Journal of Clinical Medicine

15 pages, 1362 KB

Open AccessArticle

Quantifying the Impact of Chronic Obstructive Sialadenitis on Quality of Life

by Alvaro Sánchez Barrueco, Gonzalo Díaz Tapia, Ignacio Alcalá Rueda, William Aragonés Sanzen-Baker, Jessica Mireya Santillán Coello, Pilar Benavent Marín, Alberto Valentín González, Ignacio Mahillo Fernández, Carlos Cenjor Español and José Miguel Villacampa Aubá

J. Clin. Med. 2025, 14(21), 7560; https://doi.org/10.3390/jcm14217560 (registering DOI) - 24 Oct 2025

Abstract

Objectives: To evaluate the loss of quality of life (QoL) in patients with chronic obstructive sialadenitis (COS) using the Chronic Obstructive Sialadenitis Questionnaire (COSQ). Methods: The COSQ was administered to patients diagnosed with COS, with the diagnosis confirmed by sialendoscopy. Epidemiological [...] Read more.

Objectives: To evaluate the loss of quality of life (QoL) in patients with chronic obstructive sialadenitis (COS) using the Chronic Obstructive Sialadenitis Questionnaire (COSQ). Methods: The COSQ was administered to patients diagnosed with COS, with the diagnosis confirmed by sialendoscopy. Epidemiological data, obstructive causes and potentially obstructive entities were collected. QoL was assessed using the COSQ. Results: A total of 344 glands in 278 patients with COS were analyzed. Most patients were women (71.94%), and the main obstructive cause was stenosis (47.96%), followed by lithiasis, lack of papilla distensibility (LPD), and mucus plug. Stenosis was significantly more frequent in the parotid gland and in women, whereas lithiasis predominated in the submandibular gland and in men. The mean COSQ score was 30.55 and it was significantly higher in women (p < 0.005), parotid gland (p < 0.005), and in long-standing cases (p < 0.05). Stenosis and LPD were the obstructive causes with the greatest impact on QoL (p < 0.005), while lithiasis had the least impact. Potentially Obstructive Entities (POEs), such as eosinophilic sialodochitis, Sjögren’s syndrome, or radioiodine-induced sialadenitis, were associated with a notable loss of QoL. Likewise, patients without associated POEs presented significantly lower COSQ values (p < 0.05). Conclusions: COS significantly affects QoL, particularly in women and in cases of parotid gland, stenosis, and LPD. Lithiasis has the least impact on QoL. It is important to standardize a thorough evaluation of COS using validated tools such as the COSQ, which are fundamental for understanding the disease and predicting the outcomes of therapeutic interventions. Full article

(This article belongs to the Special Issue Clinical Management of Salivary Gland Disorders)

12 pages, 520 KB

Open AccessArticle

Abiraterone-Associated Renal Damage in Patients with Advanced Prostate Cancer as a Risk Factor for Mortality and Chronic Kidney Disease

by Marina Pujol-Pujol, Marta Rivero-Martínez, Javier Puente, Natalia Vidal, Marta Calvo, Cristina Riaza, Marta Álvarez-Nadal, Antolina Rodríguez-Moreno, Ana I. Sánchez-Fructuoso and Clara García-Carro

J. Clin. Med. 2025, 14(21), 7559; https://doi.org/10.3390/jcm14217559 (registering DOI) - 24 Oct 2025

Abstract

Background: Prostate cancer is the most frequent malignancy in men, with an incidence of 21% of all diagnosed tumors in this population in Spain. Between 10 and 20% of patients with prostate cancer develop castration-resistant prostate cancer (CRPC). Abiraterone is widely used [...] Read more.

Background: Prostate cancer is the most frequent malignancy in men, with an incidence of 21% of all diagnosed tumors in this population in Spain. Between 10 and 20% of patients with prostate cancer develop castration-resistant prostate cancer (CRPC). Abiraterone is widely used in CRPC and metastatic prostate cancer, but data on its renal safety are limited. Methods: We performed a single-center, retrospective observational study including patients with advanced prostate cancer who initiated abiraterone between January 2013 and July 2024 at Hospital Clínico San Carlos (Madrid, Spain). Patients were followed until December 2024. Renal events were defined as acute kidney injury (AKI), electrolyte imbalance, new onset or worsening hypertension (HTN), and/or volume overload. Risk factors and associations with mortality were analyzed using multivariate models. Results: Seventy-nine patients were included (mean age 76 ± 9.5 years; 70.9% CRPC; 89.9% metastatic disease). Median follow-up was 17 months. Renal events occurred in 63.3% of patients. Independent risk factors were metastatic disease (OR 13.335; 95% CI 1.418–124.444; p < 0.0235) and HTN (OR 3.336; 95% CI 1.091–10.206; p < 0.0347). Electrolyte imbalance occurred in 36.7% of patients. AKI developed in 30.4% of patients, of whom 50% progressed to chronic kidney disease. New/worsening HTN occurred in 25.5%, and volume overload occurred in 16.5%. Abiraterone discontinuation due to renal events was rare (4%). At the end of follow-up, 18.9% of patients had died. In a multivariate Cox analysis, AKI was identified as an independent predictor of mortality [HR 3.044 (95% CI 1.001–9.260); p = 0.05]. Conclusions: Renal events are common in patients treated with abiraterone, especially in those with metastatic disease and hypertension. AKI independently predicted mortality. Close monitoring of renal function and blood pressure is essential in this population. Full article

(This article belongs to the Section Nephrology & Urology)

13 pages, 594 KB

Open AccessArticle

by Hatice Kubra Sonmez, Zeynep Akkul, Hidayet Sener, Erinc Buyukpatır Deneme, Elif Er Arslantas, Cem Evereklioglu, Fatih Horozoglu, Osman Ahmet Polat and Hatice Arda

J. Clin. Med. 2025, 14(21), 7558; https://doi.org/10.3390/jcm14217558 (registering DOI) - 24 Oct 2025

Abstract

Objectives: To establish normative data for anterior segment parameters in healthy pediatric and adult populations using swept-source optical coherence tomography (SS-OCT), and to evaluate the influence of age and sex on these parameters. Methods: This retrospective study included the right eyes [...] Read more.

Objectives: To establish normative data for anterior segment parameters in healthy pediatric and adult populations using swept-source optical coherence tomography (SS-OCT), and to evaluate the influence of age and sex on these parameters. Methods: This retrospective study included the right eyes of 390 healthy participants. Subjects were divided into three age groups: Group 1 (6–17 years, n = 97), Group 2 (18–45 years, n = 144), and Group 3 (46–77 years, n = 149). All patients were categorized according to their biological sex as female and male. Exclusion criteria were corneal pathology, prior intraocular/refractive surgery, recent contact lens use, severe dry eye, ectatic disorders, low-quality imaging, and refractive error of ±2.0 D or greater. Measurements of anterior and posterior keratometry, total corneal power (TCP), central corneal thickness (CCT), thinnest corneal thickness (TCT), pupil diameter (PD), lens thickness (LT), and white-to-white distance (WTW) were obtained using the Anterion^® SS-OCT system. Data were analyzed using SPSS software. Results: Group 1 demonstrated the highest PD and CCT values, whereas LT was lowest. In adults, LT increased with age and was significantly higher in males older than 45 years. Keratometric analysis revealed greater anterior and total steep astigmatism in the pediatric group, independent of sex. Adult females had significantly higher anterior and posterior keratometry values compared with males. In the pediatric cohort, females exhibited greater CCT, while WTW varied with age. PD decreased with age, whereas LT increased. Conclusions: Anterior segment parameters measured with SS-OCT show significant variations across different age groups and between sexes. Normative data, particularly for pediatric and adult populations, may serve as valuable reference values in keratorefractive surgical planning and corneal pathology assessment. Future studies with larger cohorts, especially in pediatric populations, are warranted. Full article

(This article belongs to the Section Ophthalmology)

17 pages, 896 KB

Open AccessArticle

Spherical Coordinate System for Dyslipoproteinemia Phenotyping and Risk Prediction

by Justine Cole, Maureen Sampson and Alan T. Remaley

J. Clin. Med. 2025, 14(21), 7557; https://doi.org/10.3390/jcm14217557 (registering DOI) - 24 Oct 2025

Abstract

Background/Objectives: The factors contributing to residual atherosclerotic cardiovascular disease (ASCVD) risk in individuals are not fully understood, but knowledge of the specific type of dyslipoproteinemia may help further refine risk assessment. We developed a novel phenotyping and risk assessment system that may [...] Read more.

Background/Objectives: The factors contributing to residual atherosclerotic cardiovascular disease (ASCVD) risk in individuals are not fully understood, but knowledge of the specific type of dyslipoproteinemia may help further refine risk assessment. We developed a novel phenotyping and risk assessment system that may be applied automatically using standard lipid panel parameters. Methods: NHANES data collected from 37,056 individuals during 1999–2018 were used to develop a three-dimensional dyslipidemia phenotype classification system. ARIC data from 14,632 individuals were used to train and validate the risk model. Three-dimensional Cartesian coordinates were converted to spherical coordinates, which were used as features in a logistic regression model that provides a probability of ASCVD. UK Biobank data from 354,344 individuals were used to further validate and test the model. Results: Nine lipidemia phenotypes were defined based on the concentrations of HDLC, non-HDLC and TG. These phenotypes were related to the prevalence of metabolic syndrome, pooled cohort equation (PCE) score and ASCVD-free survival. A logistic regression model including age, sex and the spherical coordinates of the phenotype provided a composite risk score with predictive accuracy comparable to that of the PCEs. Conclusions: We provided an example of how a multidimensional coordinate system may be used to define a novel lipoprotein phenotyping system to examine disease associations. When applied to an ASCVD risk model, the composite spherical coordinate risk marker, which can be fully automated, provided an F1 performance score almost as good as the PCEs, which requires other risk factors besides lipids. Full article

(This article belongs to the Section Vascular Medicine)

13 pages, 529 KB

Open AccessArticle

Systemic Administration of Tranexamic Acid Improves Postoperative Outcome in Abdominoplasty

by Leila Sahinovic, Marie Louise Kohne, Jun Jiang, Hans-Guenther Machens, Haydar Kükrek, Ulf Dornseifer, Daniel Schmauss and Philipp Moog

J. Clin. Med. 2025, 14(21), 7556; https://doi.org/10.3390/jcm14217556 (registering DOI) - 24 Oct 2025

Abstract

Background/Objectives: In plastic surgery, the administration of tranexamic acid (TXA) has gained increasing support by current literature, highlighting its relevance in clinical practice. This study evaluates the perioperative impact of prophylactic intravenous TXA administration in abdominoplasty, focusing on surgical outcome, drainage pattern, complications, [...] Read more.

Background/Objectives: In plastic surgery, the administration of tranexamic acid (TXA) has gained increasing support by current literature, highlighting its relevance in clinical practice. This study evaluates the perioperative impact of prophylactic intravenous TXA administration in abdominoplasty, focusing on surgical outcome, drainage pattern, complications, and laboratory parameters (hematocrit/hemoglobin). Methods: This retrospective, single-center cohort study analyzed 58 abdominoplasties, which were divided into two groups: patients treated perioperatively with tranexamic acid for 48 h (TXA group; n = 24) and without TXA (no-TXA group; n = 34). Results: Patients in the TXA group had a significantly shorter length of hospital stay (p = 0.008) and a lower postoperative daily drainage volume on postoperative days: 3 (p = 0.047), 4 (p = 0.011), 7 (p = 0.014), 8 (p = 0.024), and 9 (p = 0.042). The overall complication rate was also significantly reduced with TXA (25.0% vs. 52.9% in the no-TXA group; p = 0.033). Postoperative declines in hematocrit and hemoglobin were less pronounced in the TXA group (p = 0.353 and p = 0.255, respectively). Furthermore, the intravenous administration of TXA was well tolerated, and no associated thromboembolic events were observed. Conclusions: Intravenous TXA appears to reduce complications, drainage volumes, and hospital stay in abdominoplasty patients, while being safe and well tolerated. Although further studies are needed to define optimal dosing, administration protocols, and long-term safety, these findings support the potential benefits of TXA for both patients and healthcare systems, thereby enabling a standardized approach to body contouring surgery. Full article

(This article belongs to the Special Issue Advances in Plastic and Reconstructive and Aesthetic Surgery of Face, Breast and Body)

28 pages, 1050 KB

Open AccessPerspective

Toward Artificial Intelligence in Oncology and Cardiology: A Narrative Review of Systems, Challenges, and Opportunities

by Visar Vela, Ali Yasin Sonay, Perparim Limani, Lukas Graf, Besmira Sabani, Diona Gjermeni, Andi Rroku, Arber Zela, Era Gorica, Hector Rodriguez Cetina Biefer, Uljad Berdica, Euxhen Hasanaj, Adisa Trnjanin, Taulant Muka and Omer Dzemali

J. Clin. Med. 2025, 14(21), 7555; https://doi.org/10.3390/jcm14217555 (registering DOI) - 24 Oct 2025

Abstract

Background: Artificial intelligence (AI), the overarching field that includes machine learning (ML) and its subfield deep learning (DL), is rapidly transforming clinical research by enabling the analysis of high-dimensional data and automating the output of diagnostic and prognostic tests. As clinical trials become [...] Read more.

Background: Artificial intelligence (AI), the overarching field that includes machine learning (ML) and its subfield deep learning (DL), is rapidly transforming clinical research by enabling the analysis of high-dimensional data and automating the output of diagnostic and prognostic tests. As clinical trials become increasingly complex and costly, ML-based approaches (especially DL for image and signal data) offer promising solutions, although they require new approaches in clinical education. Objective: Explore current and emerging AI applications in oncology and cardiology, highlight real-world use cases, and discuss the challenges and future directions for responsible AI adoption. Methods: This narrative review summarizes various aspects of AI technology in clinical research, exploring its promise, use cases, and its limitations. The review was based on a literature search in PubMed covering publications from 2019 to 2025. Search terms included “artificial intelligence”, “machine learning”, “deep learning”, “oncology”, “cardiology”, “digital twin”. and “AI-ECG”. Preference was given to studies presenting validated or clinically applicable AI tools, while non-English articles, conference abstracts, and gray literature were excluded. Results: AI demonstrates significant potential in improving diagnostic accuracy, facilitating biomarker discovery, and detecting disease at an early stage. In clinical trials, AI improves patient stratification, site selection, and virtual simulations via digital twins. However, there are still challenges in harmonizing data, validating models, cross-disciplinary training, ensuring fairness, explainability, as well as the robustness of gold standards to which AI models are built. Conclusions: The integration of AI in clinical research can enhance efficiency, reduce costs, and facilitate clinical research as well as lead the way towards personalized medicine. Realizing this potential requires robust validation frameworks, transparent model interpretability, and collaborative efforts among clinicians, data scientists, and regulators. Interoperable data systems and cross-disciplinary education will be critical to enabling the integration of scalable, ethical, and trustworthy AI into healthcare. Full article

(This article belongs to the Section Clinical Research Methods)

16 pages, 1394 KB

Open AccessArticle

Effect of Concomitant Tricuspid Valve Repair on Clinical and Echocardiographic Outcomes in Patients Undergoing Left Ventricular Assist Device Implantation

by Olga N. Kislitsina, Sandeep N. Bharadwaj, Tingqing Wu, Rebecca Harap, Jane Kruse, Esther B. Vorovich, Jane E. Wilcox, Clyde W. Yancy, Patrick M. McCarthy and Duc T. Pham

J. Clin. Med. 2025, 14(21), 7554; https://doi.org/10.3390/jcm14217554 (registering DOI) - 24 Oct 2025

Abstract

Objectives: The purpose of this study was to determine whether concomitant tricuspid valve repair (TVr) at the time of left ventricular assist device (LVAD) implantation improves outcomes in patients with ≥moderate tricuspid regurgitation (TR) and to evaluate the prognostic value of preoperative right [...] Read more.

Objectives: The purpose of this study was to determine whether concomitant tricuspid valve repair (TVr) at the time of left ventricular assist device (LVAD) implantation improves outcomes in patients with ≥moderate tricuspid regurgitation (TR) and to evaluate the prognostic value of preoperative right ventricular (RV) strain. Methods: In a retrospective analysis of 100 LVAD recipients (44 TVr; 56 No-TVr), preoperative (preop) and postoperative (postop) clinical, echocardiographic, and hemodynamic variables, including pulmonary vascular resistance (PVR) and pulmonary artery pulsatility index (PAPI), were analyzed. RV free wall strain (RV-FWS) and RV fractional area change (RV-FAC) were measured by speckle tracking. Early right heart failure (RHF) was modeled with multivariable logistic regression, and 2-year mortality was assessed with Fine–Gray competing risk regression. Preoperative and three-month measurements were compared within each of the 100 patients. Results: Baseline invasive hemodynamics, RV-FWS, and RV-FAC were similar between the TVr and No-TVr groups. TVr at the time of LVAD implantation reduced postoperative TR grade, but it did not improve RV-FWS or RV-FAC at 3 months. The No-TVr patients were more often discharged home and had lower 30-day readmissions. PVR was comparable preoperatively and at 3 months postoperatively. In adjusted analyses, preop PVR, PAPI, and TVr were not independently associated with early RHF, whereas decreased preoperative RV-FWS and lower preop RV-FAC independently predicted higher 2-year mortality. Conclusions: In LVAD recipients with ≥moderate TR, concomitant TVr lowers postoperative TR severity but does not improve early RHF, RV strain-based remodeling, or 2-year mortality. Preoperative RV deformation metrics, rather than preoperative PVR or PAPI, independently predict survival following LVAD implantation with or without TVr. Full article

(This article belongs to the Special Issue Advanced Therapy for Heart Failure and Other Combined Diseases)

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13 pages, 530 KB

Open AccessArticle

Sedentary Behavior as a Risk Factor for Liver Fibrosis Development in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Cross-Sectional Study

by Antonella Bianco, Caterina Bonfiglio, Isabella Franco, Claudia Beatrice Bagnato, Nicola Verrelli, Dolores Stabile and Endrit Shahini

J. Clin. Med. 2025, 14(21), 7553; https://doi.org/10.3390/jcm14217553 (registering DOI) - 24 Oct 2025

Abstract

Background: Metabolic dysfunction-associated fatty liver disease (MASLD) affects nearly 20% of the Italian population, with an annual economic burden of € 7.94 billion on the National Health Service, largely due to advanced liver disease and metabolic comorbidities. Progressive liver fibrosis remains the [...] Read more.

Background: Metabolic dysfunction-associated fatty liver disease (MASLD) affects nearly 20% of the Italian population, with an annual economic burden of € 7.94 billion on the National Health Service, largely due to advanced liver disease and metabolic comorbidities. Progressive liver fibrosis remains the strongest predictor of adverse outcomes. Early diagnosis is crucial, as fibrosis is potentially reversible in its early stages. Sedentary behavior (SB) is one of many modifiable risk factors for several chronic diseases; however, most evidence is based on self-reported data. This study investigates the association between objectively measured daily energy expenditure and liver stiffness in adults with MASLD. Methods: We conducted a cross-sectional analysis of 104 adults (18–65 years) with obesity and moderate-to-severe steatosis (CAP ≥ 248 dB/m) from the Obesity-AF study. Daily energy expenditure (METs/day) was assessed via 7-day wrist-worn actigraphy. Liver stiffness (LSM, kPa) was measured non-invasively using transient elastography (FibroScan^®). Results: Lower daily energy expenditure was independently associated with higher liver stiffness. Each 1-MET increase correlated with a −1.239 kPa reduction in LSM (95% CI: −2.012, −0.466; p = 0.002). Sedentary individuals (≤1.5 METs) exhibited significantly higher LSM (+0.73 kPa, p = 0.03) versus non-sedentary peers, even after full adjustment. Findings were robust across sensitivity analyses. Conclusions: Our study shows that SB, objectively measured by actigraphy, is independently associated with increased liver stiffness in patients with MASLD and obesity. Reducing sedentary time may represent a simple, low-cost, and scalable strategy to mitigate fibrosis progression. However, given the cross-sectional design and the specificity of our sample, longitudinal studies are needed to confirm the causal role of SB and to evaluate the effectiveness of targeted interventions in broader MASLD populations. Full article

(This article belongs to the Special Issue Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) as a Global but Not Liver-Limited Health Challenge—from Disease Pathogenesis to Therapeutic Targets)

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11 pages, 694 KB

Open AccessArticle

The Introduction of Impella 5.5 in Cardiogenic Shock: A Single-Center, Retrospective Propensity Score-Matched Analysis

by Maciej Bochenek, Mateusz Sokolski, Anna Kędziora, Barbara Barteczko-Grajek, Grzegorz Bielicki, Kinga Kosiorowska, Maciej Rachwalik, Rafał Nowicki, Michał Kosowski, Magdalena Cielecka, Michał Zakliczyński, Wiktor Kuliczkowski and Roman Przybylski

J. Clin. Med. 2025, 14(21), 7552; https://doi.org/10.3390/jcm14217552 (registering DOI) - 24 Oct 2025

Abstract

Background/Objectives: Impella 5.5 provides a higher flow rate than smaller microaxial pumps and has been increasingly adopted for cardiogenic shock (CS). This study aimed to evaluate whether its introduction into our Shock Team program in 2023 improved outcomes compared with a historical cohort [...] Read more.

Background/Objectives: Impella 5.5 provides a higher flow rate than smaller microaxial pumps and has been increasingly adopted for cardiogenic shock (CS). This study aimed to evaluate whether its introduction into our Shock Team program in 2023 improved outcomes compared with a historical cohort supported with other mechanical circulatory support (MCS) devices. Methods: We retrospectively analyzed patients with CS treated with MCS between 2020 and 2024 at a tertiary center. The Impella 5.5 group (n = 17) included patients managed after device implementation, either as stand-alone or sequential therapy. The historical cohort comprised 40 patients treated with ECMO, Impella CP, CentriMag, or IABP prior to 2023. Propensity score matching (age, sex, etiology, lactate, SCAI stage) generated 17 matched pairs. The primary outcome was survival at discharge, 30 days, 3 months, and 6 months. Secondary outcomes included bridging to recovery, heart transplantation (HTx), durable LVAD, and major complications. Results: Impella 5.5 was associated with higher survival at discharge (94.1% vs. 58.8%, p = 0.039), 30 days (94.1% vs. 58.8%, p = 0.039), and 3 months (94.1% vs. 58.8%, p = 0.039). At 6 months, survival remained higher (88.2% vs. 58.8%) but did not reach statistical significance in point analysis (p = 0.118). Bridging occurred more frequently with Impella 5.5 (HTx 64.7% vs. 52.9% (p = 0.464), recovery 17.6% vs. 5.9% (p = 0.292)), while LVAD implantation rates were similar (11.8% vs. 17.6%, p = 1.0). Major bleeding (17.6% vs. 47.1%, p = 0.141), stroke/TIA (5.9% vs. 17.6%, p = 0.601), and the need for renal replacement therapy (5.9% vs. 23.5%, p = 0.335) were numerically lower with Impella 5.5. Conclusions: In this single-center, retrospective analysis, the introduction of Impella 5.5 was associated with higher short-term survival and favorable bridging metrics; estimates are imprecise due to small, heterogeneous samples. These hypothesis-generating findings warrant confirmation in larger, prospective multicenter cohorts Full article

(This article belongs to the Special Issue State-of-the-Art in Cardiac Surgery: Progress, Challenges and Opportunities)

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9 pages, 1145 KB

Open AccessArticle

Different Types of Connections Between the Thalamus and Vestibular Nucleus in the Human Brain

by Sang-Soo Lee, Seo-Yoon Park and Sang-Seok Yeo

J. Clin. Med. 2025, 14(21), 7551; https://doi.org/10.3390/jcm14217551 (registering DOI) - 24 Oct 2025

Abstract

Background/Objectives: The vestibulothalamic tract (VTT) serves as a crucial pathway transmitting vestibular information from the brainstem nuclei to the thalamus, where integration with other sensory modalities occurs. This study aimed to investigate the structural connectivity between three vestibular nuclei and three thalamic nuclei [...] Read more.

Background/Objectives: The vestibulothalamic tract (VTT) serves as a crucial pathway transmitting vestibular information from the brainstem nuclei to the thalamus, where integration with other sensory modalities occurs. This study aimed to investigate the structural connectivity between three vestibular nuclei and three thalamic nuclei in the human brain using diffusion tensor imaging (DTI) tractography. Methods: Twelve healthy adults underwent DTI to visualize vestibulothalamic connections using probabilistic tractography. Results: Results revealed distinct patterns of connectivity: the lateral vestibular nucleus (LVN) exhibited the highest reconstruction rates to both the ventral posterolateral (95.8%) and ventral posteromedial (83.3%), while the medial vestibular nucleus (MVN) showed the strongest connection to the ventral intermediate (75.0%). All vestibulothalamic tracts predominantly passed through the tegmentum of the midbrain, with limited or absent contributions from the tectum. Conclusions: These findings indicate differential roles of vestibular nuclei in relaying information to thalamic targets, with the LVN showing preferential projections to sensory relay nuclei and the MVN contributing to motor-related thalamic regions. Such insights may have important implications for the diagnosis and treatment of vestibular disorders, as well as for advancing anatomical research. These findings provide anatomical insights that may help explain symptoms of vestibular and thalamic lesions and guide rehabilitation strategies for balance and gaze control disorders. Full article

(This article belongs to the Section Clinical Neurology)

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28 pages, 610 KB

Open AccessFeature PaperReview

The Use of Ultrasound Imaging in Continuous Blood Vessel Area and Velocity Data Acquisition for Determining the Local Pulse Wave Velocity

by Victoria Charlotte Wei Yi Ng, Hwa Liang Leo and Yoke-Rung Wong

J. Clin. Med. 2025, 14(21), 7550; https://doi.org/10.3390/jcm14217550 (registering DOI) - 24 Oct 2025

Abstract

Pulse wave velocity (PWV) is a useful biomarker in the monitoring and risk stratification of various cardiovascular diseases including hypertension. The current gold standard for non-invasive measurement is carotid-femoral PWV (cfPWV) measurement via direct tonometry. However, cfPWV provides only a global PWV measure, [...] Read more.

Pulse wave velocity (PWV) is a useful biomarker in the monitoring and risk stratification of various cardiovascular diseases including hypertension. The current gold standard for non-invasive measurement is carotid-femoral PWV (cfPWV) measurement via direct tonometry. However, cfPWV provides only a global PWV measure, which emphasises the need for an alternative capable of local PWV assessment. There are several alternatives for local PWV measurement proposed in the literature and one promising alternative is ultrasound, which offers good penetration depth, accessibility, and a relatively low cost, making it well-suited for non-invasive, real-time acquisition of haemodynamic parameters for PWV estimation. This paper aims to evaluate the different approaches for ultrasound-based acquisition while considering technical and physiological constraints to optimise the accuracy, reliability, and reproducibility of the parameters collected for estimation. In particular, this paper focuses on the flow-area (QA) and lnDiameter-velocity (lnDU) methods, which require local area and velocity data for PWV estimation. Accordingly, this paper discusses the use of ultrasound imaging in vessel data acquisition, highlights various challenges and considerations to be managed during acquisition and processing, outlines the different ultrasound-based imaging modalities for acquiring area and velocity data, and compares the simultaneous and non-simultaneous acquisition of data for PWV estimation. Full article

(This article belongs to the Section Vascular Medicine)

23 pages, 1845 KB

Open AccessFeature PaperReview

Management of Asymptomatic Severe Aortic Stenosis: Current Evidence and Future Directions

by Giulia Laterra, Federica Agnello, Orazio Strazzieri, Claudia Reddavid, Lorenzo Scalia, Salvatore Ingala, Simona Guarino, Chiara Barbera, Maria Daniela Russo, Giuliano Costa and Marco Barbanti

J. Clin. Med. 2025, 14(21), 7549; https://doi.org/10.3390/jcm14217549 (registering DOI) - 24 Oct 2025

Abstract

Systematic Severe aortic stenosis (AS) is a progressive disease and one of the most common valvular heart diseases in developed countries. The management of asymptomatic severe AS remains challenging and requires a tailored, patient-specific approach. Optimal timing of intervention in asymptomatic patients continues [...] Read more.

Systematic Severe aortic stenosis (AS) is a progressive disease and one of the most common valvular heart diseases in developed countries. The management of asymptomatic severe AS remains challenging and requires a tailored, patient-specific approach. Optimal timing of intervention in asymptomatic patients continues to be a matter of ongoing debate. In individuals with severe AS and reduced left ventricular ejection fraction (LVEF), both the ESC/EACTS and ACC/AHA guidelines recommend aortic valve replacement (AVR), regardless of symptom status. In contrast, for patients with preserved LVEF (≥50%), the decision to proceed with AVR must be individualized and based on a comprehensive risk assessment. Risk stratification plays a central role in guiding early intervention strategies and should incorporate clinical findings, echocardiographic parameters, biomarkers, and advanced imaging techniques such as cardiac magnetic resonance and computed tomography. Recent randomized controlled trials have yielded mixed results regarding the mortality benefit of early AVR but have consistently demonstrated a reduction in heart failure-related hospitalizations. Timely intervention in carefully selected high-risk patients may improve long-term outcomes, while avoiding unnecessary procedures in lower-risk individuals remains equally important. Full article

(This article belongs to the Section Cardiovascular Medicine)

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16 pages, 1741 KB

Open AccessArticle

Dysfunction in Cardiovascular Autonomic Modulation Caused by Chronic Use of Ketamine Hydrochloride Can Be Prevented by Aerobic Exercise Training in Wistar Rats

by Adriano Dos-Santos, Lucas Porto Fernandes dos Santos, Gabriela da Silva-Santos, Bruno Durante da Silva, Bruno Nascimento-Carvalho, Hunter Douglas de Souza-Lima, Nicolas da Costa-Santos, Erico Chagas Caperuto, Nathalia Bernardes, Katia De Angelis, Maria Claudia Irigoyen, Katia Bilhar Scapini and Iris Callado Sanches

J. Clin. Med. 2025, 14(21), 7548; https://doi.org/10.3390/jcm14217548 (registering DOI) - 24 Oct 2025

Abstract

Background/Objectives: Ketamine, widely used for its anesthetic and analgesic properties, has been linked to cardiotoxic effects, particularly with chronic use. Prolonged ketamine exposure may impair cardiovascular function, while aerobic exercise is known to promote protective cardiovascular adaptations. This study aimed to evaluate whether [...] Read more.

Background/Objectives: Ketamine, widely used for its anesthetic and analgesic properties, has been linked to cardiotoxic effects, particularly with chronic use. Prolonged ketamine exposure may impair cardiovascular function, while aerobic exercise is known to promote protective cardiovascular adaptations. This study aimed to evaluate whether aerobic training can mitigate the deleterious cardiovascular effects of chronic ketamine administration in rats. Methods: Twenty-four Wistar rats were randomly assigned to four groups: sedentary control (S), trained control (T), sedentary with ketamine (S-ket), and trained with ketamine (T-ket). Ketamine was administered intraperitoneally at a dose of 10 mg/kg, three times per week for six weeks. Aerobic training was conducted on a treadmill in the trained groups throughout the protocol. At the end of the experiment, cardiac function was assessed by echocardiography. Additionally, animals were cannulated in the carotid artery and jugular vein to measure blood pressure, baroreflex sensitivity, and heart rate variability using a data acquisition system (2 kHz, Windaq DATAQ). Results: Rats in the S-ket group showed elevated systolic arterial pressure and reduced baroreflex sensitivity compared to controls. Aerobic training attenuated these effects. Baroreflex sensitivity improved (bradycardic reflex—S: −1.7 ± 0.3; S-ket: −0.7 ± 0.1; T: −1.3 ± 0.2; T-ket: −1.3 ± 0.1), and cardiovascular autonomic function was preserved (total power—S: 45.6 ± 6.3; S-ket: 18.3 ± 2.1; T: 44.1 ± 5.7; T-ket: 38.9 ± 8.4) in trained animals. Conclusions: Aerobic exercise mitigates cardiovascular impairments caused by chronic ketamine exposure in rats, suggesting its potential as a non-pharmacological intervention to counteract ketamine-induced cardiotoxicity. These findings support incorporating exercise into treatment strategies for individuals chronically exposed to ketamine. Full article

(This article belongs to the Section Cardiovascular Medicine)

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12 pages, 1670 KB

Open AccessArticle

Evaluation of the Insertion Depth of the iStent Inject W and Its Association with Surgical Outcomes Using Automated Gonioscopy

by Yuki Takagi, Ryo Asano, Kana Yamashita, Ayumi Miwa, Yukihiro Sakai, Sho Yokoyama, Kei Ichikawa and Kazuo Ichikawa

J. Clin. Med. 2025, 14(21), 7547; https://doi.org/10.3390/jcm14217547 (registering DOI) - 24 Oct 2025

Abstract

Background/Objectives: The iStent is a trabecular micro-bypass device used in glaucoma management. Its depth has been evaluated using anterior segment optical coherence tomography; however, no reports have assessed it using gonioscopy. We evaluated the depth of the iStent inject W using the [...] Read more.

Background/Objectives: The iStent is a trabecular micro-bypass device used in glaucoma management. Its depth has been evaluated using anterior segment optical coherence tomography; however, no reports have assessed it using gonioscopy. We evaluated the depth of the iStent inject W using the GS-1 automated gonioscope (GS-1) and determined its association with outcomes. Methods: Patients who underwent iStent inject W implantation were followed for 1 year. Angle photographs were obtained using a GS-1. The depth was graded from the GS-1 images as Grades 1 (anterior edge of the flange protruding into the anterior chamber) and 2 (anterior edge embedded within the trabecular meshwork). Based on the two implants’ depths, the eyes were categorized into Grades 1 + 1, 2 + 2, and 1 + 2. The percentages of intraocular pressure (IOP) reduction at 12 months were compared among the groups using the Kruskal–Wallis test. Results: Data from 31 patients (41 eyes and 82 stents) were analyzed. The depth distribution for Grades 1 and 2 was 51 (62.2%) and 31 (37.8%) stents, respectively. In the Grade 1 + 1, 2 + 2, and 1 + 2 groups, the number of eyes was 18, 8, and 15, respectively. IOP reductions at 12 months were 12.81 ± 20.27%, 22.85 ± 15.30%, and 16.04 ± 20.41% for the Grade 1 + 1, 2 + 2, and 1 + 2 groups, respectively, with no significant differences (p = 0.493). Conclusions: The impact of insertion depth on outcomes appears to be minimal in eyes where the iStent inject W was visualized using the GS-1. Further studies with larger cohorts should clarify the effects of insertion depth and its interplay with position. Full article

(This article belongs to the Section Ophthalmology)

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13 pages, 921 KB

Open AccessBrief Report

Macitentan in the Treatment of Digital Ulcers in Patients with Systemic Rheumatic Autoimmune Diseases: A National Multicenter Study of 42 Patients

by Miriam Retuerto-Guerrero, Clara Moriano Morales, Ivan Castellvi Barranco, María Hildegarda Godoy Tundido, Clara Méndez Perles, Carlos de la Puente Bujidos, Ana Salome Pareja Martínez, Marta Garijo Bufort, Leyre Riancho Zarrabeitia, Elena Aurrecoechea Aguinaga, Guillermo González Arribas, Esther F. Vicente-Rabaneda, Silvia Montes García, Belén Atienza-Mateo, Vanesa Calvo-Río, Cristina Corrales Selaya, José Andrés Lorenzo Martín and Elvira Díez Álvarez

J. Clin. Med. 2025, 14(21), 7546; https://doi.org/10.3390/jcm14217546 (registering DOI) - 24 Oct 2025

Abstract

Objective: To evaluate the real-world safety and efficacy of macitentan (MACI) in patients with systemic autoimmune rheumatic diseases (SARDs) and refractory digital ulcers (DUs). Methods: We conducted a retrospective observational study of 42 patients treated with MACI (10 mg/day) on a compassionate-use basis [...] Read more.

Objective: To evaluate the real-world safety and efficacy of macitentan (MACI) in patients with systemic autoimmune rheumatic diseases (SARDs) and refractory digital ulcers (DUs). Methods: We conducted a retrospective observational study of 42 patients treated with MACI (10 mg/day) on a compassionate-use basis across Spanish reference hospitals. Given the cohort’s heterogeneity, a two-step analysis was performed: a global assessment of all patients, followed by a subgroup analysis restricted to those with systemic sclerosis (SSc) or fulfilling very early SSc (VEDOSS) criteria to explore predictors of response. Efficacy was defined as complete healing, partial response, or a lack of response based on physician assessment. Safety was evaluated through analysis of adverse events. Results: In the global cohort, MACI demonstrated a high rate of complete ulcer healing (82.9%) at the 3-month follow-up, with a significant reduction in median ulcer count (p < 0.001). Subgroup analysis within the SSc/VEDOSS cohort (n = 36) revealed that the presence of gastrointestinal involvement (GI) and a higher baseline DUs were significant predictors of a poorer therapeutic response (p = 0.022 and p = 0.028). The drug was well-tolerated; adverse events were infrequent and rarely led to treatment discontinuation. Conclusions: In this real-world refractory population, MACI was associated with rapid DU healing and a favorable safety profile. GI and higher ulcer burden predicted diminished treatment response in SSc patients. These results support the use of MACI as a valuable therapeutic option for severe digital vasculopathy in SARDs, although further prospective studies are warranted to confirm these observations. Full article

(This article belongs to the Section Immunology & Rheumatology)

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13 pages, 404 KB

Open AccessArticle

Endoscopic Ultrasound for Nodal Staging in Patients with Resectable Cholangiocarcinoma

by David M. de Jong, Lydi M. J. W. van Driel, Sundeep Lakhtakia, Mohan Ramchandani, Sana Fathima Memon, Abhishek Tyagi, Parathasarathy Kumaraswamy, Shreeyash Modak, Anuradha Sekaran, Marco J. Bruno, Duvvur Nageshwar Reddy and Hardik Rughwani

J. Clin. Med. 2025, 14(21), 7545; https://doi.org/10.3390/jcm14217545 (registering DOI) - 24 Oct 2025

Abstract

Background: Lymph node (LN) involvement is a negative prognostic factor for patients with cholangiocarcinoma (CCA). Preoperative assessment of the LN could potentially aid therapy decision making. Endoscopic ultrasound (EUS) can be used to sample suspicious LN. The aim of this study was [...] Read more.

Background: Lymph node (LN) involvement is a negative prognostic factor for patients with cholangiocarcinoma (CCA). Preoperative assessment of the LN could potentially aid therapy decision making. Endoscopic ultrasound (EUS) can be used to sample suspicious LN. The aim of this study was to evaluate the clinical impact of EUS for suspicious LN in patients with presumed resectable CCA. Methods: In this single-center cohort study, patients with potentially resectable CCA who underwent preoperative linear EUS between 2019 and 2024 were retrospectively included. The primary aims were the percentage of malignant LN detected and the clinical impact of EUS, which was defined as the percentage of patients who were precluded from surgical exploration due to pathologically confirmed LN metastases found with EUS tissue acquisition (EUS-TA). The secondary aim was the complication rate of EUS-TA. Results: A total of 135 patients were included, of whom 12 (8.9%) had intrahepatic CCA (iCCA), 65 (48.1%) had perihilar CCA (pCCA), 13 had (9.6%) middle bile duct CCA (mCCA), and 45 (33.3%) had distal CCA (dCCA). Across 148 EUS procedures, 139 LNs were identified, and EUS-TA was performed on 63 LNs among 55 patients. LN metastases were detected by EUS-TA for iCCA, pCCA, mCCA, and dCCA, in 25%, 6.2%, 15.4%, and 4.4%, respectively. EUS and EUS-TA influenced surgical work-up for iCCA, pCCA, mCCA, and dCCA in 25%, 1.5%, 15.4%, and 0.0%, respectively. No complications associated with EUS were noted. Conclusions: Preoperative EUS for nodal staging had an important clinical impact in patients with presumed resectable iCCA and mCCA, but less for pCCA and dCCA. Further prospective studies should investigate whether systematic nodal staging with EUS could improve preoperative decision making even further. Full article

(This article belongs to the Special Issue Advances in Diagnosis and Management of Pancreatobiliary Disorders—2nd Edition)

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26 pages, 3483 KB

Open AccessReview

UHPLC-MS/MS for Antipsychotic Drug Monitoring: A Systematic Review of Clinical and Analytical Performance

by Ciprian-Ionuț Băcilă, Bianca-Maria Macavei, Monica Cornea, Bogdan Ioan Vintilă, Andrei Lomnășan, Claudia Elena Anghel, Andreea Maria Grama, Cristina Elena Dobre, Claudia Marina Ichim and Gabriela Cioca

J. Clin. Med. 2025, 14(21), 7544; https://doi.org/10.3390/jcm14217544 (registering DOI) - 24 Oct 2025

Abstract

Background/Objectives: Therapeutic drug monitoring (TDM) of antipsychotic medications plays an important role in optimizing treatment efficacy, reducing adverse effects, and supporting adherence. While Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry (UHPLC–MS/MS) has long been the gold standard for antipsychotic quantification, recent advances in [...] Read more.

Background/Objectives: Therapeutic drug monitoring (TDM) of antipsychotic medications plays an important role in optimizing treatment efficacy, reducing adverse effects, and supporting adherence. While Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry (UHPLC–MS/MS) has long been the gold standard for antipsychotic quantification, recent advances in automated platforms and microsampling raise questions about its current clinical practicality. This systematic review evaluated the clinical applicability and analytical performance of UHPLC-based methods for monitoring antipsychotic drugs, focusing on precision, recovery, matrix effects, and suitability across various biological matrices. Methods: A systematic search of PubMed, Scopus, and Web of Science was conducted for studies published between 2013 and 2024 involving UHPLC-based quantification of antipsychotics in clinical samples from adult patients. Data on analytical parameters, sample matrices, and study characteristics were extracted. A custom quality checklist was used to assess methodological rigor. In addition to qualitative synthesis, non-traditional quantitative approaches were applied, including descriptive aggregation of recovery, matrix effects, and precision across studies, as well as correlation analyses to explore relationships among performance parameters. Results: Twelve studies were included, spanning a range of typical and atypical antipsychotics and metabolites. Plasma and serum demonstrated the highest analytical reliability (recovery >90%, minimal matrix effects), while dried blood spots (DBSs), whole blood, and oral fluid showed greater variability. Clinically, UHPLC–MS/MS enabled more accurate dose adjustments and identification of non-adherence, outperforming immunoassays in sensitivity, specificity, and metabolite detection. Microsampling methods showed promise for outpatient and decentralized care but require further clinical validation. Conclusions: UHPLC–MS/MS remains the most robust and reliable method for TDM of antipsychotics, especially when quantification of active metabolites is required. While logistical barriers remain, technological advances may enhance feasibility and support broader integration into routine psychiatric care. Full article

(This article belongs to the Special Issue Advancements and Future Directions in Clinical Psychosis)

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15 pages, 676 KB

Open AccessArticle

Optimization of the Use of Generic Medications in Oncology: Improving Safety and Therapeutic Quality

by Diego Gómez Abreo, Daniel F. Alarcón Cano, Fernando Ayala, Nelson Belalcázar Carvajal, Marie Claire Berrouet Mejía, Oscar Beltrán, Carlos Alberto Calderón-Ospina, Hugo Castro-Salguero, Diana Marcela Escobar Cárdenas, Mauricio Lema-Medina, Juan Ignacio Marín Zuluaga, Pilar Milla Bernabé, Rafael E. Niño Velasco, Ruth Osorio Estévez, Jorge Mario Ortiz, Leonardo J. Rojas-Melo, Marcela Urrego, Carlos Vargas and Andrés F. Zuluaga

J. Clin. Med. 2025, 14(21), 7543; https://doi.org/10.3390/jcm14217543 (registering DOI) - 24 Oct 2025

Abstract

Introduction: Oncological diseases are one of the leading causes of mortality worldwide, with the high cost of therapies representing a critical barrier for health systems. Generic drugs have emerged as an alternative to reduce costs and improve access; however, their quality, safety, [...] Read more.

Introduction: Oncological diseases are one of the leading causes of mortality worldwide, with the high cost of therapies representing a critical barrier for health systems. Generic drugs have emerged as an alternative to reduce costs and improve access; however, their quality, safety, and efficacy remain a subject of regulatory and clinical debate. This issue is particularly sensitive in oncology, where generics often involve cytotoxic agents, narrow therapeutic indices, and complex formulations, all of which amplify the risks of therapeutic interchangeability. Materials and Methods: A multidisciplinary team composed of 19 experts in oncology, hepatology, gastroenterology, toxicology, endocrinology, and pharmacology was convened based on established academic contributions, clinical expertise, and participation in regulatory or guideline development. Evidence was synthesized through a non-systematic narrative review of PubMed, Embase, and regional databases. Consensus recommendations were developed using a two-round Delphi process, with agreement defined as ≥75%. Results: The Delphi panel produced six key recommendations: (1) stricter requirements for bioequivalence and bioavailability, tailored to oncology; (2) strengthened pharmacovigilance and real-world monitoring; (3) standardized protocols for therapeutic interchangeability, particularly for narrow therapeutic index agents; (4) active physician involvement in formulary decision-making; (5) harmonized regional regulatory frameworks, informed by FDA and EMA standards; and (6) expanded research on oncology-specific pharmacokinetic markers. While safety concerns dominated discussions, experts also acknowledged the potential of generics to reduce costs, improve equity, and enhance the sustainability of oncology care. Conclusions: The findings underscore the need for oncology-specific regulatory frameworks that extend beyond conventional bioequivalence standards. A balance is required: cost savings and equity gains offered by generics must be matched with robust safety mechanisms, regulatory harmonization, and physician-led oversight. Future research should expand expert representation, integrate real-world data, and address biosimilars in dedicated analyses to ensure safe and equitable integration of non-innovator therapies in cancer care. Full article

(This article belongs to the Topic Optimization of Drug Utilization and Medication Adherence)

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11 pages, 570 KB

Open AccessArticle

High-Sensitivity Cardiac Troponin as a Predictor of Atrial Fibrillation Detected After Stroke: Implications for Subsequent Cerebrocardiovascular Events

by Bum Sung Kim, Jung Jin Park, Ji-Hoon Choi, Chang Hee Kwon, Sung Hea Kim, Kina Jeon, Yu-jin Chung, Hahn Young Kim and Hyun-Joong Kim

J. Clin. Med. 2025, 14(21), 7542; https://doi.org/10.3390/jcm14217542 (registering DOI) - 24 Oct 2025

Abstract

Background: Atrial fibrillation (AF) may be detected at the time of ischemic stroke or newly detected after stroke. While AF detected after stroke (AFDAS) is associated with poor outcomes compared to sinus rhythm, its prognostic implications relative to known-AF are inconsistent. High-sensitivity cardiac [...] Read more.

Background: Atrial fibrillation (AF) may be detected at the time of ischemic stroke or newly detected after stroke. While AF detected after stroke (AFDAS) is associated with poor outcomes compared to sinus rhythm, its prognostic implications relative to known-AF are inconsistent. High-sensitivity cardiac troponin (hs-cTn) is a biomarker of myocardial injury, but its role in predicting AFDAS in stroke patients is unclear. We aimed to evaluate hs-cTn as a predictor for AFDAS and to compare all-cause death, readmission for heart failure (HF) and readmission for stroke among patients with non-AF, AFDAS, and known-AF in the post-ischemic stroke period. Methods: From August 2014 to July 2017, 1506 patients with acute ischemic stroke were consecutively enrolled in a retrospective single-center registry. Out of these, 1019 patients were selected for analysis. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, HF-caused readmission, or stroke-caused readmission during follow-up. Results: Out of 1019 ischemic stroke patients, 121 (13.8%) developed AFDAS over a median of 22.5 months; 135 had known-AF and 763 were maintained sinus rhythm during follow-up. Elevated hs-TnI (≥99th percentile), age > 75, and left atrial volume index >34 mL/m² independently predicted AFDAS. Both AFDAS and known-AF groups had a significantly increased risk of MACCE compared to the non-AF group (adjusted hazard ratio (HR) 1.85 and 1.76, respectively; p < 0.05 for both). The known-AF group also had a higher risk of all-cause mortality (adjusted HR 2.05, p = 0.02). The risks for MACCE and all-cause death did not differ significantly between the AFDAS and known-AF groups. Conclusions: An elevated hs-TnI level is independently associated with development of AFDAS and may serve as a valuable marker for stratifying the risk of future cerebrocardiovascular events following ischemic stroke. Full article

(This article belongs to the Special Issue Atrial Fibrillation and Its Complications: Preventive Strategies and Relative Evidence)

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4 pages, 180 KB

Open AccessEditorial

Gastrointestinal Cancer: Outcomes and Therapeutic Management

by Evgenia Mela and Maximos Frountzas

J. Clin. Med. 2025, 14(21), 7541; https://doi.org/10.3390/jcm14217541 (registering DOI) - 24 Oct 2025

Abstract

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(This article belongs to the Special Issue Gastrointestinal Cancer: Outcomes and Therapeutic Management)

16 pages, 293 KB

Open AccessPerspective

Management of Patients with Nickel Hypersensitivity Undergoing Patent Foramen Ovale Closure

by Anastasios Apostolos, Stamatios Gregoriou, Maria Drakopoulou, Georgios Trantalis, Aikaterini Tsiogka, Nikolaos Ktenopoulos, Panayotis K. Vlachakis, Paschalis Karakasis, Andreas Synetos, Georgios Tsivgoulis, Alexander Stratigos, Konstantinos Tsioufis and Konstantinos Toutouzas

J. Clin. Med. 2025, 14(21), 7540; https://doi.org/10.3390/jcm14217540 (registering DOI) - 24 Oct 2025

Abstract

Patent foramen ovale (PFO) is implicated in cryptogenic stroke and other clinical syndromes, with transcatheter closure demonstrating superiority over medical therapy in selected patients. Most closure devices are composed of nitinol, a nickel–titanium alloy, raising concerns in individuals with nickel hypersensitivity, one of [...] Read more.

Patent foramen ovale (PFO) is implicated in cryptogenic stroke and other clinical syndromes, with transcatheter closure demonstrating superiority over medical therapy in selected patients. Most closure devices are composed of nitinol, a nickel–titanium alloy, raising concerns in individuals with nickel hypersensitivity, one of the most prevalent contact allergies worldwide. Although typically manifesting as localized dermatitis, nickel allergy has been associated with systemic reactions after device implantation, including chest pain, palpitations, migraines, dyspnea, and cutaneous eruptions. Recent evidence indicates that nickel-sensitive patients experience a significantly higher incidence of post-procedural device-related symptoms. Nevertheless, severe reactions remain rare, and the benefits of PFO closure generally outweigh the risks. The predictive value of pre-implantation patch testing remains uncertain, and the lack of nickel-free alternatives constrains device selection. Management strategies are empirical, relying on symptomatic treatment with corticosteroids, antihistamines, or device explantation in refractory cases. Future research should focus on elucidating the pathophysiology of nickel-induced hypersensitivity in cardiovascular implants, improving diagnostic algorithms, and developing biocompatible, nickel-free devices. A multidisciplinary approach involving cardiologists, dermatologists, and allergists is essential to optimize outcomes in this complex subset of patients. Full article

(This article belongs to the Section Dermatology)

17 pages, 631 KB

Open AccessSystematic Review

Salivary Gland Sarcoidosis: Systematic Review of Case Reports and Case Series

by Nadin Abouseif, Mohamed Jaber and Reem B. Abdelsayed

J. Clin. Med. 2025, 14(21), 7539; https://doi.org/10.3390/jcm14217539 (registering DOI) - 24 Oct 2025

Abstract

Background: Salivary gland sarcoidosis is a rare manifestation of systemic sarcoidosis that poses a challenge in terms of its diagnosis due to its similarities to disorders such as Sjögren’s syndrome, other granulomatous diseases, and infections. Objective: To systematically review reported cases [...] Read more.

Background: Salivary gland sarcoidosis is a rare manifestation of systemic sarcoidosis that poses a challenge in terms of its diagnosis due to its similarities to disorders such as Sjögren’s syndrome, other granulomatous diseases, and infections. Objective: To systematically review reported cases of salivary gland sarcoidosis and summarize clinical presentation, diagnostic methods, treatments, and outcomes. Methods: We conducted a systematic search of PubMed, Scopus, Embase, ScienceDirect, and Medline for case reports and case series published up to April 2025. This review was registered with PROSPERO (CRD42024629263) and was conducted following PRISMA guidelines. Variables assessed included age, sex, presenting symptoms, location, duration of symptoms, treatment approaches, and outcomes. Study quality assessment was assessed using The Joanna Briggs Institute (JBI) Critical Appraisal tools. Results: A total of 28 articles involving 39 participants met the inclusion criteria, with a mean age of 42.7 years. Salivary gland sarcoidosis predominantly affected female patients (66.7%). The parotid gland was the most frequently involved site (82.1%). Common presenting features included glandular swelling that is usually painless, xerostomia, and facial palsy. Sarcoidosis was newly diagnosed in 82.1% of cases, primarily through histopathological examination revealing non-caseating granulomas. Systemic corticosteroids were the most common treatment. Outcomes were favorable in nearly all cases, with complete resolution post treatment or spontaneous remission without treatment. Conclusions: Salivary gland sarcoidosis predominantly affects middle-aged women, typically presenting as a painless parotid swelling and often serving as the initial sign of systemic disease. Diagnosis requires histopathological confirmation via biopsy, as serum ACE levels are insufficient alone. The prognosis is excellent, with most patients responding favorably to corticosteroids or even experiencing spontaneous resolution. This condition must be considered in differential diagnoses for persistent salivary gland swellings to ensure accurate diagnosis and prevent unnecessary interventions. Full article

(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)

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17 pages, 706 KB

Open AccessArticle

Anxiety and Depression in Adolescents with Prelingual Hearing Loss: Prevalence and Risk Factors

by Vijayalakshmi Easwar, Jason Gavrilis, Pelle Söderström, Teresa Ching, Greg Leigh and Vicky Zhang

J. Clin. Med. 2025, 14(21), 7538; https://doi.org/10.3390/jcm14217538 (registering DOI) - 24 Oct 2025

Abstract

Objectives: The aim of this study was to evaluate the prevalence of anxiety and depression symptoms and their predictors in 16–19-year-old adolescents with prelingual hearing loss (HL) who use spoken language. Methods: Self- and parent-reported symptoms were measured using RCADS-25 in [...] Read more.

Objectives: The aim of this study was to evaluate the prevalence of anxiety and depression symptoms and their predictors in 16–19-year-old adolescents with prelingual hearing loss (HL) who use spoken language. Methods: Self- and parent-reported symptoms were measured using RCADS-25 in 250 adolescents with HL (55.2% males; mean age = 17.1 years). A normal hearing (NH) peer group of 69 adolescents (56.5% males; mean age = 16.7 years) completed the self-reported RCADS-25. Key predictor variables included audiological factors, demographic factors, non-verbal IQ, language, communication, prosocial behaviour, and peer relations. Results: The proportion of adolescents with high self-reported anxiety was similar between HL and NH groups (~8%). Depression symptoms were more common in the HL group (11.2% self-reported, 15.8% parent-reported) than in the NH group (7.2%), but the difference was not statistically significant. Across informants, females had worse symptoms, but this association was no longer significant after accounting for communication difficulty. Among hearing aid users, higher prosocial behaviour was associated with fewer depression symptoms, while peer relations were a protective factor in cochlear implant users. Parent- and self-report congruence in symptom rating was modest (r = 0.56–0.68). Predictors of symptoms were consistent across informants, with parent happiness and socio-economic status additionally influencing parent-reported symptoms. Symptoms were unrelated to device type (hearing aid/cochlear implant), degree of hearing loss, or age at intervention. Adolescents with elevated symptoms also reported increased school absenteeism. Conclusions: Adolescents with HL reported anxiety at similar rates to NH peers but may have a higher prevalence of depression. Emotional well-being was influenced primarily by psychosocial and communication factors, not audiological characteristics. Full article

(This article belongs to the Section Mental Health)

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20 pages, 963 KB

Open AccessReview

Pharmacological Management of Oral and Esophageal Candidiasis: A Clinical Pharmacotherapy Perspective

by Toshinori Hirai and Masanori Nashi

J. Clin. Med. 2025, 14(21), 7537; https://doi.org/10.3390/jcm14217537 (registering DOI) - 24 Oct 2025

Abstract

Candida spp. are common components of normal microbiota in the oral cavity. However, Candida albicans can be a primary cause of superficial infections in the oral cavity and esophagus, especially in immunocompromised individuals. While these infections are rarely life-threatening, they can significantly impair [...] Read more.

Candida spp. are common components of normal microbiota in the oral cavity. However, Candida albicans can be a primary cause of superficial infections in the oral cavity and esophagus, especially in immunocompromised individuals. While these infections are rarely life-threatening, they can significantly impair quality of life and, in severe cases, progress to hematogenous dissemination. Oral candidiasis often exhibits as pseudomembranous, erythematous (atrophic), chronic hyperplastic, denture stomatitis, or angular cheilitis. Esophageal candidiasis is typically diagnosed by upper endoscopy, which involves histological examination and brushing. Clinical guidelines recommend topical antifungal agents for mild oral candidiasis, and systemic agents for moderate-to-severe disease or when topical therapy fails. However, azole antifungals pose a substantial risk of drug–drug interactions, primarily due to the inhibition of cytochrome P450 enzymes and drug transporters, which dramatically alters the pharmacokinetics of co-administered drugs. Additionally, amphotericin B, a polyene macrolide antibiotic, may cause nephrotoxicity and electrolyte disturbances (e.g., hypokalemia and hypomagnesemia). Moreover, the co-administration of nephrotoxic drugs may augment the toxicity associated with amphotericin B. Therefore, this review aimed to provide a comprehensive overview of the management of oral and esophageal candidiasis from the viewpoint of clinical pharmacology, with a particular focus on drug–drug interactions and adverse effect profiles. Full article

(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)

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11 pages, 1499 KB

Open AccessArticle

Prehospital Defibrillation Challenges in Victims Wearing Wetsuits: A Pilot Comparison of AED Pad Placement Strategies

by Myriam Santos-Folgar, Martín Otero-Agra, David Currás-García, Felipe Fernández-Méndez, Roberto Barcala-Furelos and Antonio Rodríguez-Núñez

J. Clin. Med. 2025, 14(21), 7536; https://doi.org/10.3390/jcm14217536 (registering DOI) - 24 Oct 2025

Abstract

Objective: This pilot study compared the positions of the antero-lateral (standard) and antero-posterior (alternative) pads in a simulated cardiac arrest scenario in athletes wearing a wetsuit. Methods: Seventeen undergraduate physical education students were instructed to attend to a simulated victim, with [...] Read more.

Objective: This pilot study compared the positions of the antero-lateral (standard) and antero-posterior (alternative) pads in a simulated cardiac arrest scenario in athletes wearing a wetsuit. Methods: Seventeen undergraduate physical education students were instructed to attend to a simulated victim, with no signs of life, dressed in a wetsuit. In a randomized fashion, they were instructed to place the defibrillator pads in the standard position (antero-lateral) or in the antero-posterior option. The variables analyzed were the time required to perform the procedure and the difficulty and fatigue perceived by the rescuers. Results: Thirty-four interventions were analyzed (17 with each technique), showing that with the antero-posterior option, the time required to expose the area was less (median 6.2 vs. 12.7 s, p = 0.001), but more time was required to dry it (median 31.0 vs. 18.4 s, p = 0.002). No significant differences were found between the two options in the total time from onset to first flush or in the perception of difficulty and fatigue. Conclusions: In the case of caring for a cardiac arrest victim wearing a wetsuit, the alternative of placing the defibrillator pads in the antero-posterior position is not a significant advantage over the standard position. Both configurations may be considered acceptable in prehospital aquatic settings, depending on situational constraints and rescuer preference. Full article

(This article belongs to the Special Issue Cardiopulmonary Resuscitation in the Emergency Care Unit)

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13 pages, 1125 KB

Open AccessArticle

Comparison of Cariogenic Organic Acid Concentrations According to Combined Use of Sucrose and Sugar Alcohols

by Su-Yeon Hwang and Jung-Eun Park

J. Clin. Med. 2025, 14(21), 7535; https://doi.org/10.3390/jcm14217535 (registering DOI) - 24 Oct 2025

Abstract

Objective: This study involves a quantitative analysis of organic acids (lactate, acetate, propionate, formate, butylate, pyruvate, and valeric acid) concentrations after applying sucrose and sugar alcohols such as xylitol and erythritol in the oral cavity. Methods: Saliva samples were obtained from five volunteers [...] Read more.

Objective: This study involves a quantitative analysis of organic acids (lactate, acetate, propionate, formate, butylate, pyruvate, and valeric acid) concentrations after applying sucrose and sugar alcohols such as xylitol and erythritol in the oral cavity. Methods: Saliva samples were obtained from five volunteers before and up to 60 min after oral washing with sucrose and sugar alcohol (xylitol and erythritol). Concentrations of seven organic acids (lactate, acetate, propionate, formate, butyrate, pyruvate, and valerate) were determined by high-performance liquid chromatography using ion chromatography with conductivity detection. Results: The combination of sucrose and sugar alcohols, particularly erythritol, led to lower average lactate levels compared with 10% sucrose. Moreover, 1:1 post hoc analysis revealed that the levels of acetate and propionate decreased in the group treated with 2.5% and 7.5% of erythritol compared with those treated with xylitol (p < 0.05). However, the results did not indicate concentration dependence; owing to the small sample size (n = 5) these findings must be interpreted with care. This necessitates follow-up research, including oral bacterial testing and studies with larger sample sizes. Conclusions: The concentrations of organic acids varied with respect to the combined administration of sucrose and sugar alcohols. Further studies are necessary to investigate the effect of other sugar alcohols on bacterial growth. Full article

(This article belongs to the Special Issue Oral Health and Dental Care: Current Advances and Future Options)

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15 pages, 451 KB

Open AccessArticle

Impact of On-Demand Selective Suturing on Renal Function Preservation During Clampless Robotic-Assisted Partial Nephrectomy: Insights from a Large Multicentric Italian Cohort

by Angelo Porreca, Davide De Marchi, Filippo Marino, Marco Giampaoli, Daniele D’Agostino, Francesca Simonetti, Antonio Amodeo, Paolo Corsi, Francesco Claps, Alessandro Crestani, Daniele Romagnoli, Pier Paolo Prontera, Gian Maria Busetto and Luca Di Gianfrancesco

J. Clin. Med. 2025, 14(21), 7534; https://doi.org/10.3390/jcm14217534 (registering DOI) - 24 Oct 2025

Abstract

Objectives: To evaluate perioperative outcomes, renal function preservation, and short-term oncologic results of off-clamp, sutureless, or selectively sutured robotic-assisted partial nephrectomy (RAPN) in patients with renal tumors treated at multiple high-volume centers. Methods: This multicenter retrospective study included 250 patients who [...] Read more.

Objectives: To evaluate perioperative outcomes, renal function preservation, and short-term oncologic results of off-clamp, sutureless, or selectively sutured robotic-assisted partial nephrectomy (RAPN) in patients with renal tumors treated at multiple high-volume centers. Methods: This multicenter retrospective study included 250 patients who underwent off-clamp, sutureless/selectively sutured RAPN between January 2018 and December 2024. Patients with solitary kidneys, tumors > 7 cm, or prior renal surgery were excluded. All procedures were performed without renal artery clamping, using hemostatic agents and selective suturing when necessary. Perioperative, functional, and oncologic outcomes were compared with 313 patients who underwent standard RAPN with parenchymal suturing. Results: The median operative time was 110 min (IQR 100–140), and the median estimated blood loss was 180 mL (IQR 100–250). The overall complication rate was 8.4%, predominantly Clavien–Dindo grade I–II, with no conversions to open surgery. The median decline in estimated glomerular filtration rate (eGFR) at three months was 5.5% (IQR 3.5–8.9; p = 0.56), and no cases of acute kidney injury were recorded. The positive surgical margin rate was 3.7%, and no tumor recurrences were observed during the 12-month follow-up period. Conclusions: Off-clamp, sutureless or selectively sutured robotic-assisted partial nephrectomy (RAPN) was not associated with increased perioperative risk, renal functional decline, or compromised short-term oncologic control compared with conventional sutured RAPN. These findings indicate that the technique is feasible and safe in appropriately selected patients, although prospective studies with longer follow-up are needed to confirm long-term outcomes and refine patient selection criteria. Full article

(This article belongs to the Special Issue Current Status and Future of Urological Surgery)

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12 pages, 842 KB

Open AccessArticle

Intraoperative Application of Cold Atmospheric Plasma Reduces Inguinal Wound Healing Disorders—A Pilot Study

by Ursula E. M. Werra, Wael Ahmad, Michael Schoepal, Tran T. Trinh and Bernhard Dorweiler

J. Clin. Med. 2025, 14(21), 7533; https://doi.org/10.3390/jcm14217533 - 24 Oct 2025

Abstract

Background: Inguinal wound healing disorders have been a relevant problem in the surgical treatment of peripheral arterial occlusive disease (PAD) for decades with reported rates of up to 30%. Despite the otherwise diverse innovations in vascular surgery, there are hardly any improvements [...] Read more.

Background: Inguinal wound healing disorders have been a relevant problem in the surgical treatment of peripheral arterial occlusive disease (PAD) for decades with reported rates of up to 30%. Despite the otherwise diverse innovations in vascular surgery, there are hardly any improvements in this area, on the contrary, comorbidities such as obesity, as relevant risk factors, continue to increase. The application of cold atmospheric plasma (CAP) has in turn shown promise in approaches for the treatment of chronic wounds, we therefore evaluated the potential reduction in inguinal wound healing disorders through the intraoperative application of CAP. Methods: We carried out a pilot study including 50 patients with a high risk for inguinal wound healing disorders that underwent a peripheral arterial reconstruction with inguinal access. Alternately, these patients were treated once intraoperatively with CAP (n = 25) or served as the control group (n = 25). The wound condition was then evaluated for the next fourteen days, with a follow up of three months. Results: The two groups showed no differences regarding risk factors such as smoking, obesity, PAD stage or surgery-related aspects like incision length or duration of surgery. No differences were found regarding wound-related readmission. However, the patients who had been treated intraoperatively with CAP showed a significant reduction in the need for surgical revisions due to inguinal wound healing disorders (8% vs. 32%, p = 0.034). Conclusions: This pilot study shows that the intraoperative use of CAP could be a promising approach to reduce major inguinal wound healing disorders. Full article

(This article belongs to the Section Vascular Medicine)

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13 pages, 1964 KB

Open AccessArticle

HMGB-1 Increases Proinflammatory Reaction via TLR4 in Human Granulosa Cells of Endometriosis

by Hye In Kim, Kyung Hee Kim, SiHyun Cho, Young Sik Choi, Byung Seok Lee, Seung Joo Chon and Bo Hyon Yun

J. Clin. Med. 2025, 14(21), 7532; https://doi.org/10.3390/jcm14217532 - 24 Oct 2025

Abstract

Background/Objectives: Oxidative stress is a critical factor in the development and progression of endometriosis. Granulosa cells, which reside near oocytes in follicles, exhibit steroidogenic activity, and, consequently, influence oocyte quality. Increased oxidative stress may induce the danger signal such as HMGB-1 in granulosa [...] Read more.

Background/Objectives: Oxidative stress is a critical factor in the development and progression of endometriosis. Granulosa cells, which reside near oocytes in follicles, exhibit steroidogenic activity, and, consequently, influence oocyte quality. Increased oxidative stress may induce the danger signal such as HMGB-1 in granulosa cells and eventually change the follicular environment of patients with endometriosis. This study aimed to demonstrate that HMGB-1 and its receptors, TLR4 and RAGE, play important roles in the changes in the follicular environment in infertile patients with endometriosis. Methods: In the immortalized human granulosa cell line (hGL5), cell proliferation and apoptosis assay, ELISA for estradiol, qRT-PCR for HMGB-1 and TLR4, Western blot for apoptosis-related and NF-κB pathway-related proteins, and ELISA for inflammatory molecules IL-1β and IL-6 were performed after H₂O₂ treatment. Results: H₂O₂ treatment to the hGL5 cell line decreased cell proliferation via apoptosis and, as a result, decreased steroidogenesis. Also, it increased the gene expression of HMGB-1 and TLR4, increased the protein expression related to the NF-κB pathway, and increased the release of inflammatory molecules IL-1β and IL-6. Conclusions: The results indicate that oxidative stress associated with endometriosis may increase inflammation by interacting with HMGB-1 and TLR4 and activating the NF-κB pathway to increase proinflammatory responses. The findings of this study may provide insight into endometriosis with decreased oocyte quality. Full article

(This article belongs to the Special Issue Clinical Perspectives on Women’s Reproductive Health: Challenges and Management Strategies)

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13 pages, 845 KB

Open AccessProtocol

Acute Effects of Cannabis and THC Oils on Cardiovascular Hemodynamics and Muscle Electrical Activity in Healthy Individuals: A Controlled Clinical Crossover Trial Protocol

by Marina Lyra Lima Cabral Fagundes, Edna Karla Ferreira Laurentino, Bruno Lobão Soares, Matías Otto-Yañez, Emerson Arcoverde Nunes, Matheus de Freitas Fernandes Pedrosa, Jessica Danielle Medeiros da Fonseca, Vanessa Regiane Resqueti and Guilherme Augusto de Freitas Fregonezi

J. Clin. Med. 2025, 14(21), 7531; https://doi.org/10.3390/jcm14217531 - 24 Oct 2025

Abstract

Background/Objectives: Cannabis sativa (CS) exerts its effects through the endocannabinoid system. Although studies have shown limited evidence regarding the plant’s therapeutic efficacy, little is known about the standardization of doses and their corresponding effects. This study aims to analyze changes in muscle electrical [...] Read more.

Background/Objectives: Cannabis sativa (CS) exerts its effects through the endocannabinoid system. Although studies have shown limited evidence regarding the plant’s therapeutic efficacy, little is known about the standardization of doses and their corresponding effects. This study aims to analyze changes in muscle electrical activity and cardiovascular hemodynamics before, during, and after administering doses of full-spectrum cannabis and tetrahydrocannabinol (THC) oils. Methods: Participants will be assigned to a single group that will undergo five different interventions: CBD + THC at 12.50 mg, CBD + THC at 18.75 mg, THC intervention at 12.50 mg, THC at 18.75 mg, and placebo intervention (PI). The study will enroll healthy, self-reported men and women aged 18 to 50, with no mental health disorders and no exposure to CS in the past six months. Interventions will occur on five randomized days, following three phases: (1) pre-intervention (PRE-IN); (2) intervention (IN)—1 h after oral oil ingestion; and (3) post-intervention (POST-IN)—2 h 30 min after ingestion. At each stage, 2 min of quiet breathing (QB); 2 min with an inspiratory resistance valve (30% of maximal inspiratory pressure—PImax) and expiratory valve (10% of maximal expiratory pressure—PEmax) (VAL); and 4 min of recovery without the valve (REC) were evaluated. Register: RBR-3jsvtbr. Conclusions: This study will enhance the understanding of the dose–response effects of full-spectrum cannabis and THC oils and may serve as a model for future research in this field. Full article

(This article belongs to the Section Cardiovascular Medicine)

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J. Clin. Med., Volume 14, Issue 21 (November-1 2025) – 109 articles

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