Journal of Clinical Medicine

10 pages, 494 KB

Open AccessArticle

Mutations and Efficacy of Pembrolizumab-Based Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer: A Real-World Multicenter Analysis

by Palma Fedele, Alessandro Rizzo, Matteo Landriscina, Stefania Luigia Stucci, Maria Morritti, Francesco Giuliani, Lucia Moraca, Giuseppe Cairo, Raffaele Ardito, Marianna Giampaglia, Domenico Bilancia, Assunta Melaccio, Antonella Terenzio, Antonio Gnoni, Antonella Licchetta, Federica Fumai, Laura Lanotte and Gennaro Gadaleta-Caldarola

J. Clin. Med. 2025, 14(24), 8854; https://doi.org/10.3390/jcm14248854 (registering DOI) - 14 Dec 2025

Abstract

Background: Pembrolizumab has reshaped the neoadjuvant treatment landscape for triple-negative breast cancer (TNBC). However, the influence of BRCA1/2 mutational status on the efficacy of chemo-immunotherapy remains unclear, particularly in real-world settings. Since BRCA-mutated tumors exhibit homologous recombination deficiency (HRD) and high genomic instability, [...] Read more.

Background: Pembrolizumab has reshaped the neoadjuvant treatment landscape for triple-negative breast cancer (TNBC). However, the influence of BRCA1/2 mutational status on the efficacy of chemo-immunotherapy remains unclear, particularly in real-world settings. Since BRCA-mutated tumors exhibit homologous recombination deficiency (HRD) and high genomic instability, they may be more immunogenic and responsive to immune checkpoint inhibitors. This multicenter study investigated the association between BRCA1/2 mutations and pathologic complete response (pCR) in TNBC patients treated with pembrolizumab-based neoadjuvant chemotherapy (NACT). Methods: We retrospectively analyzed 184 patients with stage II–III TNBC treated between 2021 and 2024 across eleven Italian oncology centers. All received pembrolizumab combined with platinum- and taxane-based NACT followed by anthracyclines, according to the KEYNOTE-522 regimen. Germline BRCA1/2 status was determined by next-generation sequencing. The primary endpoint was pCR, defined as ypT0/is ypN0. Fisher’s exact test and logistic regression models were used to assess associations between clinical–pathological variables and pCR. Results: Among 184 patients, 25 (13.6%) harbored BRCA1 mutations, 12 (6.5%) BRCA2 mutations, and 147 (79.9%) were wild-type. pCR was achieved in 80.0% of BRCA1-mutated, 75.0% of BRCA2-mutated, and 61.1% of wild-type tumors. When pooled, BRCA1/2-mutated cases showed a higher likelihood of achieving pCR (78.4% vs. 61.1%; odds ratio [OR] = 2.17; 95% CI 1.01–4.97; p = 0.056). High tumor-infiltrating lymphocytes (≥30%) were also associated with increased pCR rates. The frequency of BRCA mutations (20.1%) was consistent with that reported in major TNBC series. No comparative analysis of toxicity or survival outcomes was performed due to the retrospective design and limited follow-up. Conclusions: In this multicenter real-world cohort, TNBC patients carrying BRCA1/2 mutations exhibited a trend toward higher pCR rates with pembrolizumab-based NACT compared with wild-type tumors. These findings suggest enhanced chemosensitivity and immune responsiveness in BRCA-deficient disease, warranting further validation in larger prospective studies with survival endpoints. Full article

(This article belongs to the Section Oncology)

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14 pages, 1210 KB

Open AccessArticle

Expanded Hemodialysis with Theranova 500 Improves Dialysis Adequacy and Blunts Inflammation: A 24-Week Quasi-Randomized Trial

by Nomy Levin Iaina, Elena Rotshild, Sharon Mini Goldberg and Pazit Beckerman

J. Clin. Med. 2025, 14(24), 8853; https://doi.org/10.3390/jcm14248853 (registering DOI) - 14 Dec 2025

Abstract

Background/Objectives: Uremic middle molecules contribute to chronic inflammation and symptom burden in hemodialysis patients. The Theranova 500 medium-cutoff (MCO) dialyzer enhances clearance of larger uremic toxins and may offer clinical advantages. We hypothesized that Theranova 500 would improve dialysis adequacy (spKt/V), attenuate [...] Read more.

Background/Objectives: Uremic middle molecules contribute to chronic inflammation and symptom burden in hemodialysis patients. The Theranova 500 medium-cutoff (MCO) dialyzer enhances clearance of larger uremic toxins and may offer clinical advantages. We hypothesized that Theranova 500 would improve dialysis adequacy (spKt/V), attenuate inflammation (CRP), and provide targeted improvement in symptom burden compared with the high-flux Revaclear 500. Methods: We conducted an open-label, prospective, quasi-randomized controlled trial including forty prevalent adult hemodialysis patients from two centers in Israel (Barzilai and Sheba Medical Centers). Patients were sequentially allocated 1:1 to Theranova 500 or Revaclear 500. Demographic, laboratory, and patient-reported outcomes (KDQOL-SF, Dialysis Symptom Index) were assessed at baseline and week 24. Within-group changes were analyzed using paired tests, and between-group differences using ANCOVA adjusted for baseline values. Safety monitoring included adverse events, dialyzer reactions, hospitalizations, and mortality. Results: Theranova 500 significantly increased mean spKt/V (1.24 ± 0.33 to 1.40 ± 0.36; p = 0.025), while Revaclear showed no significant change. CRP remained stable in the Theranova group but rose nearly threefold in the Revaclear group by week 24 (p < 0.001). Albumin, dry weight, anemia and mineral bone parameters remained stable in both groups. Total cholesterol increased modestly in the Theranova arm without nutritional compromise. Symptom-level analysis showed improvement in irritability, restless leg, dry skin, chest pain, and diarrhea with Theranova, whereas global KDQOL-SF domain scores improved similarly in both groups. No non-serious adverse events, hypersensitivity reactions, or dialyzer-related intolerance was observed. Hospitalizations (n = 8 per group) and mortality (two per group) were identical. Conclusions: Over 24 weeks, Theranova 500 MCO dialyzer improved dialysis adequacy and prevented the rise in inflammatory markers seen with Revaclear without compromising nutrition or safety. Targeted improvement in specific uremic symptoms suggests potential clinical benefit beyond small-molecule clearance. These findings support the safety and clinical utility of expanded hemodialysis and highlight the need for larger, fully randomized trials to validate these results. Full article

(This article belongs to the Special Issue Peritoneal Dialysis and Hemodialysis: Early and Late Outcomes)

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13 pages, 436 KB

Open AccessArticle

Ten-Year Outcomes of Patients with Left Main Coronary Artery Disease and Diabetes Mellitus Treated with Percutaneous Coronary Intervention

by Jola Bresha, Gjin Ndrepepa, Constantin Kuna, Thorsten Kessler, Isabella Hintz, Paul Justenhoven, Tareq Ibrahim, Sebastian Kufner, Heribert Schunkert, Marco Valgimigli, Gert Richardt, Karl-Ludwig Laugwitz, Salvatore Cassese, Adnan Kastrati and Jens Wiebe

J. Clin. Med. 2025, 14(24), 8851; https://doi.org/10.3390/jcm14248851 (registering DOI) - 14 Dec 2025

Abstract

Background/Objectives: Long-term outcomes of patients with left main coronary artery (LMCA) disease and diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) are incompletely investigated. The aim of this study was to assess the 10-year clinical outcomes after PCI according to diabetic status and [...] Read more.

Background/Objectives: Long-term outcomes of patients with left main coronary artery (LMCA) disease and diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) are incompletely investigated. The aim of this study was to assess the 10-year clinical outcomes after PCI according to diabetic status and antidiabetic therapy in patients with LMCA. Methods: This study represents a pooled analysis of two randomized trials (n = 1257 patients) on LMCA PCI focused on the prespecified subgroups of diabetic patients. Patients were categorized in groups according to the diabetic status and antidiabetic therapy (oral drugs or insulin therapy). The primary endpoint was 10-year all-cause mortality. Results: Overall, 361 patients had DM (246 patients on oral antidiabetic drugs and 115 patients on insulin therapy) and 896 patients had no DM. At 10 years, 477 patients died: 291 nondiabetic patients (35.7%), 111 diabetic patients (49.5%) on oral antidiabetic drugs and 75 diabetic patients (70.0%) on insulin therapy (hazard ratio [HR] = 1.57, 95% confidence interval [1.26–1.96]; p < 0.001 for diabetic patients on oral antidiabetic drugs vs. nondiabetic patients; HR = 2.80 [2.17–3.61]; p < 0.001 for diabetic patients on insulin therapy vs. nondiabetic patients; HR = 1.78 [1.33–2.39]; p <0.001 for diabetic patients on insulin therapy vs. diabetic patients on oral antidiabetic drugs). The 10-year incidence of myocardial infarction was higher in diabetic patients on insulin therapy (10.0%) versus diabetic patients on oral antidiabetic drugs (3.0%). There were no significant differences between the groups regarding the 10-year incidence of definite stent thrombosis, coronary artery bypass graft surgery, repeat PCI or stroke. Conclusions: In patients with LMCA disease undergoing PCI, DM was associated with a higher 10-year incidence of all-cause mortality than patients without DM with the worst outcomes observed in diabetic patients on insulin therapy. Full article

(This article belongs to the Section Cardiology)

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22 pages, 374 KB

Open AccessReview

Human Factors in Airway Management: Designing Systems for Safer, Team-Based Care

by Manuel Á. Gómez-Ríos, Pavel Michalek, Tomasz Gaszyński and André A. J. Van Zundert

J. Clin. Med. 2025, 14(24), 8850; https://doi.org/10.3390/jcm14248850 (registering DOI) - 14 Dec 2025

Abstract

The increasing complexity of airway management, particularly in high-stakes or emergency settings, demands a holistic approach that accounts not only for technical skill but also for the systems in which clinicians operate. Advances in airway devices such as videolaryngoscopes, videolaryngeal mask airways, flexible [...] Read more.

The increasing complexity of airway management, particularly in high-stakes or emergency settings, demands a holistic approach that accounts not only for technical skill but also for the systems in which clinicians operate. Advances in airway devices such as videolaryngoscopes, videolaryngeal mask airways, flexible intubation scopes, combined techniques, and single-use technologies offer new opportunities for improving outcomes—but also introduce new challenges. This article explores the intersection of human factors and the implementation of new airway devices, using a systems-based lens informed by the SEIPS 3.0 framework. Drawing on recent guidelines, real-world case studies, and design principles, we examine how technological changes affect team dynamics, decision-making, equipment layout, and cognitive load. We also highlight the importance of standardized processes, training, and environmental design in mitigating risk and enhancing performance. Ultimately, we propose actionable strategies to integrate human factors into airway device adoption to improve both patient safety and clinician well-being. This review underscores the fact that embedding human factor principles into the adoption and use of airway technologies is essential to build safer, more resilient, and team-centered airway management systems. Full article

(This article belongs to the Special Issue Airway Management: From Basic Techniques to Innovative Technologies)

19 pages, 1288 KB

Open AccessArticle

Scintigraphic Assessment of Lung Perfusion and Ventilation in Patients After Pneumonectomy

by Karina Witkiewicz, Małgorzata Edyta Wojtyś, Norbert Wójcik, Krzysztof Safranow, Jarosław Pieróg, Jacek Szulc, Tadeusz Sulikowski, Konrad Jarosz, Tomasz Grodzki and Janusz Wójcik

J. Clin. Med. 2025, 14(24), 8849; https://doi.org/10.3390/jcm14248849 (registering DOI) - 14 Dec 2025

Abstract

Background/Objectives: The physiological ventilation–perfusion ratio (V/Q) in the upper pulmonary field is >3 and in the lower pulmonary field it is <1 due to the effect of gravity when the body is in an upright position. Pneumonectomy leads to significant changes in ventilation [...] Read more.

Background/Objectives: The physiological ventilation–perfusion ratio (V/Q) in the upper pulmonary field is >3 and in the lower pulmonary field it is <1 due to the effect of gravity when the body is in an upright position. Pneumonectomy leads to significant changes in ventilation and perfusion conditions. The aim of this study was to evaluate perfusion and ventilation after pneumonectomy complicated by pleural empyema, including the relationship between surgical outcomes, sex, and time from pneumonectomy. Methods: The study group included 30 patients (25 men, 5 women) who underwent pneumonectomy complicated by pleural empyema. Lung function was assessed using ventilation–perfusion scintigraphy. Twenty-one patients were assessed within 5 years after pneumonectomy and nine patients >5 years after pneumonectomy. Results: Average flow was 21.1% in the upper field, 47.8% in the middle field, and 30.35% in the lower field. The mean perfusion value was significantly higher in the lower field of the right lung than in the lower field of the left lung (33.35 vs. 28.05, p = 0.001). Average ventilation was 17.21% in the upper field, 46.73% in the middle field, and 34.28% in the lower field. The mean V/Q in the upper field was in the range of 0.81–0.87, but it reached approximately 1 (0.96–1) in the middle field and exceeded 1 (1.05–1.25) in the lower field. Conclusions: Pneumonectomy led to increased perfusion in the upper pulmonary field and increased ventilation in the lower pulmonary field compared to the literature for patients with the two lungs (the two-lung system), with a reversal of the V/Q between the upper and lower field. Full article

(This article belongs to the Special Issue Innovations in Thoracic Surgery and Disease Management: Integrating Genomics, Technology, and Multidisciplinary Care)

22 pages, 1502 KB

Open AccessSystematic Review

Effectiveness of Pharmacological Treatments for Adult ADHD on Psychiatric Comorbidity: A Systematic Review

by Beniamino Tripodi, Manuel Glauco Carbone, Irene Matarese, Roberta Rizzato, Filippo Della Rocca, Francesco De Dominicis and Camilla Callegari

J. Clin. Med. 2025, 14(24), 8848; https://doi.org/10.3390/jcm14248848 (registering DOI) - 14 Dec 2025

Abstract

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) in adults is frequently accompanied by psychiatric comorbidities that worsen outcomes and complicate treatment. Pharmacological management is central in care, yet its impact on co-occurring disorders remains uncertain. This systematic review evaluated the effectiveness of commonly prescribed medications for [...] Read more.

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) in adults is frequently accompanied by psychiatric comorbidities that worsen outcomes and complicate treatment. Pharmacological management is central in care, yet its impact on co-occurring disorders remains uncertain. This systematic review evaluated the effectiveness of commonly prescribed medications for adult ADHD (methylphenidate, atomoxetine, bupropion, and lisdexamfetamine) on comorbid mood, anxiety, personality, and substance use disorders. Tricyclic antidepressants were also included in the search strategy; however, no eligible adult studies assessing imipramine or desipramine in patients with ADHD and psychiatric comorbidity were identified. Methods: A systematic search of the literature was conducted to identify studies examining these medications in adults with ADHD and at least one psychiatric comorbidity. Eligible studies reported clinical outcomes for both ADHD symptoms and the co-occurring disorder. Data were extracted and narratively synthesized, with particular attention paid to treatment effects and sources of heterogeneity. Results: Across the included studies, pharmacological treatments consistently improved core ADHD symptomatology. Their effects on psychiatric comorbidity were more variable. Some evidence suggested beneficial outcomes for selected anxiety disorder subtypes and for features of Cluster B personality disorders, possibly related to reductions in emotional dysregulation and impulsivity. Findings regarding substance use disorders were mixed: several studies reported reduced craving or substance use, but long-term stabilization was inconsistent. Marked heterogeneity in study design, populations, and outcome measures limited comparability. Conclusions: Current pharmacological treatments for adult ADHD show reliable efficacy for core symptoms but inconsistent benefits across comorbid psychiatric conditions. While targeted improvements may occur in specific domains, the evidence base is insufficient to define optimal long-term strategies for adults with ADHD and complex comorbidity. Rigorous, longitudinal studies are needed to clarify medication effects on distinct comorbid profiles and to inform integrated treatment planning. Full article

(This article belongs to the Special Issue Clinical Management of Attention Deficit Hyperactivity Disorder (ADHD))

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15 pages, 1759 KB

Open AccessArticle

Psychological Pain Measurement in the Context of Suicidal Behavior: Rasch Analysis of the Spanish Psychache Scale Version

by Jorge L. Ordóñez-Carrasco, Claudia Suárez-Yera, María Sánchez-Castelló and Antonio J. Rojas-Tejada

J. Clin. Med. 2025, 14(24), 8847; https://doi.org/10.3390/jcm14248847 (registering DOI) - 14 Dec 2025

Abstract

Background: The Psychache Scale (PS) is the most widely used scale to measure psychological pain due to its ease of application, favorable evidence of predictive validity, and adequate psychometric properties from the CTT (Classical Test Theory) approach. This paper aims to contribute [...] Read more.

Background: The Psychache Scale (PS) is the most widely used scale to measure psychological pain due to its ease of application, favorable evidence of predictive validity, and adequate psychometric properties from the CTT (Classical Test Theory) approach. This paper aims to contribute to the improvement of the Spanish version of the PS by analyzing its psychometric properties using a Rasch model. Methods: Using quota sampling, 905 young adults completed an online questionnaire with the PS. Results: The items and response categories showed an acceptable fit to the model and good performance. The separation index indicated three strata for persons. The item-person map showed that persons were placed lower on the psychological pain continuum than item, and some item pairs presented small difference in their severity. The study of men-women DIF (differential item functioning) showed a slight differential functioning only for item 6. Conclusions: This study provides new evidence that supports the use of the PS to measure psychological pain. Full article

(This article belongs to the Special Issue Psychological Pain and Suicidal Behavior: Clinical Implications)

16 pages, 1966 KB

Open AccessSystematic Review

The Impact of Surgical Approach on Mid-Term Clinical Outcomes Following Hemiarthroplasty for Femoral Neck Fractures: A Systematic Review and Meta-Analysis of Postero-Lateral Versus Direct Lateral Approaches

by Gianmarco Marcello, Francesco Rosario Parisi, Lorenzo Alirio Diaz Balzani, Alessandro Del Monaco, Emanuele Zappalà, Giuseppe Francesco Papalia, Chiara Capperucci, Erika Albo, Augusto Ferrini, Biagio Zampogna and Rocco Papalia

J. Clin. Med. 2025, 14(24), 8846; https://doi.org/10.3390/jcm14248846 (registering DOI) - 14 Dec 2025

Abstract

Background: Femoral neck fractures in the elderly often necessitate hemiarthroplasty, but the optimal surgical approach remains a highly debated topic. The postero-lateral and direct lateral approaches are commonly employed, each with benefits and drawbacks. Despite their widespread use, robust, long-term comparative studies [...] Read more.

Background: Femoral neck fractures in the elderly often necessitate hemiarthroplasty, but the optimal surgical approach remains a highly debated topic. The postero-lateral and direct lateral approaches are commonly employed, each with benefits and drawbacks. Despite their widespread use, robust, long-term comparative studies on definitive outcomes, including pain, functional recovery, and complication rates, are notably lacking. This systematic review and meta-analysis aim to address this critical gap by meticulously comparing these approaches with long-term follow-up. Methods: A systematic literature search was performed, including only comparative studies with a minimum 1-year follow-up. A meta-analysis was performed for the primary outcome measures: operative time, dislocations, infections, perioperative fractures and reoperations. Secondary outcomes included a qualitative synthesis of patient-reported outcomes (quality of life, pain, and satisfaction). Methodological quality was assessed using RoB 2.0 for randomized controlled trials and MINORS criteria for cohort studies. Results: Our meta-analysis provides robust quantitative evidence. The direct lateral approach is associated with a significantly lower risk of post-operative dislocations (I² = 58%; OR = 2.86, 95% CI: 2.53 to 3.22; p < 0.00001) and a significantly lower rate of reoperation (I² = 0%; OR = 1.25, 95% CI: 1.12 to 1.40; p = 0.0001) compared to postero-lateral approach. Operative time, infection, and perioperative fracture rates were found to be statistically comparable. However, patient-reported outcomes yielded inconsistent results across studies, often becoming non-significant after adjusting for confounders. Conclusions: This meta-analysis shows that the direct lateral approach is associated with lower rates of dislocation and reoperation compared with the postero-lateral approach, while patient-reported outcomes remain variable across studies. Further high-quality comparative trials are needed to confirm these associations and guide surgical decision-making. Full article

(This article belongs to the Special Issue Clinical Updates on Knee and Hip Arthroplasty)

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7 pages, 415 KB

Open AccessBrief Report

Intraovarian Platelet-Rich Plasma Therapy for PCOS: Unanswered Questions and Future Research Directions

by Zaher Merhi

J. Clin. Med. 2025, 14(24), 8845; https://doi.org/10.3390/jcm14248845 (registering DOI) - 14 Dec 2025

Abstract

Background: Polycystic ovary syndrome (PCOS)-related infertility remains a major challenge and the efficacy of conventional treatments is limited in certain patient groups and often fails to address the underlying causes of ovarian dysfunction. Platelet-rich plasma (PRP) is rich in growth factors and cytokines [...] Read more.

Background: Polycystic ovary syndrome (PCOS)-related infertility remains a major challenge and the efficacy of conventional treatments is limited in certain patient groups and often fails to address the underlying causes of ovarian dysfunction. Platelet-rich plasma (PRP) is rich in growth factors and cytokines and has emerged as a potential regenerative therapy for women with a diminished ovarian reserve. Methods: A literature search for studies pertaining to intraovarian PRP administration and PCOS was performed on PubMed. Results: Preclinical studies in PCOS animal models have demonstrated that intraovarian PRP can improve folliculogenesis, enhance antioxidant defenses, normalize steroid hormone levels, and downregulate pro-apoptotic pathways. Early clinical reports suggest that intraovarian PRP may restore ovulation and improve ovarian reserve in women with long-standing amenorrhea and poor responses to standard fertility treatments. The proposed mechanisms of how PRP could improve folliculogenesis include the modulation of local ovarian gene expression, the activation of dormant follicles, angiogenesis, and a reduction in oxidative stress and inflammation. Conclusions: Although preliminary data are promising, larger studies are needed to establish the efficacy, if any, of intraovarian PRP administration as a potential novel therapeutic adjunct in women with PCOS. Full article

(This article belongs to the Section Endocrinology & Metabolism)

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15 pages, 1592 KB

Open AccessArticle

Neutrophil-to-Lymphocyte Ratio and Fibroblast Growth Factor 21: Their Role in Early Cardiovascular Involvement in Rheumatoid Arthritis

by Mariusz Ciołkiewicz, Anna Kuryliszyn-Moskal, Ewa Jabłońska, Wioletta Ratajczak-Wrona, Mariusz Wojciuk and Piotr A. Klimiuk

J. Clin. Med. 2025, 14(24), 8844; https://doi.org/10.3390/jcm14248844 (registering DOI) - 14 Dec 2025

Abstract

Introduction: Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality. Left ventricular diastolic dysfunction (LVDD) represents an early sign of cardiac involvement in RA. Objectives: This study aimed to evaluate the incidence of LVDD and the association of the neutrophil-to-lymphocyte ratio [...] Read more.

Introduction: Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality. Left ventricular diastolic dysfunction (LVDD) represents an early sign of cardiac involvement in RA. Objectives: This study aimed to evaluate the incidence of LVDD and the association of the neutrophil-to-lymphocyte ratio (NLR) and circulating FGF21 levels with chosen LVDD echocardiographic parameters, as well as to assess their diagnostic utility for LVDD in a cohort of patients with RA. Patients and Methods: A total of 51 RA patients (46 females, 5 males; average age 48.8 ± 8.2 years; median disease duration of 12 years) were enrolled. NLR and serum FGF21 levels were analysed for association with echocardiographic parameters of LVDD using univariate regression models. The diagnostic performance of these markers was evaluated by receiver operating characteristic (ROC) analysis. Results: LVDD was diagnosed in 10 patients (19.6%). The NLR was associated negatively with E velocity (β = −4.99, p = 0.02), E/A ratio (β = −0.16, p = 0.004), lateral and medial e′ velocities (β = −1.05, p = 0.038 and β = −0.97, p = 0.013, respectively), and positively with left atrial diameter (β = 2.08, p = 0.006). Serum FGF21 levels were negatively associated with the E/A ratio (β = −0.0005, p = 0.009) and lateral e′ velocity (β = −0.003, p = 0.04). ROC analysis demonstrated a greater diagnostic value for NLR (Youden index 0.30, cut-off point 2.26, sensitivity 50%, specificity 80%, and area under curve [AUC] 0.58) compared to FGF21 (Youden index 0.30, cut-off value 852.85 pg/mL, 100% specificity, 30% sensitivity, and AUC 0.48). Conclusions: NLR and FGF21 are associated with the echocardiographic parameters of the left ventricular diastolic dysfunction prior to the fulfilment of LVDD diagnostic criteria. RA patients with elevated NLR and FGF21 serum levels should be considered for LVDD screening. Full article

(This article belongs to the Section Immunology & Rheumatology)

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13 pages, 647 KB

Open AccessArticle

Increased suPAR Plasma Levels May Indicate Postoperative Sepsis Following Open Thoracoabdominal Aortic Repair

by Dragos Socol, Cathryn Bassett, Bernhard Hruschka, Jelle Frankort, Moustafa Elfeky, Katja Heller, Florian Kahles, Berkan Kurt, Christian Uhl, Panagiotis Doukas and Alexander Gombert

J. Clin. Med. 2025, 14(24), 8843; https://doi.org/10.3390/jcm14248843 (registering DOI) - 14 Dec 2025

Abstract

Background/Objectives: Postoperative organ complications following open thoracoabdominal aortic aneurysm (TAAA) repair pose significant challenges during the early postoperative period, where prompt detection is crucial for improving patient outcomes. Sepsis is often a central factor in these complications. This study investigates the perioperative [...] Read more.

Background/Objectives: Postoperative organ complications following open thoracoabdominal aortic aneurysm (TAAA) repair pose significant challenges during the early postoperative period, where prompt detection is crucial for improving patient outcomes. Sepsis is often a central factor in these complications. This study investigates the perioperative dynamics of soluble urokinase plasminogen activator receptor (suPAR) plasma levels in TAAA patients undergoing elective surgical repair and evaluates its diagnostic potential for early detection of postoperative sepsis. Methods: In this retrospective, single-center study, 28 patients (mean age 52.6 ± 13.4 years; 67.9% male) underwent elective open TAAA repair between 2022 and 2024. Blood samples were collected at five perioperative time points, and suPAR levels were measured using ELISA. The primary endpoint was the onset of postoperative sepsis, with secondary endpoints including other organ complications. The predictive performance of suPAR levels was evaluated using Receiver Operator Characteristics (ROC) analysis. Results: Postoperative sepsis developed in 7 of 28 patients (25%), with the diagnostic criteria met at a mean of 9.7 ± 6.9 days. Baseline suPAR levels did not differ between groups; however, from 12 h after surgery, the sepsis group exhibited significantly higher serum concentrations (14.43 ng/mL vs. 7.23 ng/mL; p = 0.004), a difference that persisted throughout the first 24 h. At 24 h, suPAR had the highest predictive accuracy for sepsis, with an AUC of 0.90, 90% sensitivity, and 86% specificity at a 9 ng/mL cut-off (p < 0.001). Conclusions: Elevated suPAR levels in the early postoperative period are strongly associated with the later onset of sepsis. Early monitoring may enable timely intervention, potentially improving outcomes in this high-risk patient population. Full article

(This article belongs to the Section Cardiovascular Medicine)

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26 pages, 5361 KB

Open AccessArticle

Associations Between Screen Time, Sleep, and Executive Function in School-Aged Children and Adolescents: The Moderating Role of Digital Content and Age

by Csongor Toth, Brigitte Osser, Laura Ioana Bondar, Roland Fazakas, Florin Mihai Marcu, Nicoleta Anamaria Pascalau, Ramona Nicoleta Suciu and Bombonica Gabriela Dogaru

J. Clin. Med. 2025, 14(24), 8842; https://doi.org/10.3390/jcm14248842 (registering DOI) - 14 Dec 2025

Abstract

Background and Objectives: Increased and unstructured digital exposure has raised growing concerns about its potential impact on children’s cognitive and behavioral development. Executive functions (EFs)—encompassing attention, working memory, inhibition, and cognitive flexibility—are particularly sensitive to environmental influences during development. Beyond its empirical [...] Read more.

Background and Objectives: Increased and unstructured digital exposure has raised growing concerns about its potential impact on children’s cognitive and behavioral development. Executive functions (EFs)—encompassing attention, working memory, inhibition, and cognitive flexibility—are particularly sensitive to environmental influences during development. Beyond its empirical aim, this study also sought to address a theoretical gap by clarifying how multiple dimensions of digital exposure (quantity, content quality, and sleep-related timing) jointly relate to EF performance, an area insufficiently integrated into current EF frameworks. This study aimed to examine the quantitative and qualitative dimensions of digital exposure in relation to sleep duration and EF performance among Romanian school-aged children and adolescents. Materials and Methods: A cross-sectional study was conducted among 142 students aged 5–19 years, using standardized cognitive tasks and structured parent questionnaires to assess screen time, digital content type, and sleep duration. Analyses included correlational tests, group comparisons, regression models, and moderation procedures. Results: Higher daily screen time was associated with poorer attention and working-memory performance and shorter nocturnal sleep. Children and adolescents who exceeded the recommended daily screen-time limits performed worse on executive-function measures than those within recommended limits. Digital content type and sleep duration each contributed uniquely to executive performance, and recreational digital content as well as younger age intensified the negative effects of screen exposure. Conclusions: Excessive daily screen time, especially involving passive or recreational content, is associated with poorer EF performance and shorter sleep in children. Adequate sleep and educational or interactive digital engagement may mitigate these effects. The findings underscore the importance of age-appropriate, structured, and balanced digital habits to support healthy cognitive development. Full article

(This article belongs to the Special Issue Mind–Body Connection: The Impact of Mental Health on Physical Well-Being)

15 pages, 1628 KB

Open AccessArticle

Retrospective Observational Study on Implant Site Preparation Using Magnetodynamic Surgery vs. Piezoelectric and Traditional Surgery

by Lorenzo Bevilacqua, Luca De Angelis, Lucio Torelli, Antonio Scarano, Gianmarco Gronelli and Michele Maglione

J. Clin. Med. 2025, 14(24), 8841; https://doi.org/10.3390/jcm14248841 (registering DOI) - 14 Dec 2025

Abstract

Objective: This study compared magnetodynamic surgery, traditional drill-based surgery, and piezoelectric surgery for the preparation of the implant site, focusing on operative time and intra/postoperative discomfort. Methods: A total of 86 patients (69.8% female, 30.2% male) treated at the Oral Surgery Clinic, University [...] Read more.

Objective: This study compared magnetodynamic surgery, traditional drill-based surgery, and piezoelectric surgery for the preparation of the implant site, focusing on operative time and intra/postoperative discomfort. Methods: A total of 86 patients (69.8% female, 30.2% male) treated at the Oral Surgery Clinic, University of Trieste, were included: 43 underwent implant placement with the Magnetic Mallet (MM); the remaining 43 received preparations with the Piezodevice (IP) on one side and drills (Ds) on the other. All surgeries were performed by the same operator. Data included bone quality, operative time, and postoperative questionnaire responses for pain (VAS) and analgesic use. A statistical analysis was conducted using Mann–Whitney U and Kruskal–Wallis tests. Results: Significant differences emerged in operative times and pain perception, influenced by bone quality. The MM and D had comparable times in D1–D2 and D3–D4 bone, but the D produced higher VAS scores. The MM vs. IP showed significant differences in absolute times (p = 0.00018) and relative times for both D1–D2 (p = 0.01875) and D3–D4 (p = 0.00584), with qualitative VAS differences. The IP vs. D also showed significant absolute (p = 0.000005) and relative time differences for D1–D2 (p = 0.00718) and D3–D4 (p = 0.000145), with VAS variations. In the MM group, higher bone density significantly prolonged times (p = 0.04136). Conclusions: Within the limits of this study, the traditional drill-based technique remains valid and widely used, but the Magnetic Mallet can offer advantages in terms of patient comfort and postoperative recovery. The Piezodevice, while excelling in tissue preservation, is limited by longer operative times. Full article

(This article belongs to the Special Issue Novel Developments in Dental and Oral Surgery)

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21 pages, 826 KB

Open AccessArticle

Association Between Postoperative Pain Intensity and Delirium in Cardiac and Neurosurgical Patients: A Retrospective Pilot Study

by Mateusz Szczupak, Jacek Kobak, Jakub Wiśniewski, Jolanta Wierzchowska and Sabina Krupa-Nurcek

J. Clin. Med. 2025, 14(24), 8840; https://doi.org/10.3390/jcm14248840 (registering DOI) - 13 Dec 2025

Abstract

Background/Objective: Postoperative pain and delirium are frequent and clinically relevant complications in patients undergoing major cardiac or neurosurgical procedures. The interaction between these conditions remains insufficiently characterized, particularly across heterogeneous surgical populations. This study aimed to investigate the relationship between postoperative pain [...] Read more.

Background/Objective: Postoperative pain and delirium are frequent and clinically relevant complications in patients undergoing major cardiac or neurosurgical procedures. The interaction between these conditions remains insufficiently characterized, particularly across heterogeneous surgical populations. This study aimed to investigate the relationship between postoperative pain intensity and delirium severity within the first 48 h after surgery in cardiac and neurosurgical patients. Methods: This retrospective observational analysis included 408 individuals—202 following cardiac surgery and 206 after neurosurgical procedures. Pain intensity was measured using the Numerical Rating Scale (NRS), while delirium presence and severity were assessed using the CAM-ICU and CAM-ICU-7 instruments. Associations between NRS scores, delirium severity, demographic characteristics, and ICU length of stay were examined. Results: Cardiac surgery patients experienced higher pain levels on postoperative day 1 compared with neurosurgical patients; this difference was not observed on day 2. In the cardiac cohort, higher NRS scores were positively associated with greater delirium severity on both postoperative days. No such association was detected in the neurosurgical group. Pain scores also differed across procedure types within each specialty, and several demographic variables (age, sex, ICU stay duration) were linked with variations in pain intensity. On postoperative day 1, pain intensity showed a moderate association with delirium severity (Spearman ρ = 0.23; 95% CI 0.14–0.32). Patients who developed delirium had higher pain scores (r = 0.25). In ordinal logistic regression, greater pain on postoperative day 1 independently predicted higher delirium severity (OR 2.24; 95% CI 1.70–2.94). Conclusions: Significant associations between postoperative pain intensity and delirium severity were identified in cardiac surgery patients, whereas no similar pattern emerged among neurosurgical patients. Given the retrospective design and incomplete data on perioperative pharmacotherapy, the findings should be interpreted descriptively and do not support causal conclusions. These results underscore the importance of systematic monitoring of pain and cognitive function in high-risk postoperative populations and highlight the need for prospective studies to elucidate the complex interplay between pain, perioperative factors, and postoperative delirium. Full article

(This article belongs to the Special Issue Clinical Management and Long-Term Prognosis in Intensive Care)

11 pages, 657 KB

Open AccessCase Report

Malignant Syphilis in an Immunocompetent Patient: A Case Report and Review of the Literature

by Chiara Vincenza Mazzola, Eleonora Bono, Ilenia Giacchino, Cinzia Calà, Luca Pipitò and Antonio Cascio

J. Clin. Med. 2025, 14(24), 8839; https://doi.org/10.3390/jcm14248839 (registering DOI) - 13 Dec 2025

Abstract

Background: Syphilis can present with diverse clinical manifestations, earning the name “great imitator.” Malignant syphilis (MS) is a rare, severe form of secondary syphilis, typically reported in immunocompromised patients, particularly those living with HIV. However, MS can occasionally occur in immunocompetent individuals, [...] Read more.

Background: Syphilis can present with diverse clinical manifestations, earning the name “great imitator.” Malignant syphilis (MS) is a rare, severe form of secondary syphilis, typically reported in immunocompromised patients, particularly those living with HIV. However, MS can occasionally occur in immunocompetent individuals, posing diagnostic challenges due to its atypical presentation. Methods: A case report is presented alongside a PubMed literature search using the terms “(malignant syphilis OR lues maligna) AND (immunocompetent) AND (case report OR case series).” No language or temporal restrictions were applied, yielding 18 relevant publications. Results: A 60-year-old HIV-negative man presented with fever, weight loss, papular lesions, and a single ulcer on the sternum. Serology was positive for syphilis, and PCR confirmed T. pallidum DNA in the lesion. Treatment with a single intramuscular dose of benzathine penicillin G led to prompt clinical and serological improvement. Literature review (n = 18) showed that MS in immunocompetent patients affects both sexes (55% male; mean age 37.1 years), often presents with ulceronodular or rupioid crusted lesions, and frequently involves systemic symptoms. Molecular diagnostics were rarely reported, with most diagnoses relying on histopathology and serology. Treatment with benzathine penicillin G was effective in all cases, and full recovery was achieved. Conclusions: MS can occur in immunocompetent, HIV-negative individuals without obvious risk factors. Clinicians should maintain a high index of suspicion in cases of systemic, cutaneous, or ocular manifestations suggestive of MS. Molecular assays can facilitate diagnosis and prevent unnecessary invasive procedures. Benzathine penicillin G remains the treatment of choice, demonstrating high therapeutic effectiveness. MS should be considered in the differential diagnosis of ulcerative or nodular dermatoses, regardless of immune status. Full article

(This article belongs to the Special Issue Sexually Transmitted Infections as a Challenge of Modern Society: Old Problems and Modern Solutions)

11 pages, 225 KB

Open AccessArticle

Long-Term Safety and Efficacy of Partially Absorbable Transobturator Mid-Urethral Sling in Women Aged 65 Years and Older

by Réka Fábián-Kovács, Asnat Groutz, Jonatan Neuman, Menahem Neuman, Yoav Baruch and Ronen S. Gold

J. Clin. Med. 2025, 14(24), 8838; https://doi.org/10.3390/jcm14248838 (registering DOI) - 13 Dec 2025

Abstract

Objectives: To assess the long-term safety and efficacy of the Serasis^® partially absorbable transobturator mid-urethral sling (MUS) in women aged ≥65 years compared to younger women. Methods: A retrospective comparative study of 375 consecutive women who underwent Serasis^® MUS for stress [...] Read more.

Objectives: To assess the long-term safety and efficacy of the Serasis^® partially absorbable transobturator mid-urethral sling (MUS) in women aged ≥65 years compared to younger women. Methods: A retrospective comparative study of 375 consecutive women who underwent Serasis^® MUS for stress urinary incontinence (SUI). Patients were stratified into two age groups: 45–64 years (N = 118) and ≥65 years (N = 257), with further subdivision of the elderly cohort into 65–74 years (N = 208) and 75–84 years (N = 49). Primary outcomes included perioperative safety and long-term subjective cure rates, assessed via standardized telephone survey at a mean follow-up of 8.5 years (range, 6.8–10.9 years). Results: Perioperative outcomes were comparable across age groups. At 4 months postoperatively, subjective cure was achieved in 82.9% of elderly and 86.4% of younger patients. Long-term subjective cure rates were 79.6% and 85.4%, respectively (p = 0.27). Elderly patients experienced higher rates of postoperative voiding dysfunction and persistent overactive bladder symptoms, though subjective satisfaction remained high. Long-term mesh-related complications were infrequent across age groups. Specifically, vaginal mesh erosion requiring surgical removal occurred in three elderly patients (1.6%) and in only one younger patient (1.1%). A multivariate logistic regression analysis identified preoperative mixed urinary incontinence, BMI >30 kg/m² and concomitant pelvic organ prolapse repair as independent predictors of surgical failure. Age ≥65 years was not an independent predictor of surgical failure (OR 1.3, 95% CI 0.8–2.1, p = 0.31). Conclusions: The use of a partially absorbable MUS in elderly women with SUI is a safe and effective surgical approach, associated with a significant reduction in long-term mesh-related complications. Full article

(This article belongs to the Section Obstetrics & Gynecology)

16 pages, 346 KB

Open AccessReview

Exposure-Based Intervention in Virtual Reality to Address Kinesiophobia in Parkinson’s Disease: A Narrative Review

by Alice Jeanningros, Stéphane Bouchard and Alexandra Potvin-Desrochers

J. Clin. Med. 2025, 14(24), 8837; https://doi.org/10.3390/jcm14248837 (registering DOI) - 13 Dec 2025

Abstract

Background/Objectives: Physical activity alleviates symptoms and may slow Parkinson’s disease (PD) progression, yet many individuals with PD remain sedentary. Kinesiophobia, the fear of movement, may represent a significant but underexplored psychological barrier to physical activity in this population. Virtual reality (VR), already [...] Read more.

Background/Objectives: Physical activity alleviates symptoms and may slow Parkinson’s disease (PD) progression, yet many individuals with PD remain sedentary. Kinesiophobia, the fear of movement, may represent a significant but underexplored psychological barrier to physical activity in this population. Virtual reality (VR), already effective in phobias, may represent a promising approach to address this challenge. This review initially aimed to systematically examine exposure-based interventions in VR (E-IVR) directly targeting kinesiophobia in PD. Methods: Database searches using keywords such as “kinesiophobia,” “fear of movement,” and “VR” combined with “PD” yielded no eligible studies. Consequently, the scope was broadened to include populations with neurological or musculoskeletal conditions, and a narrative review format was adopted to synthesize the available evidence. Furthermore, relevant studies of interventions in VR applied in PD, although not specifically addressing kinesiophobia, are detailed to provide evidence of efficacy and feasibility of VR interventions in PD. Finally, directions are offered to support the creation of E-IVR targeting kinesiophobia in individuals with PD. Results: Meta-analyses in neurological and musculoskeletal populations demonstrate moderate to large reductions in kinesiophobia following VR interventions, although effects vary depending on assessment tools, degree of immersion, and exposure design. In PD, VR has been applied to rehabilitation, anxiety reduction, and quality of life enhancement. These interventions achieved high adherence (≥90%), were well tolerated, and reported no major adverse events. Conclusions: Kinesiophobia is prevalent in PD and could contribute to physical inactivity. E-IVR appears feasible, safe, and innovative for addressing kinesiophobia in people living with PD. Full article

(This article belongs to the Section Clinical Neurology)

15 pages, 1225 KB

Open AccessArticle

Three Decades of Spinal Cord Injury in Saudi Arabia: Trends in Incidence, Prevalence, and Disability Outcomes

by Ahmad F. Alahmary, Mishal M. Aldaihan, Vishal Vennu and Saad M. Bindawas

J. Clin. Med. 2025, 14(24), 8836; https://doi.org/10.3390/jcm14248836 (registering DOI) - 13 Dec 2025

Abstract

Background/Objective: Spinal cord injury (SCI) is a life-altering condition representing a major cause of long-term disability and substantial health burden worldwide. In the Middle East, including Saudi Arabia, rapid urbanization and evolving injury patterns may have influenced SCI trends; however, national data remain [...] Read more.

Background/Objective: Spinal cord injury (SCI) is a life-altering condition representing a major cause of long-term disability and substantial health burden worldwide. In the Middle East, including Saudi Arabia, rapid urbanization and evolving injury patterns may have influenced SCI trends; however, national data remain limited. This study aimed to examine age-standardized trends in SCI incidence, prevalence, and years lived with disability (YLDs) in Saudi Arabia from 1990 to 2021, comparing transport-related and non-transport unintentional injuries, and describing age- and sex-specific SCI patterns in 2021. Methods: Using data from the Global Burden of Diseases (GBD) 2021 study, we conducted a population-based trend analysis for Saudi Arabia from 1990 to 2021, stratified by age, sex, and injury cause. Outcomes included age-standardized incidence, prevalence, and YLD rates per 100,000 population, along with percentage changes, average annual percentage changes, and rate ratios with 95% uncertainty intervals (UIs). Results: Between 1990 and 2021, age-standardized SCI showed a point estimate increase in incidence (25.0%; 95% UI: −28.3 to 116.8) and prevalence (24.3%; 95% UI: 0.8 to 53.4), while YLDs showed a modest rise (1.4%; 95% UI: −44.5 to 83.9). Males experienced greater increases in incidence (31.9%) and prevalence (32.3%) than females. Non-transport unintentional injuries surpassed transport-related causes, accounting for nearly 75% of SCI-related YLDs in 2021. The highest burden occurred among young adult males (highest incidence) and older adults (peak prevalence). Conclusion: The burden of SCI in Saudi Arabia has increased over the past three decades, with a shift toward non-transport unintentional injuries. Because wide uncertainty intervals limit definitive conclusions on trend direction, strengthening injury prevention, rehabilitation, and surveillance programs is crucial to mitigate this growing burden. Full article

(This article belongs to the Special Issue State of the Art in Spinal Cord Injuries: Clinical Rehabilitation and Management)

15 pages, 3379 KB

Open AccessReview

The Role of Endoscopic Sinus Surgery in Children with Cystic Fibrosis

by Francesca Galluzzi, Werner Garavello, Gianluca Dalfino, Francesca De Bernardi, Paolo Castelnuovo and Mario Turri-Zanoni

J. Clin. Med. 2025, 14(24), 8835; https://doi.org/10.3390/jcm14248835 (registering DOI) - 13 Dec 2025

Abstract

Objectives: The aim of this study was to assess the role of functional endoscopic sinus surgery (FESS) in the treatment of chronic rhinosinusitis (CRS) in children with cystic fibrosis (CF). Methods: We performed a comprehensive review of the literature by searching PubMed/MEDLINE. Results: [...] Read more.

Objectives: The aim of this study was to assess the role of functional endoscopic sinus surgery (FESS) in the treatment of chronic rhinosinusitis (CRS) in children with cystic fibrosis (CF). Methods: We performed a comprehensive review of the literature by searching PubMed/MEDLINE. Results: CRS affects most children with CF. Though subjective symptoms are variable, radiological and endoscopic examination demonstrated typical objective findings. FESS is recommended for children with significant nasal symptoms that do not respond to medical treatment. At present, there are no uniform criteria for timing and extension of surgery. Primary surgery includes nasal polypectomy and correction of any bone anatomical variants that reduce ventilation of paranasal sinuses predisposing to recurrent sinusitis and complications. In case of recurrences, revision surgery supports a more expanded surgical approach. Moreover, FESS can relieve symptoms, improve patients’ quality of life, manage complications, ameliorate the delivery of medical therapy, and reduce sinonasal and lung superinfections. Conclusions: FESS has emerged as a safe and effective procedure for the treatment of CRS in children with CF. Since children with CF and CRS are difficult-to-treat patients, a multidisciplinary approach in tertiary-care referral centers is required. Full article

(This article belongs to the Section Otolaryngology)

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