Medicina

15 pages, 307 KB

Open AccessArticle

Maternal Telomere Length and Its Influence on Neonatal Parameters: A Potential Tool for Prenatal Screening

by Razvan Nitu, Tiberiu Dragomir, Simona-Alina Abu-Awwad, Flavius Olaru, Carmen-Ioana Marta, Ahmed Abu-Awwad, Bogdan Sorop and Mircea Diaconu

Medicina 2025, 61(10), 1755; https://doi.org/10.3390/medicina61101755 - 26 Sep 2025

Abstract

Background and Objectives: Maternal telomere length (TL) has been proposed as a potential biomarker of biological aging and pregnancy outcomes, yet evidence in Central and Eastern European populations remains scarce. This study aimed to investigate the association between maternal TL and neonatal [...] Read more.

Background and Objectives: Maternal telomere length (TL) has been proposed as a potential biomarker of biological aging and pregnancy outcomes, yet evidence in Central and Eastern European populations remains scarce. This study aimed to investigate the association between maternal TL and neonatal parameters in a clinically healthy cohort. Materials and Methods: We conducted a prospective observational study including 134 mother–infant pairs at the “Pius Brînzeu” Emergency County Clinical Hospital, Timișoara. All deliveries were performed by cesarean section for maternal indications unrelated to fetal condition. Maternal blood samples were collected at admission, and relative TL was measured by quantitative PCR. Neonatal outcomes included birth weight, length, head circumference, gestational age, and Apgar scores. Results: Longer maternal TL was positively correlated with birth weight (r = 0.515, p < 0.001), length (r = 0.559, p < 0.001), head circumference (r = 0.468, p < 0.001), gestational age (r = 0.444, p < 0.001), and Apgar scores at 1 (r = 0.714, p < 0.001) and 5 min (r = 0.684, p < 0.001). Logistic regression showed that shorter maternal TL independently predicted suboptimal 1 min Apgar (<8), with an adjusted odds ratio of 0.68 (95% CI: 0.51–0.91). Conclusions: Maternal TL is strongly associated with neonatal growth and vitality measures, supporting its potential as a simple, non-invasive biomarker for perinatal risk assessment. Full article

(This article belongs to the Section Obstetrics and Gynecology)

13 pages, 1825 KB

Open AccessArticle

Liraglutide Enhances Cell Viability and Reduces Oxidative Stress in Hyperglycemic H9c2 Cardiomyocytes

by Sinem Durmus, Zeki Dogan, Dilek Duzgun Ergun, Mahmut Ozdemir, Hakan Sahin, Gozde Erkanli Senturk, Remise Gelisgen and Hafize Uzun

Medicina 2025, 61(10), 1754; https://doi.org/10.3390/medicina61101754 - 26 Sep 2025

Abstract

Background and Objectives: Cardiovascular disease remains a leading cause of mortality in Diabetes mellitus (DM), where chronic hyperglycemia induces oxidative stress, mitochondrial dysfunction, and hypoxia in cardiomyocytes. Liraglutide (Lir), a glucagon-like peptide-1 receptor agonist, is widely used for type 2 DM management [...] Read more.

Background and Objectives: Cardiovascular disease remains a leading cause of mortality in Diabetes mellitus (DM), where chronic hyperglycemia induces oxidative stress, mitochondrial dysfunction, and hypoxia in cardiomyocytes. Liraglutide (Lir), a glucagon-like peptide-1 receptor agonist, is widely used for type 2 DM management and has been shown to exert cardioprotective and antioxidant effects. This study aimed to evaluate whether Lir mitigates hyperglycemia-induced oxidative and hypoxic stress in H9c2 cardiomyoblasts while preserving cellular ultrastructure. Materials and Methods: H9c2 cells were cultured under normoglycemic (5.5 mM) or hyperglycemic (30 mM) conditions, with or without Lir. Cell viability was assessed using MTT assay. Ultrastructural changes were examined by transmission electron microscopy (TEM). Hypoxia-inducible factor-1α (HIF-1α), lipid peroxidation markers (LOOH, MDA), advanced oxidation protein products (AOPP), and total antioxidant capacity (TAC) were quantified by spectrophotometric assays. Results: MTT assays revealed that Lir significantly improved cell viability under hyperglycemic conditions and the EC₅₀ was 1.05 ± 0.06 μM after 48 h of treatment. Under HG, HIF-1α, lipid hydroperoxides (LOOH), malondialdehyde (MDA) and advanced oxidation protein products (AOPP) increased and total antioxidant capacity (TAC) decreased (p < 0.001, for all); Lir significantly reversed these changes, restoring values to near-NG levels. Ultrastructural analysis of HG + Lir-treated cells revealed reduced granules, increased vacuolization, and slight rough endoplasmic reticulum dilatation, though mitochondria appeared normal. Conclusions: Lir significantly attenuated oxidative stress and cellular injury in cardiomyocytes under hyperglycemic conditions, improving viability, modulating HIF-1α expression, and restoring antioxidant balance. These findings support a dual role for Lir in diabetic cardiomyopathy: glucose-independent cytoprotection and regulation of mitochondrial and hypoxia pathways, highlighting its therapeutic potential beyond glycemic control. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Type 2 Diabetes Mellitus)

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7 pages, 256 KB

Open AccessArticle

The Effectiveness of a Sofosbuvir/Daclatasvir Combination in the Treatment of HCV Infection in Patients from Mauritania Undergoing Chronic Hemodialysis

by Sidi Mohamed Mah, Soufiane Sid’Ahmed, Mohamed Lemrabott, Delahi Welli, Jemal Awa, Abdellatif Sidi Aly and Lionel Rostaing

Medicina 2025, 61(10), 1753; https://doi.org/10.3390/medicina61101753 - 26 Sep 2025

Abstract

Background and Objectives: Hepatitis C virus (HCV) infection is highly prevalent among patients undergoing chronic hemodialysis in emerging countries and is associated with significant morbidity and mortality in this population. The objective of this study was to eradicate chronic HCV infection in [...] Read more.

Background and Objectives: Hepatitis C virus (HCV) infection is highly prevalent among patients undergoing chronic hemodialysis in emerging countries and is associated with significant morbidity and mortality in this population. The objective of this study was to eradicate chronic HCV infection in patients undergoing chronic hemodialysis in Mauritania using a combination of sofosbuvir, 400 mg, and daclatasvir, 60 mg (direct acting antiviral—DAA—therapy), for 3 months. This was a prospective, single-arm, multicenter, interventional study. Materials and Methods: A total of 553 patients undergoing hemodialysis were screened for HCV across all hemodialysis centers nationwide. Biological parameters were compared before and after DAA therapy. Results: The prevalence of HCV infection was 6.8% (n = 38); two patients had undetectable HCV RNA. Out of the 36 eligible patients, 33 received DAA treatment. The median age of the patients was 49 (25–78) years. The average duration on hemodialysis was 9.4 (4–17) years. The median viral load before treatment was 538277 (10–4258571) IU/L. The median alanine aminotransferase (ALT) level was 52.3 (14–278) IU/L. The median hemoglobin level was 10 (6–13) g/dL. HCV viral load was undetectable at week 12 (W12) and week 24 (W24). The sustained virologic response (SVR) rate was 100%. Adverse events included one case of acute pancreatitis, six cases of fatigue (17%), five cases of headache (15%), four cases of diarrhea (12%), three cases of nausea (9%), and four cases of insomnia (12%). Conclusions: The combination of sofosbuvir and daclatasvir is effective in patients with HCV undergoing chronic hemodialysis, achieving a 100% SVR rate. Full article

(This article belongs to the Section Urology & Nephrology)

14 pages, 461 KB

Open AccessArticle

Gait Pattern Differences Between Young Adults and Physically Active Older Adults

by Carmen García-Gomariz, Fernando Domínguez-Navarro, Mercedes María Fernández-Benet, José-María Blasco, David Hernández-Guillén and Enrique Sanchis-Sales

Medicina 2025, 61(10), 1752; https://doi.org/10.3390/medicina61101752 - 25 Sep 2025

Abstract

Background and Objectives: This study aimed to compare gait patterns between young adults and physically active older adults. Additionally, the relation between these parameters and age was explored. Materials and Methods: Transversal case and control study, recruiting 81 participants divided into [...] Read more.

Background and Objectives: This study aimed to compare gait patterns between young adults and physically active older adults. Additionally, the relation between these parameters and age was explored. Materials and Methods: Transversal case and control study, recruiting 81 participants divided into two groups: young adults (18–45 years) and physically active older adults (60+ years). Participants were assessed using the PodoSmart Insole^® system, which recorded spatiotemporal and kinematic gait data. Gait parameters were measured during a self-selected walking test. Data analysis included descriptive statistics, t-tests for group comparisons, and Pearson’s correlation to explore relationships between age and gait parameters. Results: Significant differences in gait parameters were found between young and older adults, particularly in stride length (right foot: p = 0.009, left foot: p = 0.001), cadence (p < 0.001), contact time (p < 0.001), swing time (p < 0.001), and support phase duration (p < 0.001), with moderate to large effect sizes. Sex differences were also observed within each group for several gait variables. Correlation analysis evidenced worsened parameters with increasing age, with moderate to strong associations in terms of cadence (r = −0.590), contact time (r = −0.504, r = −0.462), swing time (r = −0.662), and support phase duration (r = −0.524, r = −0.439). Conclusions: Evident differences in gait parameters are observed between young adults and active older adults. Although these results follow the trend of previous studies that employed more sophisticated lab-based protocols for gait analysis, slight differences between our study and these others could be attributed to the regular physical activity performed by these participants, which should be explored in more detail in future studies. Full article

(This article belongs to the Special Issue Development and Application of Objective Measures in Physiotherapy for Musculoskeletal Disorders, Orthopedics, and Sports Medicine—2nd Edition)

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13 pages, 339 KB

Open AccessArticle

Impact of Surgical Approach, Patient Risk Factors, and Diverting Ileostomy on Anastomotic Leakage and Outcomes After Rectal Cancer Resection: A 5-Year Single-Center Study

by Deividas Nekrosius, Edvinas Gvozdas, Gabriele Marija Pratkute, Algimantas Tamelis and Paulius Lizdenis

Medicina 2025, 61(10), 1751; https://doi.org/10.3390/medicina61101751 - 25 Sep 2025

Abstract

Background and Objectives: This study aimed to evaluate surgical outcomes and identify prognostic factors associated with anastomotic leakage (AL), following rectal cancer resection. Materials and Methods: A retrospective cohort study included 415 patients who underwent rectal cancer surgery between 2020 and [...] Read more.

Background and Objectives: This study aimed to evaluate surgical outcomes and identify prognostic factors associated with anastomotic leakage (AL), following rectal cancer resection. Materials and Methods: A retrospective cohort study included 415 patients who underwent rectal cancer surgery between 2020 and 2024. Patients were categorized by surgical approach (laparoscopic vs. open) and presence of AL. Results: Of the 415 patients, 160 (38.6%) underwent laparoscopic surgery, and 255 (61.4%) underwent open surgery. Operative time was significantly longer for laparoscopic surgery (213.0 ± 65.9 vs. 201.3 ± 60.4 min, p = 0.05), while stoma formation was more frequent in the open surgery group (60.0% vs. 48.1%, p = 0.018). Reoperation rate was higher in the laparoscopic group compared to the open group (13.1% vs. 6.7%, p = 0.027). The rate of AL was 20.5% in the laparoscopic group and 18.4% in the open surgery group (p = 0.434). Patients with AL had a significantly longer hospital stay (17 days, IQR 12.0–23.7 vs. 8 days, IQR 7.0–9.0, p < 0.001). The use of NOACs was associated with an increased risk of AL (p = 0.026). Multivariate analysis revealed that both a higher ASA score (p = 0.022) and older age (p = 0.044) were independent risk factors for AL, while the use of a diverting ileostomy was associated with a threefold reduction in the risk of AL (p = 0.049). Conclusions: AL rates were similar between approaches. Laparoscopic surgery had more reoperations and longer operative times. AL was associated with NOAC use, older age, and higher ASA scores. Diverting ileostomy reduced AL risk and warrants broader use in high-risk patients to improve outcomes. Full article

(This article belongs to the Special Issue Advances in Anorectal and Colorectal Surgery)

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17 pages, 1556 KB

Open AccessSystematic Review

Efficacy and Safety of Intraosseous Versus Intravenous Antibiotic in Primary and Revision Total Joint Arthroplasty: A Systematic Review and Meta-Analysis

by Sunwoo Lee, Jiyun Kang, Yonggyun Moon, Jaeyoung Hong, Hyoungtae Kim and Suenghwan Jo

Medicina 2025, 61(10), 1750; https://doi.org/10.3390/medicina61101750 - 25 Sep 2025

Abstract

Background and Objectives: Periprosthetic joint infection (PJI) is one of the most serious complications following total joint arthroplasty (TJA), leading to poor functional outcomes and increased healthcare burden. Intraosseous (IO) regional antibiotic prophylaxis has emerged as a promising method for infection prevention, [...] Read more.

Background and Objectives: Periprosthetic joint infection (PJI) is one of the most serious complications following total joint arthroplasty (TJA), leading to poor functional outcomes and increased healthcare burden. Intraosseous (IO) regional antibiotic prophylaxis has emerged as a promising method for infection prevention, offering potential advantages over conventional intravenous (IV) systemic administration. This study aimed to systematically evaluate the clinical evidence on the efficacy and safety of IO prophylaxis in TJA. Materials and Methods: A comprehensive literature search was conducted in PubMed, Embase, Scopus, Web of Science, and the Cochrane Library up to 23 June 2025. Eligible studies included randomized controlled trials and observational studies reporting outcomes of IO antibiotic administration in TJA. Primary endpoints were systemic and local antibiotic concentrations (bone and fat tissue), the incidence of PJI, and complication profiles. Risk of bias was assessed using the ROB-2 and ROBINS-I tools, and meta-analyses were conducted using RevMan v 7.2.0. Results: Fifteen studies (eight RCTs, one prospective study, and six retrospective studies) were included for qualitative synthesis, of which ten were included in the meta-analysis. As compared with IV, IO administration resulted in significantly higher local antibiotic concentrations in bone (MD: 15.52 μg/g; 95% CI: 8.60–22.45; p < 0.0001) and fat tissue (MD: 18.15 μg/g; 95% CI: 12.86–23.45; p < 0.0001). IO prophylaxis was associated with a significantly lower PJI rate (OR: 0.26; 95% CI: 0.12–0.57; p = 0.008) without a significant difference in the incidence of complications (p = 0.66). Conclusions: IO antibiotic prophylaxis is an effective and safe strategy for infection prevention in total joint arthroplasty. By achieving superior local antibiotic concentrations and reducing PJI rates without increasing complications, this approach holds promise for broader clinical application. Full article

(This article belongs to the Special Issue Updates on Risk Factors, Prevention and Treatment of Knee Disease)

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15 pages, 680 KB

Open AccessArticle

Community-Based Pilot Study of Chlamydia trachomatis and Neisseria gonorrhoeae Urogenital Infections Among Young Adults in the North and the Central Coast of Portugal

by Rafaela Rodrigues, Sónia Loureiro, Inês João, Inês Jordão, Maria José Borrego, Carlos Catalão, Ana Rita Silva, Carlos Sousa and Nuno Vale

Medicina 2025, 61(10), 1749; https://doi.org/10.3390/medicina61101749 - 25 Sep 2025

Abstract

Background and Objectives: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are among the most common sexually transmitted infections (STIs), with the highest incidence in individuals aged up to 25 years. However, data from Portugal remain scarce. This cross-sectional pilot study aimed to assess [...] Read more.

Background and Objectives: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are among the most common sexually transmitted infections (STIs), with the highest incidence in individuals aged up to 25 years. However, data from Portugal remain scarce. This cross-sectional pilot study aimed to assess the prevalence of urogenital CT and NG infections in young adults in Portugal and to identify the major CT genotypes circulating in this population. Materials and Methods: A total of 152 young adults aged 18–25 years were recruited over a six-month period from universities, a sports club, and a coworking space. Urine samples were tested using the Cobas 4800 CT/NG assay (Roche, Rotkreuz, Switzerland). CT-positive samples were further genotyped based on ompA gene diversity to identify major urogenital genotypes (D to K). All participants provided informed consent and completed a questionnaire on demographic characteristics and risk behaviors. Results: Of the 152 urine samples analyzed, five tested positive for CT, one for NG, and one sample showed co-infection with both pathogens. None of the participants with positive results reported symptoms. Genotyping of CT-positive samples identified ompA genotype E in three cases. Conclusions: Despite limitations such as small sample size and convenience sampling, this pilot study offers preliminary insights into the prevalence and genetic diversity of CT and NG infections among young adults in Portugal. The findings highlight the need for expanded screening programs, site-specific sample collection, and culture-based diagnostics to support evidence-based public health strategies targeting these infections. Full article

(This article belongs to the Section Epidemiology & Public Health)

16 pages, 739 KB

Open AccessArticle

Endometrial Carcinoma and Associated Secondary Neoplasia: The Role of Clinical Features, Pathology, and Comorbidities in a University-Affiliated Clinical Center from Western Romania

by Ioana Hurmuz, Robert Barna, Bianca Natarâș, Iuliana-Anamaria Trăilă, Denisa Anderco, Sorin Dema, Aura Jurescu, Dorela-Codruța Lăzureanu, Sorina Tăban and Alis Dema

Medicina 2025, 61(10), 1748; https://doi.org/10.3390/medicina61101748 - 25 Sep 2025

Abstract

Background and Objectives: Multiple primary malignancies involving endometrial carcinoma (EC) present complex diagnostic and management challenges. This study aimed to identify clinical, pathological, and demographic patterns among patients with EC and a second primary tumor and assess the role of comorbidities in [...] Read more.

Background and Objectives: Multiple primary malignancies involving endometrial carcinoma (EC) present complex diagnostic and management challenges. This study aimed to identify clinical, pathological, and demographic patterns among patients with EC and a second primary tumor and assess the role of comorbidities in tumor behavior. Materials and Methods: We retrospectively analyzed 35 women diagnosed with EC and a second malignancy between 2017 and 2024. We evaluated clinical variables, tumor characteristics, and comorbidities. Statistical analysis included chi-square tests, Mann–Whitney U tests, Kruskal–Wallis tests, Spearman correlations, and logistic regression. Multiple testing correction was applied using the Benjamini–Hochberg method. Results: Endometrioid EC was the most prevalent subtype (80%), most frequently associated with breast (28.5%) and colorectal cancers (11.4%). Obesity (45.7%), hypertension (62.9%), and diabetes (22.9%) were common. While univariate analysis suggested associations between comorbidities and tumor features (e.g., obesity and tumor type, ρ = 0.30, p = 0.08), no correlation remained significant after adjustment. Logistic regression identified age (OR = 0.88, CI: 0.79–0.98, p = 0.022) and obesity (OR = 0.11, CI: 0.01–0.83, p = 0.033) as independent predictors of non-endometrioid histology. Conclusions: These findings suggest that age and obesity may influence histological differentiation in EC with multiple primaries. This study suggest that age and obesity may play a role in the histological differentiation of EC in patients with multiple primary tumors. The small cohort size (n = 35) limits the statistical power and generalizability of the results; therefore, they should be regarded as exploratory and hypothesis-generating, warranting validation in larger prospective studies. Full article

(This article belongs to the Section Obstetrics and Gynecology)

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13 pages, 1011 KB

Open AccessArticle

Phenotypic Expression of Respiratory Diseases and Tailored Treatment in Patients with Intermediate Alpha-1 Antitrypsin Deficiency: Evidence from a Retrospective Analysis of a Selected Cohort of Patients

by Anna Annunziata, Giuseppe Fiorentino, Francesca Simioli, Lidia Atripaldi, Marco Balestrino, Giacomo Zuccarini, Barbara Piras, Alessandro Libra, Fabio Pino, Pierpaolo Di Micco, Carmine Siniscalchi, Ilaria Ferrarotti, Luigi Aronne, Raffaella Manzo, Carlo Vancheri and Cecilia Calabrese

Medicina 2025, 61(10), 1747; https://doi.org/10.3390/medicina61101747 - 25 Sep 2025

Abstract

Introduction: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition caused by SERPINA1 variants with variable severity. Current international guidelines do not recommend augmentation therapy for intermediate AATD; nevertheless, some patients show clinically severe phenotypes in real-world practice. We aimed to evaluate, in [...] Read more.

Introduction: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition caused by SERPINA1 variants with variable severity. Current international guidelines do not recommend augmentation therapy for intermediate AATD; nevertheless, some patients show clinically severe phenotypes in real-world practice. We aimed to evaluate, in an exploratory manner, the potential effects of augmentation therapy on exacerbations, quality of life, and lung function in this subgroup. Methods: In this multicenter retrospective study, we included 27 heterozygous patients with intermediate AATD (serum AAT 50–110 mg/dL), Chronic Obstructive Pulmonary Disease (COPD), and/or emphysema. Clinical phenotypes included emphysema-predominant disease, COPD with frequent exacerbations, and overlap with bronchiectasis/asthma; HRCT patterns were recorded. We assessed the annual number of exacerbations (moderate: steroids/antibiotics; severe: hospitalization/including pneumothorax), St. George’s Respiratory Questionnaire (SGRQ), and lung function before and after 12 months of therapy. Results: Augmentation therapy was associated with a reduction in annual exacerbations from a median (IQR) of 2 (1.5–3) to 1 (0–1) (p < 0.0001) and an improvement in SGRQ total score (58.89 ± 16.83 to 48.34 ± 21.20; p = 0.0039). The mean SGRQ change exceeded the 4-point MCID for COPD. No significant changes were observed in spirometry or Diffusing Capacity of the Lung for Carbon Monoxide (DLCO). Conclusions: These exploratory findings suggest that augmentation therapy may reduce exacerbations and improve quality of life in selected patients with intermediate AATD and COPD/emphysema. Given the retrospective design, small sample, and lack of a control group, the results should be interpreted as hypothesis-generating and warrant confirmation in prospective studies. Full article

(This article belongs to the Section Pulmonology)

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17 pages, 1688 KB

Open AccessArticle

Impact of COVID-19 Pandemic on Bronchiolitis Epidemiology in Greece

by Athina Koloi, Dimitra Dimopoulou, Dimitris Papakonstantinou, Georgios Damianos, Vasiliki Korentzelou, Marina Triantafyllia Kotzamani, Ariadni Neofytou, Christos Paraschos, Sofia D. Pasparaki, Agori Rizargioti, Kiriaki Benetatou, Maria Tampouratzi, Anastasia Konidari, Alexandra Soldatou and Maria N. Tsolia

Medicina 2025, 61(10), 1746; https://doi.org/10.3390/medicina61101746 - 25 Sep 2025

Abstract

Background and Objectives: Acute bronchiolitis is a leading cause of hospitalization and morbidity in infants and young children. The COVID-19 pandemic has impacted its epidemiology globally. This study aims to assess changes in bronchiolitis epidemiology in Greece during the period of COVID-19 restrictive [...] Read more.

Background and Objectives: Acute bronchiolitis is a leading cause of hospitalization and morbidity in infants and young children. The COVID-19 pandemic has impacted its epidemiology globally. This study aims to assess changes in bronchiolitis epidemiology in Greece during the period of COVID-19 restrictive measures and after their removal, compared to the pre-pandemic period. Materials and Methods: A retrospective non-interventional study was conducted at a tertiary pediatric hospital, including all children aged 0–24 months hospitalized for bronchiolitis between 1 November 2017 and 30 September 2024. A total of 1505 cases were included. Data were analyzed across seven seasonal periods. Results: Bronchiolitis hospitalizations decreased by 98% in 2020–2021, returned to pre-pandemic levels in 2021–2022, and increased by 58.7% in January 2022–2023. The seasonal distribution shifted earlier in 2021–2022, with a return to pre-pandemic patterns in 2022–2023 and 2023–2024. No shift was observed in the peak age group (1–3 months), although neonatal hospitalizations decreased significantly in 2020–2021 (p = 0.009). RSV-positive cases dropped notably during 2020–2021 (41.2%). There was no change in disease severity across periods, assessed by indirect indicators and the Modified Tal Score. The proportion of bronchiolitis cases among total pediatric admissions increased to 5.6% in 2023–2024, compared to 4.9% in 2022–2023 and 3.9% pre-pandemic (2017–2020). Conclusions: Bronchiolitis epidemiology was significantly impacted by the COVID-19 pandemic in Greece, though disease severity remained unchanged. Ongoing monitoring of bronchiolitis and RSV circulation is crucial particularly with the introduction of maternal RSV vaccination and new monoclonal antibodies to inform prevention strategies and reduce disease burden. Full article

(This article belongs to the Section Epidemiology & Public Health)

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13 pages, 1115 KB

Open AccessSystematic Review

Effectiveness of Classic Triple Therapy Compared with Alternative Regimens for Eradicating H. pylori: A Systematic Review

by Majid Darraj

Medicina 2025, 61(10), 1745; https://doi.org/10.3390/medicina61101745 - 25 Sep 2025

Abstract

Background: Helicobacter pylori infection is associated with peptic ulcer disease, chronic gastritis, and gastric cancer. Classic triple therapy (CTT) has been widely used, but increasing antibiotic resistance has reduced its effectiveness. Objectives: To evaluate the effectiveness of CTT compared with alternative [...] Read more.

Background: Helicobacter pylori infection is associated with peptic ulcer disease, chronic gastritis, and gastric cancer. Classic triple therapy (CTT) has been widely used, but increasing antibiotic resistance has reduced its effectiveness. Objectives: To evaluate the effectiveness of CTT compared with alternative regimens and to summarize adverse events and adherence. Methods: We searched PubMed, Scopus, Web of Science, and Cochrane Library from January 2000 to March 2025. Randomized trials and observational studies assessing eradication rates were included. Two reviewers independently screened the studies, extracted data, and assessed bias using Cochrane RoB or the Newcastle–Ottawa Scale. Outcomes included eradication rate, adverse events, and adherence. Results: Thirteen studies (n = 3490) were included. CTT eradication rates ranged from 61.9% to 88.8%. Sequential, bismuth-based quadruple and high-dose PPI regimens achieved higher rates (>90% in several trials). Adverse events were mild–moderate and most frequent in quadruple therapy, though adherence remained >90%. Evidence certainty varied (moderate to low in most comparisons). Geographic variation in resistance limited generalizability. Conclusions: CTT is less effective in high-resistance regions. Quadruple, sequential, and high-dose PPI regimens provide superior outcomes. Region-specific treatment guided by susceptibility testing is recommended. Registration: Not registered. Full article

(This article belongs to the Section Infectious Disease)

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10 pages, 282 KB

Open AccessArticle

ChatGPT in Oral Pathology: Bright Promise or Diagnostic Mirage

by Ana Suárez, Yolanda Freire, Víctor Díaz-Flores García, Andrea Santamaría Laorden, Jaime Orejas Pérez, María Suárez Ajuria, Juan Algar and Carmen Martín Carreras-Presas

Medicina 2025, 61(10), 1744; https://doi.org/10.3390/medicina61101744 - 25 Sep 2025

Abstract

Background and Objectives: The growing academic interest within the biomedical sciences regarding the diagnostic capabilities of multimodal language models, such as ChatGPT-4o, is clear. However, their ability to interpret oral clinical images remains insufficiently explored. This exploratory pilot study aimed to provide preliminary [...] Read more.

Background and Objectives: The growing academic interest within the biomedical sciences regarding the diagnostic capabilities of multimodal language models, such as ChatGPT-4o, is clear. However, their ability to interpret oral clinical images remains insufficiently explored. This exploratory pilot study aimed to provide preliminary observations about the diagnostic validity of ChatGPT-4o in identifying oral squamous cell carcinoma (OSCC), oral leukoplakia (OL), and oral lichen planus (OLP) using only clinical photographs, without the inclusion of additional clinical data. Materials and Methods: Two general dentists selected 23 images of oral lesions suspected to be OSCC, OL, or OLP. ChatGPT-4o was asked to provide a probable diagnosis for each image on 30 occasions, generating a total of 690 responses. The responses were then evaluated against the reference diagnosis set up by an expert to calculate sensitivity, specificity, predictive values, and the area under the ROC curve. Results: ChatGPT-4o demonstrated high specificity across the three conditions (97.1% for OSCC, 100% for OL, and 96.1% for OLP), correctly classifying 90% of OSCC cases (AUC = 0.81). However, this overall accuracy was largely driven by correct negative classifications, while the clinically relevant sensitivity for OSCC was only 65%. In spite of that, sensitivity was highly variable: 60% for OL and just 25% for OLP, which limits its usefulness in a clinical setting for ruling out these conditions. The model achieved positive predictive values of 86.7% for OSCC and 100% for OL. Given the small dataset, these findings should be interpreted only as preliminary evidence. Conclusions: ChatGPT-4o demonstrates potential as a complementary tool for the screening of OSCC in clinical oral images. Nevertheless, the pilot nature of this study and the reduced sample size highlight that larger, adequately powered studies (with several hundred cases per pathology) are needed to obtain robust and generalizable results. Nevertheless, its sensitivity remains insufficient, as a significant proportion of true cases were missed, underscoring that the model cannot be relied upon as a standalone diagnostic tool. Full article

(This article belongs to the Section Dentistry and Oral Health)

12 pages, 1424 KB

Open AccessArticle

Evolution in Laryngeal Cancer Mortality at the National and Subnational Level in Romania with 2030 Forecast

by Andreea-Mihaela Banța, Nicolae-Constantin Balica, Simona Pîrvu, Karina-Cristina Marin, Kristine Guran, Ingrid-Denisa Barcan, Cristian-Ion Moț, Bogdan Hîrtie, Victor Banța and Delia Ioana Horhat

Medicina 2025, 61(10), 1743; https://doi.org/10.3390/medicina61101743 - 25 Sep 2025

Abstract

Background and Objectives: Laryngeal cancer imposes a disproportionate burden on speech, airway protection and long-term quality of life. Contemporary population-based data for Central and Eastern Europe remain scarce, and the post-pandemic trajectory is uncertain. Materials and Methods: We performed a nationwide, [...] Read more.

Background and Objectives: Laryngeal cancer imposes a disproportionate burden on speech, airway protection and long-term quality of life. Contemporary population-based data for Central and Eastern Europe remain scarce, and the post-pandemic trajectory is uncertain. Materials and Methods: We performed a nationwide, retrospective ecological time-series study using Romanian mortality registers and hospital-discharge files for 2017–2023. Crude and age-standardised mortality rates (ASMRs) were calculated, county-level indirect standardisation and spatial autocorrelation assessed and joinpoint regression quantified temporal trends. Forecasts to 2040 combined Holt–Winters/ARIMA models with Elliott-wave heuristics anchored to Fibonacci retracements. Results: In 2023, 798 laryngeal cancer deaths yielded a crude mortality of 3.65/100,000 (95% CI 3.41–3.91). Male mortality (7.07/100,000) exceeded female mortality 18-fold. Rural residents experienced a higher rate than urban counterparts (4.26 vs. 3.04/100,000), a difference unchanged after indirect age standardisation. National ASMR fell by 3.7% annually (p < 0.01), yet five counties formed a high-risk corridor (standardised mortality ratios 1.59–1.82); Moran’s I = 0.27 (p < 0.01) indicated significant spatial clustering. Pandemic-era surgical throughput collapsed by 48%, generating a backlog projected to persist beyond 2030. Ensemble forecasting anticipates a doubling of discharges and mortality between 2034 and 2037 unless smoking prevalence falls by ≥30% and radon exposure is curtailed. Conclusions: Although overall laryngeal cancer mortality in Romania is declining, the pace lags behind Western Europe and is threatened by geographic inequities and pandemic-related care delays. Aggressive tobacco control, radon-remediation policies and expansion of surgical and radiotherapeutic capacity are required to avert a forecasted surge in the next decade. Full article

(This article belongs to the Section Epidemiology & Public Health)

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31 pages, 921 KB

Open AccessReview

Self-Management of Medications During Sick Days for Chronic Conditions: A Scoping Review

by Mimi Truong, Kamal Sud, Connie Van, Wubshet Tesfaye, Vani Nayak and Ronald L. Castelino

Medicina 2025, 61(10), 1742; https://doi.org/10.3390/medicina61101742 - 25 Sep 2025

Abstract

Background and Objectives: Sick-day medication guidance involves patients self-adjusting medications during sick days to prevent adverse events and minimise exacerbation of their disease states. This review aimed to summarise and synthesise all sick-day interventions provided by healthcare professionals (HCPs) for patients with [...] Read more.

Background and Objectives: Sick-day medication guidance involves patients self-adjusting medications during sick days to prevent adverse events and minimise exacerbation of their disease states. This review aimed to summarise and synthesise all sick-day interventions provided by healthcare professionals (HCPs) for patients with chronic illnesses, including diabetes, cardiovascular disease, chronic kidney disease (CKD), adrenal insufficiency (AI), rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), and asthma. Materials and Methods: A search of Embase, Medline, International Pharmaceutical Abstract, Scopus, Google Scholar, and the grey literature was conducted until July 2025. The review followed the methodological framework according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. Data were extracted using a modified TIDieR checklist, and the findings were summarised descriptively and presented thematically. Results: The search included 6932 documents, and 97 met the inclusion criteria: 57 published guidelines/education resources and 40 pieces of original research. Seventy-four interventions were identified for diabetes (18), asthma (32), AI (8), CKD (6), AKI prevention (4), COPD (4), and mixed conditions (2). The most common type of intervention was written information (action plans and information sheets), with education mostly provided by multidisciplinary teams. Novel interventions included 24h phone support and an educational mobile application. Participants showed interest in sick-day interventions and HCPs viewed these interventions as effective, important, and easy to provide. However, interventions did not always translate to improved clinical outcomes, with studies reporting mixed outcomes regarding healthcare utilisation. Nonetheless, some interventions showed improved patient knowledge and satisfaction with care. Conclusions: Multiple interventions are available for asthma and diabetes, with fewer targeting CKD or acute kidney injury (AKI) prevention. While demand for these interventions from consumers and HCPs is high, implementation challenges and inconsistent benefits remain. Further primary research is needed to clarify which intervention features are most effective in yielding meaningful clinical outcomes. Full article

(This article belongs to the Section Epidemiology & Public Health)

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16 pages, 2342 KB

Open AccessArticle

Modeling Pain Dynamics and Opioid Response in Oncology Inpatients: A Retrospective Study with Application to AI-Guided Analgesic Strategies in Colorectal Cancer

by Eliza-Maria Froicu (Armeanu), Oriana-Maria Onicescu (Oniciuc), Ioana Creangă-Murariu, Camelia Dascălu, Bogdan Gafton, Vlad-Adrian Afrăsânie, Teodora Alexa-Stratulat, Mihai-Vasile Marinca, Diana-Maria Pușcașu, Lucian Miron, Gema Bacoanu, Irina Afrăsânie and Vladimir Poroch

Medicina 2025, 61(10), 1741; https://doi.org/10.3390/medicina61101741 - 25 Sep 2025

Abstract

Background and Objectives: Cancer pain continues to be a major clinical problem nowadays. This study aims to evaluate the World Health Organization (WHO) analgesic ladder effectiveness in patients with colorectal cancer and develop machine learning models to predict treatment response for precision pain [...] Read more.

Background and Objectives: Cancer pain continues to be a major clinical problem nowadays. This study aims to evaluate the World Health Organization (WHO) analgesic ladder effectiveness in patients with colorectal cancer and develop machine learning models to predict treatment response for precision pain management. Materials and Methods: In a retrospective observational study, a total of 107 oncological patients were analyzed, with a detailed subgroup analysis of 42 patients with colorectal cancer, hospitalized between July and September in 2022. The pain assessment used numerical rating scales at baseline and 2–3 weeks follow-up. Clinical variables included demographics, disease staging, metastatic patterns, analgesic progression, and medication usage. Machine learning algorithms (e.g., Random Forest, CatBoost, XGBoost, and Neural Network) were used to predict pain reduction outcomes. The UMAP dimensionality reduction and clustering identified the patient phenotypes. Results: Statistical analyses included descriptive methods, Chi-square and Mann–Whitney tests, and the models’ performance was evaluated by AUC. Among patients with colorectal cancer, 73.8% achieved clinically pain improvement, with a mean reduction of 2.62 points and median improvement of 3.00 points. The metastatic site significantly affected outcomes: visceral metastases patients showed median improvement of 3.00 points with high variability, patients with bone metastases demonstrated heterogeneous responses (range: −2.00 to +8.00 points), while non-metastatic patients exhibited consistent improvement. Random Forest achieved optimal predictive performance (AUC: 0.9167), identifying the baseline pain score, bone metastases, Fentanyl usage, anticonvulsants, and antispasmodics as key predictive features. The clustering analysis revealed two distinct phenotypes, requiring different analgesic intensities. Conclusions: This study validates the WHO analgesic ladder effectiveness while demonstrating superior outcomes in patients with colorectal cancer. The machine learning models successfully predict the treatment response with excellent discriminative ability, supporting precision medicine implementation in cancer pain management. Full article

(This article belongs to the Section Oncology)

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25 pages, 581 KB

Open AccessReview

The Emerging Role of the Cancerous Inhibitor of Protein Phosphatase 2A in Pulmonary Diseases

by Hamza Hamza, Dinesh Nirmal, Stephanie Pappas, Ugochukwu Ebubechukwu, Sunydip Gill, Adam Al-Ajam, Michael Ohlmeyer and Patrick Geraghty

Medicina 2025, 61(10), 1740; https://doi.org/10.3390/medicina61101740 - 25 Sep 2025

Abstract

Promising protein targets are observed to play a role in multiple pathways across a variety of diseases, such as the regulation of immune responses, cell cycle, senescence, and DNA repair. The oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) can coordinate all these [...] Read more.

Promising protein targets are observed to play a role in multiple pathways across a variety of diseases, such as the regulation of immune responses, cell cycle, senescence, and DNA repair. The oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) can coordinate all these cell characteristics predominately by inhibiting the activity of the serine threonine protein phosphatase 2A (PP2A). CIP2A directly interacts with PP2A and other proteins, such as the DNA damage protein topoisomerase II-binding protein 1, to regulate signal transduction. CIP2A is overexpressed in many human cancers, including small and non-small cell lung cancers. High CIP2A expression in lung cancer correlates with poor prognosis, increased tumor proliferation, and resistance to targeted therapies or chemotherapy. Interestingly, CIP2A expression or signaling is also observed in several non-cancerous pulmonary diseases, such as chronic obstructive pulmonary disease. CIP2A can determine whether DNA-damaged cells enter mitosis and can mediate whether DNA repair occurs. CIP2A is also a regulator of inflammation and possibly fibrotic responses. Its functions are linked to altered NFκB activation and TNFα, IL-1β, IL-4, IL-6, IL-10, IL-13, and TGFβ signaling. This review outlines the possible impact of CIP2A-mediated signaling in pulmonary diseases, the processes that regulate CIP2A responses, CIP2A-dependent pathways, and potential therapeutic strategies targeting CIP2A. Substantial medicinal chemistry efforts are underway to develop therapeutics aimed at modulating CIP2A activity. The development of specific inhibitors of CIP2A that selectively target its expression or protein stability could improve our understanding of CIP2A’s function in pulmonary diseases. Full article

(This article belongs to the Section Pulmonology)

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20 pages, 1308 KB

Open AccessArticle

Cognitive and Emotional Impairments in Acute Post-Stroke Patients—A Cross-Sectional Study

by Maja Ibic, Lara Miklič, Sofia Rakusa, Jan Zmazek, Marija Menih, Kim Caf and Martin Rakusa

Medicina 2025, 61(10), 1739; https://doi.org/10.3390/medicina61101739 - 24 Sep 2025

Abstract

Background and Objectives: Stroke is widely recognised for its physical consequences. However, cognitive and emotional impairments, such as depression, anxiety, and vascular cognitive impairment (VCI), are often under-recognised and under-treated. Our study aimed to identify and characterise cognitive and emotional sequelae in [...] Read more.

Background and Objectives: Stroke is widely recognised for its physical consequences. However, cognitive and emotional impairments, such as depression, anxiety, and vascular cognitive impairment (VCI), are often under-recognised and under-treated. Our study aimed to identify and characterise cognitive and emotional sequelae in patients hospitalised for acute ischemic stroke. Materials and Methods: We conducted a cross-sectional study involving 73 patients within seven days of an acute ischemic stroke. Patients were assessed using the National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), Montreal Cognitive Assessment (MoCA), Hachinski Ischemic Score (HIS), and the Clinical Assessment of Depression (CAD) questionnaire, which includes four subscales (Depressed Mood (DM), Anxiety/Worry, Disinterest, and Physical Fatigue). K-means clustering was applied to ten standardised clinical and psychometric variables. In addition, multiple linear regression was performed to determine independent predictors of cognitive and affective outcomes, with MoCA and CAD-DM as dependent variables. Results: Three distinct patient profiles emerged: (1) Mild Impairment Profile, characterised by minimal cognitive or emotional symptoms; (2) Depressive Profile, marked by elevated emotional symptom scores despite mild physical impairment; and (3) Vascular Cognitive Impairment Profile, comprising older patients with the most severe cognitive and functional deficits. ANOVA confirmed significant differences between groups in NIHSS, mRS, MoCA, HIS, and CAD scores, but not for age or education. Linear regression revealed that older age (β = –0.10, p = 0.012) and higher NIHSS at discharge (β = –0.72, p = 0.020) predicted lower MoCA scores, whereas years of education (β = 0.58, p = 0.013) predicted better cognition (R² = 0.29). No demographic or clinical factors predicted depressive symptoms (all p > 0.29). Conclusions: Our study highlights the heterogeneity of post-stroke outcomes. Neuropsychiatric impairments may be present even in patients with minimal physical deficits and require targeted evaluation and management. Full article

(This article belongs to the Special Issue New Insights into Cerebrovascular Disease)

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13 pages, 675 KB

Open AccessArticle

Nano-Encapsulated Berberine Is a Potential Therapeutic Agent for Adipose Tissue Browning in C57BL/6J Mice

by Aslıhan Alpaslan, Kübra Uçar Baş, Elif Didem Örs Demet, Dilem Tuğal Aslan, Tuba Reçber, Süleyman Can Öztürk, Tugba Gulsun, Mustafa Çelebier and Zeynep Göktaş

Medicina 2025, 61(10), 1738; https://doi.org/10.3390/medicina61101738 - 24 Sep 2025

Abstract

Background and Objectives: Berberine is a promising phytochemical for obesity prevention due to its effects on adipogenesis and adipose tissue browning. Despite the benefits shown in cell studies, the clinical use of berberine is limited because of its low stability and bioavailability. Materials [...] Read more.

Background and Objectives: Berberine is a promising phytochemical for obesity prevention due to its effects on adipogenesis and adipose tissue browning. Despite the benefits shown in cell studies, the clinical use of berberine is limited because of its low stability and bioavailability. Materials and Methods: Our study aimed to investigate the effects of intravenous liposomal and free berberine on body weight and adipose tissue browning in C57BL/6J mice. The mice were divided into two main groups for obesity prevention and treatment: the prevention group received treatment with a high-fat diet for 10 weeks; the recovery group received treatment after 10 weeks on a high-fat diet. Treatments included liposomal berberine (10 mcM), free berberine (10 mcM), and void nano-encapsule, and PBS was used as a control. Results: Berberine did not affect body weight in the prevention group. In the treatment group, nano-berberine reduced weight gain, while free berberine caused weight loss (p < 0.05). PRDM16 and CIDEA expressions in white and brown adipose tissues were higher in the berberine-treated groups (p < 0.05). No changes were observed in UCP1, PGC1α, C/EBPβ, and FABP4 expressions. The protein concentrations of UCP1, PGC1α, and PPARγ did not change. Conclusions: The effects of liposomal berberine on gene expression and protein concentrations were not different from the free form, but the nano form had higher stability. Full article

(This article belongs to the Section Pharmacology)

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27 pages, 887 KB

Open AccessReview

The Role of Various Types of Diets in the Treatments of Depressive Disorders

by Anna Lis, Patrycja Maj, Agata Świętek and Ewa Romuk

Medicina 2025, 61(10), 1737; https://doi.org/10.3390/medicina61101737 - 24 Sep 2025

Abstract

Depression is a prevalent and disabling psychiatric disorder, characterized by persistent disturbances in mood, cognition, and physiological processes, which collectively lead to substantial impairments in daily functioning and quality of life. This review provides a comprehensive overview of the biological mechanisms implicated in [...] Read more.

Depression is a prevalent and disabling psychiatric disorder, characterized by persistent disturbances in mood, cognition, and physiological processes, which collectively lead to substantial impairments in daily functioning and quality of life. This review provides a comprehensive overview of the biological mechanisms implicated in the pathophysiology of depression, including neurotransmitter dysregulation, oxidative stress, inflammatory processes, hypothalamic-pituitary-adrenal (HPA) axis dysfunction, mitochondrial impairment, and alterations in the gut-brain axis. Furthermore, it explores the role of diet in both the prevention and management of depression, with particular emphasis on Mediterranean, anti-inflammatory, and ketogenic dietary patterns, while contrasting these with the detrimental impact of a Western dietary pattern. Specific nutrients-such as n-3 polyunsaturated fatty acids (PUFAs), B-complex vitamins, vitamins D and E, zinc, selenium, and polyphenols-are highlighted for their potential roles in modulating neurotransmission, attenuating inflammation, and supporting gut microbiota homeostasis. Despite growing scientific interest in nutrition-based interventions, current evidence on the comparative efficacy of different dietary approaches remains limited. Future research is warranted to elucidate the therapeutic potential of dietary strategies as adjuncts to conventional treatments for depression and to facilitate the development of evidence-based nutritional recommendations for clinical practice. Full article

(This article belongs to the Section Psychiatry)

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15 pages, 1926 KB

Open AccessArticle

Effect of Myofascial Release on Pain and Uterine Artery Hemodynamic Indices in Women with Primary Dysmenorrhea: A Randomized Controlled Trial

by Shiyu Jin, Jongwon Choi and Haneul Lee

Medicina 2025, 61(10), 1736; https://doi.org/10.3390/medicina61101736 - 24 Sep 2025

Abstract

Background: Primary dysmenorrhea (PD) is a common gynecological condition among women of reproductive age, often leading to pain and functional limitations. Myofascial release (MFR) has been suggested as a potential non-pharmacological intervention. This study aimed to investigate the immediate effects of a [...] Read more.

Background: Primary dysmenorrhea (PD) is a common gynecological condition among women of reproductive age, often leading to pain and functional limitations. Myofascial release (MFR) has been suggested as a potential non-pharmacological intervention. This study aimed to investigate the immediate effects of a single MFR session on pain intensity, menstrual symptoms, and uterine artery hemodynamics in women with PD. Methods: In this randomized controlled trial, 34 women with PD were randomly assigned to either the MFR group (n = 18) or the placebo MFR group (n = 16). All participants received 10 min of thermotherapy followed by 30 min of either MFR or placebo MFR. Pain intensity (NRS), pressure pain thresholds (PPT) at myofascial trigger points, menstrual symptoms (MDQ-T), and uterine artery pulsatility index (PI) and resistance index (RI) were assessed at three time points: baseline, immediately after the intervention, and 3 h post-intervention. Results: Both groups demonstrated significant within-group reductions in pain intensity and menstrual symptoms post-intervention (p < 0.01), with no significant group-by-time interaction. However, significant interaction effects were observed for the PI and RI of the right uterine artery, showing greater reductions in the MFR group compared to the placebo group at 3 h post-intervention (p < 0.05). Conclusions: A single MFR session resulted in improvements in uterine hemodynamics, suggesting autonomic modulation as a potential mechanism. Although subjective symptom improvements were observed in both groups, only MFR showed objective vascular benefits. These findings support the physiological plausibility of MFR in PD management and suggest its potential application as a personalized, non-pharmacological intervention. Further studies are warranted to explore its long-term and individualized therapeutic effects. Full article

(This article belongs to the Topic New Advances in Physical Therapy and Occupational Therapy, 2nd Edition)

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17 pages, 4341 KB

Open AccessSystematic Review

The Role of Near-Infrared Fluorescence with Indocyanine Green in Robot-Assisted Partial Nephrectomy: Results from an Updated Systematic Review and Meta-Analyses of Controlled Studies

by Andrea Panunzio, Rossella Orlando, Federico Greco, Clara Cerrato, Serena Domenica D’Elia, Laura Marinaci, Federica Manno, Aliasger Shakir, Michele Battaglia, Willy Baccaglini, Antonio Benito Porcaro, Alessandro Antonelli, Andre Abreu and Alessandro Tafuri

Medicina 2025, 61(10), 1735; https://doi.org/10.3390/medicina61101735 - 24 Sep 2025

Abstract

Background and Objectives: Partial nephrectomy is the standard treatment for small renal tumors, balancing cancer control with renal function preservation. Robot-assisted partial nephrectomy (RAPN) has improved surgical precision and reduced morbidity. Near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG) improves intraoperative visualization [...] Read more.

Background and Objectives: Partial nephrectomy is the standard treatment for small renal tumors, balancing cancer control with renal function preservation. Robot-assisted partial nephrectomy (RAPN) has improved surgical precision and reduced morbidity. Near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG) improves intraoperative visualization of renal vasculature and tissue perfusion, potentially enabling selective arterial clamping to reduce ischemic injury. This study updates contemporary evidence on NIRF/ICG-guided RAPN, focusing on intraoperative, perioperative, and renal function outcomes. Materials and Methods: We systematically queried PubMed, Scopus, and Web of Science databases up to June 2025 for controlled prospective and retrospective studies comparing NIRF/ICG-guided RAPN (selective clamping or zero-ischemia) versus conventional RAPN with main artery clamping in adults with renal masses. Data were synthesized narratively, and random-effects meta-analyses were performed on warm ischemia time (WIT), operative time, estimated blood loss, transfusion rate, length of hospital stay, complication rate, positive surgical margins, and variation in renal function. Results: Eleven studies (10 full-text and one abstract), including two randomized controlled trials, encompassing a patient population of 893 patients (403 NIRF/ICG-guided RAPN and 490 conventional RAPN), were included. Ischemia strategies varied between no clamping, selective or super-selective clamping for NIRF/ICG, and main artery clamping for controls. ICG doses ranging from 3 to 7.5 mg or 0.5–7 mL. Most evidence was classified as level 2b or 3b, indicating a moderate to serious risk of bias. Meta-analysis showed that compared to conventional RAPN, NIRF/ICG-guided RAPN was associated with a shorter WIT (MD: −1.30 min, 95% CI: −2.51 to −0.09; p = 0.039), with no differences in other outcomes. Renal function favored NIRF/ICG at discharge and short-term follow-up, although the difference was not statistically significant. Conclusions: NIRF/ICG reduces WIT during RAPN without increasing perioperative risks. The technique shows promise for better preserving functional outcomes. However, further well-designed, large-scale trials with longer follow-up are needed to confirm these benefits and define clinical indications. Full article

(This article belongs to the Special Issue Robot-Assisted Urologic Cancer Surgery: Current Challenges and Future Perspectives)

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28 pages, 836 KB

Open AccessArticle

Mental Health Among Spanish Adults During the COVID-19 Pandemic and in the Post-Pandemic Period: A Gender Analysis

by M. Pilar Matud, Lorena Medina, Ignacio Ibañez and Maria-José del Pino

Medicina 2025, 61(10), 1734; https://doi.org/10.3390/medicina61101734 - 24 Sep 2025

Abstract

Background and Objectives: The COVID-19 pandemic has had severe and far-reaching repercussions for health systems and societies, creating a global mental health crisis that has persisted after the pandemic. This study examined differences in mental health (i.e., psychological distress and well-being) by [...] Read more.

Background and Objectives: The COVID-19 pandemic has had severe and far-reaching repercussions for health systems and societies, creating a global mental health crisis that has persisted after the pandemic. This study examined differences in mental health (i.e., psychological distress and well-being) by gender and pandemic period (i.e., lockdown, second and third pandemic waves, the last year of the pandemic, and the post-pandemic period) among Spanish individuals in two stages of adulthood: established adulthood and midlife. The second objective was to identify the risk and protective factors for psychological distress and well-being during the post-pandemic period. Materials and Methods: The study design was repeated cross-sectionally. The non-probability sample included 3677 people (66.2% women) from the general Spanish population, aged 30 to 59 years. Participants were assessed between 1 June 2020 and 23 May 2024 using the following self-reports: the General Health Questionnaire-12 item version, the Scale of Positive and Negative Experience, the Brief Inventory of Thriving, the Satisfaction with Life Scale, the Rosenberg Self-Esteem Scale, the Social Support Scale, the Stressful Events Questionnaire, the Brief Resilience Scale, and the Perceived Vulnerability to Disease Questionnaire. Results: Although rates of psychological distress varied across pandemic periods, women consistently experienced higher rates than men. During the post-pandemic period, the rates of psychological distress were 47.5% for women in established adulthood and 34.7% for midlife women, compared to 28.6% and 22% for men, respectively. Low self-esteem was the main predictor of greater psychological distress and lower well-being for both genders and age groups in the post-pandemic period. Another significant predictor was lower stress resilience. Conclusions: The COVID-19 pandemic threatened women’s mental health and well-being more than men’s, and this threat persists after the pandemic, especially among women in established adulthood. The study’s findings are relevant for the design of policies, programs, and strategies to achieve better mental health and well-being among citizens and greater gender equality. Full article

(This article belongs to the Section Psychiatry)

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19 pages, 2149 KB

Open AccessArticle

Key Biomarker Correlations in Cutaneous Melanoma: Implications for Diagnostic, Prognostic, and Therapeutic Strategies—A Retrospective Single-Centered Study

by Mariana Costache, Ancuța-Augustina Gheorghişan-Gălățeanu, Diana Derewicz, Cătălin Cîrstoiu and Andreea Ilieșiu

Medicina 2025, 61(10), 1733; https://doi.org/10.3390/medicina61101733 - 24 Sep 2025

Abstract

Background and Objectives: Cutaneous melanomas are highly aggressive and prevalent malignancies that often require complex diagnostic and therapeutic procedures. Mounting evidence supports the utility of several biomarkers for improving diagnostic accuracy and treatment decisions. In this study, we aimed to evaluate the correlations [...] Read more.

Background and Objectives: Cutaneous melanomas are highly aggressive and prevalent malignancies that often require complex diagnostic and therapeutic procedures. Mounting evidence supports the utility of several biomarkers for improving diagnostic accuracy and treatment decisions. In this study, we aimed to evaluate the correlations between various histopathological and immunohistochemical markers to better understand melanoma development and its subsequent behavior. Materials and Methods: We conducted a retrospective study on 59 patients diagnosed with cutaneous melanoma to establish the significant correlations between clinical, histopathological, and immunohistochemical markers. Results: The mean age of the patients was 60.15 years, with a male-to-female ratio of 1.27:1. Our results demonstrate significant correlations between proliferative activity, evaluated both as mitotic counts and Ki-67 index, and clinicopathological parameters. Other significant correlations between melanoma immunohistochemical markers such as Melan-A, HMB45, S100 or PRAME and Breslow depth highlight their potential not only for diagnostic but also for prognostic purposes. Additionally, the significant negative correlations between p16 and patient age, Breslow depth, and the Ki-67 index emphasize the predictive value of this still insufficiently described parameter. Conclusions: Taken together, these observations underscore the importance of integrating biomarker evaluation into melanoma management, enabling more precise prognostication and the development of individualized treatment strategies. Full article

(This article belongs to the Special Issue Cutaneous Melanoma: Updating from Pathogenesis to Therapy)

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15 pages, 1156 KB

Open AccessArticle

Evaluation of Nrf2/Keap1 Pathway in Patients with Migraine

by Fatih Koçtürk, Firdevs Emekli, Kadir Eği and Seyithan Taysi

Medicina 2025, 61(10), 1732; https://doi.org/10.3390/medicina61101732 - 24 Sep 2025

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Abstract

Background and Objectives: Migraine is the most common primary headache disorder worldwide, negatively affecting quality of life and limiting the functionality of individuals. Although its pathogenesis is not fully understood, it is known that activation of the trigeminovascular system, neurogenic inflammation, and [...] Read more.

Background and Objectives: Migraine is the most common primary headache disorder worldwide, negatively affecting quality of life and limiting the functionality of individuals. Although its pathogenesis is not fully understood, it is known that activation of the trigeminovascular system, neurogenic inflammation, and oxidative stress are among the main components of migraine. In this context, we aimed to investigate the possible role of the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) signaling pathway, which plays a key role in the regulation of cellular oxidative stress, in the development of chronic diseases such as migraine. Materials and Methods: In this study, the oxidative stress parameters total oxidant level (TOS), total antioxidant level (TAS), and oxidative stress index (OSI) and changes in the Nrf2/Keap1 signaling pathway were analyzed in migraine patients. Results: The results showed that Keap1 levels were significantly higher in migraine patients compared with the control group, whereas the Nrf2 and TAS levels were low. In addition, increased levels of oxidized LDL (oxLDL) and glycogen synthase kinase-3 beta (GSK3B), which are oxidative stress markers, confirmed that the oxidative stress burden was high in migraine patients. The fact that OSI values were significantly higher in migraine patients clearly demonstrates that systemic oxidative stress was out of balance in these individuals. Conclusions: In conclusion, this study reveals that oxidative stress and the Nrf2/Keap1 signaling pathway play an important role in the pathogenesis of migraine. Decreased Nrf2 activity and increased Keap1 levels suggest that the antioxidant defense system is insufficient in migraine patients. These findings suggest that the Nrf2/Keap1 signaling pathway may be considered as a potential target for migraine treatment and that the development of new treatment strategies to reduce oxidative stress may be beneficial. Full article

(This article belongs to the Section Neurology)

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16 pages, 2836 KB

Open AccessArticle

Novel 1-(2-Aryl-2-adamantyl)piperazine Derivatives Exhibit In Vitro Anticancer Activity Across Various Human Cancer Cell Lines, with Selective Efficacy Against Melanoma

by Irida Papapostolou, Evangelia Sereti, Stavroula Chatira, Nikos Sakellaridis, George Fytas, Grigoris Zoidis and Konstantinos Dimas

Medicina 2025, 61(10), 1731; https://doi.org/10.3390/medicina61101731 - 23 Sep 2025

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Abstract

Background and Objectives: Cutaneous melanoma (CM) is widely regarded as the most aggressive form of skin cancer worldwide, showing a rising global incidence. It develops from the uncontrolled transformation of pigment-producing melanocytes. The aim of this study is to characterize the cytotoxic [...] Read more.

Background and Objectives: Cutaneous melanoma (CM) is widely regarded as the most aggressive form of skin cancer worldwide, showing a rising global incidence. It develops from the uncontrolled transformation of pigment-producing melanocytes. The aim of this study is to characterize the cytotoxic and anti-proliferative properties of two 1-(2-aryl-adamantyl)piperazine derivatives, 6 and 7, with a specific emphasis on their impact on melanoma cells. Both compounds are synthesized based on the adamantane core structure which increases drug-like properties of the lead compound phencyclidine I, without increasing toxicity. Materials and Methods: This study describes concentration-dependent effects on cell viability and clonogenicity. Results: SRB assays, clonogenic (long-term) assays, and scratch assays reveal a significant anticancer activity of these two agents at low μΜ levels with a selective activity against melanoma cells. Furthermore, Western blot experiments indicate that both 6 and 7 induce LC3 accumulation, procaspase 3 decrease, and PARP cleavage, suggesting the implication of multiple death pathways in their anticancer mechanism of action. Conclusions: This study sheds light on the in vitro anticancer potential of two novel 1-(2-aryl-2-adamantyl)piperazine derivatives. It highlights their differential activity against melanoma and emphasizes their potential as lead candidates for further therapeutic exploration. Full article

(This article belongs to the Section Oncology)

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15 pages, 1763 KB

Open AccessArticle

Comparative Effectiveness of Clopidogrel Versus Aspirin for Primary Prevention in High-Risk Patients with Type 2 Diabetes: A Nationwide Propensity Score–Matched Cohort Study

by Soo Hyun Kang, Joonpyo Lee, Jung Ho Kim and Youngwoo Jang

Medicina 2025, 61(10), 1730; https://doi.org/10.3390/medicina61101730 - 23 Sep 2025

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Abstract

Background and Objectives: The benefits of aspirin for primary prevention of atherosclerotic cardiovascular disease (ASCVD) among high-risk patients with diabetes are controversial owing to bleeding risk. Current guidelines recommend the use of aspirin in high-risk patients with diabetes; however, the supporting evidence [...] Read more.

Background and Objectives: The benefits of aspirin for primary prevention of atherosclerotic cardiovascular disease (ASCVD) among high-risk patients with diabetes are controversial owing to bleeding risk. Current guidelines recommend the use of aspirin in high-risk patients with diabetes; however, the supporting evidence is inconsistent, primarily due to an increased risk of gastrointestinal (GI) bleeding. Given these concerns, it is important to explore alternative antiplatelet strategies. Clopidogrel, a widely used P2Y12 inhibitor, has been suggested to cause fewer GI bleeding events than aspirin. Accordingly, we aimed to compare the efficacy and bleeding risk of clopidogrel versus aspirin in high- and very high-risk populations with diabetes without prior ASCVD using the Korean National Health Insurance Service data. Materials and Methods: Propensity score-matching was performed to reduce baseline imbalances. The primary endpoint was net adverse clinical events (NACEs), defined as a composite of all-cause death, myocardial infarction (MI), stroke, intracranial hemorrhage (ICH), and gastrointestinal GI bleeding. Secondary endpoints included efficacy (composite of all-cause death, MI, and stroke) and bleeding outcomes (GI bleeding and ICH). Results: Among 10,453 patients (9550 on aspirin and 903 on clopidogrel), 902 matched pairs were analyzed. Clopidogrel showed no significant difference compared with aspirin in NACE incidence (hazard ratio [HR]: 0.97; 95% confidence interval [CI]: 0.79–1.19), efficacy endpoints (HR: 1.02; 95% CI: 0.82–1.26), or individual outcomes (MI, stroke, all-cause death). Clopidogrel demonstrated a trend towards lower GI bleeding (HR: 0.48; 95% CI: 0.23–1.01), although not significant. In subgroup analysis, male patients on clopidogrel had significantly lower NACE risk than those on aspirin (HR: 0.73; 95% CI: 0.54–0.99). Conclusions: These findings suggest that clopidogrel may be considered a preferable alternative to aspirin for primary prevention in high-risk male patients with diabetes, particularly those with an elevated risk for gastrointestinal bleeding, guiding personalized antiplatelet therapy choices in clinical practice. Full article

(This article belongs to the Section Cardiology)

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12 pages, 320 KB

Open AccessReview

Quality of Life Assessment and Clinical Implications for Women with Endometriosis Through Validated Tools: A Narrative Review

by Andrei Manu, Elena Poenaru, Florentina Duica, Alexandra Irma Gabriela Bausic, Bogdan-Catalin Coroleuca, Ciprian-Andrei Coroleuca, Cristina Iacob, Ioana Rosca and Elvira Bratila

Medicina 2025, 61(10), 1729; https://doi.org/10.3390/medicina61101729 - 23 Sep 2025

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Abstract

Aim: The aim of the study was to synthesize validated patient-reported outcome measures (PROMs) for assessing health-related quality of life (HRQoL) in women with endometriosis and to outline their clinical implications. Methods: We conducted a narrative review of English-language literature indexed [...] Read more.

Aim: The aim of the study was to synthesize validated patient-reported outcome measures (PROMs) for assessing health-related quality of life (HRQoL) in women with endometriosis and to outline their clinical implications. Methods: We conducted a narrative review of English-language literature indexed in PubMed, Scopus, Web of Science, and Cochrane Library, covering the period 2014–2024, with earlier seminal studies included where relevant. We focused on validated PROMs for QoL but also considered standardized tools such as the Endometriosis Fertility Index (EFI), rASRM, and #Enzian classifications, given their role in clinical interpretation and counseling. Findings: Generic instruments (SF-36, WHOQOL-BREF, EQ-5D), disease-specific tools (EHP-30, EHP-5), and fertility-related questionnaires (FertiQoL, FPI) have demonstrated validity and responsiveness; however, these are inconsistently applied in practice. Knowledge gaps remain regarding routine implementation, timing, and frequency of assessment, and integration with clinical staging or fertility indices (e.g., EFI). Global frameworks such as the WERF EPHect platform facilitate standardized clinical and surgical data capture, though their use is primarily in research rather than routine care. Conclusions: We recommend combining a disease-specific PROM (EHP-30/EHP-5) with a generic instrument (SF-36 or EQ-5D) and adding FertiQoL when fertility is relevant. PROMs should be collected longitudinally (baseline, post-intervention, follow-up) and interpreted alongside clinical context, including pain phenotype, surgical staging (#Enzian/rASRM), and fertility goals. Embedding PROMs into multidisciplinary pathways enables shared decision-making, individualized treatment planning, and improved comparability of patient-centered outcomes. Full article

(This article belongs to the Section Obstetrics and Gynecology)

12 pages, 1450 KB

Open AccessSystematic Review

Opioid-Associated Postoperative Nausea and Vomiting in Women Undergoing Laparoscopic Hysterectomy: A Network Meta-Analysis

by Sueyoung Cho, Heesoo Bang, Sangyoon Shin, Hyunjoo Kim, Seohyeon Park, Paul S. Lee and Eunkyung Euni Lee

Medicina 2025, 61(10), 1728; https://doi.org/10.3390/medicina61101728 - 23 Sep 2025

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Abstract

Background and Objectives: This systematic review and network meta-analysis evaluated the effects of postoperative opioid use on nausea and vomiting in women undergoing laparoscopic hysterectomy. Materials and Methods: A systematic search of PubMed, EMBASE, the Cochrane Library, and RISS was conducted [...] Read more.

Background and Objectives: This systematic review and network meta-analysis evaluated the effects of postoperative opioid use on nausea and vomiting in women undergoing laparoscopic hysterectomy. Materials and Methods: A systematic search of PubMed, EMBASE, the Cochrane Library, and RISS was conducted to identify randomized controlled trials that met the eligibility criteria. The Cochrane Risk of Bias 2 tool was used to assess the quality of the included studies. A frequentist network meta-analysis was performed to compare the risks of opioid-associated postoperative nausea and vomiting (O-PONV). Quantitative statistics were presented in forest plots, and the ranking of treatments was determined using the P-score. Results: Seventeen studies involving 1315 participants and 18 postoperative analgesic interventions were included. No significant differences were found among the opioid monotherapies—buprenorphine, butorphanol, fentanyl, oxycodone, sufentanil, and tapentadol. However, among the combination therapies, oxycodone/ketorolac therapy was associated with a significantly higher risk of O-PONV than other ketorolac-containing regimens, including dexmedetomidine, remifentanil, and fentanyl. Conclusions: No significant differences in O-PONV risk were observed among the six opioid monotherapy groups. An opioid-sparing regimen, such as dexmedetomidine/ketorolac, showed a lower risk of O-PONV than an oxycodone-based regimen, underscoring the importance of incorporating patient-centered considerations, such as patient preference and route of administration, into postoperative pain management. Full article

(This article belongs to the Section Intensive Care/ Anesthesiology)

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16 pages, 298 KB

Open AccessArticle

Assessment of Bone Mineral Density in Children with Developmental Dysplasia of the Hip Joint: Possible Risk Factors for Osteopenia and Osteoporosis

by Maha A. Al Slateen, Alaa Ibrahim, Turki Abualait, Ammar Alomran, Sarah Alshahwan, Mariam Alsomali and Mohammed S. Abdelsalam

Medicina 2025, 61(10), 1727; https://doi.org/10.3390/medicina61101727 - 23 Sep 2025

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Abstract

Background and Objectives: Developmental dysplasia of the hip (DDH) in children can result in long-term skeletal complications, including a reduced bone mineral density (BMD) and an increased risk of osteoporosis. This study aimed to evaluate BMD in children with DDH and to identify [...] Read more.

Background and Objectives: Developmental dysplasia of the hip (DDH) in children can result in long-term skeletal complications, including a reduced bone mineral density (BMD) and an increased risk of osteoporosis. This study aimed to evaluate BMD in children with DDH and to identify clinical, functional, and nutritional factors associated with reduced BMD. Materials and Methods: A cross-sectional study was conducted on 25 children aged 5–10 years with confirmed DDH. Bone mineral density was measured at the total body, subtotal, and lumbar spine using dual-energy X-ray absorptiometry (DXA), and Z-scores were calculated. Functional assessments included isometric muscle strength, weight-bearing symmetry, and physical activity measured via accelerometry. Demographic data and daily calcium intake were recorded. Correlation and multiple linear regression analyses were performed to determine predictors of BMD. Results: Most participants exhibited normal growth and mobility, with mild asymmetries in limb strength and length. The mean total BMD was within normative ranges, whereas the lumbar spine Z-score (−1.41 ± 1.72) was mildly reduced. BMD positively correlated with age, anthropometric measures, weight-bearing capacity, and calcium intake, and negatively correlated with a family history of osteoporosis. Multiple regression analysis identified the muscle strength symmetry index as the strongest independent predictor of BMD across all sites (subtotal Z-score: β = 1.000, p < 0.001; total Z-score: β = 0.425, p = 0.023; lumbar Z-score: β = 0.499, p = 0.014). Physical activity levels showed no significant associations with BMD. Conclusions: Children with DDH generally demonstrate preserved overall BMD; however, mild lumbar spine deficits may occur. Muscle strength symmetry appears to be the most influential modifiable factor for optimizing bone health in this population, highlighting the importance of targeted physiotherapy interventions. Full article

(This article belongs to the Topic New Advances in Physical Therapy and Occupational Therapy, 2nd Edition)

16 pages, 280 KB

Open AccessArticle

Comparative Evaluation of Near-Term Oncologic, Urinary, Sexual, and Postoperative Outcomes in Rectal Cancer: Laparoscopic vs. Robotic Approaches

by Vagif Gurbanov, Veysel Umman, Osman Bozbiyik and Tayfun Yoldas

Medicina 2025, 61(10), 1726; https://doi.org/10.3390/medicina61101726 - 23 Sep 2025

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Abstract

Background and Objectives: This study compares laparoscopic and robotic surgical techniques for rectal cancer, focusing on oncologic outcomes, mesocolic excision quality, lymph node yield, and postoperative sexual and urinary function, while also exploring patient satisfaction and recovery trajectories through clinical outcomes and validated [...] Read more.

Background and Objectives: This study compares laparoscopic and robotic surgical techniques for rectal cancer, focusing on oncologic outcomes, mesocolic excision quality, lymph node yield, and postoperative sexual and urinary function, while also exploring patient satisfaction and recovery trajectories through clinical outcomes and validated questionnaires. Materials and Methods: A retrospective analysis was conducted on 100 patients who underwent rectal cancer surgery between 2017 and 2021 at our tertiary center—53 underwent laparoscopic and 47 robotic surgery. Demographic data, tumor characteristics, and surgical details (procedure type, lymph node yield, morbidity, and mortality) were collected, and postoperative outcomes, including local recurrence, metastasis, need for reoperation, urinary incontinence, and sexual dysfunction, were compared. Functional outcomes were evaluated using the LARS questionnaire, Wexner score, IPSS, IIEF, and FSFI. Results: No significant differences were found in age, BMI, tumor size, or ASA scores between groups. Robotic surgery was associated with shorter hospital stays (p < 0.001), no conversions to open surgery (vs. 28.3% in laparoscopy), and zero cases of positive circumferential margins (vs. 35.8% in laparoscopy; p < 0.001). Lymphatic and perineural invasion rates were similar. Tumor recurrence occurred in four robotic and six laparoscopic cases, and factors significantly associated with recurrence included pathological stage, hospital stay, and adjuvant treatment. Robotic surgery showed improved urinary and sexual function, with lower Wexner, IPSS, and FSFI scores. Conclusions: Robotic surgery is a safe, effective, and patient-friendly alternative to laparoscopy, offering better preservation of continence and sexual function, reduced conversion rates, and shorter hospitalization, and should be considered the preferred approach in appropriately selected rectal cancer patients. Full article

(This article belongs to the Special Issue Advances in Colorectal Surgery and Oncology)

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Medicina, Volume 61, Issue 10 (October 2025) – 33 articles

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