Journal of Clinical Medicine

16 pages, 1447 KB

Open AccessArticle

Personalized Prediction of Clozapine Treatment Response Using Therapeutic Drug Monitoring Data in Japanese Patients with Treatment-Resistant Schizophrenia

by Tatsuo Nakahara, Yukiko Harada, Naho Nakayama, Kijiro Hashimoto, Naoya Kida, Toshiaki Onitsuka, Hiroo Noda, Kenji Murasugi, Yoshihiro Takimoto, Wataru Omori, Tsuruhei Sukegawa, Jun Shiraishi, Kouji Tanaka, Hitoshi Maesato and Takefumi Ueno

J. Clin. Med. 2025, 14(21), 7892; https://doi.org/10.3390/jcm14217892 - 6 Nov 2025

Viewed by 944

Abstract

Background: Clozapine is the only antipsychotic medication proven effective in patients with treatment-resistant schizophrenia (TRS). However, many patients have serum concentrations outside the recommended therapeutic window, and clozapine exhibits substantial interindividual variability. This study aimed to (1) examine clozapine dosage and blood [...] Read more.

Background: Clozapine is the only antipsychotic medication proven effective in patients with treatment-resistant schizophrenia (TRS). However, many patients have serum concentrations outside the recommended therapeutic window, and clozapine exhibits substantial interindividual variability. This study aimed to (1) examine clozapine dosage and blood concentrations in patients with TRS; (2) investigate the effects of sex and age on dosage and blood concentrations; (3) assess clinical response to clozapine treatment; and (4) develop a random forest (RF) model to predict therapeutic response using clinical and therapeutic drug monitoring (TDM) data. Methods: Dried blood spots were used to measure concentrations of clozapine, norclozapine, and clozapine N-oxide. Clinical symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS). The RF algorithm was applied to analyze the relationships between biochemical and demographic factors and clinical response to clozapine. Results: A total of 754 blood samples from 167 patients were analyzed. Men received higher doses than women, and glucose levels were elevated in both sexes. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.986 for the training set and 0.852 for the testing set. Accuracy, precision, recall, and F1-score (training/testing) were 0.938/0.786, 0.936/0.736, 0.934/0.780, and 0.935/0.757, respectively. The SHapley Additive exPlanations (SHAP) analysis indicated that baseline BPRS score, treatment duration, age, and clozapine concentration were important variables contributing to the output of the model. Conclusions: Our model achieved satisfactory predictive performance for clinical response and provides valuable insights into personalized prediction of clozapine efficacy. Full article

(This article belongs to the Special Issue Clinical Therapy in Dementia and Related Diseases)

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20 pages, 921 KB

Open AccessSystematic Review

Motor Imagery for Post-Stroke Upper Limb Recovery: A Meta-Analysis of RCTs on Fugl-Meyer Upper Extremity Scores

by Luis Polo-Ferrero, Javier Torres-Alonso, Juan Luis Sánchez-González, Sara Hernández-Rubia, Rubén Pérez-Elvira and Javier Oltra-Cucarella

J. Clin. Med. 2025, 14(21), 7891; https://doi.org/10.3390/jcm14217891 - 6 Nov 2025

Viewed by 931

Abstract

Objectives: Motor imagery (MI) may enhance post-stroke recovery, but evidence of its benefit over conventional rehabilitation therapy (CRT) is inconsistent. This study evaluated the effect of MI combined with CRT on upper-limb recovery, accounting for methodological quality and publication bias. Methods: [...] Read more.

Objectives: Motor imagery (MI) may enhance post-stroke recovery, but evidence of its benefit over conventional rehabilitation therapy (CRT) is inconsistent. This study evaluated the effect of MI combined with CRT on upper-limb recovery, accounting for methodological quality and publication bias. Methods: A systematic review and meta-analysis was conducted following PRISMA guidelines. Searches were performed in multiple databases up to July 2025. Methodological quality and risk of bias were assessed using the PEDro scale and Cochrane RoB 2 tool, respectively. Analyses included the calculation of effect sizes (ES), heterogeneity, sensitivity, publication bias, and GRADE-based certainty assessment. Results: From 4074 records, 10 randomized controlled trials (n = 255) were included. The initial pooled analysis showed a small-to-moderate effect of MI + CRT versus CRT alone (ES = 0.45; 95% CI: 0.16–0.74). However, the overall ES calculated with a robust variance estimator was −0.06 (95% CI: −0.21, 0.08). Most trials had methodological limitations (mean PEDro = 6.0; high risk of bias in 7/10 studies). The GRADE evaluation indicated a very low certainty of evidence. Conclusions: The initially observed positive effect of MI combined with CRT is not robust. When accounting for statistical dependencies and potential biases, the effect vanishes and is no different from zero. Current evidence does not support the use of MI as a standalone adjunct to CRT. Larger, high-quality RCTs with standardized protocols are required to establish any potential clinical relevance. Full article

(This article belongs to the Special Issue New Insights into Physical Therapy)

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11 pages, 767 KB

Open AccessArticle

Cementless vs. Cemented Total Knee Arthroplasty: Reduced Operative Time with Comparable Perioperative Safety—A Retrospective Cohort from a Tertiary Care Center

by Marco Basso, Giuseppe Anzillotti, Luca Ruosi, Elizaveta Kon, Marco Minelli and Enrico Arnaldi

J. Clin. Med. 2025, 14(21), 7890; https://doi.org/10.3390/jcm14217890 - 6 Nov 2025

Viewed by 511

Abstract

Background: Total knee arthroplasty (TKA) is a widely performed and highly successful procedure, with cemented fixation historically considered the standard. Advances in implant design have renewed interest in cementless fixation, which shows comparable survivorship and increasing use, particularly in younger patients. Evidence on [...] Read more.

Background: Total knee arthroplasty (TKA) is a widely performed and highly successful procedure, with cemented fixation historically considered the standard. Advances in implant design have renewed interest in cementless fixation, which shows comparable survivorship and increasing use, particularly in younger patients. Evidence on perioperative outcomes remains mixed, prompting this study to compare hemoglobin decline and operative time between cemented and cementless TKA of the same design. Methods: This monocentric retrospective cohort study included consecutive patients undergoing primary TKA between 2019 and 2021, divided into cemented and cementless groups. Inclusion criteria were primary osteoarthritis, age > 45 years, hemoglobin > 13 g/dL, ferritin > 100 ng/mL, and complete perioperative hemoglobin data (preoperative, PostOperativeDay (POD)1, 3, 5). Primary outcomes were operative time and hemoglobin trajectory, analyzed using multivariable regression and mixed-effects models adjusted for age, sex, and implant design. Propensity score matching was performed as a sensitivity analysis. Results: A total of 123 TKAs were analyzed (63 cementless, 60 cemented). Cementless TKA had a shorter operative time than cemented (72.0 ± 12.0 vs. 79.8 ± 15.1 min; 95% CI −12.2 to −2.8; p < 0.01). Cementless fixation was associated with significantly shorter operative time (72.0 ± 11.8 vs. 79.8 ± 15.1 min, p < 0.01), a difference that remained significant after multivariable adjustment and propensity score matching. Postoperative hemoglobin declined in both groups, with no significant unadjusted between-group differences at any timepoint. In adjusted mixed-effects models, cementless TKA was associated with a slightly greater hemoglobin decline compared with cemented TKA, with mean adjusted differences of −0.56 g/dL on POD1 (95% CI [−0.95, −0.17]), −0.53 g/dL on POD3 (95% CI [−0.91, −0.14]), and −0.34 g/dL on POD5 (95% CI [−0.64, −0.04]). However, this was not clinically relevant, as no transfusions or anemia-related complications occurred. Conclusions: Cementless TKA was associated with reduced operative time compared with cemented fixation, an effect robust to adjustment and propensity score matching. These conclusions apply to a selected, relatively non-anemic cohort. Although hemoglobin decline was slightly greater with cementless fixation, the difference was small and not clinically meaningful. Full article

(This article belongs to the Section Orthopedics)

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17 pages, 595 KB

Open AccessReview

Bridging Dementia Care in Japan: The Emerging Role of General Medicine Physicians

by Takao Yamasaki

J. Clin. Med. 2025, 14(21), 7889; https://doi.org/10.3390/jcm14217889 - 6 Nov 2025

Viewed by 1090

Abstract

As global populations age, dementia has become a major public health challenge that warrants sustainable, person-centered, and community-integrated models of care. In Japan, the recent introduction of board-certified general medicine (GM) physicians, trained across both family medicine and hospital general medicine, has created [...] Read more.

As global populations age, dementia has become a major public health challenge that warrants sustainable, person-centered, and community-integrated models of care. In Japan, the recent introduction of board-certified general medicine (GM) physicians, trained across both family medicine and hospital general medicine, has created an opportunity to strengthen dementia care through improved continuity and coordination. This narrative review conceptually examines the emerging role of GM physicians within Japan’s Community-Based Integrated Care System and compares this evolving model with dementia care structures in the United States, the United Kingdom, and Canada. By synthesizing policy documents and published literature, this review outlines how GM physicians can serve as integrative actors bridging outpatient and inpatient care, collaborating with dementia specialists, Initial-phase Intensive Support Teams, and Community-based Comprehensive Support Centers to enhance person-centered support throughout the disease trajectory. While empirical outcome data remain limited, this conceptual framework highlights potential contributions of GM physicians to early detection, care transitions, and interdisciplinary collaboration in dementia care. However, challenges persist, including training variability, workforce shortages, and systemic fragmentation. By situating Japan’s experience within an international context, this review provides a conceptual basis for future empirical studies and policy development aimed at strengthening generalist-led dementia care in aging societies. Full article

(This article belongs to the Special Issue Clinical Therapy in Dementia and Related Diseases)

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19 pages, 2684 KB

Open AccessReview

Managing Complex Anatomical Scenarios in Tavi: Evidence and an Institutional Perspective

by Orlando Piro, Mattia Granato, Simona Covino, Emanuele Cigala, Mario Crisci, Riccardo Granata, Ida Monteforte, Paola Mocavero, Chiara Sordelli and Emilio Di Lorenzo

J. Clin. Med. 2025, 14(21), 7888; https://doi.org/10.3390/jcm14217888 - 6 Nov 2025

Viewed by 544

Abstract

Transcatheter aortic valve implantation (TAVI) is the default therapy for most elderly patients with severe aortic stenosis, but outcomes in complex anatomy depend on imaging-guided planning and disciplined technique. This article aims to present our institutional approach, supported by the current literature, in [...] Read more.

Transcatheter aortic valve implantation (TAVI) is the default therapy for most elderly patients with severe aortic stenosis, but outcomes in complex anatomy depend on imaging-guided planning and disciplined technique. This article aims to present our institutional approach, supported by the current literature, in managing several challenging anatomical scenarios. We focus on seven high-impact scenarios—bicuspid aortic valve (BAV), hostile transfemoral access, iliofemoral/aortic tortuosity, adverse aortic angulation, heavy annulus/Left Ventricular Outflow Tract (LVOT) calcification, small annulus, and risk of coronary obstruction—and propose a practical approach to minimize the risk of complications. In BAV, current generation transcatheter heart valves (THV) achieve favorable early outcomes when sizing accounts for supra-annular constraints and implantation depth is tailored. Transfemoral access remains dominant in contemporary registries, yet a meaningful minority of cases require adjunctive peripheral vascular intervention to enable THV delivery-system passage. In case of annulus or LVOT calcification, small annuli, complex aortic anatomy, high risk for coronary obstruction, and pre-procedural Computed Tomography (CT) allow for an accurate sizing of THV and tailored procedural planning. A structured, CT-driven pathway that links anatomic findings to specific facilitation and bailout steps can standardize decision-making and improve safety across these challenging scenarios. We strongly highlight the importance to build a network where most complex procedures are carried out in Valve Centers where expert operators are trained to manage high volume, high complexity, and difficult complications. Full article

(This article belongs to the Special Issue Recent Developments and Emerging Trends in Aortic Surgery)

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10 pages, 3535 KB

Open AccessTechnical Note

Bone-Preserving Robotic Conversion of Medial UKA to TKA: A Step-by-Step Technique

by Jaad Mahlouly, Alexander Antoniadis, Thibaut Royon and Julien Wegrzyn

J. Clin. Med. 2025, 14(21), 7887; https://doi.org/10.3390/jcm14217887 - 6 Nov 2025

Viewed by 381

Abstract

Converting a medial unicompartmental knee arthroplasty (UKA) to total knee arthroplasty (TKA) presents challenges in bone preservation, alignment, and soft-tissue balance. Robotic assistance enables three-dimensional CT-based planning, precise bone preparation, and real-time ligament balance assessment, thereby supporting a bone-preserving approach. We describe a [...] Read more.

Converting a medial unicompartmental knee arthroplasty (UKA) to total knee arthroplasty (TKA) presents challenges in bone preservation, alignment, and soft-tissue balance. Robotic assistance enables three-dimensional CT-based planning, precise bone preparation, and real-time ligament balance assessment, thereby supporting a bone-preserving approach. We describe a stepwise workflow using the Mako system (Stryker) to convert a failed medial UKA to a condylar-stabilizing (CS) Triathlon TKA within a functional alignment framework. Pre-explantation registration on the in situ components maintains accuracy despite potential metallic artifacts. The polyethylene insert is briefly removed solely to access reference surfaces, then registration landmarks are acquired directly on the metal components along the marked central sagittal axis. The insert is reinserted to enable dynamic intraoperative balance evaluation. After component removal, a small medial tibial or femoral defect can be filled with autologous cancellous bone graft from the resected bone surfaces. Definitive cementless components are implanted without stems or augments, and the patella is resurfaced. This technique provides a reproducible robotic workflow for UKA-to-TKA conversion in selected cases with preserved bone stock and stable soft-tissue balance and facilitates accurate and reproducible conversion with optimal bone preservation. Full article

(This article belongs to the Special Issue Cutting Edge Research on Total Knee Arthroplasty)

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8 pages, 1578 KB

Open AccessArticle

Early Results of Using AI in Mammography Screening for Breast Cancer

by Hadar Sandler Rahat, Tal Friehmann, Marva Dahan Shemesh, Shlomit Tamir, Eli Atar, Tzippy Shochat, Arnon Makori and Ahuva Grubstein

J. Clin. Med. 2025, 14(21), 7886; https://doi.org/10.3390/jcm14217886 - 6 Nov 2025

Viewed by 1020

Abstract

Background: Recent advancements in Artificial Intelligence (AI) have the potential to address the challenges of mammographic screening programs by enhancing the performance of Computer-Aided Detection (CAD) systems, improving detection accuracy, and reducing false positive rates and recall rates. These systems were mostly [...] Read more.

Background: Recent advancements in Artificial Intelligence (AI) have the potential to address the challenges of mammographic screening programs by enhancing the performance of Computer-Aided Detection (CAD) systems, improving detection accuracy, and reducing false positive rates and recall rates. These systems were mostly investigated by control trials using cancer-enriched datasets and multiple readers. Objectives: This study aims to evaluate the real-world impact of AI integration on the performance of a breast cancer screening program. Methods: In January 2021, our mammography unit integrated an AI system (iCAD version 2.0) into its mammographic screening protocol. This study evaluates audit data of 31,176 mammograms interpreted between 2017 and 2021, comparing 24,373 mammograms prior to AI implementation and 6803 after the integration. Logistic regression analysis was used to assess the statistical significance of changes in key screening metrics, with a significance level of p < 0.05. Results: This study assesses the impact of artificial intelligence (AI) on mammographic screening. The cancer detection rate increased significantly from 6.2 per 1000 in 2019 to 9.3 per 1000 in 2021, with cancers detected on mammograms rising to 98%. Stage 1 cancer detection reached 100%, and the false negative rate dropped to 0%. Additionally, ductal carcinoma in situ (DCIS) detection decreased from 36.4% in 2019 to 20% in 2021. These findings highlight AI’s effectiveness in improving cancer detection accuracy and efficiency. Conclusions: The integration of AI into mammographic screening demonstrated promising results in improving cancer detection rates and reducing false negative rates. These findings highlight AI’s potential to enhance screening efficacy. Full article

(This article belongs to the Section Oncology)

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12 pages, 735 KB

Open AccessArticle

Clinical Utility of Pan-Immune Inflammation Value (PIV) in Predicting Prognosis of Endometrial Cancer

by Nurhan Onal Kalkan, Zuhat Urakcı, Berrak Mermit Erçek, Erkan Bilen, Hayati Arvas and Mehmet Hadi Akkuş

J. Clin. Med. 2025, 14(21), 7885; https://doi.org/10.3390/jcm14217885 - 6 Nov 2025

Viewed by 470

Abstract

Background: Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. While early-stage disease has favorable outcomes, advanced or recurrent EC remains associated with poor prognosis. Novel prognostic markers are needed to refine risk stratification. Systemic inflammation-based indices such as [...] Read more.

Background: Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. While early-stage disease has favorable outcomes, advanced or recurrent EC remains associated with poor prognosis. Novel prognostic markers are needed to refine risk stratification. Systemic inflammation-based indices such as Pan-Immune Inflammation Value (PIV), Systemic Inflammation Response Index (SIRI), and Systemic Immune Inflammation Index (SII) have shown prognostic potential in solid tumors. Methods: We retrospectively evaluated 78 patients with endometrioid EC who had undergone hysterectomy with adnexectomy and lymphadenectomy. Demographic, clinicopathological, and laboratory data were extracted from electronic medical records. PIV, SII, and SIRI were calculated from the preoperative complete blood counts. Survival was assessed using Kaplan–Meier analysis, while prognostic factors were determined using univariate and multivariate Cox regression analyses. Results: The median age was 59 years, and 64.1% of the patients presented with early-stage disease. A high PIV (≥802) was significantly associated with a shorter overall survival (64 vs. 111 months, p < 0.001). PIV demonstrated the highest discriminatory accuracy (AUC = 0.776), followed by the SII (0.747) and SIRI (0.718). Univariate analysis identified that age, grade, LVSI, PNI, stage, distant metastasis, and high PIV, SII, SIRI, and NLR were predictors of poor survival. Multivariate analysis confirmed grade, distant metastasis and SIRI ≥ 1.5 as independent prognostic factors. Conclusions: Inflammation-based indices, particularly PIV and SIRI, correlated with survival outcomes in patients with EC. The SIRI retained an independent prognostic value, whereas PIV showed a strong discriminatory capacity. Incorporating these indices into established risk models may improve prognostic precision and support individualized management. Full article

(This article belongs to the Special Issue Risk Prediction for Gynecological Cancer)

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11 pages, 210 KB

Open AccessArticle

Granulomatosis with Polyangiitis (GPA) in a Polish Tertiary Centre (2010–2025): Sex-Stratified Phenotypes, Serology, and Evolving Treatment Patterns

by Aleksandra Hus, Małgorzata Wisłowska and Krzysztof Bonek

J. Clin. Med. 2025, 14(21), 7884; https://doi.org/10.3390/jcm14217884 - 6 Nov 2025

Viewed by 357

Abstract

Background/Objectives: GPA is a PR3-ANCA–predominant small vessel vasculitis with organ involvement. Real-world, single-centre data are needed to interpret evolving therapies and phenotype patterns in national conditions. Material and Methods: Retrospective cohort study of consecutive GPA patients managed at the National Institute [...] Read more.

Background/Objectives: GPA is a PR3-ANCA–predominant small vessel vasculitis with organ involvement. Real-world, single-centre data are needed to interpret evolving therapies and phenotype patterns in national conditions. Material and Methods: Retrospective cohort study of consecutive GPA patients managed at the National Institute of Geriatrics, Rheumatology and Rehabilitation (Warsaw, Poland) from 1 September 2010 to 1 September 2025. Data included demographics, phenotype, BVAS, organ involvement, PR3/MPO-ANCA serology, and induction/maintenance therapies. Results: Fifty patients were included (54.0% men). Mean age was 52.5 years; mean BMI was 26.15 kg/m². Ear-nose-throat (ENT) disease was frequent: rhinosinusitis 76.0%, nasal cartilage destruction 64.0%, subglottic stenosis 34.0%. Pulmonary nodules occurred in 52.0%, cavitation in 28.0%, and diffuse alveolar haemorrhage in 34.0%. Renal involvement included haematuria in 42.0%, chronic kidney disease (CKD) in 32.0%, and rapidly progressive kidney disease in 22.0%. Orbital inflammation was 36.0%, and PR3-ANCA was positive in 70.0%. All patients received glucocorticoids for induction; cyclophosphamide 28/50 (56.0%), rituximab 6/50 (12.0%), and mycophenolate with methotrexate 6/50 (32%). Maintenance therapy included methotrexate (78.0%), mycophenolate (64.0%), rituximab (52.0%), and azathioprine (12.0%). Conclusions: This Polish single-centre cohort shows an ear-nose-throat-lung-kidney (ELK)-dominant, PR3-predominant GPA phenotype and frequent but variable kidney involvement. Over 2010–2025, practice changed toward rituximab-based strategies, steroid minimisation, selective use of plasma exchange, and early avacopan uptake, with tofacitinib for maintenance therapy as a possible new therapeutic option. Full article

(This article belongs to the Section Immunology & Rheumatology)

21 pages, 2629 KB

Open AccessFeature PaperArticle

Three-Year Follow-Up of the First 100 Patients Treated with the Balloon-Expandable Myval Transcatheter Aortic Valve System: A Single-Centre Experience

by Balázs Magyari, Bálint Kittka, Ilona Goják, Gábor Kasza, Kristóf Schönfeld, László Botond Szapáry, Mihály Simon, Rudolf Kiss, Andrea Bertalan, Edit Várady, Péter Mátrai, István Szokodi and Iván Horváth

J. Clin. Med. 2025, 14(21), 7883; https://doi.org/10.3390/jcm14217883 - 6 Nov 2025

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Abstract

Background/Objectives: To report our single-centre experience with the first 100 patients who underwent transcatheter aortic valve replacement (TAVR) with the new balloon-expandable Myval system. We report 3-year outcomes in low- to high-risk TAVR patient populations. Methods: From November 2019 to July 2021, 100 [...] Read more.

Background/Objectives: To report our single-centre experience with the first 100 patients who underwent transcatheter aortic valve replacement (TAVR) with the new balloon-expandable Myval system. We report 3-year outcomes in low- to high-risk TAVR patient populations. Methods: From November 2019 to July 2021, 100 consecutive patients underwent TAVR, and their outcomes were classified according to the Valve Academic Research Consortium 3 definitions. Device performance was assessed using transthoracic echocardiography. Data collection was approved by the local ethical committee. Results: Among the 100 patients, most were male (n = 63), the mean age was 74.7 years, the mean EuroSCORE II score was 4.8 ± 4.9, and the mean Society of Thoracic Surgeons score was 5.6 ± 3.9. All patients were followed up for three years or until death. The rates of all-cause mortality, cardiac mortality and stroke were 28%, 7% and 5%, respectively. After three years, residual moderate aortic regurgitation was detected in eight patients without severe grade, and bioprosthetic valve dysfunction was observed in 17: structural valve deterioration in 10 (only stage 2), non-structural valve deterioration in three (paravalvular leak in one, patient–prosthesis mismatch in two), and endocarditis in four. Definite transcatheter heart valve thrombosis (hypoattenuated leaflet thickening) was not observed. Bioprosthetic valve failure was detected in four patients (stage 1: 1, stage 2: 0, stage 3: 3). After three years of follow-up, survival analysis revealed no significant differences in all-cause mortality, cardiac mortality, or the composite endpoint (including cardiac mortality, stroke and valve-related dysfunction) between patients with bicuspid (BAV) and tricuspid (TAV) aortic valve morphology and across annulus sizes (small, intermediate and large). Conclusions: TAVR resulted in significant and sustained improvements in valve haemodynamics with low rates of valve dysfunction and adverse clinical outcomes over a three-year follow-up period. Valve morphology (BAV vs. TAV) and annulus size did not significantly impact survival, haemodynamic performance, or valve durability. These results support the expanded use of TAVR in diverse patient populations, although extended follow-up is essential to fully establish long-term durability. Full article

(This article belongs to the Special Issue Recent Advances in Transcatheter Aortic Valve Replacement: Second Edition)

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21 pages, 616 KB

Open AccessReview

High Tibial Osteotomy (HTO), Unicompartmental Knee Arthroplasty (UKA), and Proximal Fibular Osteotomy (PFO) for Medial-Compartment Knee Osteoarthritis: A Narrative Review of Comparative Mechanisms, Clinical Outcomes, and Decision-Making

by Furkan Yapıcı

J. Clin. Med. 2025, 14(21), 7882; https://doi.org/10.3390/jcm14217882 - 6 Nov 2025

Viewed by 1233

Abstract

Background: Medial-compartment knee osteoarthritis with varus alignment is treated surgically by realignment (high tibial osteotomy, HTO), resurfacing (unicompartmental knee arthroplasty, UKA), or proximal fibular osteotomy (PFO), which aims to indirectly unload the medial tibial plateau. Methods: We conducted a structured narrative review (PubMed/MEDLINE, [...] Read more.

Background: Medial-compartment knee osteoarthritis with varus alignment is treated surgically by realignment (high tibial osteotomy, HTO), resurfacing (unicompartmental knee arthroplasty, UKA), or proximal fibular osteotomy (PFO), which aims to indirectly unload the medial tibial plateau. Methods: We conducted a structured narrative review (PubMed/MEDLINE, Google Scholar; 2000–2025; last search 30 August 2025) of comparative clinical, biomechanical and safety data for HTO, UKA and PFO, including prior meta-analyses and mechanistic reports. One hundred fourteen studies met prespecified criteria. Results: HTO reliably corrects coronal alignment and unloads the medial compartment; long-term survivorship varies by selection and technique, and complications include hinge fracture, delayed/nonunion and hardware problems. UKA typically yields faster early pain relief and recovery in pooled analyses, with implant-specific failure risks and mid-term revision dependent on design and surgical experience. PFO cohorts consistently report early pain and function gains with plausible biomechanical rationale, but evidence is dominated by small, heterogeneous series with short follow-up and limited comparative data. Adjusted head-to-head comparisons generally favor UKA for early pain yet show HTO and UKA can achieve similar patient-reported improvements in selected younger cohorts; robust comparative trials including PFO are lacking. Conclusions: HTO and UKA are established, mechanistically distinct options best matched to patient age, alignment, activity goals, and comorbidity. PFO is a low-burden, promising alternative with uncertain durability; longer-term, controlled evaluation and registry surveillance are required before broad adoption. Findings should inform shared decision-making while acknowledging differences in evidence maturity. Full article

(This article belongs to the Section Orthopedics)

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15 pages, 647 KB

Open AccessSystematic Review

Management of Recurrent Temporomandibular Joint Dislocation in Children: A Systematic Review

by Amelia Hoppe, Natalia Turosz, Maciej Chęciński, Kamila Chęcińska, Klaudia Kwiatkowska, Kalina Romańczyk, Adam Michcik, Barbara Wojciechowska, Tomasz Wach and Maciej Sikora

J. Clin. Med. 2025, 14(21), 7881; https://doi.org/10.3390/jcm14217881 - 6 Nov 2025

Viewed by 846

Abstract

Background/Objectives: Children’s unique physiological and behavioral needs require individualized treatment planning. It seems reasonable to investigate treatment options for recurrent temporomandibular joint (TMJ) dislocation and assess their outcomes. This review was conducted with the purpose of identifying recent therapeutic approaches for TMJ [...] Read more.

Background/Objectives: Children’s unique physiological and behavioral needs require individualized treatment planning. It seems reasonable to investigate treatment options for recurrent temporomandibular joint (TMJ) dislocation and assess their outcomes. This review was conducted with the purpose of identifying recent therapeutic approaches for TMJ dislocation in pediatric patients and evaluating their effectiveness. Methods: Searches were conducted on 21 September 2025, using BASE, PubMed, and Scopus. The review included studies with measurable outcomes, published between 2000 and 2025, that focused on patients under the age of 18 with recurrent TMJ dislocation. Studies with unclear diagnoses or undefined treatment methods were excluded. Risk of bias was evaluated using the Joanna Briggs Institute’s critical appraisal tool. The results were tabulated. Results: Based on the inclusion criteria, nine studies were included: one case-control study, three case series, and five case reports. Invasive treatment methods applied in pediatric patients were reported in two of those. Minimally invasive and conservative treatment methods were most frequently described, with botulinum toxin injections being the most commonly reported minimally invasive approach. Conclusions: Research revealed that conservative and minimally invasive methods are preferred in pediatric patients’ treatment. Due to the heterogeneity and limited number of available literature, consistent conclusions regarding the effectiveness of different treatment methods for recurrent TMJ dislocation in children could not be drawn. This study received no funding. PROSPERO ID number: CRD420251139493. Full article

(This article belongs to the Special Issue Oral Health in Children: Clinical Management)

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13 pages, 1243 KB

Open AccessArticle

Minimally Invasive Treatment of Three-Part Proximal Humerus Fractures: A Two-Center Comparative Study of Plate Fixation and Intramedullary Nailing

by Calogero Puma Pagliarello, Vito Pavone, Fabrizio Quattrini, Pietro Maniscalco, Virginia Masoni and Corrado Ciatti

J. Clin. Med. 2025, 14(21), 7880; https://doi.org/10.3390/jcm14217880 - 6 Nov 2025

Viewed by 442

Abstract

Background/Objectives: Proximal humerus fractures account for approximately 5% of all skeletal injuries, and their optimal surgical management remains debated. The optimal fixation method for three-part proximal humerus fractures remains a matter of debate. This study aimed to compare the clinical and radiological outcomes [...] Read more.

Background/Objectives: Proximal humerus fractures account for approximately 5% of all skeletal injuries, and their optimal surgical management remains debated. The optimal fixation method for three-part proximal humerus fractures remains a matter of debate. This study aimed to compare the clinical and radiological outcomes of two minimally invasive osteosynthesis techniques—plate fixation and intramedullary nailing—for the treatment of three-part proximal humerus fractures. Methods: Sixty-six patients aged 60–80 years were retrospectively analyzed across two centers adopting different institutional preferences. Thirty-three patients were treated with minimally invasive plate fixation and thirty-three with intramedullary nailing. The mean age was 67.8 ± 4.2 years, and the mean follow-up duration was 27.2 months. Functional and clinical outcomes were evaluated using the Barthel Index, DASH, Simple Shoulder Test (SST), and Visual Analog Scale (VAS). Operative time, hospitalization length, healing time, and postoperative complications were recorded and statistically analyzed. Results: Intramedullary nailing was associated with shorter operative and hospitalization times and fewer complications. Early SST and VAS improvements favored the nailing group, while long-term outcomes were comparable. Conclusions: Intramedullary nailing represents a reliable and less invasive alternative to plate fixation in the treatment of three-part proximal humerus fractures. It offers shorter operative and hospitalization times, fewer postoperative complications, and faster functional recovery while achieving comparable long-term outcomes. Surgeon experience and familiarity with the chosen technique remain key determinants of success. Full article

(This article belongs to the Special Issue Current Challenges in Orthopedic Trauma Surgery)

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10 pages, 223 KB

Open AccessArticle

Transient Osteoporosis of the Hip: Clinical and Radiological Outcomes After Combined Pharmacologic and Biophysical Therapy

by Calogero Puma Pagliarello, Vito Pavone, Antonio Kory, Luciano Costarella, Antonio Buscema, Gianluca Testa and Corrado Ciatti

J. Clin. Med. 2025, 14(21), 7879; https://doi.org/10.3390/jcm14217879 - 6 Nov 2025

Viewed by 450

Abstract

Introduction: Transient osteoporosis of the hip (TOH) is a rare, self-limiting disorder characterized by acute hip pain and reversible osteopenia. The aim of this study was to evaluate clinical outcomes following treatment with Neridronate, Clodronic Acid, Cholecalciferol, and pulsed electromagnetic field therapy [...] Read more.

Introduction: Transient osteoporosis of the hip (TOH) is a rare, self-limiting disorder characterized by acute hip pain and reversible osteopenia. The aim of this study was to evaluate clinical outcomes following treatment with Neridronate, Clodronic Acid, Cholecalciferol, and pulsed electromagnetic field therapy (PEMF). Materials and Methods: A total of 45 patients presenting with non-traumatic hip pain were screened using a standardized diagnostic protocol. Magnetic resonance imaging (MRI) identified 8 patients (17.8%) with transient osteoporosis of the hip (TOH), who were subsequently enrolled in this analysis. Pain was evaluated using the Visual Analog Scale (VAS). Patients received a three-phase therapeutic protocol, including pharmacological therapy and PEMF. Clinical evaluations using the Harris Hip Score (HHS) were performed monthly, and follow-up MRI was conducted at the end of treatment. Results: We identified 8 cases of TOH (17.8%); the mean baseline HHS for these patients was 68.5 (range 51–83, SD 10.36). Pain reduction became evident within the first month of treatment. At the end of treatment, clinical improvement was observed in 7 patients, with mean HHS increasing to 88.0 (range 67–95, SD 8.84). Post-treatment MRI demonstrated complete resolution of bone marrow edema in all patients. One patient developed avascular necrosis despite therapy and required surgical intervention. Conclusions: TOH remains a controversial condition in terms of diagnosis and treatment. Early diagnosis and timely intervention are essential to progression to osteonecrosis. A combined therapeutic approach using bisphosphonates, vitamin D, and PEMF appears effective in reducing symptoms, promoting bone healing, and ensuring good patient compliance. Full article

(This article belongs to the Special Issue Current Challenges in Orthopedic Trauma Surgery)

14 pages, 256 KB

Open AccessArticle

Bipolar Disorder in Disabled Adult Spanish Population—Factors Associated with Self-Reported Health Status in These Subjects: Population-Based Cross-Sectional Study

by Inmaculada Failde, Jenifer Palomo-Osuna and Alejandro Salazar

J. Clin. Med. 2025, 14(21), 7878; https://doi.org/10.3390/jcm14217878 - 6 Nov 2025

Viewed by 344

Abstract

Background/Objectives: We aimed to determine the prevalence of bipolar disorder (BD) in a Spanish disabled adult population (DAP), the differences in sociodemographic and clinical variables in the DAP with and without BD, and the factors associated with self-reported health status in the DAP [...] Read more.

Background/Objectives: We aimed to determine the prevalence of bipolar disorder (BD) in a Spanish disabled adult population (DAP), the differences in sociodemographic and clinical variables in the DAP with and without BD, and the factors associated with self-reported health status in the DAP with BD. Methods: This is a population-based cross-sectional study including N = 11,130 adults from the “Disability, Personal Autonomy and Dependency Situations Survey 2020” carried out in Spain by the Spanish National Institute of Statistics (INE). We used secondary data with self-reported information on sociodemographic, mental and physical health status (HS), difficulties in daily living, and use of health services. We estimated the prevalence of BD in the DAP. Bivariate analyses were carried out to compare the DAP with/without BD and multinomial logistic regression was performed to analyse factors associated with self-reported HS in the DAP with BD. Results: The prevalence of BD in the DAP is 2.42%. People with BD were younger, showed more anxiety and musculoskeletal diseases, reported worse HS, performed less physical and social activities, had more social difficulties and less contact with other people, used more health services, and reported discrimination due to their disability. Older age (OR = 1.030) and the presence of anxiety (OR = 4.479) were related to worse self-reported HS. Conclusions: BD is present in 2.42% of the Spanish DAP with significant consequences for their HS. Our findings summarise some of the main factors that characterise the BD population with disability versus those without BD and show that anxiety is an important factor affecting the perception of HS. Full article

(This article belongs to the Section Mental Health)

16 pages, 1948 KB

Open AccessArticle

Bruxism Simulation in Aligner Therapy: Effects on Restored Posterior Teeth

by Amelia Anita Boitor (Andreica), Adriana Objelean, Cristina Gasparik, Alexandru Victor Burde, Horațiu Alexandru Colosi and Diana Dudea

J. Clin. Med. 2025, 14(21), 7877; https://doi.org/10.3390/jcm14217877 - 6 Nov 2025

Viewed by 500

Abstract

Background/Objectives: Parafunctional habits such as bruxism generate high occlusal forces that can significantly compromise the performance of dental restorations during orthodontic treatment. This ex vivo study aimed to evaluate the surface wear of Class II composite restorations and the integrity of clear aligners [...] Read more.

Background/Objectives: Parafunctional habits such as bruxism generate high occlusal forces that can significantly compromise the performance of dental restorations during orthodontic treatment. This ex vivo study aimed to evaluate the surface wear of Class II composite restorations and the integrity of clear aligners (CAs) under simulated parafunctional loading. Methods: Thirty-four posterior teeth restored with composite materials were subjected to either normal masticatory forces or high-intensity cyclic forces mimicking bruxism while being fitted with orthodontic aligners. The collected experimental data were analyzed using R (version 4.3) under the Jamovi project (version 2.5.3). Differences between groups were assessed using paired samples t-tests and Wilcoxon tests for paired samples, with robust t-tests applied when data normality could not be confirmed. Statistical significance was set at α = 0.05. Results: Parafunctional loading led to significantly greater surface degradation of restorations and increased aligner wear. Compared with functional forces, RMS errors were substantially higher under parafunctional forces (33.5 vs. 21.5 units; p < 0.001), indicating reduced positional accuracy. Aligner thickness decreased more under parafunctional conditions (0.0304 mm) than under normal function (0.0122 mm), with all comparisons showing high statistical significance and large effect sizes. Conclusions: Parafunctional forces were found to significantly increase surface wear in Class 2 resin composite restorations during clear aligner therapy. Simulated bruxism also compromised aligner integrity, indicating the need for more durable materials and tailored treatment strategies for patients with bruxing habits. These findings highlight the importance of selecting durable restorative and aligner materials for bruxer patients to ensure long-term treatment success. Full article

(This article belongs to the Special Issue Orthodontics: State of the Art and Perspectives)

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15 pages, 271 KB

Open AccessReview

Obesity: An Underlying Risk for Acute Aortic Dissection

by Han Zhang, Yu Lun and Jian Zhang

J. Clin. Med. 2025, 14(21), 7876; https://doi.org/10.3390/jcm14217876 - 6 Nov 2025

Viewed by 472

Abstract

Obesity is a significant risk factor for cardiovascular diseases. Although previous studies have shown uncertainty about its role in aortic dissection (AD), our clinical observations showed that most younger patients with acute AD have a significantly higher body mass index. The underlying reasons [...] Read more.

Obesity is a significant risk factor for cardiovascular diseases. Although previous studies have shown uncertainty about its role in aortic dissection (AD), our clinical observations showed that most younger patients with acute AD have a significantly higher body mass index. The underlying reasons are yet to be investigated. Recent studies have suggested that obesity is linked to vascular pathophysiology, including endothelial injury, medial remodeling and deficiency, perivascular adipose tissue dysfunction, and systemic dysfunction. Understanding the association between obesity and acute AD can aid in recognizing high-risk populations, providing an earlier chance of diagnosis and intervention, and improving clinical outcomes for acute AD in young obese patients. This review analyzes and integrates current data to explain the potential role of obesity in acute AD pathogenesis. Full article

(This article belongs to the Section Vascular Medicine)

10 pages, 467 KB

Open AccessArticle

Type I Interferon-Related Gene Expression and Laboratory Abnormalities in Acute Infection Are Associated with Long COVID Symptom Burden

by Mary Emmanouil, Vasiliki E. Georgakopoulou, Konstantinos Drougkas, Panagiotis Lembessis, Charalampos Skarlis, Aikaterini Gkoufa, Nikolaos V. Sipsas and Clio P. Mavragani

J. Clin. Med. 2025, 14(21), 7875; https://doi.org/10.3390/jcm14217875 - 6 Nov 2025

Viewed by 410

Abstract

Background: Long COVID—defined as the persistence of symptoms or the development of new symptoms beyond four weeks after acute SARS-CoV-2 infection—affects an estimated 10–30% of individuals recovering from COVID-19, posing a significant public health burden. Emerging evidence suggests that type I interferons (IFNs) [...] Read more.

Background: Long COVID—defined as the persistence of symptoms or the development of new symptoms beyond four weeks after acute SARS-CoV-2 infection—affects an estimated 10–30% of individuals recovering from COVID-19, posing a significant public health burden. Emerging evidence suggests that type I interferons (IFNs) (a critical group of cytokines in the antiviral defense) and hematologic alterations, such as lymphopenia and elevated inflammatory markers, are linked to both the severity of acute COVID-19 and the likelihood of developing long-term symptoms. The aim of this study is to explore the association between type I IFN signatures and long COVID. A second aim is to examine the relationship between laboratory findings during acute infection and long COVID. Methods: The study included 61 patients investigated for the presence of long COVID symptoms 16.5 ±1.5 months after acute infection. Patients were divided into two groups of higher symptom burden of long COVID and those with milder symptoms based on demographic, laboratory, and clinical data as well as type I IFN-inducible gene expression (MX-1, IFIT-1, and IFI-44) measured in peripheral blood by real-time PCR. Data collected during acute infection were recorded. Peripheral blood samples were collected during the acute phase of infection, within the first 48 h of hospital admission. IFN-inducible gene expression was measured prospectively at that time, and RNA was extracted immediately for subsequent analysis. Results: History of intubation emerged as a significant associated factor of severe long COVID, with 75% of intubated patients reporting >8 persistent symptoms approximately 16 months post-infection. Higher white blood cell (WBC) and neutrophil counts but lower eosinophil and monocyte counts in acute infection were found to be associated with a high burden of long COVID symptoms. Interestingly, absolute monocyte count was found to independently correlate with higher long COVID symptom burden. Lactate dehydrogenase (LDH) and serum glutamic-oxaloacetic transaminase (SGOT) also differed significantly between groups, with higher levels correlating with a high burden of long COVID symptoms. Notably, MX-1 transcript levels in peripheral blood at the time of acute infection were reduced in patients with a high burden of long COVID symptoms, suggesting that dysregulated immune responses during the acute phase may contribute to persistent symptoms. Conclusions: These findings suggest the potential association of hematological and immune markers with long COVID severity, as well as the importance of monitoring these parameters to identify at-risk patients for early interventions. Full article

(This article belongs to the Section Clinical Laboratory Medicine)

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13 pages, 603 KB

Open AccessArticle

Hearing Preservation and Complications of the Middle Cranial Fossa Approach for Otolaryngological Diseases: Twelve-Year Single-Center Experience

by Toshihito Sahara, Takeshi Fujita, Yujiro Hoshi, Hajime Koyama, Anjin Mori, Yasuhiro Osaki, Akinori Kashio, Yasuhiro Sanada and Katsumi Doi

J. Clin. Med. 2025, 14(21), 7874; https://doi.org/10.3390/jcm14217874 - 6 Nov 2025

Viewed by 437

Abstract

Objectives: The middle cranial fossa (MCF) approach is valued for preserving hearing while accessing the internal auditory canal (IAC), petrous apex, inner ear, and related structures. This study evaluated its clinical outcomes across otolaryngological diseases, focusing on postoperative complications, hearing preservation, and the [...] Read more.

Objectives: The middle cranial fossa (MCF) approach is valued for preserving hearing while accessing the internal auditory canal (IAC), petrous apex, inner ear, and related structures. This study evaluated its clinical outcomes across otolaryngological diseases, focusing on postoperative complications, hearing preservation, and the effect of IAC manipulation on auditory function. Methods: We retrospectively analyzed 35 patients who underwent MCF otologic surgery at a single center over twelve years. We calculated the proportion of MCF cases among all otologic surgeries and assessed postoperative complications and hearing changes (bone conduction thresholds). Outcomes were compared between patients with and without IAC manipulation. Results: MCF procedures comprised 1.4% of all otologic surgeries. Petrous bone cholesteatoma was the leading indication (15 cases). Intracranial complications occurred in 4 patients (11.4%): seizures, epidural abscess, and cerebral infarction. Facial nerve paralysis occurred in 3 (10.7%) patients without any cerebrospinal fluid leaks. In patients without IAC manipulation, hearing functions were preserved (22.3 ± 7.8 dB HL pre- vs. 25.7 ± 9.5 dB HL postoperatively), whereas those with IAC manipulation showed significantly greater deterioration. Conclusions: The middle cranial fossa approach, though technically demanding and infrequently used, offers a safe and effective option across various otolaryngological diseases. This approach achieved favorable hearing preservation with a low complication rate, particularly when intradural manipulation of the IAC was not required. Full article

(This article belongs to the Section Otolaryngology)

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17 pages, 2184 KB

Open AccessArticle

Multiple-Site Lichen Planus: An Italian Case Series of 44 Patients

by Federico Bardazzi, Lidia Sacchelli, Giacomo Clarizio, Federica Filippi, Camilla Loi and Michelangelo La Placa

J. Clin. Med. 2025, 14(21), 7873; https://doi.org/10.3390/jcm14217873 - 6 Nov 2025

Viewed by 564

Abstract

Background: Lichen planus (LP) is a chronic immune-mediated inflammatory disorder affecting skin, mucosae, nails, and appendages, often with significant impact on quality of life. While associations between oral LP (OLP) and other localizations have been described, comprehensive analyses of patients presenting with [...] Read more.

Background: Lichen planus (LP) is a chronic immune-mediated inflammatory disorder affecting skin, mucosae, nails, and appendages, often with significant impact on quality of life. While associations between oral LP (OLP) and other localizations have been described, comprehensive analyses of patients presenting with multiple LP localizations remain limited. The aim of the study was describing the association of multisite LP among our patients in order to contribute to knowledge about this rare, but possible, clinical situation and its clinical implications in terms of follow-up. Methods: We conducted a retrospective observational study including 44 adult patients with histologically confirmed OLP and at least two additional LP subtypes. Data were collected at the joint dermatology–oral pathology clinic of Policlinico Sant’Orsola Malpighi, Bologna, between January 2022 and December 2024. Demographic characteristics, clinical manifestations, comorbidities, and therapeutic approaches were analyzed. Results: The cohort comprised 31 women and 13 men (mean age at first LP diagnosis: 56 years). All patients presented OLP, predominantly erosive (73%). During a follow-up, 39 patients developed three LP subtypes, and 5 patients developed four LP subtypes. Cutaneous LP was universal, while mucosal involvement included genital LP (n = 23), esophageal/pharyngeal/laryngeal LP (n = 8), and vulvar lichen sclerosus (n = 6). Nail LP was diagnosed in seven cases and frontal fibrosing alopecia in ten cases. Autoimmune comorbidities were frequent, including thyroiditis, psoriasis, systemic sclerosis, lupus, and Sjögren’s syndrome. First-line therapy consisted of topical and systemic corticosteroids, with adjuvant retinoids, cyclosporine, or immunosuppressants in refractory cases. No malignant transformation or dysplasia was detected during the observation period, and the mean follow-up period was 24 months (range: 12–36 months). Conclusions: Multisite LP is a complex, underrecognized condition requiring multidisciplinary management. OLP frequently represents the initial manifestation, followed by progressive involvement of cutaneous and mucosal sites. Regular full-body, oral, and genital examinations, together with tailored systemic treatments, are essential to prevent scarring sequelae and improve quality of life. Our findings highlight the need for heightened clinical vigilance and integrated care pathways for patients with multi-site LP. Full article

(This article belongs to the Special Issue New Insights into Infectious Skin and Mucosal Diseases)

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16 pages, 754 KB

Open AccessReview

Next-Generation Spectacle Lenses for Myopia Control: Optical Designs, Mechanisms, and Clinical Efficacy

by Neeraj K. Singh and Pablo De Gracia

J. Clin. Med. 2025, 14(21), 7872; https://doi.org/10.3390/jcm14217872 - 6 Nov 2025

Viewed by 1967

Abstract

Myopia prevalence has risen dramatically worldwide, underscoring the critical need for effective interventions to slow its progression. Recent advancements in spectacle lens technology offer promising solutions, demonstrating significant efficacy in controlling myopia. This review critically examines next-generation spectacle lenses for myopia management, emphasizing [...] Read more.

Myopia prevalence has risen dramatically worldwide, underscoring the critical need for effective interventions to slow its progression. Recent advancements in spectacle lens technology offer promising solutions, demonstrating significant efficacy in controlling myopia. This review critically examines next-generation spectacle lenses for myopia management, emphasizing their optical principles, mechanisms of action, clinical effectiveness, visual performance, compliance, and safety. Spectacle lenses incorporating technologies such as Defocus Incorporated Multiple Segments (DIMS), Highly Aspherical Lenslet Target (HALT), Diffusion Optics Technology (DOT), and Cylindrical Annular Refractive Element (CARE) lenses show a 40–60% reduction in refractive progression and axial elongation compared to traditional single-vision lenses. These lenses utilize optical strategies like simultaneous myopic defocus, peripheral contrast modulation, and controlled aberrations without compromising visual acuity, contrast sensitivity, accommodation, or binocular vision. High wearer compliance is attributed to excellent visual comfort, minimal adaptation issues, and favorable cosmetic appearance. Long-term studies further confirm sustained efficacy and safety profile. Ongoing research aimed at direct comparative trials, extended follow-up, and individualized lens designs will further define the role of these interventions. Collectively, the evidence positions next-generation spectacle lenses as a promising, evidence-based approach that may become an important component of global myopia management. Full article

(This article belongs to the Special Issue Unraveling Myopia: Current Science, Clinical Impact, and Future Horizons)

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17 pages, 1817 KB

Open AccessArticle

Prolonged Normal Thyroid Function After ¹³¹I Radioiodine Therapy Using a Minute LT3 Suppression Test (LT3s-RIT) in Patients with Thyroid Unifocal Autonomy and Baseline Detectable TSH

by Jérôme Clerc, Paul Bodin-Cufi, Louise Giraud, Aurélie Forbes, Emmanuelle Laroche-Masse, Lionel Groussin Rouiller, Louis Schubert, Yvan Mouraeff, Kawtar Hilmy, Anne-Ségolène Cottereau and Eve Piekarski

J. Clin. Med. 2025, 14(21), 7871; https://doi.org/10.3390/jcm14217871 - 6 Nov 2025

Viewed by 629

Abstract

Background: Subclinical hyperthyroidism grade 1 (SCH G1, TSH > 0.1 mU/L) is common in patients with thyroid unifocal autonomy (UFA) and associated with cardiovascular risks and increased mortality. While ¹³¹I radioiodine therapy (¹³¹I-RIT) effectively treats UFA, it frequently induces [...] Read more.

Background: Subclinical hyperthyroidism grade 1 (SCH G1, TSH > 0.1 mU/L) is common in patients with thyroid unifocal autonomy (UFA) and associated with cardiovascular risks and increased mortality. While ¹³¹I radioiodine therapy (¹³¹I-RIT) effectively treats UFA, it frequently induces hypothyroidism, partly due to extra-nodular absorbed dose (AD) enhanced by residual TSH stimulation. Objective: We hypothesized that short-term LT3-induced TSH suppression at the time of RIT would promote long-term euthyroidism. Patients and Methods: A retrospective study was conducted on 95 UFA patients with SCH G1 (2001–2024). Patients underwent baseline and post-LT3 thyroid scintigraphy, and then received ¹³¹I-RIT with individualized dosimetry. Long-term bioclinical follow-up was achieved. Results: Short-term low-dose LT3 suppression caused no adverse events and significantly reduced TSH (0.45 to 0.047 mU/L). Whole-gland ¹²³I uptake decreased moderately (11.0 to 8.4%), while extra-nodular lobe uptake dropped markedly (1.77 to 0.73%) (all p < 0.0001). This focused activity on the UFA (2.5-fold increase), maintaining mean UFA AD (about 260 Gy) but reducing extra-nodular AD (61 to 37 Gy, p < 0.0001). Despite low ¹³¹I doses (mean 181 MBq), a dose–response relationship was observed: higher AD correlated with greater nodular lobe volume reduction (p < 0.033). At the 88-month follow-up, 93% of patients achieved normal thyroid function; one had persistent SCH G1, two were borderline hypothyroid, and two required LT4. Conclusions: ¹³¹I-RIT under brief LT3-induced TSH suppression induces sustained euthyroidism in SCH G1 with UFA. This simple, low-risk strategy reduces radioprotection concerns and is under evaluation to determine cardiovascular benefits. Full article

(This article belongs to the Special Issue Thyroid Disease: Updates from Diagnosis to Treatment: 2nd Edition)

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14 pages, 1263 KB

Open AccessArticle

Serum Phosphorus Is a Fast and Highly Sensitive Marker Predictive of a Complete Cure of Tumor-Induced Osteomalacia

by Seung Hyun Kim, Young Han Lee, NamKi Hong, Sungjoon Cho and Yumie Rhee

J. Clin. Med. 2025, 14(21), 7870; https://doi.org/10.3390/jcm14217870 - 6 Nov 2025

Cited by 1 | Viewed by 333

Abstract

Background/Objectives: Tumor-induced osteomalacia (TIO) is a rare acquired paraneoplastic syndrome caused by phosphaturic mesenchymal tumors (PMTs). FGF23, which is overproduced by PMTs, causes hypophosphatemia and osteomalacia, ultimately leading to multiple insufficiency fractures, which are the cause of TIO symptoms. Therefore, recovery from TIO [...] Read more.

Background/Objectives: Tumor-induced osteomalacia (TIO) is a rare acquired paraneoplastic syndrome caused by phosphaturic mesenchymal tumors (PMTs). FGF23, which is overproduced by PMTs, causes hypophosphatemia and osteomalacia, ultimately leading to multiple insufficiency fractures, which are the cause of TIO symptoms. Therefore, recovery from TIO symptoms often takes several months. Due to its paracrine effects, even minuscule amounts of residual PMT can cause treatment to fail. To further compound this, the most confident methods for residual PMTs, serum FGF23 level and ⁶⁸Ga DOTA-based PET/CT, are not readily available. For these reasons, there is currently no established method for early prediction of TIO treatment outcomes after surgery. This study focuses on mineral metabolism and bone turnover markers to identify a clinically practical and readily available biomarker that can predict TIO treatment outcomes. Methods: During treatment, we analyzed repeated measurements during treatment of mineral metabolism and bone turnover markers for 19 cases of TIO—Ca, inorganic phosphate (Pi), parathyroid hormone (PTH), 25-hydroxyvitamin D, alkaline phosphatase, Procollagen 1 N-terminal Polypeptide, and β-CrossLaps—in relation to treatment outcomes. We selected predictive marker candidates from among these markers by analyzing their patterns of change during treatment based on three viewpoints—association with (1) cure status, (2) time after treatment, and (3) the interaction effects between (1) and (2) using Linear Mixed Model analysis. We also validated the predictive performance of the selected candidates. Results: In long-term follow-up, only serum Pi and PTH levels were significantly associated with all three metrics mentioned above, suggesting that their patterns of change reflect the clinical course and results of TIO treatment. Pi was the only marker that displayed the same associations during short-term follow-up (two weeks and six weeks after treatment), suggesting that it is a rapidly responsive marker. The serum Pi level two weeks after treatment (Odds Ratio = 7.314, p = 0.028, AUC value of 0.907) and the normalization of Pi at two weeks post-treatment (Relative Risk = 9.975, p = 0.010; sensitivity = 100.0% [95% Confidence Interval (CI) 0.860 to 1.000], specificity = 60.0% [95% CI, 0.208 to 0.600]) were both significantly associated with a complete cure. Conclusions: Serum Pi is a fast, simple, and highly sensitive marker that can replace serum FGF23 and ⁶⁸Ga DOTA-based PET/CT in clinical practice for predicting a complete cure of TIO within two weeks of surgery. Full article

(This article belongs to the Section Orthopedics)

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21 pages, 2187 KB

Open AccessArticle

A Cohort Study Characterizing the Outcomes Following an Acute SARS-CoV-2 Infection in Pregnancy

by Clementine Adeyemi, Leticia Breuer, Raghad Kodvawala, Delia Miller and Margaret V. Powers-Fletcher

J. Clin. Med. 2025, 14(21), 7869; https://doi.org/10.3390/jcm14217869 - 6 Nov 2025

Viewed by 466

Abstract

Background/Objectives: Current estimates suggest that 6% of COVID-19 survivors develop a post-viral sequela known as Long COVID. Among those at risk for this sequela, pregnant individuals are a vulnerable patient population, but they are understudied as to the nature of their symptomology and [...] Read more.

Background/Objectives: Current estimates suggest that 6% of COVID-19 survivors develop a post-viral sequela known as Long COVID. Among those at risk for this sequela, pregnant individuals are a vulnerable patient population, but they are understudied as to the nature of their symptomology and potential adverse outcomes. Methods: This retrospective study evaluated a cohort of 150 pregnant individuals with a history of acute SARS-CoV-2 infection during pregnancy, observing for Long COVID symptoms and assessing for adverse outcomes. Of this cohort, 64% identified as Black and/or Latina, which provides a more diverse representation compared to previously published studies. Results: Within this cohort, 26.7% of individuals experienced at least one symptom of Long COVID; subcohorts, which were categorized based on presence or absence of Long COVID symptomology, presented with varying phenotypes. Pain, mental health dysfunction or psychological problems, and fatigue were the predominant symptoms documented for patients who averaged two Long COVID symptoms after at least 30 days following a COVID-19 diagnosis. Different adverse outcomes were higher in frequency among subcohorts, highlighting a need for continued study to explore the nuances of the impact of COVID-19 on this unique and vulnerable population. The most notable trends between subcohorts related to treatment patterns for acute COVID-19, vaccine status, and cesarean delivery rates. Conclusions: By providing a description of the documented health experience for a predominantly non-White cohort of individuals who were diagnosed with an acute SARS-CoV-2 during pregnancy, our study contributes to a foundation upon which future studies can build. Full article

(This article belongs to the Special Issue New Advances in COVID-19 and Pregnancy)

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12 pages, 240 KB

Open AccessArticle

Predictors of In-Hospital Cardiac Arrest Outcomes: A Single-Center Observational Study

by Maria Aggou, Barbara Fyntanidou, Andreas S. Papazoglou, Marios G. Bantidos, Nikolaos Vasileiadis, Dimitrios Vasilakos, Haralampos Karvounis, Dimitrios V. Moysidis, Athina Nasoufidou, Panagiotis Stachteas, Paschalis Karakasis, Konstantinos Fortounis, Eleni Argyriadou, Efstratios Karagiannidis and Vasilios Grosomanidis

J. Clin. Med. 2025, 14(21), 7868; https://doi.org/10.3390/jcm14217868 - 5 Nov 2025

Viewed by 566

Abstract

Background/Objectives: In-hospital cardiac arrest (IHCA) carries high mortality and substantial risk of neurological and functional impairment. Given that contemporary, clinically relevant risk models remain limited, especially within Southern European systems, the aim of this study was to develop a process-aware model for bedside [...] Read more.

Background/Objectives: In-hospital cardiac arrest (IHCA) carries high mortality and substantial risk of neurological and functional impairment. Given that contemporary, clinically relevant risk models remain limited, especially within Southern European systems, the aim of this study was to develop a process-aware model for bedside risk stratification. Methods: We retrospectively analyzed a single-center cohort from a prospectively maintained resuscitation registry (AHEPA University General Hospital, Thessaloniki). Adults (≥18 years) with index IHCA in 2017–2019 were included. Utstein-defined variables underwent univariable screening, LASSO selection, and collinearity checks before multivariable logistic regression for in-hospital mortality. We assessed discrimination (AUC) and calibration (Hosmer–Lemeshow). Results: Among 826 IHCAs, 137 survived to discharge and 689 died. Higher mortality was independently associated with longer CPR (aOR = 1.115, 95% CI: 1.080–1.158), older age (aOR = 1.034, 95% CI: 1.014–1.055), and CCU location (aOR = 7.303, 95% CI: 2.557–25.798), while operating room (aOR = 0.029, 95% CI: 0.003–0.252), ICU/HDU (aOR = 0.203, 95% CI: 0.065–0.630), and an initial shockable rhythm (aOR = 0.297, 95% CI: 0.144–0.611) were protective. Longer time to CPR initiation also predicted mortality (aOR = 1.746, 95% CI: 1.001–3.162). Model performance was strong (AUC = 0.897, 95% CI: 0.865–0.928) with good calibration (Hosmer–Lemeshow p = 0.879). Conclusions: A process-aware model integrating patient factors, intra-arrest metrics, and location showed excellent internal performance for predicting IHCA mortality. Findings reaffirm the prognostic importance of age, rhythm, and resuscitation timeliness/intensity and support future work extending prediction to neurological/functional outcomes and testing targeted care bundles in high-risk strata. Full article

(This article belongs to the Special Issue Optimizing Outcomes in Emergency Medicine and Cardiopulmonary Resuscitation)

12 pages, 244 KB

Open AccessArticle

Kinesiophobia, Physical Limitations and Psychological Distress as Barriers to Physical Activity in Heart Transplantation Patients: A Qualitative Study

by Elena Marques-Sule, Juan Luis Cabanillas-García, Luis Almenar-Bonet, Amalia Sillero-Sillero, Maria Cruz Sánchez-Gómez, Raquel Ayuso-Margañon, Raquel López Vilella and Noemí Moreno-Segura

J. Clin. Med. 2025, 14(21), 7867; https://doi.org/10.3390/jcm14217867 - 5 Nov 2025

Viewed by 472

Abstract

Background/Objectives: Heart transplantation substantially improves survival and quality of life in patients with advanced heart failure; however, many heart transplantation patients fail to recover normal physical activity levels. Persistent inactivity compromises secondary prevention and long-term outcomes. Kinesiophobia—an excessive and irrational fear of [...] Read more.

Background/Objectives: Heart transplantation substantially improves survival and quality of life in patients with advanced heart failure; however, many heart transplantation patients fail to recover normal physical activity levels. Persistent inactivity compromises secondary prevention and long-term outcomes. Kinesiophobia—an excessive and irrational fear of movement—may act as a central barrier limiting physical activity after heart transplantation. This study aimed to explore how kinesiophobia develops and interacts with physical and psychological factors that influence adherence to an active lifestyle after heart transplantation. Methods: A qualitative study was conducted in 24 adult heart transplantation patients (mean age 62.1 years; 83% male) at a tertiary hospital in Spain. Semi-structured interviews lasting 35–60 min were transcribed verbatim and analysed using reflexive thematic analysis. Methodological rigour was ensured through triangulation, reflexivity, and transparent documentation of analytic decisions. Results: Three interrelated themes were identified: (1) Kinesiophobia, characterised by fear of overexertion and avoidance of performing physical activity; (2) physical limitations, including fatigue, muscle weakness, treatment side effects, and intensified perceptions of vulnerability; and (3) psychological distress, encompassing anxiety, demotivation, and frustration, which intensified inactivity. These domains formed a self-perpetuating cycle that restricted participation in physical activity. Some participants reported simple adaptive strategies, such as pacing, walking and social support that enhanced their sense of safety and confidence. Conclusions: Kinesiophobia, physical limitations, and psychological distress interact to restrict physical activity in heart transplantation patients. Our findings suggest that rehabilitation should integrate psychological support, cognitive-behavioural strategies, and tailored education to reduce fear, enhance self-efficacy, and promote sustainable physical activity engagement. Full article

(This article belongs to the Special Issue Physical Activity, Exercise and Health: Clinical Management and Research)

13 pages, 241 KB

Open AccessArticle

Development of an Adapted Version of the Motor Competence Assessment (MCA) for Older Adults

by Bruno Silva, Luís Paulo Rodrigues, Pedro Bezerra and José Maria Cancela Carral

J. Clin. Med. 2025, 14(21), 7866; https://doi.org/10.3390/jcm14217866 - 5 Nov 2025

Viewed by 449

Abstract

Background/Objectives: Age-related declines in motor and functional abilities can compromise independence and quality of life in later life. Motor competence (MC) plays an important role in maintaining quality of life and independence. However, few reliable instruments exist to assess MC in this [...] Read more.

Background/Objectives: Age-related declines in motor and functional abilities can compromise independence and quality of life in later life. Motor competence (MC) plays an important role in maintaining quality of life and independence. However, few reliable instruments exist to assess MC in this population. The study adapts the Motor Competence Assessment (MCA) battery to meet the MC assessment and safety requirements of community-dwelling older adults. Methods: Seventy-six community-dwelling, physically active older adults (age = 73.4 ± 7.0 years) enrolled in a multi-phase adaptation process involving expert review, pilot and field testing, and validation of six motor tasks across three MC domains. Adaptations emphasized in the following four stages: accomplishing participant safety, autonomy, and the reliability of MC measurement principles. Results: The adapted version demonstrated very high completion rates, being safe and reliable for accessing MC, showing strong reliability in the manipulative domain. The use of the Challenge by Choice principle improved participant autonomy, confidence, and perceived motor competence. The main alterations to stability and locomotor tasks allow feasibility while maintaining test validity. Adjustments in instructions and practice trials reduced cognitive load and improved performance, addressing age-related perceptual and comprehension challenges. Ball Kicking and Throwing Velocity tests showed high reliability (ICC between 0.828 and 0.925), with minor gender-related differences. Conclusions: The adapted MCA is a safe, feasible, and reliable instrument for assessing MC in community-dwelling older adults. It preserves the conceptual foundations of MC while accommodating age-related MC alterations, offering a valuable resource for research and clinical applications. Full article

(This article belongs to the Section Geriatric Medicine)

11 pages, 232 KB

Open AccessArticle

Comparative Analysis of the Occurrence of Depression, Stress, and Anxiety in Pregnant Women Requiring Hospitalization and Those Not Hospitalized

by Agnieszka Ptak, Kinga Przylibska, Małgorzata Stefańska and Joanna Kowalska

J. Clin. Med. 2025, 14(21), 7865; https://doi.org/10.3390/jcm14217865 - 5 Nov 2025

Viewed by 478

Abstract

Background/Objectives: The aim of the study was to assess the emotional state (stress, mood, and anxiety level, including labor anxiety) of pregnant women depending on the course of pregnancy and the related place of stay (hospital pregnancy pathology department, home). Methods: A total [...] Read more.

Background/Objectives: The aim of the study was to assess the emotional state (stress, mood, and anxiety level, including labor anxiety) of pregnant women depending on the course of pregnancy and the related place of stay (hospital pregnancy pathology department, home). Methods: A total of 100 participants were recruited between 25 and 38 weeks of pregnancy. A total of 88 fully completed questionnaires of women qualified for analysis, including 45 women staying in the hospital (G1) and 43 women who did not require hospitalization (G2). The Depression Anxiety Stress Scale (DASS-42), the Labor Anxiety Questionnaire (KLP II), the Fatigue Assessment Scale (FAS), and a self-administered questionnaire were used. Results: All subjects showed an average moderate level of depression and stress and a high level of anxiety. A statistically significant difference in mood level (DASS depression) was noted between group G1 and group G2 (p = 0.0217). About 35% of all subjects in total and both groups achieved a result indicating a severe or extremely severe level of stress. About 66% of subjects in both groups showed a severe and extremely severe level of anxiety. None of the women studied had values interpreted as a physiological level of anxiety. Conclusions: Regardless of the course of pregnancy and the related place of residence, the risk of emotional disorders is high. It seems reasonable to perform screening tests on pregnant women to identify those who may or already have these problems. Full article

(This article belongs to the Section Obstetrics & Gynecology)

16 pages, 237 KB

Open AccessArticle

Nocturnal Heart Rate Variability in Unexplained Syncope and Sleep Apnea—The SINCOSAS Study

by María-José Muñoz-Martínez, Manuel Casal-Guisande, Bernardo Sopeña, María Torres-Durán, Enrique García-Campo, Dolores Corbacho-Abelaira, Ana Souto-Alonso and Alberto Fernández-Villar

J. Clin. Med. 2025, 14(21), 7864; https://doi.org/10.3390/jcm14217864 - 5 Nov 2025

Viewed by 906

Abstract

Background/Objectives: Heart rate variability (HRV) reflects autonomic nervous system modulation and may be altered in both unexplained syncope and obstructive sleep apnea (OSA). However, the nocturnal autonomic patterns underlying these conditions and their coexistence remain poorly understood. This study aimed to characterize nocturnal [...] Read more.

Background/Objectives: Heart rate variability (HRV) reflects autonomic nervous system modulation and may be altered in both unexplained syncope and obstructive sleep apnea (OSA). However, the nocturnal autonomic patterns underlying these conditions and their coexistence remain poorly understood. This study aimed to characterize nocturnal autonomic modulation in patients with unexplained syncope, OSA, or both, compared with individuals without these conditions. Methods: In this multicenter, cross-sectional, comparative study, 304 adults were assigned to four groups: controls (no syncope or OSA), OSA without syncope, syncope without OSA, and syncope with OSA. Time- and frequency-domain HRV parameters were derived from overnight respiratory polygraphy and compared across groups. Results: OSA was associated with increased root mean square of successive differences (RMSSD) and reduced low-frequency (LF) power, indicating enhanced vagal activity and lower nocturnal sympathetic tone. Syncope was characterized by further reductions in sympathetic indices (LF and very low frequency, VLF) with increased RMSSD, suggesting blunted sympathetic reserve. Patients with both conditions exhibited a mixed autonomic profile—elevated overall HRV with concurrent reductions in both sympathetic and parasympathetic components—indicating more profound dysautonomia despite milder OSA severity. Conclusions: OSA and syncope show distinct nocturnal autonomic patterns, and their coexistence leads to deeper autonomic imbalance. Incorporating nocturnal HRV analysis into routine polygraphy may improve pathophysiological stratification of unexplained syncope and identify clinically significant OSA. Full article

(This article belongs to the Section Respiratory Medicine)

12 pages, 239 KB

Open AccessArticle

Pelvic Organ Prolapse-Health-Preserving Attitudes According to Sociodemographic Factors

by Aleksandra Zaborowska, Katarzyna Tomczyk, Małgorzata Kampioni and Paweł Rzymski

J. Clin. Med. 2025, 14(21), 7863; https://doi.org/10.3390/jcm14217863 - 5 Nov 2025

Viewed by 399

Abstract

Objectives: Pelvic organ prolapse (POP) disorders are a significant problem with a society-wide dimension, affecting the quality of life of many women around the world. The purpose of this study is to assess the influence of sociodemographic factors on health-preserving behaviors in [...] Read more.

Objectives: Pelvic organ prolapse (POP) disorders are a significant problem with a society-wide dimension, affecting the quality of life of many women around the world. The purpose of this study is to assess the influence of sociodemographic factors on health-preserving behaviors in relation to pelvic organ prolapse in women of reproductive age. Method: The survey was conducted using a questionnaire made available electronically and a paper questionnaire distributed to female patients of the Gynecology and Obstetrics Clinical Hospital of the Karol Marcinkowski Medical University in Poznan. In total, 160 women aged 15–49 years voluntarily participated in the study. The distribution of variables was assessed using the Shapiro–Wilk test. The Mann–Whitney U and Kruskal–Wallis ANOVA tests were used for comparisons between groups. Comparisons between assessment scores and self-assessment of knowledge were made using Wilcoxon’s paired rank order test and the Chi2 NW (highest reliability) test. A p-value < 0.05 was considered statistically significant. Results: The level of knowledge about POP prevention and conservative treatment methods is low. The group with a higher level of knowledge was characterized by younger age, higher education, and living in areas with a large population. Conclusions: The results suggest only a partial understanding of the topic of pelvic organ prolapse, while lacking full awareness of prevention. Full article

(This article belongs to the Section Obstetrics & Gynecology)

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J. Clin. Med., Volume 14, Issue 21 (November-1 2025) – 441 articles

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