Diseases

18 pages, 1237 KB

Open AccessArticle

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

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

► Show Figures

Graphical abstract

8 pages, 814 KB

Open AccessCase 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

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)

► Show Figures

Figure 1

31 pages, 2344 KB

Open AccessReview

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

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

► Show Figures

Figure 1

14 pages, 447 KB

Open AccessArticle

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

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)

► Show Figures

Figure 1

14 pages, 733 KB

Open AccessArticle

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

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)

► Show Figures

Figure 1

12 pages, 258 KB

Open AccessArticle

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

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

Open AccessArticle

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-Cruz Show full author list Hide full author list

Diseases 2026, 14(4), 133; https://doi.org/10.3390/diseases14040133 - 7 Apr 2026

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)

► Show Figures

Figure 1

20 pages, 1092 KB

Open AccessArticle

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

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

► Show Figures

Figure 1

15 pages, 279 KB

Open AccessArticle

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

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

Open AccessArticle

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

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)

► Show Figures

Figure 1

11 pages, 1667 KB

Open AccessCase 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

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)

► Show Figures

Figure 1

11 pages, 1380 KB

Open AccessArticle

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

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

► Show Figures

Figure 1

25 pages, 3245 KB

Open AccessCase 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

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)

► Show Figures

Figure 1

13 pages, 1599 KB

Open AccessArticle

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

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)

► Show Figures

Figure 1

8 pages, 330 KB

Open AccessCase 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

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

► Show Figures

Figure 1

10 pages, 809 KB

Open AccessCase 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

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

► Show Figures

Figure 1

14 pages, 1183 KB

Open AccessArticle

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

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

► Show Figures

Figure 1

16 pages, 1323 KB

Open AccessSystematic 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

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

► Show Figures

Figure 1

37 pages, 2507 KB

Open AccessSystematic 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

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

► Show Figures

Figure 1

Journal Description

Diseases

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI