Journal of Clinical Medicine

10 pages, 277 KiB

Open AccessReview

The Role of Mifepristone in Cervical Maturation and Induction of Labor: A Narrative Review of the Literature

by Francesco Pio Toscano, Maria D'Angelo, Alice Giorno, Alessandra Gallo, Marco Piccolo, Gabriele Saccone, Antonio Mollo and Giuseppe Laurelli

J. Clin. Med. 2025, 14(12), 4061; https://doi.org/10.3390/jcm14124061 (registering DOI) - 8 Jun 2025

Abstract

Background: The objective of this review is to demonstrate the efficacy of mifepristone as an inducing agent of labor by analyzing its impact on cervical maturation and maternal and neonatal outcomes. The research results showed that mifepristone facilitates cervical ripening and enhances uterine [...] Read more.

Background: The objective of this review is to demonstrate the efficacy of mifepristone as an inducing agent of labor by analyzing its impact on cervical maturation and maternal and neonatal outcomes. The research results showed that mifepristone facilitates cervical ripening and enhances uterine sensitivity. Methods: A narrative review of the literature was conducted to descriptively summarize and compare available data. No formal meta-analytic model was applied. The analysis was descriptive and based on pooled aggregated data without the use of inferential modeling. Studies published through November 2024 were retrieved using the Medline, Ovid, Scopus, and Web of Science databases. The search was based on a combination of keywords: “mifepristone”, “induction”, and “labor”. Randomized clinical trials and prospective and retrospective studies concerning full-term pregnancies with unfavorable cervices were included, while studies concerning termination of pregnancy or intrauterine death were excluded. The outcomes analyzed included cesarean section rates, neonatal intensive care unit admissions, and oxytocin and prostaglandin use. Results: Ten studies were analyzed, with a total of 1561 patients. The use of mifepristone showed a reduction in the use of oxytocin (RR = 0.84; 95% CI: 0.70–1.01), although this difference did not reach statistical significance (p = 0.065), and a highly significant reduction in prostaglandin use (42.7% vs. 78.9%; RR = 0.54; 95% CI: 0.48–0.60; p < 0.0001), with no significant difference in cesarean section rate (18.9% vs. 23.6%; RR = 0.80; 95% CI: 0.63–1.01; p = 0.068). However, a significantly higher rate of neonatal ICU admissions was observed in the mifepristone group (13.9% vs. 9.3%; RR = 1.48; 95% CI: 1.08–2.02; p = 0.014). Only studies excluding patients with a previous cesarean section were included for the analyses of cesarean sections, oxytocin, and prostaglandin use, while all studies were retained for NICU evaluation. Conclusions: Mifepristone represents a promising option for labor induction due to its ability to improve cervical maturation and reduce the need for additional uterotonic agents. Our pooled analysis confirmed a significant reduction in prostaglandin and oxytocin use, and a non-significant trend toward fewer cesarean deliveries. However, the observed increase in NICU admissions in the mifepristone group raises important concerns regarding neonatal safety. Further studies are needed to investigate whether this association reflects underlying clinical factors, variations in NICU admission policies, or a true pharmacological effect. Future research should focus on optimizing dosing regimens, identifying patient subgroups who benefit most, and clarifying neonatal outcomes through long-term follow-up. Full article

(This article belongs to the Special Issue Challenges in Diagnosis and Treatment of Gynecological Malignancies in Young Adults)

► Show Figures

Figure 1

20 pages, 535 KiB

Open AccessReview

Intestinal Fibrosis in Crohn’s Disease: Pathophysiology, Diagnosis, and New Therapeutic Targets

by Fotios S. Fousekis, Konstantinos Mpakogiannis, Ioanna Nefeli Mastorogianni, Georgios D. Lianos, Dimitrios K. Christodoulou and Konstantinos H. Katsanos

J. Clin. Med. 2025, 14(12), 4060; https://doi.org/10.3390/jcm14124060 (registering DOI) - 8 Jun 2025

Abstract

Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract that often leads to intestinal fibrosis, an irreversible complication associated with strictures and the need for surgical intervention. Fibrosis occurs due to prolonged inflammation and abnormal wound healing, involving complex interactions [...] Read more.

Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract that often leads to intestinal fibrosis, an irreversible complication associated with strictures and the need for surgical intervention. Fibrosis occurs due to prolonged inflammation and abnormal wound healing, involving complex interactions between immune cells, mesenchymal cells, cytokines, and the gut microbiota. Key fibrogenic mechanisms include the activation of fibroblasts and myofibroblasts, cytokine signaling, and disrupted turnover of the extracellular matrix. Advancements in imaging techniques, such as MRI and CT enterography, have improved the detection and monitoring of fibrosis. Additionally, molecular techniques targeting fibroblast activation proteins show promise as a new imaging method. However, there are currently no approved anti-fibrotic therapies for CD. Emerging strategies focus on key pathways and novel therapeutic targets, including growth factor modulators, intracellular enzyme and kinases modulators, and interventions targeting the modulation of inflammation and extracellular matrix, which are being evaluated in preclinical and clinical settings. This review discusses the pathophysiology, diagnostic advancements, and therapeutic perspectives related to intestinal fibrosis in CD, emphasizing the urgent need for targeted anti-fibrotic therapies to prevent long-term complications and improve the life quality of patients. Full article

(This article belongs to the Special Issue Novel Therapeutic Targets with Inflammatory Bowel Diseases)

13 pages, 481 KiB

Open AccessArticle

Prognostic Value of Systemic Inflammatory Response Markers for CIN2+ Recurrence After Loop Electrosurgical Excision Procedure: A Retrospective Cohort Study

by Sevim Ezgi Katran, Kevser Arkan, Süleyman Cemil Oğlak, İpek Betül Özçivit Erkan, Gözde Cebeci and Engin Çelik

J. Clin. Med. 2025, 14(12), 4059; https://doi.org/10.3390/jcm14124059 (registering DOI) - 8 Jun 2025

Abstract

Objectives: To evaluate the prognostic value of systemic inflammatory response (SIR) parameters in predicting the recurrence of cervical intraepithelial neoplasia (CIN2+) in women undergoing a loop electrosurgical excision procedure (LEEP). Methods: This retrospective study included women aged ≥18 years who underwent an LEEP [...] Read more.

Objectives: To evaluate the prognostic value of systemic inflammatory response (SIR) parameters in predicting the recurrence of cervical intraepithelial neoplasia (CIN2+) in women undergoing a loop electrosurgical excision procedure (LEEP). Methods: This retrospective study included women aged ≥18 years who underwent an LEEP at a tertiary center between 2013 and 2023. Patients who were pregnant and those who had malignancies, immune disorders, or prior cervical surgery were excluded. The data collected included age, parity, cervical cytology, HPV DNA status, histology, LEEP specimen size, and preoperative blood count parameters. Follow-up was performed every six months using cytology, colposcopy, and histology to assess recurrence. The SIR markers evaluated included the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and lymphocyte count. Statistical analyses included ROC curves and Cox regression. Results: Of the 1068 patients included, 726 had follow-up data, and 32 (4.4%) experienced a recurrence after a mean interval of 24 ± 20 months. Recurrence-negative patients had higher median lymphocyte counts (2.40 vs. 2.15, p = 0.031) and LMRs (4.57 vs. 3.86, p = 0.011). The disease-free survival period was longer in patients with high lymphocyte counts, a low NLR and PLR, and a high LMR. However, the discriminatory power of these markers was limited. In the multivariate analysis, only a PLR > 118.4 remained independently associated with an increased recurrence risk (HR 3.06, p = 0.011). Due to the small number of cases of recurrences and the small amount of HPV DNA results, the findings should be interpreted with caution. Conclusions: Preoperative SIR markers such as the PLR, NLR, LMR, and lymphocyte count showed statistical associations with CIN2+ recurrence after an LEEP, but their clinical utility appears to be limited. Further prospective studies are needed to validate these findings. Full article

(This article belongs to the Section Obstetrics & Gynecology)

13 pages, 480 KiB

Open AccessBrief Report

A Brief Overview of Uveal Melanoma Treatment Methods with a Focus on the Latest Advances

by Krystian Wdowiak, Joanna Dolar-Szczasny, Robert Rejdak, Agnieszka Drab and Agnieszka Maciocha

J. Clin. Med. 2025, 14(12), 4058; https://doi.org/10.3390/jcm14124058 (registering DOI) - 8 Jun 2025

Abstract

Background: Uveal melanoma (UM) is a relatively rare malignancy, yet it remains the most common primary intraocular cancer in adults. Several risk factors have been identified, including light iris color, fair skin tone, and cutaneous freckles. Methods: The aim of this article was [...] Read more.

Background: Uveal melanoma (UM) is a relatively rare malignancy, yet it remains the most common primary intraocular cancer in adults. Several risk factors have been identified, including light iris color, fair skin tone, and cutaneous freckles. Methods: The aim of this article was an overview of the treatment methods for uveal melanoma, with a particular focus on emerging therapies such as tebentafusp and da-rovasertib. The research method was a review of the latest literature. Results: Genetic studies have uncovered key mutations in GNAQ and GNA11, which significantly contribute to UM pathogenesis. Treatment selection depends on tumor location and disease stage. In localized disease, radiotherapy—especially brachytherapy—is commonly used and generally effective. However, the prognosis worsens significantly once distant metastases, most often to the liver, develop, as no standard systemic therapy has demonstrated high efficacy in this setting. Recent years have seen the emergence of promising therapies, including tebentafusp, which stimulates immune responses against gp100-expressing melanoma cells, and darovasertib, a potent PKC inhibitor that targets MAPK pathway activation driven by GNAQ/GNA11 mutations. Both agents have shown encouraging tolerability; tebentafusp has demonstrated clinical benefit in Phase II and III trials, while darovasertib is still under investigation. Additionally, melphalan-based liver-directed therapy, particularly via hepatic arterial infusion (approved by the FDA), has shown potential in controlling liver-dominant disease in metastatic UM. This localized approach may provide significant benefit for patients with limited extrahepatic spread. Conclusions: Future research should focus on optimizing these novel strategies—tebentafusp, darovasertib, melphalan, and combination therapies—and on expanding our understanding of UM’s molecular drivers to enable the development of more effective, personalized treatments. Full article

(This article belongs to the Special Issue Clinical Highlights in Uveal Melanoma)

11 pages, 651 KiB

Open AccessArticle

Impact of Surgical Margin Distance on Oncologic Outcomes in Vulvar Squamous Cell Carcinoma

by Caroline Lenz, Su Ir Lyu, Peter Mallmann, Bernd Morgenstern and Fabinshy Thangarajah

J. Clin. Med. 2025, 14(12), 4057; https://doi.org/10.3390/jcm14124057 (registering DOI) - 8 Jun 2025

Abstract

Introduction: Vulvar carcinoma is a rare malignancy with approximately 3090 cases annually in Germany. Squamous cell carcinoma of the vulva (SCC) can be HPV-associated or non-HPV-associated. Surgical excision is the primary treatment, but the optimal tumor-free resection margin remains debated. This study evaluates [...] Read more.

Introduction: Vulvar carcinoma is a rare malignancy with approximately 3090 cases annually in Germany. Squamous cell carcinoma of the vulva (SCC) can be HPV-associated or non-HPV-associated. Surgical excision is the primary treatment, but the optimal tumor-free resection margin remains debated. This study evaluates the impact of resection margin distance on disease prognosis in SCC patients. Methods: A retrospective analysis was conducted on patients diagnosed with SCC of the vulva at the University Hospital of Cologne between 2007 and 2022. Patients with TNM stage pT1a or higher who underwent primary surgical treatment with a tumor-free resection margin status were included. The cohort of 73 patients was divided into three groups based on resection margin distance: >0.01–<0.3 cm (Group 1), ≥0.3–<0.8 cm (Group 2), and ≥0.8 cm (Group 3). Statistical analyses including logrank tests were performed to assess correlations between resection margin distance and recurrence, disease-free survival (DFS), and overall survival (OS). Results: A total of 37.0% of patients were categorized into Group 1, 48.0% into Group 2, and 15.1% into Group 3. Disease recurrence occurred in 26% of patients, with rates of 31.6% in Group 1 (minimum resection margin distance), 42.1% in Group 2, and 26.3% in Group 3. The prevalence of recurrence was not dependent on resection margin distance (p = 0.28). Similarly, the prevalence of deaths was not dependent on resection margin distance (p = 0.43). Disease-free survival (DFS) and overall survival (OS) did not show significant differences between the groups (p = 0.25 and p = 0.87, respectively). Conclusions: This study found no significant impact of pathological tumor-free resection margin distance on DFS or OS in patients with SCC of the vulva. Given the heterogeneity in international guidelines and existing literature, further studies with larger patient cohorts are needed to establish definitive surgical recommendations. Full article

(This article belongs to the Section Obstetrics & Gynecology)

12 pages, 2345 KiB

Open AccessArticle

Low Cholesterol Concentrations and the Risk of Peptic Ulcer Bleeding: A Retrospective Cohort Study

by Mehmet Kök, Süleyman Dolu, Mehmet Emin Arayici, Gökhan Köker, Lütfullah Zahit Koç and Ayhan Hilmi Cekin

J. Clin. Med. 2025, 14(12), 4056; https://doi.org/10.3390/jcm14124056 (registering DOI) - 8 Jun 2025

Abstract

Background: Hypolipidemia has been shown to be a factor that elevates the risk of bleeding. This study aimed to investigate the relationship between cholesterol levels and the risk of peptic ulcer bleeding (PUB). Methods: A total of 15,547 patients who underwent esophagogastroduodenoscopy [...] Read more.

Background: Hypolipidemia has been shown to be a factor that elevates the risk of bleeding. This study aimed to investigate the relationship between cholesterol levels and the risk of peptic ulcer bleeding (PUB). Methods: A total of 15,547 patients who underwent esophagogastroduodenoscopy (EGD) between May 2017 and December 2020 were screened. Of these, 317 were included in this retrospective cohort study. PUB was diagnosed by EGD. Serum cholesterol levels were measured at six-month intervals, and cumulative mean cholesterol concentrations were calculated using all available data during the observation period. Results: Ulcer bleeding was detected in 173 (45.6%) patients with peptic ulcer. Patients with bleeding peptic ulcer exhibited significantly lower TC, LDL-C, and HDL-C levels compared to non-bleeding peptic ulcer patients and controls (p < 0.001). The optimal LDL cut-off was 91.50 (p < 0.001), with 75.1% sensitivity and 24.1% specificity. For HDL, the cut-off was 42.50 (p < 0.001), yielding 72.3% sensitivity and 30.1% specificity. A one-unit increase in LDL and HDL reduced the risk of PUB by 0.95-fold and 0.97-fold, respectively. Conclusions: Our findings suggest that reduced cholesterol levels, particularly LDL-C and HDL-C, may elevate the risk of PUB. Therefore, monitoring cholesterol levels in peptic ulcer patients, especially those at higher bleeding risk, could be beneficial. Full article

(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)

► Show Figures

Figure 1

13 pages, 1228 KiB

Open AccessArticle

Radiographic and Clinical Outcomes of Laser-Enhanced Disinfection in Endodontic Therapy

by Janos Kantor, Sorana Maria Bucur, Eugen Silviu Bud, Victor Nimigean, Ioana Maria Crișan and Mariana Păcurar

J. Clin. Med. 2025, 14(12), 4055; https://doi.org/10.3390/jcm14124055 (registering DOI) - 8 Jun 2025

Abstract

Background and Objectives: Periapical healing and bone regeneration are key indicators of endodontic success. This study evaluated the effectiveness of laser-assisted disinfection compared to conventional chemical irrigation in promoting periapical healing across various bone densities (D1–D5), using cone-beam computed tomography (CBCT) over [...] Read more.

Background and Objectives: Periapical healing and bone regeneration are key indicators of endodontic success. This study evaluated the effectiveness of laser-assisted disinfection compared to conventional chemical irrigation in promoting periapical healing across various bone densities (D1–D5), using cone-beam computed tomography (CBCT) over multiple follow-up intervals. Materials and Methods: A total of 120 patients with radiographically confirmed periapical lesions were enrolled and allocated into two groups: an experimental group (n = 60, chemical irrigation + Er,Cr:YSGG laser disinfection) and a control group (n = 60, chemical irrigation only). CBCT scans were obtained at 6 months, 1 year, 2 years, and 2.5 years post-treatment to assess lesion size and CBCT-PAI scores. Lesions were classified radiographically as either well-defined radiolucent lesions or undefined periapical radiolucencies. Paired t-tests and ANOVA were used for statistical comparisons. Results: The experimental group demonstrated significantly greater reductions in lesion size and improvements in CBCT-PAI scores at all time points. Healing was especially enhanced in low-density bone (D4–D5). Complete healing rates were higher in the laser group for well-defined radiolucent (89.5% vs. 68.4%) and undefined lesions (81.8% vs. 59.1%). Post hoc power analysis confirmed statistical reliability (Cohen’s d = 3.48; power > 0.99). Conclusions: Laser-assisted endodontic disinfection significantly accelerates periapical healing and promotes bone regeneration, particularly in low-density bone. CBCT imaging supports its clinical superiority over conventional irrigation methods. Full article

(This article belongs to the Special Issue Endodontic and Periodontal Medicine: Systemic Implications of Oral Infections)

► Show Figures

Figure 1

11 pages, 596 KiB

Open AccessArticle

The Effectiveness of Sacubitril/Valsartan in Systemic Sclerosis Patients with Heart Failure: A Retrospective Analysis

by Nouran Eshak, Mahmoud Abdelnabi, Jaxon Quillen, Micheal Pham, Joseph Hentz and Vivek Nagaraja

J. Clin. Med. 2025, 14(12), 4054; https://doi.org/10.3390/jcm14124054 (registering DOI) - 8 Jun 2025

Abstract

Introduction: Cardiac involvement in patients with systemic sclerosis (SSc) can present variably from being asymptomatic to manifesting with heart failure, conduction abnormalities, pulmonary hypertension, and pericardial effusion. Symptomatic cardiac involvement portends a poor prognosis and worse overall survival. Sacubitril/valsartan (SV), an angiotensin receptor [...] Read more.

Introduction: Cardiac involvement in patients with systemic sclerosis (SSc) can present variably from being asymptomatic to manifesting with heart failure, conduction abnormalities, pulmonary hypertension, and pericardial effusion. Symptomatic cardiac involvement portends a poor prognosis and worse overall survival. Sacubitril/valsartan (SV), an angiotensin receptor neprilysin inhibitor, has been shown to significantly reduce hospitalization rates and morbidity in patients with heart failure with reduced ejection fraction (HFrEF). This study aimed to investigate the effects of SV treatment in patients with SSc and heart failure. Methods: A retrospective analysis of patients with SSc was conducted using an electronic data capture tool. Patients with SSc treated with SV between January 2015 and August 2023 were identified. Comprehensive clinical phenotyping and longitudinal data analysis were performed to characterize the sub-type of patients and evaluate clinical outcomes, including hospitalizations and mortality, laboratory markers, and echocardiographic findings. Results: Twenty-four patients with SSc were treated with SV for a mean duration of 20.6 months. HFrEF was the primary indication for SV use in 91% of patients, primarily due to non-ischemic cardiomyopathy (87.5%). There was a significant reduction in systolic blood pressure from 128 mmHg to 114 mmHg (p < 0.001) and NT-proBNP levels from 15,130 pg/mL to 5082 pg/mL (p = 0.046). In the 19 patients with baseline and follow-up echocardiograms, there was a significant improvement in LVEF from 40.3% to 47.7% (p = 0.014). Hypotension was a common side effect leading to discontinuation of SV (n = 4, 16.7%). Serum creatinine had trends of improvement (1.9 mg/dL to 1.3 mg/d), though it did not reach statistical significance (p = 0.057). Conclusions: This study showed that SV effectively improved cardiac symptoms and function in patients with SSc presenting with HFrEF. Further prospective studies are needed to confirm these findings and explore the role of SV in the treatment of other manifestations of SSc. Full article

(This article belongs to the Special Issue Clinical Diagnostics and Therapeutics Advances in Acute and Chronic Heart Failure)

► Show Figures

Figure 1

19 pages, 524 KiB

Open AccessArticle

by Lucia Jiménez-Sierra, Ana López-de-Andres, Valentín Hernández-Barrera, Rodrigo Jiménez-Garcia, David Carabantes-Alarcon, Andrés Bodas-Pinedo, Elena Labajo-Gonzalez and José J. Zamorano-León

J. Clin. Med. 2025, 14(12), 4053; https://doi.org/10.3390/jcm14124053 (registering DOI) - 8 Jun 2025

Abstract

Background/Objectives: We aim to describe and analyze the clinical characteristics and hospital outcomes of alcohol-related hospital admissions (ARHAs) among adolescents and young adults (12 to 35 years) with type 1 diabetes (T1D) in Spain from 2016 to 2023. We also aim to determine [...] Read more.

Background/Objectives: We aim to describe and analyze the clinical characteristics and hospital outcomes of alcohol-related hospital admissions (ARHAs) among adolescents and young adults (12 to 35 years) with type 1 diabetes (T1D) in Spain from 2016 to 2023. We also aim to determine factors associated with admission to the intensive care unit (ICU). Methods: A descriptive observational study was carried out based on the Spanish Hospital Discharge Database (SHDD). ICD-10 codes were used to identify ARHAs in T1D patients. Joinpoint regression was used to analyze the time trend, and multivariable logistic regression was conducted to identify predictors of ICU admission. Results: We recorded 39,091 discharges with T1D (52.59% females); of these, 1274 (3.26% prevalence) were identified as ARHAs (74.10% males vs. 25.90% females). Joinpoint regression showed a significant increase among females and stable prevalence in males. Females with T1D and ARHAs were younger than males, and more frequently had diabetic ketoacidosis (DKA), mental disorders, and external causes of morbidity and mortality, whereas greater drug use was detected among males. Overall, 20.80% of ARHAs required ICU admission. Predictors of ICU admission included DKA, drug use, hypoglycemia, and female sex (OR: 1.39; 95% CI: 1.02–1.90). Conclusions: The frequency of ARHAs in young people with T1D in Spain rose between 2016 and 2023, mainly owing to the increase in the percentage of females requiring ARHA. DKA and drug and tobacco consumption were very common in ARHAs. Admission to the ICU is frequent, increases over time, and is associated with female sex, DKA, hypoglycemia, and drug use. Full article

(This article belongs to the Section Endocrinology & Metabolism)

10 pages, 1863 KiB

Open AccessCase Report

Corneal Perforation as a Possible Ocular Adverse Event Caused by Cabozantinib: A Clinical Case and Brief Review

by Carmelo Laface, Luca Scartozzi, Chiara Pisano, Paola Vanella, Antonio Greco, Agostino Salvatore Vaiano and Gianmauro Numico

J. Clin. Med. 2025, 14(12), 4052; https://doi.org/10.3390/jcm14124052 (registering DOI) - 8 Jun 2025

Abstract

Background: Cabozantinib is a Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor (VEGFR-TKI). These drugs are employed as therapy for several malignancies. In detail, Cabozantinib has demonstrated its efficacy against several malignancies. On the other hand, Cabozantinib and other VEGFR-TKIs can be responsible [...] Read more.

Background: Cabozantinib is a Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor (VEGFR-TKI). These drugs are employed as therapy for several malignancies. In detail, Cabozantinib has demonstrated its efficacy against several malignancies. On the other hand, Cabozantinib and other VEGFR-TKIs can be responsible for various adverse events (AEs), in particular hepatic and dermatological AEs. Methods: To date, limited data are available in the literature regarding ocular AEs due to therapy with these drugs. In this regard, one case of corneal perforation during treatment with a VEGFR-TKI, Regorafenib, has been reported, while there are no data about Cabozantinib. In this paper, we present another clinical case of corneal perforation in a patient affected by advanced RCC and treated with Cabozantinib as a second-line therapy. The patient started Cabozantinib at the dosage of 60 mg/die although it was necessary to apply some dose reductions because of grade 2 AEs (according to CTCAE v6.0), such as asthenia, diarrhea, dysgeusia, and loss of appetite. Results: After approximately 15 months of treatment, the patient began to experience pain and vision loss in the right eye. A diagnosis of corneal perforation was made, followed by medical and surgical treatment. As regards the etiology of this pathology, all other possible causes were excluded, including a history of ocular disease, contact trauma, exposure to damaging agents (e.g., chemical agents and prolonged use of drugs such as topical NSAIDs), infections, or dry eye. Therefore, we hypothesized a correlation with Cabozantinib’s mechanisms of action and paused its administration. Conclusions: Cabozantinib may alter the ocular environment due to a lack of or imbalance in growth factors in the tear film, with a reduction in corneal epithelium proliferation. This condition might cause dry eye and a delay in corneal healing. Therefore, particular importance should be placed on ophthalmologic surveillance during treatment with these drugs in patients who develop ocular symptoms. Further in vitro and in vivo studies are necessary to deepen the knowledge about VEGFR-TKI-mediated ocular AEs. Full article

(This article belongs to the Section Ophthalmology)

► Show Figures

Figure 1

9 pages, 193 KiB

Open AccessArticle

CT Evaluation of Hematuria in Adults Younger than 50 Years in Military Service: Is Contrast-Enhanced Phase Needed?

by Gil N. Bachar, Inna Tsitman, Nir Popel, Shahar Porat, Tomer Erlich and Eli Atar

J. Clin. Med. 2025, 14(12), 4051; https://doi.org/10.3390/jcm14124051 (registering DOI) - 8 Jun 2025

Abstract

Background: Limited data exist on the comparative diagnostic value of CT urography (CTU) versus unenhanced CT in evaluating the upper urinary tract in young adults (<50 years) with hematuria in active military service. This population may face an increased risk of urinary tract [...] Read more.

Background: Limited data exist on the comparative diagnostic value of CT urography (CTU) versus unenhanced CT in evaluating the upper urinary tract in young adults (<50 years) with hematuria in active military service. This population may face an increased risk of urinary tract malignancies due to occupational exposures. Methods: We conducted a retrospective cohort study of 277 consecutive Israel Defense Forces personnel under 50 years old with new-onset hematuria referred for CT evaluation between 2011 and 2020. Two experienced radiologists first interpreted unenhanced CT images, followed by a review of contrast-enhanced phases. Findings were classified based on their detectability on unenhanced CT and whether contrast phases were required. Results: Of the 277 patients, 270 had microscopic hematuria and 7 had macroscopic hematuria. Imaging was normal in 158 cases. Among 119 patients (43%) with positive findings, 46 (16.6%) had clinically significant findings requiring follow-up or treatment. Of these, 42 (91%) were detectable on unenhanced CT alone. Contrast phases were requested in 15 cases (5.4%) and revealed additional benign findings. No urinary tract malignancies were identified. Conclusions: Unenhanced CT may be sufficient for evaluating new-onset hematuria in adults under 50, including active military personnel, minimizing the need for contrast administration. Full article

(This article belongs to the Section Nephrology & Urology)

12 pages, 655 KiB

Open AccessReview

Supra Inguinal Fascia Iliac Versus PENG Block for Post-Operative Pain Management of Hip Arthroplasty: A Narrative Review

by Shahab Ahmadzadeh, Megan S. Walker, Mary O’Dell Duplechin, Drake P. Duplechin, Charles J. Fox, Sahar Shekoohi and Alan D. Kaye

J. Clin. Med. 2025, 14(12), 4050; https://doi.org/10.3390/jcm14124050 (registering DOI) - 7 Jun 2025

Abstract

Effective post-operative pain management following hip arthroplasty is critical to improving recovery, reducing opioid consumption, enhancing mobility, and reducing the risk of complications for patients. Multimodal anesthesia strategies, including the supra inguinal fascia iliac block (SIFIB) and the periarticular nerve group (PENG) block [...] Read more.

Effective post-operative pain management following hip arthroplasty is critical to improving recovery, reducing opioid consumption, enhancing mobility, and reducing the risk of complications for patients. Multimodal anesthesia strategies, including the supra inguinal fascia iliac block (SIFIB) and the periarticular nerve group (PENG) block have become the new point of focus as opposed to traditional methods previously used. This narrative review compares the SIFIB and the PENG block in their efficacy to treat post-operative pain management. Mechanism of action, safety, patient outcomes, and clinical applications are compared between the two blocks for evaluation. Clinical studies have indicated that both blocks reduce post-operative pain and reduce opioid use. In contrast, SIFIB has shown to be more preferred in more complex procedures such as total hip arthroplasty, which requires extensive nerve coverage despite its longer onset time. The SIFIB has been shown to carry a higher risk of impairing motor function, making the PENG highly preferred in patients where quick mobility improvement is prioritized. The PENG block also showed slightly higher efficacy in reducing pain associated with post-operative passive limb movements, and a slight decrease in opioid consumption in comparison to SIFIB in the early post-operative time frame. Although the PENG shows more benefits in the early stages of post-operative recovery, the SIFIB shows similar outcomes to PENG over longer durations of recovery. Future studies can aid in establishing a framework for tailoring block selection to individual patient needs to optimize clinical outcomes. Full article

(This article belongs to the Special Issue Clinical Advances in Pain Management)

► Show Figures

Figure 1

12 pages, 425 KiB

Open AccessPerspective

Exploring Use-Rates of and Scientific Evidence on Sutureless Devices in Aortic Valve Replacement: A Bibliographic Meta-Analysis and Clinical Considerations

by Cristiano Spadaccio, Arnaldo Dimagli, Clayton J. Agler, Dane C. Paneitz, Stanley B. Wolfe, Antonio Nenna, Asishana A. Osho and David Rose

J. Clin. Med. 2025, 14(12), 4049; https://doi.org/10.3390/jcm14124049 (registering DOI) - 7 Jun 2025

Abstract

Sutureless aortic valve replacement (SuAVR) has emerged as a potential alternative to conventional surgical aortic valve replacement (SAVR), particularly in minimally invasive settings. However, its global adoption remains limited, with a notable concentration of use and scientific production in select European countries. This [...] Read more.

Sutureless aortic valve replacement (SuAVR) has emerged as a potential alternative to conventional surgical aortic valve replacement (SAVR), particularly in minimally invasive settings. However, its global adoption remains limited, with a notable concentration of use and scientific production in select European countries. This bibliographic meta-analysis systematically reviewed 538 studies to assess the evidence landscape surrounding SuAVR, highlighting a predominance of observational data, sparse randomized controlled trials (1.3%), and significant geographical imbalances in research output. Europe accounted for 80% of publications, while North America contributed less than 10%. Key structural factors—including reimbursement policies, earlier regulatory approvals, and population characteristics—appear to influence SuAVR adoption. Despite procedural advantages such as reduced cross-clamp times, concerns over cost, pacemaker implantation rates, and uncertain long-term durability persist. Importantly, SuAVR may offer its greatest clinical value by facilitating minimally invasive surgery, a niche still underutilized worldwide. The limited randomized data and industrial focus on transcatheter approaches have further hindered widespread acceptance. Our findings underscore the need for high-quality comparative trials and standardized guidelines to define the role of SuAVR in modern valve therapy. Full article

(This article belongs to the Section Cardiology)

► Show Figures

Figure 1

15 pages, 640 KiB

Open AccessArticle

Myocardial Performance Improvement After Iron Replacement in Heart Failure Patients: The IRON-PATH II Echo-Substudy

by Raúl Ramos-Polo, Maria del Mar Ras-Jiménez, María del Carmen Basalo Carbajales, Sílvia Jovells-Vaqué, José Manuel Garcia-Pinilla, Marta Cobo-Marcos, Javier de Juan-Bagudá, Cândida Fonseca, Josep Francesch Manzano, Andreea Eunice Cosa, Sergi Yun-Viladomat, Cristina Enjuanes, Marta Tajes Orduña and Josep Comin-Colet

J. Clin. Med. 2025, 14(12), 4048; https://doi.org/10.3390/jcm14124048 (registering DOI) - 7 Jun 2025

Abstract

Background: Iron deficiency (ID) is a commonly seen comorbidity in heart failure (HF) patients. It is often associated with a poor prognosis and impaired physical capacity. The functional limitations linked to ID may lead to cardiac function abnormalities. The functional limitations linked to [...] Read more.

Background: Iron deficiency (ID) is a commonly seen comorbidity in heart failure (HF) patients. It is often associated with a poor prognosis and impaired physical capacity. The functional limitations linked to ID may lead to cardiac function abnormalities. The functional limitations linked to ID may lead to cardiac function abnormalities, that can be reversible after iron repletion. Some echocardiographic parameters, such as global longitudinal strain (GLS), myocardial work (MW) and its derivatives constructive work (CW), wasted work (WW) and work efficiency (WE), may be of added value in advanced cardiac performance assessment. Methods: IRON-PATH II was a multicenter, prospective and observational study designed to describe the pathophysiological pathways associated with ID. The echo-substudy included 100 HF patients that had undergone a specific pilot echocardiographic evaluation. Patients had a left ventricular ejection fraction (LVEF) ≤50%, were in stable clinical condition and on standard HF medication with hemoglobin ≥11 g/dL. The final cohort included 98 patients. Results: The ID group showed worse cardiac function, with lower GLS (−8.5 ± 9% vs. −10 ± 10%), WE (74 ± 10% vs. 80 ± 10%) and MW (665 [453–1013] vs. 947 [542–1199] mmHg%), as well as higher WW (290 [228–384] vs. 212 [138–305] mmHg%) and lower RV free wall strain (−13 [−20–(−11)]% vs. −17 [−23–(−14)]%). Following iron repletion, ID patients demonstrated improved LV (GLS, MW, WE and WW) and RV performance (RV free wall strain), aligning with non-ID patients (all p-values >0.05 compared to the non-ID group). Conclusions: Among HF patients with reduced LVEF, ID was associated with worse myocardial performance in both the LV and RV. All the alterations seen were reversible after intravenous iron repletion. Full article

(This article belongs to the Special Issue Clinical Management of Patients with Heart Failure—2nd Edition)

► Show Figures

Figure 1

37 pages, 340 KiB

Open AccessArticle

Context, Timing and Individualized Care: A Realist Evaluation of Safety Planning for Individuals Living with Suicide-Related Thoughts and Behaviours, Their Families and Friends and Service Providers

by Elisa Hollenberg, Hwayeon Danielle Shin, Nadine Reid, Vicky Stergiopoulos, Laurent Lestage, Gina Nicoll, Alyna Walji and Juveria Zaheer

J. Clin. Med. 2025, 14(12), 4047; https://doi.org/10.3390/jcm14124047 (registering DOI) - 7 Jun 2025

Abstract

Background/Objectives: This research aimed to identify and investigate how context facilitates or hinders safety planning interventions (SPIs) intended to manage suicidal ideation (SI) and behaviour (SB) from the perspective of service users, friends, family members, service providers and other key informants. Additionally, [...] Read more.

Background/Objectives: This research aimed to identify and investigate how context facilitates or hinders safety planning interventions (SPIs) intended to manage suicidal ideation (SI) and behaviour (SB) from the perspective of service users, friends, family members, service providers and other key informants. Additionally, this research aimed to identify underlying mechanisms influencing the effective and acceptable management of SI and SB across these groups. Methods: A realist evaluation framework (i.e., Context + Mechanism = Outcome; CMO) was used to inform the qualitative study design, which explores whether SPIs are perceived as effective (i.e., outcome) and examines the underlying mechanism(s) and specific contexts involved. A total of 28 service users, 11 family members or friends and 15 key informants, including service providers and other stakeholders, participated in semi-structured interviews. A total of 18 frontline service providers also participated in three focus groups. These interviews and focus groups were analyzed to develop a shared model capturing the mechanisms and contexts influencing effective SPI implementation. Data was collected between September 2019 and December 2021. Results: The model consists of three pillars: (1) understanding the importance of context, timing and relationships in safety planning, (2) identifying perceived barriers and facilitators to safety planning as described by service users, family members and service providers, (3) bridging the gap between evidence and experience in implementing safety planning interventions. Conclusions: While SPIs are evidence-based interventions, contextual factors and perceived barriers and facilitators can impact implementation and outcomes in mental health care settings. Understanding these factors can help to explain differences in outcomes within and across patient populations and care settings, and addressing perceived challenges can improve implementation and experiences for service users, family members and service providers. Full article

(This article belongs to the Special Issue New Insights into Suicide and Mental Health Conditions)

16 pages, 1310 KiB

Open AccessSystematic Review

Acromioclavicular Reconstruction Using the Lockdown Technique: A Case Series and Systematic Review

by Krisztian Kovacs, Szilárd Váncsa, Zsolt Abonyi-Tóth, Peter Hegyi, Gergely Soos, Kalman Rabai, Tibor Bogosi and Gyorgy Kocsis

J. Clin. Med. 2025, 14(12), 4046; https://doi.org/10.3390/jcm14124046 (registering DOI) - 7 Jun 2025

Abstract

Background: Acromioclavicular (AC) joint dislocations are frequent, especially kocsisamong young male athletes. While over 150 surgical techniques exist, consensus on optimal treatment—particularly for Rockwood type III injuries—remains elusive. This study evaluates the Lockdown procedure’s efficacy, safety, and patient satisfaction, a synthetic ligament technique [...] Read more.

Background: Acromioclavicular (AC) joint dislocations are frequent, especially kocsisamong young male athletes. While over 150 surgical techniques exist, consensus on optimal treatment—particularly for Rockwood type III injuries—remains elusive. This study evaluates the Lockdown procedure’s efficacy, safety, and patient satisfaction, a synthetic ligament technique for AC joint stabilization. Methods: A multicenter prospective study was conducted on 39 patients across three Hungarian hospitals (2018–2023). Outcomes included shoulder function, pain levels, and complication rates, with subgroup analysis of acute (≤3 weeks) versus chronic (>3 weeks) cases. A systematic review of nine studies (205 cases) was also performed to assess broader outcomes and complications. Results: Significant improvements were observed in functional scores (OSS, Constant, DASH, SST, ASES, Nottingham, Imitani) and pain reduction, especially in acute cases with no prior shoulder surgery. The mean patient age was 38.9 ± 12.68 years, with a 24.5-month average follow-up. OSS improvement between acute and chronic cases was 14.96 (95% CI: 6.45–23.47; p = 0.0017). Complications (30.8%) occurred in eleven patients, mainly minor infections; implant failure necessitated revision in 5.1%. The systematic review reported a 34.6% complication rate (predominantly minor complications, like asymptomatic subluxation −16%) and 5.4% implant removal due to failure. A meta-analysis was not feasible due to data heterogeneity. Conclusions: The Lockdown procedure significantly enhances shoulder function and reduces pain, particularly in acute dislocations. However, the procedure showed a moderate complication rate, underscoring the need for careful patient selection and postoperative management. Full article

(This article belongs to the Special Issue Clinical Management of Elbow and Shoulder Surgery)

► Show Figures

Figure 1

15 pages, 549 KiB

Open AccessReview

Treating IgA Nephropathy: Looking at the Future Without Forgetting the Past

by Rosanna Coppo

J. Clin. Med. 2025, 14(12), 4045; https://doi.org/10.3390/jcm14124045 (registering DOI) - 7 Jun 2025

Abstract

IgA nephropathy (IgAN) is an inflammatory glomerular disease caused by the production of galactose-deficient IgA1 (Gd-IgA1), which induces the formation of autoantibodies and IgA immune complexes (IgAICs) that are ultimately deposited in the mesangium. This event triggers mesangial cell proliferation, cytokine release and [...] Read more.

IgA nephropathy (IgAN) is an inflammatory glomerular disease caused by the production of galactose-deficient IgA1 (Gd-IgA1), which induces the formation of autoantibodies and IgA immune complexes (IgAICs) that are ultimately deposited in the mesangium. This event triggers mesangial cell proliferation, cytokine release and complement activation, and both glomerular and interstitial damage, eventually leading to kidney function decline. Persisting proteinuria is the most relevant marker of disease progression. Systemic corticosteroids (CSs), a powerful anti-inflammatory approach, have shown kidney protective effects in early trials involving patients with IgAN at risk of progression with persistent proteinuria. However, later studies raised concerns regarding severe adverse events associated with high doses of methylprednisolone and questioned the long-term benefits. As a result, the KDIGO 2021 guidelines recommended limiting CS therapy to selected patients who accepted the high risk of adverse events. The treatment landscape shifted when reduced doses of methylprednisolone, combined with Pneumocystis pneumonia prophylaxis, demonstrated similar kidney protection compared to full methylprednisolone doses with fewer adverse events. An innovative approach involves a targeted budesonide formulation acting on Peyer’s patches, the main site of Gd-IgA1 production. This treatment showed benefits comparable to systemic CSs, with valuable limitations of adverse events. Several new drugs targeting key pathogenetic events of IgAN are under investigation, with promising results published in recent months. These new therapies target B cell activation (and subsequent Gd-IgA1 production), the complement cascade triggered by IgAIC deposition and the endothelin system, a key amplifier of kidney damage that contributes to the chronicity of IgAN. Full article

(This article belongs to the Special Issue Novelties in the Treatment of Glomerulonephritis)

► Show Figures

Figure 1

12 pages, 4677 KiB

Open AccessArticle

Comparison of Surgical Outcomes Between Single-Site Laparoscopic Adenomyomectomy and Fundusectomy: Experience from a Single Center

by Jae Hyeok Jeong, Yoo Ri Kim, Bo Ram Kim, Ji Won Lee, Seung Yeon Oh, Jeong Hye Yun, Myoung Seok Han, Yong Jung Song and Ki Hyung Kim

J. Clin. Med. 2025, 14(12), 4044; https://doi.org/10.3390/jcm14124044 (registering DOI) - 7 Jun 2025

Abstract

Objective: This study aimed to introduce clinical experience using a new surgical technique, single-port access laparoscopic fundusectomy, a more efficient uterus-sparing surgical method for adenomyosis in patients with no plans for pregnancy. Methods: We performed single-port access laparoscopic myomectomy in 141 [...] Read more.

Objective: This study aimed to introduce clinical experience using a new surgical technique, single-port access laparoscopic fundusectomy, a more efficient uterus-sparing surgical method for adenomyosis in patients with no plans for pregnancy. Methods: We performed single-port access laparoscopic myomectomy in 141 patients and single-port access laparoscopic fundusectomy in 124 patients and compared the surgical outcomes. Results: Significant differences in surgical outcomes were observed between the two operating methods. Operative time was 158.19 min (±42.93) in the fundusectomy group and 179.11 min (±56.95) in the adenomyomectomy group (p = 0.001). Estimated blood loss was 175.04 mL (±142.76) in the fundusectomy group and 347.97 mL (±409.78) in the adenomyomectomy group (p = 0.000). The fundusectomy group showed smaller uterus size and volume, and lower postoperative CA125 levels than the adenomyomectomy group for 24 months (p = 0.000). Conclusions: This study suggests that single-port access laparoscopic fundusectomy is more effective in terms of operative time, estimated blood loss, and postoperative CA125 decrease than single-port access laparoscopic adenomyomectomy. Full article

(This article belongs to the Section General Surgery)

► Show Figures

Figure 1

16 pages, 1010 KiB

Open AccessArticle

Prognostic Value of a Serological-Based Clinical Model for Gastric Cancer Patients

by Hai-Huan Feng, Wei-Han Zhang, Kai Liu, Xiao-Long Chen, Lin-Yong Zhao, Xin-Zu Chen, Kun Yang and Jian-Kun Hu

J. Clin. Med. 2025, 14(12), 4043; https://doi.org/10.3390/jcm14124043 (registering DOI) - 7 Jun 2025

Abstract

Background:Surgery remains the cornerstone of diagnosis and treatment for gastric cancer. This study aims to develop and validate a serology-based clinical scoring system to predict and evaluate the prognosis of gastric cancer patients. Methods: Clinicopathological data of primary gastric cancer patients [...] Read more.

Background:Surgery remains the cornerstone of diagnosis and treatment for gastric cancer. This study aims to develop and validate a serology-based clinical scoring system to predict and evaluate the prognosis of gastric cancer patients. Methods: Clinicopathological data of primary gastric cancer patients who underwent surgical treatment from 2009 to 2018 were collected and divided into training and validation cohorts. Preoperative serological indicators were screened, and a serum risk score (SerScore) was developed using LASSO-Cox analysis. Prognosis prediction models incorporating the SerScore were established and validated. Results: A total of 5493 patients were screened, and 43 serological indicators were assessed. Twelve serological indicators were selected to construct the SerScore. Patients with a SerScore below the cut-off value of −1.73 had significantly better survival rates compared to those with higher scores. Multivariate Cox analysis identified SerScore, age, tumor location, T stage, and N stage as independent prognostic factors for overall survival in the training cohort. A multivariate nomogram was developed, achieving a C-index of 0.745 in the training cohort and 0.750 in the validation cohort. The nomogram demonstrated superior predictive accuracy compared to the SerScore alone, with AUC values of 0.783 versus 0.639 in the training cohort and 0.805 versus 0.657 in the validation cohort. Calibration curves closely aligned with ideal predictions in both cohorts. Conclusions: The SerScore model provides an effective tool for prognostic assessment in primary gastric cancer patients. This model not only enhances prognostic evaluation but also establishes a foundation for developing advanced prediction tools for gastric cancer. Full article

(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)

Journal Description

Journal of Clinical Medicine

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI