Medicina

21 pages, 624 KiB

Open AccessReview

Integrated Hospital–Territory Organizational Models and the Role of Family and Community Nurses in the Management of Chronic Conditions: A Scoping Review

by Gianluca Azzellino, Patrizia Vagnarelli, Mauro Passamonti, Luca Mengoli, Lia Ginaldi and Massimo De Martinis

Medicina 2025, 61(7), 1175; https://doi.org/10.3390/medicina61071175 (registering DOI) - 28 Jun 2025

Abstract

Background and Objectives: One of the challenges of modern healthcare systems, in terms of economic and organizational sustainability and the impact on patients’ quality of life, is the progressive increase in chronicity and care complexity. In this scenario, hospital–community integration models represent [...] Read more.

Background and Objectives: One of the challenges of modern healthcare systems, in terms of economic and organizational sustainability and the impact on patients’ quality of life, is the progressive increase in chronicity and care complexity. In this scenario, hospital–community integration models represent possible strategies to ensure the continuity of care, reduce readmission rates, and improve clinical outcomes. This study aims to map integrated care models for patients with chronic diseases, with active involvement of the family and community nurse, describing their functions and associated clinical, organizational, and economic outcomes, as well as barriers and facilitators to their implementation. Materials and Methods: The review was conducted using the JBI methodology and the PRISMA-ScR protocol and identified 26 studies with a publication range from 2000 to 2025. Results: The emerging results highlight the use of integrated and personalized organizational models in the post-discharge phases, with a leading role for the family and community nurse in the assessment, planning, and coordination of various steps. Conclusions: The interventions are associated with an increase in patient and caregiver satisfaction, a reduction in outcomes such as the rehospitalization rate, and greater continuity of care. Full article

(This article belongs to the Special Issue Advances in Public Health and Healthcare Management for Chronic Care)

13 pages, 418 KiB

Open AccessArticle

Association of Helicobacter pylori with Serum HIF-1α, HIF-2α, and Human Transmembrane Prolyl 4-Hydroxylase Activity in Patients with Chronic Gastritis

by Sefa Ergün, Fadime Kutluk, Basar Can Turgut, Seyma Dumur, Uğurcan Sayılı, Dilek Duzgun Ergun and Hafize Uzun

Medicina 2025, 61(7), 1174; https://doi.org/10.3390/medicina61071174 (registering DOI) - 28 Jun 2025

Abstract

Background and Objectives: Chronic mucosal infection with Helicobacter pylori (H. pylori) plays a key role in the development of gastroduodenal disorders such as chronic gastritis, peptic ulcers, gastric lymphoma, and gastric cancer by triggering local immune responses and inducing hypoxic [...] Read more.

Background and Objectives: Chronic mucosal infection with Helicobacter pylori (H. pylori) plays a key role in the development of gastroduodenal disorders such as chronic gastritis, peptic ulcers, gastric lymphoma, and gastric cancer by triggering local immune responses and inducing hypoxic and inflammatory conditions in the gastric mucosa. This study aims to evaluate the potential diagnostic value of hypoxia-inducible factors HIF-1α and HIF-2α, along with transmembrane prolyl 4-hydroxylase (P4H-TM), as biomarkers in H. pylori-positive patients. Additionally, the study investigates the association between these markers and alterations in lipid profiles, as well as their involvement in the molecular mechanisms underlying gastric conditions like gastritis, particularly in the context of H. pylori infection. Materials and Methods: This study was conducted at Istanbul Avcılar Murat Kölük State Hospital’s General Surgery Outpatient Clinic. A total of 60 participants were included: 40 patients diagnosed with chronic gastritis (20 H. pylori-positive and 20 H. pylori-negative) and 20 healthy controls confirmed negative by 13C-urea breath test. Blood samples were collected for ELISA analysis of HIF-1α, HIF-2α, and P4H-TM levels. Additionally, lipid profiles were measured and compared among the groups. Results: No significant differences were found among the groups in terms of demographic factors such as age, sex, or body mass index (BMI). However, significant variations were observed in the levels of HIF-1α, HIF-2α, and P4H-TM across all groups (p < 0.001 for each marker). These markers were substantially elevated in the H. pylori-positive gastritis group compared to both the H. pylori-negative and healthy control groups. Receiver Operating Characteristic (ROC) curve analysis revealed that all evaluated markers exhibited strong diagnostic accuracy in differentiating H. pylori-positive individuals from other groups. HIF-1α (AUC: 0.983) and HIF-2α (AUC: 0.981) both achieved 100% sensitivity with specificities of 93.3% and 91.1%, respectively. P4H-TM showed an AUC of 0.927, with 85% sensitivity and 95.6% specificity. Conclusions: These findings indicate that HIF-1α, HIF-2α, and P4H-TM may serve as effective biomarkers for diagnosing H. pylori-positive patients and may be linked to changes in lipid metabolism. The elevated expression of these markers in response to H. pylori infection highlights their potential roles in the inflammatory and hypoxic pathways that contribute to the pathogenesis of gastric diseases such as gastritis. Full article

(This article belongs to the Section Gastroenterology & Hepatology)

15 pages, 503 KiB

Open AccessArticle

Pre-Exercise Ingestion of Hydrogen-Rich Cold Water Enhances Endurance Performance and Lactate Response in Heat

by Mariem Khlifi, Nidhal Jebabli, Nejmeddine Ouerghi, Fatma Hilal Yagin, Ashit Kumar Dutta, Reem Alwhaibi and Anissa Bouassida

Medicina 2025, 61(7), 1173; https://doi.org/10.3390/medicina61071173 (registering DOI) - 28 Jun 2025

Abstract

Background and Objectives: Hyperthermia significantly limits endurance performance in hot environments. To enhance heat loss and optimize athletic performance, pre-cooling interventions can be employed to accelerate body cooling. Therefore, the aim of this study was to evaluate the effects of an internal pre-cooling [...] Read more.

Background and Objectives: Hyperthermia significantly limits endurance performance in hot environments. To enhance heat loss and optimize athletic performance, pre-cooling interventions can be employed to accelerate body cooling. Therefore, the aim of this study was to evaluate the effects of an internal pre-cooling intervention combined with external pre-cooling or hydrogen-rich water on endurance performance in the heat. Materials and Methods: In a double-blind crossover with counterbalanced trials, all participants underwent a shuttle run test after 30 min under the following conditions: (1) hydrogen-rich cold water ingestion (HRCW); (2) cold water ingestion and external pre-cooling (IEPC); and (3) cold-water ingestion (control). Maximal aerobic speed (MAS), number of shuttle run repetitions, dehydration, temperature, heart rate (HR), rate of perceived exertion (RPE), blood lactate, and feeling scale (FS) were measured during the 20 m shuttle run test. Results: Our results revealed a significant variation in dehydration, MAS, number of shuttle run repetitions, blood lactate, RPE, and FS (p = [0.001–0.036]); additionally, a significant group × time interaction was found for body temperature (p = 0.021). Post hoc tests revealed a significant change for MAS (HRCW: p < 0.001), number of shuttle run repetitions (HRCW: p < 0.001), dehydration (HRCW: p= 0.009; IEPC: p = 0.008), blood lactate (HRCW: p < 0.001; IEPC: p < 0.001), RPE (HRCW: p = 0.05; IEPC: p = 0.004), and FS (HRCW: p = 0.05; IEPC: p = 0.004), as well as a significant decrease in body temperature (IEPC: p < 0.001; HRCW: p = 0.028) compared to the control condition after the test. However, no significant differences were reported in HR among the different conditions. Conclusions: In conclusion, findings from this study suggest that ingesting hydrogen-rich cold water effectively mitigates the effects of heat stress, thereby improving endurance performance, enhancing mood, and reducing ratings of perceived exertion. Full article

(This article belongs to the Section Sports Medicine and Sports Traumatology)

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19 pages, 737 KiB

Open AccessReview

by Maurizio Marchesini, Diego Fornasari, Silvia Natoli, Elena Vegni and Arturo Cuomo

Medicina 2025, 61(7), 1172; https://doi.org/10.3390/medicina61071172 (registering DOI) - 28 Jun 2025

Abstract

Background and Objectives: Chronic pain (CP), defined as pain persisting for over 3 months, is a significant cause of global disability and affects more than 20% of individuals in Western countries, including Italy. Substantial evidence indicates a higher prevalence of CP among women, [...] Read more.

Background and Objectives: Chronic pain (CP), defined as pain persisting for over 3 months, is a significant cause of global disability and affects more than 20% of individuals in Western countries, including Italy. Substantial evidence indicates a higher prevalence of CP among women, who also experience greater sensitivity, increased frequency, and a longer duration of pain. The impact of CP on quality of life, daily functioning, and employment is profound, particularly for women. However, chronic pain research has insufficiently addressed sex and gender differences, contributing to suboptimal and inequitable care. This neglect limits the development of personalized treatment strategies and, when combined with an aging population and women’s longer life expectancy, highlights an increasing societal and economic burden. Materials and Methods: The authors conducted a narrative review of studies examining biological, psychological, or social determinants of sex-related differences in CP perception or treatment. Each thematic area was reviewed by at least two authors, who critically appraised the literature. Their analyses were refined through iterative group discussions to develop concise, evidence-informed recommendations for personalized and equitable pain management. Results: Sex differences in CP arise from a range of factors, including biological mechanisms such as hormonal and genetic influences, psycho-social factors such as depression and anxiety, and socio-economic determinants, such as income and education levels. These factors also affect sex-specific outcomes of analgesic treatments currently available. Identifying these risk factors and tailoring treatment strategies to sex differences can significantly improve CP management. Such a personalized approach is essential for advancing precision medicine in CP management. Even in the absence of molecular or genomic biomarkers, adopting a biopsychosocial model that considers sex and gender differences, symptoms, physiological indicators, medical history, lifestyle, and psychological aspects may substantially enhance patient outcomes. Conclusions: This review provides a comprehensive analysis of sex differences in CP perception, stressing the importance of individualized, interdisciplinary approaches in pain management. Addressing both the biological and psycho-social contributors to pain in men and women is critical for guiding healthcare professionals in implementing precision pain medicine strategies, ultimately fostering more equitable and effective care. Full article

(This article belongs to the Special Issue Treatment in Patients with Chronic Pain Syndrome)

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16 pages, 727 KiB

Open AccessArticle

Outcome of Preterm Neonates > 32 Weeks Gestation in Relation to Three-Tiered Fetal Heart Rate Categorization

by Jelena Sabljić, Klara Čogelja, Edita Runjić, Blagoja Markoski, Marijana Barbača, Toni Modrić and Boris Bačić

Medicina 2025, 61(7), 1171; https://doi.org/10.3390/medicina61071171 (registering DOI) - 28 Jun 2025

Abstract

Background and Objectives: Electronic fetal heart rate monitoring is mandatory for preterm labor. Moderate to late preterm neonates have an increased risk of overall morbidity, neonatal intensive care (NICU) admission, and consequently, medication use. The outcome of preterm neonates > 32 weeks of [...] Read more.

Background and Objectives: Electronic fetal heart rate monitoring is mandatory for preterm labor. Moderate to late preterm neonates have an increased risk of overall morbidity, neonatal intensive care (NICU) admission, and consequently, medication use. The outcome of preterm neonates > 32 weeks of gestation in relation to three-tiered fetal heart rate (FHR) categorization was analyzed. Materials and Methods: This was a single-center, retrospective case-control study conducted from January 2021 to December 2023. The study included 25 FGR and 131 control cases born from 33 to 36 6/7 gestational weeks. Outcome was defined as the need for assistance after birth in first 15 min of life, respiratory outcome, and first day dopamine use and fresh frozen plasma transfusion. Maternal characteristics as risk factors for non-normal categories within three-tiered FHR categorization were also analyzed. Results: There was no significant difference in neonatal outcome among groups, except significantly lower 1 min APGAR and longer LOS in the FGR group. An increasing category within the three-tiered FHR categorization positively correlated with the need for assistance after birth, respiratory outcome, dopamine use, fresh frozen plasma transfusion, and length of hospital stay. Negative correlations were revealed between the increasing category within the three-tiered FHR categorization and first and fifth minute APGAR scores. Oligohydramnios and male sex were risk factors for non-normal categories within three-tiered FHR categorization. The correlation was tested using the Spearman correlation coefficient. A logistic regression model was employed to identify maternal risk factors for the non-normal category within three-tiered FHR categorization. All differences were statistically significant (p < 0.05). Conclusions: The increasing category within three-tiered FHR categorization may alert neonatologists to be highly suspicious of RDS, respiratory support, dopamine use, and fresh frozen plasma transfusion in neonates born from 33 to 36 6/7 gestational weeks. Oligohydramnios and male sex increase the probability for non-normal categories in the three-tiered FHR categorization. Full article

(This article belongs to the Section Obstetrics and Gynecology)

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16 pages, 909 KiB

Open AccessSystematic Review

Systematic Review and Meta-Analysis of AI-Assisted Mammography and the Systemic Immune-Inflammation Index in Breast Cancer: Diagnostic and Prognostic Perspectives

by Sebastian Ciurescu, Maria Ciupici-Cladovan, Victor Bogdan Buciu, Diana Gabriela Ilaș, Cosmin Cîtu and Ioan Sas

Medicina 2025, 61(7), 1170; https://doi.org/10.3390/medicina61071170 (registering DOI) - 27 Jun 2025

Abstract

Background and Objectives: Breast cancer remains a significant global health burden, demanding continuous innovation in diagnostic and prognostic tools. This meta-analysis and systematic review aims to synthesize evidence from 2015 to 2025 regarding the diagnostic utility of artificial intelligence (AI) in mammography [...] Read more.

Background and Objectives: Breast cancer remains a significant global health burden, demanding continuous innovation in diagnostic and prognostic tools. This meta-analysis and systematic review aims to synthesize evidence from 2015 to 2025 regarding the diagnostic utility of artificial intelligence (AI) in mammography and the prognostic value of the Systemic Immune-Inflammation Index (SII) in breast cancer patients. Materials and Methods: A systematic literature search was conducted in PubMed, Google Scholar, EMBASE, Web of Science, and Scopus. Studies evaluating AI performance in mammographic breast cancer detection and those assessing the prognostic significance of SII (based on routine hematologic parameters) were included. The risk of bias was assessed using QUADAS-2 and the Newcastle–Ottawa Scale. Meta-analyses were conducted using bivariate and random-effects models, with subgroup analyses by clinical and methodological variables. Results: Twelve studies were included, five assessing AI and seven assessing SII. AI demonstrated high diagnostic accuracy, frequently matching or surpassing that of human radiologists, with AUCs of up to 0.93 and notable reductions in radiologist reading times (17–91%). Particularly in dense breast tissue, AI improved detection rates and workflow efficiency. SII was significantly associated with poorer outcomes, including reduced overall survival (HR ~1.97) and disease-free survival (HR ~2.07). However, variability in optimal cut-off values for SII limits its immediate clinical standardization. Conclusions: AI enhances diagnostic precision and operational efficiency in mammographic screening, while SII offers a cost-effective prognostic biomarker for systemic inflammation in breast cancer. Their integration holds promise for more personalized care. Nevertheless, challenges persist regarding prospective validation, standardization, and equitable access, which must be addressed through future translational research. Full article

(This article belongs to the Special Issue New Developments in Diagnosis and Management of Breast Cancer)

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16 pages, 2000 KiB

Open AccessArticle

The Impact of Frailty Indices on Predicting Complications and Functional Recovery in Proximal Humerus Fractures: A Comparative Study

by Ekrem Özdemir, Oya Olcay Özdeş, Fatih Emre Topsakal, Nasuhi Altay and Esra Demirel

Medicina 2025, 61(7), 1169; https://doi.org/10.3390/medicina61071169 (registering DOI) - 27 Jun 2025

Abstract

Background and Objectives: This retrospective cohort study aimed to evaluate the predictive validity of four frailty indices—Modified Frailty Index-5 (mFI-5), Edmonton Frail Scale (EFS), Clinical Frailty Scale (CFS), and Trauma-Specific Frailty Index (TSFI)—in forecasting postoperative complications and functional outcomes in elderly patients with [...] Read more.

Background and Objectives: This retrospective cohort study aimed to evaluate the predictive validity of four frailty indices—Modified Frailty Index-5 (mFI-5), Edmonton Frail Scale (EFS), Clinical Frailty Scale (CFS), and Trauma-Specific Frailty Index (TSFI)—in forecasting postoperative complications and functional outcomes in elderly patients with proximal humerus fractures (PHFs) treated either surgically or conservatively. Materials and Methods: A total of 244 patients aged ≥60 years with PHFs treated at Erzurum Hospital between January 2018 and January 2023 were included. Patients were categorized into surgical (n = 110) and conservative (n = 134) groups. Surgical procedures included open reduction and internal fixation (n = 88), hemiarthroplasty (n = 10), and reverse shoulder arthroplasty (n = 12). Frailty was retrospectively assessed using mFI-5, EFS, CFS, and TSFI based on 24-month follow-up data. Outcomes included complications, reoperations, rehospitalizations, and functional results measured by the American Shoulder and Elbow Surgeons (ASES) score. Results: The overall complication rate was 13.1%, with nonunion being the most common. Reoperation and rehospitalization rates were 10.6% and 20%, respectively. The mean ASES score was 71.3 ± 15.2, with 60% of patients achieving good or excellent outcomes. Frailty scores, particularly mFI-5 and EFS, were significantly higher in the conservatively treated group compared to the surgical group (p < 0.01). Across both treatment modalities, patients with higher frailty scores had significantly increased complication rates; however, this effect was more pronounced in the surgical group. Multivariate logistic regression revealed that mFI-5 significantly predicted complications, reoperations, and rehospitalizations (p < 0.001). EFS was associated with reoperation risk (p = 0.018), while CFS and TSFI were not significantly correlated with any of the outcomes. Conclusions: Among the evaluated indices, mFI-5 showed the strongest predictive accuracy for adverse outcomes in elderly PHF patients. Notably, the negative impact of frailty was more evident among surgically treated patients. Routine frailty assessment may facilitate better risk stratification and individualized treatment planning in this population. Full article

(This article belongs to the Section Orthopedics)

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11 pages, 3071 KiB

Open AccessArticle

Pathologic Response and Survival Outcomes on HER2-Low vs. HER2-Zero in Breast Cancer Receiving Neoadjuvant Chemotherapy

by Rumeysa Colak, Caner Kapar, Ezgi Degerli, Seher Yildiz Tacar, Aysegul Akdogan Gemici, Nursadan Gergerlioglu, Serdar Altinay and Mesut Yilmaz

Medicina 2025, 61(7), 1168; https://doi.org/10.3390/medicina61071168 (registering DOI) - 27 Jun 2025

Abstract

Background and Objectives: The clinical value of HER2-low breast cancer (BC), defined by immunohistochemistry (IHC) scores of 1+ or 2+/ISH-negative without HER2 amplification, remains unclear in the neoadjuvant setting. This study aimed to determine whether HER2-low and HER2-zero tumors differ in pathological [...] Read more.

Background and Objectives: The clinical value of HER2-low breast cancer (BC), defined by immunohistochemistry (IHC) scores of 1+ or 2+/ISH-negative without HER2 amplification, remains unclear in the neoadjuvant setting. This study aimed to determine whether HER2-low and HER2-zero tumors differ in pathological complete response (pCR) rates and disease-free survival (DFS) among early-stage breast cancer patients undergoing neoadjuvant chemotherapy (NAC). Materials and Methods: We retrospectively analyzed 134 early BC patients treated with NAC between 2017 and 2023. Patients were categorized as HER2-zero (IHC 0) or HER2-low (IHC 1+ or 2+/ISH–). The primary endpoint was total pCR (tpCR); secondary endpoints included breast (bpCR), nodal (npCR), and radiologic complete response (rCR), alongside DFS analysis stratified by hormone receptor (HR) status. Results: Of the cohort, 91 patients (67.9%) were HER2-zero and 43 (32.1%) were HER2-low. There was no statistically significant difference in tpCR (26.4% vs. 27.9%, p = 0.852), bpCR (28.6% vs. 30.2%, p = 0.843), npCR (37.4% vs. 32.6%, p = 0.588), and rCR (23.1% vs. 30.2%, p = 0.374) between HER2-zero and HER2-low groups. DFS did not significantly differ between HER2-zero and HER2-low groups overall (p = 0.714), nor within HR-positive (p = 0.540) or TNBC (p = 0.523) subgroups. Conclusions: HER2-low tumors demonstrated similar pathological responses and survival outcomes compared to HER2-zero tumors. While a HER2-low status does not appear to define a distinct biological subtype in early BC, it remains a relevant classification for emerging HER2-targeted therapies, needing further investigation in prospective studies. Full article

(This article belongs to the Section Oncology)

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35 pages, 2186 KiB

Open AccessReview

Exercise Interventions in Breast Cancer: Molecular Mechanisms, Physical Benefits, and Practical Recommendations

by Vasiliki Michou, Stefanos Zervoudis, Panagiotis Eskitzis, Georgios Tsamos, Dimitra Vasdeki, Andriani Vouxinou, Anisa Markja and Georgios Iatrakis

Medicina 2025, 61(7), 1167; https://doi.org/10.3390/medicina61071167 (registering DOI) - 27 Jun 2025

Abstract

Exercise interventions are increasingly recognized as effective non-pharmacological strategies to improve clinical outcomes in patients with breast cancer. This review provides a comprehensive framework linking physical activity with breast cancer risk reduction, disease progression, and survivorship. We first outline the robust epidemiological evidence [...] Read more.

Exercise interventions are increasingly recognized as effective non-pharmacological strategies to improve clinical outcomes in patients with breast cancer. This review provides a comprehensive framework linking physical activity with breast cancer risk reduction, disease progression, and survivorship. We first outline the robust epidemiological evidence demonstrating that regular exercise significantly reduces breast cancer incidence, recurrence, and disease-specific mortality. The review then delves into the molecular mechanisms by which exercise exerts its protective effects, including modulation of sex hormones, metabolic hormones, systemic inflammation, oxidative stress, circulating microRNAs, and breast cancer-related DNA methylation. Furthermore, we summarize findings from clinical trials evaluating the effects of exercise on cardiorespiratory fitness, functional capacity, and quality of life in breast cancer patients. Emerging research on the synergistic potential of exercise with conventional cancer treatments and bioactive dietary components, particularly polyphenols such as saffron and curcumin, is also discussed. Finally, we present evidence-based exercise recommendations tailored to breast cancer patients, emphasizing the importance of individualized prescriptions to optimize safety and therapeutic benefit. Collectively, this review highlights the multifaceted role of exercise in breast cancer prevention, treatment, and survivorship. Full article

(This article belongs to the Special Issue Recent Advances in Diagnosis and Therapy of Gynecologic and Breast Cancers)

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14 pages, 2139 KiB

Open AccessArticle

Cross-Sectional Study: Associations of A20 and Cezanne with Leukocyte Accumulation in B-Cell Acute Lymphoblastic Leukemia

by Le Thuy Ha, Nguyen Hoang Giang, Nguyen Linh Toan, Nguyen Van Giang, Can Van Mao, Nguyen Quoc Nhat, Tran Dang Quan, Nguyen Huy Hoang, Ngo Thu Hang and Nguyen Thi Xuan

Medicina 2025, 61(7), 1166; https://doi.org/10.3390/medicina61071166 (registering DOI) - 27 Jun 2025

Abstract

Background and Objectives: Acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by the aberrant proliferation of immature lymphoid cells. Lymphoblasts derived from the B-cell lymphoid lineage are identified as B-ALL. A20, CYLD and Cezanne are deubiquitinase genes that inhibit inflammatory response and [...] Read more.

Background and Objectives: Acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by the aberrant proliferation of immature lymphoid cells. Lymphoblasts derived from the B-cell lymphoid lineage are identified as B-ALL. A20, CYLD and Cezanne are deubiquitinase genes that inhibit inflammatory response and tumor progression. Age-related increases in tumor necrosis factor (TNF)-α are associated with poor outcomes in ALL. Little is known about the associations of A20, CYLD and Cezanne with leukocyte accumulation in B-ALL. Materials and Methods: Blood samples of 147 patients with B-ALL and 144 healthy subjects were examined. Gene expression profiles were determined by quantitative PCR, gene polymorphisms by direct DNA sequencing, immunophenotype by flow cytometry and secretion of inflammatory cytokines by an ELISA. Results: Genetic analysis of the A20 gene identified six nucleotide changes in exon 7. Sequencing of the Cezanne gene identified three variants in intron 10. The results indicated that B-ALL patients carrying the A20 p.P348L and Cezanne rs1230581026 variants had higher variant frequencies and lower expression levels than healthy controls. Importantly, carriers of the A20 p.P348L variant had a higher numbers of CD20⁺ and HLA DR⁺ cells than those with a normal genotype, and carriers of the Cezanne rs1230581026 variant had increases in neutrophil, basophil, monocyte, lymphocyte, and CD38⁺ cell counts as well as age-related increases in the levels of TNF-α. Conclusions: The results indicate that the A20 p.P348L and Cezanne rs1230581026 variants are associated with low expression levels of A20/Cezanne, leukocyte expansion and poor outcomes in B-ALL patients. Full article

(This article belongs to the Section Genetics and Molecular Medicine)

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7 pages, 504 KiB

Open AccessArticle

Association Between Perinasal Uptake on Radioactive Iodine Whole-Body Scan and Nasolacrimal Duct Obstruction

by Minjung Seo, Hongje Lee, Na Ri Park, Ju-Hyang Lee and Seol Hoon Park

Medicina 2025, 61(7), 1165; https://doi.org/10.3390/medicina61071165 (registering DOI) - 27 Jun 2025

Abstract

Background and Objectives: This study reports an association between nasolacrimal duct obstruction (NLDO) and perinasal uptake on radioactive iodine (RAI) whole-body scan. Materials and Methods: This is a retrospective study of 37 patients from May to November 2017 who underwent thyroidectomy and [...] Read more.

Background and Objectives: This study reports an association between nasolacrimal duct obstruction (NLDO) and perinasal uptake on radioactive iodine (RAI) whole-body scan. Materials and Methods: This is a retrospective study of 37 patients from May to November 2017 who underwent thyroidectomy and I-131 ablation for papillary thyroid cancer (PTC) and had a follow-up I-123 diagnostic WBS and dacryoscintigraphy. Ophthalmic examinations assessed punctal stenosis, NLDO, tear film break-up time, Schirmer’s test, punctate keratopathy, tear meniscus height, epiphora, and ocular dryness. Perinasal and nasal uptake on whole-body scans (WBSs) were assessed as negative (no uptake) or positive (focal uptake). The associations between perinasal uptake on WBS, dacryoscintigraphy findings, and ophthalmic assessments were assessed. Results: Nasal uptake on I-131 post-ablation WBS were observed in 60 eyes (81%); perinasal uptake was observed in 8 eyes (11%). Nasal uptake on I-123 post-ablation WBS were observed in all eyes; perinasal uptake was observed in 15 eyes (20%). Perinasal and nasal uptake on I-131 post-ablation WBS were significantly associated with delayed excretion on dacryoscintigraphy (p < 0.001 and p = 0.03, respectively). Perinasal uptake on I-123 WBS was associated with both abnormal dacryoscintigraphy findings and ocular dryness (p < 0.001 and p = 0.02, respectively). Conclusions: Perinasal uptake on I-131 post-ablation and I-123 diagnostic WBS was significantly associated with delayed excretion on dacryoscintigraphy, suggesting NLDO. Full article

(This article belongs to the Section Surgery)

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12 pages, 470 KiB

Open AccessArticle

A Comparative Study on the Multidimensional Features of Hereditary and Sporadic Medullary Thyroid Carcinoma Patients: A Single-Center Retrospective Study

by Muzaffer Serdar Deniz, Narin Nasiroglu Imga, Belma Ozlem Tural Balsak, Asiye Safak Bulut, Furkan Savas, Busranur Cavdarli, Cevdet Aydin, Oya Topaloglu, Reyhan Ersoy and Bekir Cakir

Medicina 2025, 61(7), 1164; https://doi.org/10.3390/medicina61071164 (registering DOI) - 27 Jun 2025

Abstract

Background and Objectives: Medullary thyroid carcinoma is a rare neuroendocrine malignancy, with sporadic and hereditary forms accounting for 75% and 25% of cases, respectively. This study compares the clinicopathological features of sporadic medullary thyroid carcinoma (sMTC) and hereditary medullary thyroid carcinoma (hMTC) using [...] Read more.

Background and Objectives: Medullary thyroid carcinoma is a rare neuroendocrine malignancy, with sporadic and hereditary forms accounting for 75% and 25% of cases, respectively. This study compares the clinicopathological features of sporadic medullary thyroid carcinoma (sMTC) and hereditary medullary thyroid carcinoma (hMTC) using real-world data to provide risk factors that aid in the early detection of the disease. Materials and Methods: The retrospective study comprised 77 patients with confirmed MTC treated at a tertiary referral center between January 2019 and December 2024. Patients were classified as hMTC (n = 11) or sMTC (n = 66) based on RET proto-oncogene (RET) genetic testing, whereas harboring a germline RET mutation indicated hMTC. Demographic, clinical, laboratory, radiological, histopathological, and genetic data were collected. Results: hMTC patients were significantly younger at diagnosis, with a comparable gender distribution (p = 0.738), and more often had a previous case of MTC within the family history. Pheochromocytoma occurred exclusively in hMTC. Multicentric tumors were more frequent in hMTC, and non-diagnostic Bethesda I cytology was higher in hMTC. Conclusions: While confirming established differences, this study provides detailed pre-operative diagnostic parameters and surgical approaches that can guide clinical decision-making in resource-limited settings where genetic testing may not be immediately available. Full article

(This article belongs to the Section Endocrinology)

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12 pages, 844 KiB

Open AccessArticle

High Rate of Inappropriate Utilization of an Ophthalmic Emergency Department: A Prospective Analysis of Patient Perceptions and Contributing Factors

by Helena Siegel, Vera Anna Widmer, Paola Kammrath Betancor, Daniel Böhringer and Thomas Reinhard

Medicina 2025, 61(7), 1163; https://doi.org/10.3390/medicina61071163 (registering DOI) - 27 Jun 2025

Abstract

Background and Objectives: In Germany, access to medical care is often hindered by long wait times for specialist appointments and emergency department care. Inappropriate utilization of emergency services further exacerbates delays for truly urgent cases. To evaluate the utilization of the statutory [...] Read more.

Background and Objectives: In Germany, access to medical care is often hindered by long wait times for specialist appointments and emergency department care. Inappropriate utilization of emergency services further exacerbates delays for truly urgent cases. To evaluate the utilization of the statutory ophthalmic emergency service in Freiburg and identify patient- and system-level factors contributing to inappropriate use. Materials and Methods: A paper-based, anonymous questionnaire was distributed to patients attending the ophthalmologic emergency practice (Notfallpraxis) of the Association of Statutory Health Insurance Physicians (Kassenärztliche Vereinigung), which is located within the premises of the Eye Center of the University Hospital Freiburg, Germany, at selected periods between July and September 2020, alongside a short physician assessment. Standardized instruments were used to assess symptom severity, urgency perception, and healthcare-seeking behavior. Statistical analyses were performed using R and Excel. Results: A total of 157 questionnaires were included (response rate: 63%). Most visits occurred on weekends (47%) and before 10 p.m. (83%). While 68% of patients believed their symptoms required same-day treatment, physicians assessed only 30% of cases as clinically urgent. A total of 60% of patients did not attempt to contact an outpatient ophthalmologist beforehand, and only 38% reported having a regular ophthalmologist. Patients’ perceived urgency was significantly associated with symptom severity and older age, whereas physician-assessed urgency was strongly linked to symptom duration. Conclusions: A substantial proportion of ophthalmic emergency visits in Freiburg are for non-urgent conditions. These findings underscore the need for improved coordination with outpatient care providers, better patient education, and structural reforms to reduce inappropriate utilization and ensure timely access for truly urgent cases. Full article

(This article belongs to the Section Ophthalmology)

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14 pages, 311 KiB

Open AccessArticle

Role of Early Trauma on Defense Mechanisms and Coping Strategies in Personality Disorders

by Fabrizio Turiaco, Fiammetta Iannuzzo, Clara Lombardo, Valentina Clementi, Carmela Mento, Antonio Drago, Antonio Bruno, Maria Rosaria Anna Muscatello and Gianluca Pandolfo

Medicina 2025, 61(7), 1162; https://doi.org/10.3390/medicina61071162 - 26 Jun 2025

Abstract

Background and Objectives: We investigated whether early psychological trauma can contribute to the development of dysfunctional personality traits and emotional dysregulation. Personality disorders (PDs) are often characterized by using immature defense mechanisms and maladaptive coping strategies. Materials and Methods: We evaluated [...] Read more.

Background and Objectives: We investigated whether early psychological trauma can contribute to the development of dysfunctional personality traits and emotional dysregulation. Personality disorders (PDs) are often characterized by using immature defense mechanisms and maladaptive coping strategies. Materials and Methods: We evaluated the relationship between early traumatic experiences, PDs, defense mechanisms, and coping strategies. A total of 90 patients aged between 18 and 70 with PDs were studied to detect different subtypes of early trauma, along with the defensive mechanisms and the prevailing coping strategies. Correlation and regression analyses aimed at establishing if specific trauma subtypes were associated with specific defense mechanisms and coping strategies. The Childhood Trauma Questionnaire—Short Form (CTQ-SF), the Defense Style Questionnaire 40 (DSQ-40), and the Coping Orientation to Problem Experienced (COPE) were used as psychodiagnostic tools. Results: Our findings determine emotional abuse, emotional neglect, and physical neglect as the most represented subtypes of trauma and underline the use of immature defense mechanisms in PD patients, while adaptive coping strategies, such as social support and positive aptitude were used. Conclusions: Early trauma, such as abuse and neglect, can be associated with dysfunctional defense mechanisms and coping strategies. This may have significant implications for managing not only pathological areas of the patient but also the functional ones. Moreover, being aware of these aspects can be useful for psychotherapy, reinforcing therapeutic alliance and reducing symptoms. Full article

(This article belongs to the Section Psychiatry)

11 pages, 979 KiB

Open AccessArticle

Effects of Metformin on Survival and Toxicity in Patients with Metastatic Non-Small Cell Lung Cancer Treated with Nivolumab

by Heves Surmeli, Sedat Yildirim, Deniz Isik, Oguzcan Kinikoglu, Yunus Emre Altintas, Ugur Ozkerim and Sıla Oksuz

Medicina 2025, 61(7), 1161; https://doi.org/10.3390/medicina61071161 - 26 Jun 2025

Abstract

Background and Objectives: This study evaluated the effects of concurrent metformin use on clinical outcomes in patients with metastatic non-small cell lung cancer (NSCLC) treated with nivolumab. Materials and Methods: A total of 152 patients were analyzed, including 110 non-users and 42 metformin [...] Read more.

Background and Objectives: This study evaluated the effects of concurrent metformin use on clinical outcomes in patients with metastatic non-small cell lung cancer (NSCLC) treated with nivolumab. Materials and Methods: A total of 152 patients were analyzed, including 110 non-users and 42 metformin users with type 2 diabetes. Results: A significant gender imbalance was observed, with a higher proportion of females in the metformin group (33.3% vs. 8.2%, p < 0.05). The metformin group showed a numerically higher body mass index (BMI), though not statistically significant (26.53 vs. 24.97, p = 0.065). Overall survival was significantly longer in the metformin group (5.02 ± 3.93 vs. 4.6 ± 3.79 years, p < 0.05), while progression-free survival did not differ significantly (1.32 ± 0.97 vs. 1.04 ± 0.75 years, p = 0.385). Although most adverse events were similar across groups, grade 3–4 thrombocytopenia was more frequent in metformin users (p < 0.05). Multivariate analysis showed that increased nivolumab treatment cycles were significantly associated with reduced mortality risk (OR = 0.64, 95% CI: 0.54–0.75, p < 0.05). Conclusions: These findings suggest that concurrent metformin use may enhance overall survival but also increase hematologic toxicity, warranting closer monitoring in NSCLC patients receiving nivolumab. Full article

(This article belongs to the Section Oncology)

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13 pages, 1375 KiB

Open AccessArticle

Prognostic Role of Inflammatory and Nutritional Indices in NSCLC Patients Treated with Immune Checkpoint Inhibitors: Retrospective, Multicenter, Turkish Oncology Group Study of Overall and Elderly Populations

by Ozkan Alan, Tugba Akın Telli, Sinem Akbas, Selver Isik, Eyyüb Çavdar, Kubilay Karaboyun, Aysegül Merc Cetinkaya, Ferhat Ekinci, Atike Pınar Erdoğan, Mahmut Büyükşimsek, Muhammed Muhittin Er, Melek Karakurt Eryilmaz, Taliha Güçlü Kantar, Gamze Gököz Doğu, Teoman Sakalar, Ertuğrul Bayram, Ali Inal, Fatma Akdağ Kahvecioğlu, İlhan Hacibekiroğlu, Fatih Selçukbiricik, Ali Murat Tatli and Perran Fulden Yumuk Show full author list Hide full author list

Medicina 2025, 61(7), 1160; https://doi.org/10.3390/medicina61071160 - 26 Jun 2025

Abstract

Background and Objectives: Despite advances in immunotherapy, predicting survival outcomes in patients with non-small-cell lung cancer (NSCLC) remains challenging. Inflammatory and nutritional indices such as the Prognostic Nutritional Index (PNI), Geriatric Nutritional Risk Index (GNRI), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Inflammatory [...] Read more.

Background and Objectives: Despite advances in immunotherapy, predicting survival outcomes in patients with non-small-cell lung cancer (NSCLC) remains challenging. Inflammatory and nutritional indices such as the Prognostic Nutritional Index (PNI), Geriatric Nutritional Risk Index (GNRI), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Inflammatory Burden Index (IBI) have emerged as promising prognostic markers associated with overall survival (OS) in NSCLC patients. Materials and Methods: We retrospectively analyzed a total of 196 NSCLC patients treated with second-line nivolumab across multiple centers in Turkey. Of these, 101 patients aged ≥ 65 years were included in the elderly subgroup analysis. PNI, GNRI (in patients aged ≥ 65), and inflammation-based indices were calculated using pre-treatment laboratory values. ROC analysis determined optimal cut-off values. The Kaplan–Meier method and Cox proportional hazards models were used for survival analysis. Results: Median overall survival (OS) was 12.9 months in the full cohort and 12.1 months in patients aged ≥ 65. In univariate analysis, ECOG performance status (0–1), lower NLR (<3.3), lower PLR (<196.8), higher PNI (≥45.2), and higher GNRI (≥98.0) were significantly associated with longer OS. However, in the multivariate analysis adjusted for ECOG PS, NLR, PLR, and GNRI, only PNI remained an independent prognostic factor for OS in both the overall cohort [HR: 0.49, 95% CI: 0.26–0.92; p = 0.02] and elderly patients [HR: 0.45, 95% CI: 0.24–0.84; p = 0.01]. PNI is an independent prognostic biomarker for OS in NSCLC patients treated with immune checkpoint inhibitors. Conclusions: These findings support incorporating simple, cost-effective nutritional indices into clinical decision-making, particularly in elderly patients with NSCLC. Full article

(This article belongs to the Section Oncology)

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12 pages, 545 KiB

Open AccessSystematic Review

Risk of Osteonecrosis of the Jaw in Patients Treated with Zoledronic or Alendronic Acid: A Systematic Review

by Aine Jakonyte, Egle Gustainyte, Zygimantas Petronis, Aviad Hafizov, Audra Janovskiene and Dainius Razukevicius

Medicina 2025, 61(7), 1159; https://doi.org/10.3390/medicina61071159 - 26 Jun 2025

Abstract

Background and Objectives: Bisphosphonates (BP) like zoledronic acid (ZA) and alendronic acid (AA) are used for osteoporosis (OP) or other bone-related conditions as well as to prevent the spread of metastases and in rheumatoid arthritis treatment. However, they have been associated with an [...] Read more.

Background and Objectives: Bisphosphonates (BP) like zoledronic acid (ZA) and alendronic acid (AA) are used for osteoporosis (OP) or other bone-related conditions as well as to prevent the spread of metastases and in rheumatoid arthritis treatment. However, they have been associated with an increased risk of osteonecrosis of the jaw (ONJ). This systematic review aimed to assess the incidence and risk of ONJ in osteoporotic patients treated with ZA or AA and evaluate the impact of treatment duration. Material and Methods: The systematic literature review was conducted following PRISMA guidelines. The keywords “Zoledronic acid,” “Alendronic acid,” “Osteoporosis,” and “Osteonecrosis” were searched in PubMed and ScienceDirect databases. Selection criteria included studies on humans written in English, published from 2014. The systematic review protocol was registered in the PROSPERO register under the following number: CRD42024587046. Results: A total of 7 studies with 98,717 osteoporotic patients met the criteria, showing a higher ONJ incidence with ZA than AA. Six studies linked longer BP use to increased ONJ risk, which quadrupled after 5 years of AA use. A positive correlation was found between BP use (≥3 years) and ONJ in OP patients, primarily affecting females over 60. ONJ appeared after 1 year with AA, increasing over time, while ZA-related ONJ emerged as early as 5 months with a higher overall incidence. Conclusions: ZA poses a higher ONJ risk and incidence and earlier onset than AA, occurring within 5 months versus 1 year for AA. These findings emphasize the need for careful monitoring, especially in long-term BP therapy with additional risk factors. Full article

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

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10 pages, 452 KiB

Open AccessArticle

Stress Hyperglycemia Ratio as a Predictor of In-Hospital Stent Thrombosis in STEMI Patients Undergoing Primary PCI: A Retrospective Cohort Study

by Evliya Akdeniz, Cennet Yıldız, Mehmet Karaca, Mehmet Pişirici, Hasan Ali Sinoplu, Onur Akpınar, Atakan Arpac, Didem Mirgün Manioğlu, Dilay Karabulut and Fatma Nihan Turhan Çağlar

Medicina 2025, 61(7), 1158; https://doi.org/10.3390/medicina61071158 - 26 Jun 2025

Abstract

Background and Objectives: and Objectives: Admission hyperglycemia (AH) is common in acute ST-elevation myocardial infarction (STEMI) and linked to poor prognosis. The stress hyperglycemia ratio (SHR) reflects relative hyperglycemia and may more accurately predict outcomes. This study examined AH, SHR, and in-hospital [...] Read more.

Background and Objectives: and Objectives: Admission hyperglycemia (AH) is common in acute ST-elevation myocardial infarction (STEMI) and linked to poor prognosis. The stress hyperglycemia ratio (SHR) reflects relative hyperglycemia and may more accurately predict outcomes. This study examined AH, SHR, and in-hospital stent thrombosis (ST) in STEMI patients undergoing primary percutaneous coronary intervention (p-PCI). Material and Methods: Retrospective analysis included 1034 patients. AH was defined as glucose ≥ 11.1 mmol/L at admission. SHR was calculated as admission glucose divided by estimated average glucose derived from hemoglobin A1c (HbA1c). The primary outcome was in-hospital stent thrombosis. Patients were grouped by the occurrence of in-hospital ST. Univariable, multivariable, and LASSO (Least Absolute Shrinkage and Selection Operator) logistic regression identified predictors of ST. Results: In-hospital ST occurred in 1.5% of patients. ST patients had higher Killip class, heart rate, white blood cell, platelet counts, creatinine, AH, and SHR. SHR was an independent predictor of ST (OR 3.15, 95% CI 1.88–5.27, p < 0.001), whereas AH was not (p = 0.182). Neutrophil count, correlated with WBC, was also a significant risk factor. ROC analysis showed SHR ≥ 1.26 as an optimal cutoff predicting ST. Conclusions: SHR is a strong independent predictor of in-hospital ST after STEMI, superior to AH. Monitoring and managing stress-induced hyperglycemia play a crucial role in the setting of STEMI. Further studies are needed. Full article

(This article belongs to the Section Cardiology)

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13 pages, 7485 KiB

Open AccessArticle

Saroglitazar Ameliorates Pulmonary Fibrosis Progression in Mice by Suppressing NF-κB Activation and Attenuating Macrophage M1 Polarization

by Yawen Zhang, Jiaquan Lin, Xiaodong Han and Xiang Chen

Medicina 2025, 61(7), 1157; https://doi.org/10.3390/medicina61071157 - 26 Jun 2025

Abstract

Background and Objectives: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease with limited therapeutic options. Current therapies (pirfenidone, nintedanib) exhibit modest efficacy and significant side effects, underscoring the need for novel strategies targeting early pathogenic drivers. Saroglitazar (SGZ), [...] Read more.

Background and Objectives: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease with limited therapeutic options. Current therapies (pirfenidone, nintedanib) exhibit modest efficacy and significant side effects, underscoring the need for novel strategies targeting early pathogenic drivers. Saroglitazar (SGZ), a dual PPARα/γ agonist with anti-inflammatory properties approved for diabetic dyslipidemia, has not been explored for IPF. We aimed to investigate SGZ’s therapeutic potential in pulmonary fibrosis and elucidate its mechanisms of action. Materials and Methods: Using a bleomycin (BLM)-induced murine pulmonary fibrosis model, we administered SGZ therapeutically. A histopathological assessment (H&E, Masson’s trichrome, collagen I immunofluorescence), Western blotting, and qRT-PCR analyzed the fibrosis progression and inflammatory markers. Flow cytometry evaluated the macrophage polarization. In vitro studies used RAW264.7 macrophages stimulated with BLM/LPS and MRC-5 fibroblast co-cultures. The NF-κB/NLRP3 pathway activation was assessed through protein and gene expression. Results: SGZ significantly attenuated BLM-induced histopathological hallmarks, including alveolar wall thickening, collagen deposition, and inflammatory infiltration. Fibrotic markers (OPN, α-SMA) and pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) were downregulated in the SGZ-treated mice. Mechanistically, SGZ suppressed the M1 macrophage polarization (reduced CD86⁺ populations) and inhibited the NF-κB/NLRP3 pathway activation in the alveolar macrophages. In the RAW264.7 cells, SGZ decreased the NLRP3 inflammasome components (ASC, cleaved IL-1β) and cytokine secretion. Co-cultures demonstrated that the SGZ-treated macrophage supernatants suppressed the fibroblast activation (α-SMA, collagen I) in MRC-5 cells. Conclusions: SGZ attenuates pulmonary fibrosis by suppressing macrophage-driven inflammation via NF-κB/NLRP3 inhibition and disrupting the macrophage–fibroblast crosstalk. These findings nominate SGZ as a promising candidate for preclinical optimization and future clinical evaluation in IPF. Full article

(This article belongs to the Special Issue Pulmonary Fibrosis: Current Understanding and Future Directions)

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