Journal of Clinical Medicine

16 pages, 595 KB

Open AccessSystematic Review

Effects of Barefoot and Minimalist Footwear Strength-Oriented Training on Foot Structure and Function in Athletic Populations: A Systematic Review

by Celia Rodríguez-Longobardo, Miguel Ángel Gómez-Ruano and Lorena Canosa-Carro

J. Clin. Med. 2025, 14(21), 7629; https://doi.org/10.3390/jcm14217629 (registering DOI) - 28 Oct 2025

Abstract

Background/Objectives: The popularity of barefoot and minimalist footwear training has increased in recent years, yet its impact on foot strength, morphology, and functional outcomes remains unclear, particularly in strength-training contexts beyond running-focused studies. Although some biomechanical and anecdotal evidence exists, no systematic review [...] Read more.

Background/Objectives: The popularity of barefoot and minimalist footwear training has increased in recent years, yet its impact on foot strength, morphology, and functional outcomes remains unclear, particularly in strength-training contexts beyond running-focused studies. Although some biomechanical and anecdotal evidence exists, no systematic review has specifically addressed the effects of foot-specific strength training interventions performed barefoot or with minimalist footwear. This review aimed to evaluate the effects of barefoot and minimalist footwear strength training interventions on foot muscle structure, force production, and neuromuscular function in healthy and athletic adults. Methods: A systematic review was conducted in accordance with the PRISMA and PICOS guidelines (PROSPERO number CRD420251134329). Comprehensive database searches were performed in July 2025. Eligible studies included barefoot or minimalist strength interventions in healthy and sportive adults, assessing outcomes related to foot muscle morphology, strength, functional performance, or neuromuscular adaptations. Methodological quality was evaluated using the PEDro and MINORS scales. Results: Seven studies involving 213 participants met the inclusion criteria. Most interventions led to significant improvements in intrinsic and extrinsic foot muscle volume, medial arch function, toe flexor strength, and neuromuscular control. Adaptations were particularly evident in interventions combining strength, balance, and agility exercises over multiple weeks. However, heterogeneity in protocols and outcome measures limited comparability. Some studies reported morphological gains without proportional improvements in strength or function. Conclusions: Barefoot and minimalist strength training can elicit beneficial morphological and functional adaptations in the foot. Nevertheless, inconsistencies in study design, small sample sizes, absence of follow-up assessment and lack of standardized protocols highlight the need for high-quality research to guide training recommendations beyond running-focused populations. Full article

(This article belongs to the Special Issue Exercise, Injury and Rehabilitation: Integrated Perspectives in Sports Medicine)

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28 pages, 1026 KB

Open AccessReview

Neuropsychological Assessments to Explore the Cognitive Impact of Cochlear Implants: A Scoping Review

by Brenda Villarreal-Garza and María Amparo Callejón-Leblic

J. Clin. Med. 2025, 14(21), 7628; https://doi.org/10.3390/jcm14217628 (registering DOI) - 27 Oct 2025

Abstract

Background/Objectives: Hearing loss constitutes a modifiable risk factor for dementia. Auditory rehabilitation with devices such as cochlear implants (CIs) has been reported to prevent cognitive decline in older adults. However, post-implant cognitive effects remain highly heterogeneous across studies. Thus, the aim of [...] Read more.

Background/Objectives: Hearing loss constitutes a modifiable risk factor for dementia. Auditory rehabilitation with devices such as cochlear implants (CIs) has been reported to prevent cognitive decline in older adults. However, post-implant cognitive effects remain highly heterogeneous across studies. Thus, the aim of this review is to synthesize the evidence on cognitive outcomes and their interplay with speech perception, quality of life (QoL), and psychological status. Methods: A bibliographic search was conducted following PRISMA guidelines from January 2015 to July 2025. Studies were eligible if they included adult CI candidates who completed cognitive and audiometric assessments. In total, 43 studies, including longitudinal and cross-sectional designs, were reviewed. Several studies also assessed hearing aid (HA) users and normal-hearing (NH) controls. Principal results were identified and analyzed across cognitive domains, audiological performance, QoL, and psychological outcomes. Results: CIs significantly improved cognition across longitudinal studies, with a higher number of assessments reporting gains in memory (61%), global cognition (57%), and executive function (46%); while attention, language, and visuospatial skills were less frequently evaluated. Though findings are not fully consistent, interactions between speech intelligibility and cognitive subdomains have also been found in several studies: global cognition (25%), executive function (22%), visuospatial skills (20%), attention (21%), language (17%), and memory (12%). Improvements in QoL, social engagement, depression, and anxiety are frequently observed. Conclusions: The lack of unified and adapted neurocognitive tools may prevent the observation of consistent outcomes across studies. Further research and multimodal data are still needed to fully understand the interaction between cognition, speech intelligibility, and QoL in CI users. Full article

(This article belongs to the Special Issue The Challenges and Prospects in Cochlear Implantation)

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12 pages, 657 KB

Open AccessArticle

Echocardiographic Hemodynamics After Aortic Valve Replacement, Wheat, and Bentall Procedure

by Wakana Niwa, Yoshiyuki Takami, Atsuo Maekawa, Koji Yamana, Kiyotoshi Akita, Kentaro Amano, Kazuki Matsuhashi, Yasushi Takagi and Tomonobu Abe

J. Clin. Med. 2025, 14(21), 7627; https://doi.org/10.3390/jcm14217627 (registering DOI) - 27 Oct 2025

Abstract

Background: Compared with isolated aortic valve replacement (AVR), echocardiographic hemodynamics after Wheat and Bentall procedures, both involving replacement of the proximal ascending aorta with a smaller-diameter graft, have been less thoroughly investigated. Methods: We analyzed 213 patients who received 21 mm or [...] Read more.

Background: Compared with isolated aortic valve replacement (AVR), echocardiographic hemodynamics after Wheat and Bentall procedures, both involving replacement of the proximal ascending aorta with a smaller-diameter graft, have been less thoroughly investigated. Methods: We analyzed 213 patients who received 21 mm or 23 mm aortic bioprostheses (AVR, n = 138; Wheat, n = 43; Bentall, n = 32). Transthoracic echocardiography was performed before and after surgery, and the proximal ascending aortic area (Aa) was assessed using contrast-enhanced computed tomography. Results: The maximal pressure gradient (PG max), derived from the simplified Bernoulli equation, was significantly lower in the Bentall group, whereas pressure recovery (PR), calculated using Voelker’s equation, was lower in the AVR group. A smaller Aa was associated with a higher PG max in the AVR group. The Bentall group exhibited significantly lower energy loss (EL). In propensity score-matched analyses to minimize potential confounding factors, the AVR group showed a significantly lower PR and higher EL than the Wheat group; a significantly higher PG max, lower PR, and higher EL than the Bentall group; and a significantly similar PR but lower EL in the Bentall group compared with the Wheat group. Conclusions: Although limited to bioprosthetic valves, caution is warranted when interpreting echocardiographic PG max after AVR in patients with a small ascending aorta. However, overestimation of PG max was not observed in either the Wheat or Bentall groups, even though both demonstrated higher PR and lower EL compared with the AVR group. Full article

(This article belongs to the Section Cardiology)

15 pages, 1253 KB

Open AccessSystematic Review

A Systematic Review of the Literature on the Current Revascularization Strategies for Aberrant Left Vertebral Artery During Total Endovascular and Hybrid Treatment of Aortic Arch Disease

by Marta Minucci, Ottavia Borghese, Antonio Luparelli, Domenico Pascucci, Laura Rascio, Giovanni Tinelli, Tommaso Donati and Yamume Tshomba

J. Clin. Med. 2025, 14(21), 7626; https://doi.org/10.3390/jcm14217626 (registering DOI) - 27 Oct 2025

Abstract

Background/Objectives: The aim of this study was to assess the current management strategies of Isolated Left Vertebral Artery (ILVA) arising directly from the aortic arch during total endovascular or hybrid repair of aortic arch pathologies and their safety and efficacy. Methods: A systematic [...] Read more.

Background/Objectives: The aim of this study was to assess the current management strategies of Isolated Left Vertebral Artery (ILVA) arising directly from the aortic arch during total endovascular or hybrid repair of aortic arch pathologies and their safety and efficacy. Methods: A systematic literature review was undertaken to assess the current management strategies for ILVA during total endovascular or hybrid repair of aortic arch pathologies on three databases (PubMed, SCOPUS and Web of Science) from inception to February 2025, according to PICO and PRISMA guidelines (PROSPERO CRD42024562104). The safety (overall and aortic-related mortality; neurological complications) and efficacy (revascularization patency, endoleak and reintervention rate) of both approaches were investigated. Results: Out of 224 articles found, seven retrospective cohort studies (178 patients) were included. Overall, 149 patients (74.2% male, mean age 63 years) underwent ILVA revascularization. Two studies reported open ILVA revascularization through transposition; three studies reported endovascular revascularization strategies, and one study reported both open and endovascular techniques. The overall mortality rate was 1.3% at 30 days and 5.4% at a mean follow-up of 46 months (range 6–120) with a reported rate of aortic mortality of 0.7%. In the transposition group (55 patients), the rate of minor neurological complications was 16.6%, and the rate of major neurological complications was 7.3%; loss of patency rate was 16.3% and reintervention rate was 11.7%. Endovascularly treated patients (94 patients) experienced a rate of minor neurological complications of 2.1% and major neurological complications of 1%; the loss of patency rate was 2.1%, and the reintervention rate was 3.1%. Conclusions: Both surgical and endovascular techniques for ILVA revascularization seem to assure an acceptable rate of mortality and neurological complications during treatment of arch pathologies. However, currently available data are poor, non-standardized and based on single-center experiences. Therefore, until more robust data are available to indicate the superiority of one approach over another, the management strategies for aberrant ILVA should be individualized based on the anatomic characteristics and the center experience. Our findings underscore the need for prospective studies with standardized protocols. Full article

(This article belongs to the Special Issue Vascular Surgery: Current Status and Future Perspectives)

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13 pages, 1193 KB

Open AccessReview

Importance of Capillary Leak and Nocturia in Defining and Successfully Treating Idiopathic Edema

by John K. Maesaka, Louis J. Imbriano, Candace Grant, Minesh Khatri and Nobuyuki Miyawaki

J. Clin. Med. 2025, 14(21), 7625; https://doi.org/10.3390/jcm14217625 (registering DOI) - 27 Oct 2025

Abstract

Background/Objectives: Idiopathic edema (IE) in women is characterized by swelling of hands and face followed by increasing abdominal and truncal girth, bloating, edema, >1.4 kg weight gain when in upright posture, and nocturia that eliminates the retained fluid. A capillary leak is the [...] Read more.

Background/Objectives: Idiopathic edema (IE) in women is characterized by swelling of hands and face followed by increasing abdominal and truncal girth, bloating, edema, >1.4 kg weight gain when in upright posture, and nocturia that eliminates the retained fluid. A capillary leak is the primary pathophysiologic abnormality that induces different clinical presentations that were considered untreatable. Methods: We utilized different aspects of Starling forces of edema formation and treated four uncomplicated cases of IE by reducing salt intake with or without diuretics and two cases of life-threatening cases due to seizures and coma induced by acute hyponatremia in one and postural dizziness, fainting, and fractures and dislocations of joints in another. Results: All four uncomplicated cases of IE were treated by reducing salt intake with or without diuretics that eliminated the weight gain and nocturia. The patient with hyponatremia never developed hyponatremia by reducing water intake and signs and symptoms of IE by salt restriction and diuretic therapy and eliminated the postural hypotension, falls, and fainting by use of support hose that increased interstitial hydrostatic pressure to eliminate fluid shifting from intravascular to interstitial spaces. Conclusions: A leaky capillary induces pathophysiologic changes that activate different metabolic pathways. IE is now a treatable condition, following: 1. Salt restriction with or without diuretics for the cyclical weight gain, and 2. Water restriction for hyponatremia, hyponatremic seizures, and coma and 3. support hose for postural hypotension, postural dizziness, and fainting. IE is unrecognized and probably more common than it is perceived. Full article

(This article belongs to the Section Nephrology & Urology)

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21 pages, 1414 KB

Open AccessSystematic Review

Effectiveness of Occupational Therapy-Based Intervention on Gross Motor Function and Independence in Activities of Daily Living in Children with Cerebral Palsy: A Systematic Review with Meta-Analysis

by Diego Fernandez-Cardenas, Celia Sánchez-Gomez, Edgar Vásquez-Carrasco, Jordan Hernandez-Martinez, Joaquín Pérez-Cárcamo, Cristian Sandoval, Pablo Valdés-Badilla, Eduardo Carmine-Peña, Constanza Lorca and Eduardo Fernández-Rodríguez

J. Clin. Med. 2025, 14(21), 7624; https://doi.org/10.3390/jcm14217624 (registering DOI) - 27 Oct 2025

Abstract

Background/Objectives: Children with cerebral palsy (CP) commonly present impairments in gross motor function and limitations in activities of daily living (ADLs), which negatively impact independence and quality of life. Identifying effective rehabilitation strategies is essential to promote functional development. To evaluate the effectiveness [...] Read more.

Background/Objectives: Children with cerebral palsy (CP) commonly present impairments in gross motor function and limitations in activities of daily living (ADLs), which negatively impact independence and quality of life. Identifying effective rehabilitation strategies is essential to promote functional development. To evaluate the effectiveness of occupational therapy (OT) interventions on gross motor function and independence in ADLs among children with CP. Methods: Seven electronic databases were searched through August 2025. The review protocol was registered in PROSPERO (CRD42025634706) and conducted in accordance with PRISMA guidelines. Methodological quality and certainty of evidence were assessed using the Oxford Centre for Evidence-Based Medicine scale, the Risk of Bias 2 (RoB 2) tool, and GRADEpro. Randomized controlled trials reporting OT interventions targeting gross motor and ADL outcomes were included. Results: Of 594 identified records, 14 studies met the inclusion criteria. Meta-analysis indicated that OT interventions significantly improved gross motor function (GMFM-66; ES = 0.32 [0.01–0.63], p = 0.04), mobility (PEDI-Mobility; ES = 0.46 [0.05–0.87], p = 0.02), and occupational performance (COPM-Performance; ES = 2.63 [1.14–4.11], p = 0.001) and satisfaction (COPM-Satisfaction; ES = 2.17 [0.82–3.51], p = 0.002). No significant changes were observed in self-care (PEDI-Self-Care; ES = 0.19 [–0.14–0.53], p = 0.26). Conclusions: Evidence suggests that OT interventions effectively enhance gross motor function, mobility, and occupational performance in children with CP. These results support the integration of OT within pediatric rehabilitation programs to optimize functional outcomes. Full article

(This article belongs to the Special Issue Cerebral Palsy: Clinical Rehabilitation and Treatment)

14 pages, 685 KB

Open AccessArticle

AKI Subtyping and Prognostic Analysis Based on Serum Electrolyte Features in ICU

by Wentie Liu, Tongyue Shi, Haowei Xu, Huiying Zhao and Guilan Kong

J. Clin. Med. 2025, 14(21), 7623; https://doi.org/10.3390/jcm14217623 (registering DOI) - 27 Oct 2025

Abstract

Objective: To identify distinct subtypes of ICU patients with Acute Kidney Injury (AKI) using serum electrolyte data and assess their associations with in-hospital mortality risk. Methods: This study used the eICU Collaborative Research Database (eICU-CRD) as its primary data source. AKI [...] Read more.

Objective: To identify distinct subtypes of ICU patients with Acute Kidney Injury (AKI) using serum electrolyte data and assess their associations with in-hospital mortality risk. Methods: This study used the eICU Collaborative Research Database (eICU-CRD) as its primary data source. AKI patients were identified according to the KDIGO clinical practice guidelines. Using K-Medoids clustering, we identified distinct AKI subtypes based on the first serum electrolyte measurements taken within 24 h of AKI diagnosis in the ICU. Logistic regression analysis was then employed to assess associations between these subtypes and in-hospital mortality risk. Within each subtype, we further examined the relationship between two AKI-related treatments, diuretics and renal replacement therapy (RRT), and mortality risk. Finally, to validate the identified subtypes, we replicated the entire analysis using a critical care dataset from a grade A tertiary hospital in Beijing, China. Results: We identified three distinct AKI subtypes from 15,838 eligible patients in the eICU-CRD. Subtype 1 (6364 patients, 40.2%) showed the lowest risk of in-hospital death and had all serum electrolyte levels within normal ranges. Subtype 2 (6624 patients, 41.8%) carried a moderate death risk and was characterized by abnormally high chloride levels. Subtype 3 (2850 patients, 18.0%) had the highest death risk, presenting with high serum phosphate and low bicarbonate levels. Importantly, the associations between treatments and mortality risk differed significantly by subtype. In the high-risk Subtype 3, both diuretics (OR = 0.71, p = 0.010) and RRT (OR = 0.78, p = 0.045) were associated with a lower risk of in-hospital death. However, in Subtype 2, both diuretics (OR = 1.30, p = 0.044) and RRT (OR = 1.56, p = 0.003) were associated with an increased risk. Neither treatment showed a significant association with death risk in Subtype 1. These findings were validated in the critical care database (431 AKI patients) from a Chinese local hospital, where the same three subtypes emerged with consistent electrolyte patterns, death risk profiles, and associations between treatments and mortality risks, validating the stability of the identified subtypes. Conclusions: Serum electrolyte data can help identify ICU AKI subtypes with different mortality risks. Additionally, associations between treatments (diuretics and RRT) and mortality risk vary significantly across these subtypes. These results generate the hypothesis that AKI subtyping could potentially inform personalized management strategies. Full article

(This article belongs to the Section Nephrology & Urology)

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12 pages, 1685 KB

Open AccessArticle

Symmetry After Breast Reconstruction Surgery: A Comparison of Immediate vs. Delayed-Immediate Breast Reconstruction Using Smartphone-Based 3D Surface Imaging

by Robin Hartmann, Nikolas Chrobot, Christian Festbaum, Michael Alfertshofer, Katharina Theresa Obermeier, Wenko Smolka, Tobias Ettl, Lukas Prantl and Vanessa Brébant

J. Clin. Med. 2025, 14(21), 7622; https://doi.org/10.3390/jcm14217622 (registering DOI) - 27 Oct 2025

Abstract

Background: Breast reconstruction surgery (BRS) is a vital coping mechanism for patients undergoing mastectomy. Various methods have been introduced, including immediate and delayed-immediate BRS. This study employs a smartphone-based approach for three-dimensional (3D) surface imaging to compare outcomes after immediate vs. delayed-immediate BRS. [...] Read more.

Background: Breast reconstruction surgery (BRS) is a vital coping mechanism for patients undergoing mastectomy. Various methods have been introduced, including immediate and delayed-immediate BRS. This study employs a smartphone-based approach for three-dimensional (3D) surface imaging to compare outcomes after immediate vs. delayed-immediate BRS. Methods: Twenty-six patients who underwent BRS using the deep inferior epigastric perforator (DIEP) flap at our institution from 1 October 2018 to 1 October 2023 were included in this study. Thirteen patients underwent immediate BRS and thirteen underwent delayed-immediate BRS. Following successful BRS, each patient underwent a digital anthropometric examination that included 14 measurements and the calculation of the symmetry index (SI) using the iPhone 15 Pro along with the 3D Scanner App and the Vectra Analysis Module (VAM). Measurements were subsequently compared between immediate and delayed-immediate BRS using the t-test for independent samples. Results: For 11 of 14 measurements, no significant differences were detected between immediate and delayed-immediate BRS. The SI did not differ significantly between immediate (M = 0.85) and delayed-immediate (M = 0.88) BRS (t-test for independent samples; p = 0.23, n = 26, two-tailed). Additionally, no significant differences were found between patients’ age, height, weight, BMI, time since first diagnosis, and flap weight using a t-test for independent samples. Conclusions: No statistically significant differences in breast symmetry were detected between immediate and delayed-immediate reconstruction in this cohort. This study supports the integration of smartphone-based 3D imaging into routine plastic surgery. Full article

(This article belongs to the Section General Surgery)

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16 pages, 601 KB

Open AccessArticle

Resilience Factors and Physical Activity Engagement in Adolescents with Chronic Musculoskeletal Pain: A Cross-Sectional Study

by William R. Black, Haley Hart, Jennifer Christofferson, Mark Connelly, Liesbet Goubert, Dustin P. Wallace, Laura Ellingson-Sayen and Ann M. Davis

J. Clin. Med. 2025, 14(21), 7621; https://doi.org/10.3390/jcm14217621 (registering DOI) - 27 Oct 2025

Abstract

Background/Objectives: Chronic musculoskeletal pain (CMSKP) affects up to 40% of adolescents and leads to substantial disability, reduced quality of life, and long-term health risks. Physical activity is central to treatment, but adherence to moderate-to-vigorous physical activity (MVPA) is inconsistent. We evaluated higher-resilience [...] Read more.

Background/Objectives: Chronic musculoskeletal pain (CMSKP) affects up to 40% of adolescents and leads to substantial disability, reduced quality of life, and long-term health risks. Physical activity is central to treatment, but adherence to moderate-to-vigorous physical activity (MVPA) is inconsistent. We evaluated higher-resilience constructs—self-efficacy, pain acceptance, motivational stage, and affect—and hypothesized that higher resilience would be associated with greater objectively measured physical activity, better daily functioning, and higher quality of life in adolescents with CMSKP. Methods: Forty-three adolescents (13–18 years) with CMSKP completed measures of physical activity-specific self-efficacy, acceptance (AFQ-Y), motivational stage (PSOCQ-A), and affect (PANAS-C). Participants wore activPAL monitors to assess MVPA, light activity, and sedentary time. Physical function endurance was measured by the six-minute walk test (6MWT) and the Functional Disability Inventory (FDI); quality of life by the Pediatric Quality of Life Inventory (PedsQL). Spearman’s correlations assessed associations among resilience variables, physical activity metrics, 6MWT distance, FDI, and PedsQL. Results: MVPA was correlated positively with 6MWT distance (ρ = 0.48, p = 0.002) and negatively with FDI scores (ρ = −0.56, p < 0.001). Self-efficacy related to higher MVPA (ρ = 0.41, p = 0.009), better endurance (ρ = 0.36, p = 0.017), and lower disability (ρ = −0.38, p = 0.013). Acceptance was correlated with PedsQL total (ρ = 0.45, p = 0.004); motivation (specifically maintenance) scores were correlated with higher quality of life (ρ = 0.33, p = 0.027). Light activity and sedentary time were not significantly linked to functional or psychosocial outcomes. In a step-wise regression, only physical activity self-efficacy for ambulation at school predicted MVPA, B = 1.56, p = 0.008. Conclusions: Resilience constructs—including self-efficacy, acceptance, and readiness to change—were meaningfully associated with MVPA, daily functioning, and quality of life, and may have implications for treatment development. Full article

(This article belongs to the Special Issue Chronic Pain: Non-Pharmacological Treatments and Rehabilitation Strategies)

9 pages, 2004 KB

Open AccessArticle

The Safety and Efficacy of Platelet-Rich Plasma in Enhancing Outcomes Following Circumcision in Children

by Tahsin Onat Kamci, Mustafa Azizoglu, Sergey Klyuev, Mehmet Hanifi Okur, Hakkari Aydogdu, Maria Escolino, Asli Pinar Zorba Yildiz, Ciro Esposito and Sameh Shehata

J. Clin. Med. 2025, 14(21), 7620; https://doi.org/10.3390/jcm14217620 (registering DOI) - 27 Oct 2025

Abstract

Background: The primary objectives of platelet-rich plasma (PRP) therapy are to enhance the wound-healing process, reduce pain, and minimize the loss of productivity due to recovery time. Localized application of PRP, which is enriched with growth factors such as PDGF, TGF-β1, IGF-1, [...] Read more.

Background: The primary objectives of platelet-rich plasma (PRP) therapy are to enhance the wound-healing process, reduce pain, and minimize the loss of productivity due to recovery time. Localized application of PRP, which is enriched with growth factors such as PDGF, TGF-β1, IGF-1, VEGF, and FGF-2, as well as interleukins (IL-1, IL-4, IL-6, IL-10, and IL-13), has been documented to accelerate the healing process by approximately 30–40%. This study aimed to assess the safety and efficacy of platelet-rich plasma (PRP) in enhancing outcomes following circumcision in male children. Methods: The patients were divided into two groups: one undergoing standard circumcision and the other receiving PRP application during circumcision. Pain scores, edema level, bleeding, local infection, and safety of PRP were evaluated. Results: This study evaluated 80 male children undergoing circumcision, divided into two groups: Group CS (n = 44) underwent classical circumcision, and Group PRP (n = 36) received PRP application. Median ages were comparable (p = 0.101). Penile edema occurred less frequently in the PRP group (5.6%) compared to the CS group (18.2%) (p = 0.089), with no severe edema observed in the PRP group. Postoperative bleeding was present in 6.8% of the CS group but absent in the PRP group (p = 0.110). Other complications, such as nausea (CS: 6.8%, PRP: 5.6%, p = 0.816), vomiting (CS: 4.5%, PRP: 2.8%, p = 0.679), local infection (CS: 2.3%, PRP: 0%, p = 0.363), wound dehiscence (CS: 2.3%, PRP: 0%, p = 0.363), and skin tunnel formation (CS: 6.8%, PRP: 2.8%, p = 0.409), showed no significant differences. No cases of necrosis, chordee, rotational anomaly, or secondary phimosis were observed. Safety analysis of PRP revealed minor complications during blood draw: hypotension in one patient (2.8%) and local ecchymosis in two patients (5.6%), resolving without intervention. During PRP application, one allergic reaction (2.8%) occurred, presenting as a transient rash that resolved spontaneously. Group PRP consistently reported lower pain scores than Group CS at all time points. Conclusions: PRP application during circumcision is safe. The findings provide preliminary but important evidence regarding the potential benefits of PRP in pediatric circumcision. Full article

(This article belongs to the Section General Surgery)

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14 pages, 321 KB

Open AccessArticle

Maternal Systemic Inflammation and Fetal Thymic Size in Diabetic Pregnancies: Predictive Role of Hematological Biomarkers

by Gülay Balkaş and Şevki Çelen

J. Clin. Med. 2025, 14(21), 7619; https://doi.org/10.3390/jcm14217619 (registering DOI) - 27 Oct 2025

Abstract

Background/Objectives: This study aimed to evaluate the relationship between maternal systemic inflammatory indices, hematological parameters, and fetal thymus size, as measured by the thymus–thoracic ratio (TTR), among diabetic pregnancies, and to establish predictive cut-off values for reduced thymus size. Methods: This prospective cohort [...] Read more.

Background/Objectives: This study aimed to evaluate the relationship between maternal systemic inflammatory indices, hematological parameters, and fetal thymus size, as measured by the thymus–thoracic ratio (TTR), among diabetic pregnancies, and to establish predictive cut-off values for reduced thymus size. Methods: This prospective cohort study enrolled 532 pregnant women, divided into four groups: pregestational diabetes mellitus (PGDM, n = 44), diet-controlled gestational diabetes mellitus (GDM, n = 73), insulin-treated GDM (n = 49), and normoglycemic controls (n = 366). Fetal thymus size, alongside serum levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), aggregate index of systemic inflammation (AISI), fibrinogen-to-albumin ratio (FAR), and C-reactive protein (CRP)-to-albumin ratio, were assessed in the third trimester. Results: All maternal diabetes subgroups demonstrated significantly reduced fetal thymus size compared with controls, with the most pronounced reduction observed in the PGDM group (p < 0.001). NLR, PLR, MLR, SIRI, AISI, and MPV were significantly elevated in the PGDM cohort, whereas CAR, FAR, and fibrinogen levels were markedly increased in the insulin-treated GDM group. Albumin levels were significantly decreased in both the PGDM and the insulin-treated GDM groups (p < 0.001). Among the evaluated biomarkers, AISI and FAR exhibited the highest diagnostic accuracy for predicting reduced fetal thymus size, with optimal cut-off values of 640.3 (sensitivity 82.3%, specificity 86.7%) and 0.114 (sensitivity 74.3%, specificity 88.7%), respectively. Conclusions: Maternal systemic inflammatory burden, as indicated by hematological biomarkers, is significantly associated with reduced fetal thymic size in diabetic pregnancies. These findings suggest that readily accessible blood-derived biomarkers, particularly AISI and FAR, may complement ultrasonographic evaluation, offering a cost-effective, non-invasive approach to predict compromised fetal immune development, especially in settings where direct thymic imaging is impractical. Full article

(This article belongs to the Section Obstetrics & Gynecology)

11 pages, 540 KB

Open AccessPerspective

Microplastics, Nanoplastics and Heart Contamination: The Hidden Threat

by Gian Luca Iannuzzi, Michele D’Alto, Giorgio Bosso, Antonio Pio Montella, Veronica D’Oria, Luigi Pellegrino, Giuseppe Boccaforno, Alessandro Masi, Antonio Orlando, Renato Franco, Andrea Ronchi, Carmine Nicastro and Marisa De Feo

J. Clin. Med. 2025, 14(21), 7618; https://doi.org/10.3390/jcm14217618 (registering DOI) - 27 Oct 2025

Abstract

The global spread of micro- and nanoplastics (MNPs) has emerged as an environmental and medical concern, with growing evidence of their role in cardiovascular disease (CVD). These particles, originating from the degradation of larger plastics and consumer products, can be ingested or inhaled, [...] Read more.

The global spread of micro- and nanoplastics (MNPs) has emerged as an environmental and medical concern, with growing evidence of their role in cardiovascular disease (CVD). These particles, originating from the degradation of larger plastics and consumer products, can be ingested or inhaled, cross biological barriers, and accumulate in human tissues, including blood, myocardium, and atherosclerotic plaques. Experimental and clinical studies suggest that MNPs contribute to CVD through multiple mechanisms: activation of systemic inflammation and inflammasomes, oxidative stress, endothelial dysfunction, prothrombotic activity, and direct myocardial injury, ultimately promoting fibrosis and impaired contractility. Epidemiological data further indicate that populations exposed to higher plastic pollution or with pre-existing cardiovascular risk factors may be particularly vulnerable. Taken together, these findings identify MNPs as a potential novel environmental cardiovascular risk factor. Advancing detection methods, mechanistic research, and public health strategies will be essential to mitigate their impact and reduce plastic-related cardiovascular burden. Full article

(This article belongs to the Section Cardiology)

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18 pages, 3698 KB

Open AccessArticle

A Temporal Validation Study of Diagnostic Prediction Models for the Screening of Elevated Low-Density and Non-High-Density Lipoprotein Cholesterol

by Wuttipat Kiratipaisarl, Vithawat Surawattanasakul, Wachiranun Sirikul and Phichayut Phinyo

J. Clin. Med. 2025, 14(21), 7617; https://doi.org/10.3390/jcm14217617 (registering DOI) - 27 Oct 2025

Abstract

Background/Objectives: Limited accessibility to hypercholesterolemia diagnosis hinders the primary prevention of cardiovascular disease. Therefore, we conducted a prospective, temporal validation study of two diagnostic prediction models, targeting endpoints of elevated low-density lipoprotein cholesterol (LDL-C, ≥160 mg/dL) and non-high-density lipoprotein cholesterol (non-HDL-C, ≥160 [...] Read more.

Background/Objectives: Limited accessibility to hypercholesterolemia diagnosis hinders the primary prevention of cardiovascular disease. Therefore, we conducted a prospective, temporal validation study of two diagnostic prediction models, targeting endpoints of elevated low-density lipoprotein cholesterol (LDL-C, ≥160 mg/dL) and non-high-density lipoprotein cholesterol (non-HDL-C, ≥160 mg/dL). Methods: We prospectively recruited workers aged 20–40 years from a single-center, university hospital from March to June 2024 (n = 1099). We determined two diagnostic endpoints: elevated LDL-C and non-HDL-C. The predicted probabilities were derived from the binary logistic regression based on gender, metabolic age, and diastolic blood pressure. We assessed three prediction performances: discrimination from area under the receiver-operating characteristic curve (AuROC); calibration slope (C-slope) and calibration-in-the-large (CITL) from the calibration plot; clinical net benefit from decision curve analysis. Recalibration was based on C-slope and CITL, with a socioeconomic subgroup fairness assessment of AuROC, C-slope, and CITL. Results: From 1099 eligible participants, we identified 135 (12.3%) elevated LDL-C and 251 (22.8%) elevated non-HDL-C cases. The LDL-C model had poor discrimination (AuROC 0.59; 95%-CI, 0.56–0.62), miscalibration (C-slope 0.64; 95%-CI, 0.39–0.88 and CITL −0.14; 95%-CI, −0.27–−0.02), and negligible investigation reduction. The non-HDL-C model had fair discrimination (AuROC 0.67; 95%-CI, 0.64–0.69), miscalibration (C-slope 0.71; 95%-CI, 0.59–0.83 and CITL −0.07; 95%-CI, −0.17–0.03), and 20% investigation reduction at prevalence threshold probability. Updated model fairness improved compared to the original models. Conclusions: Temporal validation demonstrated modest replicability for the elevated non-HDL-C model, with a potential limitation in participants with normal BMI but low muscle and high fat mass. Health practitioners may use updated elevated non-HDL-C models as a non-invasive triage strategy in young adults, with threshold probabilities within the positive clinical net benefit ranges. Further external validation studies in a larger and more diverse population are necessary. Full article

(This article belongs to the Special Issue Clinical Updates on Dyslipidemia)

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13 pages, 562 KB

Open AccessArticle

Early Pregnancy Termination with Mifepristone and Misoprostol: Concurrent vs. 48-Hour Interval Administration in a Randomized Controlled Trial

by Meirav Braverman, Adi Dayan-Schwartz, Yehuda Ben-David, Orly Kachta and Noah Zafran

J. Clin. Med. 2025, 14(21), 7616; https://doi.org/10.3390/jcm14217616 (registering DOI) - 27 Oct 2025

Abstract

Background: The standard protocol for early first-trimester termination of pregnancy (TOP) involves administration of mifepristone followed by misoprostol after a 48-h interval. While concurrent administration may improve convenience and access, evidence regarding its effectiveness remains limited. This study aims to compare the [...] Read more.

Background: The standard protocol for early first-trimester termination of pregnancy (TOP) involves administration of mifepristone followed by misoprostol after a 48-h interval. While concurrent administration may improve convenience and access, evidence regarding its effectiveness remains limited. This study aims to compare the efficacy, safety, and acceptability of concurrent oral administration of mifepristone and misoprostol with the 48-h interval regimen for early TOP. Methods: In this randomized controlled trial (ClinicalTrials.gov: NCT03440866), 250 patients with intrauterine pregnancies up to 49 days’ gestation were randomized to receive either concurrent treatment (600 mg mifepristone and 400 mcg misoprostol) or the same medications administered 48 h apart. The primary outcome was complete abortion without additional intervention. Secondary outcomes included adverse events, pain, and patient satisfaction. Follow-up occurred approximately two weeks post-treatment. Data were available for 220 participants. Results: The concurrent group had a significantly lower success rate compared to the control group (68.8% vs. 84.3%, p = 0.007). Continuing pregnancy was more frequent with concurrent administration (13.4% vs. 2.8%, p = 0.004). No significant differences were observed in hemoglobin change, adverse events, or pain scores. Patient satisfaction was higher in the control group (81.1% vs. 63.6%, p = 0.04), though preferences for future abortion methods did not differ between groups. Conclusions: Concurrent administration of mifepristone and misoprostol is less effective and less satisfactory than the standard 48-h regimen, although safety and pain profiles are comparable. It should not replace the interval protocol, and patients choosing concurrent treatment should be counseled about its lower efficacy and higher likelihood of requiring additional intervention. Full article

(This article belongs to the Section Obstetrics & Gynecology)

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15 pages, 7681 KB

Open AccessCase Report

Multinodular Hydropic Leiomyoma in a 41-Year-Old Patient: A Case Report

by Diana Xie Freire, Alissia Blumer, Teresa Teixeira da Silva, Sonali Düblin, Joachim Diebold and Ivo Fähnle-Schiegg

J. Clin. Med. 2025, 14(21), 7615; https://doi.org/10.3390/jcm14217615 (registering DOI) - 27 Oct 2025

Abstract

Uterine leiomyomas are a heterogenous group of benign mesenchymal tumours. While diagnosis is usually achieved through clinical assessment and pelvic ultrasound (PU), atypical subtypes are not as easily recognisable and can be mistaken for malignant tumours such as leiomyosarcoma or ovarian carcinoma. We [...] Read more.

Uterine leiomyomas are a heterogenous group of benign mesenchymal tumours. While diagnosis is usually achieved through clinical assessment and pelvic ultrasound (PU), atypical subtypes are not as easily recognisable and can be mistaken for malignant tumours such as leiomyosarcoma or ovarian carcinoma. We describe the case of a 41-year-old patient who presented with increasing bulk symptoms, urinary frequency and growth of a hydropic leiomyoma (HLM) of the left lateral and posterior uterine wall that had been known for 10 years, confirmed with previous biopsy. The tumour filled the entire pelvic cavity in PU and was increasingly difficult to delineate; therefore an abdominal hysterectomy without oophorectomy was performed. Gross tissue examination showed an irregularly enlarged, asymmetric uterus with an intrauterine subserosal mass and an extrauterine papillary tumour arising from the right and posterior uterine wall. The tumour measured 20 × 17 × 10 cm in size. Numerous smooth muscle nodules were observed within the uterus and extending into the extrauterine component in a continuous transition, exhibiting a benign, bland appearance. The nodules were separated by abundant edematous connective tissue with increased vascularization. Histopathological analysis revealed low mitotic activity with no evidence of nuclear atypia, pleomorphism, or necrosis. Immunohistochemical staining confirmed the diagnosis of a benign smooth muscle tumour. Our findings confirm a rare, benign smooth muscle neoplasm with both intrauterine and extrauterine involvement, and add to the existing literature regarding presentation, diagnostic and therapeutic challenges associated with HLM. Full article

(This article belongs to the Section Oncology)

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20 pages, 347 KB

Open AccessReview

Laparoscopy in the Surgical Management of Gynecological Cancer: A Comprehensive Update

by Stamatios Petousis, Georgia Margioula-Siarkou, Chrysoula Margioula-Siarkou, Aristarchos Almperis, Frederic Guyon and Konstantinos Dinas

J. Clin. Med. 2025, 14(21), 7614; https://doi.org/10.3390/jcm14217614 (registering DOI) - 27 Oct 2025

Abstract

A laparoscopic approach has been incorporated into the surgical management of a great variety of gynecologic pathologies during the decades following the first description of the method. As knowledge and experience about the use of laparoscopy is accumulating, it is gradually being recognized [...] Read more.

A laparoscopic approach has been incorporated into the surgical management of a great variety of gynecologic pathologies during the decades following the first description of the method. As knowledge and experience about the use of laparoscopy is accumulating, it is gradually being recognized as an oncologically safe and effective option for the surgical management of various types of gynecological cancer, and the indications for its applications are increasing, as controversial topics are resolved through research. Endometrial cancer is the gynecological malignancy with the most straightforward indications of laparoscopy in its treatment, since a minimally invasive approach is considered the standard of care for both the surgical treatment of early-stage disease and surgical staging through sentinel lymph node biopsy. The role of laparoscopy was significantly decreased in the surgical management of cervical cancer after the publication of the LACC trial which reported worse survival outcomes for patients treated with laparoscopy, and laparotomy has emerged as the preferred approach. However, laparoscopy can be acceptable for carefully selected cases of early-stage cervical cancer and has also been introduced as an effective method for the surgical staging of the disease. The use of laparoscopy in the diagnostic and therapeutic management of ovarian cancer is not fully established but is receiving growing attention, as increasing evidence supports the safety of this approach, especially in the treatment of early-stage disease, where it is considered an acceptable alternative approach to laparotomy. Finally, as laparoscopic advancements are continuously achieved, new indications for laparoscopy have been explored for both vulvar and breast cancer. Future research will identify and highlight new ways to further integrate laparoscopy into the diagnostic and therapeutic management of gynecological malignancies. Full article

(This article belongs to the Special Issue Laparoscopy and Surgery in Gynecologic Oncology)

13 pages, 746 KB

Open AccessSystematic Review

Technical Details of Lateral Tenodesis at the Fascia Lata: A Systematic Review of the Literature

by François Laudet, Thibaut Noailles, Christian Lutz and Alexandre Hardy

J. Clin. Med. 2025, 14(21), 7613; https://doi.org/10.3390/jcm14217613 (registering DOI) - 27 Oct 2025

Abstract

Background/Objectives: Anterior cruciate ligament (ACL) reconstruction stabilizes the knee and treats associated lesions. Control of rotational laxity can be optimized by an extra-articular plasty, historically known as the Lemaire plasty or tenodesis at the fascia lata. The risk of iterative rupture is [...] Read more.

Background/Objectives: Anterior cruciate ligament (ACL) reconstruction stabilizes the knee and treats associated lesions. Control of rotational laxity can be optimized by an extra-articular plasty, historically known as the Lemaire plasty or tenodesis at the fascia lata. The risk of iterative rupture is reduced, by stabilising anterior translation and tibial internal rotation. In the literature, many different technical details are described, for example regarding the position and the method of femoral fixation. Although these parameters are fundamental to achieving graft isometry and avoiding overconstraint, no consensus or standardized recommendations have yet been established. The aim of the study was to summarize the position of fixation of a lateral tenodesis to the fascia lata, the degrees of flexion and rotation during fixation, its mode of fixation and its passage in relation to the lateral collateral ligament (LCL). Methods: In April 2024, a systematic review was conducted by two independent authors to identify studies describing lateral tenodesis with fascia lata with details about femoral fixation position, method of fixation, the graft’s passage relative to the lateral collateral ligament and flexion/rotation during fixation. From 111 records initially identified, 22 studies met the inclusion criteria. Results: Most authors described passing the graft beneath the LCL to achieve controlled anisometry. The preferred femoral fixation point was proximal and posterior to the lateral epicondyle, with fixation performed at approximately 30° of flexion and neutral tibial rotation. Various fixation methods have been reported, including staples, screws, cortical buttons, and anchors, but no biomechanical evidence demonstrated the superiority of one technique over another. Conclusions: Lateral tenodesis at the fascia lata is a well-established adjunct to ACL reconstruction, providing additional control of rotational laxity. While consistent trends are emerging regarding graft passage and femoral fixation landmarks, technical heterogeneity persists, and no definitive guidelines currently exist. Standardization of these parameters through high-level clinical and biomechanical studies is warranted to optimize outcomes and reduce variability in surgical practice. Full article

(This article belongs to the Special Issue Advancements in Anterior Cruciate Ligament Injury: From Diagnosis to the Return-to-Sports: 2nd Edition)

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12 pages, 709 KB

Open AccessArticle

Effects of Personality Styles on Clinical Response to Intermittent Theta Burst Stimulation for Depression

by Mohamed A. Abdelnaim, Tobias Hebel, Katharina Kerkel, Berthold Langguth, Martin Schecklmann, Susanne Staudinger and Andreas Reissmann

J. Clin. Med. 2025, 14(21), 7612; https://doi.org/10.3390/jcm14217612 (registering DOI) - 27 Oct 2025

Abstract

Introduction: Major depressive disorder (MDD) is a common and often treatment-resistant condition, with many patients showing only partial or minimal response to standard therapies. Repetitive transcranial magnetic stimulation (rTMS) is a well-established, non-invasive treatment for depression, though individual response varies considerably. While demographic [...] Read more.

Introduction: Major depressive disorder (MDD) is a common and often treatment-resistant condition, with many patients showing only partial or minimal response to standard therapies. Repetitive transcranial magnetic stimulation (rTMS) is a well-established, non-invasive treatment for depression, though individual response varies considerably. While demographic and clinical predictors have been explored, the impact of personality styles on rTMS outcomes remains underinvestigated. Herein, we aimed to explore whether personality styles influence treatment response to rTMS. Methods: This retrospective study included 63 in- and outpatients with depressive episodes treated with intermittent theta-burst stimulation (iTBS) between September 2020 and December 2022. Patients were assessed before and after treatment using the 21-item Hamilton Depression Rating Scale (HAMD-21) and the self-reported Major Depression Inventory (MDI). Personality styles were evaluated using the German Persönlichkeits-Stil-und-Störungs-Inventar (PSSI), a dimensional measure of 14 personality styles. Statistical analyses included paired-samples t-tests to assess symptom change and linear regression models to examine whether personality styles predicted treatment outcomes. Effect sizes were reported as Cohen’s d. Results: Patients showed a significant reduction in depressive symptoms following iTBS (HAMD-21: t(62) = 10.86, p < 0.001, d = 1.37. MDI: t(62) = 8.55, p < 0.001, d = 1.06). Stepwise regression for the MDI identified critical–negativistic (NT) and reserved–schizoid (SZ) styles as significant predictors, explaining approximately 16% of the variance (R² = 0.159, p = 0.007). When entered simultaneously in a regression model for the HAMD-21, these same traits also predicted symptom change, though the effect was smaller (R² = 0.108, p = 0.033). Higher scores of critical–negativistic (NT) style were associated with better improvement, whereas higher scores of reserved–schizoid (SZ) style were associated with less improvement. Conclusions: This study confirms the overall efficacy of rTMS in reducing depressive symptoms. While SZ and NT traits showed some predictive value for treatment response—particularly on self-reported outcomes—their influence was modest and inconsistent. Based on our findings, there is no reason why patients with depression and specific personality styles, or even comorbid personality disorders, should be denied rTMS treatment. Full article

(This article belongs to the Section Mental Health)

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12 pages, 1549 KB

Open AccessArticle

Clinical Outcomes Associated with Stellate Ganglion Block Across Multiple Pain Phenotypes

by Zeki Boga, Cagatay Kucukbingoz, Ahmet Yilmaz, Semih Kivanc Olguner, Ali Arslan, Mehmet Ozer, Mustafa Emre Sarac and Yurdal Gezercan

J. Clin. Med. 2025, 14(21), 7611; https://doi.org/10.3390/jcm14217611 (registering DOI) - 27 Oct 2025

Abstract

Background/Objectives: Stellate ganglion block (SGB) is an interventional technique frequently applied to manage pain associated with sympathetic dysfunction. This study aimed to evaluate the short-term clinical outcomes and tolerability of SGB in patients with different pain phenotypes. Methods: From 1 January [...] Read more.

Background/Objectives: Stellate ganglion block (SGB) is an interventional technique frequently applied to manage pain associated with sympathetic dysfunction. This study aimed to evaluate the short-term clinical outcomes and tolerability of SGB in patients with different pain phenotypes. Methods: From 1 January 2024 through 1 March 2025, 96 patients who underwent fluoroscopy-guided SGB at a single center were retrospectively analyzed. The Oswestry Disability Index (ODI) was used to assess functional status, the SF-36 was applied to evaluate health-related quality of life, and the Visual Analog Scale (VAS) was employed to measure pain intensity. This study included baseline measurements and follow-up evaluations at 1, 3, and 6 months after the procedure. Results: Statistically significant improvements were observed in VAS, ODI, and SF-36 scores across all pain groups (p < 0.001). The largest median VAS reductions were observed in the migraine (4.0 [3.5–5.0]) and complex regional pain syndrome (CRPS) (3.7 [3.0–4.5]) groups, both exceeding the minimal clinically important difference (MCID). Patients with neuropathic and nociceptive pain showed smaller median reductions (3.4 [2.8–4.0] and 3.0 [2.5–3.8], respectively). The highest proportion of responders (≥50% VAS reduction) was noted in the migraine group (64.3%), while the lowest occurred in the nociceptive group (37.5%). Multivariate analysis identified pain phenotype as the only independent predictor of favorable outcomes, particularly in migraine and CRPS. Minor transient complications occurred in 9.4% of patients, all resolving spontaneously. Conclusions: SGB was well tolerated and associated with significant pain reduction and functional improvement. The observed clinical benefits may reflect mechanisms involving both peripheral and central sympathetic modulation. Larger multicenter prospective studies with extended follow-up are warranted to confirm these findings. Full article

(This article belongs to the Section Clinical Neurology)

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