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Med. Sci., Volume 13, Issue 4 (December 2025) – 122 articles

Cover Story (view full-size image): The objective of this study was to evaluate changes in platelet indices (MPC, MPV, MPM) and reticulated platelets (RtcPlts) obtained using the ADVIA 2120 hematology analyzer (Siemens Hematology system) in the early stages of an infection and in acute coronary syndrome (ACS). Platelet indices (MPV, MPM) and RtcPlts were significantly altered (p > 0.005) in patients with suspected sepsis and in patients with ACS compared to the control subjects. Our data showed that a state of early platelet activation exists but is not disease-specific. View this paper
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17 pages, 887 KB  
Article
Drug-Induced Intestinal Angioedema: A Disproportionality Analysis Using the United States Food and Drug Administration Adverse Event Reporting System Database and Literature Review
by Poovizhi Bharathi Rajaduraivelpandian, Rashmi R. Rao and Ashwin Kamath
Med. Sci. 2025, 13(4), 327; https://doi.org/10.3390/medsci13040327 - 18 Dec 2025
Viewed by 1305
Abstract
Background: Intestinal angioedema is an important drug-induced adverse effect that is often misdiagnosed due to vague and nonspecific symptoms. This study aimed to identify drugs with potential to cause intestinal angioedema by performing a disproportionality analysis, supplemented with literature review. Methods: Using OpenVigil, [...] Read more.
Background: Intestinal angioedema is an important drug-induced adverse effect that is often misdiagnosed due to vague and nonspecific symptoms. This study aimed to identify drugs with potential to cause intestinal angioedema by performing a disproportionality analysis, supplemented with literature review. Methods: Using OpenVigil, we extracted relevant individual case safety reports from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. Drugs with signal of disproportionate reporting (SDR) of intestinal angioedema were identified. A literature review was performed using PubMed and Embase databases to identify potential suspect drugs. Results: During 2004–2024, 303 cases of intestinal angioedema were reported to FAERS. Fourteen suspect medications showed SDR; of these, seven drugs were also reported in the literature to have caused intestinal angioedema, including angiotensin-converting enzyme inhibitors, losartan, and acetylsalicyclic acid. A literature search identified 89 relevant articles, providing details of 121 cases. Some drugs linked to intestinal angioedema in the literature did not show SDR. Conclusions: Disproportionality analysis as well as a literature review showed that most patients were middle-aged females on antihypertensive therapy. The results will assist health professionals in determining the temporal association of acute abdomen with the suspected drug, potentially avoiding unnecessary interventions and their attendant complications. Full article
(This article belongs to the Section Translational Medicine)
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17 pages, 290 KB  
Article
Transcriptomic, Redox Status and Adipocytokine Profiles in Metabolic Dysfunction-Associated Steatotic Liver Disease: Impact of Coexisting Type 2 Diabetes
by Sanja Erceg, Ana Ninić, Jelena Kotur-Stevuljević, Omar Ben Mariem, Miloš Mitrović, Jelena Munjas, Miron Sopić, Boško Misita, Milica Mamić, Aleksandra Klisic and Ratko Tomašević
Med. Sci. 2025, 13(4), 326; https://doi.org/10.3390/medsci13040326 - 18 Dec 2025
Viewed by 919
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) commonly coexists with type 2 diabetes (T2D), but their independent contributions to redox imbalance, inflammation and immune signaling remain uncertain. Objectives: This study aimed to evaluate whether the presence of MASLD alone, and the presence of [...] Read more.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) commonly coexists with type 2 diabetes (T2D), but their independent contributions to redox imbalance, inflammation and immune signaling remain uncertain. Objectives: This study aimed to evaluate whether the presence of MASLD alone, and the presence of T2D within MASLD, are independently associated with high-risk profiles of oxidative/antioxidant markers, peripheral blood mononuclear cell (PBMC) gene expression and adipocytokines. Methods: A total of 190 participants were categorized via abdominal ultrasound as controls (n = 46), MASLD (n = 83) or MASLD with T2D (n = 61). Measurements included advanced oxidation protein products (AOPP) and paraoxonase-1 (PON1) activity in serum; messenger ribonucleic acids expression of cluster of differentiation 36 (CD36), Toll-like receptor 9 (TLR9), and glutathione peroxidase-1 in PBMC; and adiponectin, leptin, and resistin in plasma. Biomarker values were adjusted and statistical comparisons among groups were performed using the Quade test. Subsequently, biomarkers were stratified into tertiles to examine associations between high-risk biomarker levels and the presence of MASLD or T2D in patients with MASLD using multivariate binary logistic regression. Results: Multivariate analysis showed that MASLD presence was independently associated with both increased AOPP and decreased resistin levels in the circulation. Furthermore, T2D presence in patients with MASLD was independently associated with increased CD36 and decreased TLR9 gene expression in PBMCs, as well as elevated circulating leptin levels. Conclusions: Collectively, these findings underscore the complex interplay between oxidative stress, insulin resistance, inflammation, and immune signaling in the pathogenesis of MASLD, which are fundamental factors contributing to this condition. Full article
(This article belongs to the Section Hepatic and Gastroenterology Diseases)
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13 pages, 1372 KB  
Systematic Review
IL-6 and Surgical Outcomes in Carotid Endarterectomy: A Systematic Review
by Antónia Rocha-Melo-Sousa, Márcio Brazuna, Carmen Tavares, Sai Guduru, Mariana Fragão-Marques and João Rocha-Neves
Med. Sci. 2025, 13(4), 325; https://doi.org/10.3390/medsci13040325 - 18 Dec 2025
Cited by 1 | Viewed by 962
Abstract
Background: Interleukin-6 (IL-6) is a key inflammatory cytokine implicated in atherosclerotic plaque progression and carotid vulnerability. Although elevated IL-6 levels have been linked to cerebrovascular risk, its prognostic value in patients undergoing carotid endarterectomy (CEA) remains undefined. This systematic review aimed to investigate [...] Read more.
Background: Interleukin-6 (IL-6) is a key inflammatory cytokine implicated in atherosclerotic plaque progression and carotid vulnerability. Although elevated IL-6 levels have been linked to cerebrovascular risk, its prognostic value in patients undergoing carotid endarterectomy (CEA) remains undefined. This systematic review aimed to investigate the available evidence on the relationship between IL-6 levels, surgical outcomes and mechanistic evidence in CEA patients. Materials and Methods: The review followed the PRISMA statement and AMSTAR-2 critical appraisal guidelines, with the protocol registered on PROSPERO (CRD420251120023). PubMed/MEDLINE, Scopus, and Web of Science were systematically searched up to July 2025 using the terms “interleukin-6” and “carotid endarterectomy”. Original studies in humans assessing IL-6 in relation to clinical outcomes after CEA or mechanistic evidence were included without language or date restrictions. Study quality was evaluated using the Cochrane Risk of Bias 2 and NHLBI tools, and evidence certainty was appraised using the GRADE framework. Given the heterogeneity of studies, only a qualitative synthesis was performed. Results: From 1232 records identified, 13 studies encompassing 1396 patients met the inclusion criteria. Most were prospective observational cohorts, with a mean participant age of 68.52 years and 81.16% male predominance. Perioperative stroke and mortality rates were uniformly low (≤2%), consistent with contemporary registry data. Across studies, elevated IL-6 levels—whether systemic or plaque-derived—were consistently associated with symptomatic carotid disease, plaque vulnerability, and adverse long-term outcomes. However, not all studies presented quantitative data on IL-6 levels, limiting the ability to draw definitive prognostic conclusions. Conclusions: Current evidence supports a mechanistic link between IL-6–mediated inflammation and carotid plaque instability, yet robust clinical validation in surgical populations is lacking. Future large-scale, prospective studies incorporating IL-6 measurement are warranted to establish its prognostic utility, guide anti-inflammatory therapeutic strategies, and refine postoperative risk stratification in patients undergoing CEA. Full article
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12 pages, 5633 KB  
Article
Serum Calcium Concentration Is Associated with Bone Mineral Density and Synonymous Variants in the RYR1 Gene in a Mexican-Mestizo Population
by Tania V. López-Pérez, Rogelio F. Jiménez-Ortega, Armando Cruz-Rangel, Diana I. Aparicio-Bautista, Juan C. Fernández-López, Adriana Becerra-Cervera, Juan P. Reyes-Grajeda, Jorge Salmerón, Alberto Hidalgo-Bravo, Berenice Rivera-Paredez and Rafael Velázquez-Cruz
Med. Sci. 2025, 13(4), 324; https://doi.org/10.3390/medsci13040324 - 17 Dec 2025
Viewed by 793
Abstract
Background/Objectives: Serum calcium concentrations have been associated with bone mineral density (BMD), but results seem to depend on sex. Genetic variants in the Ryanodine Receptor1 (RYR1) gene have been previously associated with low BMD in postmenopausal women. Serum RYR1 concentration was [...] Read more.
Background/Objectives: Serum calcium concentrations have been associated with bone mineral density (BMD), but results seem to depend on sex. Genetic variants in the Ryanodine Receptor1 (RYR1) gene have been previously associated with low BMD in postmenopausal women. Serum RYR1 concentration was found to be higher in osteopenia and osteoporosis groups. The function and biological relevance of RYR1 in bone remodeling remains unknown. This cross-sectional study explored the relationship between serum calcium concentrations, BMD, and genetic variants in RYR1 in a Mexican-mestizo population. Methods: Serum samples from 966 participants were obtained from the third measurement of the Health Workers Cohort Study (HWCS) 2017–2019, conducted by the Mexican Social Security Institute (IMSS). All participants included in this study were of Mexican Mestizo origin and had data on BMD. We measured ionized calcium and genotyped the genetic variants rs2288888 (g.38455542G>A) and rs11083462 (g.38469040C>T) of the RYR1 gene. BMD of the total hip, lumbar spine, and femoral neck was measured using a Lunar DPX NT DEXA device. Results: Our results show that elevated serum calcium concentrations in females are associated with lower BMD at the hip and femoral neck. In contrast, higher calcium concentrations in males were associated with greater total hip BMD. In our study, the variants rs2288888 and rs11083462 were associated with higher serum calcium concentrations (under-adjusted and unadjusted data) in males but not females. Conclusions: Serum calcium levels are associated with BMD, depending on sex. The RYR1 gene variants rs2288888 and rs11083462 may have a protective effect in men. Full article
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14 pages, 467 KB  
Article
Respiratory Muscle Strength in Hypertensive Adults: Age- and Sex-Specific Reference Values for a Brazilian Population
by Simone de Faria Rossetto, Juscelio Pereira da Silva, Afonso Santos de Lima, Anderson Geremias Macedo, Dalton Muller Pessôa Filho, Albená Nunes Silva, Thiago Roberto Lima Romero and Giovane Galdino
Med. Sci. 2025, 13(4), 323; https://doi.org/10.3390/medsci13040323 - 17 Dec 2025
Viewed by 586
Abstract
Background/Objectives: Hypertension is a major modifiable risk factor for cardiovascular disease and may negatively affect muscle strength through vascular and metabolic mechanisms. Nevertheless, reference values for respiratory muscle strength (RMS) in hypertensive adults remain unavailable. This study aimed to establish sex- and age-specific [...] Read more.
Background/Objectives: Hypertension is a major modifiable risk factor for cardiovascular disease and may negatively affect muscle strength through vascular and metabolic mechanisms. Nevertheless, reference values for respiratory muscle strength (RMS) in hypertensive adults remain unavailable. This study aimed to establish sex- and age-specific reference values for maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) in Brazilian adults with hypertension and to investigate clinical factors associated with these measures. Methods: This cross-sectional study included 234 hypertensive adults (109 women and 125 men; 30–80 years) enrolled in a cardiovascular rehabilitation program. Anthropometric, hemodynamic, and clinical data were collected. RMS was assessed using standardized procedures for MIP and MEP with an analog manovacuometer (−300 to +300 cmH2O). Participants were stratified by age and sex. Statistical analyses included the Mann–Whitney U and Kruskal–Wallis tests and multivariate linear regression (p < 0.05). Results: Men exhibited significantly higher MIP and MEP values than women across most age groups. RMS declined progressively with age, with a more marked reduction after 60 years. MIP was identified as the primary predictor of MEP in both sexes, with higher coefficients of determination in men. The reference values obtained were largely comparable to those reported for healthy individuals. Conclusions: This study provides clinically relevant reference values for RMS Brazilian individuals with hypertension, offering useful parameters for respiratory assessment and individualized rehabilitation strategies. Full article
(This article belongs to the Section Cardiovascular Disease)
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20 pages, 5337 KB  
Article
Obesogenic Dysregulation of Human Periprostatic Adipose Tissue Promotes the Viability of Prostate Cells and Reduces Their Sensitivity to Docetaxel and Cabazitaxel
by Mariana Feijó, Lara R. S. Fonseca, Gonçalo Catarro, Cátia V. Vaz, Carlos Rabaça, Bruno J. Pereira, Eugenia Gallardo, Endre Kiss-Toth, Sara Correia and Sílvia Socorro
Med. Sci. 2025, 13(4), 322; https://doi.org/10.3390/medsci13040322 - 16 Dec 2025
Viewed by 1250
Abstract
Background: Periprostatic adipose tissue (PPAT) has been shown to play a significant role in prostate cancer (PCa) development and progression. This relationship is further exacerbated by obesity, as PPAT-secreted factors increase PCa aggressiveness and have also been implicated in chemotherapy resistance. Therefore, identifying [...] Read more.
Background: Periprostatic adipose tissue (PPAT) has been shown to play a significant role in prostate cancer (PCa) development and progression. This relationship is further exacerbated by obesity, as PPAT-secreted factors increase PCa aggressiveness and have also been implicated in chemotherapy resistance. Therefore, identifying the molecular mediators of PPAT–prostate interorgan communication and the factors that disrupt this crosstalk is pivotal for better disease management. Obesogens, i.e., endocrine-disrupting chemicals that dysregulate adipose tissue towards an “obese” phenotype, have recently been implicated in disrupting this crosstalk, with an impact on prostate cell fate. Objectives: This study aimed to investigate whether obesogenic dysregulation of human PPAT secretory activity affects PCa cell viability and their response to docetaxel and cabazitaxel. Methods/Results: Through ex vivo culture of human PPAT and conditioned medium assays, we demonstrated that exposure to the model obesogen tributyltin (TBT) induced an “obese” phenotype in human PPAT, characterised by adipocyte enlargement and increased secretion of leptin and C-C motif chemokine ligand 7. The TBT-treated PPAT secretome enhanced cell viability and decreased the sensitivity of PCa cells to taxanes. Conclusions: This study provides preliminary evidence that lays the groundwork for future investigations, dissecting the molecular pathways underpinning prostate carcinogenesis and resistance to chemotherapy induced by obesogen-dysregulated PPAT. Full article
(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)
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18 pages, 1122 KB  
Review
Why and How Are Infants with Hutchinson–Gilford Progeria Syndrome Born Without Severe Manifestations?
by Mariia A. Erokhina, Ekaterina A. Vorotelyak, Andrey V. Vasiliev and Vepa K. Abdyev
Med. Sci. 2025, 13(4), 321; https://doi.org/10.3390/medsci13040321 - 15 Dec 2025
Viewed by 1241
Abstract
Children with Hutchinson–Gilford progeria syndrome (HGPS) are born without height and weight abnormalities, and postnatal development is delayed from two months of age. The pathophysiological manifestations of HGPS can be categorized into the three tissue systems that are primarily affected: bone and cartilage, [...] Read more.
Children with Hutchinson–Gilford progeria syndrome (HGPS) are born without height and weight abnormalities, and postnatal development is delayed from two months of age. The pathophysiological manifestations of HGPS can be categorized into the three tissue systems that are primarily affected: bone and cartilage, the smooth muscular layer of the vasculature, and the dermis layer. To understand the biology of the syndrome’s complications resulting from the inherited dominant mutation of the LMNA gene, HGPS has to be considered in embryogenesis. Since the development of the primarily affected HGPS tissues involves a simultaneous contribution of mesodermal and neural crest cells, we hypothesized that the stochastic and heterogeneous coexistence of mesoderm and neural crest cells might be crucial for the onset and manifestation of HGPS. In addition, the expression of Lamin A and/or progerin during embryonic development tends to accumulate in the cell nucleus, causing the syndrome manifestation. Then, how and why are infants with the LMNA gene mutation born without severe deviations? Migration is a distinguishing property of mesoderm and neural crest cells, so that they are continuously subjected to mechanical stimuli throughout development and require normal lamina function. However, the viscoelastic property and the mechanosensor capability to respond to mechanical stress of the HGPS cell nucleus are disturbed. Despite the presence of progerin in development, we assume that high levels of Lamin B1 in cells determine the delayed onset of HGPS after birth. We also hypothesized that progerin toxicity could be managed and prevented, potentially allowing for rescue by the presence of Lamin B1. Full article
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13 pages, 1230 KB  
Article
Is a Single Lipoprotein(a) Measurement Once in a Lifetime Sufficient? The Results from the STAR-Lp(a) Study
by Monika Burzyńska, Piotr Jankowski, Maciej Banach and Michał Chudzik
Med. Sci. 2025, 13(4), 320; https://doi.org/10.3390/medsci13040320 - 15 Dec 2025
Cited by 1 | Viewed by 1981
Abstract
Background: Guidelines suggest that a single lifetime measurement of lipoproteina(a) [Lp(a)] is sufficient for most patients as its levels are largely genetically determined and do not significantly change over time. The aim of the study was to assess the midterm variability in Lp(a) [...] Read more.
Background: Guidelines suggest that a single lifetime measurement of lipoproteina(a) [Lp(a)] is sufficient for most patients as its levels are largely genetically determined and do not significantly change over time. The aim of the study was to assess the midterm variability in Lp(a) levels and its determinants. Methods: The analysis included 1263 patients (68.7% women, median age 69.0 [59.0–75.0] years) who underwent two measurements of Lp(a) levels at an interval of at least one year and up to a maximum of three years. Results: The median Lp(a) level in the first measurement was 9.0 ± 19.0 mg/dl, compared to 8.8 ± 19.1 mg/dL in the second measurement (p < 0.001). The mean increase in Lp(a) level (N = 692) was 4.1 ± 6.9 mg/dL, while the mean decrease (N = 483) was 5.6 ± 11.4 mg/dL. A total of 64.7% of patients exhibited a change in Lp(a) level ≥ 10%, 44.3% ≥ 20%; 28.2% ≥ 30% and 14.0% ≥ 50% of the baseline values. We found no significant differences in the Lp(a) level change related to sex, age, or comorbidities. Conclusions: A significant change in Lp(a) levels was observed in the midterm follow-up. These findings potentially have a profound clinical importance. The current expert recommendation to measure Lp(a) at least once in a lifetime appears to be inaccurate and should be revised. Full article
(This article belongs to the Section Cardiovascular Disease)
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19 pages, 428 KB  
Article
Empowering Patients: A Multicomponent Workshop Improves Self-Management and Quality of Life in Chronic Pain
by María Victoria Ruiz-Romero, María Begoña Gómez-Hernández, Ana Porrúa-Del Saz, María Blanca Martínez-Monrobé, Natalia Gutiérrez-Fernández, Almudena Arroyo-Rodríguez, Rosa Anastasia Garrido-Alfaro, Néstor Canal-Diez, María Dolores Guerra-Martín and Consuelo Pereira-Delgado
Med. Sci. 2025, 13(4), 319; https://doi.org/10.3390/medsci13040319 - 15 Dec 2025
Cited by 2 | Viewed by 1279
Abstract
Background: Chronic pain is a prevalent and disabling condition, affecting 20–30% of the global population, which requires multidisciplinary approaches integrating non-pharmacological therapies and promoting patient engagement in self-management. Objective: To describe the structure, content, outcomes, and lessons learned from multicomponent workshops for chronic [...] Read more.
Background: Chronic pain is a prevalent and disabling condition, affecting 20–30% of the global population, which requires multidisciplinary approaches integrating non-pharmacological therapies and promoting patient engagement in self-management. Objective: To describe the structure, content, outcomes, and lessons learned from multicomponent workshops for chronic non-cancer pain using non-pharmacological therapies. Methods: A quasi-experimental before–after study was conducted in patients attending a chronic pain workshop at San Juan de Dios Hospital (Bormujos, Seville, Spain) between November 2021 and May 2024, with a 3-month follow-up, Validated scales and an ad hoc patient survey were administered at baseline, immediately post-workshop, and at 3-month follow-up. Furthermore, comparative analysis was conducted 4 months before and after the intervention for emergency visits and consultations, medication consumption, and employment status. Analyses employed Chi-square or Fisher’s exact tests (categorical variables); student’s t-tests or Mann–Whitney U (between-group); paired t-tests or Wilcoxon (within-group pre–post); and effect sizes (Cohen’s d, Rosenthal’s r). Significance was set at p < 0.05. Results: 197 patients completed the workshop; 178 (90.4%) were women, mean age: 55.0; 114 (57.9%) had fibromyalgia. Reductions were observed in: pain (scale 0–10) (baseline: 7.0; end of workshop: 5.0; 3 months: 5.0; p < 0.001); anxiety (13.0; 9.0; 11.0; p < 0.001); and depression (11.4; 7.2; 6.8; p < 0.001) (scales 0–21). Increases were noted in: well-being (scale 0–10) (4.0; 6.0; 5.0; p < 0.001); quality of life (scale 0–1) (0.399; 0.581; 0.556; p < 0.001); health status (scale 0–100) (40.0; 60.0; 60.0; p < 0.001); self-esteem (scale 9–36) (23.5; 27.1; 26.6; p < 0.001); and resilience (scale 6–30) (17.0; 18.0; 18.0; p = 0.002, p < 0.001). PROMs were completed by 189 patients at the end of the workshop and 110 at 3 months: pain decreased (end of workshop: 76.7%; 3 months: 80.7%); medication decreased (80.5%; 78.1%); and habits improved (87.2%; 87.6%). 40 patients (37.4%) reduced emergency visits and scheduled consultations. Overall satisfaction: 9.7. Conclusions: The workshop enhanced patients’ self-management and produced improvements in pain, quality of life, emotional well-being, and self-esteem, with effects maintained at 3 months. Full article
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18 pages, 4873 KB  
Article
Effect of N-Acetyl-L-Cysteine (NAC) on Inflammation After Intraperitoneal Mesh Placement in an Escherichia coli Septic Rat Model: A Randomized Experimental Study
by Styliani Parpoudi, Ioannis Mantzoros, Orestis Ioannidis, Konstantinos Zapsalis, Thomai Gamali, Dimitrios Kyziridis, Christos Gekas, Elissavet Anestiadou, Savvas Symeonidis, Stefanos Bitsianis, Efstathios Kotidis, Manousos-Georgios Pramateftakis, Dimosthenis Miliaras, Anastasia Bikouli, Georgios Iosifidis and Stamatios Angelopoulos
Med. Sci. 2025, 13(4), 318; https://doi.org/10.3390/medsci13040318 - 14 Dec 2025
Cited by 1 | Viewed by 1064
Abstract
Background/Objectives: The safety of intraperitoneal mesh placement in contaminated fields remains controversial because of the increased risk of inflammation and adhesion formation. N-acetyl-L-cysteine (NAC) has antioxidant, pro-fibrinolytic and antibiofilm actions that could attenuate this response. The aim of this study is to [...] Read more.
Background/Objectives: The safety of intraperitoneal mesh placement in contaminated fields remains controversial because of the increased risk of inflammation and adhesion formation. N-acetyl-L-cysteine (NAC) has antioxidant, pro-fibrinolytic and antibiofilm actions that could attenuate this response. The aim of this study is to determine whether NAC reduces mesh-related inflammation in a septic model created by intraperitoneal Escherichia coli (E.coli) inoculation. The primary comparison was prospectively defined between E. coli–inoculated animals treated with NAC (D) and those without NAC (B). Groups without E. coli (A,C,E) are presented for context and were compared previously. Methods: In this randomized, double-blind experimental model (five groups, n = 20 per group), all rats underwent midline laparotomy with intraperitoneal placement of a composite mesh, followed by standardized ciprofloxacin administration. The septic groups received intraperitoneal E. coli, while the NAC-treated groups additionally received intraperitoneal NAC (150 mg/kg). Serum levels of IL-1α, IL-6, and TNF-α were measured on postoperative days 7, 14, and 21. On day 21, adhesions were graded using the Modified Diamond system, histology (inflammatory infiltration, fibrosis, neovascularization) was scored, and mesh cultures were obtained. Cytokine data were analyzed with repeated-measures ANOVA, while categorical or ordinal outcomes were assessed using χ2 or Fisher’s exact tests with Bonferroni-adjusted pairwise comparisons. Results: E. coli inoculation significantly increased adhesion burden and worsened histologic scores compared with controls (both p < 0.001). NAC administration in the septic model significantly reduced adhesions and improved all histologic domains relative to E. coli alone (all p ≤ 0.003), with values comparable to controls (non-significant across domains). For cytokines, there was a significant overall group effect for IL-1α, IL-6, and TNF-α (all p < 0.001), without a main effect of time or time × group interaction. Pairwise contrasts showed lower IL-1α (p = 0.024), IL-6 (p < 0.001), and TNF-α (p < 0.001) levels in group D versus B, and lower IL-6 and TNF-α in group D versus A (both p < 0.001). Mesh culture positivity rate was higher in group B than A (p < 0.001) and showed a non-significant reduction in group D versus B (p = 0.10). No perioperative deaths occurred. Conclusions: NAC attenuated septic, mesh-associated inflammation—normalizing adhesions and histology and reducing IL-6 and TNF-α— supporting its role as a host-directed adjunct alongside antibiotics. Further translational studies are warranted to define the optimal dose, timing, and clinical indications. Full article
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5 pages, 195 KB  
Editorial
Ethical Horizons in Robotic Rehabilitation: Ensuring Safe AI Use Under the EU AI Act
by Rocco Salvatore Calabrò
Med. Sci. 2025, 13(4), 317; https://doi.org/10.3390/medsci13040317 - 14 Dec 2025
Viewed by 733
Abstract
Artificial intelligence (AI) is reshaping robotic rehabilitation and shifting practice beyond pre-programmed repetitive movement patterns toward data-driven and personalised therapeutic interventions for people with neurological and musculoskeletal impairments [...] Full article
(This article belongs to the Section Neurosciences)
20 pages, 1573 KB  
Article
Determinants of Entero-Invasive and Non-Entero-Invasive Diarrheagenic Bacteria Among HIV-Positive and HIV-Negative Adults in Ghana
by Hagen Frickmann, Fred Stephen Sarfo, Betty Roberta Norman, Albert Dompreh, Shadrack Osei Asibey, Richard Boateng, Veronica Di Cristanziano, Tafese Beyene Tufa, Ulrike Loderstädt, Ramona Binder, Andreas Erich Zautner, Tom Luedde, Torsten Feldt and Kirsten Alexandra Eberhardt
Med. Sci. 2025, 13(4), 316; https://doi.org/10.3390/medsci13040316 - 12 Dec 2025
Viewed by 882
Abstract
Objectives: This observational and cross-sectional study investigated differential associations between entero-invasive and non-entero-invasive enteric pathogens and HIV infection, considering socioeconomic, clinical and immunological aspects. In a Ghanaian population with a high prevalence of enteric pathogens, stool samples from people living with HIV (PLWH) [...] Read more.
Objectives: This observational and cross-sectional study investigated differential associations between entero-invasive and non-entero-invasive enteric pathogens and HIV infection, considering socioeconomic, clinical and immunological aspects. In a Ghanaian population with a high prevalence of enteric pathogens, stool samples from people living with HIV (PLWH) were screened for Salmonella spp., Shigella spp./EIEC (enteroinvasive Escherichia coli), and Campylobacter jejuni as entero-invasive bacteria, for enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), and enteroaggregative E. coli (EAEC) as non-entero-invasive bacteria. Arcobacter butzleri, with uncertain enteropathogenicity, was also included. Methods: Stool samples from PLWH (with and without antiretroviral therapy) and HIV-negative controls were analyzed by real-time PCR for the presence and quantity of the selected enteropathogens. Results were correlated with socioeconomic, clinical, and immunological parameters. Results: The presence of Shigella spp. /EIEC in stool was both qualitatively and quantitatively associated with reduced CD4+ T lymphocyte counts and was qualitatively associated with clinically apparent diarrhea. EAEC showed a weak positive association with HIV infection, supported by a negative correlation between EAEC DNA quantity and CD4+ T lymphocyte counts. EPEC colonization was associated with HIV negativity, higher CD4+ T lymphocyte counts, and lower socioeconomic status. Abundance of Salmonella enterica was associated with clinically apparent diarrhea. Conclusions: This explorative, hypothesis-forming study suggests species- or pathovar-specific associations between enteric bacterial pathogens and HIV-related immunosuppression. Observed relationships with clinically apparent diarrhea largely align with findings from sub-Saharan African children, except for a more pronounced association between diarrhea and Salmonella in this cohort. Full article
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13 pages, 594 KB  
Article
Outcome and Toxicity of Moderately Hypofractionated Post-Prostatectomy Radiotherapy: A Retrospective Study
by Rocchina Vilella, Fiorella D’Auria, Luciana Valvano, Barbara D’Andrea, Antonietta Montagna, Giovanni Castaldo, Ilaria Benevento, Angela Pia Solazzo, Manuela Botte, Grazia Lazzari, Teodora Statuto and Luciana Rago
Med. Sci. 2025, 13(4), 315; https://doi.org/10.3390/medsci13040315 - 12 Dec 2025
Cited by 1 | Viewed by 882
Abstract
Background: In this study, we retrospectively analyzed clinical and toxicity outcomes of 67 prostate cancer (PCa) patients undergoing moderately hypofractionated radiotherapy (RT) after prostatectomy, with adjuvant or salvage intent. Methods: Irradiation was delivered by volumetric modulated arc therapy. The median follow-up [...] Read more.
Background: In this study, we retrospectively analyzed clinical and toxicity outcomes of 67 prostate cancer (PCa) patients undergoing moderately hypofractionated radiotherapy (RT) after prostatectomy, with adjuvant or salvage intent. Methods: Irradiation was delivered by volumetric modulated arc therapy. The median follow-up was 48 months. The 3- and 5-year biochemical relapse-free survival rates were 80% and 69%. The RT schedule consisted of a median total dose of 67.5 Gy with a median number of 25 fractions and a median fraction dose of 2.7 Gy to the prostate bed (PB) and 60% of patients simultaneously received whole pelvis irradiation (WP; fraction dose: 1.8 Gy, median total dose of 46.8 Gy). Results: The rate of acute toxicity was 54% for gastrointestinal (GI) and 36% for genitourinary (GU). No grade 3 acute toxicity was observed. Late toxicity was as follows: G1, G2, and G3 GI events in 25.5%, 3.6%, and 1.8% of the cases, respectively; G1, G2, and G3 GU events in 37.1%, 11.1%, and 7.4%, respectively. The toxicity-free survival (TFS) curves showed a different trend for acute and late toxicity. TFS was significantly associated with RT volume, except for acute GI toxicity. Specifically, the concomitant irradiation of PB and WP appeared to be a significant risk factor for late GI and GU toxicity (p = 0.029 and p = 0.012, respectively). Conclusions: At the 48-month median timepoint considered by our study, postoperative hypofractionated RT achieved promising results in terms of clinical outcomes with acceptable toxicity. Only the irradiated volume seems to be an important predictor for toxicity. Full article
(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)
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15 pages, 3293 KB  
Article
Evaluation of Cell Mimics as Potential Quality Controls for Human Leukocyte Immunophenotyping
by Louis Waeckel, Brigitte Le Mauff, Jacques Trauet, Julie Demaret, Ahmed Boumediene, Margarita Hurtado-Nedelec, Arnaud Ciree, Gwladys Bourdenet and Claude Lambert
Med. Sci. 2025, 13(4), 314; https://doi.org/10.3390/medsci13040314 - 11 Dec 2025
Viewed by 673
Abstract
Background. Routine lymphocyte counting requires quality assurance validation using quality controls (QCs) that closely resemble fresh human blood leukocytes. This study aimed to evaluate a novel artificial product designed to mimic leukocyte light scatters and marker expression. Methods. FlowCytes and TruCytes, [...] Read more.
Background. Routine lymphocyte counting requires quality assurance validation using quality controls (QCs) that closely resemble fresh human blood leukocytes. This study aimed to evaluate a novel artificial product designed to mimic leukocyte light scatters and marker expression. Methods. FlowCytes and TruCytes, “artificial cell mimics” (Slingshot Biosciences, Emeryville, CA, USA), were tested on CE-IVD-certified systems, namely FACSCanto, FACSLyric (BD Biosciences), Navios, and DxFlex (Beckman Coulter), using routine staining, lysing, fixation, and no-wash procedures for T, B, and NK counting. Results. FlowCytes and TruCytes provided forward and side scatter profiles comparable to human leukocytes on the FACSCanto, FACSLyric, and DxFlex systems but not on Navios despite adapting the process to be slightly different from the manufacturer’s recommendations. TruCytes demonstrated robust immunolabeling of CD3, CD4, CD8, and CD19 on the FACSCanto, FACSLyric, and DxFlex systems, with fluorescence intensities and subset distributions being similar to those usually observed in fresh human blood. However, CD16 and CD56 labeling was inconsistent and depended on the antibody clones used. Regrettably, monocyte and granulocyte mimics lacked expression of CD4, CD16, and CD14. TruCytes also displayed significantly lower concentrations of TBNK lymphocyte subsets compared to healthy human blood. Conclusions. FlowCytes and TruCytes show promises as internal quality controls for T cell and B cell immunophenotyping, but not NK cells. They are compatible with most CE-IVD cytometers, even when using lysis/fixation/no-wash routine diagnosis procedures. Further multicentric studies are warranted to assess their performance relative to existing products, such as stabilized human blood. Full article
(This article belongs to the Section Translational Medicine)
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11 pages, 855 KB  
Article
Echocardiographic Alterations in Subjects with Sarcopenia and Right Heart Failure
by Arturo Orea-Tejeda, Luis Aldo Delgado-Pérez, Benigno Valderrábano-Salas, Dulce González-Islas, Álvaro Montañez-Orozco, José Carlos Ruan-Díaz, María José Hernández-Hernández, Edgar Lozano-Hernández, Carlos Patricio Chávez-Guzmán and Karla García-Díaz
Med. Sci. 2025, 13(4), 313; https://doi.org/10.3390/medsci13040313 - 10 Dec 2025
Viewed by 846
Abstract
Background: Chronic heart failure (HF) is a significant public health issue. The principal risk factors for left ventricular diastolic dysfunction (LVDD) include older age, female sex, obesity, hypertension, smoking, and diabetes, among others, all of which can reduce physical activity. Additionally, peripheral factors [...] Read more.
Background: Chronic heart failure (HF) is a significant public health issue. The principal risk factors for left ventricular diastolic dysfunction (LVDD) include older age, female sex, obesity, hypertension, smoking, and diabetes, among others, all of which can reduce physical activity. Additionally, peripheral factors such as skeletal muscle mass (SMM) abnormalities decrease maximal oxygen consumption. In elderly HF patients, the prevalence of sarcopenia is higher than in those without HF; however, the relationship between sarcopenia and HF remains insufficiently explained, particularly in right HF (RHF). Our objective was to describe the echocardiographic alterations between sarcopenic and non-sarcopenic subjects with RHF. Methods: A cross-sectional study was conducted. Outpatients aged 18 years or older with a confirmed diagnosis of RHF were included. Sarcopenia was defined according to EWGSOP2. Results: A total of 183 patients were included; 24.5% had sarcopenia. The mean age was 64.34 ± 13.97 years. Echocardiographic characteristics revealed evidence of LVDD in sarcopenic subjects, as indicated by lower E wave velocity, E/A ratio, and e’ lateral and medial values, as well as lower right ventricular (RV) wall thickness compared with non-sarcopenic subjects. The multivariate model showed that sarcopenia subjects had lower RV wall thickness (B: −1.36 mm, 95% CI: −2.30 to −0.42), e’ medial (B: −1 cm/s, 95% CI: −1.99 to −0.02), and e’ lateral (B: −1.78 cm/s, 95% CI: −2.97 to −0.60). Conclusions: The prevalence of sarcopenia in RHF patients was 24.6%, which was associated with LVDD and lower RV wall thickness, suggesting a loss of cardiac muscle mass. Full article
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16 pages, 281 KB  
Article
Montreal Cognitive Assessment (MoCA) Norms for Older Patients with a Depressive Disorder
by Myrthe E. Scheenen, Rob H. S. van den Brink, Styliani Konstantinidou, Astrid Lugtenburg, Jasmijn Spit, Gert-Jan Hendriks, Paul Naarding, Nathalie R. de Vent, Roy P. C. Kessels, Richard C. Oude Voshaar and Hans W. Jeuring
Med. Sci. 2025, 13(4), 312; https://doi.org/10.3390/medsci13040312 - 10 Dec 2025
Viewed by 2498
Abstract
Background: Interpretation of cognitive performance in older patients with depression is challenging considering the association between late-life depression and (early-stage) neurodegenerative disease. The Montreal Cognitive Assessment (MoCA) is widely used to screen for mild cognitive impairment in community-dwelling older adults. Objective: [...] Read more.
Background: Interpretation of cognitive performance in older patients with depression is challenging considering the association between late-life depression and (early-stage) neurodegenerative disease. The Montreal Cognitive Assessment (MoCA) is widely used to screen for mild cognitive impairment in community-dwelling older adults. Objective: The aim of the present study was to examine the need for and to develop dedicated MoCA norms for older people with depressive disorder. Methods: We used data from the Routine Outcome Monitoring for Geriatric Psychiatry & Science (ROM-GPS) study and the Advanced Neuropsychological Diagnostics Infrastructure (ANDI) database, which consisted of 859 patients with a depressive disorder according to DSM-5 criteria and 320 healthy controls, aged ≥60 years. Linear regression was used to examine the relationship between late-life depression and MoCA scores, adjusted for age, sex, and education. Results: The presence of a depressive disorder was associated with lower MoCA scores, and this effect was larger for persons with 12 years or less of education than for those with more education (B = −0.76 [95% CI −0.61; −0.91] vs. −0.53 [−0.36; −0.70]). Among depressed patients, depressive symptom severity was not associated with the MoCA score. Regression-based normative data for the MoCA were computed and adjusted for age, education, sex, and type of depressive disorder. Conclusions: Our findings demonstrate that depressive disorder, but not symptom severity within depression, is associated with lower MoCA scores. Clinical interpretation of MoCA scores in depressed older persons can be facilitated by using MoCA reference tables stratified by age, sex and level of education. Full article
11 pages, 878 KB  
Article
Universal Hip Ultrasound Screening in Newborns: A 21-Month Prospective Observational Study in a Spoke Center
by Neftj Ragusa, Nefer Roberta Gianotto, Virginia Deut, Chiara Mattivi, Francesca Compagno, Marta Cherubini Scarafoni, Silvia Dominici and Massimo Berger
Med. Sci. 2025, 13(4), 311; https://doi.org/10.3390/medsci13040311 - 10 Dec 2025
Viewed by 941
Abstract
Background: Developmental dysplasia of the hip (DDH) encompasses a spectrum of neonatal hip abnormalities that, if not detected and treated early, may lead to long-term orthopedic sequelae. Universal ultrasound screening using Graf’s method has been proposed to improve early diagnosis, though its implementation [...] Read more.
Background: Developmental dysplasia of the hip (DDH) encompasses a spectrum of neonatal hip abnormalities that, if not detected and treated early, may lead to long-term orthopedic sequelae. Universal ultrasound screening using Graf’s method has been proposed to improve early diagnosis, though its implementation remains heterogeneous in Italy. Objectives: This study aimed to describe the outcomes of a universal ultrasound screening program for DDH conducted in a first-level birth center in northern Italy, evaluating DDH incidence, risk factors, management outcomes, and program feasibility. Methods: A prospective observational study was conducted from February 2024 to October 2025 at the Ivrea birth center (Piedmont region, Italy). All consecutive live-born infants (n = 904) underwent hip ultrasound according to Graf’s method, between 0 and 11 weeks of age. Hips were classified as type I (normal), type IIa (physiologically immature), or type IIb–IV (pathological). Infants with type IIa hips were re-evaluated after 2–4 weeks; those with type IIb or worse were referred to pediatric orthopedics. Results: Of 1808 hips examined, 92% were Graf type I and 8% type IIa. After follow-up, 93% of type IIa hips matured spontaneously. Pathological DDH (Graf IIb or worse) was diagnosed in 8 infants (0.88%), of whom 75% were female; 50% had no identifiable risk factors. All affected infants were treated with harness before 12 weeks of age, with complete recovery and no late diagnoses. No infant required surgical treatment. Conclusions: Universal ultrasound screening for DDH was feasible and effective in a first-level birth center, ensuring early diagnosis and absence of late-presenting cases. These findings support universal screening as a safe and equitable approach to reduce DDH-related morbidity and align with national recommendations for standardized early detection programs. Full article
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32 pages, 2795 KB  
Review
Emerging Insights into the Interplay Between PANoptosis and Autophagy in Immune Regulation and Immune-Mediated Inflammatory Diseases
by Ferenc Sipos and Györgyi Műzes
Med. Sci. 2025, 13(4), 310; https://doi.org/10.3390/medsci13040310 - 8 Dec 2025
Cited by 1 | Viewed by 1923
Abstract
PANoptosis is an integrated form of regulated cell death that combines pyroptosis, apoptosis, and necroptosis through a coordinated molecular platform known as the PANoptosome. Autophagy, in parallel, maintains immune homeostasis by controlling cellular stress responses. Although both pathways are essential for innate and [...] Read more.
PANoptosis is an integrated form of regulated cell death that combines pyroptosis, apoptosis, and necroptosis through a coordinated molecular platform known as the PANoptosome. Autophagy, in parallel, maintains immune homeostasis by controlling cellular stress responses. Although both pathways are essential for innate and adaptive immunity, their functional interplay has only recently been explored. This review summarizes current knowledge on the bidirectional relationship between PANoptosis and autophagy, with emphasis on how autophagy can restrain PANoptotic signaling or, under certain conditions, promote inflammatory cell death. We discuss cell-type-specific aspects of this crosstalk in macrophages, dendritic cells, monocytes, neutrophils, T cells, and B cells, focusing on key PANoptosis mediators and autophagy-related proteins. We then examine how dysregulated autophagy and exaggerated PANoptotic signaling contribute to chronic inflammation and tissue damage in immune-mediated inflammatory disease, including systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, psoriasis, and inflammatory bowel disease. Finally, we outline shared molecular principles that position the autophagy–PANoptosis axis as a fundamental immunoregulatory mechanism and a promising source of therapeutic targets in chronic inflammatory and autoimmune disorders. Full article
(This article belongs to the Section Immunology and Infectious Diseases)
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12 pages, 1295 KB  
Article
Cytokine Profiles and Inflammatory Implications in Chagas Disease: Associations with Ventricular Function and Conduction Disorders
by Mario Principato, Maria Victoria Carvelli, Analia Gladys Paolucci, Silvia Miranda, Guillermo Alberto Keller, Manuel Lago, Guillermo Di Girolamo and Justo Carbajales
Med. Sci. 2025, 13(4), 309; https://doi.org/10.3390/medsci13040309 - 8 Dec 2025
Viewed by 717
Abstract
Background: The roles of cytokines and chemokines in the pathogenesis of Chagas cardiomyopathy (CC) have been proposed, yet their clinical significance with respect to conduction disturbances and left ventricular ejection fraction (LVEF) remains unclear. Aim: The objective of this study was to analyze [...] Read more.
Background: The roles of cytokines and chemokines in the pathogenesis of Chagas cardiomyopathy (CC) have been proposed, yet their clinical significance with respect to conduction disturbances and left ventricular ejection fraction (LVEF) remains unclear. Aim: The objective of this study was to analyze the associations between cytokine levels and systolic function, comparing patients with preserved and reduced ejection fractions. As a secondary objective, we evaluated whether differences were present in cytokine levels within the subgroup with preserved ejection fraction, depending on the presence or absence of intraventricular conduction disturbances. Methods: We conducted an analytical cross-sectional study involving patients with Chagas disease and a healthy control group. Among patients with Chagas disease, those with preserved (>50%) and reduced (<35%) left ventricular ejection fraction (LVEF) were selected. The preserved-LVEF group included individuals with and without conduction disorders. Cytokines (IFN-γ, IL-1β, IL-6, IL-10, IL-12p70, IL-15, IL-17A, MCP-1, MIP1α, TNF-α, and IL-2) were quantified using a magnetic bead-based multiplex assay. Results: Forty-four patients with CD (26 men, 59%) and 14 seronegative controls were included. In the CD group, 50% (n = 22) had preserved LVEF (LVEF > 50%), and 50% (n = 22) had decreased LVEF (≤35%). No significant differences in cytokine concentrations were observed between patients with preserved and reduced LVEF for TNF-α (19.74 ± 8.32 vs. 22.23 ± 6.40 pg/mL; p = 0.189), IL-6 (2.17 ± 2.41 vs. 5.40 ± 6.40 pg/mL; p = 0.145), IL-2 (2.61 ± 1.05 vs. 2.97 ± 1.79 pg/mL; p = 0.481), MCP-1 (214.18 ± 96.99 vs. 183.83 ± 63.21 pg/mL; p = 0.481) and IFN-γ (9.04 ± 4.90 vs. 7.64 ± 3.78 pg/mL; p = 0.372). Within the subgroup with preserved LVEF (n = 22), those with conduction disorders (n = 10) exhibited higher levels of IL-10 (24.49 vs. 9.83 pg/mL; q = 0.009), IL-12p70 (13.20 vs. 9.02 pg/mL; q = 0.027), IL-2 (2.70 vs. 2.07 pg/mL; q = 0.023), IL-15 (7.09 vs. 3.36 pg/mL; q = 0.018), MIP1α (10.33 vs. 3.35 pg/mL; q = 0.014) and IFN-γ (10.83 vs. 7.25 pg/mL; q = 0.005), compared to those without conduction disorders (n = 12). Notably, patients with CD and preserved LVEF (>50%) without conduction disturbances presented cytokine profiles similar to those of seronegative healthy controls with LVEF ≥ 50%. Conclusions: Elevated levels of specific cytokines were associated with conduction disturbances in patients with preserved LVEF. Despite this finding, a causal relationship cannot be established, and future studies are needed to explore their prognostic or therapeutic significance. Full article
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23 pages, 1636 KB  
Review
Nuclear Medicine Imaging Biomarkers in Parkinson’s Disease: Past, Present, and Future Directions
by Anna Lisa Martini, Stelvio Sestini, Dinahlee Saturnino Guarino and Paola Feraco
Med. Sci. 2025, 13(4), 308; https://doi.org/10.3390/medsci13040308 - 7 Dec 2025
Viewed by 2114
Abstract
Parkinson’s disease (PD) is a multifaceted neurodegenerative disorder characterized by dopaminergic neuronal loss and widespread α-synuclein pathology. Nuclear medicine imaging offers essential in vivo tools for early diagnosis, differential assessment, and monitoring disease progression. This review summarizes key PET and SPECT radiotracers targeting [...] Read more.
Parkinson’s disease (PD) is a multifaceted neurodegenerative disorder characterized by dopaminergic neuronal loss and widespread α-synuclein pathology. Nuclear medicine imaging offers essential in vivo tools for early diagnosis, differential assessment, and monitoring disease progression. This review summarizes key PET and SPECT radiotracers targeting dopaminergic synthesis and transport, vesicular storage, post-synaptic receptors, neuroinflammation, and protein aggregation, highlighting their roles in clinical evaluation and phenotyping. Clinically, these modalities support earlier recognition of PD, distinction from atypical parkinsonian syndromes, and assessment of non-motor involvement. Future directions include the development of selective α-synuclein tracers and multimodal imaging strategies to refine prodromal detection and guide personalized therapeutic interventions. Full article
(This article belongs to the Collection Advances in the Pathogenesis of Neurodegenerative Diseases)
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9 pages, 1226 KB  
Communication
Short-Term Outcomes of a Structured Self-Rehabilitation Program After Mini-Open Latarjet Procedure in Military Personnel: A Prospective Observational Study
by Kyriakos Bekas, Ioannis Bampis, Alexandros Stamatopoulos, Apostolos-Apollon Papadimitriou, Konstantinos Vamvakeros, Ioannis Kechagias and Achilleas Boutsiadis
Med. Sci. 2025, 13(4), 307; https://doi.org/10.3390/medsci13040307 - 7 Dec 2025
Viewed by 821
Abstract
Background/Objectives: The COVID-19 pandemic limited access to in-person physiotherapy, raising concerns about post-operative rehabilitation outcomes. This prospective observational study, without a control group, evaluated whether a self-rehabilitation protocol following a mini-open Learjet procedure influenced short-term clinical outcomes in active military personnel. Materials and [...] Read more.
Background/Objectives: The COVID-19 pandemic limited access to in-person physiotherapy, raising concerns about post-operative rehabilitation outcomes. This prospective observational study, without a control group, evaluated whether a self-rehabilitation protocol following a mini-open Learjet procedure influenced short-term clinical outcomes in active military personnel. Materials and Methods: We prospectively enrolled 18 patients (19 shoulders) undergoing mini-open Latarjet between May and October 2020. Patients performed a standardized self-rehabilitation protocol starting on the first post-operative day, with progressive range-of-motion (ROM) exercises added at two weeks. Pain was assessed using the Visual Analog Scale (VAS), ROM was recorded at each follow-up, complications were noted, and patient satisfaction was evaluated at 12 weeks. Results: A total of eighteen patients were prospectively enrolled in the study. At 12 weeks, mean VAS decreased from 1.2 ± 0.6 at week 1 to 0 at week 4 onward. The mean drug consumption was 2.5 ± 0.7 tablets/day only for the first week. Mean assisted forward flexion improved from 155° ± 10° at week 1 to 180° in all patients by week 4. External rotation reached 60° ± 5°at 4 weeks, 75° ± 4° at 8 weeks, and 80° ± 3°at 12 weeks, with no deficits compared to the contralateral side. Internal rotation improved to the T7 level by week 8 and remained stable in week 12. No complications, recurrent instability, or graft displacements were reported. Patient satisfaction at 12 weeks was assessed using a 0–10 numeric rating scale, with a mean score of 9.5 ± 0.4. Conclusions: Implementation of a self-rehabilitation protocol after mini-open Latarjet surgery was associated with favorable short-term outcomes in young military patients, including early recovery, high satisfaction, and absence of complications. Further validation of these findings will require larger, rigorously controlled studies. Full article
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16 pages, 2288 KB  
Article
Exploring New Frontiers: A Cross-Sectional Analysis of Explosive Phase and Muscle Activation During Maximal Biting in Women with Temporomandibular Disorder and Orofacial Pain
by Bianca Rossi Botim, Mayra Evelise Cunha dos Santos, Arthur Ferreira Esquírio, Kariny Realino do Rosário Ferreira, Ana Clara Leal, Gabriel Alves Godinho, Maria de Cássia Souza Macedo, Thaís Carvalho Oliveira, Gabriela Lopes Gama, Michelle Cristina Sales Almeida Barbosa and Alexandre Wesley Carvalho Barbosa
Med. Sci. 2025, 13(4), 306; https://doi.org/10.3390/medsci13040306 - 6 Dec 2025
Viewed by 927
Abstract
Background: Temporomandibular disorders (TMDs) are associated with altered masticatory muscle function and pain. Although electromyographic parameters have been extensively studied, the rate of force development (RFD) remains an underexplored biomarker in this context. Objective: Analyze the RFD differences in women diagnosed with and [...] Read more.
Background: Temporomandibular disorders (TMDs) are associated with altered masticatory muscle function and pain. Although electromyographic parameters have been extensively studied, the rate of force development (RFD) remains an underexplored biomarker in this context. Objective: Analyze the RFD differences in women diagnosed with and without TMD. As a secondary outcome, the masseter and temporalis muscle pre-activation values were compared between groups based on the biting force onset. Additionally, neuromuscular efficiency analysis was also performed. Methods: A retrospective analysis of 62 medical records (41 with TMD, 21 controls) was conducted. Electromyographic activity and bite force were measured during three 5-s maximal biting tasks using synchronized surface electromyography (sEMG) and a laboratory-grade load cell. RFD was computed from force–time curves. Muscle pre-activation was assessed based on sEMG activity immediately preceding contraction onset. Results: The TMD group showed a significantly smaller RFD (mean = 85.5 N/s) compared to controls (mean = 109.0 N/s; p = 0.03; Cohen’s d = 0.5). No significant differences were found in neuromuscular efficiency and pre-activation or post-activation levels of the masseter and temporalis muscles between groups. Conclusions: RFD distinguishes women with TMD from healthy controls and may represent a sensitive biomechanical marker of neuromuscular adaptation in TMD, although confirmatory studies are needed. The absence of neuromuscular efficiency and pre-activation differences suggests compensatory neuromuscular mechanisms. Further prospective studies are needed to validate these findings and explore clinical applications. Full article
(This article belongs to the Special Issue The Impact of Temporomandibular Disorders on the Wellbeing)
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15 pages, 1444 KB  
Article
Durvalumab Is Associated with Prolonged Progression-Free Survival, While Concomitant Chemoradiotherapy May Improve Both Locoregional and Local Control in Elderly Patients with Unresectable NSCLC Stage III: Subanalysis of the Austrian Radio-Oncological Lung Cancer Study Association Registry (ALLSTAR)
by Franz Zehentmayr, Josef Karner, Markus Stana, Elvis Ruznic, Barbara Zellinger, Marisa Klebermass, Ayurzana Purevdorj, Georg Gruber, Danijela Minasch, Martin Heilmann, Raphaela Moosbrugger, Falk Roeder and Brane Grambozov
Med. Sci. 2025, 13(4), 305; https://doi.org/10.3390/medsci13040305 - 5 Dec 2025
Viewed by 879
Abstract
Introduction: The incidence of NSCLC increases with age, with a median of approximately 70 years at diagnosis. Historically, treatment strategies for locally advanced cancers have been developed predominantly in younger populations, often excluding elderly patients who may present with multiple comorbidities, severely impaired [...] Read more.
Introduction: The incidence of NSCLC increases with age, with a median of approximately 70 years at diagnosis. Historically, treatment strategies for locally advanced cancers have been developed predominantly in younger populations, often excluding elderly patients who may present with multiple comorbidities, severely impaired lung function, or decreased performance status, leading to a lack of age-relevant clinical data. Therefore, we performed a subanalysis of real-world data from the ALLSTAR study to investigate the impact of durvalumab and the radiation regimen (sequential versus concurrent) on clinical outcome in elderly patients with unresectable stage III NSCLC. Methods: We included a total of 171 patients in this subanalysis. All patients were diagnosed with unresectable stage III NSCLC. Patients were divided into two age groups, ≥70 (41%) and <70 years (59%). All of them received curative chemoradiotherapy with (66%) or without (34%) durvalumab. Results: Patients were followed up for a median time of 25.1 months (range: 3.3–52.1). In the elderly group, patients who did not receive durvalumab consolidation had a median PFS of 17 months (95%-CI: 12.4—not reached) and a higher risk of progression (HR = 2.2; 95%-CI: 1–4.6) than those treated with durvalumab, which had a median PFS of 37 months (95%-CI: 24.5—not reached). This difference was statistically significant (log rank p = 0.026). Moreover, the Cox model yielded a hazard ratio suggesting a higher risk of locoregional (HR = 3.8; 95%-CI: 1.28–11.48; log rank p-value =0.01) as well as local recurrence (HR = 5.5: 95%-CI: 1.67–18.1: p-value =0.002) in patients who received sequential chemoradiotherapy compared to those with concomitant chemoradiotherapy in the same age group. In an exploratory analysis based on a Mann–Whitney U test, we did not find significant difference in toxicity between the two age groups. Conclusions: Durvalumab was associated with prolonged progression-free survival, while concomitant radiotherapy showed a trend towards improvement in locoregional and local control in patients aged ≥70. There was no significant difference in treatment toxicity found in the exploratory Mann–Whitney U analysis between the two age groups. Full article
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11 pages, 836 KB  
Article
Evaluation of Bone Mineral Density: Correlating MRI Cervical Vertebral Bone Quality, CT Hounsfield Units, and DEXA T-Scores
by Rose Fluss, Riana Lo Bu, Alireza Karandish, Sertac Kirnaz, Rafael De la Garza Ramos, Saikiran G. Murthy, Reza Yassari and Yaroslav Gelfand
Med. Sci. 2025, 13(4), 304; https://doi.org/10.3390/medsci13040304 - 4 Dec 2025
Viewed by 1422
Abstract
Background/Objectives: Dual-energy X-ray absorptiometry (DEXA), the gold standard for assessing bone mineral density (BMD), may yield inaccurate results in certain populations. This has prompted interest in alternative imaging methods, including the MRI-based cervical and lumbar vertebral bone quality (CVBQ and LVBQ) scores. The [...] Read more.
Background/Objectives: Dual-energy X-ray absorptiometry (DEXA), the gold standard for assessing bone mineral density (BMD), may yield inaccurate results in certain populations. This has prompted interest in alternative imaging methods, including the MRI-based cervical and lumbar vertebral bone quality (CVBQ and LVBQ) scores. The lumbar VBQ score is a validated MRI-based metric with excellent inter- and intra-rater reliability and established clinical utility in preoperative spine assessment, whereas the newer cervical VBQ (CVBQ) score has shown mixed results in early studies. This study investigates associations between a novel CVBQ score derived from MRI and established BMD metrics (Hounsfield unit (HU) measurements and DEXA values) to evaluate the comparative utility of these methods. Methods: A retrospective review was performed on patients who underwent cervical CT, DEXA, and non-contrast MRI of the cervical and lumbar spine between 2016 and 2022. BMD was assessed using DEXA T-scores, cervical HU measurements, and CVBQ and LVBQ scores derived from T1-weighted MRI sequences. Statistical comparisons between patients with and without osteoporosis were conducted using t-tests and Pearson correlation coefficients. Results: A total of 133 patients were included for CVBQ scoring and 127 for LVBQ. The CVBQ score showed poor correlation with both DEXA (r = −0.09, p < 0.001) and HU measurements (r = −0.34, p < 0.001), whereas a moderate correlation was found between LVBQ and DEXA scores (r = −0.34, p < 0.001). Conclusions: The LVBQ score demonstrates moderate correlation with DEXA and may serve as a reliable tool for preoperative BMD assessment. However, the CVBQ score showed weak correlation with both DEXA and HU, limiting its clinical utility in its current form. Further refinement of the CVBQ methodology is needed to enhance its accuracy and relevance for surgical risk assessment and postoperative outcome prediction. Full article
(This article belongs to the Section Neurosciences)
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11 pages, 228 KB  
Article
Assessment of Changes in Glycaemic Control and Blood Viscosity Determinants: Does Glycaemia Impact on Haematocrit, Proteinaemia or Dyslipidaemia?
by Jovita Igwebuike Mbah, Phillip Taderera Bwititi, Prajwal Gyawali and Ezekiel Uba Nwose
Med. Sci. 2025, 13(4), 303; https://doi.org/10.3390/medsci13040303 - 4 Dec 2025
Cited by 2 | Viewed by 737
Abstract
Background: The relationship between glycaemia and the variables of haematocrit, serum total protein and lipids possibly plays a role in pathological processes and hence is a subject of interest. Estimated blood viscosity causes impaired blood flow and is a factor in other vascular [...] Read more.
Background: The relationship between glycaemia and the variables of haematocrit, serum total protein and lipids possibly plays a role in pathological processes and hence is a subject of interest. Estimated blood viscosity causes impaired blood flow and is a factor in other vascular diseases. Blood viscosity is correlated with glycated haemoglobin, but the mechanism of this association has not been extensively investigated. Objective: To assess if changes in glycated haemoglobin translate into changes in blood viscosity through impact on haematocrit, serum protein or dyslipidaemia. Method: This was a clinical laboratory-based retrospective data analysis of patients attending a diabetic clinic. Analysis involved seven variables comprising serum total protein level, high-density lipoprotein cholesterol, total cholesterol, triglyceride, age and glycated haemoglobin. The statistical evaluations were descriptive, comparative and correlational. Results: A total of 12,986 sets of data represented the participants in this study. After excluding three with incomplete data of interest, the groups that were created for comparison comprised the following: good glycaemic control (2694), moderate glycaemic control (4075) and poorly controlled (6194). Serum levels of high-density lipoprotein cholesterol, total cholesterol, haematocrit and proteinaemia gradually decreased with worsening glycaemic control, while serum triglyceride and age increased. In the correlation analysis, serum triglyceride level was positively correlated with glycated haemoglobin r = 0.177, while haematocrit and proteinaemia were negatively related, at −0.045 and −0.103, respectively. Conclusions: Increase in glycated haemoglobin was inversely related to haematocrit and proteinaemia; therefore, this did not always increase with the determinants of estimated whole blood viscosity. The implication of this is that further studies are required to substantiate the observation of higher whole blood viscosity levels in patients with poorly controlled diabetes. Full article
27 pages, 2917 KB  
Review
Microbiome and Heart Failure: A Comprehensive Review of Gut Health and Microbiota-Derived Metabolites in Heart Failure Progression
by Chukwudi Kingsley Orjichukwu, Rita Ogochukwu Orjichukwu, Peter Kanayochukwu Akpunonu, Paul Chikwado Ugwu and Somtochukwu Godfrey Nnabuife
Med. Sci. 2025, 13(4), 302; https://doi.org/10.3390/medsci13040302 - 4 Dec 2025
Viewed by 2265
Abstract
A multifaceted clinical disease, heart failure (HF) is typified by decreased cardiac function and systemic symptoms caused by anatomical or functional abnormalities in the heart. Although traditional studies have concentrated on hemodynamic and neurohormonal processes, new data highlight the vital role that the [...] Read more.
A multifaceted clinical disease, heart failure (HF) is typified by decreased cardiac function and systemic symptoms caused by anatomical or functional abnormalities in the heart. Although traditional studies have concentrated on hemodynamic and neurohormonal processes, new data highlight the vital role that the gut microbiota and its byproducts play in the pathogenesis of HF. An imbalance in the microbial structure known as gut dysbiosis is common in HF patients and is linked to increased gut permeability, systemic inflammation, and changed bioactive metabolite synthesis. Prominent metabolites generated by the microbiota, including phenylacetylglutamine, short-chain fatty acids (SCFAs), secondary bile acids, and trimethylamine N-oxide (TMAO), have a major impact on endothelial function, cardiac remodeling, and inflammation. Together with gut-derived lipopolysaccharides, these metabolites interact with host systems to exacerbate the course of HF. Further impacting HF outcomes are comorbidities such as diabetes, obesity, and chronic renal disease, which intensify gut dysbiosis. The importance of metabolites originating from the microbiota in the progression of HF is highlighted in this review, which summarizes recent findings regarding the gut-heart axis. Additionally, it investigates how dietary changes, probiotics, prebiotics, and multi-omics techniques can all be used to improve the management of HF. This thorough analysis emphasizes the necessity of integrative therapy approaches and longitudinal research to better address the complex link between HF and the gut microbiota. Full article
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18 pages, 1927 KB  
Review
Delirium Management in Critical Care: Are We Moving Forward or Still Treading Water?
by Sergej Marjanovic, Ivana Berisavac, Vladimir Tutus, Stefan Boskovic, Maja Omcikus, Tea Jankovic, Adi Hadzibegovic, Sanja Ratkovic, Jasmina Opacic and Jovana Stanisavljevic
Med. Sci. 2025, 13(4), 301; https://doi.org/10.3390/medsci13040301 - 3 Dec 2025
Cited by 2 | Viewed by 4047
Abstract
Delirium is one of the most common yet most elusive syndromes in the ICU, marked by fluctuating disturbances in awareness and attention arising from complex, multifactorial pathophysiological processes. Despite decades of research and the identification of numerous risk factors, delirium continues to evade [...] Read more.
Delirium is one of the most common yet most elusive syndromes in the ICU, marked by fluctuating disturbances in awareness and attention arising from complex, multifactorial pathophysiological processes. Despite decades of research and the identification of numerous risk factors, delirium continues to evade full understanding and remains a major therapeutic challenge. Its consequences are profound: higher morbidity and mortality, prolonged ICU and hospital length of stay, and a substantial economic burden of thousands of dollars in excess costs. Beyond being a clinical complication, delirium has become a silent disruptor of modern critical care. This raises an urgent and challenging question: rather than endlessly treating the aftermath of delirium, could the key breakthrough lie in reimagining the ICU itself? Transformative investments in architecture, infrastructure, and human-centered design—together with elevating nonpharmacological strategies alongside pharmacological therapies—may hold the potential to prevent delirium at its roots. In this narrative review, we synthesize current knowledge on the epidemiology, etiology, pathophysiology, diagnosis, prevention, and management of ICU delirium. We highlight how innovative ICU redesign, holistic care approaches, and integrated evidence-based strategies may reshape the fight against delirium, turning the ICU into not just a site of survival but a therapeutic tool in its own right. Full article
(This article belongs to the Section Critical Care Medicine)
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20 pages, 753 KB  
Review
Predictors of Early Death in Acute Promyelocytic Leukemia
by Joana Brioso Infante
Med. Sci. 2025, 13(4), 300; https://doi.org/10.3390/medsci13040300 - 3 Dec 2025
Cited by 1 | Viewed by 1507
Abstract
Acute promyelocytic leukemia (APL) evolved from the most lethal to the most curable subtype of acute leukemia today, owing to targeted therapy with all-trans retinoic acid (ATRA) and arsenic trioxide. Despite cure rates exceeding 90% and the rarity of relapse or refractoriness, early [...] Read more.
Acute promyelocytic leukemia (APL) evolved from the most lethal to the most curable subtype of acute leukemia today, owing to targeted therapy with all-trans retinoic acid (ATRA) and arsenic trioxide. Despite cure rates exceeding 90% and the rarity of relapse or refractoriness, early death (ED)—occurring within 30 days of diagnosis—remains unacceptably high, reaching up to 30% in population-based studies. ED is the major barrier to universal cure, with fatal hemorrhage as the predominant cause, followed by infection, differentiation syndrome, and thrombosis. Patients who survive the initial month generally achieve excellent long-term outcomes. This review synthesizes data from clinical trials and large real-world cohorts to provide a comprehensive overview of the incidence, causes, and predictors of ED in APL. Higher white blood cell count and older age emerge as the most consistently validated predictors, followed by increased IRB/BICcreatinine, low albumin, thrombocytopenia, and coagulopathy, although their predictive value is not uniform across studies. Risk scores such as the Sanz classification, the Österroos ED model, and dynamic disseminated intravascular coagulation (DIC) assessments represent practical tools for identifying patients at high risk of ED. Importantly, ED rates remain significantly higher in real-world populations than in clinical trials, highlighting the impact of age and comorbidities, delayed diagnosis, and barriers to immediate ATRA initiation and supportive care. Addressing ED in APL requires intensified early supportive strategies, physician awareness and education, and rapid treatment initiation. Refinement and validation of predictive models may guide tailored interventions and inform strategies to finally overcome this persistent unmet need. Full article
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15 pages, 703 KB  
Article
Misreporting of Patient-Relevant and Study Design Elements in Anesthesiology Randomized Controlled Trials: An Observational Study
by Igor Vuković and Shelly Melissa Pranić
Med. Sci. 2025, 13(4), 299; https://doi.org/10.3390/medsci13040299 - 3 Dec 2025
Viewed by 798
Abstract
Background/Objectives: The quality of trial data reporting within the field of anesthesiology has, to date, been insufficiently examined. This study aims to investigate the consistency of reporting for WHO Data Set Items, trial outcomes, and adverse events between the data reported in [...] Read more.
Background/Objectives: The quality of trial data reporting within the field of anesthesiology has, to date, been insufficiently examined. This study aims to investigate the consistency of reporting for WHO Data Set Items, trial outcomes, and adverse events between the data reported in ClinicalTrials.gov and the corresponding peer-reviewed publications in a cohort of anesthetic-related randomized controlled trials (RCTs) subject to the FDAAA. Methods: In a cross-sectional study, we investigated RCTs performed on 29 drugs in anesthesiology. We examined data reporting for eight categories, including the results and outcome probability measures, adverse events, all-cause mortality, study size, study outcome, study arm, selection criteria, and date of enrollment. We also examined compliance with the ClinicalTrials.gov registration deadline. Using descriptive statistics, we described the reporting reliability in both trial registration and corresponding publication data. Differences in the frequencies of discrepant or inadequate data reporting between selected subgroups were analyzed. Results: We identified 258 trials from 2009 to 2022 from ClinicalTrials.gov with corresponding publications. Of these, 28.7% were retrospectively registered. Discrepancies in reporting results occurred in 33.3% of the trials, with serious adverse events in 62.4% and other adverse events in 67.4% of the trials. Primary outcomes were reported much more consistently than secondary ones (77.5% vs. 27.9%). The selection criteria (24%) and enrollment date (29.5%) were the least consistently reported data categories. The only data item with improved reporting over time was all-cause mortality. Conclusions: Trial data in anesthesiology clinical trials continue to be misreported. Responsible parties involved in the peer-review process should consider using trial data registration forms as valuable sources for validating the integrity of trial data. Additionally, discrepancies along manuscript progression from submission to publication raise the question about the reliability of both registered and published data as sources for clinical decisions and meta-research. Full article
(This article belongs to the Section Translational Medicine)
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12 pages, 808 KB  
Article
Assessment of Oral Hygiene Behavioral and Demographic Risk Factors for Extrahepatic Manifestations of Hepatitis C
by Mihai Oprea, Andreea Cândea, Alexandra Roman, Ion Rogoveanu, Allma Roxana Pitru, Claudiu Marinel Ionele, Dorin Nicolae Gheorghe, Flavia Mirela Nicolae, Dora Maria Popescu, Adina Turcu-Stiolica, Sergiu Ciobanu and Petra Surlin
Med. Sci. 2025, 13(4), 298; https://doi.org/10.3390/medsci13040298 - 3 Dec 2025
Viewed by 725
Abstract
Background: Hepatitis C (HC) remains a major public health concern, affecting approximately 50 million people globally. In addition to hepatic damage, HC induces extrahepatic manifestations (EHMs), including oral conditions such as oral lichen planus (OLP), xerostomia, and Sjögren syndrome-like (SS-like), which impair quality [...] Read more.
Background: Hepatitis C (HC) remains a major public health concern, affecting approximately 50 million people globally. In addition to hepatic damage, HC induces extrahepatic manifestations (EHMs), including oral conditions such as oral lichen planus (OLP), xerostomia, and Sjögren syndrome-like (SS-like), which impair quality of life. The aim of this study was to investigate the possible association between certain extrahepatic manifestations of HC and the presence of risk factors. Methods: A cross-sectional study was conducted on 38 adults (22 males and 16 females; mean age 56.5 ± 8.6 years) with inactive HC. For each patient, demographic and clinical data were collected, including the following: frequency of dental brushing, frequency of professional dental hygiene visits, smoking, alcohol consumption, the presence of xerostomia, OLP, and SS-like. Logistic regression analyses and ROC curves were performed using R software to identify independent predictors for each condition. Results: OLP was present in 39.5%, xerostomia in 47.4%, and SS-like in 15.8% of patients. Female gender significantly predicted OLP and showed a borderline association with xerostomia. Smoking was weakly associated with xerostomia. No predictors were significant for SS-like. Conclusions: Oral hygiene and smoking are risk factors for oral EHM, their good control being important for the quality of life of these patients. Gender has also been shown to be a risk factor for these manifestations. Full article
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