Journal of Clinical Medicine

2 pages, 124 KiB

Open AccessReply

Reply to Trudzinski et al. Comment on “Akil et al. Nonintubated versus Intubated Lung Volume Reduction Surgery in Patients with End-Stage Lung Emphysema and Hypercapnia. J. Clin. Med. 2023, 12, 3750”

by Ali Akil, Stephanie Rehers, Stephan Ziegeler, Erik Ernst, Jan Haselmann, Nicolas Johannes Dickgreber and Stefan Fischer

J. Clin. Med. 2025, 14(12), 4161; https://doi.org/10.3390/jcm14124161 (registering DOI) - 12 Jun 2025

Abstract

In response to the comment letter by Trudzinski et al. [...] Full article

(This article belongs to the Section Emergency Medicine)

11 pages, 505 KiB

Open AccessArticle

MRI-Based Prediction of Meniscal Tear Repairability Demonstrates Limited Accuracy and Reliability

by Christopher T. Holland, Shannon Tse, Cyrus P. Bateni, Dillon Chen and Cassandra A. Lee

J. Clin. Med. 2025, 14(12), 4160; https://doi.org/10.3390/jcm14124160 - 11 Jun 2025

Abstract

Background: While magnetic resonance imaging (MRI) is commonly used to identify meniscal tears, intraoperative assessment typically dictates repairability. This study evaluated whether a simplified MRI-based scoring system could reliably predict meniscal repair versus meniscectomy. Methods: Patients who underwent meniscectomy or meniscal repair between [...] Read more.

Background: While magnetic resonance imaging (MRI) is commonly used to identify meniscal tears, intraoperative assessment typically dictates repairability. This study evaluated whether a simplified MRI-based scoring system could reliably predict meniscal repair versus meniscectomy. Methods: Patients who underwent meniscectomy or meniscal repair between 2010 and 2018 were retrospectively identified. Preoperative MRIs were independently reviewed in a blinded fashion by two radiologists and one orthopedic sports surgeon. Reviewers scored images based on four arthroscopic criteria for tear repairability, with one point awarded for each of the following criteria—(1) proximity within 4 mm of the meniscosynovial junction, (2) length >10 mm, (3) presence of intact inner meniscal segment, and (4) >50% meniscal thickness. Tears scoring four points were considered repairable. Accuracy, sensitivity, and positive and negative predictive values were calculated against the actual procedure performed. Inter- and intraobserver reliability were evaluated using kappa statistics. The predictive performance of each individual criterion was also analyzed. Results: A total of 202 meniscal tears were included (134 meniscectomies and 68 repairs). Reviewer accuracy in predicting repairability ranged from 48% to 76%. Intraobserver reliability was moderate to substantial (κ = 0.42–0.66), whereas interobserver reliability was poor to moderate (pairwise κ = 0.07–0.43; Fleiss’ κ = 0.11). Analysis of individual MRI criteria demonstrated limited predictive value, with most criteria achieving less than 50% accuracy across reviewers. Conclusions: MRI-based prediction of meniscal repairability using arthroscopic criteria demonstrated limited accuracy and poor interobserver reliability. Overall predictive reliability remains insufficient for clinical decision-making. Further investigation, integrating advanced imaging techniques and artificial intelligence, may improve the preoperative assessment of meniscal repairability. Full article

(This article belongs to the Section Sports Medicine)

11 pages, 765 KiB

Open AccessArticle

Thoracic Ultrasound for Acute Dyspnea in Interstitial Lung Disease

by Betsega A. Bayeh, Sylvain Marchand-Adam, Sylvie Legué, David Luque Paz, Laurent Plantier and Thomas Flament

J. Clin. Med. 2025, 14(12), 4159; https://doi.org/10.3390/jcm14124159 - 11 Jun 2025

Abstract

Background: Lung ultrasound (LUS) can be used at follow-up for patients with stable interstitial lung disease (ILD). LUS could also help guide the diagnosis of etiology for acute respiratory episodes. Methods: We conducted a prospective, one-center, observational study including patients with ILD hospitalized [...] Read more.

Background: Lung ultrasound (LUS) can be used at follow-up for patients with stable interstitial lung disease (ILD). LUS could also help guide the diagnosis of etiology for acute respiratory episodes. Methods: We conducted a prospective, one-center, observational study including patients with ILD hospitalized in the pulmonology unit or in the intensive care unit of the Tours University Hospital for acute dyspnea. LUS was performed at admission and then at a follow-up visit in the six months following discharge. We compared the number of B-lines between the two LUSs. We also compared the features of the first LUS between the different etiologies responsible for increased dyspnea. Results: Of 24 patients, 16 had acute ILD exacerbation (67%), 6 had pulmonary infections (25%) and 2 had acute heart failure (8%). LUS was feasible in all patients and always showed lung sliding, pleural irregularities and B-lines. There were pleural effusions in four cases (17%) and pulmonary consolidations in two cases (8%). Seven patients had A-lines in at least one thoracic space on the initial LUS. We found a significant decrease in the number of B-lines at follow-up (76; IQR, [59–86.75]) compared to admission (86.5; IQR, [71.5–94.5]) (p-value = 0.02). There was a trend of more A-lines in patients with infection (1 [0.25–1.75]) compared to AE-ILD (0 [0–0]). Conclusions: Following an episode of acute dyspnea in patients with ILD, LUS shows a decrease in the number of B-lines. Patients with ILD and concurrent pulmonary infection may have more A-lines than patients with AE-ILD. Full article

(This article belongs to the Section Respiratory Medicine)

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13 pages, 952 KiB

Open AccessFeature PaperArticle

Impact of Polyvascular Disease on Long-Term Prognosis of Patients with Acute Coronary Syndrome—A Retrospective Cohort Study in Italy

by Gian Francesco Mureddu, Stefano Rosato, Paola D’Errigo, Pompilio Faggiano, Paola Ciccarelli, Gabriella Badoni, Marco Ambrosetti, Francesco Fattirolli and Giovanni Baglio

J. Clin. Med. 2025, 14(12), 4158; https://doi.org/10.3390/jcm14124158 (registering DOI) - 11 Jun 2025

Abstract

Background: Atherothrombosis is a systemic disease that may affect one or more than one vascular bed. Data on the impact of polyvascular disease (PVD) on the long-term prognosis of patients with coronary artery disease (CAD) are still scarce. Aim: To assess the [...] Read more.

Background: Atherothrombosis is a systemic disease that may affect one or more than one vascular bed. Data on the impact of polyvascular disease (PVD) on the long-term prognosis of patients with coronary artery disease (CAD) are still scarce. Aim: To assess the prevalence of symptomatic PVD in a cohort of patients with a new episode of acute coronary syndrome (ACS) and to investigate the impact of multiple vascular beds involvement on long-term outcomes. Methods: We analysed a nationwide, comprehensive administrative database of consecutive patients aged ≥ 40 years admitted for a new episode of ACS in Italy in 2017–2018. Patients with ACS were stratified according to the presence of peripheral artery disease (PAD) only; cerebrovascular disease (CeVD) only; PAD+CeVD; or neither (no PAD/noCeVD, i.e., ACS only). A multivariate Cox proportional hazards model was used to assess the impact of PAD only; CeVD only and PAD+CeVD on 5-year MACCE. Results: A total of 342,052 patients hospitalised with ACS were identified. Among them, 24,727 (7.2%) were patients with PAD only, 16,887 (4.9%) with CeVD only, and 5810 (1.7%) with PAD+CeVD. After adjusting for age, sex, and comorbidities, the hazard ratio (HR) for 5-year MACCE was 1.37 (95% CI: 1.35–1.40), 1.36 (95% CI: 1.33–1.39), and 1.45 (95% CI: 1.40–1.50) in patients with PAD only, CeVD only, and PAD+CeVD, respectively, compared with patients with ACS only. Conclusions: In patients with ACS, the involvement of a second vascular bed increases the risk of long-term outcomes; the simultaneous involvement of three vascular beds further increases the risk of long-term outcomes. Full article

(This article belongs to the Section Cardiology)

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18 pages, 9264 KiB

Open AccessReview

Laser Prophylaxis for Dry Age-Related Macular Degeneration: Current Evidence

by Jeffrey K. Luttrull, Stephen H. Sinclair and Igor Kozak

J. Clin. Med. 2025, 14(12), 4157; https://doi.org/10.3390/jcm14124157 - 11 Jun 2025

Abstract

Purpose: To review the role of prophylactic panmacular laser treatment for age-related macular degeneration (AMD). Method: A narrative review of studies employing laser treatment for non-exudative (“dry”) AMD listed in the PubMed database. Results: In multiple published studies, macular laser treatment that causes [...] Read more.

Purpose: To review the role of prophylactic panmacular laser treatment for age-related macular degeneration (AMD). Method: A narrative review of studies employing laser treatment for non-exudative (“dry”) AMD listed in the PubMed database. Results: In multiple published studies, macular laser treatment that causes laser-induced retinal damage (LIRD) has shown either no overall benefit or has accelerated disease progression and vision loss in eyes with dry AMD, particularly in high-risk eyes with more severe pre-treatment disease. Conversely, other studies, including randomized and matched propensity-scored real-world-data (RWD) clinical studies, indicate that avoidance of LIRD may allow laser to be used safely and effectively to prevent vision loss from AMD by slowing disease progression and preventing neovascular conversion without adverse treatment effects, benefiting the highest-risk eyes most. Conclusions: AMD is the leading cause of irreversible vision loss worldwide. Current evidence suggests that laser prophylaxis for dry AMD may hold great promise in preventing age-related vision loss. More studies, especially prospective clinical trials, from more investigators, are needed. If current evidence is confirmed, laser prophylaxis would rise to a preeminent position as the safest, most effective, and most economical and accessible approach to reducing vision loss from AMD. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration: 2nd Edition)

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11 pages, 932 KiB

Open AccessArticle

Analysis of Forward Trunk Bending in Women with Chronic Low Back Pain Undergoing Functional Training

by Aleksandra Adamik, Piotr Krężałek and Edyta Mikołajczyk

J. Clin. Med. 2025, 14(12), 4156; https://doi.org/10.3390/jcm14124156 - 11 Jun 2025

Abstract

Background/Objectives: This paper analyzes the movement and relationships within the lumbopelvic–hip complex during forward trunk bending in young women with chronic low back pain. Methods: This study involved 24 women aged 20–24 with chronic low back pain. They were randomly divided into [...] Read more.

Background/Objectives: This paper analyzes the movement and relationships within the lumbopelvic–hip complex during forward trunk bending in young women with chronic low back pain. Methods: This study involved 24 women aged 20–24 with chronic low back pain. They were randomly divided into two equal-sized groups: Group 1 participated in a 12-week functional training program, and Group 2 was a control without any intervention. The level of perceived pain was assessed using the Visual Analog Scale (VAS). Qualitative motion analysis was performed using the BTS SMART-D system. Custom indicators were developed to evaluate the angular relationships and ranges of motion in the lumbar spine and the lumbopelvic–hip complex. The functional training program consisted of three sections: motor control and stabilization, muscle strengthening, and stretching exercises. Statistical analysis was performed using Statistica 13.3. Results: The therapy resulted in a reduction in perceived pain levels reported by the participants. There was a significant improvement in the quality of the forward trunk bending pattern in women who underwent functional training. Conclusions: Significant modifications in the quality, technique, and angular relationships within the lumbopelvic–hip complex were observed during the forward trunk bending pattern in women undergoing functional training. It has proven to be an effective form of therapy for chronic low back pain. Full article

(This article belongs to the Section Sports Medicine)

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14 pages, 993 KiB

Open AccessArticle

Early Outcomes of the PhysioFlex Semi-Rigid Open Annuloplasty Ring: A Minimally Invasive Mitral Valve Repair Cohort Analysis

by Martina Dini, Serdar Akansel, Kristin Wilkens, Emilija Miskinyte, Stephan Jacobs, Volkmar Falk, Jörg Kempfert and Markus Kofler

J. Clin. Med. 2025, 14(12), 4155; https://doi.org/10.3390/jcm14124155 - 11 Jun 2025

Abstract

Objectives: New generations of annuloplasty rings are designed to combine structural support with enhanced flexibility, allowing for better adaptation to the dynamic nature of the mitral annulus. This study investigated the early clinical and echocardiographic outcomes of minimally invasive mitral valve repair [...] Read more.

Objectives: New generations of annuloplasty rings are designed to combine structural support with enhanced flexibility, allowing for better adaptation to the dynamic nature of the mitral annulus. This study investigated the early clinical and echocardiographic outcomes of minimally invasive mitral valve repair (MI-MVr) with a new semi-rigid open ring (PhysioFlex, annuloplasty ring, Edwards Lifesciences, Irvine, CA, USA). Methods: A total of 150 consecutive patients who underwent MI-MVr for severe degenerative mitral regurgitation (DMR) using the PhysioFlex annuloplasty ring between June 2021 and April 2024 were included in the study. Preoperative, intraoperative, and postoperative data were collected for the entire population. A three-dimensional mitral valve reconstruction analysis was performed across the entire cohort using a semi-automated software package (4D Mitral Valve Analysis; Tomtec Imaging Systems, Munich, Germany). Results: The median age was 59 (50–67) years and 25.3% patients were female. The median Euroscore II and left ventricular ejection fraction were 0.72 (0.56–0.99) and 60% (55–65), respectively. The median implanted ring size was 34 mm (32–36). The entire cohort was discharged with no residual mitral regurgitation greater than mild and a median mean transmitral pressure gradient of 2.4 mmHg (2–3). The median hospitalization time was 7 days (6–11) and in-hospital mortality occurred in 1 (0.7%) patient. Conclusions: MI-MVr was safely performed using the novel semi-rigid partial PhysioFlex ring in the DMR patient cohort with favorable early results. The PhysioFlex annuloplasty ring may be used as an alternative to complete rings in MI-MVr. Further research is needed to conduct comparisons with other currently available annuloplasty rings. Full article

(This article belongs to the Special Issue Clinical Advances in Cardiovascular Interventions)

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12 pages, 589 KiB

Open AccessArticle

Non-Anemic Iron Deficiency Predicts COPD Exacerbations and Hospitalizations: Results from a Prospective Cohort

by Carlos A. Amado, Cristina Ghadban, Juan Agüero, Bernardo A. Lavín, Paula Martín-Audera, Armando R. Guerra, Ana Berja, Nieves Aranda, Anastasia Guzun, Ana Isabel Insua and Mayte García-Unzueta

J. Clin. Med. 2025, 14(12), 4154; https://doi.org/10.3390/jcm14124154 - 11 Jun 2025

Abstract

Background: Non-anemic iron deficiency (NAID) has been increasingly recognized as a potential factor affecting chronic obstructive pulmonary disease (COPD) outcomes. However, its prognostic role in COPD exacerbations and hospitalizations remains poorly understood. This study aimed to evaluate the prevalence of NAID in COPD [...] Read more.

Background: Non-anemic iron deficiency (NAID) has been increasingly recognized as a potential factor affecting chronic obstructive pulmonary disease (COPD) outcomes. However, its prognostic role in COPD exacerbations and hospitalizations remains poorly understood. This study aimed to evaluate the prevalence of NAID in COPD patients, its impact on functional parameters, and its predictive value for exacerbations and hospitalizations. Methods: This prospective observational study included 238 patients with stable COPD and 60 age- and sex-matched smokers without COPD as a control group. NAID was defined as serum ferritin < 100 ng/mL or serum ferritin between 100 and 299 ng/mL with transferrin saturation < 20%. Clinical assessments included pulmonary function tests, 6 min walk distance (6MWD), handgrip strength, and fat-free mass index (FFMI). Patients were followed for 12 months to record moderate and severe COPD exacerbations. Cox regression analysis was used to determine the predictive value of NAID for exacerbations and hospitalizations. Results: NAID was present in 68.9% of COPD patients compared to 46.7% of smokers without COPD (p = 0.001). COPD patients with NAID had lower 6MWD (430 (330–500) m vs. 462 (390–510) m, p = 0.029), reduced FFMI (17.9 (15.5–20.2) kg/m² vs. 20.6 (17.6–22.6) kg/m², p < 0.001), and weaker handgrip strength (26 (22–33) kg vs. 34 (27–40) kg, p < 0.001) compared to non-NAID COPD patients. During the 12-month follow-up period, 140 patients developed moderate COPD exacerbations (107 in the NAID group), and 43 patients were hospitalized due to severe exacerbations (36 in the NAID group). Cox regression analysis showed that NAID was an independent predictor of moderate COPD exacerbations (HR 1.846, 95% CI 1.249–2.729, p = 0.002) and hospitalization (HR 2.537, 95% CI 1.129–5.703, p = 0.024) after adjusting for age, sex, lung function, and comorbidities. Conclusions: NAID is highly prevalent in COPD and is associated with worse exercise capacity, lower muscle mass, and increased exacerbation risk independently of sex and age. These findings suggest that NAID could be a valuable biomarker for risk stratification in COPD patients, warranting further research on potential therapeutic interventions targeting iron metabolism. Full article

(This article belongs to the Special Issue Clinical Advances in Chronic Obstructive Pulmonary Disease and Its Complications: Part II)

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12 pages, 371 KiB

Open AccessEditorial

AI in Medical Imaging and Image Processing

by Karolina Nurzynska, Michał Strzelecki, Adam Piórkowski and Rafał Obuchowicz

J. Clin. Med. 2025, 14(12), 4153; https://doi.org/10.3390/jcm14124153 - 11 Jun 2025

Abstract

Artificial intelligence methods have evolved sufficiently to be widely applied in automatic data analysis, providing standardized and reproducible results comparable to those of highly skilled specialists, while assisting less experienced personnel [...] Full article

(This article belongs to the Topic AI in Medical Imaging and Image Processing)

18 pages, 469 KiB

Open AccessReview

CA125 as a Potential Biomarker in Non-Malignant Serous Effusions: Diagnostic and Prognostic Considerations

by Lavinia Alice Bălăceanu, Cristiana Grigore, Ion Dina, Cristian-Dorin Gurău, Mara Mădălina Mihai and Beatrice Bălăceanu-Gurău

J. Clin. Med. 2025, 14(12), 4152; https://doi.org/10.3390/jcm14124152 - 11 Jun 2025

Abstract

Background/Objectives: Carbohydrate antigen 125 (CA125) is a glycoprotein commonly overexpressed in epithelial ovarian cancer and widely recognized as a tumor marker. However, elevated CA125 levels are also observed in various non-malignant conditions, including diseases affecting mucosal surfaces, pleural or peritoneal effusions, cirrhosis (with [...] Read more.

Background/Objectives: Carbohydrate antigen 125 (CA125) is a glycoprotein commonly overexpressed in epithelial ovarian cancer and widely recognized as a tumor marker. However, elevated CA125 levels are also observed in various non-malignant conditions, including diseases affecting mucosal surfaces, pleural or peritoneal effusions, cirrhosis (with or without ascites), endometriosis, uterine fibroids, adenomyosis, pelvic inflammatory disease, and pregnancy. This review aims to explore the role of CA125 in non-malignant serous effusions, highlighting its diagnostic and prognostic potential beyond the realm of oncology. Methods: A comprehensive literature search was conducted across multiple databases and clinical trial registries. Eligible studies included full-text original research articles, reviews, and case reports published in English over the past 10 years. Inclusion criteria were limited to studies involving human subjects and focused on the role of CA125 in non-malignant serous effusions. Results: CA125 is produced by coelomic epithelial cells lining the ovary, pleura, pericardium, and peritoneum. Its serum concentration is not significantly influenced by age, body weight, or renal function, even in the advanced stages of the disease. In peritoneal conditions, CA125 is synthesized by mesothelial cells and serves as a potential marker of peritoneal involvement. The prevailing pathophysiological mechanism suggests that mechanical stretching of mesothelial cells due to ascitic pressure stimulates CA125 release. Similarly, in heart failure, mesothelial cells of the pericardium produce CA125, which correlates with congestion severity, supports risk stratification, and may inform diuretic therapy. Conclusions: While a threshold of 35 U/mL is established for malignancy, no standardized cutoff exists for CA125 in non-malignant conditions. The utility of CA125 measurement in peritoneal, pleural, or pericardial effusions—and cardiovascular diseases such as acute heart failure—for purposes of differential diagnosis, treatment guidance, or prognostication warrants further investigation through prospective clinical trials. Full article

(This article belongs to the Section Oncology)

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11 pages, 312 KiB

Open AccessArticle

The Efficacy of Intradetrusor Onabotulinumtoxin A Injection for Refractory Overactive Bladder Syndrome—A Single-Center Prospective Study

by Chie Nakai, Kosei Miwa, Yasuhide Kitagawa, Moemi Kikuchi, Sanae Namiki, Mina Kikuchi, Kota Kawase, Koji Iinuma, Yuki Tobisawa, Keita Nakane and Takuya Koie

J. Clin. Med. 2025, 14(12), 4151; https://doi.org/10.3390/jcm14124151 - 11 Jun 2025

Abstract

Background/Objectives: Intradetrusor botulinum toxin injection is a well-established third-line therapy for patients with refractory overactive bladder (OAB) and detrusor overactivity (DO). Botulinum toxin type A (BoNT-A) is most commonly used due to its prolonged therapeutic duration. We aimed to evaluate the effectiveness of [...] Read more.

Background/Objectives: Intradetrusor botulinum toxin injection is a well-established third-line therapy for patients with refractory overactive bladder (OAB) and detrusor overactivity (DO). Botulinum toxin type A (BoNT-A) is most commonly used due to its prolonged therapeutic duration. We aimed to evaluate the effectiveness of intradetrusor BoNT-A injection therapy in managing refractory OAB by performing a urodynamic study (UDS). Methods: The patients were prospectively enrolled between February 2020 and March 2021. The patients received treatment regimens comprising behavioral modification therapy, pelvic floor muscle physiotherapy, and/or OAB medications for at least three months. The UDS procedure was carried out by a single examiner, in accordance with the International Continence Society standards for good urodynamic practice. A total of 100 units of BoNT-A was dissolved in 10 mL of saline, and 0.5 mL (5 units) was injected at 20 sites on the posterior wall of the bladder. The primary endpoint was the change in DO, which was measured using the UDS from the baseline to two months after treatment with BoNT-A. Results: Prior to treatment initiation, DO was observed in all the patients during the UDS. The occurrence of DO during the filling phase demonstrated a significant decrease following treatment, with DO no longer identified in 27.3% of the patients. The first sensation of bladder filling, maximum cystometric capacity, DO, and terminal DO all demonstrated significant improvement after intradetrusor BoNT-A injection, based on the UDS. The OAB symptom scores also significantly decreased after BoNT-A therapy. Conclusions: The present study demonstrated that intradetrusor BoNT-A injection significantly improved symptoms in patients with OAB who had been unresponsive to various treatments. This study also demonstrated the usefulness of performing a UDS before and after treatment to prove the efficacy of BoNT-A. Full article

(This article belongs to the Section Nephrology & Urology)

10 pages, 374 KiB

Open AccessArticle

Pilot Trial to Individualize the Dose of Follitropin Delta in Oocyte Donors: REKO15

by Ignacio Cristóbal Quevedo, Manuel Piró, Sonia Matey, Abigail Álvarez, Mónica Toribio, Alfredo Guillén and Juan A. García-Velasco

J. Clin. Med. 2025, 14(12), 4150; https://doi.org/10.3390/jcm14124150 - 11 Jun 2025

Abstract

Objectives:This research aimed to study the effect of 15mcg/day of follitropin delta on normo-responding women. Methods: A single-center, open-label, matched case–control pilot trial was carried out from September 2021 to June 2022. In this trial, normo-responding oocyte donors were given 15mcg/day [...] Read more.

Objectives:This research aimed to study the effect of 15mcg/day of follitropin delta on normo-responding women. Methods: A single-center, open-label, matched case–control pilot trial was carried out from September 2021 to June 2022. In this trial, normo-responding oocyte donors were given 15mcg/day of follitropin delta or 225IU/day of follitropin alfa, as well as medroxyprogesterone acetate for pituitary suppression during the cycle. The main outcome measured was the number of oocytes retrieved. Results: A fixed dose of 15mcg/day of follitropin delta for ovarian stimulation in normo-responders achieved an average of 17 oocytes retrieved. No differences were observed vs. 225IU/day of follitropin alfa in the number of oocytes [17.8 ± 7.8 vs. 18.5 ± 7.7, respectively, p = 0.156], the number of metaphase II oocytes [13.5 ± 6.9 vs. 15 ± 6.3, p = 0.105], the fertilization rates (71.1% vs. 72.9%, p = 0.523), the number of usable blastocysts (4.9 ± 2.4 vs. 4.5 ± 2.5, p = 0.466), and the implantation rate (64% vs. 57%, p = 0.575). In the follitropin delta group, the duration of the stimulation was significantly shorter (9.4 ± 1.2 vs. 10.9 ± 1.2, p < 0.01), and the overall gonadotropin intake was lower. There were no clinically relevant differences between treatment groups regarding the safety profile. Global patient satisfaction with the follitropin delta ovarian stimulation was very high (7.7 ± 2.2). Conclusions: A daily dose of 15mcg of follitropin delta may provide a similar ovarian response to 225IU/day of follitropin alfa; aiming to retrieve 17 oocytes in normo-responders undergoing progestin-primed ovarian stimulation, it could reduce gonadotropin intake by reducing the duration of the stimulation cycle, with a possible high patient satisfaction level. Full article

(This article belongs to the Section Obstetrics & Gynecology)

11 pages, 468 KiB

Open AccessArticle

The Influence of Orthogeriatric Co-Management on Economical Outcomes After Treatment of Proximal Femoral Fractures: Real-World Data of Comparable Cohorts Originating from the Same Geographic Area

by Samuel Känel, Manuel Känel, Method Kabelitz, Kim Aggeler and Michael Dietrich

J. Clin. Med. 2025, 14(12), 4149; https://doi.org/10.3390/jcm14124149 - 11 Jun 2025

Abstract

Background: The global number of operatively treated proximal femoral fractures is steadily growing, driven by the demographic shift toward an increasingly elderly, frail, and comorbid population. This clinical condition profoundly impacts not only patient health but also the finances of healthcare systems. The [...] Read more.

Background: The global number of operatively treated proximal femoral fractures is steadily growing, driven by the demographic shift toward an increasingly elderly, frail, and comorbid population. This clinical condition profoundly impacts not only patient health but also the finances of healthcare systems. The aim of this economic analysis was to investigate the impact on direct costs of orthogeriatric co-management (OGCM) compared to standard of care (SOC). Methods: A retrospective analysis was conducted investigating two comparable cohorts of patients aged 75 and above, originating from the exact same geographic area, who underwent surgical treatment for proximal femoral fractures in 2023. The two cohorts differed in their perioperative care protocols: one followed an OGCM (n = 143) protocol, while the other adhered to a SOC protocol (n = 141). Economic data were retrieved from the centralised finance department managing the two hospital sites under investigation. Results: The findings revealed that the OGCM protocol was associated with direct costs that were not higher (CHF 16,019 vs. CHF 16,713, p = 0.78) compared to SOC, despite higher daily costs in the OGCM cohort (CHF 2504 vs. CHF 2202, p < 0.0001). This difference was largely driven by a significantly shorter length of stay in the OGCM group (6 days vs. 7 days, p = 0.002). Conclusions: Optimising resource allocation through tailored geriatric care protocols suggests not only an improvement in clinical outcomes but also a reduction in economic burden, thereby alleviating pressure on the healthcare system. Full article

(This article belongs to the Section Orthopedics)

12 pages, 735 KiB

Open AccessArticle

Comparison of Demographics and Oxford Knee Score in Total Knee Arthroplasty Patients Between the United Kingdom and Saudi Arabia: A Cohort Study

by Omar W. Althomali, Bodor Bin sheeha, David Sands Johnson, Zizi M. Ibrahim, Shaimaa Abdelhamid Altoury and Richard Jones

J. Clin. Med. 2025, 14(12), 4148; https://doi.org/10.3390/jcm14124148 - 11 Jun 2025

Abstract

Background/Objectives:Total knee arthroplasty (TKA) is considered as important final line of treatment for several conditions such as knee osteoarthritis. Interestingly, culture, demographics, and health care systems may differ between countries, leading to different outcomes. Understanding this variation can help in enhancing patient [...] Read more.

Background/Objectives:Total knee arthroplasty (TKA) is considered as important final line of treatment for several conditions such as knee osteoarthritis. Interestingly, culture, demographics, and health care systems may differ between countries, leading to different outcomes. Understanding this variation can help in enhancing patient care and rehabilitation therapy. This study aimed to compare primary TKA patients from the Kingdom of Saudi Arabia (KSA) and the United Kingdom (UK) pre- and post-surgery, representing two different populations and cultural backgrounds. Methods: A retrospective cohort sample was collected from the UK and one prospective cohort sample was collected in the KSA. Demographic characteristics and the Oxford knee score (OKS) were compared preoperatively and 6 and 12 months postoperatively. Results: A total of 259 patients were included in the study. Significant differences were observed in demographic characteristics. Patients in the UK cohort were five years older and 7 kg/m² lower in body mass index (BMI) than those in the KSA cohort. The proportion of male patients was higher in the UK cohort (37%) compared to the KSA cohort (17%). Preoperatively, the OKS was significantly (p = 0.001) worse in the Saudi cohort (15 ± 4) compared to the UK cohort (19 ± 6). After 6 months postoperatively, both groups improved; however, there was a significant difference, with a higher value for the KSA cohort compared to the UK cohort. By 12 months post-TKA, the difference in OKS between the populations no longer existed. Conclusion: Although there are notable differences in demographics and preoperative OKS, the functional outcomes at 12 months post-TKA were comparable between the two populations. These findings suggest that while cultural and demographic factors may influence early postoperative recovery, 12-month outcomes tend to converge across different populations. Full article

(This article belongs to the Special Issue Clinical Perspectives on Surgical Management of Knee Injuries)

30 pages, 1367 KiB

Open AccessReview

Emerging Age-Specific Therapeutic Approaches for Dry Eye Disease

by Tatiana Suárez-Cortés and Itxaso Herrera

J. Clin. Med. 2025, 14(12), 4147; https://doi.org/10.3390/jcm14124147 - 11 Jun 2025

Abstract

Dry eye disease (DED) is a common, multifactorial disorder of the ocular surface. Although DED can affect individuals at any age, its prevalence, clinical manifestations, underlying mechanisms, and optimal management strategies differ considerably across the lifespan. In children, symptoms are frequently associated with [...] Read more.

Dry eye disease (DED) is a common, multifactorial disorder of the ocular surface. Although DED can affect individuals at any age, its prevalence, clinical manifestations, underlying mechanisms, and optimal management strategies differ considerably across the lifespan. In children, symptoms are frequently associated with atopy and allergic disorders and environmental factors, whereas in young adults, digital device usage and contact lens wear are the predominant contributors. In older adults, systemic diseases and polypharmacy significantly elevate the risk of DED. Across all age groups, tear film instability, decreased tear production, and chronic inflammation are central pathogenic features. Key tear biomarkers, such as pro-inflammatory cytokines, have been widely linked to disease development. Cathepsin S and tumor necrosis factor-alpha have recently been implicated in age-related DED. A nuanced understanding of these age-related differences is crucial for improving diagnostic accuracy and tailoring interventions to specific patient populations. This review synthesizes current evidence on DED across age groups, focusing on prevalence, risk factors, pathophysiology, molecular mechanisms, coexisting conditions, biomarkers, and treatment options. Finally, it highlights critical unmet clinical needs in the management of age-related DED. Full article

(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment: 2nd Edition)

10 pages, 379 KiB

Open AccessArticle

Screening for Systemic Light-Chain Amyloidosis in Patients Over 60 with λ Monoclonal Gammopathies

by Ping Zhou, Mahesh M. Mansukhani, Raymond Yeh, Jiesheng Lu, Hongai Xia, Lahari Koganti, Jiuhong Pang, Denis Toskic, Stephanie Scalia, Xun Ma, Lisa X. Lee, Sandy W. Wong, Alfred Chung, Sascha A. Tuchman, Terry Fogaren, Nancy Coady Lyons, Cindy Varga, Suzanne Lentzsch and Raymond L. Comenzo

J. Clin. Med. 2025, 14(12), 4146; https://doi.org/10.3390/jcm14124146 - 11 Jun 2025

Abstract

Background/Objectives: To reduce the early mortality of light-chain amyloidosis (AL), earlier diagnosis is needed. To pursue this goal, we conducted a multicenter study screening for AL λ-type (NCT04615572) in subjects > 60 years of age with λ smoldering myeloma (SMM) or monoclonal gammopathy [...] Read more.

Background/Objectives: To reduce the early mortality of light-chain amyloidosis (AL), earlier diagnosis is needed. To pursue this goal, we conducted a multicenter study screening for AL λ-type (NCT04615572) in subjects > 60 years of age with λ smoldering myeloma (SMM) or monoclonal gammopathy of undetermined significance (MGUS), a light-chain differential (dFLC, λ minus κ) > 23 mg/L, and no prior amyloid diagnosis. Methods: Variables included AL-related IGVL gene usage and clonal plasma cell cytogenetic abnormalities, such as t(11;14) or gain 1q, which are present in 75% of AL cases. Here, 9 out of 33 λ IGVL genes, accounting for 90% of AL λ cases, were considered to be AL-related. Bone marrow was obtained, plasma cell cytogenetics and next generation sequencing for IGVL genes were performed, and subjects with AL-related IGVL genes were screened for AL using tissue studies. Results: From 2021 to 2023, we enrolled 30 subjects (19 M/11 F) with a median age of 68.5 years old (IQR 64.3–73), 17 SMM and 13 MGUS, with a median of 6% marrow plasma cells (range, 3.5–40). Here, 11 SMM and 4 MGUS cases had t(11;14) or gain 1q; 10/17 SMM and 12/13 MGUS had AL-related genes, and AL was ultimately confirmed by tissue biopsy in 3 with SMM. SMM, AL-related IGVL genes, and t(11;14) or gain 1q were found in 6 SMM subjects, including the 3 with AL (3/6 vs. 0/16; p < 0.05, Fisher’s exact, two-tailed). Conclusions: These results justify a larger study screening for AL in SMM to develop a likelihood algorithm for AL using dFLC, IGVL gene usage, and the presence of t(11;14) or gain 1q. Full article

(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Amyloidosis)

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16 pages, 272 KiB

Open AccessReview

Enhancing Safety and Quality of Cardiopulmonary Resuscitation During Coronavirus Pandemic

by Diána Pálok, Barbara Kiss, László Gergely Élő, Ágnes Dósa, László Zubek and Gábor Élő

J. Clin. Med. 2025, 14(12), 4145; https://doi.org/10.3390/jcm14124145 - 11 Jun 2025

Abstract

Background: Professional knowledge and experience of healthcare organization went through continuous change and development with the progression of COVID-19 pandemic waves. However, carefully developed guidelines for cardiopulmonary resuscitation (CPR) remained largely unchanged regardless of the epidemic situation, with the largest change being a [...] Read more.

Background: Professional knowledge and experience of healthcare organization went through continuous change and development with the progression of COVID-19 pandemic waves. However, carefully developed guidelines for cardiopulmonary resuscitation (CPR) remained largely unchanged regardless of the epidemic situation, with the largest change being a more prominent bioethical approach. It would be possible to further improve the quality of CPR by systematic data collection, the facilitation of prospective studies, and further development of the methodology based on this evidence, as well as by providing information and developing provisions on interventions with expected poor outcomes, and ultimately by refusing resuscitation. Methods: This study involved the critical collection and analysis of literary data originating from the Web of Science and PubMed databases concerning bioethical aspects and the efficacy of CPR during the COVID-19 pandemic. Results: According to the current professional recommendation of the European Resuscitation Council (ERC), CPR should be initiated immediately in case of cardiac arrest in the absence of an exclusionary circumstance. One such circumstance is explicit refusal of CPR by a well-informed patient, which in practice takes the form of a prior declaration. ERC prescribes the following conjunctive conditions for do-not-attempt CPR (DNACPR) declarations: present, real, and applicable. It is recommended to take the declaration as a part of complex end-of-life planning, with the corresponding documentation available in an electronic database. The pandemic has brought significant changes in resuscitation practice at both lay and professional levels as well. Incidence of out-of-hospital resuscitation (OHCA) did not differ compared to the previous period, while cardiac deaths in public places almost halved during the epidemic (p < 0.001) as did the use of AEDs (p = 0.037). The number of resuscitations performed by bystanders and by the emergency medical service (EMS) also showed a significant decrease (p = 0.001), and the most important interventions (defibrillation, first adrenaline time) suffered a significant delay. Secondary survival until hospital discharge thus decreased by 50% during the pandemic period. Conclusions: The COVID-19 pandemic provided a significant impetus to the revision of guidelines. While detailed methodology has changed only slightly compared to the previous procedures, the DNACPR declaration regarding self-determination is mentioned in the context of complex end-of-life planning. The issue of safe environment has come to the fore for both lay and trained resuscitators. Future Directions: Prospective evaluation of standardized methods can further improve the patient’s autonomy and quality of life. Since clinical data are controversial, further prospective controlled studies are needed to evaluate the real hazards of aerosol-generating procedures. Full article

(This article belongs to the Special Issue Cardiopulmonary Resuscitation—from Research to Clinical Implementation)

17 pages, 2884 KiB

Open AccessArticle

Evolution of Chronic Kidney Disease in Different Regions of the World

by Shoaib Junejo, Mengxuan Chen, Muhammad Usman Ali, Shobha Ratnam, Deepak Malhotra and Rujun Gong

J. Clin. Med. 2025, 14(12), 4144; https://doi.org/10.3390/jcm14124144 - 11 Jun 2025

Abstract

Background/Objectives: Chronic kidney disease (CKD) is a major global public health issue, affecting over 690 million individuals worldwide. The prevalence, diagnosis, and treatment of kidney disease vary considerably across different geographical regions. However, comprehensive and in-depth research on CKD remains limited due to [...] Read more.

Background/Objectives: Chronic kidney disease (CKD) is a major global public health issue, affecting over 690 million individuals worldwide. The prevalence, diagnosis, and treatment of kidney disease vary considerably across different geographical regions. However, comprehensive and in-depth research on CKD remains limited due to its diverse etiologies. Methods: This study provides a detailed assessment of the disease burden of CKD, considering its etiological basis and utilizing the latest data reflecting changing trends. This research synthesizes findings from previous studies, with the necessary literature sourced from online platforms such as Google Scholar, EMBASE, and PubMed/MEDLINE databases, as well as Global Burden of Disease (GBD), to compare visualizations of the world’s CKD levels and trends from 1990 to 2021. Results: The study results demonstrated that eating patterns are affected by historical and industrial factors, which likely contribute to the high prevalence of CKD in Western countries. The data also indicated that the global number of new CKD cases increased from just over 7.8 million in 1990 to nearly 19 million after 30 years. Additionally, the results showed that age and sex together accounted for the observed prevalence and disease-attributable disability-adjusted life year (DALY) rates in CKD, with the highest rates seen in older age groups, except for CKD attributed to type 1 diabetes, where the incidence was higher in children, and the burden was greater in middle-aged adults. Conclusions: Overall, these findings are a valuable addition to the existing literature and provide evidence that CKD studies over a similar time frame reveal notable global trends and regional differences in highlighting this increasing burden. Full article

(This article belongs to the Section Nephrology & Urology)

21 pages, 2041 KiB

Open AccessArticle

Effects of Neuromuscular Priming with Spinal Cord Transcutaneous Stimulation on Lower Limb Motor Performance in Humans: A Randomized Crossover Sham-Controlled Trial

by Simone Zaccaron, Lara Mari, Mattia D’Alleva, Jacopo Stafuzza, Maria Parpinel, Stefano Lazzer and Enrico Rejc

J. Clin. Med. 2025, 14(12), 4143; https://doi.org/10.3390/jcm14124143 (registering DOI) - 11 Jun 2025

Abstract

Background: Lower limb motor output contributes to determining functional performance in many motor tasks. This study investigated the effects of non-invasive spinal cord transcutaneous stimulation (scTS) applied during an exercise-based priming protocol on lower limb muscle force and power generation. Methods: [...] Read more.

Background: Lower limb motor output contributes to determining functional performance in many motor tasks. This study investigated the effects of non-invasive spinal cord transcutaneous stimulation (scTS) applied during an exercise-based priming protocol on lower limb muscle force and power generation. Methods: Twelve young, physically active male volunteers (age: 22.7 ± 2.1 years) participated in this randomized crossover, sham-controlled study. The maximal voluntary contraction and low-level torque steadiness of knee extensors, as well as the maximal explosive extension of lower limbs, were assessed before and after the priming protocol with scTS or sham stimulation over a total of four experimental sessions. Further, characteristics of evoked potentials to scTS related to spinal circuitry excitability were assessed in the supine position before and after the scTS priming protocol. The exercise component of the ~25 min priming protocol consisted of low-volume, low- and high-intensity lower limb motor tasks. Results: scTS priming protocol tended to increase or maintain maximum isometric torque during knee extension (4.7%) as well as peak force (0.2%) and rate of force development (6.0%) during explosive lower limb extensions, whereas sham priming protocol tended to decrease them (−4.3%, −3.3%, and −15.1%, respectively). This resulted in significant interactions (p = 0.001 to 0.018) and medium–large differences between scTS and sham protocols. These findings were associated with meaningful trends of some neurophysiological variables. Conversely, priming protocols did not affect low-level torque steadiness. Conclusions: scTS counteracted the unexpected fatigue induced by the exercise-based priming protocol, supporting lower limb performance during maximal efforts. Future studies are warranted to assess the implementation of scTS with optimized exercise-based priming protocols during training and rehabilitation programmes that include high-intensity neuromuscular efforts. Full article

(This article belongs to the Section Sports Medicine)

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