aimed to evaluate the efficacy and identify predictors of response to induction treatment with ustekinumab in patients with ulcerative colitis. Methods: This is a multicenter, prospective cohort study. Clinical response (CR) at week 16 was the primary endpoint, and steroid-free clinical remission (SFCRem) and endoscopic response were the secondary endpoints. Baseline histology, mucosal gene expression, and pharmacokinetics were studied for their effect on response to treatment. Results: We included 123 patients (mean age = 50.3 years). CR was recorded in 70.8% (75/106), SFCRem in 48% (59/123), endoscopic improvement in 71.4% (40/56), and mucosal healing in 28.6% (16/56). Higher PRO-stool frequency (OR = 0.49, p = 0.027), concomitant use of 5-ASA (OR = 3.69, p = 0.021), platelet number of ≥284 × 109/L (OR = 6.52, p = 0.001) at baseline, and a drop in the total count of platelets by 108/L (OR = 1.23, p = 0.022) at week 8 were independently associated with CR. Elevated trough levels of ustekinumab at week 16 were associated with a higher probability of endoscopic improvement (median difference = 3784 ng/mL, p = 0.013), with an optimal cut-off value of 3500 ng/mL (AUC = 0.82, 95% CI: 0.66–0.96). Increased mucosal mRNA expression for IL-23 (p = 0.007) and IL-23R (p = 0.031) at baseline was associated with increased probability of CR. Higher continuous Geboes scores at baseline were associated with a lower probability of CR (OR = 0.80, p = 0.045), with an optimal cut-off value of 14 (AUC = 0.75, 95% CI: 0.57–0.93). Conclusions: Clinical, laboratory, and molecular markers may identify patients with ulcerative colitis who are more likely to respond to ustekinumab. Full article
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20 pages, 1175 KB  
Review
Early Detection of Gastric Cancer: Linking Epidemiology, Pathophysiology, and Innovations in Digestive Endoscopy
by Marta La Milia, Mario Capasso, Tommaso Pessarelli, Guido Manfredi and Arnaldo Amato
Diseases 2026, 14(4), 148; https://doi.org/10.3390/diseases14040148 - 18 Apr 2026
Viewed by 551
Abstract
Background/Objectives: Despite substantial progress in understanding its pathophysiology and risk factors, gastric cancer remains a significant global health burden. Advances in endoscopic technology have improved the potential for early detection, yet variability in clinical practice persists. In this comprehensive narrative review, we summarize [...] Read more.
Background/Objectives: Despite substantial progress in understanding its pathophysiology and risk factors, gastric cancer remains a significant global health burden. Advances in endoscopic technology have improved the potential for early detection, yet variability in clinical practice persists. In this comprehensive narrative review, we summarize the most recent epidemiological trends in gastric pre-neoplastic and neoplastic lesions and critically appraise current evidence on optimizing endoscopic techniques and strategies for the detection of early gastric neoplasia, with an emphasis on emerging innovations. Methods: The relevant literature on epidemiology, risk factors, pathophysiology, and endoscopic management of GC was selectively reviewed based on the authors’ expertise and appraisal of contemporary evidence. Results: Marked global disparities persist in GC incidence, mortality, and stage at diagnosis. Interval GC—including missed lesions and so-called “true” interval cancers—remains a clinically relevant challenge and is frequently identified at advanced stages. These gaps are partly attributable to inconsistent quality in diagnostic esophagogastroduodenoscopy (EGD). High-quality EGD relies on adequate mucosal inspection time, systematic photodocumentation, optimal gastric preparation, and the use of standardized terminology, including mucosal visibility scores. Routine integration of chromoendoscopy and magnification techniques further enhances detection rates. Looking ahead, artificial intelligence holds promise as a transformative adjunct to standardize and augment real-time lesion recognition and quality assurance. Conclusions: High-quality endoscopic evaluation, coupled with tailored surveillance strategies, enables earlier detection of pre-neoplastic lesions and early gastric cancer, improving clinical outcomes. Future priorities include broadening access to high-quality endoscopy, harmonizing performance standards, and promoting continuous training alongside technological integration. Full article
(This article belongs to the Special Issue Gastric Cancer: New Trends in Endoscopic Diagnosis Staging and Treatment)
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12 pages, 844 KB  
Article
Towards a Better Understanding of MASLD: Patient Health Literacy, Illness Perception, and Awareness
by Irini Gergianaki, Foteini Anastasiou, Sophia Papadakis, Marilena Anastasaki, Manolis Linardakis, Juan Mendive, Leen J. M. Heyens, Ger Koek, Jean Muris and Christos Lionis
Diseases 2026, 14(4), 147; https://doi.org/10.3390/diseases14040147 - 17 Apr 2026
Viewed by 257
Abstract
Objectives: The objective of this study was to investigate metabolic dysfunction-associated steatotic liver disease (MASLD)-related awareness, health literacy (HL), and illness perception among patients at risk of MASLD in European primary care settings. Methods: Participants aged ≥50 years with either obesity, metabolic syndrome [...] Read more.
Objectives: The objective of this study was to investigate metabolic dysfunction-associated steatotic liver disease (MASLD)-related awareness, health literacy (HL), and illness perception among patients at risk of MASLD in European primary care settings. Methods: Participants aged ≥50 years with either obesity, metabolic syndrome (MetS), or type 2 diabetes mellitus (T2DM), and attending general practices (GPs) in Greece, Spain, or The Netherlands were included in the study. The participants completed surveys to collect data on their socio-demographic characteristics and health habits, including the European Health Literacy Survey (HLS-E-Q16), the Brief Illness Perception Questionnaire [B-IPQ], and the Public Awareness of NAFLD Questionnaire. Results: Overall, 234 patients participated in the study (mean age: 66.5 ± 9.5 years; 45.7% were male). Among the participants, 64.5%, 66.2%, and 59.8% had a diagnosis of diabetes, obesity, and MetS, respectively. Almost one-third (27.9%) had never heard about MASLD or discussed MASLD with their GP. Twelve percent (12.1%) had never heard about cirrhosis, and 20.5% were unaware that liver disorders may cause serious health problems. Overall, 43.6% of the patients had a sufficient level of HL (score >13) with a mean score of 11.5 ± 3.3. Illness perception (B-IPQ score) was low at 41.6 ± 11.6. Significantly higher B-IPQ scores were documented for female compared to male respondents (43.1 vs. 39.8; p < 0.01). Multivariate analysis found that knowledge about MASLD was associated with higher HLS-E-Q16 (p = 0.017) and B-IPQ (p = 0.028) scores. Conclusions: Despite being at risk, a significant proportion of the study participants were unaware of MASLD, its risk factors, and their personal susceptibility. This study underscores the importance of enhancing patient HL and promoting prevention and risk reduction, particularly among high-risk patient populations. Full article
(This article belongs to the Section Gastroenterology)
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15 pages, 454 KB  
Systematic Review
Cow’s Milk Protein Allergy, a Systematic Review of Clinical Characteristics, Diagnosis, Management, and Economic Impact
by Fabiola Menco Contreras, Karina Pastor-Sierra and Nany Castilla Herrera
Diseases 2026, 14(4), 146; https://doi.org/10.3390/diseases14040146 - 17 Apr 2026
Viewed by 686
Abstract
Introduction: Cow’s milk protein allergy (CMPA) is one of the most common food allergies in early infancy and poses important clinical and economic challenges for affected children, their families, and healthcare systems. In Latin America, variability in diagnostic and therapeutic approaches remains substantial. [...] Read more.
Introduction: Cow’s milk protein allergy (CMPA) is one of the most common food allergies in early infancy and poses important clinical and economic challenges for affected children, their families, and healthcare systems. In Latin America, variability in diagnostic and therapeutic approaches remains substantial. Objective: We aim to systematically review the available evidence on CMPA, with emphasis on clinical characteristics, diagnosis, management, and economic impact, and to provide a complementary cost analysis of specialized formulas in the Colombian context. Methods: A systematic review was conducted according to PRISMA guidelines to synthesize current evidence on CMPA in pediatric populations. Studies published between 2010 and 2023 were screened using predefined eligibility criteria, and 46 studies were included in the qualitative synthesis. A complementary cost analysis was also performed to estimate the six-month costs associated with specialized infant formulas in Colombia, based on average age-specific formula consumption and standardized 2025 market prices. Results: The reviewed evidence confirms that CMPA is a heterogeneous condition with variable clinical manifestations and persistent diagnostic challenges, particularly in non-IgE-mediated presentations. Elimination of cow’s milk protein followed by oral food challenge remains the reference diagnostic approach. Breastfeeding with maternal dairy exclusion is consistently recommended as the preferred first-line strategy, whereas extensively hydrolyzed and amino-acid-based formulas are used when breastfeeding is not feasible or is insufficient. Estimated six-month costs ranged from COP 4,337,640 to COP 14,480,700 (approximately USD 1100–3600), depending on formula type. Conclusions: CMPA requires early recognition, careful clinical evaluation, individualized nutritional management, and improved access to effective and affordable treatment strategies. Full article
(This article belongs to the Section Clinical Nutrition)
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20 pages, 1287 KB  
Systematic Review
Neuromodulatory Interventions in Experimental Acute Pancreatitis: A Systematic Review of Rodent Studies
by Maxim Rantsev, Alexey Sarapultsev and Valeriy Chereshnev
Diseases 2026, 14(4), 145; https://doi.org/10.3390/diseases14040145 - 16 Apr 2026
Viewed by 363
Abstract
Background/Objectives: Acute pancreatitis (AP) lacks disease-modifying pharmacotherapy. Neuroimmune, serotonergic, and redox-regulated pathways may modulate inflammatory amplification and acinar injury, although pharmacovigilance data link some psychotropic drug classes to AP risk. This review synthesized controlled rodent studies evaluating neuromodulatory interventions with serotonergic, stress-axis, [...] Read more.
Background/Objectives: Acute pancreatitis (AP) lacks disease-modifying pharmacotherapy. Neuroimmune, serotonergic, and redox-regulated pathways may modulate inflammatory amplification and acinar injury, although pharmacovigilance data link some psychotropic drug classes to AP risk. This review synthesized controlled rodent studies evaluating neuromodulatory interventions with serotonergic, stress-axis, or ferroptosis-linked targets in experimental AP. Methods: PubMed, Scopus, eLIBRARY.ru, and Elicit were searched in January 2026, supplemented by Google Scholar audit and citation chasing. Eligible studies were controlled in vivo rodent experiments using validated AP models with quantitative outcomes. Intervention timing was classified a priori as a primary analytic variable. Risk of bias was assessed with SYRCLE. A prespecified audit showed that no subset met the criteria for quantitative pooling because of heterogeneity in model class, compounds, timing, outcome definitions, units, and sampling timepoints. Mechanism-stratified qualitative synthesis was therefore performed. The protocol was registered on OSF (doi: 10.17605/OSF.IO/CZXDJ). Results: Nine studies (1992–2023) yielded 410 outcome rows across three mechanistic strands. Serotonergic modulation (5-HT2/5-HT2A-focused; six studies) reduced serum amylase/lipase (−37% to −65% vs. disease controls) and histological injury, with receptor-selectivity data supporting 5-HT2A-mediated mechanisms. Stress-axis modulation with thiadiazine L-17 reduced 7-day mortality in two severe models (from 50–70% to 30%). Olanzapine attenuated ferroptosis-linked injury via off-target antioxidant activity independent of serotonergic receptors. All interventions were prophylactic, peri-induction, or very early post-induction; no delayed therapeutic-window studies were identified. Most SYRCLE domains were unclear, particularly allocation concealment and blinding-related procedures. Conclusions: Neuromodulatory pathways modulate experimental AP in rodents, but evidentiary strength differs across mechanistic strands. Inference is constrained by absent therapeutic-window testing, heterogeneous endpoints, and reporting deficits. The findings support mechanism-level target prioritization rather than clinical repurposing. Full article
(This article belongs to the Special Issue Diseases: From Molecular to the Clinical Perspectives)
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16 pages, 281 KB  
Article
Physical and Lifestyle Predictors of Vascular Health in Premenopausal East Asian Women: The Women’s Vascular Health Project
by Wei Xiong, Fei Tang, Beck Graefe, Ana Raquel Calzada Bichili, Duncan Ryan, Joseph Bonner and Arlette Perry
Diseases 2026, 14(4), 144; https://doi.org/10.3390/diseases14040144 - 15 Apr 2026
Viewed by 497
Abstract
Background/Objectives: Cardiovascular disease is the leading cause of adult deaths globally and has recently been reported to be on the rise in younger adult women. The present study examined the impact of physical and lifestyle predictors of vascular health in 125 apparently [...] Read more.
Background/Objectives: Cardiovascular disease is the leading cause of adult deaths globally and has recently been reported to be on the rise in younger adult women. The present study examined the impact of physical and lifestyle predictors of vascular health in 125 apparently healthy premenopausal East Asian volunteers. Methods: Vascular health outcomes included carotid–femoral pulse wave velocity (cfPWV), central augmentation index (cAIx), and mean arterial pressure (MAP). Body composition/anthropometric predictors included total adiposity, visceral adipose tissue (VAT) and skeletal muscle mass (SMM), as well as body mass index (BMI) and waist circumference (WC). Lifestyle predictors included the International Physical Activity Questionnaire (IPAQ) and dietary recall. Multivariate linear regression was used to identify independent predictors of combined vascular health and individual vascular outcome variables. The analysis for independent vascular outcomes was repeated after age stratification (<35 years versus ≥35 years). Results: VAT showed a significant multivariate effect on combined vascular health outcomes (p = 0.002) and independently contributed to cfPWV (p = 0.013). WC positively predicted cAIx (p = 0.010) while SMM was inversely related to cAIx (p = 0.024). BMI positively predicted MAP (p = 0.039) in the multivariate analysis. After age adjustment however, only BMI emerged as a significant independent predictor of both cfPWV (p = 0.040) and MAP (p = 0.024). Furthermore, WC remained positively associated with cAIx (p = 0.042) while SMM remained inversely related to cAIx (p = 0.038). After age stratification, IPAQ was inversely related to cfPWV while BMI was positively associated with MAP (p = 0.035) in women < 35 years only. However, in older women, total adiposity (p = 0.040) and total cholesterol (p = 0.011) were both positively, while SMM (p = 0.046) was negatively associated with cAIx. Conclusions: With the exception of age, VAT was the single best predictor of general vascular health in East Asian women. Independent of age, however, BMI, WC, and SMM significantly contributed to independent vascular outcome measures and in combination with age, substantially add to the prediction of vascular risk. Furthermore, stratifying younger versus older premenopausal women resulted in different associations with independent vascular outcome measures demonstrating that across a large age range of premenopausal women, it is important to consider age in the evaluation of vascular health. Full article
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11 pages, 596 KB  
Article
Clinicopathological Characteristics and Postoperative Outcomes Following Parotidectomy: A Ten-Year Retrospective Study from a Tertiary Center
by Mohammad Aljarba, Mishari Alanezi, Majed A. Alali, Azzam Alotaibi, Faisal Alkhunein and Khalid Alqahtani
Diseases 2026, 14(4), 143; https://doi.org/10.3390/diseases14040143 - 11 Apr 2026
Viewed by 300
Abstract
Background/Objective: The parotid gland is the largest salivary gland, and tumors arising from it exhibit wide histopathological diversity. Management approaches vary according to tumor characteristics and carry a risk of postoperative complications, particularly facial nerve injury. However, local data remain limited. This study [...] Read more.
Background/Objective: The parotid gland is the largest salivary gland, and tumors arising from it exhibit wide histopathological diversity. Management approaches vary according to tumor characteristics and carry a risk of postoperative complications, particularly facial nerve injury. However, local data remain limited. This study aimed to describe the clinicopathological characteristics, surgical approaches, and postoperative outcomes of patients undergoing parotidectomy. Method: A retrospective cohort study was conducted at a high-volume tertiary center in Saudi Arabia. All consecutive patients who underwent parotidectomy between June 2015 and January 2025 were included. Demographic data, histopathological diagnoses, surgical procedures and postoperative complications were extracted from electronic medical records. Statistical analyses were performed using SPSS version 26, with A p-value of <0.05 considered statistically significant. Results: A total of 154 patients were included, with a mean age of 45.2 ± 12.6 years; 61% were male. Benign lesions constituted 87% of cases, with pleomorphic adenoma being the most common histopathological diagnosis. Malignancies accounted for 13% of cases, most frequently mucoepidermoid carcinoma. The most common postoperative complications were facial nerve palsy, followed by sensory numbness. Conclusions: The majority of parotid gland tumors in this cohort were benign, with pleomorphic adenoma as the most common histological subtype. Facial nerve palsy and sensory disturbances were the most common postoperative complications. These findings provide valuable local data on parotid gland lesions in Saudi Arabia and support current surgical management practices. Full article
(This article belongs to the Section Oncology)
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20 pages, 3725 KB  
Article
Establishment of a Thioacetamide-Induced Hepatotoxicity Model in Synanthropic Rats with Translational Relevance
by Lesly Adelis Valdivia Quispe, Lucio Velasco Lopez, Daysi Zulema Díaz Obregón, Alexis German Murillo Carrasco, Joel de León Delgado, Luis Lloja Lozano, Jhon Wilfredo Pando Mayta, Anthony Brayan Rivera Prado, Kelly Geraldine Yparraguirre Salcedo, Víctor Hugo Carbajal Zegarra and Claudio Willbert Ramírez Atencio
Diseases 2026, 14(4), 142; https://doi.org/10.3390/diseases14040142 - 11 Apr 2026
Viewed by 367
Abstract
Background/Objectives: Chemically induced hepatotoxicity is widely used in experimental research to model liver disease pathophysiology and to support preclinical studies. Thioacetamide (TAA) is a well-established hepatotoxic agent in conventional laboratory rodents; however, its effects in synanthropic rats—characterized by genetic heterogeneity and chronic [...] Read more.
Background/Objectives: Chemically induced hepatotoxicity is widely used in experimental research to model liver disease pathophysiology and to support preclinical studies. Thioacetamide (TAA) is a well-established hepatotoxic agent in conventional laboratory rodents; however, its effects in synanthropic rats—characterized by genetic heterogeneity and chronic environmental exposure—remain poorly defined. This study aimed to establish and characterize a preclinical model of TAA-induced hepatotoxicity in synanthropic rats and to assess its relevance for experimental liver disease research. Methods: Female synanthropic rats representing four phenotypic variants (albino, mottled, black, and brown; total n = 132) were housed under controlled conditions and assigned to control or TAA-treated groups. TAA was administered intraperitoneally at doses ranging from 200 to 300 mg/kg. Clinical parameters, including body weight and vital signs, were periodically monitored. Hematological profiles and serum biochemical markers of liver function were analyzed. Hepatic injury was evaluated by histopathological examination using hematoxylin–eosin staining. Statistical analyses were performed using R software, with p ≤ 0.05 considered statistically significant. Results: TAA-treated rats developed consistent clinical manifestations of hepatotoxicity, including progressive weight loss and reduced activity. Biochemical analyses revealed significant increases in serum transaminases, gamma-glutamyl transferase, and alkaline phosphatase, accompanied by alterations in hematological parameters. Histological evaluation demonstrated dose-dependent liver injury characterized by centrilobular necrosis, inflammatory infiltration, hepatocellular degeneration, and architectural disruption across all synanthropic rat variants. Conclusions: Synanthropic rats exhibit reproducible biochemical, hematological, and histopathological features of TAA-induced liver injury comparable to those reported in conventional laboratory strains. This model represents a robust preclinical approach for studying chemically induced hepatotoxicity and may provide enhanced translational relevance due to its genetic and environmental heterogeneity. Full article
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19 pages, 1694 KB  
Article
Persistent Symptoms After SARS-CoV-2 Infection in a Referred Occupational Clinical Registry: Symptom Patterns and Associated Factors
by Agnessa Kozak, Jana Wischnat, Corinna Rademacher, Andreas Gonschorek, Ingo Schmehl, Susann Seddigh, Andrea Fürst, Kai Wohlfarth, Lynn Engel, Jakob Wefers, Kerrin Kobes, Olaf Kleinmüller, Majid Essa, Martin Tegenthoff, Albert Nienhaus and Peter Schwenkreis
Diseases 2026, 14(4), 141; https://doi.org/10.3390/diseases14040141 - 9 Apr 2026
Viewed by 328
Abstract
Background/Objectives: Persistent symptoms following SARS-CoV-2 infection pose a substantial burden in occupational settings. This study aimed to characterize symptoms following work-related SARS-CoV-2 infection and to assess their associations with sociodemographic and clinical factors. Methods: Data were obtained from a multicenter clinical registry of [...] Read more.
Background/Objectives: Persistent symptoms following SARS-CoV-2 infection pose a substantial burden in occupational settings. This study aimed to characterize symptoms following work-related SARS-CoV-2 infection and to assess their associations with sociodemographic and clinical factors. Methods: Data were obtained from a multicenter clinical registry of insured individuals referred for persistent symptoms 12 weeks after laboratory-confirmed work-related SARS-CoV-2 infection. Participants were assessed within a standardized post-COVID diagnostic program at six specialized clinics for occupational accident insurance in Germany. Persistent symptoms reported by ≥50% of participants were analyzed using generalized linear mixed models with random intercepts for center. Results: A total of 1511 participants (76.7% women; median age 54 years) were included, with a median interval of 16 months between infection and assessment. On average, participants reported ten persistent symptoms. The most frequent complaints were limited physical capacity (95.6%), concentration difficulties (78.8%), dyspnea (70.5%), exhaustion/tiredness (68.9%), and memory difficulties (67.5%). Individuals reporting more than ten acute symptoms had increased odds of persistent complaints (ORs between 2.1 and 4.66). Hospitalization was independently associated with persistent dyspnea (OR 1.62; 95%CI 1.17–2.25). Reinfections were linked to exhaustion and cognitive fatigue. Compared with Omicron, wild-type infection was associated with higher odds of concentration difficulties (OR 1.65; 95%CI 1.17–2.33). Comorbidities demonstrated symptom-specific associations. Conclusions: Among individuals with work-related SARS-CoV-2 infection, limited physical capacity and cognitive impairments were the most frequently reported symptoms, and higher acute symptom burden was strongly associated with the development of persistent symptoms. These findings support course-oriented evaluation and symptom-specific approaches in occupational disease assessment and management. Full article
(This article belongs to the Section Infectious Disease)
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21 pages, 4126 KB  
Article
Adropin and Endothelin-1 as Complementary Signals Associated with Early Vascular Aging in Middle-Aged Type 2 Diabetes
by Rooban Sivakumar, Arul Senghor Kadalangudi Aravaanan, Vinodhini Vellore Mohanakrishnan and Janardhanan Kumar
Diseases 2026, 14(4), 140; https://doi.org/10.3390/diseases14040140 - 9 Apr 2026
Viewed by 482
Abstract
Background: Early vascular aging (EVA) is a common complication of type 2 diabetes mellitus. Early identification is crucial in middle-aged individuals with T2DM, as vascular stiffness can occur gradually for years before cardiovascular disease. However, EVA is rarely considered in routine care. [...] Read more.
Background: Early vascular aging (EVA) is a common complication of type 2 diabetes mellitus. Early identification is crucial in middle-aged individuals with T2DM, as vascular stiffness can occur gradually for years before cardiovascular disease. However, EVA is rarely considered in routine care. Adropin is a vasoprotective peptide that may counter-regulate endothelin-1 (ET-1). Therefore, this study aims to examine the association between circulating adropin, ET-1, oxLDL, MMP-2, VEGFA, and EVA. Methods: This observational study included 300 adults aged 25–55 years (150 T2DM; 150 age/sex-matched controls). ePWV was calculated from age and mean blood pressure. EVA was classified using a residual-based, age-specific ePWV threshold derived from controls. Associations were tested using correlation and logistic regression. ROC and decision curve analyses were performed to evaluate diagnostic performance and clinical utility. Results: EVA prevalence was 38.6% overall, occurring in 7.3% of controls and increasing across T2DM with good and poor glycemic control (56.1% and 80.95%, respectively, p < 0.001). Compared with normal vascular aging, EVA showed lower adropin and higher ET-1, oxLDL and MMP-2, with lower VEGFA (all p < 0.05). In fully adjusted models, adropin (OR 0.991 per pg/mL; p < 0.001) and ET-1 (OR 1.017 per pg/mL, p = 0.005) remained independently associated with EVA. A combined adropin + ET-1 predictor improved discrimination (AUC 0.901, 95% CI 0.868–0.934), at a predicted-probability cutoff of 0.607, 78.7% sensitivity and 87.0% specificity. Conclusions: In middle-aged T2DM, EVA was associated with lower adropin and higher ET-1 in T2DM. These findings support an association between these biomarkers and the EVA phenotype. Full article
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18 pages, 1237 KB  
Article
Knowledge and Determinants of Nonalcoholic Fatty Liver Disease Among Adults in Northern Border Region, Saudi Arabia: A Cross-Sectional Study
by Yusef Muhana Alenezi, Rana Awad S. Alanazi, Danah Ashwi S. AlShalikhi, Rimas Naif A. Alanazi, Aryam Meshal S. Alanazi, Sarah Ahmed S. Alanazi, Renad Abdulrahman O. Alanazi, Noor Awad S. Alanazi, Baraah Abu Alsel, Fathia Ahmed Mersal, Safya E. Esmaeel and Manal S. Fawzy
Diseases 2026, 14(4), 139; https://doi.org/10.3390/diseases14040139 - 9 Apr 2026
Viewed by 490
Abstract
Background/Objectives: Nonalcoholic fatty liver disease (NAFLD), also referred to as metabolic dysfunction-associated steatotic liver disease (MASLD), affects roughly one-quarter of the global population and represents a major public health concern. Despite its rising prevalence and potential for serious complications, NAFLD remains underrecognized and [...] Read more.
Background/Objectives: Nonalcoholic fatty liver disease (NAFLD), also referred to as metabolic dysfunction-associated steatotic liver disease (MASLD), affects roughly one-quarter of the global population and represents a major public health concern. Despite its rising prevalence and potential for serious complications, NAFLD remains underrecognized and poorly understood in many communities. This study aimed to assess knowledge of NAFLD and its determinants among adults in the Northern Border Region of Saudi Arabia. Methods: A descriptive, population-based cross-sectional study was conducted using a previously validated online questionnaire adapted from published NAFLD awareness instruments, administered to adults residing in the Northern Border Region of Saudi Arabia. Data were analyzed using Python (statsmodels, version 0.14), and non-parametric tests, correlation analyses, and multivariable linear regression were used to examine NAFLD knowledge and its associated determinants. Results: A total of 1016 adults (mean age 34.7 ± 11.8 years) were included in the analysis. The mean NAFLD knowledge score was 14.6 ± 8.3 out of 30 (48.7% correct responses), with a median of 16 (interquartile range 8–21). Overall, 59.2% of participants had poor knowledge, 26.8% had moderate knowledge, and 14% had good knowledge. In bivariate analyses, educational level (χ2 = 15.62, p < 0.001), family history of liver disease (p = 0.001), body weight category (p = 0.003), and smoking status (p = 0.007) were significantly associated with NAFLD knowledge. In multivariable linear regression, university education (B = 2.783, 95% CI 0.627–4.940, p = 0.011) was an independent positive predictor of higher knowledge scores. Current smoking (B = −1.857, 95% CI −3.477 to −0.237, p = 0.025), private-sector employment (B = −1.934, 95% CI −3.867 to −0.001, p = 0.050), and overweight status (B = −4.119, 95% CI −7.337 to −0.901, p = 0.012) were independently associated with lower knowledge scores. The final model explained 2.2% of the variance in knowledge (adjusted R2 = 0.022). Conclusions: This study demonstrates generally low levels of NAFLD knowledge among adults in the Northern Border Region of Saudi Arabia, with only a minority achieving good knowledge scores. The findings underscore the need for targeted health promotion initiatives, educational interventions, and public campaigns to improve awareness of NAFLD and to support its prevention and management. Full article
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8 pages, 814 KB  
Case Report
Atypical Skull Base Osteomyelitis of the Clivus Mimicking a Malignant Lesion: A Case Report
by Magdalena Stocker, Johanna Felber and Patricia Bäck
Diseases 2026, 14(4), 138; https://doi.org/10.3390/diseases14040138 - 9 Apr 2026
Viewed by 363
Abstract
Background/Objectives: Atypical skull base osteomyelitis (ASBO) is a rare disease, typically involving the basisphenoid and basiocciput. Diagnosis consists of clinical examination, imaging methods such as PET-CT scans and MRI, microbiological testing, and possibly native tissue samples. Long-term intravenous antibiotic therapy is the treatment [...] Read more.
Background/Objectives: Atypical skull base osteomyelitis (ASBO) is a rare disease, typically involving the basisphenoid and basiocciput. Diagnosis consists of clinical examination, imaging methods such as PET-CT scans and MRI, microbiological testing, and possibly native tissue samples. Long-term intravenous antibiotic therapy is the treatment of choice. Methods/Case Report: We present a case of ASBO of the clivus initially suspected to be a malignant lesion due to malignant melanoma in the patient’s history. Several tissue biopsies were taken, and microbiological testing of native tissue biopsies in combination with PET-CT and MRI imaging led to the diagnosis of ASBO. The patient received long-term antibiotic therapy with meropenem and drastically improved in his overall health. Discussion and Conclusions: This case highlights the challenges encountered in the diagnosis and management of ASBO, especially with relevant possible differential diagnoses. Full article
(This article belongs to the Section Infectious Disease)
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29 pages, 2344 KB  
Review
Glycation at the Crossroads of Disease Pathogenesis: Mechanistic Insights and Therapeutic Frontiers
by Sneha Krishnamoorthi, Rupachandra Saravanakumar and Vivek Kumar
Diseases 2026, 14(4), 137; https://doi.org/10.3390/diseases14040137 - 8 Apr 2026
Viewed by 516
Abstract
Protein glycation is a nonenzymatic modification that links sugar chemistry to molecular aging and chronic disease. Sequential reactions involving Schiff bases, Amadori products, and reactive α dicarbonyl intermediates generate advanced glycation end products (AGEs) that irreversibly alter protein structure and function. AGEs also [...] Read more.
Protein glycation is a nonenzymatic modification that links sugar chemistry to molecular aging and chronic disease. Sequential reactions involving Schiff bases, Amadori products, and reactive α dicarbonyl intermediates generate advanced glycation end products (AGEs) that irreversibly alter protein structure and function. AGEs also act as ligands for the receptor for advanced glycation end products (RAGE), initiating oxidative stress, inflammation, and tissue remodeling. This review synthesizes the molecular pathways of AGE formation, their structural diversity, and the biological factors influencing glycation kinetics. Advances in analytical detection methods—including fluorescence spectroscopy, LC–MS/MS, and immunochemical approaches—are highlighted for their role in monitoring AGE accumulation. Particular attention is given to the contribution of glycation to diabetes, cardiovascular disease, neurodegeneration, and cancer, alongside emerging therapeutic strategies to limit AGE formation or block AGE–RAGE signaling. Glycation thus represents a central mechanism in human disease pathogenesis and an emerging therapeutic frontier. Full article
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14 pages, 447 KB  
Article
The Relationship Between Obesity, Overweight, and the Prevalence of Depression and Anxiety Among University Students: Evidence from a Nationally Representative Cross-Sectional Study in Greece
by Olga Alexatou, Konstantinos Papadimitriou, Exakousti-Petroula Angelakou, Sousana K. Papadopoulou, Myrsini Pappa, Apostolia Ntovoli, Aspasia Serdari, Konstantina Apostolidou, Theophanis Vorvolakos and Constantinos Giaginis
Diseases 2026, 14(4), 136; https://doi.org/10.3390/diseases14040136 - 8 Apr 2026
Viewed by 507
Abstract
Background and Objectives: Rates of obesity have been consistently increasing in recent years across all age groups, with a notable rise among young people. Obesity represents a persistent inflammatory condition and a key contributor to various chronic health problems, such as cardiovascular disorders, [...] Read more.
Background and Objectives: Rates of obesity have been consistently increasing in recent years across all age groups, with a notable rise among young people. Obesity represents a persistent inflammatory condition and a key contributor to various chronic health problems, such as cardiovascular disorders, metabolic abnormalities, cancer, and psychological conditions. The move from high school to university is a transitional phase accompanied by specific pressures that can affect both body weight control and mental health in students. This cross-sectional investigation aimed to investigate potential associations between excess weight and the presence of depressive and anxiety symptoms in university populations. Methods: This cross-sectional analysis included 5298 students enrolled at universities across ten geographic areas of Greece. Participants filled out questionnaires concerning demographic information and lifestyle behaviors. Levels of depression and anxiety were measured using the Beck Depression Inventory (BDI-II) and the short form of the State Anxiety Inventory (STAI-6), respectively. Measurements of height and body weight were obtained to compute Body Mass Index (BMI). Results: The presence of overweight or obesity among students was significantly and independently related to female sex, urban residence, living independently, tobacco use, and lower academic performance (p = 0.0103, p = 0.0102, p = 0.0203, p = 0.0075, and p = 0.0168, respectively). Individuals reporting insufficient physical activity had 85% higher odds of being overweight or obese (p = 0.0068). Similarly, participants experiencing depressive or anxious symptomatology had more than double odds of excess body weight compared with those without such symptoms (p = 0.0015 and p = 0.0012, respectively). Furthermore, poor Mediterranean diet adherence was linked to more than a twofold increase in the odds of overweight or obesity (p = 0.0005). Conclusions: These findings offer considerable evidence that symptoms of depression and anxiety may serve as significant contributors to the development of overweight and obesity among university students. Additional longitudinal studies are strongly encouraged to substantiate these observations. Full article
(This article belongs to the Section Neuro-psychiatric Disorders)
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14 pages, 733 KB  
Article
A Pilot Randomized, Controlled Trial of Nighttime Peanut Butter Supplementation in Firefighters: Blood Pressure and Body Composition Outcomes
by Austin A. Kohler, David H. Shuler, Leke O. Adeleye, Andrew R. Moore, Nicole Peritore and A. Maleah Winkler
Diseases 2026, 14(4), 135; https://doi.org/10.3390/diseases14040135 - 8 Apr 2026
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Abstract
Background/Objectives: Dietary approaches to combating risk factors for cardiovascular disease are valuable, especially for individuals in high-stress occupations like first responders. The purpose of this pilot randomized control trial was to determine the effect of regular peanut butter (PB) supplementation on blood [...] Read more.
Background/Objectives: Dietary approaches to combating risk factors for cardiovascular disease are valuable, especially for individuals in high-stress occupations like first responders. The purpose of this pilot randomized control trial was to determine the effect of regular peanut butter (PB) supplementation on blood pressure and primary measures of body composition (body fat %, fat mass, and lean mass) in firefighters. Methods: Full-time firefighters (N = 40; 1 woman) were randomly assigned to a control group or a peanut butter group for 7 weeks. Participants in the peanut butter group consumed one serving of peanut butter before bed at least 5 days per week for the intervention period. Participants in the control group continued with their usual diet. Indices of body composition and blood pressure were collected before and after the intervention period and compared using mixed-factorial ANOVAs (α = 0.05). Results: No interaction effects between group and time were observed for blood pressure variables (p = 0.619–0.650). Similarly, the changes among the PB group over time in percent body fat (Δ = −0.53 ± 1.74%), fat mass (Δ = −0.73 ± 2.21 kg), and lean body mass (Δ = 0.04 ± 1.65 kg) were not significantly different than the changes over time in the control group (p ≥ 0.067 for all). Conclusions: Seven-week PB supplementation did not affect male firefighter body composition or blood pressure; however, future studies should investigate longer durations with sophisticated dietary recall methods. ClinicalTrials.gov Identifier: NCT06364202. Full article
(This article belongs to the Special Issue Functional Foods and Supplements: Special Focus on Mechanisms of Action and Potential Clinical Application)
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12 pages, 258 KB  
Article
Quality of Life, Fear of COVID-19, Psychological Distress, and Resilience Among Individuals with Chronic Conditions: Evidence from the Later Phases and Aftermath of the COVID-19 Crisis
by Elpida Stratou, Georgia-Nektaria Porfyri, Stavros Antonopoulos, Afroditi Biziou, Aikaterini Kalogeropoulou, Katerina Theodorou, Kalliopi Kalogeropoulou, Aikaterini Kyriaki Timotheou, Maria Kapouralou, Aikaterini Gamvroula and Maria Saridi
Diseases 2026, 14(4), 134; https://doi.org/10.3390/diseases14040134 - 8 Apr 2026
Viewed by 626
Abstract
Background/Objectives: The COVID-19 pandemic posed significant challenges to quality of life, particularly for individuals living with chronic physical and/or mental conditions. Psychological factors such as fear of COVID-19, psychological distress, and resilience may be associated with quality-of-life outcomes during prolonged public health crises. [...] Read more.
Background/Objectives: The COVID-19 pandemic posed significant challenges to quality of life, particularly for individuals living with chronic physical and/or mental conditions. Psychological factors such as fear of COVID-19, psychological distress, and resilience may be associated with quality-of-life outcomes during prolonged public health crises. This study aimed to examine quality of life and its psychological correlates among individuals with chronic conditions during the later phases and aftermath of the COVID-19 pandemic crisis. Methods: A cross-sectional study was conducted among 293 adults with chronic physical and/or mental conditions attending the General Hospital of Argolida, Greece. Participants completed validated self-report measures assessing quality of life (MVQOLI), fear of COVID-19 (FCV-19S), depression, anxiety, and stress (DASS-21), and psychological resilience (CD-RISC-25). Descriptive statistics, Spearman correlation analyses, and multivariable regression models were used to examine associations and identify factors associated with quality-of-life domains. Results: Higher levels of fear of COVID-19 and depressive symptoms were significantly associated with poorer quality of life across multiple domains. Depressive symptoms showed consistent negative associations with functional, interpersonal, transcendent, and overall quality-of-life scores. In contrast, psychological resilience was positively associated with interpersonal, transcendent, and overall quality of life. Regression analyses showed that depressive symptoms were negatively associated with overall quality of life, while resilience was independently associated with better quality-of-life outcomes. Conclusions: Psychological distress, particularly depressive symptoms and fear related to COVID-19, was associated with lower quality of life among individuals with chronic conditions during the later phases and aftermath of the COVID-19 crisis. Psychological resilience was positively associated with better quality-of-life outcomes, underscoring its relevance for supporting well-being during and after public health crises. Full article
16 pages, 1757 KB  
Article
Dengue Epidemiology in Mexico: Temperature as a Contributing Factor to National Dengue Trends
by Juan Manuel Bello-López, Dulce Milagros Razo Blanco-Hernández, Andres Emmanuel Nolasco-Rojas, Emilio Mariano Durán-Manuel, Víctor Hugo Gutiérrez-Muñoz, Carol Vivian Moncayo-Coello, Jesus Alberto Meléndez-Ordoñez, José Alberto Díaz-Quiñonez, Magnolia del Carmen Ramírez-Hernández, Adolfo López-Ornelas, María Concepción Tamayo-Ordóñez, Yahaira de Jesús Tamayo-Ordóñez, Francisco Alberto Tamayo-Ordóñez, Benito Hernández-Castellanos, Luis Gustavo Zárate-Sánchez, Oscar Sosa-Hernández, Julio César Castañeda-Ortega, Claudia Camelia Calzada-Mendoza, Alejandro Cárdenas-Cantero, Clemente Cruz-Cruz and Miguel Ángel Loyola-Cruzadd Show full author list remove Hide full author list
Diseases 2026, 14(4), 133; https://doi.org/10.3390/diseases14040133 - 7 Apr 2026
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Abstract
The increasing burden of dengue represents a growing global public health concern. Among the factors associated with rising dengue incidence, climate change, particularly increasing temperatures, has been frequently highlighted, alongside other environmental, biological, and social determinants. The emergence of dengue in previously non-endemic [...] Read more.
The increasing burden of dengue represents a growing global public health concern. Among the factors associated with rising dengue incidence, climate change, particularly increasing temperatures, has been frequently highlighted, alongside other environmental, biological, and social determinants. The emergence of dengue in previously non-endemic areas and its sustained increase in incidence have become increasingly common in recent decades. Objective: The aim of this study was to describe national dengue case trends in Mexico from 1990 to 2023 and to assess their association with temperature over the same period using a descriptive, retrospective analysis of epidemiological surveillance and temperature data. Methods: Epidemiological data on confirmed dengue cases and incidence were obtained from the Morbidity Yearbook of the General Directorate of Epidemiology (DGE) of the Mexican Ministry of Health. These data were used to construct epidemic curves and to analyze the geographic distribution of incidence using quartiles. Temperature data were derived from the national annual mean calculated from monthly reports issued by the National Water Commission (CONAGUA). Associations between temperature and dengue cases and incidence were explored over the study period. Results: Temporal analysis revealed a significant increase in both dengue cases and incidence in Mexico, with a positive association with temperature during the same period. Quartile-based geographic analysis showed that state-level classifications remained relatively stable across periods, with several states clustering within or tending toward the group considered endemic. Conclusions: The results of this study show an increase in cases and incidence of dengue over time, as well as a positive association between cases/incidence of dengue in Mexico and the increase in the national average temperature during the study period; however, due to its descriptive and retrospective design, causal inference is not possible. Dengue transmission is inherently multifactorial, and the observed trends likely reflect the combined influence of climatic conditions, historical expansion of transmission cycles, vector establishment, and unmeasured socio-epidemiological factors. The absence of entomological indicators, additional climatic variables, and spatially or seasonally disaggregated analyses limits the ability to capture localized dynamics. Overall, temperature should be interpreted as a contributing factor within a complex system rather than as the sole driver of dengue trends, underscoring the need for integrated surveillance and control strategies in both endemic and non-endemic regions. Full article
(This article belongs to the Section Infectious Disease)
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20 pages, 1092 KB  
Article
Predictive Analysis of Drug-Resistant Tuberculosis: Integrating Molecular Markers, Clinical Governance, and Community-Engaged Education in Rural South Africa
by Siphosihle Conham, Ncomeka Sineke, Ntandazo Dlatu, Lindiwe Modest Faye, Mojisola Clara Hosu and Teke Apalata
Diseases 2026, 14(4), 132; https://doi.org/10.3390/diseases14040132 - 3 Apr 2026
Viewed by 372
Abstract
Background: Drug-resistant tuberculosis remains a major challenge in resource-limited settings, particularly in rural regions of the Eastern Cape Province, where limited laboratory infrastructure, constrained access to advanced molecular diagnostics, shortages of specialized healthcare personnel, and prolonged diagnostic turnaround times can delay appropriate treatment [...] Read more.
Background: Drug-resistant tuberculosis remains a major challenge in resource-limited settings, particularly in rural regions of the Eastern Cape Province, where limited laboratory infrastructure, constrained access to advanced molecular diagnostics, shortages of specialized healthcare personnel, and prolonged diagnostic turnaround times can delay appropriate treatment initiation. This study examined whether routinely detectable genomic resistance markers could be integrated with parsimonious machine learning approaches to support early risk stratification for isoniazid (INH) and/or rifampicin (RIF) resistance and multidrug-resistant tuberculosis (MDR-TB). Methods: We conducted a retrospective analysis of clinical, demographic, and genomic data from 207 Mycobacterium tuberculosis isolates representing 207 unique patients. Resistance was classified as INH and/or RIF resistance or MDR-TB (concurrent resistance to both drugs). Predictors included age, sex, and canonical resistance-associated mutations (katG S315T, inhA −15C>T, and rpoB codon substitutions). Logistic regression was used to estimate adjusted odds ratios (aORs), while Random Forest models were applied to assess non-linear feature importance. Internal validation was performed using 10-fold cross-validation. A systems network analysis mapped the integration of model-derived risk bands into Clinical Governance structures and Community-Engaged Education pathways, including interventions delivered by Community Health Workers (CHWs). Results: INH and/or RIF resistance was identified in 58.9% of isolates, with 21.7% classified as MDR-TB. The most frequently detected mutations were katG S315T (29.0%) and rpoB S450L (26.6%). Logistic regression identified rpoB S450L (aOR 4.20; 95% CI: 2.10–8.45) and katG S315T (aOR 2.85; 95% CI: 1.40–5.80) as the strongest independent predictors, while age and sex were not statistically significant. Models demonstrated strong internal discrimination (AUCs of 0.96 for INH and/or RIF resistance and 0.99 for MDR-TB). Risk stratification categorized 18% of patients as high risk. Scenario-based modelling suggested that prioritizing high-risk patients for reflex Line Probe Assay testing could reduce the median time to appropriate treatment from 14 to 3 days and may reduce progression from isoniazid-resistant TB to MDR-TB under specified operational assumptions. Conclusions: Mutation-informed predictive modelling demonstrates strong internally validated discrimination and provides a structured framework for risk-stratified intervention. Integrating probability-based risk thresholds within Clinical Governance systems and community-level support structures, including CHW-led adherence and education strategies, may support earlier treatment optimization in high-burden rural settings. External validation and prospective implementation studies are required before broader programmatic adoption. Full article
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15 pages, 279 KB  
Article
Preoperative Systemic Inflammatory Indices and Their Association with Tumor Burden and Surgical Outcomes in High-Grade Serous Ovarian Cancer
by Alexandru Marius Petrusan, Catalin Vladut Ionut Feier, Calin Muntean, Vasile Gaborean, Andrei Stefan Petrusan, Dragos Stefan Morariu, Ionut Flaviu Faur, Alaviana Monique Faur and Patriciu Achimas-Cadariu
Diseases 2026, 14(4), 131; https://doi.org/10.3390/diseases14040131 - 3 Apr 2026
Viewed by 384
Abstract
Background/Objectives: High-grade serous ovarian cancer (HGSOC) represents the most aggressive subtype of epithelial ovarian cancer and is frequently diagnosed at advanced stages. Increasing evidence suggests that systemic inflammation plays an important role in tumor progression and clinical outcomes. This study aimed to evaluate [...] Read more.
Background/Objectives: High-grade serous ovarian cancer (HGSOC) represents the most aggressive subtype of epithelial ovarian cancer and is frequently diagnosed at advanced stages. Increasing evidence suggests that systemic inflammation plays an important role in tumor progression and clinical outcomes. This study aimed to evaluate the association between preoperative systemic inflammatory indices and tumor burden, perioperative outcomes, and recurrence risk in patients with HGSOC undergoing primary debulking surgery. Methods: We conducted a retrospective study including 125 patients with histopathologically confirmed HGSOC who underwent primary debulking surgery between January 2020 and December 2025. Preoperative hematological parameters obtained within 24 h before surgery were used to calculate inflammatory indices including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI). Associations between inflammatory markers, clinicopathological characteristics, perioperative outcomes, and recurrence were analyzed using non-parametric tests and logistic regression models. Results: The mean patient age was 53.66 ± 9.14 years, and most patients presented with advanced disease (FIGO III–IV: 70.4%). Patients with T3 tumors showed significantly higher monocyte (0.66 vs. 0.50 × 109/L, p = 0.003), neutrophil (5.43 vs. 4.99 × 109/L, p = 0.042), and platelet counts (325 vs. 280 × 109/L, p = 0.006) and lower lymphocyte counts (1.79 vs. 1.96 × 109/L, p = 0.009). Composite inflammatory indices were also increased in advanced disease, including PLR (177 vs. 153, p = 0.009), AISI (492 vs. 341, p = 0.002), and SIRI (1.65 vs. 1.18, p = 0.018). Patients requiring postoperative blood transfusion had higher neutrophil counts (7.65 vs. 4.97 × 109/L, p < 0.001) and elevated SIRI (2.56 vs. 1.55, p < 0.001). Patients with recurrence had significantly higher platelet counts (339 vs. 293 × 109/L, p = 0.001) and SII values (2849 vs. 2586, p = 0.012). In multivariate analysis, SII remained independently associated with recurrence (OR 1.022 per 100-unit increase; 95% CI 1.002–1.043; p = 0.033) together with advanced FIGO stages (OR 2.863; 95% CI 1.011–8.104; p = 0.048). Conclusions: Preoperative systemic inflammatory markers are significantly associated with tumor burden, surgical outcomes, and recurrence risk in HGSOC. An elevated SII appears to be an independent predictor of recurrence and may represent a practical biomarker for improving preoperative risk stratification and postoperative surveillance. Full article
(This article belongs to the Special Issue Diseases: From Molecular to the Clinical Perspectives)
20 pages, 2504 KB  
Article
Diagnostic and Prognostic Utility of Cell-Surface Vimentin Positive Circulating Tumor Cells in Breast Cancer Using an Automated Negative Selection Platform
by Ming-Hsin Yeh, Mei-Chun Lin, Hui-Ju Tsai, Yi-Chou Liu, Tzu-Min Wang, Wei-Shan Hung, Chih-Peng Lin, Ching-Hsing Liang and Chih-Jen Tseng
Diseases 2026, 14(4), 130; https://doi.org/10.3390/diseases14040130 - 3 Apr 2026
Viewed by 543
Abstract
Background/Objectives: Breast cancer (BC) is the most commonly diagnosed cancer in women, and metastasis is the leading cause of BC-related death. Circulating tumor cells (CTCs) are a prerequisite for metastasis. This study examined the diagnostic and prognostic value of CTCs for assessing metastatic [...] Read more.
Background/Objectives: Breast cancer (BC) is the most commonly diagnosed cancer in women, and metastasis is the leading cause of BC-related death. Circulating tumor cells (CTCs) are a prerequisite for metastasis. This study examined the diagnostic and prognostic value of CTCs for assessing metastatic risk and recurrence in BC. Methods: The Chiline CATCH® Circulating Target Cell Enrichment System, an automated negative selection platform, was used to enrich and enumerate CTCs from the peripheral blood of patients with BC. Epithelial cell adhesion molecule (EpCAM) and cell-surface Vimentin (CSV) were used as markers for CTC identification. Results: CSV+ CTC counts, but not EpCAM+ CTC counts, were increased in patients with BC at higher metastatic risk. A cut-off of >4.5 CSV+-CTCs/2 mL blood yielded a sensitivity of 0.56 and specificity of 0.92 for identifying patients at high metastatic risk. CSV+-CTCs outperformed conventional serum tumor markers, including cancer antigen 15-3 (CA 15-3), cancer antigen 125 (CA 125), and carcinoembryonic antigen (CEA), in identifying patients with high metastatic risk, and their combined use further improved risk stratification. An elevated CSV+-CTC count (≥5 cells/2 mL blood) was significantly associated with worse progression-free survival in patients with BC. Conclusions: These findings suggest that CSV+-CTCs may serve as a biomarker for metastatic risk stratification and recurrence monitoring in BC when measured using an automated negative selection platform. Full article
(This article belongs to the Section Oncology)
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11 pages, 1667 KB  
Case Report
Diffuse Large B-Cell Lymphoma Arising from Cauda Equina: A Rare Case Report and Review of the Literature
by Yuma Terada, Takafumi Yayama, Akira Nakamura, Kanji Mori, Narihito Kodama, Tomohiro Mimura, Kosei Ando, Kosuke Kumagai, Yoshinori Takemura and Shinji Imai
Diseases 2026, 14(4), 129; https://doi.org/10.3390/diseases14040129 - 2 Apr 2026
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Abstract
Background: Malignant lymphoma is the most common hematological malignancy; however, primary central nervous system lymphoma accounts for only a small percentage of non-Hodgkin lymphoma (NHL). Among these, primary cauda equina lymphoma (CEL) is extremely uncommon. Its rarity and atypical clinical presentation often make [...] Read more.
Background: Malignant lymphoma is the most common hematological malignancy; however, primary central nervous system lymphoma accounts for only a small percentage of non-Hodgkin lymphoma (NHL). Among these, primary cauda equina lymphoma (CEL) is extremely uncommon. Its rarity and atypical clinical presentation often make diagnosis challenging. Case Presentation: An 80-year-old man presented with progressive gait disturbance, lower-extremity weakness, and numbness. MRI revealed diffuse swelling and homogeneous gadolinium enhancement of the cauda equina at T12–L1; additionally, CSF cytology identified malignant lymphocytes. Open biopsy confirmed a diagnosis of diffuse large B-cell lymphoma. At diagnosis, the patient was classified as Ann Arbor stage IV, and the clinical parameters corresponded to a high-risk International Prognostic Index (IPI) category. The patient received five courses of immunochemotherapy with rituximab, methotrexate, vincristine, and procarbazine (R-MPV), resulting in marked radiological improvement and functional recovery, achieving a complete response. However, consolidation therapy was discontinued as the patient did not wish to continue. Unfortunately, intracranial relapse occurred four months later, and the patient ultimately succumbed to infectious complications. Only 29 cases of primary CEL have been reported. For all cases, a biopsy with histopathological examination is required for a definitive diagnosis. Currently, combined chemotherapy and radiotherapy are considered the standard treatment. This case was diagnosed through nerve biopsy with cauda equina at T12 to L1 levels, and immunochemotherapy successfully reduced the lesion while improving lower extremity function. Conclusions: Despite the considerable burden on patients, nerve biopsy is necessary for primary CEL to obtain a diagnosis and an early therapeutic approach for both neurological and vital prognoses. Full article
(This article belongs to the Section Oncology)
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11 pages, 1380 KB  
Article
Hemodialysis Tends to Improve Thyroid Function by Restoring Hormone Levels in ESRD Patients Compared to Non-Dialysis Kidney Disease Patients: A Case–Control Study
by Hasibul Islam, Shahad Saif Khandker, Anwara Khatun, Ehsan Suez, Alif Hasan Pranto, Dewan Zubaer Islam, Rahima Begum, Md. Nizam Uddin, Md. Ashraful Hasan, Md. Shah Alam and A. N. M. Mamun-Or-Rashid
Diseases 2026, 14(4), 128; https://doi.org/10.3390/diseases14040128 - 1 Apr 2026
Viewed by 544
Abstract
Background: Chronic kidney disease (CKD) represents an escalating global health burden, fundamentally altering morbidity and mortality trajectories across the world, particularly as it advances into end-stage renal disease (ESRD). Beyond the primary decline in renal filtration and excretion, a wide spectrum of endocrine [...] Read more.
Background: Chronic kidney disease (CKD) represents an escalating global health burden, fundamentally altering morbidity and mortality trajectories across the world, particularly as it advances into end-stage renal disease (ESRD). Beyond the primary decline in renal filtration and excretion, a wide spectrum of endocrine and metabolic derangements frequently accompanies kidney failure, with thyroid dysfunction emerging as a critical complication. Methods: The current study was designed to rigorously evaluate the nuanced association between thyroid hormone dynamics—specifically thyrotropin (TSH), triiodothyronine (T3), and thyroxine (T4)—and renal status in three distinct cohorts: individuals with suspected thyroid issues but normal renal function (NPs), non-dialysis kidney disease patients (NDKPs), and patients undergoing maintenance hemodialysis (DPs). Data were collected from a clinical setting in Bangladesh, involving 161 subjects. Results: The results demonstrated that patients in the DP cohort exhibited slightly elevated thyroid hormone levels relative to those in the NDKP cohort. Specifically, within the subgroups of patients exhibiting normal or sub-reference hormonal levels, dialysis patients maintained higher concentrations than their non-dialysis counterparts. Demographic stratification further revealed that males, females, and individuals younger than 45 years were more likely to demonstrate restorative hormonal profiles in the DP group than in the NDKP group. Conclusions: These collective outcomes suggest that renal replacement therapy, specifically hemodialysis, may serve to stabilize or improve thyroid function in ESRD patients by potentially mitigating the suppressive effects of uremic toxins and normalizing homeostatic feedback loops. Full article
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25 pages, 3245 KB  
Case Report
Aggrecanopathy as an Underrecognized Cause of Idiopathic Short Stature: The Importance of Early Genetic Confirmation for Timely Diagnosis and Management—Case Reports and Literature Review
by Aleksandra Sosin, Tetiana Tkachuk, Aleksandra Furtak, Magdalena Janeczko, Karol Stożek, Teofila Książek, Helena Poławska, Damian Loska, Sebastian Wardak, Jerzy Starzyk and Dominika Januś
Diseases 2026, 14(4), 127; https://doi.org/10.3390/diseases14040127 - 1 Apr 2026
Viewed by 541
Abstract
Background: Short stature is a frequent clinical problem with a broad differential diagnosis. Emerging evidence indicates that pathogenic variants in the ACAN gene represent an underrecognized cause of growth failure and are often misclassified as idiopathic short stature. Case presentation: We report two [...] Read more.
Background: Short stature is a frequent clinical problem with a broad differential diagnosis. Emerging evidence indicates that pathogenic variants in the ACAN gene represent an underrecognized cause of growth failure and are often misclassified as idiopathic short stature. Case presentation: We report two pediatric patients harboring pathogenic ACAN gene variants, both presenting with short stature and distinctive facial dysmorphism. The first patient, a 15-year-old boy, exhibited short stature, advanced bone age, and a characteristic facial gestalt, including ptosis, hypertelorism, down-slanting palpebral fissures, and fleshy auricles, features not previously described in association with aggrecanopathy. Genetic analysis revealed a novel heterozygous frameshift variant, c.5677_5684del (p.Glu1893TrpfsTer8), in exon 12 of the ACAN gene. The second patient, a 5.5-year-old girl, presented with short stature, mild facial dysmorphism (down-slanting palpebral fissures and retracted mandible), and feeding difficulties. Copy number variation analysis identified a heterozygous deletion encompassing exons 15–19 of the ACAN gene. In both patients, the endocrine evaluation was unremarkable, and no chronic systemic disease was identified. The genetic findings were concordant with the clinical phenotype, confirming aggrecanopathy as the underlying cause of growth failure. Conclusions: These cases further delineate the phenotypic spectrum of ACAN-related short stature and underscore the diagnostic value of genetic testing in children with unexplained or idiopathic growth failure. Importantly, we expand the dysmorphological phenotype of aggrecanopathy by describing previously unreported facial features, which may facilitate earlier clinical recognition and diagnosis. The timely identification of pathogenic variants in the ACAN gene may have significant implications for patient management and long-term outcomes. Full article
(This article belongs to the Special Issue ‘Rare Syndromes: Diagnosis and Treatment’ in 2024–2026)
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13 pages, 1599 KB  
Article
Genotypic Distribution and Epidemiological Analysis of Hepatitis C Virus in the Epirus Region of Northwestern Greece (2014–2024)
by Petros Bozidis, Christos Kittas, Alexandra Myari, Konstantinos Patras and Konstantina Gartzonika
Diseases 2026, 14(4), 126; https://doi.org/10.3390/diseases14040126 - 1 Apr 2026
Viewed by 428
Abstract
Background/Objectives: This retrospective study investigates the prevalence and distribution of HCV genotypes among 233 genotyped patients from the Epirus region of Northwestern Greece from 2014 to 2024. Methods: Genotypes were detected by molecular diagnostic assays, and their association with demographic parameters and viral [...] Read more.
Background/Objectives: This retrospective study investigates the prevalence and distribution of HCV genotypes among 233 genotyped patients from the Epirus region of Northwestern Greece from 2014 to 2024. Methods: Genotypes were detected by molecular diagnostic assays, and their association with demographic parameters and viral load was analyzed. Results: The most prevalent subtype was 3a (50.2%), especially among younger and male patients, followed by subtypes 1b and 1a. A statistically significant association was found between genotype and both age and sex, while genotype distribution did not significantly differ by national origin. Furthermore, subtype 6c-I was found only in a non-native case, suggesting a possible introduction of this rare strain. Viral load showed no significant difference by sex, genotype, or age group. A notable decline in HCV cases was documented during the COVID-19 pandemic, underscoring the impact of the public health crisis on HCV diagnosis. Despite the decreasing need for genotyping in the direct-acting antiviral (DAA) era, our findings support the continued molecular surveillance of circulating HCV strains. Conclusions: This is the first study to longitudinally assess HCV genotype dynamics over a full decade (2014–2024) in the Epirus region of Northwestern Greece, capturing trends during the COVID-19 era and documenting the emergence of rare genotypes. It contributes to the evolving knowledge of HCV epidemiology in Southeastern Europe. Full article
(This article belongs to the Section Infectious Disease)
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8 pages, 330 KB  
Case Report
Non-Responder to Inclisiran and Evolocumab—A Female Patient with Heterozygous Familial Hypercholesterolemia and Statin Intolerance
by Paweł Muszyński, Małgorzata Chlabicz, Joanna Kruszyńska, Katarzyna Wilk-Śledziewska, Piotr Kazberuk, Dominika Musiałowska, Monika Groth and Kinga Dudzińska
Diseases 2026, 14(4), 125; https://doi.org/10.3390/diseases14040125 - 1 Apr 2026
Viewed by 618
Abstract
Despite the availability of numerous lipid-lowering agents, the treatment of lipid disorders remains a public health challenge. A substantial portion of patients, especially those with severe dyslipidemia or familial hypercholesterolemia (FH), fail to achieve the LDL-C goal. The leading causes of suboptimal LDL-C [...] Read more.
Despite the availability of numerous lipid-lowering agents, the treatment of lipid disorders remains a public health challenge. A substantial portion of patients, especially those with severe dyslipidemia or familial hypercholesterolemia (FH), fail to achieve the LDL-C goal. The leading causes of suboptimal LDL-C control include underprescription and poor adherence; however, in rare cases, it may result from an unusual biological response to treatment. In the presented case, a 78-year-old female with a history of transient ischemic attack and myocardial infarction was diagnosed with a heterozygous variant of FH and true statin intolerance following trials of simvastatin, rosuvastatin and pitavastatin. Initially, inclisiran was added to ezetimibe, leading to an unexpected increase in LDL-C. Due to the patient’s refusal of another statin re-challenge and the unavailability of bempedoic acid, nutraceuticals were introduced. After 6 months, inclisiran was discontinued because only a 22% reduction in LDL-C was achieved, likely attributable to the nutraceutical’s effect. Another PCSK9 inhibitor, evolocumab, was subsequently initiated. Shortly after the treatment onset, the patient complained of paraesthesia in the upper extremities and discontinued therapy. LDL-C levels increased by 7% after one month of treatment with evolocumab. The patient refused treatment with lipid apheresis. Possible causes of poor response to PCSK9 inhibitors include elevated lipoprotein(a) and FH. Full article
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10 pages, 809 KB  
Case Report
Fatal Necrotizing Soft Tissue Infection Following Continuous Glucose Monitoring in a Patient with Type 1 Diabetes: A Case Report and Literature Review
by Constantin Popazu, Cristiana Voineag, Ionica Grigore, Cristina Șerban, Mădălin Guliciuc, Dragoș Voicu and Alexandra Toma
Diseases 2026, 14(4), 124; https://doi.org/10.3390/diseases14040124 - 31 Mar 2026
Viewed by 534
Abstract
Background: Continuous glucose monitoring (CGM) systems have significantly improved glycemic management in patients with type 1 diabetes mellitus and are generally considered safe. However, transcutaneous sensor insertion disrupts the skin barrier and, in susceptible individuals, may contribute to infectious complications. Severe soft tissue [...] Read more.
Background: Continuous glucose monitoring (CGM) systems have significantly improved glycemic management in patients with type 1 diabetes mellitus and are generally considered safe. However, transcutaneous sensor insertion disrupts the skin barrier and, in susceptible individuals, may contribute to infectious complications. Severe soft tissue infections occurring in temporal association with CGM use are exceedingly rare. Case Presentation: We report a fatal case of necrotizing soft tissue infection in a 54-year-old male with long-standing type 1 diabetes mellitus occurring in temporal association with CGM use. The patient initially developed localized inflammation at a prior sensor insertion site that failed to fully resolve. Over subsequent weeks, he experienced progressive systemic symptoms and worsening local findings, culminating in advanced necrotizing infection. Despite emergency surgical debridement, broad-spectrum antimicrobial therapy, and intensive care support, the clinical course was complicated by septic shock and multiorgan failure, resulting in death. Discussion: This case highlights the role of patient-specific vulnerability, persistent insertion-site inflammation, and delayed clinical recognition in the progression from localized skin changes to life-threatening infection. Importantly, this report does not establish a direct causal relationship between CGM use and necrotizing soft tissue infection but underscores the need for heightened vigilance in high-risk individuals. Conclusions: Although CGM systems have a favorable safety profile, careful inspection of insertion sites, avoidance of sensor reapplication over incompletely healed tissue, and early evaluation of persistent or progressive symptoms are essential to minimize the risk of severe outcomes in susceptible patients. Full article
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14 pages, 1183 KB  
Article
Endothelial Activation Phenotypes and Interleukin-6 Response After Therapeutic Plasma Exchange in Severe COVID-19-Associated Sepsis: A Retrospective Cohort Study
by Nicoleta Sgavardea, Ovidiu Bedreag, Greeshmasree Kambam, Tamara Mirela Porosnicu, Ciprian Gîndac, Claudiu Barsac, Cristian Oancea, Patricia Hogea, Alexandru Crisan and Voichita Elena Lazureanu
Diseases 2026, 14(4), 123; https://doi.org/10.3390/diseases14040123 - 28 Mar 2026
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Abstract
Background and Objectives: Severe COVID-19 frequently fulfills Sepsis-3 criteria and is characterized by thrombo-inflammation and endothelial injury. We evaluated whether a bedside endothelial activation index (EAI = D-dimer/fibrinogen) identifies biologically distinct phenotypes and relates to interleukin-6 (IL-6) response after therapeutic plasma exchange (TPE), [...] Read more.
Background and Objectives: Severe COVID-19 frequently fulfills Sepsis-3 criteria and is characterized by thrombo-inflammation and endothelial injury. We evaluated whether a bedside endothelial activation index (EAI = D-dimer/fibrinogen) identifies biologically distinct phenotypes and relates to interleukin-6 (IL-6) response after therapeutic plasma exchange (TPE), and whether baseline IL-6 predicts a ≥50% IL-6 reduction. Methods: Retrospective single-center ICU cohort of adults with SARS-CoV-2 infection, sepsis-related organ dysfunction, and ≥1 TPE session (n = 51). Patients were stratified by median EAI (low vs. high). Outcomes included peri-procedural biomarker/physiology changes (post–baseline), IL-6 responder status (≥50% reduction), correlations with IL-6 reduction (%), and multivariable predictors of response. Results: Compared with low EAI (n = 25), high EAI (n = 26) had higher baseline D-dimer (6.2 vs. 2.2 µg/mL) and lower fibrinogen (2.9 vs. 7.1 g/L) (both p < 0.001). Low EAI showed larger CRP decreases (ΔCRP −84.0 vs. −2.3 mg/L; p = 0.001) and larger fibrinogen falls (Δ −3.1 vs. −0.4 g/L; p < 0.001), while high EAI had larger D-dimer decreases (Δ −2.5 vs. −0.6 µg/mL; p = 0.004) and a modest SOFA improvement (Δ −0.3 vs. +0.1; p = 0.026). IL-6 responders (n = 20) had higher baseline IL-6 than non-responders (365.2 vs. 47.1 pg/mL; p < 0.001). Baseline IL-6 independently predicted response (per doubling: OR 1.94, 95% CI 1.27–2.95; p = 0.002), while age reduced odds (OR 0.91/year, 95% CI 0.84–0.99; p = 0.032). IL-6 reduction correlated with ΔCRP (ρ = −0.41; p = 0.003) and ΔPaO2/FiO2 (ρ = 0.37; p = 0.01). Conclusions: EAI stratifies distinct thrombo-inflammatory patterns around TPE, while baseline IL-6 is the dominant predictor of achieving large IL-6 reductions. To emphasize the novelty and clarify the study objective, this exploratory analysis used a phenotype-stratified framework to test whether a simple bedside endothelial activation index could enrich biological response assessment to adjunctive TPE. The prespecified primary outcome was achievement of a ≥50% IL-6 reduction after completion of the TPE course; secondary outcomes included peri-procedural biomarker, oxygenation, SOFA, and ICU endpoints. Full article
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16 pages, 1323 KB  
Systematic Review
Impact of Resuscitative Endovascular Balloon Occlusion of the Aorta on In-Hospital and Short-Term Mortality: A Systematic Review and Meta-Analysis
by Hiroyuki Kamide, Shingo Kato, Naofumi Yasuda, Shungo Sawamura, Yoshinobu Ishiwata, Nobuyuki Horita, Ryusuke Sekii, Tomohiro Oshima, Zenjiro Sekikawa and Daisuke Utsunomiya
Diseases 2026, 14(4), 122; https://doi.org/10.3390/diseases14040122 - 27 Mar 2026
Viewed by 425
Abstract
Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is increasingly employed in patients with hemorrhagic shock and cardiovascular collapse; however, its impact on mortality remains controversial. Differences in geographic regions and patient populations may influence clinical outcomes. Methods: We conducted a systematic [...] Read more.
Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is increasingly employed in patients with hemorrhagic shock and cardiovascular collapse; however, its impact on mortality remains controversial. Differences in geographic regions and patient populations may influence clinical outcomes. Methods: We conducted a systematic review and meta-analysis of observational studies comparing mortality between patients receiving REBOA and those managed without REBOA. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analyses were performed according to propensity score (PS) matching, trauma versus non-trauma populations, and geographic regions. Results: A total of 10 studies involving 18,611 patients were included. Overall, REBOA was not associated with a significant reduction in mortality compared with non-REBOA (pooled OR = 0.52, 95% CI: 0.19–1.39, p = 0.19). In PS-matched studies, the pooled OR was 0.82 (95% CI: 0.34–1.98, p = 0.66), whereas in non-PS-matched studies it was 0.40 (95% CI: 0.12–1.26, p = 0.12). Geographic analyses revealed no significant mortality benefit in either Western studies (OR = 0.47, 95% CI: 0.12–1.89; p = 0.29) or non-Western studies (OR = 0.60, 95% CI: 0.11–3.38; p = 0.56). No survival benefit was observed among trauma patients (OR = 0.57, 95% CI: 0.20–1.61; p = 0.29), whereas a significant reduction in mortality was observed in non-trauma patients (OR = 0.21, 95% CI: 0.05–0.88; p = 0.03). Conclusions: In this systematic review and meta-analysis, REBOA was not associated with a significant reduction in mortality in the overall population or in trauma patients. However, in a single small non-trauma study (n = 53), REBOA was associated with significantly reduced mortality; this finding is exploratory and requires confirmation in larger prospective studies. These findings suggest that the clinical benefit of REBOA may depend on patient population and underlying etiology of hemorrhage. Full article
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37 pages, 2507 KB  
Systematic Review
Efficacy and Safety of Endoscopic Strictureplasty and Stricturotomy for Crohn’s Disease-Associated Strictures: A Systematic Review and Current Perspective
by Elisa Abreu, Rolando Pinho, Fernando Magro and Maria Manuela Estevinho
Diseases 2026, 14(4), 121; https://doi.org/10.3390/diseases14040121 - 27 Mar 2026
Viewed by 589
Abstract
Objectives: Strictures are a major complication of Crohn’s disease (CD) affecting up to 20% of patients at diagnosis. Endoscopic balloon dilation (EBD) is the first-line endoscopic approach; however, it entails complications and a need for reintervention. Endoscopic stricturotomy (ESt) and stricturoplasty (ESTx) are [...] Read more.
Objectives: Strictures are a major complication of Crohn’s disease (CD) affecting up to 20% of patients at diagnosis. Endoscopic balloon dilation (EBD) is the first-line endoscopic approach; however, it entails complications and a need for reintervention. Endoscopic stricturotomy (ESt) and stricturoplasty (ESTx) are promising alternatives. This review aims to provide an up-to-date and comprehensive assessment of their efficacy and safety in CD-associated strictures. Methods: A literature search was performed until August 2025. Primary outcomes were clinical and technical success. Secondary outcomes included adverse events, additional endoscopic or surgical treatments, medication escalation, emergency department visits and hospitalization following intervention. A minimum of four studies were required for meta-analysis, and pooled estimates were calculated using random-effects meta-analysis. Study quality was assessed using CASP checklist. Results: Fifteen studies including 1050 IBD patients (470 CD) were included. Strictures were short (0.9–2.4 cm) and some had prior EBD (7.8–57.1%) or surgery (3.6–91%). Technical success of ESt ranged from 88% to 100% and clinical success from 50% to 96%. The bleeding rate was up to 11.8%, but perforation rate was mostly <2%. The need for additional intervention, endoscopic (18.2–66.6%) or surgical (0–18.2%), varied considerably. Additionally, ESTx’s technical success ranged from 91.7% to 100% whereas clinical success ranged from 71.4% to 91%, with bleeding ranging from 5.2% to 8.8% and perforation from 0% to 3.4%. Similarly, the need for additional endoscopic procedures (7.1–57.1%) and surgery (9.5–25%) varied considerably. Conclusions: ESt and ESTx are safe and effective for managing CD-related strictures, particularly when short, straight, accessible, fibrotic, anastomotic, or refractory to EBD. Full article
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