Diseases doi: 10.3390/diseases14080295

Authors: Yin Yin Bashir Rahaf AL-Huneiti Anfal AL-Dalaeen Firas S. Azzeh

Background: Obesity is a chronic, multifactorial disease that demands personalized and sustainable management approaches. Digital health technologies, such as artificial intelligence, wearable devices, mobile health apps, and virtual reality (VR), may support obesity care by providing enhanced behavioral monitoring, personalized feedback, and patient engagement. Objective: This critical narrative review discusses the current evidence on artificial intelligence, wearable technologies, and VR in the context of precision nutrition and obesity management and their possible clinical applications and limitations. Method: A critical narrative review was conducted using peer-reviewed literature published between 2019 and 2026 and identified through PubMed and Google Scholar. Search terms included combinations of “precision nutrition,” “personalized nutrition,” “obesity,” “weight management,” “metabolic health,” “digital health,” “artificial intelligence,” “machine learning,” “mobile health,” “wearable devices,” and “omics” using Boolean operators. Evidence from randomized controlled trials, systematic reviews, meta-analyses, and key conceptual studies was critically synthesized due to substantial heterogeneity in interventions and outcomes. Result: Wearables and mobile applications can enable continuous self-monitoring of physical activity, dietary intake, sleep, and physiological measures. Artificial intelligence may improve dietary personalization, risk prediction, glycemic control, and adaptive feedback. VR offers an immersive way to tackle behavioral and cognitive mechanisms related to overeating such as cravings, food cue reactivity, and inhibitory control. However, the evidence is heterogeneous, with many studies limited by short follow-up periods, small samples, variable adherence, and insufficient clinical validation. Conclusions: Artificial intelligence, wearable technologies, and VR are promising tools for precision obesity management, but their long-term clinical effectiveness remains uncertain. Future research should prioritize adequately powered trials, longer follow-up, standardized outcomes, transparent algorithms, ethical data governance, and integration with multidisciplinary nutrition and obesity care.

Diseases doi: 10.3390/diseases14080294

Authors: Victor Ivanovich Seledtsov

Inflammation can either encourage or suppress tumor growth, thus having a two-sided effect on cancer development. This depends on the balance between pro-tumor and anti-tumor immune responses within the tumor microenvironment (TME). Pro-tumor inflammation, driven by specific immune cells, enhances blood flow and nutrient supply to tumors, promoting the activation of dormant cancer cells (DCCs). Conversely, antitumor inflammation hinders blood flow and can force active cancer cells into a state of dormancy. Tumors actively shift this balance towards pro-tumor inflammation to create a favorable environment for growth. Therefore, anti-inflammatory therapy may be an integral part of comprehensive cancer immunotherapy. This review explores how different anti-inflammatory medications, such as glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), antihistamines, anti-leukotrienes, statins, drugs that block pro-inflammatory cytokines, agents that inhibit oxidative phosphorylation, antioxidant vitamins, anti-angiogenic drugs, and low-dose chemotherapy, can be used to combat cancer. Granulocyte counts and erythrocyte sedimentation rate (ESR) can be used to assess inflammation levels and the effectiveness of anti-inflammatory treatments. We advocate for a paradigm shift in cancer treatment, moving away from aggressive tumor destruction, which triggers uncontrolled tumor regeneration, toward long-term immunological control of tumor growth while preserving the patient’s overall health.

Diseases doi: 10.3390/diseases14080293

Authors: Erik Shorabaev Amankeldi Sadanov Baiken Baimakhanova Saltanat Orasymbet Irina Ratnikova Bakhytzhan Kerimzhanova Zhanar Assilova Zaure Datkhayeva Aknur Turgumbayeva

Background/Objectives: Intestinal diseases are a major global health problem due to their high prevalence, chronic course, and significant impact on quality of life. Increasing attention has been given to the extra-skeletal effects of vitamin D, particularly its role in immune regulation, maintenance of intestinal barrier integrity, and modulation of the gut microbiota. The aim of this review was to evaluate current evidence regarding the role of vitamin D in immune regulation, intestinal barrier function, and the pathogenic mechanisms of intestinal diseases, including inflammatory and functional gastrointestinal disorders. Methods: A structured narrative review was conducted using the PubMed, Scopus, and Web of Science databases to identify publications addressing the role of vitamin D in intestinal diseases. The literature search was updated in May 2026 and included studies published between 2004 and 2026. The aim of this review was to summarize current evidence on the effects of vitamin D on immune regulation, intestinal barrier integrity, gut microbiota, and their clinical relevance in intestinal diseases. Results: The included studies demonstrated that vitamin D plays an important role in maintaining intestinal homeostasis through regulation of innate and adaptive immune responses, preservation of epithelial barrier integrity, and modulation of gut microbiota composition. Vitamin D deficiency was associated with impaired VDR-dependent signalling, increased intestinal permeability, dysbiosis, and enhanced pro-inflammatory immune responses, which may contribute to the development and progression of inflammatory bowel disease, Crohn’s disease, ulcerative colitis, irritable bowel syndrome, and celiac disease. Conclusions: Current evidence supports the important role of vitamin D in immune regulation, intestinal barrier protection, and maintenance of gut microbial balance. Further clinical studies are required to better understand its therapeutic potential in intestinal diseases.

Diseases doi: 10.3390/diseases14080292

Authors: Theodoros A. Voulgaris Dimitrios I. Ziogas Ioannis Stasinos Eleni Koukoulioti Eleni Koukouvaidou Antonios Vezakis Ioannis S. Papanikolaou

The Functional Lumen Imaging Probe (EndoFLIP®) system is an impedance-based technology providing real-time measurements of cross-sectional area (CSA) and intraballoon pressure across a luminal segment. Initially developed for esophagogastric junction (EGJ) evaluation in achalasia, the application of EndoFLIP has subsequently expanded to the assessment of both sphincteric and non-sphincteric regions throughout the gastrointestinal tract in a variety of clinical conditions, including eosinophilic esophagitis (EoE), post-fundoplication states, and gastroparesis. Its unique ability to be utilized in both the diagnostic and therapeutic settings, including the assessment of treatment response, makes it a valuable tool in the overall management of gastrointestinal motility disorders. The present review extends beyond a simple overview of EndoFLIP applications by providing a comprehensive evaluation of its performance in comparison with other diagnostic modalities, as well as the current knowledge gaps regarding its use. Study limitations and procedure-related aspects requiring further investigation are critically discussed, with the aim of supporting and guiding future research in this field.

Diseases doi: 10.3390/diseases14080291

Authors: Naomi Gerzvolf Mieres Kauanna Oliveira Nathália Carolina Barreiro Marques Nicole Milagritos Cardoso Azorza Helena Hiemisch Lobo Borba Roberto Pontarolo Marcel Henrique Marcondes Sari Juliana Sartori Bonini Jéssica Brandão Reolon Raul Edison Luna Lazo Luana Mota Ferreira

Background/Objectives: Melanoma remains one of the most aggressive skin cancers worldwide, with rising incidence and persistent therapeutic challenges, particularly in advanced diseases. Drug repositioning has emerged as a cost- and time-efficient strategy for identifying adjunctive treatments, and antihypertensive medications have attracted attention for their potential off-target antitumor and immunomodulatory effects. This scoping review aimed to map and critically appraise the evidence on the repositioning of antihypertensive drugs for melanoma management. Methods: The review followed the JBI methodology, and the results were reported in accordance with the PRISMA-ScR guidelines. Searches were conducted in July 2025 and updated in May 2026 in PubMed, Scopus, and Web of Science. For Methodological Quality and Risk-of-bias assessment, the SYRCLE Risk of Bias tool was employed for animal studies. Results: This review included 37 studies. β-Blockers, particularly propranolol, were the most frequently investigated agents (n = 21). Several studies reported antiproliferative, pro-apoptotic, antiangiogenic, and immunomodulatory effects; however, these findings were not uniform. Absent direct antiproliferative effects, biphasic dose responses, lack of angiogenic effects, and outcomes dependent on drug concentration, treatment schedule, and experimental model were also reported. Agents targeting the renin–angiotensin system and calcium channels similarly produced heterogeneous and context-dependent findings. The animal studies frequently presented high or unclear risk of bias, particularly because of incomplete reporting of randomization, allocation concealment, and blinding. No formal methodological quality assessment was performed for the in vitro studies. Conclusions: Antihypertensive agents, particularly β-blockers, show promising but heterogeneous preclinical signals in melanoma. However, the available evidence is not sufficient to establish reproducible efficacy or translational validity. Standardized and methodologically rigorous preclinical studies are required before these agents can be considered for clinical investigation as adjunctive melanoma therapies.

Diseases doi: 10.3390/diseases14080290

Authors: Manuela Arbune Pantelie Nicolcescu Anamaria Ciubara Pompiliu Mircea Bogdan Constantin-Marinel Vlase Anca-Adriana Arbune

Background/Objectives: Neuroinflammation is increasingly recognized as a key mechanism linking infectious diseases with psychiatric disorders through interactions between peripheral immune activation, metabolic pathways, and brain network alterations. This review aimed to synthesize current evidence on the neuroimmune mechanisms and biomarkers underlying infection-associated psychiatric disorders. Methods: A narrative literature review structured according to the SANRA (Scale for the Assessment of Narrative Review Articles) criteria was conducted using the Web of Science Core Collection, PubMed/MEDLINE, Scopus and PsycINFO databases. Boolean search strategies identified studies investigating neuroinflammatory biomarkers, neuroimmune mechanisms, and psychiatric outcomes associated with infectious diseases. The search (January 2022–30 June 2026) included 76 studies in the final qualitative analyses. Results: The reviewed evidence consistently identified inflammatory cytokines and chemokines, complement proteins, blood–brain barrier markers, glial activation biomarkers, neuroaxonal injury markers, kynurenine pathway metabolites, neurotrophic factors, and neuroimaging markers as complementary indicators of infection-induced neuroimmune dysfunction. Across diverse bacterial, viral, parasitic, and systemic infections, these mechanisms converged on peripheral immune activation, blood–brain barrier disruption, microglial activation, kynurenine pathway dysregulation, impaired neurotrophic signaling, synaptic dysfunction, and altered brain network connectivity, contributing to depression, anxiety, psychosis, cognitive impairment, and fatigue. Based on these findings, a unified neuroimmune model integrating peripheral and central mechanisms is proposed. Conclusions: Neuroinflammation emerges as a shared biological pathway linking infections with transdiagnostic psychiatric phenotypes. Although no single biomarker currently demonstrates sufficient diagnostic specificity, integrated multimodal biomarker panels may improve biological stratification, facilitate earlier identification of high-risk patients, and support the development of mechanism-based precision approaches—including candidate anti-inflammatory pharmacological strategies currently under clinical investigation—for infection-associated psychiatric disorders.

Diseases doi: 10.3390/diseases14080289

Authors: Luz María González Huerta Miguel Ángel Fonseca Sánchez Marcela Esquivel Velázquez Jaime Toral López

Neurodevelopmental disorder, speech impairment, and dysmorphic facies (NEDSID) is an autosomal dominant condition primarily driven by SETD1A haploinsufficiency. While most documented cases are sporadic, genomic mechanisms underlying intrafamilial phenotypic heterogeneity remain poorly understood. This study presents a comprehensive clinical, neurophysiological, and molecular characterization of a two-generation Mexican family segregating a novel heterozygous missense SETD1A variant. Whole-exome sequencing (WES) identified a c.1604G>A (p.Gly535Glu) substitution localized within the critical Functional Location on SETD1A (FLOS) domain, which was validated via automated Sanger sequencing across all family members and 100 ethnically matched controls. The proband exhibited a moderate NEDSID phenotype, including global developmental delay, macrocephaly, borderline IQ (79) with pronounced information-processing deficits, and abnormal EEG sharp waves. Conversely, first-degree relatives carrying the identical variant presented with mild, non-intellectually disabling phenotypes characterized primarily by isolated psychiatric disorders (bipolar disorder, depression) and minimal dysmorphism. Structural 3D modeling and multi-algorithmic in silico profiling confirmed high evolutionary conservation and a deleterious impact (CADD: 22.2, SIFT: 0.00, GERP: 2.924), classifying the variant as a Variant of Uncertain Significance (VUS)/Likely Pathogenic according to ACMG/AMP criteria (PM2, PP1, PP3, PP4). Furthermore, epigenetic dysregulation and chromatin remodeling defects increasingly link these histone-modifier variants to broader psychiatric landscapes. Emerging transcriptomic profiling confirms that dosage-sensitive COMPASS complex disruptions alter downstream neurodevelopmental gene cascades. Our findings present observational evidence of intrafamilial clinical variability in a single pedigree with a SETD1A missense alteration, supporting the hypothesis that non-catalytic domain substitutions may contribute to diverse neurodevelopmental outcomes.

Diseases doi: 10.3390/diseases14080288

Authors: Alejandro Castañeda-López Fernando Suárez-Sánchez Fengyang Huang Miguel Cruz Adrián Hernández-Díazcouder

Coffee is one of the most widely consumed beverages worldwide. Coffee and its bioactive compounds, including caffeine, chlorogenic acid, and caffeic acid, have attracted increasing attention because of their potential health benefits. Evidence from pediatric and adult populations supports a positive association between fructose intake from sugar-sweetened beverages and the increasing prevalence of obesity and other non-communicable diseases. In this context, coffee consumption may represent a potential protective dietary factor against high fructose intake-induced metabolic alterations, including obesity, type 2 diabetes, liver disease, cardiovascular disease, and alterations in gut microbiota composition. Therefore, this review summarizes current evidence on the potential role of coffee consumption and coffee-derived bioactive compounds in modulating fructose-induced metabolic alterations and discusses the mechanisms involved. However, current evidence from human studies remains limited, and the clinical relevance of the beneficial effects observed in experimental models requires confirmation through well-designed clinical trials.

Diseases doi: 10.3390/diseases14080287

Authors: Artur Rebelo Sara Seyedinia Nepomuk Sochor Jessica Döbereiner Matthias Sommerer Ulrich Ronellenfitsch Johannes Klose Andreas Odparlik Alexander Heinzel Jörg Kleeff

Introduction: Delayed gastric emptying (DGE) is a common complication after pancreatoduodenectomy, occurring in up to two-thirds of patients. Although rarely life-threatening, DGE prolongs hospitalization and increases healthcare costs. The International Study Group of Pancreatic Surgery (ISGPS) definition enables retrospective grading but lacks objective physiological assessment. This pilot study evaluated the feasibility and clinical relevance of standardized postoperative gastric scintigraphy. Methods: Six patients undergoing pancreatoduodenectomy between January and May 2025 received one or two standardized liquid gastric emptying scintigraphies on postoperative days (POD) 4–6 and 10–13. Quantitative analysis included half-emptying time (T½) and residual activity (RA%) at 30 and 60 min. Findings were correlated with ISGPS-defined DGE. Results: Eleven scintigraphic examinations were performed. Clinically relevant ISGPS Grade B/C DGE occurred in two patients and was associated with persistently elevated RA% at 60 min and prolonged T½ on early scintigraphy. Two additional patients showed scintigraphic abnormalities without meeting clinical DGE criteria, without confirmed outcome-level consequences. Conclusions: Standardized gastric scintigraphy may provide an objective and reproducible method for evaluating DGE after pancreatoduodenectomy and may complement clinically based ISGPS definitions.

Diseases doi: 10.3390/diseases14080286

Authors: Ali Abduwani Abdullah Al Lawati Ruai Al Abri Reem Al Mayyahi Hoor Al Barhi Shatha Al Hussaini Moath Shummo Hanan Al Lawati Nawaf Al-Muqaimi Srijit Das

Background: Complex wounds present significant reconstructive challenges owing to impaired healing, infections, and tissue loss. Skin grafting remains a widely used reconstructive technique; however, outcome data from the Gulf region are limited to a few studies. This study aimed to evaluate early graft outcomes and complications following skin graft reconstruction for complex wounds at a tertiary hospital. Methods: A retrospective, hospital-based study was conducted at Sultan Qaboos University Hospital (SQUH), including all patients who underwent split-thickness or full-thickness skin grafting between 2023 and 2025. Demographic, clinical, surgical, and wound-related data were collected. The main outcomes were graft take on postoperative days 5–7, time to complete re-epithelialization, and the occurrence of postoperative complications. Results: A total of 50 patients were included; 72% were males, with a median age of 45.5 years. Diabetes mellitus was present in 34% of patients. Trauma (28%) and infection/necrotizing causes (22%) were the most common etiologies of wounds. Complete graft take (>90%) was achieved in 90% of the patients, whereas 10% had partial graft take. The median time to complete re-epithelialization was 13 days. Complications were infrequent and minor, including postoperative infection (8%), hypertrophic scar formation (6%), and wound dehiscence (2%). No significant differences in healing time were observed between the diabetic and non-diabetic patients. Conclusions: In this descriptive institutional cohort, a combined protocol of wound-bed preparation, skin graft reconstruction, and postoperative NPWT-assisted stabilization was associated with favorable early graft take and fewer complications. These findings should be interpreted cautiously because of wound heterogeneity, unavailable wound size measurements, and limited subgroup sizes. Larger prospective studies are needed to evaluate the predictors of graft success.

Diseases doi: 10.3390/diseases14080285

Authors: Bozhidar Krastev Natalia Spasova Georgi Dimitrov Elena Kinova Assen Goudev

Background: Cancer-associated thrombosis is a clinically important complication of malignancy. The systemic immune–inflammation index (SII), calculated from platelet, neutrophil, and lymphocyte counts, may reflect the inflammatory background of cancer, but its value in matched heterogeneous cancer cohorts remains unclear. Objective: To evaluate whether SII is associated with thrombotic status and recorded all-cause mortality in patients with solid cancers. Methods: This retrospective matched cohort study was derived from 2020 consecutive adult patients hospitalized with solid malignancies between September 2023 and December 2025 at the Oncology Clinic of University Hospital “Tsaritsa Yoanna—ISUL”, Sofia, Bulgaria. Patients with documented thrombosis were matched 1:2 to non-thrombotic controls using a nearest propensity-score approach, with preference for exact matching on sex and cancer type. The final cohort included 110 thrombotic patients and 220 matched controls. SII was analyzed in relation to thrombotic status and recorded all-cause mortality using logistic regression. Results: Thrombotic patients and controls were well balanced for matching variables. Mortality was similar between groups: 29.1% versus 28.2%. SII did not differ significantly between thrombotic patients and controls: 772 (516–1471) versus 783 (501–1292), p = 0.655, and showed poor discrimination for thrombotic status, with an AUC of 0.515. In the overall matched cohort, higher SII was associated with recorded all-cause mortality after adjustment for thrombotic status, age, sex, cancer type, stage, and metastatic disease: OR 1.31 per 1000-unit increase, 95% CI 1.05–1.64, p = 0.016. The association was numerically stronger among thrombotic patients, but interaction testing was not statistically significant. Conclusions: SII was not associated with thrombotic status in this matched cancer cohort. Higher SII was associated with recorded all-cause mortality, suggesting that SII may better reflect systemic inflammatory burden than cancer-associated thrombosis itself.

Diseases doi: 10.3390/diseases14080284

Authors: Ahmed Bishara Huma Saeed Layan Akkielah Noor BuMurah David K. Driman Michael Silverman Reza Rahimi Shahmirzadi

Background: Malakoplakia is a rare chronic granulomatous inflammatory disorder characterized by defective macrophage phagolysosomal activity and accumulation of Michaelis–Gutmann bodies on histopathology. It occurs predominantly in immunocompromised individuals and may mimic infectious, inflammatory, or neoplastic processes, creating significant diagnostic challenges. We describe four cases of malakoplakia occurring in distinct immunocompromised states and review the published literature to better characterize its clinical spectrum, management, and outcomes. Methods: We conducted a retrospective case series of four patients diagnosed with histologically confirmed malakoplakia at our institution. Cases occurred in the setting of liver transplantation, kidney transplantation, relapsed acute myeloid leukemia, and ulcerative colitis treated with immunosuppressive therapy. A literature review was performed using PubMed and Google Scholar to identify published cases of malakoplakia in immunocompromised hosts. Demographic, clinical, microbiological, therapeutic, and outcome data were extracted and analyzed descriptively. Results: Four patients with malakoplakia involving the gastrointestinal tract or renal allograft were identified. Clinical presentations ranged from incidental endoscopic findings and tumor-like colonic masses to recurrent bacteremia and graft dysfunction. Histopathologic examination demonstrated characteristic Michaelis–Gutmann bodies in all cases. Management included antimicrobial therapy, observation, and surgical intervention when necessary. Two patients achieved complete clinical and histologic resolution, one required transplant nephrectomy because of persistent allograft infection, and one died from progressive acute myeloid leukemia. Combined with 48 cases identified in the literature, 52 patients were analyzed. The gastrointestinal tract was the most frequently affected site (76.9%), followed by the genitourinary tract (19.2%). Malignancy (32.7%), solid-organ transplantation (26.9%), and autoimmune disease (21.2%) were the most common underlying conditions. Conclusions: Malakoplakia should be considered in the differential diagnosis of mass lesions, persistent infections, and inflammatory lesions in immunocompromised patients, particularly those with malignancy or receiving immunosuppressive therapy. Early histopathologic diagnosis is essential to distinguish malakoplakia from malignancy and guide appropriate management. Our findings highlight the heterogeneous clinical manifestations and outcomes of this uncommon condition and emphasize the importance of multidisciplinary evaluation in affected patients.

Diseases doi: 10.3390/diseases14080283

Authors: Yuji Shimizu Asuka Oyama Yuko Noguchi Mutsumi Matsuu-Matsuyama Koichiro Hamada Shin-Ya Kawashiri Hirotomo Yamanashi Seiko Nakamichi Yasuhiro Nagata Takahiro Maeda Naomi Hayashida

Background/Objectives: Subclinical hypothyroidism (SCH) has been reported to be associated with chronic kidney disease (CKD). Anti–thyroid peroxidase antibody (TPO-Ab) positivity, a known cause of autoimmune thyroid disease, has been reported to be positively associated with SCH with hypertension, but not with SCH without hypertension. Therefore, hypertension status might indicate latent thyroid damage among individuals with SCH. This distinction suggests that categorizing SCH by hypertension status could be useful for evaluating its association with CKD. Methods: A cross-sectional study of 1479 Japanese aged 40–69 years, all of whom had thyroid hormone levels (free triiodothyronine and free thyroxine) within the normal range, was conducted to evaluate the association between CKD and SCH categorized by hypertension status. Results: No significant association between SCH without hypertension and CKD was observed. However, a significant positive association between SCH with hypertension and CKD was identified. The potential confounders-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 0.96 (0.39, 2.38) for SCH without hypertension and 2.76 (1.37, 5.59) for SCH with hypertension. Conclusions: Although further investigation is warranted, categorizing SCH by hypertension status may be useful for understanding the association between SCH and CKD. These findings may help clarify the biological significance of SCH in the development of CKD.

Diseases doi: 10.3390/diseases14080282

Authors: Seth Greenspan Michele Branigan Naomi Nguyen Saba Gulzar Stephen Probst Meng Wang

Alpha-gal syndrome (AGS) is an acquired allergy characterized as a delayed hypersensitivity reaction to the galactose-alpha-1,3-galactose carbohydrate, which is present on mammalian meat. AGS can cause severe anaphylactic reactions and has been implicated in intraoperative reactions to medications or surgical products that are derived from mammalian meat. This narrative review will describe the current literature on alpha-gal etiology, epidemiology, and perioperative management. Additionally, our institution is present in Suffolk County, New York, US, a highly endemic area, and we share our centers’ recommendations for managing AGS patients from their initial preoperative presentation throughout the perioperative period. We propose a detailed pathway for detection, preparedness, and intraoperative management of AGS patients undergoing elective surgery as well as alternative management suggestions for AGS patients undergoing emergency surgery.

Diseases doi: 10.3390/diseases14080281

Authors: Aleksandra Hejnosz Bartosz Migda Natalia Madetko-Alster Dagmara Otto-Ślusarczyk Piotr Alster

Background/Objectives: Evidence suggests that inflammation contributes to the pathogenesis of neurodegenerative disorders. The utility of blood-derived inflammatory biomarkers in differentiating neurodegenerative disorders remains incompletely understood. The aim of this study was to compare peripheral inflammatory markers in patients with essential tremor (ET), Parkinson’s disease (PD), progressive supranuclear palsy (PSP), and control participants. Methods: This retrospective study included 44 patients with ET, 47 with PD, 44 with PSP, and 45 control participants. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) were calculated from routine complete blood counts. Between-group comparisons were performed using the Kruskal–Wallis test, with a Holm correction across the six indices. The effect sizes were also estimated. Results: The PLR was the only inflammatory marker that significantly differentiated the analyzed groups (p = 0.045), with the highest value observed in PSP patients and the lowest in ET patients. A post hoc analysis indicated different PLR values in PSP than in ET patients (Cliff’s delta = 0.336, small-to-moderate effect). However, the overall association did not remain statistically significant after Holm correction across the six indices (adjusted p = 0.268), and the diagnostic group was not independently associated with PLR after adjustment for age and sex. No statistically significant differences were observed for the NLR, MLR, SII, SIRI, or AISI. Nevertheless, PSP patients consistently exhibited the highest median values of the NLR, SII, and AISI, whereas ET patients generally showed lower inflammatory marker levels. Conclusions: PLR was the only inflammatory marker that significantly differentiated the analyzed groups and was the highest among patients with PSP. The observed trends suggest a tendency toward greater peripheral immune activation in PSP compared with PD and ET. Larger prospective studies incorporating both inflammatory and neurodegenerative biomarkers are warranted to validate these findings.

Diseases doi: 10.3390/diseases14080280

Authors: Ciro Gargiulo Isacco Van Hung Pham Huong Thien Pham Kieu Cao Diem Nguyen Toai Cong Tran Thach Huy Le Felicita Jirillo Emilio Jirillo Luigi Santacroce

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma, also known clinically as gastric MALT lymphoma (GML) or MALToma, is an indolent B-cell neoplasm strongly associated with chronic Helicobacter pylori (H. pylori) infection. While early-stage disease is based on persistent antigenic stimulation and chronic inflammation, the metabolic and molecular transitions that drive monoclonal B-cell autonomy remain poorly understood. Importantly, H. pylori maintain this long-term colonization by defusing the host’s innate immunity; specifically, its lipid A portion features unique elongated acyl chains, composed of 16–18 carbon atoms, that fail to bind to and activate host TLR4/MD2 receptors, resulting in exceptionally weak endotoxic potency. Persistent colonization relies on key oncoproteins, particularly cytotoxin-associated gene A (CagA) and vacuolar cytotoxin A (VacA), which orchestrate early inflammatory infiltration (neutrophils, Th1, Th2 and Th17 cells) before shifting the microenvironment toward a suppressive regulatory T cell (Treg) phenotype. In this study, we propose a new critical step in the oncogenesis of gastric metastasis: chronic mitochondrial and immunometabolic adaptation within the gastric microenvironment. We claim that H. pylori act not only as a trigger for infection but also as a chronic driver of mitochondrial adaptation to oxidative stress and hypoxia, which subsequently results in defective mitophagy. CagA- and VacA-mediated mitochondrial damage induces reactive oxygen species (ROS) and functional hypoxia, stabilizing HIF-1α to force a glycolytic metabolic shift, while incomplete mitophagy rescues metabolically altered, apoptosis-resistant clones to drive monoclonal B-cell expansion. Within this ecological-microenvironmental framework, the predominantly cytoplasmic sequestration of BCL10 and the NF-κB subunit p65 observed in GML is reinterpreted not as evidence of signaling inactivity, but as a dynamically regulated adaptive state. This configuration is orchestrated by mitochondrial stress responses that enable adaptation to the chronic microenvironmental pressures imposed by H. pylori, acting in concert with the metabolic programs governed by MYC, NRF2, and BCL2. Overall, this review outlines the multi-step pathogenesis of H. pylori-mediated GML, highlighting how mitochondrial dysfunction and metabolic remodeling drive the transition from chronic infection to malignant transformation.

Diseases doi: 10.3390/diseases14080279

Authors: Giuseppe Losurdo Francesco Squeo Angela Marotti Antonio Giangaspero Enzo Ierardi Mariabeatrice Principi

Background: Celiac disease (CD) is an immune-mediated enteropathy associated with extra-intestinal manifestations. Sleep disorders may be frequent in CD patients. We aimed to investigate the quality of sleep in CD patients and to assess its relationship with clinical and biochemical parameters. Methods: We included patients with a proven diagnosis of CD under a gluten free diet at least twelve months prior to enrolment. All the participants completed the Sleep Scale from the Medical Outcomes Study (MOS sleep scale) and the Sleep Problems Index II was calculated. A high SLP9 score indicated a bad quality of sleep and values >20 revealed sleep disturbance. Moreover, blood samples were collected and demographic and clinical data were recorded from each subject. Linear logistic regression was used for uni- and multivariate analyses; the b coefficient and 95% confidence intervals (CI) were calculated. Results: We enrolled 53 patients, with the mean age being 42.75 ± 11.19 and 84.9% being females. The average hours of sleep per night were 6.47 ± 1.11. The mean SLP9 was 37.44 ± 20.65. Forty patients (75.5%) showed sleep disturbance, and 81.1% of patients had vitamin D insufficiency. According to univariate analysis, high SLP9 values (worse sleep) were inversely related to the number of sleep hours (b = −0.38, 95%CI: −11.8 to −2.2, p = 0.005) and to vitamin D levels (b = −0.57, 95%CI: −2.7 to −0.46, p = 0.009). In multivariate analysis only serum levels of vitamin D were inversely related to SLP9 (b = −0.47, 95%CI −12.8 to −0.43, p = 0.05). Conclusions: Low serum levels of vitamin D are independently associated with poor sleep quality in celiac patients. These findings need to be confirmed in future experimental and clinical studies.

Diseases doi: 10.3390/diseases14080278

Authors: Merita Hashani Arjeta Podrimaj-Bytyqi

Background/Objective: Melanoma is an aggressive skin malignancy characterized by significant molecular heterogeneity. Among the molecular alterations identified in melanoma, BRAF mutations represent one of the most common genetic abnormalities and play an important role in activating the MAPK signaling pathway. BRAF mutation status has become clinically important because of its prognostic significance and implications for targeted therapy. This study aimed to evaluate the frequency of BRAF mutations and their associations with demographic, histopathological, and clinicopathological characteristics in melanoma patients at the only referral center for BRAF testing in Kosova, the Institute of Pathology, University Clinical Center of Kosova (UCCK). Methods: This retrospective study included 127 melanoma patients. Descriptive statistics, frequency analysis, Spearman’s correlation and multivariable binary logistic regression analyses were performed to evaluate associations between BRAF mutation status and clinicopathological variables, including age, gender, Breslow thickness, histological type, ulceration, and anatomical localization. Results: BRAF mutation was identified in 76 of 127 melanoma patients (59.8%). The BRAF V600E/V600E2/V600D variants represented the predominant molecular subtype (75%). BRAF-positive melanoma was more frequently observed in younger patients and was significantly associated with increased Breslow thickness, nodular melanoma, ulceration, and trunk localization. Conclusions: BRAF mutations were highly prevalent in melanoma patients from Kosova and were associated with clinicopathological features of a more aggressive disease. The findings establish an important baseline for molecular epidemiology in the country and support the integration of routine BRAF testing into personalized melanoma management and future regional research.

Diseases doi: 10.3390/diseases14080277

Authors: Irena Gencheva-Angelova Radka Nuneva-Doncheva

Background: In our recent research, we established a strong and statistically significant association between the highest quartile of lipoprotein(a) [Lp(a)] and mildly reduced estimated glomerular filtration rate (eGFR). Comparisons with similar studies were hindered by varying Lp(a) analytical methods and different eGFR equations. We analyzed how replacing the diagnostic standard CKD-EPI 2021 equation with alternatives (CKD-EPI 2009, CKD-MDRD, CKD-EKFC) affects predictive models under comprehensive demographic and clinical confounder adjustments. Methods: We calculated eGFR for 310 adults using the four equations. Creatinine and Lp(a) were measured via IFCC-recommended methods. The cohort was divided into a main (eGFR 60–80 mL/min/1.73 m2) and a control group (eGFR > 80 mL/min/1.73 m2). Multivariable logistic regression and Area Under the Curve (AUC) metrics evaluated model performance. Results: Alternative equations systematically underestimated eGFR, artificially increasing the reduced filtration group. After full multivariable adjustment, only CKD-EPI 2021 preserved the independent association between the highest Lp(a) quartile and mildly decreased eGFR (OR = 2.65, p = 0.008), achieving an AUC of 0.732. Conversely, CKD-EPI 2009 lost significance; CKD-MDRD exhibited mathematical instability from control group depletion, and EKFC showed severe over-adjustment when demographic covariates were included. Conclusions: Older equations and the age-embedded EKFC equation may influence regression models, potentially obscuring the true biomarker associations. CKD-EPI 2021 demonstrated the highest precision, successfully isolating physiological aging and suggesting an independent association between high Lp(a) and mildly reduced eGFR, irrespective of metabolic and vascular confounders.

Diseases doi: 10.3390/diseases14080276

Authors: Raghad Saeed Asiri Khaled Abdulwahab Amer Leen Abdulmohsin Sarhan Najla Ahmad Jahash Riham Hamoud Alharbi

Chronic spontaneous urticaria (CSU) is a mast cell-driven disorder defined by recurrent wheals, angioedema, or both, persisting for longer than six weeks without an identifiable external trigger. Second-generation H1-antihistamines remain first-line therapy, yet a large share of patients stay symptomatic after the dose is raised up to fourfold, and for more than a decade, omalizumab was the only targeted option for those who failed antihistamines. This began to change in 2025, when the interleukin-4 receptor alpha (IL-4Rα) antagonist dupilumab and the oral, covalent Bruton tyrosine kinase (BTK) inhibitor remibrutinib were approved for antihistamine-refractory CSU within months of one another, while the anti-KIT monoclonal antibody barzolvolimab, which depletes mast cells, advanced into the largest phase 3 program the disease has seen. This narrative review outlines the guideline framework that still anchors CSU care, appraises the pivotal efficacy and safety data for omalizumab, dupilumab, remibrutinib, and barzolvolimab, and considers how these mechanistically distinct agents might be positioned and sequenced. The widening choice makes individualized, mechanism-informed treatment a realistic goal, but it also sharpens unresolved questions about patient selection, optimal treatment duration in a naturally remitting disease, and the long-term safety of newer oral and mast cell-depleting approaches.

Diseases doi: 10.3390/diseases14080275

Authors: Elisabeth A. Mates Alexandrea Kilgore-Gomez Claire Phibbs

Background: Thiamine deficiency (TD) causes thiamine deficiency disorders (TDDs) which are frequently overlooked in food-secure countries such as the United States (U.S.). Lack of awareness and the absence of validated, rapidly available biomarkers perpetuate underdiagnosis. Our objective was to determine prevalence of TD in hospitalized U.S. veterans without alcohol use disorder (AUD) and describe clinical characteristics of TDDs. A secondary objective was to evaluate the utility of plasma and whole-blood thiamine biomarkers in identifying thiamine-responsive disorders (TRDs). Methods: Newly hospitalized veterans without AUD were recruited. Fasting plasma and whole-blood thiamine were obtained. Interview, physical exam, and chart review were completed to assess clinical signs of TD. Participants were invited to return after thiamine repletion and changes in symptoms and exam findings were noted. Results: A total of 286 participants were enrolled: 261 had plasma thiamine results, 259 had whole-blood thiamine results, 179 completed interviews, 164 completed initial examination, and 60 returned for reexamination after repletion. A majority (86.59%) had potential signs or symptoms of TDDs, 26.44% had low plasma thiamine, 2.70% had low whole-blood thiamine, and 97.92% with low plasma thiamine had clinical signs of TDDs and many experienced multiple TD syndromes. Those with low plasma thiamine who returned after repletion showed improvements in cognitive scores (p = 0.0093) and motor strength (p = 0.0417), and most reported symptom improvement. Whole-blood thiamine missed many cases of TRDs. Conclusions: TD affects one quarter of hospitalized veterans without AUD. Low plasma thiamine identifies TRDs more frequently than low whole-blood thiamine. Using clinical criteria alone to diagnose TDDs overestimates cases and biomarker confirmation appears necessary.

Diseases doi: 10.3390/diseases14080274

Authors: Alessandra Pizzo Marco Zeppieri Filippo Marano Alessandro Vasco Corrado Pizzo Antonio M. Vicari Fabiana D’Esposito Caterina Gagliano Francesco Cappellani

Cocaine-induced ocular toxicity is an increasingly acknowledged but often underestimated clinical condition that includes a wide range of eye-related symptoms. The extensive recreational use of cocaine, together with its powerful sympathomimetic and vasoconstrictive effects, leads to various ocular problems that can impact all anatomical components of the eye. This narrative review aims to deliver a thorough and current synthesis of the existing research on the epidemiology, pathophysiology, clinical symptoms, and therapy of cocaine-related ocular illness. Evidence suggests that cocaine-induced ocular damage involves vascular, local toxic, neuronal, and immunological processes. Reported manifestations in the literature include the ocular surface, optic nerve, posterior segment, orbit, and adnexal tissues. Novel imaging techniques have revealed subclinical retinal microvascular changes in chronic users, suggesting a continuum from initial vascular dysregulation to manifest ischemic injury. Notwithstanding increased awareness, the existing evidence is constrained by heterogeneity, small sample sizes, and a prevalence of case reports. A comprehensive understanding of the pathophysiological mechanisms and long-term ocular effects is crucial for enhancing diagnostic precision, directing management, and informing preventive measures. Enhanced multidisciplinary collaboration between ophthalmologists and addiction experts is essential to tackle this intricate and dynamic clinical dilemma.

Diseases doi: 10.3390/diseases14080273

Authors: Maedeh Mirasheh Zahra Shahabinia Afrooz Mazidimoradi Toktam Soleimani Leila Allahqoli Hamid Salehiniya

Environmental exposure to pesticides is considered a risk factor for gynecological cancers, contributing to their onset and progression through various mechanisms. This narrative review investigates the role of different pesticides in the development and progression of ovarian, endometrial, and cervical cancers, and provides a comprehensive synthesis of epidemiological findings along with molecular mechanisms, highlighting carcinogenic pathways, conflicting findings, and potential therapeutic implications. Relevant epidemiological and experimental studies published between 2000 and 2025 were identified through searches of major scientific databases. Various pesticides, particularly organochlorines, contribute to gynecological cancers through mechanisms such as estrogen mimicry, DNA damage, oxidative stress, increased pro-inflammatory cytokines, and disruption of cellular signaling pathways. However, most studies found no significant association between certain pesticides, such as Triazines and Atrazine, and gynecological cancers. Furthermore, some pesticides, like Carbendazim, exhibit a dual role; while carcinogenic, they can also serve therapeutic purposes in cancer treatment when utilized with nanotechnology. Overall, pesticide exposure is a significant factor in the development and progression of women’s cancers, although the strength of the evidence varies across pesticide classes. Despite numerous studies, contradictory findings necessitate further research to clarify causal relationships.

Diseases doi: 10.3390/diseases14080272

Authors: Karim Chamari Wissem Dhahbi Sumaya ElMadhoun James England Mohammad Mansi Hala Al Ali Jallal Toufiq Khalifa Alkuwari

Background/Objectives: Substance use disorders (SUDs) remain a major public health challenge, with high relapse rates despite established pharmacological and behavioral treatments. This scoping review maps evidence on structured exercise interventions as therapeutic approaches in SUD treatment, focusing on direct clinical outcomes, substance-specific effects, and implementation strategies. Methods: Following PRISMA-ScR and JBI guidance, searches of PubMed, Scopus, PsycINFO, and SPORTDiscus identified human studies published from 2000 to 31 December 2024 that evaluated supervised exercise interventions in adults with SUDs. Results: Evidence from randomized trials and recent network meta-analyses indicates clinically relevant benefits for abstinence, craving reduction, mood symptoms, cognitive function, treatment retention, and withdrawal management. Moderate-to-vigorous aerobic exercise delivered three to four times weekly for at least 12 weeks, at approximately 180 MET-minutes per week, appears particularly effective, while combined aerobic and muscle-performance protocols may yield broader benefits. Conclusions: Exercise interventions show strong potential as adjuncts to SUD care. Implementation should incorporate individualized prescription, substance-specific safety screening, cardiovascular and psychiatric monitoring, and multidisciplinary coordination. Further long-term randomized trials, mechanistic studies, and cost-effectiveness evaluations are needed.

Diseases doi: 10.3390/diseases14080271

Authors: Michał Kutyłowski Piotr Alster Natalia Madetko-Alster Bartosz Migda

Background/Objectives: Progressive supranuclear palsy (PSP) and Parkinson’s disease (PD) share several clinical manifestations, which may complicate differential diagnosis. The aim of this study was to evaluate whether automated volumetric measurements of the pallidum and ventral diencephalon can differentiate PSP from PD. Methods: Thirty-two patients were included, comprising 20 patients with PD and 12 patients with PSP. All participants underwent 3-T brain magnetic resonance imaging. Automated segmentation and volumetric analysis were performed using the vol2Brain pipeline. Absolute and normalized volumes of the pallidum and ventral diencephalon were compared between groups. Receiver operating characteristic (ROC) analysis was used to assess diagnostic performance. Results: Patients with PSP demonstrated lower pallidal and ventral diencephalic volumes than patients with PD. Differences were observed for both absolute and normalized volumetric measurements (all p ≤ 0.002). Total pallidal volume showed the highest diagnostic performance, with an area under the ROC curve (AUC) of 0.958, sensitivity of 85%, and specificity of 100%. Total ventral diencephalon volume also differentiated PSP from PD, yielding an AUC of 0.829, seNsitivity of 70%, and specificity of 92%. Conclusions: Pallidal and ventral diencephalic volumes differed between patients with PSP and PD. Automated measurements of pallidal and ventral diencephalic volumes may complement conventional MRI findings in patients with parkinsonian syndromes. Further studies are needed to validate these findings in larger cohorts.

Diseases doi: 10.3390/diseases14080270

Authors: Emmanuel U. Azu Gulzar H. Shah Toktam Naderimoghaddam Lili Yu

Background/Objectives: Multimorbidity is increasingly recognized as a major contributor to mortality worldwide, yet its underlying patterns and prognostic implications remain poorly understood in the United States. This study identified distinct multimorbidity patterns and examined their association with all-cause mortality in a nationally representative sample of U.S. adults. Methods: We conducted a retrospective cohort study using data from the 2004 National Health Interview Survey linked to the National Death Index through 2019 (n = 28,598). Latent class analysis identified unobserved multimorbidity classes based on patterns of co-occurring physician-diagnosed chronic conditions, and Cox proportional hazards models were fitted to estimate mortality risk while accounting for complex survey design. Six distinct multimorbidity classes were identified, reflecting cardiometabolic, respiratory, cardiovascular, and inflammatory disease profiles. Results: Compared with the Low Multimorbidity group, all other classes were associated with increased mortality risk. In fully adjusted analyses, the Severe Cardiopulmonary–Metabolic (HR 3.71, 95% CI 2.99–4.60) and Advanced Cardiovascular (HR 2.81, 95% CI 2.52–3.14) classes showed the highest risks. Intermediate risks were observed in the Cardiometabolic–Arthritis (HR 2.45, 95% CI 2.13–2.81) and Respiratory–Musculoskeletal (HR 1.39, 95% CI 1.22–1.58) classes, while the Inflammatory Pain–Airway class showed a more modest increase. Subgroup analyses suggested stronger relative effects among younger adults and women in the most severe classes. Conclusions: The study findings highlight the heterogeneous nature of multimorbidity and suggest that specific disease clusters carry substantially different mortality risks. Recognizing these patterns may improve risk stratification and support more targeted, patient-centered care strategies.

Diseases doi: 10.3390/diseases14080269

Authors: Denisa-Catalina Dragomir Adelaida-Sorana Trifu Amelia-Damiana Trifu

Background: Subclinical eating-disorder tendencies may reflect early psychological vulnerability before the development of clinically diagnosed eating disorders. Body image concerns, perceived social support, and control-related beliefs are established correlates of eating pathology. However, their joint pattern across several eating-disorder tendency profiles has received less attention in Romanian nonclinical adult samples. Objective: We examined differences in perceived social support, locus of control, and body image concerns among participants with and without subclinical tendencies associated with anorexia, bulimia, and binge eating. We investigated the association between locus of control and body image concerns. Methods: A cross-sectional quantitative design was used. The sample included 108 participants who completed online self-report measures assessing perceived social support, eating-disorder tendencies, body image concerns, and locus of control. Independent-samples t-tests and Welch tests were used for group comparisons. Bonferroni correction was applied within families of comparisons. Effect sizes were reported using Hedges’ g. Pearson correlation and simple linear regression were used to examine the association between locus of control and body image concerns. Results: Body image concerns were significantly higher among participants with anorexic, binge-eating, and bulimic tendencies. Perceived social support was lower among participants with binge-eating and bulimic tendencies, but not among those with anorexic tendencies. Locus of control differed significantly only in the exploratory bulimia comparison after correction. External locus of control was positively associated with body image concerns and explained a small but significant proportion of variance. Conclusions: Body image concerns emerged as the most consistent correlate of subclinical eating-disorder tendencies. The findings support the relevance of body image, interpersonal resources, and control-related beliefs in early eating-disorder vulnerability.

Diseases doi: 10.3390/diseases14080268

Authors: Vasile Calin Arcas Iulian Roman-Filip Doru Florian Cornel Moga Adriana Saceleanu Anca Maria Fratila Lucia Nicola Fratila Corina Roman-Filip

Background: Multiple sclerosis and periodontal disease are chronic inflammatory conditions that may share immune-mediated mechanisms, including cytokine activation, oral dysbiosis, oxidative stress, and systemic inflammatory burden. This systematic review aimed to synthesize recent evidence on common inflammatory pathways linking periodontal disease and multiple sclerosis. Methods: The review was conducted according to PRISMA 2020 guidelines. PubMed/MEDLINE, Cochrane Library, and Scopus were searched for English-language studies published between June 2020 and June 2026. Eligible studies addressed multiple sclerosis, periodontal disease, oral microbiome alterations, systemic inflammation, or neuroinflammatory outcomes. Study selection and data extraction were performed independently by three reviewers. Risk of bias was assessed using AMSTAR 2, the Newcastle–Ottawa Scale, and the Joanna Briggs Institute checklist, according to study design. Results: Seventeen studies were included in the qualitative synthesis. The main shared mechanisms were cytokine-mediated inflammation involving TNF-α, IL-1β, IL-6, and IL-17; NF-κB signaling; Th17/Treg imbalance; blood–brain barrier disruption; oxidative stress; matrix metalloproteinase activity; complement activation; and oral–gut–brain axis dysregulation. The evidence suggests that periodontal inflammation may contribute to systemic immune activation and may amplify neuroinflammatory processes in multiple sclerosis. Conclusions: Current evidence supports a biologically possible association between periodontal disease and multiple sclerosis through shared inflammatory and microbial pathways. However, causality remains unproven, and further longitudinal and interventional studies are needed.

Diseases doi: 10.3390/diseases14080267

Authors: Ariel Torres Paloma González Martha Fors Gisselle Trujillo

Background: Tuberculosis remains a major public health challenge in Latin America, where social inequalities, fragmented health systems, and barriers to care continue to undermine disease control. Although effective treatment is available, treatment abandonment and loss to follow-up remain persistent obstacles to successful outcomes. Methods: A structured critical analysis of the contemporary literature on tuberculosis treatment abandonment and retention in care was conducted using a narrative evidence synthesis approach. Forty scientific documents published between 2018 and 2026 were included. Of these, 23 Latin American studies informed the results synthesis, while 13 international studies supported the comparative critical reflection. Results: Findings were organised into five domains: social vulnerability, clinical complexity, health system barriers, priority populations, and protective factors and innovation. The evidence indicates that treatment abandonment is not an isolated individual behaviour, but a phenomenon associated with the convergence of social, clinical, and institutional determinants across the care trajectory. Poverty, migration, drug resistance, incarceration, weak follow-up systems, and fragmented care were repeatedly associated with discontinuity, whereas social support, active follow-up, digital tools, and economic measures were linked to improved adherence and retention in care. Conclusions: From a biopsychosocial perspective, treatment abandonment should be understood as a systemic and preventable failure across the tuberculosis care continuum. The proposed Latin American Integrated Model for Retention in Tuberculosis Care (MILERTB) offers an anticipatory, equity-oriented, and person-centred framework to strengthen retention in care and guide future implementation research.

Diseases doi: 10.3390/diseases14080266

Authors: Bouchra Nour El Houda Baiski Zoulikha Mokrani Sara Mimi Atmani Fatma Zohra Ider Nabila Lakri Fatma Zohra Souid Samia Chaib Assia Galleze

Objective: Axonal injury is a key determinant in irreversible disability in multiple sclerosis (MS). Reliable biomarkers of neuroaxonal damage are essential for improving diagnosis, monitoring disease progression, and evaluating treatment response. This study investigated the relationship between phosphorylated neurofilament heavy chain (pNF-H), clinical characteristics, and conventional cerebrospinal fluid (CSF) and serum biomarkers in Algerian patients with MS. Methods: A total of 102 participants were enrolled. Clinical, immunological, and biochemical parameters were assessed, including the Expanded Disability Status Scale (EDSS), oligoclonal bands (OCBs), IgG index, albumin quotient, and pNF-H concentrations in paired CSF and serum samples. Results: OCBs were detected in 85.5% of patients, and 65.21% exhibited intrathecal immunoglobulin synthesis, with a median IgG index of 0.87. Patients with progressive MS were significantly older and more disabled than those with relapsing–remitting MS (age: p = 0.01; EDSS: p = 0.0007). OCB-positive patients had significantly higher IgG index values (p = 0.0004), but OCB status was not associated with age, EDSS, or albumin quotient. EDSS correlated positively with age (p = 0.0007), albumin quotient (p = 0.01), and IgG index (p = 0.001). Both CSF and serum pNF-H levels were significantly elevated in MS patients compared with NSDs group (p < 0.001). Increased pNF-H concentrations were associated with progressive disease and greater disability (EDSS ≥ 5). Conclusions: Elevated pNF-H levels in CSF and serum are associated with disease severity and progressive MS, supporting their potential as complementary biomarkers of neuroaxonal damage and clinical disability in routine MS assessment.

Diseases doi: 10.3390/diseases14080265

Authors: Christian Spiegel Riham Shanti Friederike Weschenfelder Michelle Mueller Spiegel Maik Neumann Mark Lenz Wolfram Weschenfelder

Background: Wound complications and unplanned revision surgery remain common after soft tissue sarcoma (STS) resection. Established risk models focus on patient- and tumour-related factors, while the role of operative and perioperative variables is less well defined. Methods: This retrospective single-centre study included 95 patients undergoing STS resection between 2021 and 2025. Associations with unplanned revision surgery were evaluated using univariate and exploratory multivariable logistic regression analyses. Receiver operating characteristic (ROC) analysis assessed the discriminatory performance of postoperative drainage output. Results: Unplanned revision surgery occurred in 23 patients (24%). On univariate analysis, several intraoperative and postoperative variables were associated with revision, whereas most patient- and tumour-related factors were not statistically significant. In multivariable analysis, intraoperative crystalloid administration was the only intraoperative factor associated with unplanned revision (OR 1.45 per 500 mL, 95% CI 1.05–2.02; p = 0.026). Among postoperative parameters, drainage output remained associated with revision (OR 1.45 per 100 mL, 95% CI 1.15–1.82; p = 0.005). In patients without planned secondary reconstruction, drainage output showed good exploratory discriminatory performance (AUC 0.927), with a cutoff of 925 mL providing high specificity (94.4%) with acceptable sensitivity (75%). Conclusions: In this cohort, unplanned revision was more frequently associated with markers of surgical complexity, including higher intraoperative crystalloid administration, and the early postoperative course, particularly drainage output. Drainage output appears to reflect an evolving complication rather than an independent predictor and may serve as an early clinical warning signal. Findings are hypothesis-generated and require external validation.

Diseases doi: 10.3390/diseases14070264

Authors: Camilla Laureti Dario Benelli Federica Zoccali Gabriele Riccardi Mattia Umberto Di Michele Stefano Venarubea Christian Barbato Antonio Minni Carla Petrella

Background: Bacteria colonizing the nasal cavity contribute to mucosal homeostasis, and altered sinonasal bacterial communities have been associated with chronic rhinosinusitis with nasal polyps (CRSwNP). Whether routine, culture-based microbiology can distinguish the cultivable bacterial profile of CRSwNP patients from that of controls remains unclear. Methods: In this single-center observational pilot study, middle-meatus swabs from 30 patients with CRSwNP and 30 controls were cultured on four media, and isolates were identified with the VITEK 2 system. For each species, presence or absence per subject was compared between groups using Fisher’s exact test with Benjamini–Hochberg correction for multiple comparisons; the number of cultivable species per subject was compared with the Mann–Whitney test. Results: The two groups were comparable in age and sex. Patients yielded more cultivable bacterial species per subject than controls (mean 4.4 vs. 2.9; Mann–Whitney p < 0.001). Several species were numerically more frequent in patients (e.g., Staphylococcus hominis, S. lugdunensis) and others in controls (e.g., S. epidermidis, S. aureus), but no individual species difference remained significant after correction. Conclusions: Using routine culture, CRSwNP was characterized chiefly by a higher number of cultivable bacterial species, whereas individual species differences were not statistically robust. These hypothesis-generating findings warrant confirmation in larger, sequencing-based studies.

Diseases doi: 10.3390/diseases14070263

Authors: Ana De Maya-Martínez Omar Cauli María del Carmen Giménez-Espert Cristina Buigues

Background: Healthcare-associated infections (HAIs) remain a major preventable challenge in healthcare systems worldwide. Nursing students play a key role in infection prevention during clinical training; therefore, adequate education in hand hygiene (HH), standard precautions (SPs), and infection prevention and control (IPC) is essential. This systematic review aimed to evaluate nursing students’ knowledge of HAI prevention according to international recommendations and to identify factors associated with higher knowledge levels. Methods: A systematic review was conducted following Joanna Briggs Institute methodology and PRISMA guidelines. Searches were performed in MEDLINE (PubMed), CINAHL, Cochrane Library, Embase, Scopus, and Web of Science. Observational studies assessing nursing students’ knowledge of HH, SPs, or IPC were included. Methodological quality was assessed using the Joanna Briggs Institute critical appraisal checklist for analytical cross-sectional studies. Results: Fifty-two studies involving 13,912 nursing students across five continents were included. Most studies focused on HH, followed by SPs and IPC. The WHO Five Moments for Hand Hygiene (14 of 26 (53.8%)) was the most frequently used instrument for HH assessment, while the Compliance with Standard Precautions Scale (5/11 (45.5%)) was the most used for SPs. Regarding IPC, most studies (5/7 (71.4%)) evaluated it by study-specific questionnaires developed/adapted by the researchers. Higher knowledge and compliance levels were generally associated with advanced academic year, prior training, positive attitudes, and supportive clinical environments. However, substantial heterogeneity was identified across study designs, assessment instruments, outcome measures, and methodological quality. Conclusions: Continued and updated education in HH, SPs, and IPC appears essential for improving nursing students’ knowledge and preventive practices. Greater standardization of assessment methods is needed to improve comparability across studies.

Diseases doi: 10.3390/diseases14070262

Authors: Loredana Sabina Pascu Simona Dana Mitincu-Caramfil Andrei Vlad Bradeanu Ancuța Iacob Mihaela Lungu Ileana Marinescu Eduard Polea Drima

Background: Multiple sclerosis (MS) is a neurodegenerative and chronic inflammatory disease, often associated with psychiatric comorbidities, particularly depression and anxiety, which play a major role in disability, cognitive dysfunction, and quality of life. Growing evidence suggests that affective symptoms in MS are not only related to psychosocial burden but also to structural and functional abnormalities in the brain that can be identified using magnetic resonance imaging (MRI). Methods: A systematic database search was performed to identify studies for a structured narrative review. Original articles that examined MRI correlates of depression and anxiety in adult MS patients were included. Structural MRI, diffusion imaging, and functional MRI studies evaluating lesion distribution, cortical and subcortical atrophy, white matter microstructure, and network connectivity were analyzed alongside psychometric instruments used to assess affective symptoms. Results: Depression in MS was consistently associated with fronto-limbic and subcortical abnormalities including cortical thinning, hippocampal and thalamic atrophy, white matter disconnection and altered connectivity within the default mode, salience and executive control networks. Diffusion MRI studies have shown microstructural damage in associative white matter tracts, and functional MRI studies have supported a model of network-level dysfunction. In contrast, anxiety had less robust and reproducible associations with conventional MRI findings, indicating a more complex interaction between inflammatory, neurobiological and psychosocial mechanisms. Conclusions: Multimodal MRI approaches may increase our knowledge of the neurobiological substrates of depression and anxiety in MS and may contribute to more personalized diagnostic and therapeutic strategies.

Diseases doi: 10.3390/diseases14070261

Authors: Hirotaka Fukuda Akihisa Sugawa Takashi Miyamoto Akira Nonoue Terumi Fujimoto Kazuki Tobita Tomoyuki Arai

Background: Transcatheter Edge-to-Edge Repair (TEER) is a therapeutic option established for older patients with heart failure and concomitant mitral regurgitation. Frailty is associated with prognosis after transcatheter valve interventions. However, despite clinical potential, evidence for gait speed as a simplified prognostic marker in patients undergoing TEER remains insufficient. Objectives: This study aimed to investigate the association between preoperative gait speed and mid- to long-term mortality after TEER. Methods: We conducted a single-center retrospective cohort study of 97 patients (mean age: 78.9 ± 8.7 years; 56.7% male) who survived the first 7 days after TEER and had available preoperative gait speed data. Preoperative gait speed was assessed, and clinical data were obtained from medical records. Cox regression analysis was performed to elucidate the association between preoperative gait speed and mortality. Results: In Cox proportional hazards models, higher gait speed (per 0.1 m/s increase) was associated with lower mortality after adjustment for the Society of Thoracic Surgeons risk score and handgrip strength (hazard ratio: 0.81; 95% confidence interval: 0.68–0.97; p = 0.02). In time-dependent receiver operating characteristic curve analysis, gait speed showed moderate discriminative ability for mortality, with area under the curve values of 0.749 at 1 year and 0.710 at 2 years. A gait speed of 0.8 m/s was used as an exploratory threshold for survival stratification, and patients with gait speed < 0.8 m/s had lower survival than those with gait speed ≥ 0.8 m/s (log-rank p < 0.01). Conclusions: Lower preoperative gait speed was associated with higher mid- to long-term mortality after TEER. Preoperative gait speed may provide clinically useful information for exploratory risk stratification, although the cutoff-based findings require external validation.

Diseases doi: 10.3390/diseases14070260

Authors: Giusi Santangelo Lucrezia Lamorgese Noemi Tonti Maria Grazia Porpora Innocenza Palaia Federica Tomao Violante Di Donato Margherita Fischetti Daniele Di Mascio Antonella Giancotti Giorgia Perniola Ludovico Muzii

Background: The human microbiota plays a crucial role in maintaining physiological homeostasis and influencing the development of chronic diseases not only in the gut but in the whole body. Material and Methods: This literature review is based on a comprehensive search of the PubMed database covering the period from 2008 to 2026. Approximately 65 key studies were included in the final analysis. Only articles published in English were included. The search included keywords such as microbiota, inflammaging, eubiosis, diet, gut diseases, cardiovascular diseases, diabetes, and osteoporosis. This narrative review explores the composition, development, and functional significance of the gut microbiota across the human lifespan, highlighting its dynamic interaction with environmental factors. Early-life microbial colonization, shaped by factors including delivery mode and breastfeeding, has long-term implications for immune system maturation and disease susceptibility. Results: A balanced gut microbiota (eubiosis) supports host health through metabolic activities, mainly by the production of short-chain fatty acids (SCFAs), which regulate intestinal barrier integrity, immune responses, and systemic inflammation. Contrarily, dysbiosis—characterized by reduced microbial diversity and an overrepresentation of pro-inflammatory species—is associated with chronic low-grade inflammation (inflammaging) and contributes to the pathogenesis of multiple diseases. Age-related changes in microbial composition are shown to activate inflammatory processes and impair immune regulation, thereby increasing disease risk. Therefore, it is important to recognize the role of microbiota alterations in key pathological conditions, including neurodegenerative diseases, cardiovascular diseases, type 2 diabetes mellitus, and osteoporosis. Conclusions: Finally, the potential of microbiome-targeted interventions, such as probiotics, prebiotics, and dietary modulation—in particular the Mediterranean diet is recognized as the most balanced—is discussed as a promising strategy to restore microbial balance and mitigate inflammaging. Further research is needed to better understand the association between microbiota and host health and to optimize therapeutic approaches for aging populations.

Diseases doi: 10.3390/diseases14070259

Authors: Martha Alvarado Ibarra Alma B. Mera-González Ana L. Tapia-Enriquez Ana P. Ramirez-Hoyos Annel Martínez-Ríos Atenas Villela-Peña Carlos Martínez-Murillo Carolina F. Cruz-García Carolina García-Castillo Cristina E. Madera-Maldonado Daniel Cabello-Modesto David Ávila-Castro Eleazar Hernández-Ruiz Emmanuel R. Rodríguez-Cedeño Eugenia P. Paredes-Lozano Faustino Leyto-Cruz Fernando Montero-Palomo Fernando Perez-Zincer Flavio Rojas-Castillejos Geraldin M. Gutiérrez-Gómez Gonzalo Iván Gómez López Irene Anaya-Cuellar Israel Cervantes-Sánchez Jaime García-Chávez Javier de Jesús Morales Adrián J. Antonio De la Peña-Celaya José L. Alvarez-Vera José L. López-Arroyo Josué I. Ruiz-Contreras Juan M. Pérez Zúñiga Juan P. Macías Flores Karina Silva-Vera Laura E. Merino Pasaye Leire Montoya Jiménez Luara L. Arana-Luna Lucy González-Villarroel M. Cecilia Gómez-Núñez de Cáceres Maria D. Valencia Rivas M. Eugenia Espitia-Ríos M. Raquel Miranda-Madrazo Nishalle Ramírez-Muñiz Óscar Teomitzi-Sánchez Pablo A. García Chávez Ramón A. Bates-Martín Roberto Ovilla Martínez Sergio J. Loera-Fragoso Yessica Torres-Giron Alberto Villalobos-Prieto Lénica A. Chávez-Aguilar W. Herrera-Olivares

Hemophilia is an X-linked inherited bleeding disorder, classified as type A or type B. Therapeutic advances offer new treatment options that improve disease control and reduce associated complications, including inhibitor development and hemophilic arthropathy. This document aims to update the Mexican hemophilia consensus, reviewing current evidence on diagnosis and management, and addressing gaps in the treatment and follow-up of patients in Mexico, aligning local needs with international recommendations. A PubMed literature search covering the last five years (up to September 2025) was conducted, prioritizing consensus statements, guidelines, and systematic reviews. Using the Delphi methodology, a structured questionnaire was submitted electronically to forty-four experts. Aspects without initial agreement were discussed at an in-person meeting. Consensus was defined as at least 80% of votes in favor. Recommendations were issued across six domains: laboratory diagnosis, genetic testing, management of hemophilia A and B without and with inhibitors, adjuvant treatments, and gene therapy. The recommendations address prophylaxis with coagulation factor concentrates, non-factor therapies, immune tolerance induction, perioperative management, pain management, and eligibility criteria and follow-up protocols for gene therapy with adeno-associated viral vectors. This consensus provides updated, evidence-based recommendations adapted to the Mexican healthcare context, identifying priority areas, including timely access to non-factor therapies and gene therapy, development of a national referral network for complex cases, and inclusion of novel therapeutic agents in the institutional essential medicines list, with the aim of improving the quality of life of people with hemophilia in Mexico.

Diseases doi: 10.3390/diseases14070258

Authors: José Luis Sánchez-Reynoso Sol Ramírez-Ochoa Berenice Vicente-Hernández Gabino Cervantes-Guevara Alejandro González-Ojeda Clotilde Fuentes-Orozco Francisco Javier Hernández-Mora Mauricio Alfredo Ambriz-Alarcón Luis Asdruval Zepeda-Gutiérrez Enrique Cervantes-Pérez

Background: Nutritional abnormalities, alterations in body composition, and impaired muscle function are increasingly recognized as clinically relevant features in patients with Systemic Lupus Erythematosus (SLE). However, the relationship between multidimensional nutritional assessment and disease activity remains incompletely characterized. This study aimed to evaluate the associations between nutritional status, body composition, muscle strength, nutritional risk indices, and disease activity in patients with SLE. Materials and Methods: This exploratory retrospective study included hospitalized patients with SLE. Clinical data, anthropometric measurements, and nutritional status were assessed using the body mass index (BMI), prognostic nutritional index (PNI), controlling nutritional status (CONUT), and nutritional risk index (NRI). Muscle function was evaluated using the SARC-F scale. Disease activity was measured using the SLE Disease Activity Index 2000 (SLEDAI-2K). Multivariable linear regression models were constructed to assess the independent association between nutritional indices and disease activity, adjusting for age, sex, glucocorticoid exposure, and immunosuppressive therapy. Correlation analyses were performed between nutritional indices and disease activity-related variables, and supplementary exploratory Spearman correlations were performed between the SARC-F score and SLEDAI-2K, CRP, complement C3, complement C4, and ESR. False discovery rate correction using the Benjamini–Hochberg procedure was applied to exploratory correlation analyses. Results: A total of 67 patients were included. Nutritional indices (BMI, PNI, CONUT, and NRI) were not independently associated with SLEDAI-2K in multivariable regression analyses. In correlation analyses, after FDR adjustment, the PNI remained significantly associated with SLEDAI-2K, lymphocyte counts, and complement C3 levels, while CONUT remained significantly associated with lymphocyte count and C3 levels. The BMI and NRI were not significantly associated with disease activity or inflammatory markers after correction. SARC-F showed a weak positive correlation with SLEDAI-2K (r = 0.328; p = 0.008; qFDR = 0.040), which remained statistically significant after FDR correction. No significant correlations were observed between SARC-F and CRP, complement C3, complement C4, or ESR after FDR adjustment. Conclusions: Nutritional indices showed limited independent association with disease activity in SLE after adjustment for available confounders. Although the PNI and CONUT retained selected correlations with disease activity-related or immunological markers after FDR correction, these associations should be interpreted cautiously, as albumin- and lymphocyte-based indices may reflect inflammatory activity or disease burdens rather than nutritional status alone. SARC-F remains significantly associated with disease activity (SLEDAI-2K) after FDR adjustment. These findings should be validated in future prospective studies with a larger number of patients.

Diseases doi: 10.3390/diseases14070257

Authors: Josef Yayan

Background: Chest radiography remains one of the most widely used imaging modalities for the detection of thoracic abnormalities, including pneumothorax and pulmonary masses. However, the frequency with which these findings are identified may vary according to demographic characteristics and radiographic acquisition techniques. Understanding such variability is important for interpreting large imaging datasets and may improve diagnostic assessment and epidemiological research. Therefore, this study aimed to evaluate sex-, age-, and projection-related differences in the dataset-derived detection frequencies of pneumothorax and pulmonary mass annotations in a large chest radiograph dataset. Methods: A retrospective cross-sectional analysis of 112,120 frontal chest radiographs obtained from 30,805 adult patients in the NIH ChestX-ray14 dataset was performed. Only anteroposterior (AP) and posteroanterior (PA) projections were included. Patients younger than 18 years, radiographs lacking demographic metadata, and lateral projections were excluded. Pneumothorax and pulmonary mass annotations were defined according to the corresponding NIH ChestX-ray14 labels generated from radiology reports using natural language processing. Patients were stratified according to sex and age group. Statistical analyses included chi-square tests, adjusted odds ratios (adjusted ORs), image-level multivariable logistic regression analyses, and corresponding patient-level generalized estimating equation (GEE) analyses to account for repeated radiographs from the same patient. Sensitivity analyses, including simulated annotation misclassification scenarios, were conducted to evaluate the robustness of the observed associations. Results: A total of 4988 pneumothorax and 5588 pulmonary mass annotations were identified. Pneumothorax detection frequencies were significantly higher among females aged 41–80 years (adjusted OR range: 0.66–0.68; p < 0.0001), whereas pulmonary mass annotations were more frequently detected in males, particularly in individuals aged 21–40 years (adjusted OR 1.52; p < 0.0001). Female patients were older on average and underwent PA imaging more frequently than male patients. AP projection was associated with lower pneumothorax annotation detection frequencies, whereas its association with pulmonary mass annotation detection was attenuated after patient-level analysis. Patient-level GEE analyses confirmed the robustness of the primary image-level findings. Conclusions: Detection frequencies of pneumothorax and pulmonary mass annotations varied systematically according to sex, age, and projection type, demonstrating substantial demographic and technical variability within a large chest radiograph dataset. These findings highlight the importance of considering demographic characteristics and imaging acquisition factors when interpreting large chest radiograph datasets. Because the findings were based on NLP-derived dataset annotations rather than reference-standard diagnoses, they should be interpreted as dataset-level associations rather than estimates of disease prevalence. Improved recognition of demographic and projection-related variability may contribute to more accurate interpretation of chest radiographs and more reliable imaging-based epidemiological research.

Diseases doi: 10.3390/diseases14070256

Authors: Ilenia Pinna Paolo Solla Gianni Orofino Tommaso Ercoli Francesco Salis Francesco Loy Carla Masala

Background/Objectives: COVID-19 has triggered a global health crisis with sequelae extending beyond the acute phase of infection. Long COVID-19 is characterized by the persistence or new onset of symptoms weeks to months after the initial infection, including fatigue, cognitive impairment, and chemosensory dysfunction. Despite growing clinical evidence, the underlying pathophysiological mechanisms remain incompletely understood. This study aimed to evaluate the prevalence, distribution, and evolution of symptoms during the post-acute phases, with particular emphasis on olfactory and gustatory alterations. Methods: An observational study used a structured online questionnaire to collect demographic and clinical data from individuals with prior SARS-CoV-2 infection. Participants (n = 798) with persistent symptoms beyond 4–8 weeks were included. A subgroup of participants living in Sardinia underwent objective chemosensory assessment using the Sniffin’ Sticks test and the Taste Strips test for olfactory and gustatory function, respectively. Results: A high percentage of participants reported persistent symptoms consistent with long COVID-19, including fatigue, dyspnea, cognitive impairment, and chemosensory alterations. Olfactory and gustatory dysfunctions were among the most frequent manifestations. Objective assessments confirmed the presence and severity of these deficits, in accordance with data obtained using self-reported questionnaires. Symptom profiles evolved, suggesting possible central nervous system involvement and persistent inflammatory mechanisms. Conclusions: Long COVID-19 is a complex multisystem condition with a significant impact on quality of life. Chemosensory dysfunctions may serve as useful clinical markers for patient monitoring and stratification. Integrating subjective and objective data improves diagnostic accuracy and supports the development of targeted therapeutic strategies.

Diseases doi: 10.3390/diseases14070255

Authors: Margarita Hernández-Mixteco Olga Valenzuela Hanna Baranda-Jiménez Ricardo Soria-Herrera Manuel Carmen Paola Castillo-Juárez Karla Domínguez-González Oscar Villavicencio-Carrisoza Moises León-Juárez Addy Helguera-Repetto Victoria Campos-Peña Eliud Garcia-Montalvo Jorge Cerna-Cortés

Background/Objectives: Depression ranks among the most prevalent mental health disorders worldwide. Numerous studies have linked the C-1019G (rs6295) polymorphism in the serotonin 1A (5-HT1A) receptor gene to increased susceptibility to depression. In this study, sociodemographic variables and clinical characteristics were integrated with targeted genotyping of the C-1019G polymorphism to identify risk factors associated with depressive symptoms in a Mexican cohort. Methods: Sociodemographic and clinical data were collected from 257 volunteers (202 healthy controls, 55 with depressive symptoms). Genotyping for C-1019G was performed using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Sociodemographic variables, clinical characteristics, and genotype frequencies were analyzed relative to Beck Depression Inventory II (BDI-II) scores. Results: BDI scores were significantly lower among males, participants aged < 40 years, unmarried individuals, and those with a high school education (p < 0.05). Females were three times more likely to exhibit depressive symptoms than males (p = 0.004; OR = 3.08). Compared with participants aged < 40 years, those aged 40–65 and >65 years were two (p = 0.026; OR = 2.19) and five times (p < 0.001; OR = 5.71) more likely to report depressive symptoms, respectively. Participants with type 2 diabetes mellitus had twice the odds of depressive symptoms (p = 0.025; OR = 2.38). Odds increased twelvefold among those with diabetes plus arterial hypertension (p < 0.001; OR = 12.25). Among males, the C/C genotype was observed exclusively in controls (p = 0.010). Furthermore, the genotypic distribution of this study population differed from that of European and Asian populations. Conclusions: These findings advance the understanding of depressive symptoms’ multifactorial etiology and may inform targeted screening and prevention strategies.

Diseases doi: 10.3390/diseases14070254

Authors: Andrea Frosolini Simone Benedetti Luigi Angelo Vaira Guido Gabriele Paolo Gennaro

Introduction: The COVID-19 pandemic profoundly disrupted healthcare, prompting adaptations in oncological practices. This systematic review evaluates the pandemic’s impact on the management of non-melanoma skin cancer (NMSC) of the head and neck (H&N) region. Methods: The review was reported according to PRISMA guidelines. Eligible studies compared pre-pandemic and pandemic periods in adult patients treated for head and neck NMSC reporting outcomes related to histological distribution, time to treatment initiation, reconstructive method, and surgical margin status. Risk of bias was assessed using the Newcastle–Ottawa Scale. Random-effects meta-analyses were performed for outcomes with sufficient extractable data. Results: The review comprised five studies involving 1318 cases. The relative distribution of basal cell carcinoma and squamous cell carcinoma did not differ significantly between pre-pandemic and pandemic periods. Time to treatment initiation showed no significant overall change, although heterogeneity was high, indicating substantial variability among healthcare settings. Reconstruction shifted significantly toward primary closure compared with flap reconstruction during the pandemic period (OR 1.90; 95% CI: 1.46–2.47; p < 0.0001). Negative surgical margins were reported in 1119 of 1266 excisions/cases with available data (88.4%), with no significant difference between pre-pandemic and pandemic periods (OR 0.77; 95% CI: 0.46–1.32; p = 0.34). Conclusions: The pandemic was associated with a shift toward simpler reconstructive strategies, particularly increased use of primary closure, likely reflecting attempts to reduce operative complexity and resource use. While short-term oncologic outcomes appeared broadly preserved, long-term functional, aesthetic, and patient-reported outcomes remain insufficiently characterized. Future studies should evaluate these outcomes to better inform crisis-adapted oncologic and reconstructive care pathways.

Diseases doi: 10.3390/diseases14070253

Authors: Hanneke Fanhole Moussonda-Mouele Eldridge Fedricksen Oloumbou Otniel Adjala-Ondémé Jeordy Dimitri Engone-Ondo Christ Eddy Ognari-Ayoumi Moussa Yaro Roseanne Mounanga-Mourimarodi Krist Makosso Ivan Sosthène Mfouo-Tynga Augustin Mouinga-Ondémé

Background/Objectives: Human T-cell lymphotropic virus type 1 (HTLV-1) is an oncogenic retrovirus that infects an estimated 5–10 million people worldwide. In Gabon, despite a high seroprevalence (7.3–8.7%), documented cases of associated pathologies remain rare, suggesting significant underdiagnosis driven by a lack of clinical awareness. This study evaluated the knowledge, attitudes, and practices (KAP) concerning HTLV-1 among Gabonese healthcare professionals. Methods: A descriptive cross-sectional study was conducted among 392 healthcare professionals across four provinces in Gabon using a standardized questionnaire. Bivariate comparisons were performed using chi-square (χ2) and Mann–Whitney U tests, followed by multivariable binary logistic regression to identify independent predictors of HTLV-1 awareness. Results: Overall, 79.9% of the participants had never heard of HTLV-1. Awareness of the virus was critically low among nursing and obstetric staff (7.2%), whereas physicians demonstrated the highest level of knowledge (57.1%). In the multivariable analysis, independent predictors of higher HTLV-1 awareness included being male (aOR = 2.93; 95% CI: 1.60–5.39; p < 0.001), holding a university degree (aOR = 3.43; 95% CI: 1.66–6.89; p < 0.001), and working as a physician (aOR = 2.75; 95% CI: 1.24–6.10; p = 0.013). Conclusions: A critical HTLV-1 knowledge deficit exists among healthcare professionals in Gabon, particularly among frontline nursing staff, which likely explains the low reporting of associated diseases. Integrating HTLV-1 into medical and paramedical curricula, launching targeted educational campaigns, and implementing national screening protocols are urgently required to improve diagnosis and prevent transmission.

Diseases doi: 10.3390/diseases14070252

Authors: Qiao Lian Li-Bing Liang Cai-Qin Wu Yan Zhu Kun-Peng Li

Background: Knee osteoarthritis (KOA) affects over 300 million people globally, yet current therapies face limitations in efficacy and safety. Chitosan, a natural polysaccharide, has shown conflicting evidence in KOA management. This systematic review evaluates chitosan’s clinical effectiveness and defines its optimal application scenarios. Methods: Randomized controlled trials (RCTs) published before the end of November 2024 on chitosan and knee osteoarthritis were systematically retrieved from PubMed, Web of Science, Cochrane Library, EBSCO, PsycINFO, ClinicalTrials.gov, SINOMED, Chinese Medical Journal Network, CNKI, VIP, Wanfang Data, Embase, and SCOPUS. After screening the references, publications meeting the inclusion and exclusion criteria was selected. RevMan5.4 software was used to perform the meta-analysis of the data. Results: A total of 231 articles were retrieved, and 14 RCTs involving 1504 participants were included. For the primary efficacy outcome, pooled analysis of 10 RCTs showed a significantly higher overall clinical response rate in the chitosan group compared with the control group (OR = 5.43, 95% CI = 3.21, 9.18, p < 0.001), with no observed heterogeneity (I2 = 0%). Additionally, meta-analysis of 12 RCTs demonstrated a significant reduction in visual analog scale (VAS) pain scores (MD = −1.06, 95% CI = −1.38, −0.73, p < 0.001) in patients receiving intra-articular chitosan injection. Subgroup analysis of VAS scores showed that pain reduction varied significantly by follow-up duration (I2 for subgroup differences = 62.5%, p = 0.03). Conclusions: Intra-articular injection of medical chitosan shows potential benefits for pain relief and clinical efficacy in patients with knee osteoarthritis, with a low incidence of adverse reactions. Nevertheless, the evidence remains promising but preliminary.

Diseases doi: 10.3390/diseases14070251

Authors: Sally Kempa Thomas S. Weiss Hauke Christian Tews Lukas Prantl Martina Müller Christa Buechler

Background: Lipedema is a chronic disorder that predominantly affects women and is characterized by abnormal subcutaneous adipose tissue accumulation, pain, and vascular dysfunction. However, reliable circulating biomarkers that reflect disease-specific pathophysiology are still lacking. This study investigated serum markers associated with adipose tissue, inflammation, and angiogenesis to further elucidate the pathophysiology of lipedema. Methods: In this cross-sectional observational study, fasting serum levels of adiponectin, chemerin, lipopolysaccharide-binding protein (LBP), proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble CD163 (sCD163), and soluble CD137 (sCD137)—proteins associated with obesity and inflammation—were measured in 23 premenopausal women with lipedema and 23 age-matched healthy premenopausal controls. Serum endostatin levels, an angiogenesis inhibitor, and insulin-like growth factor binding protein 2 (IGFBP2), a potent proangiogenic factor, were also assessed. Results: Patients with lipedema and obese controls had comparable body mass index, glucose, and serum lipid profiles. No significant differences were observed between groups in circulating levels of adiponectin, chemerin, LBP, PCSK9, sCD163, sCD137 and IGFBP2. In contrast, serum endostatin levels were significantly reduced in patients with lipedema (p = 0.038). Additional analyses demonstrated markedly higher endostatin expression in human subcutaneous adipose tissue than in the liver, suggesting that circulating endostatin levels may be related to adipose tissue mass. However, serum endostatin levels were lower in obese compared with normal-weight women (p < 0.001). Conclusion: Lipedema was not associated with altered circulating levels of adiponectin, chemerin, LBP, PCSK9, sCD163, sCD137 or IGFBP2. Reduced serum endostatin levels support a potential role for vascular dysfunction in the pathophysiology of lipedema.

Diseases doi: 10.3390/diseases14070250

Authors: Morgan Uebinger Megan Gremillion Stephanie M. Provenzano Carliss Sampognaro Lindsey Settoon Emma Mayfield Mason Granger Courtlin Wadleigh Ahmed I. Anwar Alan D. Kaye Ammar Husan

Background: Food insecurity (FI), which is defined as limited or uncertain access to sufficient, nutritious food, disproportionately affects low-income populations and has been linked to poor control of chronic diseases including type 2 diabetes mellitus (T2DM) with North Louisiana having one of the highest rates of FI in the United States. The interaction between FI and neighborhood-level socioeconomic disadvantage has not been well characterized in relation to microvascular diabetic complications. Objective: This study aimed to evaluate the relationship between FI, socioeconomic disadvantage, and microvascular complications in patients with T2DM. Methods: A retrospective cohort study of 163 adult patients with T2DM who received care at Ochsner LSU Health clinics in Shreveport and Monroe, Louisiana, between January 2018 and January 2023 were reviewed. FI status, Area Deprivation Index (ADI), a validated measure on neighborhood socioeconomic disadvantage, and microvascular complication outcomes including nephropathy, neuropathy, and retinopathy were obtained from electronic medical records. FI was assessed using the validated two-item Hunger Vital Sign screening tool. Results: The study found that FI alone was not a statistically significant predictor of nephropathy based on microalbumin-to-creatinine ratio (MACR). However, the combination of FI and high ADI (≥7) was significantly associated with neuropathy (p = 0.024) and retinopathy (p < 0.001), particularly among patients with T2DM for more than five years. Additionally, the interaction between FI and high ADI was also found to influence MACR values significantly (p = 0.026), indicating that socioeconomic stressors may exacerbate kidney dysfunction. Conclusions: Food insecurity, coupled with socioeconomic adversity, was associated with an increased risk of microvascular complications in T2DM. These results highlight the importance of integrating FI screening and addressing social determinants of health in high-risk populations. Early identification and targeted interventions could help mitigate disease progression and reduce health disparities.

Diseases doi: 10.3390/diseases14070249

Authors: Dongheng Ma Hinano Nishikubo Tomoya Sano Masakazu Yashiro

Background: Pancreatic ductal adenocarcinoma (PDAC) carries a dismal prognosis, and KRAS and TP53 mutational status is increasingly recognized as both prognostic and therapeutically actionable. Because next-generation sequencing has long turnaround times, high costs, and substantial tissue requirements, we aimed to develop and externally validate a deep-learning framework for inferring KRAS and TP53 mutation status directly from routine hematoxylin-and-eosin (H&E) whole-slide images (WSIs) of PDAC. Methods: A training cohort was assembled from TCGA-PAAD (n = 206) and CPTAC-PAAD (n = 147), and an independent external validation cohort (n = 86) was obtained from Osaka Metropolitan University (OMU) Hospital. We benchmarked 28 model configurations per gene, comprising three pathology foundation models (CONCH-v1.5, CTransPath, and Prov-GigaPath) crossed with nine multiple-instance-learning (MIL) aggregators (ABMIL, CLAM-SB, CLAM-MB, DSMIL, TransMIL, MeanMIL, MaxMIL, AEM, and MIL-Dropout), plus a ResNet-50 + MeanMIL baseline. Performance was evaluated by patient-level five-fold cross-validation (AUC, accuracy, precision, sensitivity, and specificity) and external AUC; attention heatmaps were generated for interpretability. Results: For KRAS, CONCH-v1.5 + MeanMIL achieved the best internal AUC of 0.717 and CONCH-v1.5 + ABMIL the best external AUC of 0.705. For TP53, CTransPath + DSMIL achieved the best internal AUC of 0.668 and CTransPath + MeanMIL the best external AUC of 0.744. Conclusions: H&E-based deep learning can infer KRAS and TP53 mutation status in PDAC with moderate but reproducible discrimination, supporting its potential as a low-cost upstream prescreening tool that triages candidates for confirmatory molecular sequencing and genotype-directed targeted therapy.

Diseases doi: 10.3390/diseases14070248

Authors: Patchareeya Amput Sirintip Kumfu Sirima Wongphon

Background: Positive end-expiratory pressure (PEEP) influences respiratory mechanics, ventilation distribution, and lung aeration. However, comparative responses to incremental PEEP among healthy individuals, cigarette smokers, electronic cigarette users, and individuals with asthma remain poorly understood. This study aimed to characterize differential respiratory responses to incremental PEEP across these populations. Methods: A secondary analysis was conducted using an open-access respiratory physiology dataset obtained from PhysioNet. Eighty adults were included and categorized into four groups (n = 20 per group): healthy controls, cigarette smokers, electronic cigarette users, and individuals with asthma. Airway pressure, respiratory flow, tidal volume, chest circumference, abdominal circumference, and global aeration were evaluated across incremental PEEP levels ranging from 4 to 12 cmH2O. Results: Increasing PEEP significantly affected all respiratory and aeration outcomes (all p < 0.001). Significant Group × PEEP interactions were observed for airway pressure (p < 0.001), respiratory flow (p = 0.009), chest circumference (p = 0.002), and abdominal circumference (p = 0.005), indicating differential physiological responses among groups. In contrast, tidal volume (p = 0.067) and global aeration (p = 0.170) demonstrated similar response patterns across groups despite significant overall PEEP effects. Conclusions: Incremental PEEP significantly influenced respiratory mechanics, thoracoabdominal motion, and lung aeration. Respiratory responses differed among healthy controls, cigarette smokers, electronic cigarette users, and individuals with asthma, suggesting group-specific adaptations to increasing PEEP.

Diseases doi: 10.3390/diseases14070247

Authors: Sonja Jandroković Sania Vidas Pauk Dina Lešin Gaćina Lorena Karla Šklebar Martina Tomić Tomislav Bulum Iva Bešlić Ivan Škegro

Background/Objectives: We aim to determine whether prior cataract surgery affects the intraocular pressure (IOP)-lowering effect of selective laser trabeculoplasty (SLT) in patients with primary open-angle glaucoma (POAG). Methods: This prospective interventional cohort study initially included 92 patients with POAG who were inadequately controlled or intolerant to topical therapy and were treated with SLT. Of these, 84 patients completed all scheduled visits and constituted the final analyzed dataset. Patients were divided into phakic and pseudophakic groups, with cataract surgery performed at least one year before SLT in all pseudophakic eyes. All patients underwent standardized 360-degree SLT by a single specialist. The primary outcome was IOP reduction at one year. Secondary outcomes included percentage IOP reduction and treatment success, defined as ≥20% IOP reduction. Data were analyzed using StatisticaTM 14.0.1.25 (TIBCO Software Inc., Palo Alto, CA, USA, USA). Results: Before SLT, the median IOP was 20.5 mmHg in phakic eyes and 21 mmHg in pseudophakic eyes. One year after SLT, median IOP decreased insignificantly in phakic eyes (4.0 mmHg; p = 0.262), whereas it decreased significantly in pseudophakic eyes (5.5 mmHg; p = 0.004). At one year post-SLT, an IOP reduction of ≥20% was observed in 53.6% of phakic and 72.7% of pseudophakic eyes. Pseudophakic patients were significantly older than phakic patients, as expected, because age-related senile cataract is more common in older individuals, and the groups also differed by gender distribution. This gender imbalance was coincidental and reflected the non-randomized inclusion of POAG patients according to clinical need for SLT rather than predefined matching. In unadjusted analyses, one-year IOP reduction was positively associated with age (p = 0.048), pretreatment IOP (p < 0.001), and prior cataract surgery (p = 0.047). However, after adjusting for age, gender, and baseline IOP in a multivariate sensitivity analysis, prior cataract surgery was not an independent predictor of success; only pretreatment IOP predicted a significant reduction (p = 0.031) in the analysis of 84 eyes. Conclusion: Although pseudophakic eyes showed greater unadjusted IOP reduction after SLT over one year, lens status was not an independent predictor after adjustment for potential confounders. Therefore, the observed pseudophakic advantage should be interpreted as a hypothesis-generating association warranting further research into the effect of pseudophakia on SLT response.

Diseases doi: 10.3390/diseases14070246

Authors: Francisco Alejandro Lagunas-Rangel

Acute myeloid leukemia (AML) is a genetically and biologically heterogeneous hematologic neoplasm that arises from the clonal transformation of hematopoietic progenitor cells. AML cells undergo extensive metabolic reprogramming to sustain proliferation, survival, and adaptation to therapeutic stress. Among these alterations, cholesterol metabolism has emerged as a critical determinant of leukemic cell fitness. AML cells enhance cholesterol biosynthesis, uptake, trafficking, and storage, generating a dynamic network that supports membrane organization, mitochondrial function, oncogenic signaling, and resistance to therapy. Beyond these tumor-intrinsic roles, accumulating evidence indicates that cholesterol and its metabolites actively shape communication between leukemic and immune cells, influencing immune checkpoint expression, inflammatory signaling, and antitumor immune responses within the bone marrow microenvironment. This narrative review examines the mechanisms underlying cholesterol reprogramming in AML and discusses how alterations in cholesterol homeostasis integrate metabolic adaptation with immune regulation. Particular emphasis is placed on the interplay between cholesterol metabolism, leukemic stem cell persistence, therapeutic resistance, and immune dysfunction. Emerging therapeutic strategies targeting cholesterol-related pathways are also considered. Collectively, these findings position cholesterol metabolism as a central interface between tumor-intrinsic biology and immune crosstalk, highlighting its potential as a therapeutic vulnerability in AML.

Diseases doi: 10.3390/diseases14070245

Authors: Flaminia Tomassetti Martina Pelagalli Federico Cortese Alfredo Giovannelli Enrico Maria Carloni Maria Morello Eleonora Nicolai Alessandro Terrinoni Massimo Pieri Sergio Bernardini

Background: Vitamin D is a key regulator of skeletal homeostasis, and hypovitaminosis D is highly prevalent among postmenopausal women, who are at increased risk of osteoporosis, sarcopenia, and related complications. Accurate assessment of serum 25-hydroxyvitamin D [25(OH)D] is therefore essential. However, substantial variability exists among analytical methods, particularly between automated chemiluminescent immunoassays (CLIA) and liquid chromatography–tandem mass spectrometry (LC-MS/MS), the latter considered the reference technique. This study aimed to compare four analytical methods, three CLIA platforms, and LC-MS/MS for measuring circulating 25(OH)D levels in a cohort of menopausal and postmenopausal women. Methods: A total of 425 serum samples from menopausal and postmenopausal women representing the real-world distribution of vitamin D levels in this population were analyzed using three automated CLIA systems and LC-MS/MS. Method comparison, agreement, precision through quality control assessment, total error, and sigma were evaluated. Results: The evaluated CLIA platforms (Abbott, Snibe, and Siemens) showed strong correlation with LC-MS/MS, with r = 0.919, r = 0.978, and r = 0.879. Furthermore, all assays showed excellent precision (CV < 5%), with good-to-acceptable total error (TE) and Sigma-metric performance. Conclusions: In conclusion, these findings demonstrate that while CLIA platforms offer a reliable and precise alternative for routine clinical use, these findings underscore the importance of method selection and result interpretation in the clinical assessment of vitamin D status in postmenopausal women. Furthermore, it highlights the ongoing need to minimize inter-assay variability and ensure consistent vitamin D assessment.

Diseases doi: 10.3390/diseases14070244

Authors: Omar Anwar Saleh Al Nakhebi Răzvan Susan Adriana Mihai Gheorghe Adrian Bumbu Florina Mădălina Mindru Cristian Mornoș Virgil-Radu Enătescu

Background: Traditional cardiovascular risk models often overlook “residual risk” driven by psychopathological factors. This study investigates the exploratory prognostic baseline associations of Type D personality (TDP) and specific symptomatic dimensions with long-term all-cause mortality in patients with coronary artery disease (CAD). Methods: We conducted a retrospective case study based on hospital records evaluating 221 patients with confirmed CAD. Anatomical complexity was quantified via the SYNTAX Score (SS). Psychological profiling utilized the DS14 scale for TDP and the SCL-90 for granular symptoms (depression, anxiety, and hostility). Mortality was analyzed over a mean follow-up of 1026 days using multivariate Cox proportional hazards models. Results: Over a mean follow-up of 1026 days, the overall all-cause mortality rate was 33.0% (n=73). TDP prevalence was 19.0% (n=42) and significantly correlated with higher anatomical complexity (SS: 26.21 vs. 15.49; p<0.001). In the adjusted psychological model, baseline anxiety symptom severity presented an exploratory, borderline relationship with survival (HR = 0.941; p=0.049), with the 95% confidence interval upper bound reaching the null threshold (1.000), suggesting a potential, hypothesis-generating “Anxiety Paradox”. The psychological model demonstrated variations in descriptive validation indices (C-index = 0.624) compared to a baseline model integrating trait metrics and anatomical severity (C-index = 0.527). Significant correlations were confirmed between SS and psychological distress (r=0.493). Conclusions: TDP components and granular psychological tracks show significant baseline associations with coronary anatomical distributions, while anxiety dimensions present an exploratory relationship with long-term survival. Given the lack of adjustment for major clinical determinants of mortality (such as age, comorbidities, or ventricular function), these findings must be interpreted strictly as hypothesis-generating and exploratory.

Diseases doi: 10.3390/diseases14070243

Authors: Tiana Dodd Arpit Sharma Nisar Amin Veysel Tahan Ebubekir Daglilar Nikki Duong

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease (CLD) globally and is closely linked to metabolic risk factors and systemic inflammation. Emerging evidence suggests that vitamin D deficiency may influence MASLD severity and outcomes, though limited real-world data often assess long-term clinical outcomes in MASLD patients stratified by vitamin D status. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network (2006–2025). Adult patients with MASLD were stratified into two cohorts based on serum 25-hydroxyvitamin D levels: normal (≥30 ng/mL) and deficient (<20 ng/mL). Patients with other CLD, malignancy, decompensated cirrhosis, and relevant confounding conditions were excluded. Primary outcomes included all-cause mortality, hospital readmissions, and ICU admissions at 1-year and 5-year follow-up. Results: After propensity score matching, 6959 patients were included in each cohort. Compared with patients with normal vitamin D levels, those with vitamin D deficiency had significantly higher rates of hospital readmissions, ICU admissions, and all-cause mortality at both 1-year and 5-year follow-up. A 1 year, readmissions occurred in 10% vs. 6%, ICU admissions 2.6% vs. 1.2%, and mortality 1.5% vs. 0.5% of patients (p = 0.01). Similar findings were observed at 5 years, with higher rates of readmissions 15% vs. 10%, ICU admissions 4.4% vs. 2.4% and mortality 3.2% vs. 1.3% in the vitamin D-deficient cohort (p = 0.01). Conclusions: Vitamin D deficiency was associated with significantly increased mortality, hospital readmissions, and ICU admissions among patients with MASLD. Our findings suggest that vitamin D status may represent a valuable prognostic indicator in this population. Although the observational nature of this study precluded establishing causality, our results support the consideration of routine assessment of vitamin D levels in patients with MASLD. Further prospective and mechanistic studies are needed to determine whether vitamin D supplementation can improve outcomes in this population.

Diseases doi: 10.3390/diseases14070242

Authors: Tran Cong Ly Suchaorn Saengnipanthkul Phanthila Sitthikarnkha Leelawadee Techasatian Kaewjai Thepsuthammarat Pope Kosalaraksa Rattapon Uppala

Background: While pediatric obesity prevalence is rising, the association between ICD-coded obesity, healthcare resource utilization, and inpatient outcomes in middle-income countries remains poorly quantified. This study examined inpatient diagnostic patterns, resource utilization, and in-hospital mortality among hospitalized pediatric patients with ICD-coded obesity in Thailand’s Universal Coverage scheme during a 9-year period. Methods: We analyzed nationwide inpatient administrative data from January 2015 to December 2023 for children aged 1 month to <18 years. ICD-coded obesity was defined using ICD-10-TM codes recorded as either a principal diagnosis or a comorbidity. Outcomes included length of stay, hospital costs, and in-hospital mortality. Univariable and multivariable regression models were used to estimate associations between ICD-coded obesity and inpatient outcomes, with adjustment for age, sex, region, hospital level, admission year, and disease categories. Results: Among 14,483,566 hospitalized children, 42,168 had ICD-coded obesity. Notably, 95.7% of children with ICD-coded obesity were recorded as a comorbidity rather than the primary reason for admission. Children with ICD-coded obesity as a comorbidity had 156.8% higher median hospital costs. Across all major categories of common acute diseases (respiratory, intestinal, digestive), children with ICD-coded obesity had significantly higher median costs and longer length of stay compared to children without ICD-coded obesity. In regression analyses, ICD-coded obesity remained associated with longer length of stay (adjusted ratio, 1.21; 95% CI, 1.16–1.26; p < 0.001) and higher hospitalization cost (adjusted cost ratio, 1.42; 95% CI, 1.32–1.53; p < 0.001). The association with in-hospital mortality was observed in the unadjusted model but was attenuated after adjustment and was not statistically significant (adjusted odds ratio, 1.14; 95% CI, 0.89–1.45; p = 0.303). Conclusions: In Thailand’s national universal coverage scheme, ICD-coded obesity was associated with greater inpatient resource utilization, especially longer length of stay and higher hospitalization costs. These findings support the need for weight-aware inpatient management and adjusted funding models for hospitals treating this higher-resource-utilization subgroup.

Diseases doi: 10.3390/diseases14070241

Authors: Shubhendu Bajpai Abdullah Sultany Muhammad Sarmad Aleem Sahil Grover Ashraf Ullah Eshal Amir Kevin Carroll Rahul Zain Rewanth Katamreddy Dushyant Singh Dahiya Michelle Bernshteyn Adam Breslin

Background: Respiratory failure (RF) is a frequently fatal complication of chronic liver disease (CLD), yet population-level data on RF-related mortality trends among adults with CLD are lacking. This study characterized temporal trends and demographic disparities in RF-related mortality among U.S. adults with CLD from 1999 to 2024. Methods: Death certificate data were obtained from the CDC WONDER database for adults aged ≥25 years with both RF (ICD-10: J96) and CLD (ICD-10: K70–K76) listed as an underlying or contributing cause of death. Age-adjusted mortality rates (AAMRs) per 100,000 were calculated using the 2000 U.S. standard population. Joinpoint regression identified temporal inflection points and annual percentage change (APC). Results: Among 241,075 deaths, the overall AAMR increased 3.2-fold from 2.237 (1999) to 7.162 (2021) per 100,000, then declined to 6.132 by 2024. Joinpoint analysis identified four segments: moderate increase (1999–2006; APC +2.40%), accelerated increase (2006–2018; APC +5.37%), late acceleration period (2018–2021; APC +13.10%), and post-pandemic decline (2021–2024; APC −4.32%; all p < 0.001). The 2024 AAMR remained 174.2% above baseline. The male-to-female rate ratio narrowed from 2.02 to 1.50, with females showing steeper acceleration (+14.38% vs. +12.36%). American Indian or Alaska Native individuals had the highest AAMRs and the most dramatic surge (APC +26.90%). Rural areas surpassed urban AAMRs by 2020, with steeper post-2007 acceleration (+8.74% vs. +5.51%). The Western U.S. consistently had the highest regional rates. Younger adults aged 25–34 and 35–44 showed 2.96-fold and 2.37-fold increases in crude mortality rates, respectively. Approximately 80% of deaths occurred in inpatient settings. Conclusions: RF-related mortality among U.S. adults with CLD increased more than threefold from 1999 to 2021, with a dramatic surge followed by incomplete decline. Persistent disparities by sex, race/ethnicity, urbanization, and region highlight the need for targeted interventions, including expanded screening for alcohol-associated and metabolic liver disease and improved access to hepatology services in underserved communities.

Diseases doi: 10.3390/diseases14070240

Authors: Marwa Omar

Background/Objectives: The coccidian protozoan Toxoplasma gondii (T. gondii) is among the most prevalent zoonotic parasites worldwide. Nitric oxide (NO) production by macrophages is considered a critical microbicidal mechanism against various intracellular pathogens, including T. gondii. While the role of the inducible nitric oxide synthase isoenzyme (iNOS) has been widely investigated in both acute and chronic T. gondii infections, the specific functions of the neuronal (nNOS) isotype in the antiparasitic immune response, particularly during chronic toxoplasmosis, remain largely uncovered. Hence, this report seeks to bridge the gap regarding the potential participation of nNOS in experimental chronic T. gondii infection. Methods: The study included 56 Swiss albino mice, equally allocated into four experimental groups: (G1) negative control, (G2) infected control, (G3) infected-L-arginine-treated, and (G4) infected-7-Nitroindazole-treated. All groups except (G1) were orally infected with the avirulent (ME49) T. gondii strain. Nine weeks post-infection, all mice were euthanized for parasitological, histopathological, immunohistochemical, and biochemical analyses. Results: The NO donor, L-arginine, induced a significant reduction in the number of T. gondii cysts, together with strong nNOS immunoreactivity in the brain sections of the treated mice. Conversely, the highest parasitic burden was observed following selective nNOS inhibition with 7-Nitroindazole, exacerbating parasite-induced pathology. Conclusions: The neuronal isotype serves as a critical source of NO production during the chronic stage of T. gondii infection, thereby enhancing parasite elimination and contributing to host tissue protection.

Diseases doi: 10.3390/diseases14070239

Authors: Julia Leszkowicz Kinga Miaśkiewicz Marcin Wieczorek Magdalena Dettlaff-Dunowska Agnieszka Szlagatys-Sidorkiewicz

Background: Constipation in children often presents with non-specific symptoms, which can complicate its recognition in the pediatric emergency department (PED). Aim: This study aimed to characterize the clinical presentations, diagnostic context and testing patterns of children discharged with constipation from a tertiary pediatric emergency center. Methods: A retrospective analysis of medical records of patients under 18 years of age was conducted for patients who presented to the PED of a tertiary hospital in northern Poland from 2021–2024 and were ultimately discharged as K59.0 ICD-10 code (constipation). Demographic data, symptoms reported upon admission, and laboratory and imaging tests performed were collected and reviewed. Results: PED visits discharged with ICD-10 code K59.0 accounted for 2.97% of all 34,278 PED visits during study period. Among 1017 patients discharged with ICD-10 code K59.0, only 26.5% reported constipation as their main complaint. The most common complaints were abdominal pain (61.6%), vomiting (14.4%), and urinary symptoms (4.9%). Commonly suspected initial diagnoses were urinary tract infections or acute appendicitis. More complete documentation of constipation-related symptoms showed an exploratory association with less intensive diagnostic testing. Conclusions: Constipation should be routinely considered in children presenting to the PED with abdominal pain, vomiting, urinary symptoms, or rectal bleeding, even when bowel problems are not the main complaint. Structured history taking supported by simple diagnostic tools could help standardize assessment and support patient selection for further testing, although prospective studies are needed to determine clinical outcomes.

Diseases doi: 10.3390/diseases14070238

Authors: Alex Liripa Kwendra Augustin Mouinga-Ondeme Jéordy Dimitri Engone-Ondo Roger Buju Tsedha Justin Byaruhanga Ngona Salomon Batina Agasa Herman Chelo Ngadjole Ivan S. Mfouo-Tynga Zacharie Tsongo Kibendelwa

Background: The fight against HIV in the Democratic Republic of Congo (DRC) is hindered by systemic challenges; notably, limited access to HIV viral load (VL) testing. Achieving VL suppression is the primary global target for eliminating HIV as a public health threat by 2030. This study aimed to determine the rate of VL suppression and identify associated factors among people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in Bunia. Methods: A descriptive and analytical cross-sectional study was conducted among PLHIV receiving care at treatment sites in Bunia over a period of 11 months. Participants were selected using a two-stage sampling approach, consisting of non-random quota sampling followed by simple random sampling. The primary endpoint was the proportion of PLHIV achieving VL suppression, while associated factors were identified using multiple logistic regression analysis. Results: Overall, 603 PLHIV were enrolled, including 180 males (29.9%) and 423 females (70.1%). The median age was 40 years (IQR: 32–48), median duration on ART was 38 months (IQR: 15–91), and VL suppression was achieved by 75% of the participants. While this indicates significant progress, it remains below the UNAIDS 95-95-95 targets. Adherence to antiretroviral therapy (aOR = 139.43; 95% CI: 66.63–291.76; p < 0.001) and being female (aOR = 2.15; 95% CI: 1.02–4.53; p = 0.044) emerged as independent predictors of virological success. Conclusions: Enhancing access to VL testing and optimizing ART adherence support strategies are critical to improving VL suppression rates in Bunia. Addressing these gaps is essential for the DRC to align with the global health objectives.

Diseases doi: 10.3390/diseases14070237

Authors: Shahzaib Chughtai Shofikur Shuhag Daksh Saksena Manum Zaman Muhammad Usman Ghani

Cancer and atherosclerotic cardiovascular disease (ASCVD) represent two of the leading causes of death worldwide. Increasingly, these two are being recognized as biologically related conditions rather than entirely segregated disease states. In addition to traditional risk factors such as aging, smoking, and obesity, chronic inflammation may be a key factor connecting the two illnesses. Endothelial dysfunction, oxidative stress, plaque progression, and thrombosis are all facilitated by inflammatory signaling in ASCVD. Similar pathways are known to contribute to cancer growth and invasion. Emerging epidemiologic data demonstrate increased cancer incidence among patients with cardiovascular disease, while cancer survivors and recipients of cardiotoxic therapies exhibit accelerated vascular disease. This narrative review aims to describe the bidirectional relationship between ASCVD and cancer. Targeting shared pathways using statins, colchicine, canakinumab, IL-6 inhibition, and lifestyle modification may provide dual benefits. Future biomarker-guided trials with integrated cardiovascular and oncologic endpoints are needed to clarify causality and optimize prevention and management.

Diseases doi: 10.3390/diseases14070236

Authors: Severo Vázquez-Prieto Antonio Vaamonde Liste

In recent years, numerous countries have recorded a steady increase in opioid use. Although prescribing practices vary considerably among them, fentanyl is among the most frequently prescribed strong opioids in several European countries and in Spain. In this study, we analyzed the evolution of outpatient fentanyl dispensing in Galicia, Spain, between January 2019 and December 2025, using the Anatomical Therapeutic Chemical Classification/Defined Daily Dose (ATC/DDD) system. We paid particular attention to differences between provinces and explored temporal trends broken down by route of administration (buccal, nasal, sublingual and transdermal). Dispensing data were obtained from the General Sub-directorate of Pharmacy of the Galician Health Service (SERGAS) from the monthly billing database of official prescriptions dispensed in Galician pharmacies and were expressed as defined daily dose per 1000 inhabitants per day (DID). Dispensing rates between provinces were compared using the non-parametric Kruskal–Wallis test, considering a p-value less than 0.05 as statistically significant. We observed an increase in fentanyl use between 2019 and 2021, followed by a systematic decrease during the 2022–2025 period. Significant differences (p < 0.001) were found in the defined daily dose per 1000 inhabitants per day (DID) among the four Galician provinces, and demographic and socioeconomic factors partially explain the observed disparities. Regarding pharmaceutical presentations, transdermal patches were the most frequently used form during the study period. While some limitations should be noted, the results suggest that the observed decrease in fentanyl dispensing in Galicia could be associated with the implementation of the Ministry of Health’s 2021 optimization plan, with a sustained reduction in its dispensing from 2022 onwards. However, it is necessary to maintain pharmacovigilance at the provincial level.

Diseases doi: 10.3390/diseases14070235

Authors: Narcisa Jianu Teodor Nicolae Onea Dana Emilia Movilă Valentina Oana Buda Bianca Tot Adina Nour Silvia Luca Diana Evelyne Buzzi Laurențiu Brăescu Minodora Andor

Background: Osteoporosis is increasingly understood as a complex population health condition shaped by interacting behavioral, metabolic, pharmacological, and healthcare system determinants rather than isolated skeletal risk factors. However, comparative studies integrating these dimensions across distinct healthcare and sociocultural settings remain scarce. We aimed to characterize cross-national differences in osteoporosis-related risk clustering between Romanian and Tunisian adults using an integrative multidimensional framework. Methods: We performed a comparative cross-sectional analysis of harmonized data from two pharmacy-based studies conducted in Romania and Tunisia, including adults aged ≥ 40 years (n = 349). Osteoporosis-related knowledge, lifestyle and metabolic risk factors, pharmacological exposures, preventive behaviors, and treatment patterns were assessed. Multivariable regression and mediation analyses were used to identify independent predictors of screening uptake and to evaluate the relationship between knowledge and preventive behavior. An exploratory cumulative preventive deficit score was used to estimate overall preventive burden within the pharmacy-based study sample. Results: Romanian participants demonstrated significantly higher osteoporosis knowledge than Tunisian participants (8.90 ± 2.20 vs. 7.83 ± 2.99; p < 0.001); however, knowledge was not independently associated with Dual-Energy X-ray Absorptiometry (DXA) uptake and did not mediate country-related differences in screening behavior. Compared with the Romanian cohort, the Tunisian cohort exhibited lower DXA screening rates (11.2% vs. 22.8%; p = 0.005), lower vitamin D supplementation (11.9% vs. 38.6%; p < 0.001), greater sedentary behavior, and a significantly higher cumulative preventive deficit burden (3.39 ± 1.08 vs. 2.77 ± 1.26; p < 0.001). Medication-related osteoporosis risk was also greater in Tunisia, particularly due to markedly higher corticosteroid exposure (7.5% vs. 0.5%; p = 0.002). Despite this less favorable preventive profile, the treatment gap among participants with diagnosed osteoporosis was significantly lower in Tunisia than in Romania (4.8% vs. 42.9%; p = 0.003). Conclusions: Distinct but convergent osteoporosis-related risk patterns were identified across the two populations, suggesting that osteoporosis vulnerability emerges through context-specific clustering of behavioral, pharmacological, and healthcare-access determinants rather than through isolated risk factors alone. The dissociation between knowledge and preventive behavior highlights the limited impact of awareness-based strategies when structural barriers remain unaddressed. These findings support a shift toward integrated, population-tailored osteoporosis prevention models that incorporate healthcare-system, medication-related, and behavioral determinants, in addition to conventional educational approaches.

Diseases doi: 10.3390/diseases14070234

Authors: Cristiana Grapa Tudor Mocan Daniel Leucuta Rares Craciun Lavinia-Patricia Mocan Miroslaw T. Kornek Emil Mois Nadim Al Hajjar Florin Graur Teodora Mocan Zeno Sparchez

Background and Aims: To develop an inclusive, predictive framework for hepatocellular carcinoma patients, beyond what the Barcelona Clinic Liver Cancer (BCLC) staging system captures alone, non-invasive scores have emerged as potential contributors. Among them, the CRAFITY score (CRP and AFP in ImmunoTherapY), originally developed for immunotherapy-treated HCC populations, and the Platelet-Albumin-Bilirubin (PALBI) score have shown promising prognostic performance in selected cohorts. Likewise, the macrotrabecular-massive (MTM) histological subtype has been identified as a strong independent predictor of tumor recurrence, particularly in surgical series; whether it retains the prognostic significance in a mixed-treatment cohort remains unexplored. We aimed to evaluate the independent prognostic performance of CRAFITY and PALBI across all HCC treatment modalities, determine MTM prevalence and assess whether histological subtyping adds prognostic value beyond these readily available clinical scores. Methods: The study included 500 consecutive, pathologically confirmed HCC patients at a tertiary gastroenterology center in Cluj-Napoca, Romania. MTM subtype was defined as >50% macrotrabecular architectural pattern on histological review by two senior pathologists. Overall survival (OS) and recurrence-free survival (RFS) were assessed by Kaplan–Meier analysis and multivariable Cox regression. A random survival forest (RSF) model was constructed to identify dominant prognostic predictors. Results: MTM was identified in 14 patients (2.8%) and did not independently predict OS (HR 0.94, 95% CI 0.49–1.81, p = 0.85) or recurrence (OR 3.78, p = 0.116). In this heterogeneous cohort spanning multiple treatment modalities, CRAFITY (HR 1.68, 95% CI 1.42–1.98, p < 0.001) and PALBI (HR 1.51, 95% CI 1.22–1.87, p < 0.001) were strong independent predictors of OS after BCLC stage. RSF analysis confirmed this hierarchy with a C-index of 0.734. Conclusions: CRAFITY and PALBI demonstrated strong, independent predictive performance for a large, underrepresented, heterogenous Eastern European HCC cohort. In contrast, MTM subtype showed limited prognostic value in this cohort. The results support the broader applicability of CRAFITY beyond its original immunotherapy context and underline the low prevalence of MTM subtype.

Diseases doi: 10.3390/diseases14070233

Authors: Rehab Abdullah Alanazi Abir Shiban Alenezi Raghad Jamal Aldhafeeri Razan Fawaz Alanazi Aryam Hussain Alshammari Ghadah Dhiyab Alanazi Mohammed Khalaf Alenzi Areen Amer A. Alenezi Baraah Abu Alsel Fathia Ahmed Mersal Eslam K. Fahmy Safya E. Esmaeel Manal S. Fawzy

Background/Objectives: Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide. Individuals with hypertension (HTN) and type 2 diabetes mellitus (T2DM) are at particularly high risk; however, awareness of cardiovascular risk within the broader community and among high-risk subgroups remains suboptimal. This study aimed to assess CVD risk awareness and its correlates among adults in the Northern Border Region of Saudi Arabia, with a particular focus on individuals with HTN and/or T2DM. Methods: A descriptive, quantitative, cross-sectional survey was conducted among adults aged 18–50 years residing in the Northern Border Region of Saudi Arabia. An anonymous online questionnaire was distributed via social media between October 2025 and January 2026. The survey incorporated a 22-item scale assessing HTN knowledge, T2DM knowledge, and CVD risk awareness (Heart Disease Fact items). Participants were categorized according to self-reported diagnosis (no diagnosis, HTN, T2DM, or both). Descriptive statistics, non-parametric tests, and multivariable regression analyses were used to evaluate knowledge scores and predictors of CVD risk awareness. Results: A total of 458 participants completed the survey. Overall knowledge was moderate (mean 12.40/22; 56.4%), with relatively higher scores for HTN (73.2%) and T2DM knowledge (68.8%), but markedly lower CVD risk awareness (30.8%). Fewer than half of participants correctly answered key CVD items, particularly those related to asymptomatic disease progression and lipid (HDL) concepts. Only 21.6% achieved good awareness (≥75%). In multivariable analyses, higher educational level, positive family history of cardiometabolic disease, and the presence of HTN and/or T2DM were independent predictors of higher awareness. Conclusions: CVD risk awareness is suboptimal among adults in the Northern Border Region, including those with established HTN and T2DM. The observed gap between disease-specific knowledge and CVD risk awareness highlights the need for targeted, structured risk communication strategies in primary care, particularly for individuals with lower educational attainment and no family history of CVD.

Diseases doi: 10.3390/diseases14070232

Authors: Nadeem Pervez Benazir Mir Khan Sharjeel Usmani Hasan Al-Sayegh Iqbal Al Amri Mahmoud Alfishawy Sercan Yilmaz Sulaiman Al Saadi Munjid Al Harthy Javeria Ahmed Zahid Almandhari

Background/Objectives: Metastatic prostate cancer is increasing in the Gulf Cooperation Council countries. This study presents a multimodal treatment protocol incorporating radiotherapy to primary and metastatic sites, guided by PSMA PET/CT, combined with systemic therapy for non-metastatic pelvic node-positive and de novo low-volume metastatic prostate cancer. Methods: We conducted a retrospective cohort study of patients treated with radical radiotherapy doses (68 Gy/25 Fr or 78 Gy/39 Fr) to the prostate gland and gross pelvic disease, and SBRT (35–40 Gy/5 Fr) to distant bone metastases. All patients received LHRH agonists ± abiraterone/prednisone or enzalutamide. Results: Twenty-four consecutive patients were analyzed. The median age was 70.1 years (IQR, 65.7–77.7), the median baseline PSA was 27.9 ng/mL (IQR = 19.7–53.8), and median follow up was 24 months (IQR = 20.4–31.2). Clinical staging was cT3b in (46%), cT2 in (25%), cT4 in (17%), cT3a in (13%) of patients. Pelvic nodal involvement (cN1) was present in 91.7% of patients, while 54.1% had metastatic disease. Treatment was well tolerated. Acute toxicity was predominantly grade 1 genitourinary (GU) toxicity, occurring in 87.5% of patients, with grade 2 GU toxicity observed in 8.2% and no acute gastrointestinal (GI) toxicity. Late toxicity remained minimal, with grade 1 and grade 2 GU toxicity reported in 45.8% and 4.2% of patients, respectively, and no late GI toxicity. Mild systemic treatment-related toxicities were reported in 25% of patients, including sexual dysfunction, hypokalemia, muscle weakness, osteoporosis and depression/anxiety. At the six-month follow-up PSMA PET/CT assessment, 85.7% achieved a complete metabolic response, and 14.2% achieved a partial response. Biochemically, 75% of patients achieved undetectable PSA levels (<0.01 ng/mL), with all patients achieving a PSA nadir < 0.2 ng/mL. Conclusions: This first, hypothesis-generating real-world experience from the GCC, suggests that an integrated approach combining systemic therapy with metastasis-directed therapy is feasible. Prospective randomized studies are required to validate these results.

Diseases doi: 10.3390/diseases14070231

Authors: Yuting He Xintian Huang Kaiyi Rong Yongxiang Hong Fanzhuoran Lou Bowen Zheng Weijuan Tan Quan Chen Huibo Shi Li Xiao

Background/Objectives: Reducing corticosteroid exposure has become an important objective in the management of chemotherapy-induced nausea and vomiting (CINV), given the dose-related toxicity of dexamethasone (DEX). This prospective phase III randomized (LD-NEPA: low-dose dexamethasone plus netupitant/palonosetron) study evaluated whether a reduced dose of 5 mg DEX could maintain antiemetic efficacy when combined with NEPA in patients receiving highly or moderately emetogenic chemotherapy (HEC/MEC). Methods: Adult patients were randomly assigned (1:1) to receive NEPA with either 5 mg DEX (5D group) or 8 mg DEX (8D group). Among 186 randomized patients, 180 were included in the analysis (89 in the 5D group and 91 in the 8D group). The primary endpoint was the complete response rate (CRR; no emesis and no rescue medication use) during the 0–168 h period. Secondary endpoints included phase-specific CRR, total control rate (TCR), complete control rate (CCR), daily incidence of nausea and vomiting, and safety outcomes. Results: The overall CRR was 78.7% in the 5D group and 70.3% in the 8D group. The between-group difference was 8.4% (95% CI: −1.5% to 19.0%), demonstrating the reduced-dose regimen was non-inferior, with the lower bound exceeding the prespecified −15% margin. Consistent results were observed across secondary endpoints. Treatment-related adverse events were mostly grade 1–2 and occurred with broadly comparable frequencies between the two groups. Conclusions: A single lower dose of 5 mg DEX is noninferior to an 8 mg dose combined with NEPA for preventing 168 h nausea and vomiting of diverse HEC/MEC, offering comparable efficacy while reducing corticosteroid exposure.

Diseases doi: 10.3390/diseases14070230

Authors: Shuaibu Abdullahi Hudu Muhannad Alruwaili Mohamed Soliman Emad A. Morad Ghusun M. Alhazimi Abdulgafar Olayiwola Jimoh

Background: Messenger RNA (mRNA) vaccines have emerged as a versatile platform beyond SARS-CoV-2, with expanding applications in infectious diseases and oncology. However, comprehensive evidence synthesis of non-SARS-CoV-2 mRNA vaccines remains limited. Methods: This systematic review followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD420261323500). MEDLINE, Embase, Web of Science, Scopus, ClinicalTrials.gov, and WHO ICTRP were systematically searched for studies published between 1 January 2000 and 28 February 2026. Eligible studies included phase I–III clinical trials and in vivo preclinical studies evaluating non-SARS-CoV-2 mRNA vaccines. Two reviewers independently screened studies, extracted data, and assessed risk of bias using RoB 2, ROBINS-I, and SYRCLE tools. Findings were synthesized narratively because of substantial heterogeneity. Results: A total of 40 studies met the eligibility criteria and were included in the review, comprising 20 clinical studies and 20 preclinical studies. Advanced clinical programs targeted influenza and respiratory syncytial virus (RSV), with phase III trials displaying seroconversion rates above 70% with good safety profiles. Preliminary phase I studies for HIV, cytomegalovirus, rabies, and personalized cancer mRNA vaccines showed promising humoral and cellular immune responses. Preclinical studies showed strong antibody and T-cell responses against malaria, tuberculosis, Group B Streptococcus, and Zika virus. Most adverse events were mild to moderate, while serious vaccine-related adverse events were uncommon. Conclusions: Non-SARS-CoV-2 mRNA vaccines demonstrate substantial translational potential across infectious disease and oncology applications. Although the vaccine candidates have demonstrated promising immunogenicity and safety, most are in the early stages of development. This highlights the need for large trials, long-term safety follow-up and better global representation.

Diseases doi: 10.3390/diseases14070229

Authors: Ioana Luca Laura Bleotu Oana Gabriela Falup-Pecurariu

Background: Influenza infections have reached an approximate number of one billion cases annually in the general population. Hospitalization due to this infection is associated with high morbidity, and a proportion of hospitalized children may require ICU admission. In the United States of America, one in five children hospitalized due to influenza requires transfer to the intensive care unit (ICU). The real burden of this disease is not accurately known, especially for the pediatric population. Objective: The objective of this study was to define the characteristics of influenza-associated complications in pediatric patients hospitalized at a tertiary hospital in Brasov, Romania. Methods: This was an observational, retrospective study that gathered 258 influenza-infected patients aged from 0 up to 18 years old, hospitalized during the period from 1 January 2020 to 31 December 2025 at the Children’s Hospital of Brasov (a single-center study, but in a tertiary unit). The complications from this disease were categorized into respiratory, hematological, musculoskeletal, renal, ENT, cutaneous, rheumatological, and bacterial superinfections. Results: The patients were stratified according to their influenza type (A or B) and length of hospital stay. The length of stay was categorized as 0–4 days, 5–10 days, or >10 days. No significant association was observed between the influenza type and admission duration (χ2 = 2.185, df = 2, p = 0.3354). The most frequent complications were respiratory—bronchiolitis and pneumonia (22.8%)—followed by hematological (13.5%). Conclusions: The length of stay did not differ significantly between patients with influenza A and those with influenza B in the selected sample. The most common complications were respiratory, hematological, ENT, and neurological.

Diseases doi: 10.3390/diseases14070228

Authors: Piotr Żarczyński Patrycja Brzóska-Ritter Maciej Haberka

Background: Cardiovascular (CV) risk estimation is usually based on the assessment of classic risk factors and the extent of coronary artery stenosis. However, a substantial rate of acute coronary syndromes (ACS) and sudden cardiac deaths (SCD) is observed in patients with high-risk atherosclerotic plaques (HRP), even in the absence of significant stenosis. Therefore, this study aimed to evaluate the predictive value of traditional clinical risk factors for the presence of HRP in patients scheduled for coronary computed tomography (CCT). Methods: This single-center study included 123 patients undergoing CCT for suspected coronary artery disease (CAD). Atherosclerotic plaque morphology (HRP) and the degree of coronary artery stenosis (CAD-RADS categories) were assessed in all the patients. CV risk factors, including LDL serum levels and CT Calcium score (CS), were analyzed. Results: The study cohort was mostly males (54.5%), with an average age of 60.40 ± 12.45 years and typical risk factors: hypertension (70%), diabetes (22%), obesity (30%), and smoking (20%). Most patients (88%) were found to have coronary atherosclerosis with nonobstructive disease (CAD-RADS 1–2) in 39% of patients. HRP was confirmed in over one-fifth of the participants (22%), with half of the patients in the CAD-RADS 2 category. There were no differences in CV risk factors between patients with and without HRP in CCT. No significant clinical predictor of HRP in CCT was identified. Conclusions: CV risk factors do not predict HRP in CCT, which may underestimate the real risk of ACS and SCD.

Diseases doi: 10.3390/diseases14070227

Authors: Ummi Maimunah Andrio Palayukan Juniastuti Brahmana Askandar Tjokroprawiro Muhammad Miftahussurur

Background: A complex interplay between viral activity and host immune responses drives the progression of liver fibrosis in chronic hepatitis B. The T helper 17 (Th17) immune pathway, which produces the pro-inflammatory cytokine interleukin-17A (IL-17A), has been implicated in hepatic fibrogenesis. However, the relationship between IL-17A levels, IL-17A G197A (rs2275913) gene SNP, and the degree of liver fibrosis across different phases of the natural history of chronic hepatitis B remains insufficiently explored. Methods: This study employed an analytical observational design with a cross-sectional approach in treatment-naïve patients with chronic hepatitis B. The degree of liver fibrosis was assessed using liver elastography. IL-17A (rs2275913) gene SNP was analysed using Real-Time PCR, while serum IL-17A levels were measured using enzyme-linked immunosorbent assay. Statistical analyses included Spearman’s correlation, the contingency coefficient, the Chi-square test, the Kruskal–Wallis test, and the Mann–Whitney test, with a significance level set at p < 0.05. Results: A total of 76 patients with chronic hepatitis B were included in this study. The phase of disease progression was significantly associated with the degree of liver fibrosis (p = 0.016). Median IL-17A levels increased in parallel with fibrosis severity (p = 0.003), with a particularly significant association observed during the R phase (p = 0.002). However, no significant association was found between the IL-17A G197A (rs2275913) gene SNP and either liver fibrosis severity or serum IL-17A levels. Conclusions: Elevated serum IL-17A levels were associated with greater liver fibrosis severity, particularly during the reactivation phase of chronic hepatitis B. These findings suggest a potential relationship between IL-17A-mediated immune responses and liver fibrosis in patients with chronic hepatitis B.

Diseases doi: 10.3390/diseases14070226

Authors: Sonia Roxana Burtic Bogdan Florin Capastraru Panche Taskov Daian Ionel Popa Codrina Mihaela Levai Livia Stanga Melania Lavinia Bratu Adelina Maria Jianu

Background: Recovery after major head-and-neck reconstruction extends beyond flap survival and wound closure, involving swallowing, psychological adaptation, body image, and overall quality of life. Integrated multidimensional assessments remain limited in routine reconstructive outcomes research. Aim: The aim of this study was to characterize and compare six-month multidimensional recovery—clinical, functional, nutritional, psychological, and body-image outcomes—between microvascular free-flap and regional pedicled-flap reconstruction and to identify factors that stratify risk for persistent functional and psychosocial impairment. Methods: We conducted a single-center prospective cohort study at the “Victor Babeș” University of Medicine and Pharmacy, Timișoara, Romania, enrolling 87 adults undergoing major reconstructive surgery after ablative treatment of head-and-neck defects (52 microvascular free flaps; 35 regional pedicled flaps). Patients were assessed at baseline and 6 months using the SF-36, WHOQOL-BREF, Body Image Scale (BIS), HADS, PHQ-9, GAD-7, Functional Oral Intake Scale (FOIS), speech intelligibility, and PEG/tracheostomy dependence. Results: At 6 months, most SF-36 and WHOQOL-BREF domains improved with moderate effect sizes (d = 0.3–0.7; all p ≤ 0.009), and body image distress decreased significantly (ΔBIS −2.9 ± 4.6; p < 0.001), whereas social functioning showed no robust gain (p = 0.098; not surviving false-discovery-rate correction). Pedicled reconstruction was associated with higher PEG dependence (37.1% vs. 9.6%; p = 0.005) and worse FOIS (4.7 ± 1.4 vs. 5.6 ± 1.2; p = 0.003). Major complications were linked to blunted or worsening psychological trajectories and a threefold higher rate of clinically significant depression (HADS-D ≥ 11: 66.7% vs. 18.7%; p = 0.001). In a reduced four-predictor multivariable model, pedicled flap (aOR 4.6), adjuvant radiotherapy (aOR 2.8), major complication (aOR 3.3), and lower baseline FOIS (aOR 0.5 per point) were independently associated with PEG dependence (optimism-corrected AUC 0.79). Clustering identified three recovery phenotypes—functional/emotional responders, psychological/body-image responders, and global slow recovery—with significantly different PEG rates (5.9%, 21.4%, 40.0%; p = 0.006). Exploratory mediation analysis suggested that the association between reconstruction technique and mental quality-of-life recovery was partly statistically accounted for by swallowing and body-image improvement. Conclusions: Recovery after major head-and-neck reconstruction is multidimensional and heterogeneous. Baseline swallowing function, reconstruction technique, radiotherapy, and major complications jointly stratify risk for persistent functional and psychosocial impairment, supporting risk-adapted multidisciplinary rehabilitation and early psycho-oncologic screening.

Diseases doi: 10.3390/diseases14070225

Authors: Noor Albusta Mohamed Abdulla Ali Bosta Rehab Almarzooq

Background/Objectives: Functional vulnerability may identify older adults hospitalized with Crohn’s disease flares who are at increased risk for adverse outcomes, but its prognostic significance in this setting remains incompletely defined. We evaluated the association between administratively defined functional vulnerability, identified using administrative diagnostic codes, and short-term clinical outcomes among adults aged ≥65 years hospitalized with Crohn’s disease flares. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Research Network through February 2026. Functional vulnerability was identified using ICD-10-CM codes for frailty, sarcopenia, cachexia, abnormal weight loss, muscle weakness, gait/mobility abnormalities, or reduced mobility within 12 months before or during the index hospitalization. Patients coded only for nonspecific weakness or fatigue were excluded from the functional vulnerability cohort. Patients underwent 1:1 propensity score matching using demographic, comorbidity, Crohn’s disease-related, medication, nutritional, and laboratory variables. The primary outcome was 30-day all-cause mortality. Results: Among 18,420 eligible patients, 2846 met criteria for functional vulnerability, and 15,574 did not. After matching, 2720 patients remained in each cohort. Functional vulnerability was associated with higher 30-day mortality (RR 1.61, 95% CI 1.21–2.14), 90-day mortality (RR 1.40, 95% CI 1.14–1.72), bowel surgery (RR 1.29, 95% CI 1.07–1.56), sepsis (RR 1.41, 95% CI 1.18–1.68), acute kidney injury (RR 1.26, 95% CI 1.10–1.44), ICU admission (RR 1.32, 95% CI 1.13–1.55), TPN use (RR 1.47, 95% CI 1.20–1.79), and 90-day readmission (RR 1.17, 95% CI 1.07–1.29). Functionally vulnerable patients also had longer hospital stays (8.9 vs. 6.7 days; mean difference 2.2 days, 95% CI 1.9–2.5). Conclusions: Administratively defined functional vulnerability identified through diagnostic coding was associated with worse short-term outcomes among older adults hospitalized with Crohn’s disease flares. Although functional vulnerability is a recognized predictor of adverse outcomes across hospitalized populations broadly, these findings quantify its prognostic significance specifically in Crohn’s disease flare hospitalizations and suggest that functional vulnerability may identify a high-risk geriatric IBD phenotype that could benefit from early multidisciplinary assessment, nutritional optimization, rehabilitation planning, and post-discharge care coordination.

Diseases doi: 10.3390/diseases14070224

Authors: Maria L. Perepechaeva Alevtina Y. Grishanova Valentin A. Vavilin

The respiratory system is directly exposed to various environmental factors, and specifically allergens and environmental pollutants, which are ligands/agonists of the aryl hydrocarbon receptor (AhR) and promote chronic lung diseases in humans. AhR, a ligand-activated transcription factor, is involved in the metabolism of xenobiotics, assigning their carcinogenic and toxic effects, and is also involved in normal homeostasis, organogenesis, and immune system function. Exogenous and endogenous AhR ligands are both high-molecular-weight compounds with a planar structure and low-molecular-weight compounds of diverse chemical structures. After entering the cell, the ligands bind to AhR and induce the activation of signaling cascades. The lung immune system responds to pathogens and environmental toxins first with a pro-inflammatory innate immune response, and then with an anti-inflammatory adaptive immune response. An imbalance between these immune systems may have an effect on the course of the disease. Activation of AhR by exogenous or endogenous ligands can affect this balance and lead to dysregulation of the immune response, leading to inflammatory complications in the lungs. Individual features of AhR expression or components of the AhR-dependent signaling pathway may also play a role in the superposition of the functions of these two links of immunity. This review summarizes advances in the comprehension of AhR’s role in immunomodulation and inflammatory responses in the lungs following data in experimental rodent models, in vitro studies utilizing lung structural cells and isolated immune cell lines, and humans. The molecular mechanisms of AhR’s regulation of immunity and inflammation and the potential of AhR as a therapeutic target for inflammatory lung disease are also considered.

Diseases doi: 10.3390/diseases14070223

Authors: Fatouma Mohamed Abdoul-Latif Rohit Kumar Yahya Ali Ismael Houda Mohamed Ali Merito Saber Ali Ahmed Reetu Yadav Pannaga Pavan Jutur Arpana Vibhuti

Brucellosis and tuberculosis (TB) are chronic infectious diseases of international public health importance, with developing countries being most affected. The diagnosis of brucellosis and tuberculosis co-infection remains challenging because both diseases present with overlapping nonspecific clinical manifestations, such as prolonged fever, fatigue, and weight loss, and elicit similar cell-mediated immune and inflammatory responses, which can complicate differential diagnosis, particularly in endemic regions. Recently, it has been shown that chronic infections affect cell stress pathways such as oxidative stress and telomere function. The current literature review provides an overview of the relationship between brucellosis and TB at a molecular level, focusing on telomere biology, oxidative stress and the mechanisms of antimicrobial resistance. Due to chronic immune response in brucellosis and TB patients, an increase in reactive oxygen species (ROS) levels is observed, leading to DNA damage and subsequent telomere shortening and alteration of telomerase activity. These alterations might be responsible for immune senescence, weakened defense response and persistent infection. In addition, different methods of drug resistance have been discovered among brucellae and mycobacteria, such as mutation in target sites, efflux systems and intracellular persistence, making their eradication difficult. Finally, the potential role of telomere-related genes and biomarkers of oxidative stress in diagnosis and prognosis is also highlighted. Insights into these interrelated pathways would allow us to have a better understanding of host–pathogen interactions and hence offer a possible means of developing new strategies in the fight against co-infection by finding new biomarkers.

Diseases doi: 10.3390/diseases14060222

Authors: Antonia Ioana Vasile Andreea Arsene Ioana Raluca Petru

Background: Medication adherence is a major determinant of treatment effectiveness in psychiatric care and is influenced by patients’ attitudes toward medication and beliefs about treatment. Objective: This study aimed to evaluate medication adherence, drug attitudes, and beliefs about medicines, and to examine their relationships in the study population. Methods: A total of 300 participants were assessed using the Medication Adherence Rating Scale (MARS), Drug Attitude Inventory-10 (DAI-10), and Beliefs about Medicines Questionnaire (BMQ-General and BMQ-Specific). Descriptive statistics, independent-samples t-tests, Pearson correlation analyses, and multiple linear regression were performed. Results: The mean DAI-10 score was 3.57 ± 3.44, indicating an overall positive attitude toward medication, although 27.33% of participants had neutral or negative attitudes. The mean MARS score was 6.27 ± 2.24, suggesting moderate adherence. Mean BMQ-General and BMQ-Specific scores were 21.70 ± 5.81 and 31.64 ± 6.13, respectively. Significant gender differences were found across all scales. DAI-10 was positively correlated with MARS, while BMQ-General was negatively correlated with MARS. Multiple regression showed that DAI-10, BMQ-General, and BMQ-Specific significantly predicted MARS scores, explained 30.8% of variance after adjustment. Conclusions: Medication adherence was moderate and was significantly associated with treatment attitudes and beliefs about medicines. The findings support multidimensional assessment and targeted interventions addressing both positive attitudes and negative medication beliefs.

Diseases doi: 10.3390/diseases14060221

Authors: Moshawa Calvin Khaba Morongwa Dikotope Thato Nkwagatse Ramokone Maphoto Thandekile Manzini Khomotso Maaga Ndivhuho Agnes Makhado

Background: Infectious diseases remain a leading cause of mortality in South Africa, compounded by a high HIV prevalence. This study aimed to delineate the spectrum and clinicopathological characteristics of fatal infectious diseases through a postmortem audit to inform clinical practice and public health strategy. Methods: A retrospective, cross-sectional descriptive study was conducted on all autopsies with a final cause of death attributed to infectious disease at a National Health Laboratory Service, in Northern Pretoria, Gauteng, South Africa, from 2012 to 2021. Using the Systematised Nomenclature of Medicine Clinical Terms (SNOMED) code and word search engines codes, 55 cases were identified. Data on demographics, clinical presentation, HIV status, antiretroviral therapy (ART), comorbidities, and final autopsy diagnosis were extracted from the laboratory information system. Histological confirmation was performed using standard stains. Descriptive statistical analysis was conducted using STATA-18. Results: The cohort (n = 55) had a median age of 31 years (IQR 19–45) and was predominantly female (67%). HIV prevalence was 35%, with 68% of those on ART. The leading cause of death was multilobar pneumonia (36%), followed by bronchopneumonia (22%). AIDS-defining illnesses were present in 27% of cases, with disseminated tuberculosis being the most common (46%). Septic shock was identified in 18% of decedents. A significant proportion (60%) of the cohort was HIV-negative. Conclusions: This autopsy series reveals a high burden of fatal community-acquired pneumonias and HIV-associated opportunistic infections, with a notable proportion of deaths occurring in HIV-negative individuals. The findings underscore diagnostic gaps and highlight the critical role of autopsy in accurate mortality surveillance, advocating for enhanced antemortem diagnostic protocols and targeted public health interventions.

Diseases doi: 10.3390/diseases14060220

Authors: Alessia Di Salvo Chiara Motisi Matteo Bulati Letizia Scola Carmela Rita Balistreri

Background and Objectives: Blood group antigens are well known for their importance in transfusion medicine and transplant compatibility; however, their biological role extends beyond these functions and includes associations with the risk of several diseases. In this study, we investigated the relationship between ABO blood groups and the circulating levels of 73 different molecules. Patients and Methods: Fifty-six healthy donors were enrolled, including 24 individuals with blood group O, 19 with blood group A, and 13 with blood group B. Blood samples were collected and analyzed in a single laboratory using Luminex fluorescent bead-based assay panels to determine the concentrations of 73 circulating molecules. Depending on data distribution, ANOVA or Kruskal–Wallis tests and Student’s t-test or Kolmogorov–Smirnov tests were applied to identify significant differences among groups. Associations were further assessed by binary logistic regression analysis. Results: Subjects with blood group A showed significantly higher circulating levels of IL-1R1, IL-13, IL-23, PDGF-BB, VEGF-A, VEGF-D, soluble VEGF-R2 (KDR), soluble VEGF-R3 (FLT-4), VLA-4, CD141, MMP-1, syndecan-1 (SDC-1), and mannose-binding lectin (MBL) compared with the other blood groups. In contrast, individuals with blood group B exhibited significantly higher levels of IL-22, IL-23, PDGF-BB, CD62P (P-selectin), and amyloid β1–42. Several significant associations were identified by logistic regression analysis. Conclusions: Our findings indicate that ABO blood groups are associated with distinct circulating molecular profiles, supporting the existence of biological differences that may contribute to variations in disease susceptibility among individuals with different blood types. Nevertheless, given the exploratory’s nature and limited sample size of this study, further investigations are required to validate these findings, confirm the observed associations, and clarify their potential clinical implications.

Diseases doi: 10.3390/diseases14060219

Authors: Anas Khaleel Sara Khaleel Ruqaya Mohammed Ahmed Ahmad Al Athamneh Nour Amin Elsahoryi Ahmed S. A. Ali Agha

Background/Objectives: Liposarcoma is a heterogeneous soft tissue sarcoma in which anthracycline-based chemotherapy, including doxorubicin, remains a cornerstone of treatment for advanced disease. However, variable and often limited therapeutic responses highlight the need for improved understanding of disease-associated transcriptional adaptation under chemotherapeutic stress. In this study, a bioinformatics-driven transcriptomic analysis was performed to characterize gene expression alterations associated with doxorubicin treatment in liposarcoma using publicly available data from the Gene Expression Omnibus (GSE12972). Results: Differential expression analysis identified 365 significantly altered genes, including 164 upregulated and 201 downregulated transcripts in treated samples compared with untreated controls. Functional interpretation using Ingenuity Pathway Analysis identified transforming growth factor beta 1 (TGFB1), tumor necrosis factor (TNF), and SMARCA4 as prominent predicted upstream regulators associated with transcriptional programs related to extracellular matrix remodeling, inflammatory and immune modulation, epithelial-to-mesenchymal transition-like states, and chromatin-mediated transcriptional plasticity. Enriched canonical pathways included Liposarcoma tumor microenvironment-associated signaling and fibrosis-related pathways, reflecting stromal activation and immune-related transcriptional changes. Notably, fibroblast growth factor 1 (FGF1) emerged as a supportive regulatory node linked to survival- and anti-apoptotic gene expression patterns. Conclusions: Collectively, these findings provide a disease-oriented, cross-subtype systems-level view of the transcriptional changes associated with doxorubicin treatment in liposarcoma. This work is intended as a hypothesis-generating framework that may inform future functional studies and integrative approaches aimed at understanding therapeutic response and disease progression.

Diseases doi: 10.3390/diseases14060218

Authors: Giuseppe Rovere Federica Messina Cesare Meschini Maria Serena Oliva Matteo Caredda Fernando De Maio Pasquale Farsetti Giulio Maccauro Antonio Ziranu

Background: Pathological fractures of the humerus secondary to metastatic disease represent a significant cause of pain, disability, and reduced quality of life in oncologic patients. Surgical management aims to restore stability, reduce pain, and allow early mobilization. However, the optimal strategy between intramedullary nailing and modular megaprosthesis remains debated, particularly in relation to functional outcomes and long-term results. Methods: A retrospective observational study was conducted on 48 patients treated for pathological or impending humeral fractures between January 2015 and January 2025. Twenty-six patients underwent intramedullary nailing (IMN group), while twenty-two were treated with tumor resection and modular megaprosthesis reconstruction (MP group). Functional outcomes were assessed using the Musculoskeletal Tumor Society (MSTS) score, Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH), and Western Ontario Shoulder Instability Index (WOSI) at 1, 12, 24, 36, and 60 months, and at 10 years. Complications and overall survival were also analyzed. Results: Intramedullary nailing demonstrated significantly superior early functional outcomes, with higher MSTS scores at 1 month (78% vs. 63%, p < 0.001) and lower QuickDASH scores in the first 24 months (p = 0.002). WOSI scores also favored IMN in the early postoperative period (p = 0.004). Megaprosthesis showed a slower initial recovery but a progressive improvement over time, reaching comparable functional outcomes at long-term follow-up (p > 0.05). The overall complication rate was similar between groups (p = 0.28), although periprosthetic infections occurred only in the MP group. Survival analysis did not show significant differences between groups (p = 0.74). Conclusions: Both intramedullary nailing and modular megaprosthesis represent effective surgical options for pathological and impending humeral fractures. Intramedullary nailing provides faster early functional recovery, whereas megaprosthetic reconstruction offers a durable reconstructive solution for extensive proximal lesions. Functional outcomes progressively converged between the two techniques approximately 2–3 years after surgery. Mid-term outcomes up to five years appeared comparable, suggesting that surgical decision-making should be individualized according to lesion characteristics, tumor biology, expected survival, and functional demands.

Diseases doi: 10.3390/diseases14060217

Authors: Unathi A. Tshoni Thokozani P. Mbonane Phoka C. Rathebe

Prostate cancer (PCa) is the most prevalent cause of cancer-related deaths worldwide. This review aims to synthesize the contemporary literature (2018–2026) on various diagnostic approaches of PCa for clinicians. Currently, the standard approach to PCa diagnosis includes (1) prostate-specific antigen (PSA) testing, (2) its derivatives, and (3) digital rectal examination (DRE). This approach is readily available and cost-effective but lacks specificity, thus resulting in a high incidence of overdiagnosis and overtreatment of PCa patients. This review aims to compare the traditional approaches with the newly developed approaches to PCa diagnosis and investigate their suitability for research purposes, including urine-based markers, liquid biopsy, and histopathology. Each of these approaches has advantages and disadvantages. Advanced imaging techniques like multiparametric magnetic resonance imaging (mpMRI) are helpful in the localization of PCa and can prevent unnecessary biopsies. Histopathology remains the gold standard in the confirmation of PCa diagnosis. Newly developed blood-based markers and advanced imaging techniques are more sensitive and specific in the diagnosis of PCa and are likely to result in a better clinical outcome than the traditional approaches. However, the cost of these approaches remains a global challenge in developing and developed countries alike. PCa diagnosis tools and strategies are presented in a clinical and cost-effective manner and are integrated in a tiered approach with the aim of controlling and managing PCa and its diagnosis.

Diseases doi: 10.3390/diseases14060216

Authors: Andrei Manu Elena Poenaru Arina-Ilinca Gheorghe Smaranda Stoleru Alexandra Irma Gabriela Baușic Bogdan-Cătălin Coroleucă Ciprian-Andrei Coroleucă Cristina-Maria Iacob Mihaela Arina Banu Anca-Mihaela Hashemi Maria-Bianca Nițescu Oana-Miruna Peiu Elvira Brătilă

Background: Deep infiltrating endometriosis (DIE), particularly when involving the bowel, significantly impairs health-related quality of life (HRQoL) and gastrointestinal function. This study aimed to evaluate the short- and mid-term impact of minimally invasive excision on these parameters in a large multicenter cohort. Methods: A retrospective observational study was conducted on 837 patients treated for endometriosis in two tertiary referral centers between 2018 and 2024. All patients underwent laparoscopic or robotic-assisted excision. Quality of life was assessed preoperatively and at 6 months (VAS: n = 69; SF-36: n = 100; GIQLI: n = 98) and 12 months (VAS: n = 30; SF-36: n = 46; GIQLI: n = 44) postoperatively, using validated patient-reported outcome measures (PROMs): the Visual Analog Scale (VAS) for pain, the Short Form-36 (SF-36) survey, and the Gastrointestinal Quality of Life Index (GIQLI). Results: The study population presented with predominantly advanced disease (Stage III–IV in 83.4% of cases), with 39.7% of patients undergoing segmental bowel resection. Postoperatively, a statistically significant reduction was observed in dysmenorrhea (VAS 7.6 vs. 5.0, p < 0.001) and chronic pelvic pain. The SF-36 scores improved significantly across all eight domains at 6 months, with the most dramatic recovery seen in Role Physical (p < 0.001) and Bodily Pain (p < 0.001). Regarding digestive function, the mean GIQLI score showed a progressive increase, reaching statistical significance at 12 months compared to baseline (112.6 vs. 106.6, p = 0.027), indicating superior long-term functional outcomes. Conclusions: Multidisciplinary minimally invasive surgery for deep infiltrating endometriosis was associated with significant and sustained improvements in quality of life among patients with available follow-up. Gastrointestinal quality of life, as measured by GIQLI, improved significantly at 12 months postoperatively, including in patients who underwent segmental bowel resection. Systematic use of PROMs is essential for accurate patient counseling and outcome monitoring.

Diseases doi: 10.3390/diseases14060215

Authors: Silviu Gabriel Vlăsceanu Radu Șerban Matache Beatrice Mahler Alexandru Stoichiță Camelia Alexandra Paruschi Alina Elena Tucana Andrei Cristian Bobocea Cornel Florentin Savu

Background: Hydatid disease, caused primarily by Echinococcus granulosus, remains a significant public health challenge in endemic regions. While hepatic (80–85%) and pulmonary (15–20%) involvements are common, multi-organ dissemination involving rare sites such as the pericardium, diaphragm, and mediastinum occurs in less than 0.1–2% of cases. Case presentation: We present a rare case of a 26-year-old male, a farmer for 10 years, with occupational exposure to dogs and horses, with a personal history of multiple surgically treated abdominal cysts in 2016, admitted after abdominal computed tomography revealed liver cysts greater than 5 cm, as well as mediastinal and diaphragmatic cysts. Histopathological examination of the surgically resected hepatic cyst material confirmed echinococcosis. Serology was also positive for echinococcosis. Echocardiography revealed a pericardial cyst, posterior to the left atrium. Under these circumstances, antiparasitic treatment was initiated by an infectious disease specialist, followed by surgical treatment of the abdominal cysts, confirming the final diagnosis of hydatid disease, and subsequently, surgical treatment of the thoracic hydatid cysts was performed. The postoperative course was complicated by bronchial superinfection with Stenotrophomonas maltophilia, identified from bronchial aspirate culture after extended incubation and managed with trimethoprim–sulfamethoxazole. Conclusions: This case underscores the necessity of lifelong surveillance in hydatid disease, the potential role of postoperative antiparasitic therapy in preventing long-term recurrence, and the vital role of a multidisciplinary team in managing complex, disseminated relapses.

Diseases doi: 10.3390/diseases14060214

Authors: Lavinia Alice Bălăceanu Andreea Taisia Tiron Ion Daniel Baboi Claudia Georgeta Iacobescu Beatrice Bălăceanu-Gurău Cristian-Dorin Gurău Ioana Valeria Grigorescu Ion Dina

Background: Advanced chronic kidney disease (CKD) and cardiovascular comorbidities frequently coexist in patients with multiple myeloma and are particularly common among hospitalized patients. However, the relationship between common cardiovascular comorbidities and advanced CKD in routine clinical practice remains incompletely characterized. Methods: We conducted a retrospective single-center cohort study including 137 hospitalized patients diagnosed with multiple myeloma between January 2015 and February 2026. Demographic, clinical, and laboratory data were extracted from electronic medical records. Advanced CKD was defined as eGFR < 30 mL/min/1.73 m2, calculated using the CKD-EPI 2021 equation. Patients with isolated acute kidney injury were excluded. Cross-sectional associations between cardiovascular comorbidities and advanced CKD were assessed using logistic regression models. Results: The median age was 69 years (IQR 63–77), and 56.9% of patients were women. Renal impairment was common, with a median creatinine level of 2.82 mg/dL and a median eGFR of 22.4 mL/min/1.73 m2. Advanced CKD was identified in 55 of 116 patients (47.4%) with available CKD classification. Cardiovascular comorbidities were common, including hypertension (42/55, 76.4%), diabetes mellitus (18/55, 32.7%), myocardial ischemia (41/55, 74.5%), and heart failure (25/55, 45.5%). In univariate analysis, atrial fibrillation showed a significant cross-sectional association with advanced CKD (OR 4.43, 95% CI 1.30–15.07, p = 0.017), as was myocardial ischemia (OR 2.89, 95% CI 1.07–7.80, p = 0.039). In multivariable analysis, atrial fibrillation demonstrated a trend toward an association with advanced CKD but did not remain statistically significant after adjustment. Conclusions: Advanced CKD and cardiovascular comorbidities frequently coexist in hospitalized patients with multiple myeloma. Atrial fibrillation and myocardial ischemia were associated with advanced CKD in univariate analyses; however, these associations were attenuated after multivariable adjustment. Overall, these findings provide insight into the coexistence of advanced CKD and cardiovascular comorbidities in hospitalized patients with multiple myeloma.

Diseases doi: 10.3390/diseases14060213

Authors: Fatina W. Dahadhah Mohanad Odeh Adnan A. Dahadha Heba A. Ali Eman Hussein Alshdaifat Emad Freihat Manal Issam Abu Alarjah Mazhar Salim Al Zoubi

Background/Objectives: Male infertility is a significant global public health concern, with sperm abnormalities contributing to nearly half of all cases. This retrospective study addressed a critical gap by analyzing 1182 semen records from subfertile Jordanian men at the IVF unit. Methods: We quantified the prevalence of specific abnormalities, oligozoospermia, asthenozoospermia, teratozoospermia, and azoospermia, and investigated the interrelationships between sperm count, motility, and morphology. Results: Oligozoospermia was the most prevalent single abnormality (29%), while normozoospermia was found in 28% of cases. Combined defects were frequent; oligoasthenoteratozoospermia, with low count, poor motility, and abnormal morphology, was identified in 17% of cases, highlighting the multifactorial nature of subfertility. Correlation analysis showed significant interdependencies. A strong positive correlation was found between normal morphology and progressive motility (r = 0.484, p < 0.0001), suggesting structural integrity is closely linked to movement. Sperm count showed moderate positive correlations with normal morphology (r = 0.508, p < 0.0001) and non-progressive motility (r = 0.522, p < 0.0001). Abnormal morphology exhibited the strongest positive correlation with immotile sperm (r = 0.559, p < 0.0001), consistent with asthenoteratozoospermia. Conclusions: These findings suggest semen issues in Jordanian men include multiple parameters simultaneously. Comprehensive semen analysis is essential for accurate fertility assessment, as focusing on a single parameter like sperm count may overlook critical factors contributing to infertility.

Diseases doi: 10.3390/diseases14060212

Authors: Andreea Ungureanu Maria-Cristina Marinescu Adriana-Nicoleta Trandafir Valeria Coviltir Carmen Giuglea Silviu-Adrian Marinescu

Background: Burn injuries are increasingly being recognized as chronic conditions with long-term physical, emotional, and social consequences. As survival after acute burn trauma improves, greater attention has shifted toward health-related quality of life (QoL) in survivors, particularly in regions where data remain limited. Methods: This study included burn survivors treated between January 2022 and December 2023 in the Department of Plastic Surgery and Reconstructive Microsurgery of the Emergency Clinical Hospital “Bagdasar-Arseni,” Bucharest, Romania. Patients who survived hospitalization and follow-up were invited to complete a Romanian-adapted version of the Burn Specific Health Scale-Brief (BSHS-B). Demographic and clinical data were collected from medical records, including burn type, total body surface area (TBSA), burn depth, burn localization, and access to rehabilitation services. Statistical analysis included descriptive methods, chi-square tests, t-tests, Kendall’s tau-b, Cramer’s V, Cronbach’s alpha, and exploratory factor analysis. Results: Thirty-eight patients were included. Most burns were thermal (94.74%), while burns involving <10% TBSA were most frequent (60.53%). Functional outcomes were generally favorable, with most patients reporting no difficulty in basic daily activities such as bathing, dressing, and writing. However, fine motor activities and return to previous work were more frequently affected. Emotional recovery appeared less complete, with persistent mild-to-moderate loneliness, sadness, and emotional distress reported by many participants. Women reported higher levels of loneliness (p = 0.015), while third-degree burns were associated with more frequent depressive symptoms (p = 0.008). Depressive symptoms were also significantly associated with functional limitations (such as getting dressed, p = 0.002) and work impairment (p < 0.001). The adapted functional and emotional subscales showed excellent internal consistency. Conclusions: Post-burn recovery extends beyond physical healing. Although most patients regained functional independence, emotional distress and occupational difficulties often persisted. These findings support the need for multidisciplinary long-term burn care integrating physical rehabilitation, psychological screening, and psychosocial support.

Diseases doi: 10.3390/diseases14060211

Authors: Georgiana-Adriana Toma Elena Coman Antonia Ioana Vasile Simona Trifu

Background/Objectives: Thyroid dysfunction is frequently associated with mood and anxiety disorders, yet the directionality and diagnostic specificity of this relationship remain debated. Although numerous studies have examined major depressive disorder (MDD) and bipolar disorder (BD) separately, comparative data including generalized anxiety disorder (GAD) and accounting for non-thyroidal illness (NTI) effects remain scarce. This study aimed to evaluate thyroid function and its correlation with affective symptom severity across MDD, GAD, and BD in an inpatient cohort. Methods: Eighty-eight hospitalized patients with MDD, GAD, or BD were included in the study (MDD = 30, GAD = 30, BD = 28). Serum levels of TSH, FT4, and FT3 were measured 24–48 h after admission to minimize the influence of NTI. Psychiatric assessment included the Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Anxiety Scale (HAM-A), and Young Mania Rating Scale (YMRS). Between-group differences were analyzed using ANOVA, and associations between thyroid parameters and symptom severity were examined using correlation and regression analyses. Results: ANOVA revealed that patients with MDD had significantly higher TSH levels compared with those with GAD and BD (p < 0.01). MDD patients also showed a higher prevalence of subclinical hypothyroidism (33.3%) than patients with GAD (13.3%) and BD (7.1%), as well as a higher prevalence of overt hypothyroidism (13.3%) compared with GAD (0%) and BD (7.1%). TSH levels correlated positively with MADRS scores (r = 0.45, p < 0.05) and HAM-A scores (r = 0.38, p < 0.05), particularly within the MDD group. In BD, FT4 and FT3 levels were elevated and positively correlated with YMRS scores (FT4: r = 0.30, p < 0.05; FT3: r = 0.42, p < 0.05). In regression analysis within the MDD subgroup, both hypothyroidism and male sex were independently associated with higher MADRS scores, indicating greater depressive symptom severity. Conclusions: These findings suggest diagnosis-specific patterns of thyroid dysfunction among psychiatric inpatients. Higher TSH levels and increased rates of hypothyroidism were most prominent in MDD and were associated with greater depressive and anxiety symptom severity, whereas elevated FT4 and FT3 levels in BD were associated with manic symptom severity. The results support systematic thyroid screening in depressive admissions, hormone-informed monitoring in bipolar disorder, and a more integrated endocrine–psychiatric approach to clinical care.

Diseases doi: 10.3390/diseases14060210

Authors: Ana Maria Mihai Ovidiu Rosca Florina Lucaciu Alexandra Herlo Talida Georgiana Cut Ioana-Melinda Luput-Andrica Radu Gheorghe Dan Matilda Radulescu Andreea Cristina Floruncut Adelina Marinescu Alexandra Sima

Background: Diabetic patients face increased severity in viral respiratory infections, yet during the longitudinal progression of lung recovery, the radiological clearance is poorly quantified. Methods: This prospective study at an infectious diseases hospital analyzed 430 patients with confirmed viral pneumonia. Radiological severity (Rx) and pleural effusion were scored (0–3) at admission (day 1) and follow-up (day 6). Results: Diabetics presented with significantly higher baseline severity (Median 2.0 vs. 1.0, p < 0.0001). While both groups improved at identical rates (Median Δ = −1.0), a significant radiological lag persisted in diabetics at day 6 (Median 1.0 vs. 0.0, p < 0.0001). Attrition analysis (N = 75) revealed a divergent lethal split: attrition in the non-diabetic cohort was almost exclusively driven by low-severity early departures against medical advice (94.2%), whereas diabetic attrition was primarily characterized by early mortality (60.9%; p < 0.0001). Although the diabetic state was associated with a pronounced radiographic resolution delay in unadjusted comparisons, this disadvantage was substantially attenuated and lost statistical significance after adjustment for admission radiological severity (adjusted OR 2.04, 95% CI 0.88–4.76) and chronic comorbidity burden (adjusted OR 1.37, 95% CI 0.56–3.39), indicating that the diabetic lag is largely explained by a higher presenting severity and comorbidity burden rather than by an independent acute effect of diabetes itself. Sensitivity analyses suggest that the observed lag in survivors likely underestimates the true disease burden, given the concentration of early mortality among high-risk diabetic cases.

Diseases doi: 10.3390/diseases14060209

Authors: Jayakrishna Pamarthi Sugan Panneerselvam Nanda Amarnath Rajesh Venkataratna Bharat Gangireddy Mohanram Murugan Leela Kakithara Vajaravelu Jayaprakash Thulukanam Mansour Alanazi Janardanan Subramonia Kumar

Background: Chronic hepatitis B virus (HBV) infection remains a major global health challenge and a leading cause of liver cirrhosis and hepatocellular carcinoma. Interleukin-6 (IL-6), a key pro-inflammatory cytokine, plays an important role in immune regulation and hepatic inflammation. However, its relationship with HBV viral load and disease severity remains incompletely understood. Methods: A hospital-based cross-sectional study was conducted among 293 HBsAg-positive patients. Serum IL-6 levels were measured using ELISA, and HBV DNA was quantified using real-time quantitative PCR. Patients were stratified according to viral load. Statistical analyses included non-parametric tests, Spearman correlation, principal component analysis (PCA), and multiple linear regression. Results: The median age was 45 years (IQR: 34–57), among which 54.6% were male. The median HBV DNA was 3.37 log10 IU/mL (IQR: 2.45–3.75), and IL-6 concentration was 2.38 log10 pg/mL (IQR: 2.21–2.49). IL-6 levels increased significantly across viral load categories (p < 0.001) and were higher in HBeAg-positive patients (p = 0.002), with no significant differences across age, sex, or cirrhosis. IL-6 levels correlated with HBV DNA (r = 0.40, p < 0.001). PCA identified distinct viral-inflammatory and biochemical axes. Regression analysis confirmed HBV DNA as the significant independent predictor (β = 0.461, p < 0.001; adjusted R2 = 0.206). Conclusion: IL-6 was closely associated with HBV DNA levels, while the association with conventional biochemical markers of hepatocellular injury was significantly less in this cohort, suggesting that IL-6 may serve as an adjunct biomarker of disease activity in patients with chronic hepatitis B.

Diseases doi: 10.3390/diseases14060208

Authors: Pavol Zubor Kristen Olav Lind Jozef Visnovsky Petra Zuborova Guri Grimnes Cato Kjærvik

Background: Pregnancy-related transient osteoporosis of the hip (PR-TOH) is an uncommon and frequently underdiagnosed condition that typically presents with acute hip pain during late pregnancy or the early postpartum period. Because its clinical presentation is nonspecific and overlaps with pregnancy-related pelvic girdle pain, the diagnosis is often delayed, and the initial management is suboptimal. Although bilateral involvement has been reported, comparative data on diagnostic work-up, multidisciplinary management, and follow-up remain limited. Case Presentation: We report a case of bilateral PR-TOH in a 35-year-old Caucasian primigravida (G1, P0) who presented at 31 + 6 weeks of gestation with progressively worsening bilateral hip pain that culminated in severe functional impairment and wheelchair dependence. Initial ultrasound, laboratory work-up, and rheumatological screening were inconclusive, and intra-articular corticosteroid injections failed to relieve symptoms and were temporally associated with deterioration of glycaemic control and a periorbital and palmar eczematous rash. Magnetic resonance imaging (MRI) demonstrated diffuse bone marrow oedema in both femoral heads with preserved articular cartilage and no evidence of avascular necrosis, supporting a diagnosis of bilateral PR-TOH. Postpartum dual-energy X-ray absorptiometry (DXA) confirmed reduced bone mineral density at both femoral necks (Z-scores below −2.0). Pregnancy was prolonged until 37 + 4 weeks, and delivery was by elective caesarean section. Postpartum care included analgesia, calcium and vitamin D supplementation, structured physiotherapy, and a graded weight-bearing rehabilitation programme. Bone mineral density improved markedly on follow-up DXA at six months, with complete clinical recovery and no further imaging abnormalities at 12, 24, and 30 months. Conclusions: PR-TOH should be considered in pregnant or postpartum women with persistent hip pain and progressive functional limitation. MRI is the key imaging modality for early diagnosis and for excluding alternative causes, whereas DXA remains the reference standard for quantifying bone mineral density and monitoring recovery. Bilateral presentations require a multidisciplinary, individualised approach that addresses both maternal and obstetric outcomes.

Diseases doi: 10.3390/diseases14060207

Authors: Alessandro Avitabile Marco Zeppieri Ludovica Cannizzaro Giuseppe Gagliano Maria Francesca Cordeiro Fabiana D’Esposito Francesco Cappellani Maria Vadalà Vincenza Maria Elena Bonfiglio

Photonic imaging technologies have profoundly transformed neuro-ophthalmic diagnostics by enabling non-invasive visualization of neurodegenerative processes at the retinal level. This review examines how advanced light-based modalities provide unprecedented insights into the structural, physiologic, and biologic relationships between the eye and brain in conditions such as optic neuritis, multiple sclerosis, and glaucoma. Optical coherence tomography has emerged as an essential tool for quantifying thinning of the retinal nerve fiber layer and ganglion cell layer, serving as reliable biomarkers of axonal loss and disease progression across multiple sclerosis subtypes and optic neuropathies. Detection of apoptosing retinal cells imaging enables real-time visualization of retinal ganglion cell apoptosis preceding irreversible structural damage, offering a critical window for early intervention in various neurodegenerative conditions, in particular, glaucoma. Two-photon microscopy with adaptive optics enables subcellular-resolution imaging of retinal neurons, microvascular dynamics, and inflammatory processes in vivo, facilitating the characterization of neurodegenerative mechanisms at unprecedented spatial scales and redefining neuro-ophthalmology by positioning the retina as an accessible extension of the central nervous system. This review critically examines how established and investigational photonic imaging modalities may support earlier disease detection, longitudinal monitoring, and biomarker development in neuro-ophthalmic and neurodegenerative disorders, with potential implications for more timely and targeted management strategies.

Diseases doi: 10.3390/diseases14060206

Authors: Stanislav Kotlyarov Alexander Lyubavin

Background: Atrial fibrillation (AF) is a common arrhythmia with a high incidence, and patients with chronic obstructive pulmonary disease (COPD) are at particularly high risk. However, there are currently no tools available for early risk stratification of AF in this population. Objectives: To develop and validate a neural network diagnostic model based on transthoracic echocardiography to address two clinical challenges in patients with COPD: risk stratification for AF; and detection of occult supraventricular arrhythmias (including “micro-AF”) based on 24 h ECG monitoring data. Methods: The study consisted of three consecutive stages: development of a neural network (NN) based on transthoracic echocardiography (TTE) parameters, validation of the model’s predictive ability in patients (n = 311, including 99 with COPD), and assessment of the ability to detect occult atrial arrhythmias (n=207) in patients with COPD. The model architecture consists of a fully connected multilayer perceptron (MLP) with 13 inputs, 4 hidden layers of 130 neurons each, and 2 output neurons. Training was performed on 684 TTE scans (292 without AF, 392 with AF). The echocardiographic parameters were validated on an independent test set (n = 100). Statistical analysis included pairwise and multiple comparisons, logistic regression analysis, and ROC analysis with assessment of the area under the ROC curve (AUC). The median follow-up period for study participants was 18 months. Results: The neural network demonstrated high classification metrics for AF on the test set (AUC = 0.80). A threshold value of the first output layer neuron > 0.75 allowed for the identification of a high-risk subgroup, in which the incidence of AF in patients with COPD was 14.8% versus 0% in the low-risk subgroup (p = 0.0073). Logistic regression models of the relationship between AF development and the neural network output value were statistically significant in both patients with COPD and patients without COPD (p < 0.0001). In patients with COPD without a history of AF, the neural network identified a high-risk group. In this group, 24 h ECG monitoring more frequently recorded episodes of AF, group supraventricular extrasystoles, and the combined endpoint (AF + GSE) compared to the low-risk group (55.32% vs. 17.5%; p < 0.0001). The area under the ROC curve for detecting latent AF in patients with sinus rhythm based on the neural network prediction was 0.93. Conclusions: The developed neural network model, which integrates a set of TTE parameters into a single quantitative measure of the severity of myocardial remodeling, is an effective tool for risk stratification for AF. The model may help identify COPD patients who could benefit from intensified rhythm monitoring; however, external validation is required before clinical implementation.

Diseases doi: 10.3390/diseases14060205

Authors: Otilia-Rodica Butiu Ema Burlacu Rebeca-Isabela Molnar Adriana Mihai Teodora Popescu

Background/Objectives: Parents of children with autism spectrum disorder (ASD) often face sustained emotional, practical, and social demands. However, evidence from Romania remains limited, particularly regarding the combined assessment of caregiver burden, emotional distress, and coping strategies of parents. This exploratory study compared these outcomes between parents of children/adolescents with ASD and parents of typically developing children and examined whether coping patterns varied according to selected sociodemographic characteristics. Methods: We conducted a cross-sectional comparative study in Târgu-Mureș, Romania, between 2024 and 2025. The sample included 92 parents: 46 parents of children/adolescents with clinician-confirmed ASD and 46 parents of typically developing children. Participants completed a demographic questionnaire, the Caregiver Burden Inventory (CBI), the Depression Anxiety Stress Scales-21 (DASS-21), and the Strategic Approach to Coping Scale (SACS). DASS-21 data were available for 44 ASD caregivers and 46 controls. Between-group comparisons were performed using t-tests, Mann–Whitney U tests, chi-square tests, or Fisher’s exact tests, as appropriate. Results: The groups were comparable in sex, age, residence, number of children, and household size, but differed significantly in marital status and educational level. Clinically relevant caregiver burden (CBI ≥ 36) was more frequent among parents of children with ASD than among controls (30% vs. 17%), although this difference was not statistically significant. Parents of children with ASD showed trend-level higher depressive and anxiety symptoms, with small effect sizes, whereas stress scores were similar between groups. Coping patterns varied according to sociodemographic characteristics. Marital status was associated with aggressive coping, urban residence was associated with indirect and aggressive coping, and number of children was associated with seeking social support. Conclusions: Parents of children with ASD showed a higher proportion of clinically relevant caregiver burden and trend-level elevations in depressive and anxiety symptoms, while stress scores were comparable between groups. Exploratory adjusted analyses suggested that ASD caregiver status remained associated with caregiver burden and depressive symptoms after controlling for educational level and marital status. Coping strategies appeared heterogeneous and context-dependent. Given the exploratory design, modest sample size, and multiple comparisons, these findings should be interpreted as preliminary and hypothesis-generating.

Diseases doi: 10.3390/diseases14060204

Authors: Ho Yeung Lam Shalomie Shadrach Ben Brimblecombe Hannah Woodall Brianna Moss Teresa McGorm Rikki Graham Mohana Rajmokan Gino Micalizzi Stephen B. Lambert

Background: Invasive Haemophilus influenzae type b (Hib) infection in children has become rare following the introduction of highly effective conjugate vaccines under national immunisation programmes. However, breakthrough invasive infections in fully immunised individuals can still occur. We report a case of invasive Hib infection presenting as epiglottitis and bacteraemia in a fully vaccinated 5-year-old boy in regional Queensland, Australia. Case presentation: The child, with no history of immunodeficiency, presented with a 3-day history of fever, progressive throat pain and reduced oral intake. Subsequent investigations revealed leukocytosis with left shift, markedly elevated C-reactive protein, and radiographic features consistent with epiglottitis. Blood culture grew H. influenzae type b. He was treated with intravenous cefotaxime and made a full recovery without complications. Immunological evaluation demonstrated Hib-specific IgG levels consistent with prior vaccinations, with normal immunoglobulin and lymphocyte profiles supporting the absence of immunodeficiency. Whole-genome sequencing of the isolate identified sequence type 6, a known circulating strain, and duplication of the capsule (cap-b) locus which has been associated with increased capsular polysaccharide production and reduced susceptibility to immune-mediated clearance. Conclusions: This case demonstrates that invasive Hib disease can occur in fully vaccinated, immunocompetent individuals and highlights the need for continued clinical vigilance. Pathogen-related factors, such as cap-b locus duplication, may reduce the effectiveness of the immune response. Despite this, immunisation can still confer partial protection, potentially contributing to the relatively mild clinical course. Ongoing surveillance and detailed microbiological investigation are essential to better understand and monitor vaccine breakthrough infections.

Diseases doi: 10.3390/diseases14060203

Authors: Lavinia Alice Bălăceanu Claudia Georgeta Iacobescu Ioana Valeria Grigorescu Ion Daniel Baboi Marian-Vlad Lapadat Ion Dina

Background: Decompensated cirrhosis is associated with high in-hospital mortality, influenced by disease severity and underlying etiology. The COVID-19 pandemic may have altered both the etiological spectrum and clinical presentation of hospitalized patients. This study aimed to assess longitudinal changes in etiology and identify predictors of in-hospital mortality over a 10-year period. Methods: We conducted a retrospective cohort study including 812 patients hospitalized with decompensated liver cirrhosis between 2015 and 2025. Patients were grouped into pre-COVID-19 (2015–2019), COVID-19 (2020–2021) and post-COVID-19 (2022–2025) periods. Etiological factors and mortality rates were compared using chi-square tests. Independent predictors were identified through multivariate analysis. A clinical risk score based on Child–Pugh stage, platelet count and age was developed and evaluated using ROC analysis. Results: Alcohol-related cirrhosis increased significantly from 51.2% (pre-COVID-19) to 90.4% (COVID-19) and remained high post-COVID-19 (86.3%) (p < 0.001), while HCV decreased from 34.4% to 13.5% and stabilized at 14.8% (p < 0.001). HBV showed no significant variation. All-cause in-hospital mortality increased from 19.7% pre-COVID-19 to 42.3% during COVID-19 and remained elevated post-COVID-19 at 34.5% (p < 0.001). Independent predictors of all-cause in-hospital mortality included advanced Child–Pugh stage, thrombocytopenia and age above 70 years. The risk score (0–7 points) showed good discrimination (AUC = 0.752), with mortality rates of 2.8%, 24.0% and 45.7% across increasing risk categories. A score <5 had a negative predictive value of 84.3%. Conclusions: A significant etiological shift from HCV to alcohol was observed, accompanied by persistently increased mortality after COVID-19. Thrombocytopenia remains an important predictor of mortality. The proposed score enables simple and effective risk stratification.

Diseases doi: 10.3390/diseases14060202

Authors: Lindsey Wells Myriah Hinchey Richard E. Frye Amelia Morgan

Background: Vector-borne diseases (VBDs) caused by Borrelia spp., Bartonella spp., and Babesia spp. are associated with neuropsychiatric morbidity. Cerebral folate deficiency (CFD), primarily caused by folate receptor-α autoantibodies (FRAAs) impairing folate blood–brain barrier transport, is a treatable contributor to neurodevelopmental disorders including pediatric acute-onset neuropsychiatric syndrome (PANS) and autism spectrum disorder. Despite overlapping clinical manifestations, FRAA prevalence in VBD populations has not been investigated. This study aimed to determine the prevalence of FRAA in patients with confirmed VBDs. Methods: This retrospective cohort study included 68 VBD-positive patients with and without PANS evaluated at a single clinical practice. VBD testing was performed by IGeneX Laboratories; FRAA analysis including binding, blocking, and soluble folate receptor (sFR) testing was performed by Religen Laboratories (Plymouth Meeting, PA). Statistical associations were assessed using Fisher’s exact test with Wilson 95% confidence intervals. Results: Of the 68 VBD-positive patients, 42 (61.8%; 95% CI: 49.9–72.4%) were also FRAA-positive. Soluble folate receptor (sFR) was detected in eight patients (11.8%; 95% CI: 6.1–21.5%), all of whom were binding FRAA-positive, with 87.5% carrying confirmed evidence of Borrelia species infection. Neuropsychiatric symptoms were highly prevalent across both groups but did not significantly differentiate FRAA-positive from FRAA-negative patients (all p > 0.05). Conclusions: This study demonstrates a high prevalence of FRAA in a pediatric VBD cohort. The sFR was strongly associated with Borrelia species infection, suggesting a potential mechanistic link between spirochetal infection and folate receptor autoimmunity. These findings support the consideration of FRAA testing in patients with VBDs and warrant further investigation in larger prospective cohorts.

Diseases doi: 10.3390/diseases14060201

Authors: Madina B. Baurzhan Alexandr E. Gulyayev Karlygash S. Absattarova Sayagul A. Kairgeldina Kuat Abzaliyev Akmaral Izbassarova Marzhan Lepessova Karashash Absatarova

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by irreversible extracellular matrix deposition and high mortality, with aging representing its strongest risk factor. Increasing evidence suggests that cellular senescence is not merely a consequence of tissue injury but a central driver of disease progression. Senescent alveolar epithelial cells and fibroblasts contribute to impaired tissue repair and persistent fibrotic remodeling through the acquisition of a senescence-associated secretory phenotype (SASP), which promotes chronic inflammation and amplifies profibrotic signaling. This review provides a comprehensive synthesis of current evidence on the role of cellular senescence in IPF, focusing on key molecular mechanisms, including telomere attrition, mitochondrial dysfunction, oxidative stress, DNA damage response activation, and dysregulated transforming growth factor-β (TGF-β) signaling. A structured literature search was conducted using the PubMed, Scopus, and Web of Science databases to identify mechanistic, translational, and clinical studies related to cellular senescence in IPF. Relevant studies were selected based on conceptual relevance and scientific quality, and findings were qualitatively synthesized within a narrative-review framework. These interconnected pathways form self-reinforcing feedback loops that stabilize the senescent phenotype and sustain fibroblast activation. In addition, we critically evaluate emerging therapeutic strategies targeting senescence, including senolytic and senomorphic approaches, highlighting their potential to modify fundamental disease mechanisms rather than solely attenuating fibrotic progression. Preclinical and early clinical studies suggest that selective targeting of senescent cells may represent a promising avenue for intervention, although challenges related to specificity, safety, and biomarker development remain. Overall, this review positions cellular senescence as a central mechanistic link between aging and fibrosis and underscores its relevance as a translational target in IPF.

Diseases doi: 10.3390/diseases14060200

Authors: Kyeong Min Han Dae Myoung Yoo Ho Suk Kang Hyo Geun Choi Joo-Hee Kim Nan Young Kim Kyueng-Whan Min Mi Jung Kwon

Background/Objectives: Psoriasis is a chronic systemic inflammatory disease associated with increased cancer risk; however, its relationship with colorectal cancer (CRC) remains unclear. This question is particularly relevant in Asia, where CRC incidence has been increasing rapidly in recent decades. Methods: We conducted a nationwide longitudinal cohort study using the Korean National Health Insurance Service–National Sample Cohort (2002–2019). Patients with psoriasis were identified using validated ICD-10 codes and matched 1:4 with controls by age, sex, income, and region. Propensity score overlap weighting was applied to achieve covariate balance. Incident CRC was defined using both ICD-10 codes and cancer-specific registration codes. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: A total of 16,670 patients with psoriasis and 66,680 matched controls were included. During follow-up, the incidence of CRC was comparable between the two groups. In the weighted model, psoriasis was not associated with an increased risk of CRC (aHR = 0.96; 95% CI: 0.83–1.10). Kaplan–Meier analysis showed no significant difference in cumulative incidence (log-rank p > 0.05). Subgroup analyses stratified by age, sex, income, region, and comorbidity burden yielded consistent null findings. Conclusions: In this large nationwide cohort, psoriasis was not associated with an increased risk of CRC. These findings suggest that psoriasis does not independently contribute to CRC risk at the population level and does not warrant additional CRC surveillance beyond established screening recommendations, even in a high-burden setting such as Korea.

Diseases doi: 10.3390/diseases14060199

Authors: Larisa Ionela Suiu Florentin Ananu Vreju Adina Turcu-Stiolica Cristina Elena Bita Mihail Virgil Boldeanu Paulina Lucia Ciurea

Background: Hyperuricemia is a prevalent comorbidity in psoriatic arthritis (PsA), yet its influence on the IL-1α/IL-17 cytokine balance remains unexplored. We aimed to characterize serum IL-1α and IL-17 profiles in PsA stratified by hyperuricemia status and to compare these with patients with hyperuricemia without psoriatic disease (HU). Methods: This cross-sectional study included 34 consecutively recruited PsA patients (19 hyperuricemic, 15 normouricemic) and 30 HU controls. Serum IL-1α and IL-17 were measured by ELISA. The PsA cohort was stratified by hyperuricemia status, cutaneous psoriasis, disease pattern, obesity grade, hypertension, sex, and enthesitis. Between-group comparisons used Mann–Whitney U and Kruskal–Wallis tests with Bonferroni-corrected post hoc analyses. Bivariate associations were assessed using Spearman’s rank correlation. Results: Within the PsA cohort, hyperuricemic patients had significantly lower IL-17 than normouricemic patients (31.1 ± 15.7 vs. 49.5 ± 25.3 pg/mL; p = 0.01), while IL-1α did not differ significantly (37.3 ± 11.7 vs. 34.0 ± 8.19 pg/mL; p = 0.24). No correlation was observed between IL-1α and IL-17 (ρ = −0.05), indicating independent immunological axes. In the three-group comparison, IL-17 differed significantly across PsA-normouricemic, HU, and PsA-hyperuricemic subgroups (p = 0.022), whereas IL-1α was comparable across all three groups (p = 0.584). None of the traditional clinical classifications—disease pattern, cutaneous psoriasis, or sex—were significantly associated with either cytokine. Conclusions: Hyperuricemia was associated with significantly lower circulating IL-17 in PsA without a corresponding change in IL-1α levels, and this association appeared more pronounced within the inflammatory context of psoriatic disease than in hyperuricemia alone. These exploratory findings suggest that metabolic factors may play a role in defining the immunological profile of PsA and warrant prospective validation in larger cohorts. Owing to the cross-sectional design, this study does not allow inference of causal relationships between hyperuricemia and cytokine alterations.

Diseases doi: 10.3390/diseases14060198

Authors: Russell Vo Tristan Post Daniel Smith Valerie Peters Isha Puri J. W. Hollingsworth Sai Karan Vamsi Guda

Background: Lung cancer is the second most common cause of cancer with high mortality, thereby emphasizing the importance of early detection. However, the rate of new lung cancer diagnosis has remained relatively unchanged. Despite the advancements in navigational bronchoscopy, the diagnostic yield of pulmonary nodules, particularly posterior nodules, is often limited by CT-to-body divergence. Our study aims to evaluate the feasibility and safety of prone positioning during navigational bronchoscopy and its impact on the diagnostic yield of posterior pulmonary nodules. Methods: Retrospective cohort study of nine patients who underwent Ion robotic navigational bronchoscopy in prone position and 237 patients in supine position. The study period was July 2024 to December 2024 for the prone cohort and July 2020 to September 2024 for the supine cohort. Results: In the supine cohort, the diagnostic yield was 93.3%, including a malignant yield of 62.3%, and the post-operative complication rates were 1.5% for pneumothorax, 3.5% for bronchopulmonary hemorrhage, and 1.9% for respiratory failure. In the prone cohort, the diagnostic yield was 77.8% and a malignant yield of 85.7%, and the postoperative complication rates were 0% for pneumothorax, bronchopulmonary hemorrhage, and respiratory failure. Conclusions: CT-to-body divergence is a major obstacle in the diagnostic work-up of pulmonary nodules, of which a major contributor is atelectasis. Our study demonstrates that prone positioning combined with a strict anesthesia protocol is both a feasible and safe approach in the diagnostic work-up of pulmonary nodules.

Diseases doi: 10.3390/diseases14060197

Authors: Jane Busisiwe Ncongwane Comfort Nkambule Gerda Fouche Douglas Kemboi Nyeleti Vukea Candace Davison Jo-Anne de la Mare Vuyelwa Jacqueline Tembu

Candace Davison was not included as an author in the original publication [...]

Diseases doi: 10.3390/diseases14060196

Authors: Abdullah Al-Manji Adil Al Wahaibi Amal Al Malehi Mohammed Al-Azri Moon Fai Chan

Introduction: Oman has transitioned from travel-related dengue cases to local outbreaks since 2018, with heterogeneous patterns across governorates and districts. Understanding how climate, population, and vector indicators jointly shape dengue risk at different administrative levels is essential for targeted control. Methods: This study compiled weekly data (2020–2024) on dengue cases, mosquito surveillance, climate, and population from national sources. Using Partial Least Squares Structural Equation Modelling (PLS-SEM) in SmartPLS v4, we modelled constructs for Weather, Population, Vector, and Vector-borne Disease (VBD). Measurement quality was assessed using various statistics and with 5000-sample bootstrapping. Multigroup Analysis (MGA) with permutation and Measurement Invariance of Composite Models (MICOM) tested invariance and compared structural paths across governorates (Muscat, North Al Batinah, Ad Dakhiliyah) and districts (Seeb, Sohar, Bahla). Results: Vector abundance mediated climate and population effects on dengue, with marked spatial heterogeneity. At the governorate level, the Vector → VBD path was strongest in Ad Dakhiliyah (β ≈ 0.436) and negligible in Muscat (β ≈ −0.021); indirect effects from Population and Weather to VBD were significantly higher in Ad Dakhiliyah than comparators. At the district level, Bahla showed stronger Vector → VBD and Weather → Vector relationships than Seeb and Sohar, while Seeb exhibited low explanatory power across paths. MICOM indicated partial measurement invariance, suggesting caution in cross-group comparisons. Conclusions: Dengue risk in Oman is primarily vector-driven but differs by setting. Inland/rural areas are more sensitive to climate–vector dynamics, requiring enhanced surveillance and climate-informed early warning. Urban centers may need models incorporating mobility and behavior. Findings support localized interventions and the integration of trap positivity and density into district-level prediction and control.