Journal of Clinical Medicine

11 pages, 425 KB

Open AccessEditor’s ChoiceArticle

Assessing Potential Valve-Preserving Effects of SGLT2 Inhibitors in Degenerative Aortic Stenosis: A Propensity-Matched Study

by Olivier Morel, Michael Guglieri, Antonin Trimaille, Benjamin Marchandot, Arnaud Bisson, Amandine Granier, Valérie Schini-Kerth, Anne Bernard and Laurent Fauchier

J. Clin. Med. 2026, 15(2), 714; https://doi.org/10.3390/jcm15020714 - 15 Jan 2026

Viewed by 404

Abstract

Background: Sodium–glucose cotransporter 2 inhibitors (SGLT2 inhibitors), initially developed for glycemic control in type 2 diabetes, have demonstrated robust cardiovascular and renal benefits. Emerging evidence suggests that these agents may also affect valvular pathobiology, particularly in degenerative aortic stenosis (AS), through anti-inflammatory and [...] Read more.

Background: Sodium–glucose cotransporter 2 inhibitors (SGLT2 inhibitors), initially developed for glycemic control in type 2 diabetes, have demonstrated robust cardiovascular and renal benefits. Emerging evidence suggests that these agents may also affect valvular pathobiology, particularly in degenerative aortic stenosis (AS), through anti-inflammatory and antifibrotic mechanisms. Objectives: This study evaluated whether SGLT2 inhibitor use is associated with improved clinical outcomes in degenerative AS, including all-cause mortality and the need for SAVR or TAVR, recognizing that these endpoints represent surrogate rather than direct measures of valve hemodynamic progression. Methods: A retrospective cohort analysis was conducted using TriNetX, a federated electronic medical record-based research network. Diagnoses are captured using ICD-9/ICD-10-CM codes and medications using ATC codes. Adults with non-rheumatic AS were stratified by SGLT2 inhibitors use. Propensity score matching (1:1) was performed to balance baseline characteristics between treated and untreated groups (n = 10,912 per group). Primary outcomes included all-cause mortality, TAVR, and SAVR during follow-up. Echocardiographic parameters (AVA, Vmax, mean gradient) were not systematically available. Results: After adjustment for comorbidities, SGLT2 inhibitor use was independently associated with lower all-cause mortality (6.15% vs. 9.34% HR 0.595; 95% CI 0.552–0.641; p < 0.001), TAVR (2.81% vs. 2.89% HR 0.835; 95% CI 0.746–0.934; p = 0.002), SAVR (1.28% vs. 1.90% HR 0.514; 95% CI 0.442–0.599; p < 0.001), cardiac arrest (0.82% vs. 1.21% HR 0.71; 95% CI 0.582–0.867; p < 0.001), and end-stage kidney disease (0.40% vs. 1.0% HR 0.292; 95% CI 0.222–0.384; p < 0.001). Although these associations may suggest slower disease progression, interpretation is limited by the lack of systematic echocardiographic follow-up. Conclusions: In addition to their established benefits in heart failure and renal protection, SGLT2 inhibitors may have valve-preserving effects in degenerative AS. Because true hemodynamic progression could not be evaluated, these results should be viewed as associations with surrogate clinical endpoints. Prospective studies with standardized imaging are required to determine whether SGLT2 inhibition can directly alter the course of this currently untreatable disease Full article

(This article belongs to the Special Issue Emerging Treatment Options in Aortic Valve Disease and Aortic Stenosis)

► Show Figures

Graphical abstract

7 pages, 450 KB

Open AccessEditor’s ChoicePerspective

Should Prediabetes Be Classified as a Treatable Disease?

by William E. Winter and Ishwarlal Jialal

J. Clin. Med. 2026, 15(2), 710; https://doi.org/10.3390/jcm15020710 - 15 Jan 2026

Viewed by 302

Abstract

Prediabetes is a serious and major global problem afflicting approximately 21% of the world’s population. It is the intermediate stage between normal glucose levels and type 2 diabetes mellitus (T2DM). Prediabetes is associated with major complications including the development of T2DM and increased [...] Read more.

Prediabetes is a serious and major global problem afflicting approximately 21% of the world’s population. It is the intermediate stage between normal glucose levels and type 2 diabetes mellitus (T2DM). Prediabetes is associated with major complications including the development of T2DM and increased cardiovascular disease (CVD). It can be easily diagnosed with an inexpensive plasma glucose level and/or a hemoglobin A1c (HbA1c) measurement. The mainstay of treatment is intensive lifestyle (ILS) intervention, including reduction in calories, especially saturated fats, refined carbohydrates, etc., coupled with regular physical activity of 150 min per week since ILS changes, with at least a 5% weight loss, have been shown to reduce progression to T2DM in multiple studies globally. Also, metformin therapy has been shown to prevent the progression to T2DM. In conclusion, serious consideration by guideline committees to classify prediabetes as a disease is highly recommended based on its global burden, easy and cost-effective diagnosis, association with serious conditions of diabetes and CVD, and effective ILS intervention. Therapy targeting those at an especially high risk for T2DM, such as persons with impaired glucose tolerance (IGT), impaired fasting glucose (IFG) with values ≥ 110 mg/dL (6.1 mmol/L), and/or HbA1c ≥ 6.0% (42 mmol/mol) coupled with overweightness or obesity. Full article

(This article belongs to the Section Endocrinology & Metabolism)

► Show Figures

Figure 1

16 pages, 254 KB

Open AccessEditor’s ChoiceReview

Robotic Horizons in Plastic Surgery: A Look Toward the Future

by Ali Foroutan, Diwakar Phuyal, Georgia Babb, Julia Ting, Ghazal Mashhadiagha, Niayesh Najafi, Risal Djohan, Sarah N. Bishop and Graham S. Schwarz

J. Clin. Med. 2026, 15(2), 602; https://doi.org/10.3390/jcm15020602 - 12 Jan 2026

Viewed by 448

Abstract

Background/Objectives: Robotic technology has transformed several surgical specialties, offering enhanced precision, visualization, and dexterity. In plastic and reconstructive surgery, robotic systems are increasingly utilized across a range of procedures, though their applications remain in early development. Methods: A review of the literature was [...] Read more.

Background/Objectives: Robotic technology has transformed several surgical specialties, offering enhanced precision, visualization, and dexterity. In plastic and reconstructive surgery, robotic systems are increasingly utilized across a range of procedures, though their applications remain in early development. Methods: A review of the literature was performed to identify studies reporting robot-assisted procedures in plastic and reconstructive surgery. The literature was synthesized thematically to characterize current procedural applications, emerging technologies, and areas of active clinical investigation. Results: Robotic systems have been reported in a broad range of plastic and reconstructive procedures, including flap harvest, microsurgery, breast reconstruction, craniofacial and head and neck reconstruction, esthetic surgery, and gender-affirming surgery. The existing studies primarily consist of case series and case reports with substantial variability in reported indications, techniques, and technological platforms. Comparative clinical outcomes and long-term data are limited. Conclusions: Robot-assisted reconstruction continues to expand across multiple procedural domains. However, current evidence remains largely descriptive, underscoring the need for standardized reporting and prospective studies to better define clinical value, safety, and appropriate indications. Full article

(This article belongs to the Special Issue Plastic Surgery: Challenges and Future Directions)

13 pages, 648 KB

Open AccessEditor’s ChoiceArticle

Geripausal Women—A New Challenge for Urogynecology in Upcoming Years

by Aleksandra Kołodyńska, Aleksandra Kamińska, Aleksandra Strużyk, Ewa Rechberger-Królikowska, Magdalena Ufniarz and Tomasz Rechberger

J. Clin. Med. 2026, 15(2), 530; https://doi.org/10.3390/jcm15020530 - 9 Jan 2026

Viewed by 387

Abstract

Background/Objectives: The growing population of women aged ≥ 80 years poses a new challenge for urogynecology. Advanced age, comorbidities, and polypharmacy raise concerns regarding the safety of procedures in the management of pelvic floor disorders (PFDs) such as pelvic organ prolapse (POP), stress [...] Read more.

Background/Objectives: The growing population of women aged ≥ 80 years poses a new challenge for urogynecology. Advanced age, comorbidities, and polypharmacy raise concerns regarding the safety of procedures in the management of pelvic floor disorders (PFDs) such as pelvic organ prolapse (POP), stress urinary incontinence (SUI), and overactive bladder (OAB). Individualized, frailty-based assessment is essential in this group. The aim of the study was to evaluate the safety profile of urogynecological surgical procedures among women aged ≥ 80 years at a single tertiary center. Methods: In a retrospective observational single-center study, we analyzed the medical documentation of 774 hospitalizations of women aged ≥ 80 years admitted between 2014 and 2023. The analysis included indications, comorbidities, treatment types, anesthesia, and complications. Comorbidity and surgical risk were evaluated using the Charlson Comorbidity Index (CCI) and Clavien–Dindo classification. Results: A total of 720 admissions with complete medical records were analyzed, of which 65% were for urogynecological conditions. In this group, the mean age was 83.0 years and mean BMI was 27.2 kg/m². Most patients (92.9%) had comorbidities, mainly hypertension (84.2%) and diabetes (21.1%). POP was the leading indication (52%), followed by SUI (35%) and OAB (27%). Surgical management was performed in 95% of POP cases, predominantly via vaginal native tissue repair (80%), especially LeFort colpocleisis (20%). The transobturator sling (TOT) was the most frequent SUI surgery. Intraoperative complications occurred in 1.5% of cases and postoperative ones were mainly minor (Clavien–Dindo I–II). No procedure-related deaths were recorded. Conclusions: In this cohort, surgical treatment of urogynecological problems in women ≥80 years was associated with a low rate of major complications, suggesting that it can be safely offered to elderly patients. Careful preoperative assessment based on frailty and comorbidity rather than chronological age remains essential. Full article

(This article belongs to the Special Issue Current Trends in Urogynecology: 3rd Edition)

► Show Figures

Figure 1

24 pages, 651 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Auditory Discrimination of Parametrically Sonified EEG Signals in Alzheimer’s Disease

by Rubén Pérez-Elvira, Javier Oltra-Cucarella, María Agudo Juan, Luis Polo-Ferrero, Raúl Juárez-Vela, Jorge Bosch-Bayard, Manuel Quintana Díaz, Bogdan Neamtu and Alfonso Salgado-Ruiz

J. Clin. Med. 2026, 15(1), 140; https://doi.org/10.3390/jcm15010140 - 24 Dec 2025

Viewed by 503

Abstract

Background/Objectives: Alzheimer’s disease (AD) requires accessible and non-invasive biomarkers that can support early detection, especially in settings lacking specialized expertise. Sonification techniques may offer an alternative way to convey neurophysiological information through auditory perception. This study aimed to evaluate whether human listeners [...] Read more.

Background/Objectives: Alzheimer’s disease (AD) requires accessible and non-invasive biomarkers that can support early detection, especially in settings lacking specialized expertise. Sonification techniques may offer an alternative way to convey neurophysiological information through auditory perception. This study aimed to evaluate whether human listeners without EEG training can discriminate between sonified electroencephalographic (EEG) patterns from patients with AD and healthy controls. Methods: EEG recordings from 65 subjects (36 with Alzheimer’s, 29 controls) from the Open-Neuro ds004504 dataset were used. Data were processed through sliding-window spectral analysis, extracting relative band powers across five frequency bands (delta: 1–4 Hz, theta: 4–8 Hz, alpha: 8–13 Hz, beta: 13–30 Hz, gamma: 30–45 Hz) and spectral entropy, aggregated across 10 topographic regions. Extracted features were sonified via parameter mapping to independent synthesis sources per frequency band, implemented in an interactive web interface (Tone.js v14.8.49) enabling auditory evaluation. Eight evaluators without EEG experience blindly classified subjects into two groups based solely on listening to the sonifications. Results: Listeners achieved a mean classification accuracy of 76.12% (SD = 17.95%; range: 49.25–97.01%), exceeding chance performance (p = 0.001, permutation test). Accuracy variability across evaluators suggests that certain auditory cues derived from the sonified features were consistently perceived. Conclusions: Parametric EEG sonification preserves discriminative neurophysiological information that can be perceived through auditory evaluation, enabling above-chance differentiation between Alzheimer’s patients and healthy controls without technical expertise. This proof-of-concept study supports sonification as a complementary, accessible method for examining brain patterns in neurodegenerative diseases and highlight its potential contribution to the development of accessible diagnostic tools. Full article

(This article belongs to the Special Issue Innovative Approaches to the Challenges of Neurodegenerative Disease)

► Show Figures

Figure 1

26 pages, 2236 KB

Open AccessFeature PaperEditor’s ChoiceReview

Acute Coronary Syndromes: State-of-the-Art Diagnosis, Management, and Secondary Prevention

by Xun Yuan, Stephan Nienaber, Ibrahim Akin, Tito Kabir and Christoph A. Nienaber

J. Clin. Med. 2026, 15(1), 16; https://doi.org/10.3390/jcm15010016 - 19 Dec 2025

Viewed by 6380

Abstract

Background: Acute coronary syndromes (ACSs) remain a leading cause of death and disability. Since the publication of the 2023 ESC ACS guidelines, multiple studies and an ESC/EAS dyslipidaemia update have refined how clinicians diagnose, revascularize, and treat ACS across the care continuum. Content: [...] Read more.

Background: Acute coronary syndromes (ACSs) remain a leading cause of death and disability. Since the publication of the 2023 ESC ACS guidelines, multiple studies and an ESC/EAS dyslipidaemia update have refined how clinicians diagnose, revascularize, and treat ACS across the care continuum. Content: This state-of-the-art review synthesizes advances from 2023 to 2025 across five domains. Diagnosis: High-sensitivity troponin-based accelerated pathways remain foundational; GRACE 3.0 improves calibration for early vs. delayed angiography, while selective use of CCTA and routine use of intracoronary imaging/physiology help define the mechanism and optimize PCI. Revascularization: complete revascularization continues to underpin care in multivessel disease, with recent data favouring culprit-only PCI acutely and staged non-culprit treatment during the index stay in most STEMI presentations, particularly with heart-failure physiology. Antithrombotic therapy: Aspirin remains critical early after ACS-PCI; emerging evidence supports shorter DAPT and aspirin withdrawal after 1 month in carefully selected, low-ischaemic-risk patients, whereas day-0 aspirin-free strategies in unselected ACS are not non-inferior. Secondary prevention: A “strike early and strong” approach to LDL-cholesterol—often with combination therapy in hospital—is emphasized, alongside nuanced roles for SGLT2 inhibitors and GLP-1 receptor agonists. Special populations and implementation: Sex- and age-aware tailoring (including MINOCA/SCAD evaluation), pragmatic bleeding-risk mitigation, digitally enabled cardiac rehabilitation, and registry-driven quality improvement translate evidence into practice. Summary: Contemporary ACS care is moving from uniform protocols toward risk-stratified, mechanism-informed pathways. We offer practical algorithms and checklists to align interventional timing, antithrombotic intensity/duration, and secondary prevention with individual patient risk—bridging new evidence to bedside decisions. Full article

(This article belongs to the Special Issue Acute Coronary Syndromes: From Diagnosis to Treatment)

► Show Figures

Figure 1

15 pages, 1925 KB

Open AccessEditor’s ChoiceSystematic Review

Fully Robotic Ivor-Lewis Esophagectomy Versus Hybrid Robotic Esophagectomy—A Review and Meta-Analysis of the Clinical Outcomes

by Michele Manigrasso, Anna D’Amore, Francesco Maione, Nicola Gennarelli, Carmine Iacovazzo, Marco Milone and Pietro Anoldo

J. Clin. Med. 2025, 14(24), 8902; https://doi.org/10.3390/jcm14248902 - 16 Dec 2025

Viewed by 339

Abstract

Background: Esophageal cancer ranks among the top ten most prevalent cancers worldwide and remains a significant contributor to cancer-related mortality. While surgery combined with neoadjuvant therapy stands as the cornerstone treatment, the evolution of surgical techniques towards minimally invasive procedures has shown promising [...] Read more.

Background: Esophageal cancer ranks among the top ten most prevalent cancers worldwide and remains a significant contributor to cancer-related mortality. While surgery combined with neoadjuvant therapy stands as the cornerstone treatment, the evolution of surgical techniques towards minimally invasive procedures has shown promising results. Robotic Assisted Minimally Invasive Esophagectomy (RAMIE) emerges as a potential advancement, offering precise movements and a three-dimensional endoscopic view. Against this backdrop, clarifying whether a fully robotic approach provides measurable perioperative or early oncologic advantages over a hybrid technique is clinically relevant. Despite initial skepticism, studies comparing fully robotic and hybrid approaches for esophagectomy have been conducted to evaluate their feasibility and sustainability. Methods: A systematic review and meta-analysis were performed following PRISMA guidelines. Four retrospective studies comparing fully robotic and hybrid approaches were included, comprising 1540 patients. Results: Intraoperative outcomes favored the fully robotic approach, showing shorter operative times and reduced blood loss (MD = −41 min, p = 0.056, 95% CI: −83.202; 0.994 and MD = −48.762 mL, p = 0.040, 95% CI: −95.257; −2.266, respectively). Additionally, the fully robotic approach demonstrated advantages in terms of lymph node retrieval and shorter ICU and hospital stay (MD = −0.894, p < 0.0001, 95% CI: −1.224; −0.564, MD = −1.139 days, p < 0.0001, 95% CI: −1.313; −0.965 and MD = −3.264 days, p = 0.011, 95% CI: −5.767; −0.760, respectively). Conclusions: Although limitations exist, including the retrospective nature of the studies and limited sample size, the findings suggest that the fully robotic approach may offer superior outcomes compared to the hybrid approach for Ivor-Lewis esophagectomy. These results highlight the potential of robotics in enhancing safety and effectiveness in oesophageal cancer surgery, encouraging further consideration and adoption by surgeons. Full article

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

► Show Figures

Figure 1

16 pages, 465 KB

Open AccessEditor’s ChoiceReview

Pharmacologic and Nonpharmacologic Pain Management in Patients with Traumatic Brain Injury: A Multidisciplinary Approach

by Benjamin S. Esneault, Macie B. Maddox, Ethan M. Loewe, Miguel A. Pappolla, Tomasina Q. Parker-Actlis, Sahar Shekoohi and Alan D. Kaye

J. Clin. Med. 2025, 14(24), 8713; https://doi.org/10.3390/jcm14248713 - 9 Dec 2025

Viewed by 888

Abstract

Traumatic brain injury (TBI) is a major global health problem and a leading cause of long-term neurological disability. TBI produces a spectrum of persistent symptoms, including cognitive impairment, mood and behavioral disturbances, sleep disruption, fatigue, and autonomic dysregulation. Chronic pain is among the [...] Read more.

Traumatic brain injury (TBI) is a major global health problem and a leading cause of long-term neurological disability. TBI produces a spectrum of persistent symptoms, including cognitive impairment, mood and behavioral disturbances, sleep disruption, fatigue, and autonomic dysregulation. Chronic pain is among the most debilitating sequelae, affecting physical, emotional, and social functioning. The etiology of post-TBI pain is multifactorial, arising from initial structural and biochemical injury to the nervous system, maladaptive neuroplastic changes, neuroinflammation, and psychological comorbidities that amplify pain perception and chronicity. This review explores the complex pathophysiology of post-TBI pain and outlines a multidisciplinary framework for management. Pain syndromes are classified according to the International Association for the Study of Pain’s mechanistic framework as nociceptive pain (resulting from tissue injury and inflammation), neuropathic pain (due to lesion or disease of the somatosensory nervous system), and nociplastic pain (arising from altered nociceptive processing without clear evidence of tissue or nerve damage). Many patients exhibit mixed pain phenotypes driven by neuroinflammation and central sensitization. Pharmacologic approaches, including anti-inflammatory agents, anticonvulsants, and antidepressants, require cautious titration due to TBI-related comorbidities. Equally essential are non-pharmacologic strategies such as physical and occupational therapy, cognitive behavioral therapy, and neuromodulation techniques, which target both biomechanical and psychosocial contributors. Emerging innovations, machine learning for prognostication, blood biomarkers for structural injury, and neuro-reparative agents, represent the next frontier in personalized management. Effective care for post-TBI pain requires an integrated strategy that combines mechanistic classification, multidisciplinary treatments, and advancing diagnostic technologies. Full article

(This article belongs to the Section Brain Injury)

► Show Figures

Figure 1

14 pages, 363 KB

Open AccessEditor’s ChoiceArticle

Change in Antinuclear Antibodies After Lung Transplantation in Patients with Systemic Sclerosis

by Víctor Barreales-Rodríguez, Alfredo Guillen-Del-Castillo, Cristina Berastegui, Manuel López-Meseguer, Víctor Monforte, Berta Saez-Gimenez, Ana Villar, Iñigo Ojanguren, Claudia Codina-Clavaguera, Alejandra Fernández-Luque, María Teresa Sanz-Martínez, Laura Viñas-Giménez, Janire Perurena-Prieto, Laura Triginer-Gil, Luis Alcalá-González, Carlos Bravo and Carmen Pilar Simeón Aznar

J. Clin. Med. 2025, 14(24), 8673; https://doi.org/10.3390/jcm14248673 - 7 Dec 2025

Viewed by 456

Abstract

Objectives: Lung transplantation (LT) is a rescue therapy for end-stage pulmonary diseases, including systemic autoimmune diseases. The aim of this study was to analyse the evolution of patients with systemic sclerosis (SSc) who, after undergoing LT, become negative for antinuclear antibodies (ANA) and [...] Read more.

Objectives: Lung transplantation (LT) is a rescue therapy for end-stage pulmonary diseases, including systemic autoimmune diseases. The aim of this study was to analyse the evolution of patients with systemic sclerosis (SSc) who, after undergoing LT, become negative for antinuclear antibodies (ANA) and to assess whether they have different clinical and prognostic characteristics than patients who do not become negative. Material and Methods: A retrospective, descriptive analysis was performed over a cohort of patients with a diagnosis of SSc, who underwent unilateral or bilateral LT between 2006 and 2021 at the Vall d’Hebron University Hospital. Clinical and analytical data were obtained from these patients by reviewing their electronic medical records. Two groups of patients were compared: those who tested negative for ANA after LT and those who did not. Statistical analysis was performed with SPSS Statistics 20.0. Results: Eighteen patients were included. The most frequent indication for LT was interstitial lung disease (ILD) combined with pulmonary hypertension (PH), in 13 (72%) patients. All had ANA before the LT (n = 18), and regarding specific SSc autoantibodies, anti-topoisomerase I was presented in 44% (n = 8), anti-U11/U12RNP in 17% (n = 3), anti-RNA Polymerase III in 11.1% (n = 2), anti-Ro52 in 11% (n = 2) and anti-centromere in 6% of individuals (n = 1). 39% (n = 7) of the patients had negative post-LT ANA, 44% (n = 8) had declining titres, and 17% (n = 3) had stable ANA titres. Titres did not increase in any case after LT. Those patients who became ANA-negative after LT were those who had significantly lower titres before LT. No statistically significant differences between groups were found related to pre-LT clinical characteristics, immunosuppressive regimen applied after LT, or in post-LT outcomes. A non-significant trend towards better survival was observed in patients who became ANA negative, with a cumulative survival at 5 years of 85.7% compared to 72.7% among those who remained ANA-positive. Conclusions: Most patients with SSc clear ANA or reduce their levels after LT. A trend towards better survival was observed in this group, compared to the group of transplanted patients who remained positive. Full article

(This article belongs to the Special Issue News in the Pathogenesis, Diagnosis and Treatment of Systemic Sclerosis)

► Show Figures

Figure 1

17 pages, 3297 KB

Open AccessEditor’s ChoiceArticle

Italian Systemic Lupus Erythematosus (SLE) Patients: Overview of Their Quality of Life and Unmet Needs

by Luca Moroni, Ginevra De Marchi, Rosa Pelissero, Mercedes Callori, Italia Agresta, Antonella Celano, Elisa Cosentino, Silvia Tamanini, Alessia Delli Carri, Giuseppe Alvise Ramirez, Alessia Nano, Luca Quartuccio and Lorenzo Dagna

J. Clin. Med. 2025, 14(23), 8498; https://doi.org/10.3390/jcm14238498 - 30 Nov 2025

Viewed by 568

Abstract

Background/Objectives: Systemic Lupus Erythematosus (SLE) is a multifactorial disease that significantly affects patients’ quality of life (QoL) and poses management challenges. This project combined a nationwide patient listening initiative with an Advisory Board (AB) to identify unmet needs and perceptions, aiming to [...] Read more.

Background/Objectives: Systemic Lupus Erythematosus (SLE) is a multifactorial disease that significantly affects patients’ quality of life (QoL) and poses management challenges. This project combined a nationwide patient listening initiative with an Advisory Board (AB) to identify unmet needs and perceptions, aiming to integrate patient perspectives into decision-making and enhance SLE care. Methods: The “PaLESiamoci!” project, conducted by IQVIA with two patient organizations (Gruppo LES Italiano and APMARR), included both qualitative and quantitative phases. Ten patients completed disease diaries and one-hour interviews, while 151 others voluntarily filled a PO-administered survey including the validated 12-item Medical Outcome Short Form (SF-12) and items on physical, emotional, and daily life impact. Insights from these phases informed the AB discussion involving clinicians and patient representatives on six key topics. Results: Patients with SLE showed lower Physical (−13.4) and Mental (−14.0) Component Summary scores than the Italian population, indicating reduced social and work functioning. Despite EULAR recommendations to minimize corticosteroid use, 64% of patients remained on corticosteroids. The AB discussions revealed key unmet needs, including differing awareness of organ damage risks, corticosteroid-related adverse events, and adherence challenges, as well as the need for non-pharmacological and multidisciplinary support. Conclusions: The project highlighted major gaps and opportunities in SLE management. Patient organizations and rheumatologists emphasized developing tailored educational materials, strengthening rheumatologist–patient communication, and promoting multidisciplinary, patient-centered approaches to improve overall care. Full article

(This article belongs to the Section Immunology & Rheumatology)

► Show Figures

Figure 1

15 pages, 407 KB

Open AccessEditor’s ChoiceArticle

Long-Term Biochemical and Cardiovascular Profiles 3–6 Years After Preeclampsia: Impact of Angiogenic Imbalance During Pregnancy

by Noah Costa, Judit Platero, Pablo Garcia-Manau, Olga Sanchez-Garcia, Clàudia Pellicer, Mariona Jordi, Zoraida Garcia, Carmen Garrido-Gimenez, Johana Ullmo, Madalina Nan, Josefina Mora, Alvaro Garcia-Osuna, Marta Choliz, Monica Cruz-Lemini, Maria del Carmen Medina and Elisa Llurba

J. Clin. Med. 2025, 14(23), 8389; https://doi.org/10.3390/jcm14238389 - 26 Nov 2025

Cited by 1 | Viewed by 632

Abstract

Background/Objectives: Preeclampsia is associated with long-term cardiovascular and metabolic risks. This study aimed to evaluate metabolic and cardiovascular biochemical profiles in women with a history of preeclampsia and angiogenic imbalance during pregnancy. Methods: We conducted a cross-sectional study at Hospital de la Santa [...] Read more.

Background/Objectives: Preeclampsia is associated with long-term cardiovascular and metabolic risks. This study aimed to evaluate metabolic and cardiovascular biochemical profiles in women with a history of preeclampsia and angiogenic imbalance during pregnancy. Methods: We conducted a cross-sectional study at Hospital de la Santa Creu i Sant Pau between August 2023 and July 2025. Participants had been prospectively enrolled during pregnancy (2018–2022) and were re-evaluated 3 to 6 years later. Blood and urine samples were collected after a 12-h fast to assess hematological, metabolic, and cardiovascular markers. Angiogenic profiles were determined using sFlt-1/PlGF ratios obtained during pregnancy. Multivariable linear regression models were used to assess associations with a history of PE and angiogenic imbalance, adjusting for relevant confounders. Results: 363 participants were included. 113 (31.1%) had a history of preeclampsia. Women with previous preeclampsia showed slightly higher high-sensitivity troponin T concentrations [4.0 (3.0–6.0) ng/L vs. 3.2 (3.0–5.0) ng/L, p = 0.03]. Women with sFlt-1/PlGF ≥38 exhibited significantly higher urinary protein [0.09 (0.07–0.18) g/L vs. 0.08 (0.07–0.13) g/L, p = 0.01], potassium [4.25 (4.07–4.40) mmol/L vs. 4.19 (4.02–4.37) mmol/L, p = 0.048], and LDH concentrations [168 (150–189) U/L vs. 163 (149–177) U/L, p = 0.046], and lower leukocyte counts [6150 (5348–7055) vs. 6250 (5430–7450) U/mL, p = 0.03]. Conclusions: Women with angiogenic imbalance during pregnancy display subtle alterations in renal and endothelial function markers years after delivery, whereas those with preeclampsia show slightly higher troponin concentrations. These findings, though clinically irrelevant, suggest that pregnancy-related vascular dysfunction may have different long-term manifestations depending on whether the maternal cardiovascular system was sufficiently compromised to develop overt preeclampsia. Full article

(This article belongs to the Special Issue Preeclampsia and Other Pregnancy Complications: Early Intervention, Diagnosis and Management)

► Show Figures

Graphical abstract

13 pages, 1177 KB

Open AccessEditor’s ChoiceArticle

AI-Automated Risk Operative Stratification for Severe Aortic Stenosis: A Proof-of-Concept Study

by Dorian Garin, Diego Arroyo, Ioannis Skalidis, Philippe Di Cicco, Charlie Ferry, Wesley Bennar, Serban Puricel, Pascal Meier, Mario Togni and Stéphane Cook

J. Clin. Med. 2025, 14(23), 8304; https://doi.org/10.3390/jcm14238304 - 22 Nov 2025

Viewed by 546

Abstract

Background: Accurate operative risk stratification is essential for treatment selection in severe aortic stenosis. We developed an automated workflow using large language models (LLMs) to replicate Heart Team risk assessment. Methods: We retrospectively analyzed 231 consecutive patients with severe aortic stenosis [...] Read more.

Background: Accurate operative risk stratification is essential for treatment selection in severe aortic stenosis. We developed an automated workflow using large language models (LLMs) to replicate Heart Team risk assessment. Methods: We retrospectively analyzed 231 consecutive patients with severe aortic stenosis evaluated by multidisciplinary Heart Teams (January 2022–December 2024). An automated system using GPT-4o was developed, comprising the following: (1) structured data extraction from clinical dossiers; (2) EuroSCORE II calculation via two methods (algorithmic vs. LLM-based); (3) clinical vignette generation; and (4) risk stratification comparing EuroSCORE-based thresholds versus guideline-integrated LLM approaches with/without EuroSCORE values. The primary endpoint was the risk stratification accuracy of each method compared to Heart Team decisions. Results: Mean age was 79.5 ± 7.7 years, with 58.4% female. The automated workflow processed patients in 32.6 ± 6.4 s. The LLM-calculated EuroSCORE II showed a lower mean difference from Heart Team values (−1.42%, 95% CI −2.32 to −0.53) versus algorithmic calculation (−1.88%, 95% CI −2.38 to −1.38). For risk stratification, the guideline-integrated LLM without EuroSCORE achieved the highest accuracy (90.0%) and AUC (0.93), outperforming both the EuroSCORE-based (accuracy 50.2% for high-risk, AUC 0.63) and guideline-integrated LLM with EuroSCORE approaches (accuracy 82.4%, AUC 0.76). However, systematic hallucinations occurred for cardiovascular risk factors when data were missing. Conclusions: LLMs accurately calculated EuroSCORE II and achieved 90% concordance with multidisciplinary Heart Team decisions. However, hallucinations, reproducibility concerns, and the absence of clinical outcome validation preclude direct clinical application. Full article

(This article belongs to the Special Issue Advancing Clinical Medicine Through Artificial Intelligence (AI) and Digital Technology: 2nd Edition)

► Show Figures

Figure 1

23 pages, 1940 KB

Open AccessEditor’s ChoiceSystematic Review

Complications of Percutaneous Tracheostomy-Assisting Techniques in Critically Ill Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

by Olga Grajdieru, Constantin Bodolea, Vlad Moisoiu, Cristina Petrișor and Catalin Constantinescu

J. Clin. Med. 2025, 14(22), 8050; https://doi.org/10.3390/jcm14228050 - 13 Nov 2025

Viewed by 758

Abstract

Background/Objectives: Percutaneous dilatational tracheostomy (PDT) is a commonly performed procedure in critically ill patients. Various guidance techniques, including anatomical landmark-guided (ALG), ultrasound-guided (USG) and bronchoscopy-guided (BG), aim to enhance procedural safety and efficacy. This systematic review and meta-analysis aimed to compare the safety [...] Read more.

Background/Objectives: Percutaneous dilatational tracheostomy (PDT) is a commonly performed procedure in critically ill patients. Various guidance techniques, including anatomical landmark-guided (ALG), ultrasound-guided (USG) and bronchoscopy-guided (BG), aim to enhance procedural safety and efficacy. This systematic review and meta-analysis aimed to compare the safety and efficacy across ALG, USG, and BG techniques in PDT, focusing on complications and procedure times. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. Studies identified through PubMed, CENTRAL, Scopus, and Web of Science databases up to July 2025 comparing ALG, USG, and BG PDT were included. Primary outcomes were minor and major bleeding, with transient hypoxia, transient hypotension, endotracheal tube cuff puncture, pneumothorax, and procedure time as secondary outcomes. Data were pooled using random-effects models, with risk ratios (RR) and 95% confidence intervals (CI) for complications and mean differences for procedure times. Heterogeneity was assessed using I² statistics, with Bonferroni correction for multiple comparisons. Results: This meta-analysis included five RCTs (568 patients) comparing USG vs. ALG, six RCTs (404 patients) comparing USG vs. BG, and five RCTs (448 patients) comparing ALG vs. BG. USG significantly reduced minor bleeding compared to ALG (RR 2.30, 95% CI 1.38–3.84, p = 0.001) and BG (RR 0.42, 95% CI 0.20–0.91, p = 0.02), and major bleeding compared to ALG (RR 2.62, 95% CI 1.00–6.86, p = 0.04). ALG was associated with higher minor bleeding risk than BG (RR 1.81, 95% CI 1.05–3.12, p = 0.03). No significant differences were found for transient hypoxia, hypotension, endotracheal tube cuff puncture, or pneumothorax across comparisons, though trends suggested lower hypoxia risk with USG and higher pneumothorax risk with ALG. Procedure times were similar (ALG: 10.4 min, USG: 11.7 min, BG: 12.7 min; p = 0.493). Some rare complications, like paratracheal placement and mediastinitis, were too infrequent for analysis. Conclusions: USG PDT significantly reduces the risk of minor and major bleeding relative to ALG and minor bleeding compared to BG, without prolonging procedure time. USG and BG show comparable safety for most non-bleeding outcomes. No significant differences in procedure times. Future research should focus on larger RCTs to assess rare complications and explore hybrid USG-BG approaches to optimize PDT safety and efficacy. Full article

(This article belongs to the Section Intensive Care)

► Show Figures

Figure 1

12 pages, 515 KB

Open AccessEditor’s ChoiceArticle

Impact of Finerenone in Patients with Heart Failure and Reduced/Mildly Reduced Ejection Fraction, Diabetes Mellitus, and Chronic Kidney Disease

by Yuki Hida, Teruhiko Imamura and Koichiro Kinugawa

J. Clin. Med. 2025, 14(22), 7997; https://doi.org/10.3390/jcm14227997 - 11 Nov 2025

Viewed by 1670

Abstract

Background: Heart failure (HF) remains a major global health challenge with substantial morbidity, mortality, and healthcare burden. Finerenone, a novel non-steroidal mineralocorticoid receptor antagonist (MRA), has demonstrated cardiovascular and renal benefits in patients with diabetes mellitus (DM) and chronic kidney disease (CKD), [...] Read more.

Background: Heart failure (HF) remains a major global health challenge with substantial morbidity, mortality, and healthcare burden. Finerenone, a novel non-steroidal mineralocorticoid receptor antagonist (MRA), has demonstrated cardiovascular and renal benefits in patients with diabetes mellitus (DM) and chronic kidney disease (CKD), as well as reduced HF events, in patients with HF with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). However, its efficacy and safety in patients with HF with reduced EF (HFrEF) or HFmrEF, DM, and CKD, remain unclear. Notably, finerenone is currently reimbursed only for DM and CKD but not for HF itself. Methods: We conducted a retrospective, single-center study of patients with HFrEF/HFmrEF who received finerenone between August 2022 and June 2025. Clinical data were obtained 6 months before, at baseline, and 6 months after the initiation of finerenone. The primary outcome was the change in serum NT pro-B-type natriuretic peptide (BNP). Results: Among 37 patients screened, 22 who initiated finerenone on a de novo basis were included. Median age was 75 years, 73% were male, and all had DM and CKD, which are current indications of finerenone. NT pro-BNP decreased significantly during the on-treatment period compared with the pre-treatment period (p < 0.001). Left ventricular end-diastolic diameter and left ventricular ejection fraction remained unchanged during the pre-treatment period but improved significantly during the on-treatment period (p < 0.001 for both). Renal function and serum potassium remained stable during the whole study period (p > 0.05 for both). Conclusions: In this real-world study of patients with HFrEF/HFmrEF complicated by DM and CKD, finerenone was associated with significant improvements in NT pro-BNP and cardiac remodeling indices without worsening renal function or hyperkalemia. Full article

(This article belongs to the Section Cardiology)

► Show Figures

Figure 1

22 pages, 587 KB

Open AccessEditor’s ChoiceReview

An Updated Review of Topical Tretinoin in Dermatology: From Acne and Photoaging to Skin Cancer

by Pablo Balado-Simó, Daniel Morgado-Carrasco, Sara Gómez-Armayones, Anna López-Ferrer, Didac Barco, Carla Ferrándiz-Pulido and Sebastian Podlipnik

J. Clin. Med. 2025, 14(22), 7958; https://doi.org/10.3390/jcm14227958 - 10 Nov 2025

Cited by 1 | Viewed by 9630

Abstract

Topical tretinoin (all-trans-retinoic acid) is a first-generation vitamin A derivative with well-established efficacy in acne vulgaris and photoaging. Owing to its pleiotropic effects on epidermal differentiation, collagen synthesis, and skin pigmentation, numerous off-label uses have been proposed across dermatology. This narrative review summarizes [...] Read more.

Topical tretinoin (all-trans-retinoic acid) is a first-generation vitamin A derivative with well-established efficacy in acne vulgaris and photoaging. Owing to its pleiotropic effects on epidermal differentiation, collagen synthesis, and skin pigmentation, numerous off-label uses have been proposed across dermatology. This narrative review summarizes current evidence on the efficacy and safety of topical tretinoin for multiple dermatological conditions, based on studies published between January 2000 and July 2025. Robust data from randomized clinical trials (RCTs) and systematic reviews support its benefit in acne and photoaging, whereas smaller RCTs and prospective studies indicate potential efficacy for melasma, postinflammatory hyperpigmentation, striae distensae, flat warts, alopecia areata, androgenetic alopecia, hypertrophic scars and keloids, and actinic keratosis and as pretreatment before chemical peels or laser resurfacing. However, high-quality, adequately powered trials with standardized outcome measures are still needed to establish clinical guidelines. Regarding cutaneous oncology, a large RCT demonstrated no preventive effect of tretinoin on keratinocyte carcinomas. Adverse events are typically mild, localized, and transient, and available evidence does not support an association with systemic adverse effects. Full article

(This article belongs to the Section Dermatology)

► Show Figures

Figure 1

24 pages, 1838 KB

Open AccessEditor’s ChoiceSystematic Review

Promising, but Not Completely Conclusive—The Effect of l-Theanine on Cognitive Performance Based on the Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Clinical Trials

by Rebeka Olga Mátyus, Zsóka Szikora, Diána Bodó, Bettina Vargáné Szabó, Éva Csupor, Dezső Csupor and Barbara Tóth

J. Clin. Med. 2025, 14(21), 7710; https://doi.org/10.3390/jcm14217710 - 30 Oct 2025

Cited by 1 | Viewed by 15697

Abstract

Background: Green tea (Camellia sinensis) has been consumed for centuries, and its beneficial effects on human health have been studied in recent decades. l-theanine, an active ingredient in green tea, has been used to improve cognition and mood. Although the [...] Read more.

Background: Green tea (Camellia sinensis) has been consumed for centuries, and its beneficial effects on human health have been studied in recent decades. l-theanine, an active ingredient in green tea, has been used to improve cognition and mood. Although the effects of l-theanine on cognition have been investigated in clinical trials that have reported various results, these studies have not yet been critically evaluated in meta-analyses. Objectives: Our objective was to systematically evaluate the efficacy of l-theanine on cognitive functions compared to a placebo, in a meta-analysis based on randomized controlled trials (RCTs). Methods: PubMed, the Cochrane Central Register of Controlled Trials, Embase and Web of Science were searched for relevant studies until 31 July 2024 and registered in PROSPERO (registration number: CRD42024575122). Placebo-controlled clinical trials investigating the efficacy of l-theanine in healthy adults were included. Conference abstracts, study protocols and reports of non-RCTs were excluded. For risk of bias assessment, the Cochrane Risk of Bias Tool (version 2.0) was used. A random effects model was applied to conduct the meta-analysis. Mean differences (MD) with 95% confidence intervals (CIs) were calculated. Results: Based on the included five RCTs involving 148 healthy adults, l-theanine had a dose-dependent effect on cognitive function based on rapid visual information processing and recognition visual reaction time (MD: −15.20 ms; 95%-CI [−28.99; −1.41]). The effects of l-theanine were non-significant on reaction time to a simple stimulus (MD: −0.46 ms; 95% [CI: −15.65; 14.73]) and in the Stroop test (MD: −37.38 ms; 95%-CI [−86.39; 11.62]). Conclusions: The beneficial effects of l-theanine on cognitive performance could not be confirmed by all test methods. The contradictory results could be explained by the fact that l-theanine only affects certain cognitive domains, but also by the low number of trials and the heterogeneity of the test preparations. Further trials using standardized products with larger sample sizes are required for the accurate assessment of efficacy. Full article

(This article belongs to the Section Mental Health)

► Show Figures

Figure 1

20 pages, 2791 KB

Open AccessEditor’s ChoiceArticle

Effectiveness of Photobiomodulation to Treat Motor and Non-Motor Symptoms of Parkinson’s Disease: A Randomised Clinical Trial with Extended Treatment

by Anita E. Saltmarche, Orla Hares, Brian Bicknell, Ann Liebert, Margaret Naeser, Sujith Ramachandran, Jenna Sykes, Kaley Togeretz, Ashley Namini, Gillian Z. Heller and Geoffrey Herkes

J. Clin. Med. 2025, 14(21), 7463; https://doi.org/10.3390/jcm14217463 - 22 Oct 2025

Cited by 2 | Viewed by 7218

Abstract

Background/Objective: Few treatment options improve symptoms and the quality of life of Parkinson’s disease (PD); more treatment choices are needed. This study examined the effectiveness of photobiomodulation therapy (PBMt) combined with exercise to improve PD symptoms and quality of life. Methods: Participants were [...] Read more.

Background/Objective: Few treatment options improve symptoms and the quality of life of Parkinson’s disease (PD); more treatment choices are needed. This study examined the effectiveness of photobiomodulation therapy (PBMt) combined with exercise to improve PD symptoms and quality of life. Methods: Participants were randomised into Active (n = 32) or Sham (n = 31) PBMt groups. Stage 1 was an 8-week double-blind, randomised, placebo-controlled trial using either active or sham PBMt to the head, back of the neck and abdomen three times weekly at home, followed by a 4-week washout. Stage 2 was 8 weeks of active PBMt for all participants. In Stage 3, participants chose to continue active PBMt treatment (‘continuers’) or receive no PBMt treatment (‘non-continuers’) for up to 48 weeks. Participants continued vigorous exercise throughout the study. Participants were assessed on enrolment and after each stage. The primary outcome measure was timed up-and-go, with a range of secondary motor and non-motor outcomes, including UPDRS. Results: There was no significant difference between the Active and Sham Groups after Stages 1 or 2, apart from minimal increase in MoCA score/cognition (Sham Group) in Stage 1. After Stage 3, continuers showed a significant improvement in the primary outcome measure compared to non-continuers. Anxiety and the motor experiences of daily living (MDS-UPDRS Part II) were also significantly improved, while other outcomes approached significance, including MDS-UPDRS Total score (p = 0.062). Conclusions: As the largest study to date, results add increasing weight to previous clinical trials and highlight potential for at-home, scalable treatment as adjunctive therapy alongside medication and exercise. Full article

(This article belongs to the Special Issue Innovative Approaches to the Challenges of Neurodegenerative Disease)

► Show Figures

Figure 1

22 pages, 1939 KB

Open AccessEditor’s ChoiceArticle

Development and Validation of Prognostic Models for Treatment Response of Patients with B-Cell Lymphoma: Standard Statistical and Machine-Learning Approaches

by Adugnaw Zeleke Alem, Itismita Mohanty, Nalini Pati, Cameron Wellard, Eliza Chung, Eliza A. Hawkes, Zoe K. McQuilten, Erica M. Wood, Stephen Opat and Theophile Niyonsenga

J. Clin. Med. 2025, 14(20), 7445; https://doi.org/10.3390/jcm14207445 - 21 Oct 2025

Viewed by 1426

Abstract

Background: Achieving a complete response after therapy is an important predictor of long-term survival in lymphoma patients. However, previous predictive models have primarily focused on overall survival (OS) and progression-free survival (PFS), often overlooking treatment response. Predicting the likelihood of complete response before [...] Read more.

Background: Achieving a complete response after therapy is an important predictor of long-term survival in lymphoma patients. However, previous predictive models have primarily focused on overall survival (OS) and progression-free survival (PFS), often overlooking treatment response. Predicting the likelihood of complete response before initiating therapy can provide more immediate and actionable insights. Thus, this study aims to develop and validate predictive models for treatment response to first-line therapy in patients with B-cell lymphomas. Methods: The study used 2763 patients from the Lymphoma and Related Diseases Registry (LaRDR). The data were randomly divided into training (n = 2221, 80%) and validation (n = 553, 20%) cohorts. Seven algorithms: logistic regression, K-nearest neighbor, support vector machine, random forest, Naïve Bayes, gradient boosting machine, and extreme gradient boosting were evaluated. Model performance was assessed using discrimination and classification metrics. Additionally, model calibration and clinical utility were evaluated using the Brier score and decision curve analysis, respectively. Results: All models demonstrated comparable performance in the validation cohort, with area under the curve (AUC) values ranging from 0.69 to 0.70. A nomogram incorporating the six variables, including stage, lactate dehydrogenase, performance status, BCL2 expression, anemia, and systemic immune-inflammation index, achieved an AUC of 0.70 (95% CI: 0.65–0.75), outperforming the international prognostic index (IPI: AUC = 0.65), revised IPI (AUC = 0.61), and NCCN-IPI (AUC = 0.63). Decision curve analysis confirmed the nomogram’s superior net benefit over IPI-based systems. Conclusions: While our nomogram demonstrated improved discriminative performance and clinical utility compared to IPI-based systems, further external validation is needed before clinical integration. Full article

(This article belongs to the Section Oncology)

► Show Figures

Figure 1

12 pages, 347 KB

Open AccessEditor’s ChoiceArticle

The Impact of Ursodeoxycholic Acid on Fetal Cardiac Function in Women with Gestational Diabetes Mellitus: A Randomized Controlled Study (GUARDS Trial)

by Ana Maria Company Calabuig, Jose Eliseo Blanco Carnero, Christos Chatzakis, Catherine Williamson, Kypros H. Nicolaides, Marietta Charakida and Catalina De Paco Matallana

J. Clin. Med. 2025, 14(20), 7366; https://doi.org/10.3390/jcm14207366 - 17 Oct 2025

Viewed by 1010

Abstract

Background: Gestational diabetes mellitus (GDM) is associated with subclinical alterations in fetal cardiac morphology and function. Ursodeoxycholic acid (UDCA), widely used in pregnancy for intrahepatic cholestasis, has demonstrated cardioprotective properties in experimental fetal models, preventing conduction abnormalities and improving myocardial function. Whether UDCA [...] Read more.

Background: Gestational diabetes mellitus (GDM) is associated with subclinical alterations in fetal cardiac morphology and function. Ursodeoxycholic acid (UDCA), widely used in pregnancy for intrahepatic cholestasis, has demonstrated cardioprotective properties in experimental fetal models, preventing conduction abnormalities and improving myocardial function. Whether UDCA modifies fetal or neonatal cardiac adaptation in GDM pregnancies has not been previously investigated. The objective was to evaluate the effect of ursodeoxycholic acid (UDCA) on fetal and neonatal cardiac function in pregnancies complicated by gestational diabetes mellitus (GDM). Methods: In this randomized, placebo-controlled study, 113 women with GDM were enrolled, of whom 56 received UDCA and 57 the placebo. After measurement of maternal blood UDCA concentrations, 43 participants in the treatment group had levels ≥0.5 µmol/L and were included in the per-protocol analysis. Echocardiographic and Doppler-derived cardiac indices were assessed at baseline, 36 weeks’ gestation, and postpartum. Comparisons were performed using univariable tests and mixed-effects multivariable models accounting for time and treatment. Results: In the treatment group, compared to the placebo group, there were no significant differences in cardiac indices at 36 weeks’ gestation or postpartum when assessed individually. However, in the mixed-effects longitudinal analysis, a significant treatment-by-time interaction was observed. Specifically, in the postpartum period, mitral A-wave velocity (MV-A) was higher in the treatment group compared to that under the placebo (9.58, 95% CI 2.29–16.87; p = 0.010), reflecting a more pronounced increase in the atrial contribution to left ventricular filling over time. Similarly, aortic peak velocity (Ao_Vmáx) was significantly higher in the treatment group compared to that under the placebo in the postpartum period (7.97, 95% CI 0.19–15.75; p = 0.045), indicating a greater augmentation in left ventricular outflow dynamics. Conclusions: In pregnancies complicated by GDM, UDCA did not lead to significant cross-sectional differences in fetal or neonatal cardiac indices at 36 weeks or postpartum. However, longitudinal modeling indicated that UDCA was associated with a greater increase in the atrial contribution to ventricular filling (MV-A) and aortic peak velocity (Ao_Vmáx) in the postpartum period compared to that under the placebo. These findings suggest that while UDCA does not broadly alter cardiac function, it may modulate specific aspects of diastolic filling and systolic outflow dynamics during late gestation and early neonatal adaptation. Full article

(This article belongs to the Section Obstetrics & Gynecology)

► Show Figures

Figure 1

13 pages, 1022 KB

Open AccessEditor’s ChoiceReview

Preoxygenation in the ICU

by Clément Monet, Mathieu Capdevila, Inès Lakbar, Yassir Aarab, Joris Pensier, Audrey De Jong and Samir Jaber

J. Clin. Med. 2025, 14(20), 7305; https://doi.org/10.3390/jcm14207305 - 16 Oct 2025

Viewed by 3724

Abstract

Tracheal intubation is a frequent and high-risk procedure in the intensive care unit (ICU). Unlike elective intubation in the operating room, ICU intubation is often performed under emergent conditions in physiologically unstable patients, leading to increased technical difficulty and higher complication rates. Among [...] Read more.

Tracheal intubation is a frequent and high-risk procedure in the intensive care unit (ICU). Unlike elective intubation in the operating room, ICU intubation is often performed under emergent conditions in physiologically unstable patients, leading to increased technical difficulty and higher complication rates. Among these, hypoxemia is particularly frequent and represents a major determinant of morbidity and mortality. Optimizing preoxygenation is therefore a cornerstone of safe airway management in critically ill patients. The aim of this review is to explore the advantages and limitations of each preoxygenation strategy and to provide clinicians with clear, practical guidance to optimize airway management in the ICU. Preoxygenation aims to increase oxygen reserves in order to prolong the duration of safe apnea. Conventional methods include high-flow oxygen delivery through a tightly fitted face mask, though efficacy depends on minimizing leaks. More advanced strategies include non-invasive ventilation (NIV), which improves both alveolar oxygen fraction and lung volume, and high-flow nasal cannula (HFNC), which additionally allows apneic oxygenation during intubation. Randomized controlled trials, including the recent PREOXY study, demonstrate the superiority of NIV over facemask preoxygenation in reducing peri-intubation desaturation, particularly in hypoxemic patients. HFNC is valuable when NIV is contraindicated, while combined approaches (NIV plus HFNC) may further enhance efficacy. Beyond technique, structured protocols and team organization are crucial to reduce complications. In conclusion, preoxygenation is an essential, patient-specific intervention that mitigates the risks of ICU intubation. Familiarity with available methods enables clinicians to tailor strategies, optimize oxygenation, and improve patient safety during this high-risk procedure. Full article

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

► Show Figures

Figure 1

13 pages, 1650 KB

Open AccessEditor’s ChoiceArticle

A 20-Year Real-World Study of Small Bowel Cancers: Histologic Subtypes, Clinical Features, and Survival Implications

by Jirapat Wonglhow, Patrapim Sunpaweravong, Chirawadee Sathitruangsak, Arunee Dechaphunkul and Panu Wetwittayakhlang

J. Clin. Med. 2025, 14(19), 6962; https://doi.org/10.3390/jcm14196962 - 1 Oct 2025

Cited by 1 | Viewed by 990

Abstract

Background: Small-bowel cancers (SBCs) are rare, histologically diverse malignancies with limited data from Asian populations. This study aimed to describe histological subtype distribution, clinical features, survival outcomes, and prognostic factors in SBCs over a 20-year period. Methods: We retrospectively reviewed patients diagnosed with [...] Read more.

Background: Small-bowel cancers (SBCs) are rare, histologically diverse malignancies with limited data from Asian populations. This study aimed to describe histological subtype distribution, clinical features, survival outcomes, and prognostic factors in SBCs over a 20-year period. Methods: We retrospectively reviewed patients diagnosed with SBC at a tertiary referral center in Southern Thailand (2005–2024). Clinical, pathological, and radiological data were analyzed by histologic subtype. Results: A total of 158 patients were included: adenocarcinoma (81.0%), gastrointestinal stromal tumor (GIST, 5.7%), well-differentiated neuroendocrine tumor (NET, 5.7%), other sarcomas (5.1%), and poorly differentiated neuroendocrine carcinoma (NEC, 2.5%). Adenocarcinoma predominantly affected older patients and frequently presented with advanced-stage disease and poor performance status, whereas NET and NEC occurred in younger patients typically at early NET and metastatic NEC stages. Median overall survival (OS) varied by subtype: adenocarcinoma (8.3 months), GIST (63.6 months), NEC (8.9 months), NET (not reached), and other sarcomas (9.8 months). Five-year OS rates were 14.0%, 55.6%, 0%, 88.9%, and 18.8%, respectively. Eastern Cooperative Oncology Group performance status ≥2, duodenal location, and metastatic disease were independently associated with worse OS. Conclusions: SBCs display distinct clinical and prognostic profiles by subtype. Overall prognosis remained poor, underscoring the need for earlier detection and subtype-specific management. Full article

(This article belongs to the Special Issue Diagnosis, Treatment, and Management of Gastrointestinal Oncology)

► Show Figures

Figure 1

15 pages, 3293 KB

Open AccessEditor’s ChoiceReview

Aggressiveness in Well-Differentiated Small Intestinal Neuroendocrine Tumors: A Rare Case and Narrative Literature Review

by Laurențiu Augustus Barbu, Liviu Vasile, Liliana Cercelaru, Valeriu Șurlin, Stelian-Ștefaniță Mogoantă, Gabriel Florin Răzvan Mogoș, Tiberiu Stefăniță Țenea Cojan, Nicolae-Dragoș Mărgăritescu, Marius P. Iordache and Anca Buliman

J. Clin. Med. 2025, 14(16), 5821; https://doi.org/10.3390/jcm14165821 - 18 Aug 2025

Cited by 10 | Viewed by 1079

Abstract

Background: Small intestinal neuroendocrine tumors (SI-NETs) are the most common malignancies of the small bowel. Although typically well differentiated and slow-growing, they may exhibit aggressive behavior, especially when diagnosed at an advanced stage. Objective: To illustrate the diagnostic and therapeutic challenges of advanced [...] Read more.

Background: Small intestinal neuroendocrine tumors (SI-NETs) are the most common malignancies of the small bowel. Although typically well differentiated and slow-growing, they may exhibit aggressive behavior, especially when diagnosed at an advanced stage. Objective: To illustrate the diagnostic and therapeutic challenges of advanced SI-NETs through a rare case presentation and a narrative review of recent studies in the literature. Methods: A narrative literature review was conducted using the PubMed database to examine the incidence, risk factors, diagnostic modalities, and treatment strategies for advanced-stage SI-NETs. The search included studies published between January 2010 and June 2025 and focused on human subjects, using keywords such as “small intestinal neuroendocrine tumor”, “metastasis”, “tumor grade”, and “treatment”. Results: We report the case of a 68-year-old man who presented with bowel obstruction. Imaging and surgical exploration revealed a jejunoileal SI-NET with extensive liver and peritoneal metastases, mesenteric fibrosis, and ascites. Histopathology confirmed a well-differentiated grade 2 tumor (Ki-67: 3%) positive for chromogranin A and CD56. Despite a low proliferative index, the tumor demonstrated aggressive clinical behavior. The patient underwent emergency enterectomy with ileostomy and was referred for further evaluation, including somatostatin receptor imaging and consideration for peptide receptor radionuclide therapy (PRRT). Conclusions: This case highlights the potential for aggressive progression in well-differentiated SI-NETs with low Ki-67 indices. Histological grade alone may not predict clinical behavior. Early diagnosis, comprehensive staging, and individualized multidisciplinary management—guided by functional imaging and receptor profiling—are critical to improving outcomes in advanced SI-NETs. Full article

(This article belongs to the Special Issue Clinical Advances in Abdominal Surgery)

► Show Figures

Figure 1

18 pages, 1528 KB

Open AccessEditor’s ChoiceReview

Sex Differences in Colorectal Cancer: Epidemiology, Risk Factors, and Clinical Outcomes

by Sophia Tsokkou, Ioannis Konstantinidis, Menelaos Papakonstantinou, Paraskevi Chatzikomnitsa, Eftychia Liampou, Evdokia Toutziari, Dimitrios Giakoustidis, Petros Bangeas, Vasileios Papadopoulos and Alexandros Giakoustidis

J. Clin. Med. 2025, 14(15), 5539; https://doi.org/10.3390/jcm14155539 - 6 Aug 2025

Cited by 9 | Viewed by 4261

Abstract

Colorectal cancer (CRC) constitutes a major global health concern, ranking as the third most common cancer and the second leading cause of cancer-related mortality. The current review explores sex-based differences in CRC epidemiology, risk factors, tumor biology, and clinical outcomes. Males exhibit a [...] Read more.

Colorectal cancer (CRC) constitutes a major global health concern, ranking as the third most common cancer and the second leading cause of cancer-related mortality. The current review explores sex-based differences in CRC epidemiology, risk factors, tumor biology, and clinical outcomes. Males exhibit a higher incidence and mortality rate, with left-sided (distal) CRC predominating, while females are more frequently diagnosed with right-sided (proximal) tumors, which tend to be more aggressive and less responsive to conventional chemotherapy. Genetic disparities, including microsatellite instability and X-chromosome tumor suppressor genes, contribute to sex-specific differences in tumor progression and treatment response. Immune variations also influence disease outcomes, with females exhibiting stronger immune surveillance but higher exhaustion markers. Lifestyle factors such as body mass index (BMI), smoking, and hormonal influences further modulate CRC risk. While males are more vulnerable to obesity-related CRC, central obesity (waist-to-hip ratio) emerges as a stronger predictor in females. Additionally, smoking increases CRC risk differentially by tumor location. These findings underscore the importance of sex-specific approaches in CRC prevention, screening, and treatment, advocating for personalized medicine strategies tailored to gender-based biological and clinical distinctions. Full article

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

► Show Figures

Figure 1

16 pages, 803 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Temporal Decline in Intravascular Albumin Mass and Its Association with Fluid Balance and Mortality in Sepsis: A Prospective Observational Study

by Christian J. Wiedermann, Arian Zaboli, Fabrizio Lucente, Lucia Filippi, Michael Maggi, Paolo Ferretto, Alessandro Cipriano, Antonio Voza, Lorenzo Ghiadoni and Gianni Turcato

J. Clin. Med. 2025, 14(15), 5255; https://doi.org/10.3390/jcm14155255 - 24 Jul 2025

Cited by 2 | Viewed by 1539

Abstract

Background: Intravascular albumin mass represents the total quantity of albumin circulating within the bloodstream and may serve as a physiologically relevant marker of vascular integrity and fluid distribution in sepsis. While low serum albumin levels are acknowledged as prognostic indicators, dynamic assessments [...] Read more.

Background: Intravascular albumin mass represents the total quantity of albumin circulating within the bloodstream and may serve as a physiologically relevant marker of vascular integrity and fluid distribution in sepsis. While low serum albumin levels are acknowledged as prognostic indicators, dynamic assessments based on albumin mass remain insufficiently explored in patients outside the intensive care unit. Objectives: To describe the temporal changes in intravascular albumin mass in patients with community-acquired sepsis and to examine its relationship with fluid balance and thirty-day mortality. Methods: This prospective observational study encompassed 247 adults diagnosed with community-acquired sepsis who were admitted to a high-dependency hospital ward specializing in acute medical care. The intravascular albumin mass was calculated daily for a duration of up to five days, utilizing plasma albumin concentration and estimated plasma volume derived from anthropometric and hematologic data. Net albumin leakage was defined as the variation in intravascular albumin mass between consecutive days. Fluid administration and urine output were documented to ascertain cumulative fluid balance. Repeated-measures statistical models were employed to evaluate the associations between intravascular albumin mass, fluid balance, and mortality, with adjustments made for age, comorbidity, and clinical severity scores. Results: The intravascular albumin mass exhibited a significant decrease during the initial five days of hospitalization and demonstrated an inverse correlation with the cumulative fluid balance. A greater net leakage of albumin was associated with a positive fluid balance and elevated mortality rates. Furthermore, a reduced intravascular albumin mass independently predicted an increased risk of mortality at thirty days. Conclusions: A reduction in intravascular albumin mass may suggest ineffective fluid retention and the onset of capillary leak syndrome. This parameter holds promise as a clinically valuable, non-invasive indicator for guiding fluid resuscitation in cases of sepsis. Full article

(This article belongs to the Section Intensive Care)

► Show Figures

Figure 1

21 pages, 854 KB

Open AccessEditor’s ChoiceReview

Non-Invasive Ventilation: When, Where, How to Start, and How to Stop

by Mary Zimnoch, David Eldeiry, Oluwabunmi Aruleba, Jacob Schwartz, Michael Avaricio, Oki Ishikawa, Bushra Mina and Antonio Esquinas

J. Clin. Med. 2025, 14(14), 5033; https://doi.org/10.3390/jcm14145033 - 16 Jul 2025

Cited by 1 | Viewed by 13666

Abstract

Non-invasive ventilation (NIV) is a cornerstone in the management of acute and chronic respiratory failure, offering critical support without the risks of intubation. However, successful weaning from NIV remains a complex, high-stakes process. Poorly timed or improperly executed weaning significantly increases morbidity and [...] Read more.

Non-invasive ventilation (NIV) is a cornerstone in the management of acute and chronic respiratory failure, offering critical support without the risks of intubation. However, successful weaning from NIV remains a complex, high-stakes process. Poorly timed or improperly executed weaning significantly increases morbidity and mortality, yet current clinical practice often relies on subjective judgment rather than evidence-based protocols. This manuscript reviews the current landscape of NIV weaning, emphasizing structured approaches, objective monitoring, and predictors of weaning success or failure. It examines guideline-based indications, monitoring strategies, and various weaning techniques—gradual and abrupt—with evidence of their efficacy across different patient populations. Predictive tools such as the Rapid Shallow Breathing Index, Lung Ultrasound Score, Diaphragm Thickening Fraction, ROX index, and HACOR score are analyzed for their diagnostic value. Additionally, this review underscores the importance of care setting—ICU, step-down unit, or general ward—and how it influences outcomes. Finally, it highlights critical gaps in research, especially around weaning in non-ICU environments. By consolidating current evidence and identifying predictors and pitfalls, this article aims to support clinicians in making safe, timely, and patient-specific NIV weaning decisions. In the current literature, there are gaps regarding patient selection and lack of universal protocolization for initiation and de-escalation of NIV as the data has been scattered. This review aims to consolidate the relevant information to be utilized by clinicians throughout multiple levels of care in all hospital systems. Full article

(This article belongs to the Special Issue Weaning from Non-Invasive Mechanical Ventilation Approaches (NIV-NHF): Insights on How, When and Where)

► Show Figures

Figure 1

12 pages, 1482 KB

Open AccessEditor’s ChoiceArticle

Ophthalmic Artery Doppler Indices at 11–13 Weeks of Gestation in Relation to Early and Late Preeclampsia

by Nicoleta Gana, Savia Pittokopitou, Filippos Solonos, Alina Perdeica, Marina Fitiri and Kypros H. Nicolaides

J. Clin. Med. 2025, 14(13), 4811; https://doi.org/10.3390/jcm14134811 - 7 Jul 2025

Cited by 3 | Viewed by 4424

Abstract

Background/Objective: Preeclampsia (PE) remains a leading cause of maternal and fetal morbidity and mortality. Early prediction is crucial for timely intervention and management. The ophthalmic artery (OA) Doppler assessment in the first trimester has emerged as a potential tool for predicting PE, particularly [...] Read more.

Background/Objective: Preeclampsia (PE) remains a leading cause of maternal and fetal morbidity and mortality. Early prediction is crucial for timely intervention and management. The ophthalmic artery (OA) Doppler assessment in the first trimester has emerged as a potential tool for predicting PE, particularly early PE, with delivery <37 weeks of gestation. This study aimed to evaluate and compare the relationship of ophthalmic artery Doppler parameters at 11–13 weeks of gestation with the subsequent development of early and late PE. Methods: A prospective observational analysis was conducted on 4054 pregnant women, including 114 who developed PE. OA Doppler assessment of the pulsatility index (PI) and peak systolic velocity (PSV) ratio, mean arterial pressure (MAP), uterine artery PI (UtA-PI), and serum placental growth factor (PlGF) were compared between women who later developed early PE and late PE with those who did not develop PE. Results: In the PE groups, particularly those with early PE, compared to the no PE group, the OA PSV ratio and UtA-PI were higher and PlGF was lower. Conclusion: A first-trimester OA Doppler assessment shows promise as a non-invasive method for the prediction of PE. Further prospective, multicenter studies are needed to validate these findings. Full article

(This article belongs to the Section Obstetrics & Gynecology)

► Show Figures

Figure 1

18 pages, 2406 KB

Open AccessEditor’s ChoiceSystematic Review

The Use of Medical Hypnosis to Prevent and Treat Acute and Chronic Pain: A Systematic Review and Meta-Analysis

by Adina Yerzhan, Akbota Ayazbekova, Danielle R. Lavage and Jacques E. Chelly

J. Clin. Med. 2025, 14(13), 4661; https://doi.org/10.3390/jcm14134661 - 1 Jul 2025

Cited by 4 | Viewed by 12313

Abstract

Background/Objectives: In the current opioid crisis, medical hypnosis has been proposed as an alternative to opioids to control acute and chronic pain. The aim of this study was to use a meta-analysis to conduct an objective assessment of the value of medical [...] Read more.

Background/Objectives: In the current opioid crisis, medical hypnosis has been proposed as an alternative to opioids to control acute and chronic pain. The aim of this study was to use a meta-analysis to conduct an objective assessment of the value of medical hypnosis for the management of acute and chronic pain and opioid consumption. Methods: An initial PubMed search showed 111 relevant studies out of 1115. Twelve randomized controlled studies (RCTs) were identified, published from January 2014 to December 2024, focusing on acute and chronic pain. These RCTs were analyzed to compare the effects of medical hypnosis vs. standard care. Results: The use of medical hypnosis for acute pain was found to decrease pain by 0.54 standard deviations (SD) compared to the standard care, and the effect was medium and statistically significant (95% CI [0.19–0.90]; p = 0.0024). Oral morphine equivalents (OME) in the hypnosis group were 1.5 SD lower than in the placebo group, which was statistically significant (95% CI [0.12, 2.88]; p = 0.03). Unlike the effectiveness of hypnosis for acute pain treatment, hypnosis was not found to have any impact on the treatment of chronic pain. The mean pain value difference in the hypnosis group had little effect and showed a statistically insignificant result—a Hedges’ g score of 0.07 (95% CI [−0.14–0.27]; p = 0.518). Conclusions: The use of medical hypnosis was associated with a statistically significant decrease in acute pain scores and OME, suggesting it is a potential alternative to opioids, but our analysis indicates that hypnosis does not reduce chronic pain. Full article

(This article belongs to the Section Anesthesiology)

► Show Figures

Figure 1

14 pages, 741 KB

Open AccessEditor’s ChoiceArticle

Unsupervised Machine Learning in Identification of Septic Shock Phenotypes and Their In-Hospital Outcomes: A Multicenter Cohort Study

by Song Peng Ang, Jia Ee Chia, Eunseuk Lee, Maria Jose Lorenzo-Capps, Madison Laezzo and Jose Iglesias

J. Clin. Med. 2025, 14(13), 4450; https://doi.org/10.3390/jcm14134450 - 23 Jun 2025

Cited by 2 | Viewed by 1802

Abstract

Background: Septic shock is a heterogeneous syndrome with diverse clinical presentations and pathophysiology, yet current management guidelines largely treat it as a homogenous entity. Early risk stratification relies on lactate and different predictive scoring systems, which may not capture the underlying heterogeneity in [...] Read more.

Background: Septic shock is a heterogeneous syndrome with diverse clinical presentations and pathophysiology, yet current management guidelines largely treat it as a homogenous entity. Early risk stratification relies on lactate and different predictive scoring systems, which may not capture the underlying heterogeneity in host responses. Aim: To identify discrete subphenotypes of septic shock using admission demographics and laboratory parameters, and to evaluate their relationship with in-hospital outcomes. Methods: We conducted a retrospective multicenter cohort study of 10,462 adult patients with ICD-10-defined septic shock admitted to intensive care units between 2014 and 2015. We used Two-Step Cluster Analysis using log-likelihood distance and the Bayesian Information Criterion to identify two distinct phenotypes. We compared clusters on baseline characteristics, in-hospital outcomes including mortality, days on mechanical ventilation, vasopressor use, acute kidney injury (AKI), AKI requiring renal replacement therapy (RRT), and ICU and hospital lengths of stay. Results: We identified two clusters (Cluster 1, n = 5355 and Cluster 2, n = 5107) in our study. Cluster 1 showed greater biochemical severity at presentation, including higher median lactate (2.40 vs. 2.20 mmol L⁻¹; p < 0.001), serum creatinine (1.39 vs. 1.20 mg dL⁻¹; p < 0.001), blood urea nitrogen (28 vs. 25 mg dL⁻¹; p < 0.001), and neutrophil-to-lymphocyte ratio (11.12 vs. 10.38; p < 0.001), and a higher mean SOFA score (7.05 ± 3.85 vs. 6.76 ± 3.87; p < 0.001). Despite this, Cluster 1 required mechanical ventilation more frequently (46.1% vs. 42.2%; p < 0.001) and had a higher incidence of AKI (58.1% vs. 55.6%; p = 0.009), including more stage 3 AKI (17.2% vs. 15.2%; p < 0.001) and dialysis (6.6% vs. 5.2%; p = 0.005), yet experienced similar in-hospital mortality (15.4% vs. 15.8%; p = 0.615) and comparable ICU (2.18 vs. 2.26 days; p = 0.254) and hospital lengths of stay (6.63 vs. 6.80 days; p = 0.251). Conclusions: Two septic shock phenotypes were identified, one with marked early organ dysfunction (Cluster 1) and another with milder initial derangements (Cluster 2), yet both showed convergent short-term mortality and lengths of stay despite divergent support needs. These results challenge reliance on single-parameter severity markers and underscore the need for phenotype-guided risk stratification and personalized management strategies in septic shock. Full article

(This article belongs to the Section Intensive Care)

► Show Figures

Figure 1

18 pages, 1035 KB

Open AccessEditor’s ChoiceReview

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

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

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

Cited by 8 | Viewed by 7014

Abstract

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

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

(This article belongs to the Section Oncology)

► Show Figures

Figure 1

15 pages, 1702 KB

Open AccessEditor’s ChoiceArticle

Longitudinal Changes in Cardiovascular-Kidney-Metabolic Syndrome Stages and Their Impact on Outcomes: A Nationwide Cohort Study

by Byung Sik Kim, Hyun-Jin Kim, Hasung Kim, Jungkuk Lee, Jeong-Hun Shin and Ki-Chul Sung

J. Clin. Med. 2025, 14(11), 3888; https://doi.org/10.3390/jcm14113888 - 1 Jun 2025

Cited by 5 | Viewed by 2968

Abstract

Background/Objectives: The impact of longitudinal changes in cardiovascular-kidney-metabolic (CKM) stage remains unclear. This study evaluated the association between CKM stage progression and clinical outcomes. Methods: We used the Korean National Health Insurance Database to identify adults aged ≥ 20 years who underwent [...] Read more.

Background/Objectives: The impact of longitudinal changes in cardiovascular-kidney-metabolic (CKM) stage remains unclear. This study evaluated the association between CKM stage progression and clinical outcomes. Methods: We used the Korean National Health Insurance Database to identify adults aged ≥ 20 years who underwent two health checkups between 2009 and 2012. CKM stages were assessed at both time points and categorized as decreased, maintained, or increased over a 1–2-year interval. The primary outcome was a composite of all-cause death, heart failure, stroke, and myocardial infarction, evaluated over a mean follow-up of 11.05 years. Results: Among 877,537 participants, 15.3% experienced CKM stage progression. Compared to the maintained group, the increased group had a higher risk of the composite outcome (HR: 1.071, 95% CI: 1.050–1.092). While men had a higher rate of progression, women showed greater risk of clinical events (HR: 1.124 vs. 1.040). While stage progression was more frequent in younger adults, older individuals in the increased group progressed to more advanced stages and experienced higher rates of adverse outcomes. Conclusions: CKM stage progression is independently associated with increased risk of mortality and cardiovascular events, particularly in women and older adults. Serial CKM assessment may help identify high-risk individuals for early intervention. Full article

(This article belongs to the Special Issue Cardiometabolic Disease and Atherosclerosis: Epidemiology, Prevention, Diagnosis, and Clinical Treatment)

► Show Figures

Figure 1

11 pages, 239 KB

Open AccessEditor’s ChoiceReview

When Standard Is Not Enough: A Narrative Review of Supratherapeutic SSRI Doses in Resistant Obsessive Compulsive Disorder

by Giacomo Gualtieri, Alessandro Cuomo, Simone Pardossi and Andrea Fagiolini

J. Clin. Med. 2025, 14(11), 3858; https://doi.org/10.3390/jcm14113858 - 30 May 2025

Cited by 1 | Viewed by 13332

Abstract

Background/Objectives: OCD is a chronic psychiatric disorder, often requiring long-term pharmacological treatment. Although selective serotonin reuptake inhibitors (SSRIs) are considered first-line agents, 40 to 60% of patients show only partial or no response when treated at standard dosages. In such cases, supratherapeutic [...] Read more.

Background/Objectives: OCD is a chronic psychiatric disorder, often requiring long-term pharmacological treatment. Although selective serotonin reuptake inhibitors (SSRIs) are considered first-line agents, 40 to 60% of patients show only partial or no response when treated at standard dosages. In such cases, supratherapeutic doses of SSRIs have been proposed as an alternative strategy. However, the evidence supporting this approach remains limited and fragmented. This review aims to evaluate the rationale, clinical efficacy, tolerability, and practical considerations associated with high-dose SSRI use in OCD. Methods: A structured narrative review was conducted using targeted literature searches in PubMed and Scopus. Studies were included if they reported on the use of high-dose SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, or sertraline) in patients with OCD and provided efficacy and/or tolerability data. Clinical trials, observational studies, and case reports were all reviewed. Results: Evidence shows that higher doses of SSRIs are significantly more effective than low or medium doses in reducing OCD symptoms—especially in individuals who have only partially responded to standard treatment. Smaller clinical studies and case reports have also demonstrated that supratherapeutic dosing, beyond typical regulatory limits, can be both effective and well tolerated in treatment-resistant OCD. Conclusions: High-dose SSRI treatment may be a valuable option for selected OCD patients who do not respond to standard therapy. However, careful patient selection, regular monitoring, and further controlled studies are necessary to better define its long-term safety and effectiveness. In this context, increasingly advanced technologies—such as therapeutic drug monitoring and pharmacogenetic testing for relevant polymorphisms—may support more individualized and safer treatment strategies. Full article

(This article belongs to the Special Issue Obsessive Compulsive Disorder: Clinical Advances and Future Perspectives)

18 pages, 823 KB

Open AccessEditor’s ChoiceReview

Endoscopic Management of Eosinophilic Esophagitis: A Narrative Review on Diagnosis and Treatment

by Andrea Pasta, Francesco Calabrese, Manuele Furnari, Edoardo Vincenzo Savarino, Pierfrancesco Visaggi, Giorgia Bodini, Elena Formisano, Patrizia Zentilin, Edoardo Giovanni Giannini and Elisa Marabotto

J. Clin. Med. 2025, 14(11), 3756; https://doi.org/10.3390/jcm14113756 - 27 May 2025

Cited by 8 | Viewed by 4408

Abstract

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease characterized by esophageal eosinophilic infiltration, leading to symptoms such as dysphagia and food impaction. Endoscopy is central to both diagnosis and management, allowing for the direct visualization of characteristic features, biopsy collection, and therapeutic interventions. [...] Read more.

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease characterized by esophageal eosinophilic infiltration, leading to symptoms such as dysphagia and food impaction. Endoscopy is central to both diagnosis and management, allowing for the direct visualization of characteristic features, biopsy collection, and therapeutic interventions. Despite its diagnostic value, up to one-third of patients may present with a normal-appearing esophagus, highlighting the importance of standardized scoring systems and a systematic biopsy approach. This review explores the evolving role of endoscopy in EoE, from traditional diagnostic methods to emerging technologies such as EndoFlip™ for assessing esophageal distensibility, transnasal endoscopy for non-sedated monitoring, and novel dilation techniques for fibrostenotic disease. Additionally, non-invasive biomarkers and minimally invasive tools are reshaping disease monitoring. By integrating endoscopic, histologic, and molecular approaches, future advancements may enhance diagnostic accuracy and optimize personalized treatment strategies for EoE. Full article

(This article belongs to the Special Issue Eosinophilic Esophagitis: Clinical Advances in Diagnosis, Treatment, and Monitoring)

► Show Figures

Figure 1

15 pages, 2135 KB

Open AccessEditor’s ChoiceReview

Cardiovascular Disease Risk in Women with Menopause

by María Fasero and Pluvio J. Coronado

J. Clin. Med. 2025, 14(11), 3663; https://doi.org/10.3390/jcm14113663 - 23 May 2025

Cited by 11 | Viewed by 12173

Abstract

Background and objective: Menopause is a significant physiological milestone in a woman’s life, coinciding with increased cardiovascular disease (CVD) risk due to various health-related changes. This narrative review focuses on cardiovascular health-related alterations during menopause and their implications on vascular function. Methods [...] Read more.

Background and objective: Menopause is a significant physiological milestone in a woman’s life, coinciding with increased cardiovascular disease (CVD) risk due to various health-related changes. This narrative review focuses on cardiovascular health-related alterations during menopause and their implications on vascular function. Methods: An electronic database search was performed, drawing from sources such as PubMed and Google Scholar. Publications were included if they addressed CVD risk in peri- and postmenopausal women, and examined the impact of hormonal changes, traditional risk factors (e.g., hypertension, hyperlipidemia, diabetes), or lifestyle factors (e.g., diet, physical activity) on CVD. Results: Estrogen deficiency is pivotal, leading to adverse effects such as endothelial dysfunction, increased arterial stiffness, and lipid profile deterioration. Characteristics of menopause, including the age at onset, type or stage of menopause, and severity of symptoms, further modulate CVD risk. Additionally, the impact of traditional risk factors is amplified during this period. Strategies for the prevention of CVD in menopausal women are critically assessed, with a focus on lifestyle modifications, dietary interventions, and physical activity. Conclusions: This narrative review describes the potential benefits and risks of hormone therapy, alongside lipid-lowering therapies. Emphasis is placed on individualized risk assessment and management, highlighting the need for regular cardiovascular screenings and proactive management of risk factors. Full article

(This article belongs to the Section Obstetrics & Gynecology)

► Show Figures

Figure 1

15 pages, 1066 KB

Open AccessEditor’s ChoiceArticle

Effect of Coenzyme Q10 Supplementation on Cardiac Function and Quality of Life in Patients with Heart Failure: A Randomized Controlled Trial

by Olivia Bodea, Eugen Radu Boia, Laura Maria Craciun, Mihaela Daniela Valcovici, Alexandru Catalin Motofelea, Andreea Mara Munteanu, Caius Glad Streian, Gheorghe Nicusor Pop and Simona Ruxanda Dragan

J. Clin. Med. 2025, 14(11), 3675; https://doi.org/10.3390/jcm14113675 - 23 May 2025

Cited by 2 | Viewed by 13309

Abstract

Background/Objectives: Heart failure remains a complex syndrome with high morbidity and mortality, highlighting the urgent need for alternative treatments that address underlying bioenergetic impairments. CoQ10, which plays a crucial role in mitochondrial ATP production, has shown promising results in small studies, although larger [...] Read more.

Background/Objectives: Heart failure remains a complex syndrome with high morbidity and mortality, highlighting the urgent need for alternative treatments that address underlying bioenergetic impairments. CoQ10, which plays a crucial role in mitochondrial ATP production, has shown promising results in small studies, although larger trials are needed to confirm its efficacy. Results: This randomized controlled trial investigated the effects of coenzyme Q10 (CoQ10) supplementation on cardiac function and quality of life in heart failure patients. A total of 120 patients were randomly assigned to receive either CoQ10 (2 × 60 mg daily) or a placebo for six months. Baseline characteristics were similar between groups. The primary outcomes were changes in global longitudinal strain (GLS) and left ventricular ejection fractions (LVEFs), while secondary outcomes included improvements in functional capacity and quality of life. At the 6-month endpoint, the CoQ10 group showed significant improvements in GLS (−11.7% to −14.9%, p < 0.001), NT-proBNP levels (815.6 vs. 1378.5 pg/mL, p = 0.012), blood pressure, and 6 min walk test distance (349.3 vs. 267.0 m, p = 0.008) compared to the placebo group. LVEFs improved slightly in the CoQ10 group (38.9% to 40.6%, p = 0.170) but remained unchanged in the placebo group. Conclusions: These findings suggest that CoQ10 supplementation may improve cardiac function, reduce cardiac stress, and enhance functional capacity and quality of life in heart failure patients. Further research is needed to optimize dosage and identify the subgroups that may benefit most from CoQ10 therapy. Full article

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

► Show Figures

Figure 1

35 pages, 1008 KB

Open AccessEditor’s ChoiceSystematic Review

Enhancing Intraoral Scanning Accuracy: From the Influencing Factors to a Procedural Guideline

by Anca Maria Fratila, Adriana Saceleanu, Vasile Calin Arcas, Nicu Fratila and Kamel Earar

J. Clin. Med. 2025, 14(10), 3562; https://doi.org/10.3390/jcm14103562 - 20 May 2025

Cited by 10 | Viewed by 9005

Abstract

Background/Objectives: Intraoral scanning, a fast-evolving technology, is increasingly integrated into actual dental workflows due to its numerous advantages. Despite its growing adoption, challenges related to the accuracy of digital impressions remain. The existing literature identifies most of the factors influencing intraoral scanning [...] Read more.

Background/Objectives: Intraoral scanning, a fast-evolving technology, is increasingly integrated into actual dental workflows due to its numerous advantages. Despite its growing adoption, challenges related to the accuracy of digital impressions remain. The existing literature identifies most of the factors influencing intraoral scanning accuracy (defined by precision and trueness), but it is fragmented and lacks a unified synthesis. In response to this gap, the present study aims to consolidate and structure the current evidence on the determinant factors and, based on these findings, to develop a clinically applicable procedural guideline for dental practitioners. Methods: A comprehensive literature review identified 43 distinct factors influencing intraoral scanning. Results: These factors encompass variables such as software versions and updates, implant characteristics (e.g., position, angulation, scan body design), materials, environmental conditions (e.g., lighting), and procedural elements including scanning strategy, pattern, aids, and operator experience. Subsequently, these identified factors were systematically classified into five distinct groups based on inherent similarities and relevance within the scanning workflow: IOS—characteristics and maintenance, intraoral morphology, materials, ambient conditions, and scanning strategy. To translate these findings into a practical framework, a four-step protocol was developed, designed for straightforward application by researchers and clinicians. Conclusions: This protocol—comprising: (1) Maintenance, (2) Evaluation, (3) Establishment and Execution of Scanning Strategy, and (4) Verification—aims to guide users effectively through the intraoral scanning process, mitigate common clinical challenges, and ensure broad applicability across diverse scanner systems, irrespective of the manufacturer or model. Full article

(This article belongs to the Special Issue Current Challenges in Clinical Dentistry: 2nd Edition)

► Show Figures

Figure 1

25 pages, 493 KB

Open AccessEditor’s ChoiceSystematic Review

PRF and PRP in Dentistry: An Umbrella Review

by Alfonso Acerra, Mario Caggiano, Andrea Chiacchio, Bruno Scognamiglio and Francesco D’Ambrosio

J. Clin. Med. 2025, 14(9), 3224; https://doi.org/10.3390/jcm14093224 - 6 May 2025

Cited by 10 | Viewed by 7490

Abstract

Introduction: Platelet-rich fibrin (PRF) and platelet-rich plasma (PRP) utilize autologous blood and share the objective of leveraging blood-derived growth factors to enhance the body’s natural healing process. A large extensive use has been made in various branches of dentistry. Methods: A [...] Read more.

Introduction: Platelet-rich fibrin (PRF) and platelet-rich plasma (PRP) utilize autologous blood and share the objective of leveraging blood-derived growth factors to enhance the body’s natural healing process. A large extensive use has been made in various branches of dentistry. Methods: A total of 4175 records were identified from the electronic search, specifically 291 from BioMed Central, 3406 from MEDLINE/PubMed, 304 from the Cochrane library databases, and 174 from the PROSPERO register. This review was performed in relation to the PRISMA flow chart and was annotated in the PROSPERO register. Results: In total, 3416 title abstracts were screened, and a total of 40 systematic reviews were finally included in the present umbrella review. Conclusions: Research supports the use of PRF and PRP in different fields of dentistry. This is a huge potential for the patient but also for the doctor as these products are from the patient and have zero cost. However, further studies are needed, especially RCTs, to have clearer evidence on the role of PRF and PRP. Full article

(This article belongs to the Special Issue Clinical Challenges and Advances in Periodontology and Oral Surgery)

► Show Figures

Figure 1

24 pages, 979 KB

Open AccessEditor’s ChoiceReview

Role of Respiratory Viruses in Severe Acute Respiratory Failure

by David Mokrani and Jean-François Timsit

J. Clin. Med. 2025, 14(9), 3175; https://doi.org/10.3390/jcm14093175 - 3 May 2025

Cited by 8 | Viewed by 6500

Abstract

Respiratory viruses are widespread in the community, affecting both the upper and lower respiratory tract. This review provides an updated synthesis of the epidemiology, pathophysiology, clinical impact, and management of severe respiratory viral infections in critically ill patients, with a focus on immunocompetent [...] Read more.

Respiratory viruses are widespread in the community, affecting both the upper and lower respiratory tract. This review provides an updated synthesis of the epidemiology, pathophysiology, clinical impact, and management of severe respiratory viral infections in critically ill patients, with a focus on immunocompetent adults. The clinical presentation is typically nonspecific, making etiological diagnosis challenging. This limitation has been mitigated by the advent of molecular diagnostics—particularly multiplex PCR (mPCR)—which has not only improved pathogen identification at the bedside but also significantly reshaped our understanding of the epidemiology of respiratory viral infections. Routine mPCR testing has revealed that respiratory viruses are implicated in 30–40% of community-acquired pneumonia hospitalizations and are a frequent trigger of acute decompensations in patients with chronic comorbidities. While some viruses follow seasonal patterns, others circulate year-round. Influenza viruses and Pneumoviridae, including respiratory syncytial virus and human metapneumovirus, remain the principal viral pathogens associated with severe outcomes, particularly acute respiratory failure and mortality. Bacterial co-infections are also common and substantially increase both morbidity and mortality. Despite the growing contribution of respiratory viruses to the burden of critical illness, effective antiviral therapies remain limited. Neuraminidase inhibitors remain the cornerstone of treatment for severe influenza, whereas therapeutic options for other respiratory viruses are largely lacking. Optimizing early diagnosis, refining antiviral strategies, and systematically addressing bacterial co-infections are critical to improving outcomes in patients with severe viral pneumonia. Full article

(This article belongs to the Special Issue Update on Acute Severe Respiratory Infections)

► Show Figures

Figure 1

16 pages, 579 KB

Open AccessEditor’s ChoiceSystematic Review

New Evidence About Malignant Transformation of Endometriosis—A Systematic Review

by Alexandra Ioannidou, Maria Sakellariou, Vaia Sarli, Periklis Panagopoulos and Nikolaos Machairiotis

J. Clin. Med. 2025, 14(9), 2975; https://doi.org/10.3390/jcm14092975 - 25 Apr 2025

Cited by 7 | Viewed by 6732

Abstract

Background: Endometriosis is a benign gynecologic condition that has the risk of malignant transformation in approximately 0.5–1% of cases, most of which develop into endometriosis-associated ovarian cancers (EAOCs), such as clear cell and endometrioid adenocarcinomas. The current systematic review aims to condense recent [...] Read more.

Background: Endometriosis is a benign gynecologic condition that has the risk of malignant transformation in approximately 0.5–1% of cases, most of which develop into endometriosis-associated ovarian cancers (EAOCs), such as clear cell and endometrioid adenocarcinomas. The current systematic review aims to condense recent information on the genetic and molecular mechanisms, clinical risk factors, and possible therapeutic targets of the malignant transformation of endometriosis. Methods: A systematic literature search of PubMed, Europe PMC, and Google Scholar was carried out according to PRISMA guidelines for articles published until December 2024. Following a screening of 44,629 titles, 43 full articles were included after meeting inclusion criteria. No case reports or reviews were included, and articles had to mention a malignant transformation of endometriosis and not just a diagnosis of cancer. The quality and risk of bias of studies were evaluated using ROBINS-I. Results: Malignant transformation of endometriosis is associated with genetic alterations, including ARID1A mutations, microsatellite instability, and abnormal PI3K/Akt and mTOR pathway activation. Increased oxidative stress, inflammation-driven mismatch repair deficiency, and epigenetic alterations like RUNX3 and RASSF2 hypermethylation are implicated in carcinogenesis. Clinical risk factors are advanced age (40–60 years), large ovarian endometriomas (>9 cm), postmenopausal status, and prolonged estrogen exposure. Imaging techniques like MR relaxometry and risk models based on machine learning are highly predictive for early detection. Conclusions: Endometriosis carcinogenesis is a multifactorial process driven by genetic changes, oxidative stress, and inflammatory mechanisms. Identification of high-risk individuals through molecular and imaging biomarkers may result in early detection and personalized therapy. Further research should aim at the development of more precise predictive models and exploration of precision medicine approaches to inhibit the emergence of EAOC. Full article

(This article belongs to the Special Issue Gynecologic and Obstetric Pathologies: From Birth to Menopause (Second Edition))

► Show Figures

Figure 1

15 pages, 2781 KB

Open AccessEditor’s ChoiceSystematic Review

Embolization of Middle Meningeal Artery in Patients with Chronic Subdural Hematoma: A Systematic Review and Meta-Analysis of Randomized-Controlled Clinical Trials

by Nikolaos M. Papageorgiou, Lina Palaiodimou, Konstantinos Melanis, Aikaterini Theodorou, Maria-Ioanna Stefanou, Panagiota-Eleni Tsalouchidou, Pinelopi Vlotinou, Lampis C. Stavrinou, Efstathios Boviatsis, Georgios Magoufis, Marios Themistocleous, Amrou Sarraj, Vijay K. Sharma, Nitin Goyal and Georgios Tsivgoulis

J. Clin. Med. 2025, 14(9), 2862; https://doi.org/10.3390/jcm14092862 - 22 Apr 2025

Cited by 9 | Viewed by 5172

Abstract

Background: Chronic subdural hematoma (cSDH) is a common neurosurgical condition, particularly among elderly patients. Middle meningeal artery (MMA) embolization has emerged as a minimally invasive adjunctive treatment aimed at reducing recurrence. However, its comparative efficacy and safety remain under investigation. Methods: In this [...] Read more.

Background: Chronic subdural hematoma (cSDH) is a common neurosurgical condition, particularly among elderly patients. Middle meningeal artery (MMA) embolization has emerged as a minimally invasive adjunctive treatment aimed at reducing recurrence. However, its comparative efficacy and safety remain under investigation. Methods: In this systematic review and meta-analysis, randomized-controlled clinical trial (RCT) data evaluating MMA embolization combined with best medical therapy (BMT) versus BMT alone in adult patients with symptomatic cSDH were pooled. The primary efficacy outcome was recurrence or progression of hematoma at follow-up. Secondary efficacy outcomes included good functional outcome [modified Rankin Scale (mRS) score ≤ 2], independent ambulation (mRS score ≤ 3), and hematoma thickness at follow-up. The primary safety outcome was all-cause mortality. Procedure-related complications were assessed as a secondary safety outcome. Results: Six RCTs were included, comprising 760 patients treated with MMA embolization and 788 patients treated with BMT alone. MMA embolization significantly reduced recurrence compared to BMT alone (RR: 0.50; 95% CI: 0.37–0.69; six studies; I² = 0%; number-needed-to-treat = 13). No significant differences were observed in good functional outcome (RR: 1.01; 95% CI: 0.97–1.05; three studies; I² = 0%), independent ambulation (RR: 1.01; 95% CI: 0.99–1.04; three studies; I² = 0%), or hematoma thickness at follow-up (SMD: −0.1; 95% CI: −0.3 to 0; four studies; I² = 42%). All-cause mortality was similar between the two groups (RR: 1.01; 95% CI: 0.42–2.40; five studies; I² = 44%). The pooled rate of procedure-related adverse events in the MMA embolization-group was 1% (95% CI: 0–3%; two studies; I² = 35%). Conclusions: MMA embolization significantly reduced cSDH recurrence when used as an adjunct to BMT. However, it did not demonstrate a significant impact on functional outcomes or mortality in this meta-analysis. Further research is needed to identify patient subgroups that benefit most from MMA embolization and to evaluate its impact on cognitive function and quality of life using longer follow-up periods. Full article

(This article belongs to the Section Clinical Neurology)

► Show Figures

Figure 1

32 pages, 2143 KB

Open AccessEditor’s ChoiceSystematic Review

Short-Term and Long-Term Effects of Inhaled Ultrafine Particles on Blood Markers of Cardiovascular Diseases: A Systematic Review and Meta-Analysis

by Joanna Izabela Lachowicz and Paweł Gać

J. Clin. Med. 2025, 14(8), 2846; https://doi.org/10.3390/jcm14082846 - 21 Apr 2025

Cited by 9 | Viewed by 2322

Abstract

Background/Objectives: Air pollution is the highest environmental risk factor of mortality and morbidity worldwide, leading to over 4 million deaths each year. Among different air pollutants, ultrafine particles (UFPs) constitute the highest risk factor of cardiovascular diseases (CVDs). Epidemiological studies have associated UFPs [...] Read more.

Background/Objectives: Air pollution is the highest environmental risk factor of mortality and morbidity worldwide, leading to over 4 million deaths each year. Among different air pollutants, ultrafine particles (UFPs) constitute the highest risk factor of cardiovascular diseases (CVDs). Epidemiological studies have associated UFPs with the short- and long-term imbalance of numerous blood markers. Our objective was to systematically review the short-term and long-term impact of UFP exposure on blood markers of CVDs. Methods: We prepared the systematic review of CVD blood markers and meta-analyses of the short- and long-term effects of UFP exposure on high-sensitivity C-reactive protein (hsCRP) concentration. The eligibility criteria were established with the use of the Provider, Enrollment, Chain, and Ownership System (PECOS) model, and the literature search was conducted in Web of Science, PubMed, and Scopus databases from 1 January 2013 to 9 January 2025. The risk of bias (RoB) was prepared according to a World Health Organization (WHO) template. Results: The results showed an increase in hsCRP as a result of both short-term and long-term UFPs. Moreover, IL-6 and IL-1β together with other inflammatory markers increased after short-term UFP exposure. In addition, different nucleic acids, among which were miR-24-3p and let-7d-5p, were differentially expressed (DE) as a result of short-term UFP exposure. Chronic exposure to UFPs could lead to a persistent increase in hsCRP and other blood markers of CVDs. Conclusions: Our findings underline that UFPs may lead to the development and/or worsening of cardiovascular outcomes in fragile populations living in air-polluted areas. Full article

(This article belongs to the Section Cardiology)

► Show Figures

Figure 1

30 pages, 1276 KB

Open AccessEditor’s ChoiceReview

Metabolic Syndrome and Liver Disease: Re-Appraisal of Screening, Diagnosis, and Treatment Through the Paradigm Shift from NAFLD to MASLD

by Marin Pecani, Paola Andreozzi, Roberto Cangemi, Bernadette Corica, Marzia Miglionico, Giulio Francesco Romiti, Lucia Stefanini, Valeria Raparelli and Stefania Basili

J. Clin. Med. 2025, 14(8), 2750; https://doi.org/10.3390/jcm14082750 - 16 Apr 2025

Cited by 9 | Viewed by 6594

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), encompasses a spectrum of liver diseases characterized by hepatic steatosis, the presence of at least one cardiometabolic risk factor, and no other apparent cause. Metabolic syndrome (MetS) is a [...] Read more.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), encompasses a spectrum of liver diseases characterized by hepatic steatosis, the presence of at least one cardiometabolic risk factor, and no other apparent cause. Metabolic syndrome (MetS) is a cluster of clinical conditions associated with increased risk of cardiovascular disease, type 2 diabetes, and overall morbidity and mortality. This narrative review summarizes the changes in the management of people with MetS and NAFLD/MASLD from screening to therapeutic strategies that have occurred in the last decades. Specifically, we underline the clinical importance of considering the different impacts of simple steatosis and advanced fibrosis and provide an up-to-date overview on non-invasive diagnostic tests (i.e., imaging and serum biomarkers), which now offer acceptable accuracy and are globally more accessible. Early detection of MetS and MASLD is a top priority as it allows for timely interventions, primarily through lifestyle modification. The liver and cardiovascular benefits of a global and multidimensional approach are not negligible. Therefore, a holistic approach to both conditions, MetS and related chronic liver disease, should be applied to improve overall health and longevity. Full article

(This article belongs to the Section Endocrinology & Metabolism)

► Show Figures

Figure 1

17 pages, 552 KB

Open AccessEditor’s ChoiceReview

Rethinking the Assessment of Arthrogenic Muscle Inhibition After ACL Reconstruction: Implications for Return-to-Sport Decision-Making—A Narrative Review

by Florian Forelli, Ayrton Moiroux-Sahraoui, Jean Mazeas, Jonathan Dugernier and Adrien Cerrito

J. Clin. Med. 2025, 14(8), 2633; https://doi.org/10.3390/jcm14082633 - 11 Apr 2025

Cited by 12 | Viewed by 10532

Abstract

Arthrogenic muscle inhibition (AMI) is a neuromuscular impairment commonly observed following anterior cruciate ligament reconstruction (ACLR). This condition, characterized by persistent quadricep inhibition due to altered afferent feedback, significantly impacts neuromuscular recovery, delaying return to running and sport. Despite advancements in rehabilitation strategies, [...] Read more.

Arthrogenic muscle inhibition (AMI) is a neuromuscular impairment commonly observed following anterior cruciate ligament reconstruction (ACLR). This condition, characterized by persistent quadricep inhibition due to altered afferent feedback, significantly impacts neuromuscular recovery, delaying return to running and sport. Despite advancements in rehabilitation strategies, AMI may persist for months or even years after ACLR, leading to muscle strength asymmetries, altered biomechanics, and an increased risk of reinjury. The mechanisms underlying AMI involve both peripheral (joint effusion, mechanoreceptor dysfunction) and central (corticospinal inhibition, neuroplasticity alterations) components, which collectively hinder voluntary muscle activation and movement control. AMI alters gait mechanics, reduces knee stability, and promotes compensatory patterns that increase injury risk. Current return-to-sport protocols emphasize strength symmetry and functional performance but often neglect neuromuscular deficits. A comprehensive assessment integrating neuromuscular, biomechanical, and proprioceptive evaluations is needed at specific stages to optimize rehabilitation and minimize reinjury risk. Future research should explore targeted interventions such as neuromuscular stimulation, cognitive–motor training, and advanced gait analysis to mitigate AMI’s impact and facilitate a safer, more effective return to sport. Full article

(This article belongs to the Special Issue Sports Injury: Clinical Prevention and Treatment)

► Show Figures

Figure 1

30 pages, 650 KB

Open AccessEditor’s ChoiceReview

Molecular Mechanisms and Therapeutic Role of Intra-Articular Hyaluronic Acid in Osteoarthritis: A Precision Medicine Perspective

by Wojciech Glinkowski, Dariusz Śladowski, Wiesław Tomaszewski and Pol-IAHA Study Group

J. Clin. Med. 2025, 14(8), 2547; https://doi.org/10.3390/jcm14082547 - 8 Apr 2025

Cited by 11 | Viewed by 5291

Abstract

Background: Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage breakdown, synovial inflammation, and pain, which leads to significant disability. IAHA is widely used because of its viscoelastic properties, which restore synovial fluid homeostasis and reduce symptoms. However, emerging evidence [...] Read more.

Background: Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage breakdown, synovial inflammation, and pain, which leads to significant disability. IAHA is widely used because of its viscoelastic properties, which restore synovial fluid homeostasis and reduce symptoms. However, emerging evidence suggests that IAHA exerts additional biological effects including chondroprotection, inflammatory modulation, oxidative stress reduction, and pain modulation, which may influence disease progression. Objective: This narrative review examines the biological mechanisms underlying IAHA’s role in OA management. The review explored IAHA’s effects on synovial fluid viscoelasticity, inflammatory cytokine modulation, cartilage preservation, oxidative stress regulation, and pain pathways, emphasizing the influence of molecular weight variations on therapeutic efficacy. Additionally, this review evaluates IAHA’s integration into multimodal treatment strategies, its potential disease-modifying effects, and future directions for personalized treatment approaches. Methods: A comprehensive literature review was conducted using PubMed, Cochrane Library, EMBASE, Scopus, and Web of Science for studies published between January 2000 and March 2024. The search focused on IAHA’s molecular, cellular, and biochemical effects in OA and clinical findings assessing its impact on joint function, pain relief, and disease progression. Results: IAHA improves synovial fluid lubrication, reduces proinflammatory cytokines (IL-1β, TNF-α), inhibits matrix metalloproteinases (MMPs), scavenges reactive oxygen species (ROS), and modulates nociceptive pathways. High-molecular-weight IAHA demonstrates superior efficacy in advanced OA, while low-molecular-weight formulations may be better suited for early-stage disease. Although IAHA’s symptom relief is comparable to corticosteroids and NSAIDs, its favorable safety profile and emerging disease-modifying potential support its long-term use in OA management. Conclusions: IAHA represents a multifaceted therapeutic approach bridging symptomatic relief and regenerative strategies. While long-term efficacy, optimal administration protocols, and patient-specific responses remain subjects of ongoing research, refining treatment selection criteria, dosing regimens, and combination strategies may enhance clinical outcomes. Future studies should explore biomarker-driven approaches, standardize treatment protocols, and assess IAHA’s synergy with regenerative medicine to optimize its role in OA management. Full article

(This article belongs to the Special Issue Etiopathogenesis, Prevention, Modern Diagnostics and Conservative Treatment of Osteoarthritis)

► Show Figures

Figure 1

52 pages, 823 KB

Open AccessEditor’s ChoiceSystematic Review

Acanthamoeba Keratitis Management and Prognostic Factors: A Systematic Review

by Pedro Marques-Couto, Mariana Monteiro, Ana Margarida Ferreira, João Pinheiro-Costa and Rodrigo Vilares-Morgado

J. Clin. Med. 2025, 14(7), 2528; https://doi.org/10.3390/jcm14072528 - 7 Apr 2025

Cited by 6 | Viewed by 4770

Abstract

Background/Objectives: The aim of this study was to review the therapeutic and prognostic factors influencing Acanthamoeba Keratitis (AK) management. Methods: A systematic search was performed across MEDLINE^® (via PubMed), Web of Science^®, and Scopus^®, following the [...] Read more.

Background/Objectives: The aim of this study was to review the therapeutic and prognostic factors influencing Acanthamoeba Keratitis (AK) management. Methods: A systematic search was performed across MEDLINE^® (via PubMed), Web of Science^®, and Scopus^®, following the PRISMA 2020 guidelines, and registered in PROSPERO (CRD420251010774). Studies reporting AK treatment regiments and prognostic factors were included. After extracting the data from the included articles, the relevant aspects of the treatment and the prognostic factors were compared and summarized. Results: Sixty-one articles were included: nine were prospective, including 3 randomized controlled trials (RCTs), and fifty-two were retrospective. The findings suggest that therapeutic epithelial debridement (TED), followed by an association with biguanides, diamidines, and an antibacterial agent, is a strong initial treatment option. An adjunctive medical treatment with topical voriconazole 1% or oral miltefosine may also be considered. Surgical approaches were also assessed when the pharmaceutical therapy failed, with Deep Anterior Lamellar Keratoplasty (DALK) playing an important role in the cases without a deep stroma involvement. Early Therapeutic Penetrating Keratoplasty (TPK) should be used as a salvage therapy and Optical Penetrating Keratoplasty (OPK) should be used for rehabilitation purposes. Key prognostic factors include older age, delayed diagnosis, corticosteroid use before prompt diagnosis, poor initial best corrected visual acuity (BCVA), and AK stage at presentation. Conclusions: The initial treatment with TED, biguanides, and diamidines remains the foundation of treatment. Surgical options can be considered in advanced cases. An early diagnosis, age, and initial BCVA are prognosis factors that should be considered. Future research may focus on improvement of protocols and searching for novel agents. Full article

(This article belongs to the Special Issue Clinical Advances and Management in Corneal Diseases)

► Show Figures

Figure 1

16 pages, 2520 KB

Open AccessEditor’s ChoiceArticle

Clinical and Economic Burden of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in a Spanish Mediterranean Region: A Population-Based Study

by Javier Díaz Carnicero, Inma Saurí-Ferrer, Josep Redon, Jorge Navarro, Gonzalo Fernández, Carlos Hurtado, Karine Ferreira, Carolina Alvarez-Ortega, Antón Gómez, Carlos J. Martos-Rodríguez, David Martí-Aguado, Desamparados Escudero and Marta Cedenilla

J. Clin. Med. 2025, 14(7), 2441; https://doi.org/10.3390/jcm14072441 - 3 Apr 2025

Cited by 6 | Viewed by 2403

Abstract

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition worldwide, with significant regional variability in prevalence estimates. This study aimed to determine the prevalence, demographic characteristics, and economic burden of MASLD, metabolic dysfunction-associated steatotic liver (MASL), and metabolic dysfunction-associated steatohepatitis (MASH) [...] Read more.

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition worldwide, with significant regional variability in prevalence estimates. This study aimed to determine the prevalence, demographic characteristics, and economic burden of MASLD, metabolic dysfunction-associated steatotic liver (MASL), and metabolic dysfunction-associated steatohepatitis (MASH) in the Valencian Community region of Spain. Methods: We conducted a retrospective analysis of electronic medical records from the Valencian public healthcare database of individuals aged over 24 years from 2012 to 2019. Results: Of the 3,411,069 individuals included in the database in 2019, 75,565 were diagnosed with MASLD, 74,065 with MASL, and 1504 with MASH based on the International Classification of Diseases (ICD), corresponding to a prevalence of 2.22%, 2.17%, and 0.04%, respectively. Among individuals with type 2 diabetes mellitus (T2DM) or obesity, the prevalence of MASLD was approximately three times and 2.5 times higher, respectively, compared to the overall population. The prevalence of MASLD, MASL, and MASH increased from 2012 to 2019 in all the populations studied. The highest risk of hospitalization was associated with liver-related causes, followed by all-cause hospitalization. The highest cost per subject in 2019 was observed in individuals with concomitant MASH and T2DM. Conclusions: Our findings indicate a rising prevalence of MASLD, MASL, and MASH, despite their potential underdiagnosis during the study period. The presence of MASLD or MASH was associated with high healthcare costs, particularly in patients with MASH and T2DM. Our results underline the need for more effective strategies to enhance disease awareness and improve resource allocation. 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)

► Show Figures

Figure 1

15 pages, 2483 KB

Open AccessEditor’s ChoiceArticle

Thyro-GenAI: A Chatbot Using Retrieval-Augmented Generative Models for Personalized Thyroid Disease Management

by Minjeong Shin, Junho Song, Myung-Gwan Kim, Hyeong Won Yu, Eun Kyung Choe and Young Jun Chai

J. Clin. Med. 2025, 14(7), 2450; https://doi.org/10.3390/jcm14072450 - 3 Apr 2025

Cited by 7 | Viewed by 1781

Abstract

Background: Large language models (LLMs) have the potential to enhance information processing and clinical reasoning in the healthcare industry but are hindered by inaccuracies and hallucinations. The retrieval-augmented generation (RAG) technique may address these problems by integrating external knowledge sources. Methods: We developed [...] Read more.

Background: Large language models (LLMs) have the potential to enhance information processing and clinical reasoning in the healthcare industry but are hindered by inaccuracies and hallucinations. The retrieval-augmented generation (RAG) technique may address these problems by integrating external knowledge sources. Methods: We developed a RAG-based chatbot called Thyro-GenAI by integrating a database of textbooks and guidelines with LLM. Thyro-GenAI and three service LLMs: OpenAI’s ChatGPT-4o, Perplexity AI’s ChatGPT-4o, and Anthropic’s Claude 3.5 Sonnet, were asked personalized clinical questions about thyroid disease. Three thyroid specialists assessed the quality of the generated responses and references without being blinded, which allowed them to interact with different chatbot interfaces. Results: Thyro-GenAI achieved the highest inverse-weighted mean rank for overall response quality. The overall inverse-weighted mean rankings for Thyro-GenAI, ChatGPT, Perplexity, and Claude were 3.0, 2.3, 2.8, and 1.9, respectively. Thyro-GenAI also achieved the second-highest inverse-weighted mean rank for overall reference quality. The overall inverse-weighted mean rankings for Thyro-GenAI, ChatGPT, Perplexity, and Claude were 3.1, 2.3, 3.2, and 1.8, respectively. Conclusions: Thyro-GenAI produced patient-specific clinical reasoning output based on a vector database, with fewer hallucinations and more reliability, compared to service LLMs. This emphasis on evidence-based responses ensures its safety and validity, addressing a critical limitation of existing LLMs. By integrating RAG with LLMs, it has the potential to support frontline clinical decision-making, especially helping first-line physicians by offering reliable decision support while managing thyroid disease patients. Full article

(This article belongs to the Section General Surgery)

► Show Figures

Figure 1

27 pages, 4371 KB

Open AccessEditor’s ChoiceSystematic Review

Diagnostic Accuracy of Deep Learning for Intracranial Hemorrhage Detection in Non-Contrast Brain CT Scans: A Systematic Review and Meta-Analysis

by Armin Karamian and Ali Seifi

J. Clin. Med. 2025, 14(7), 2377; https://doi.org/10.3390/jcm14072377 - 30 Mar 2025

Cited by 13 | Viewed by 6884

Abstract

Background: Intracranial hemorrhage (ICH) is a life-threatening medical condition that needs early detection and treatment. In this systematic review and meta-analysis, we aimed to update our knowledge of the performance of deep learning (DL) models in detecting ICH on non-contrast computed tomography [...] Read more.

Background: Intracranial hemorrhage (ICH) is a life-threatening medical condition that needs early detection and treatment. In this systematic review and meta-analysis, we aimed to update our knowledge of the performance of deep learning (DL) models in detecting ICH on non-contrast computed tomography (NCCT). Methods: The study protocol was registered with PROSPERO (CRD420250654071). PubMed/MEDLINE and Google Scholar databases and the reference section of included studies were searched for eligible studies. The risk of bias in the included studies was assessed using the QUADAS-2 tool. Required data was collected to calculate pooled sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with the corresponding 95% CI using the random effects model. Results: Seventy-three studies were included in our qualitative synthesis, and fifty-eight studies were selected for our meta-analysis. A pooled sensitivity of 0.92 (95% CI 0.90–0.94) and a pooled specificity of 0.94 (95% CI 0.92–0.95) were achieved. Pooled PPV was 0.84 (95% CI 0.78–0.89) and pooled NPV was 0.97 (95% CI 0.96–0.98). A bivariate model showed a pooled AUC of 0.96 (95% CI 0.95–0.97). Conclusions: This meta-analysis demonstrates that DL performs well in detecting ICH from NCCTs, highlighting a promising potential for the use of AI tools in various practice settings. More prospective studies are needed to confirm the potential clinical benefit of implementing DL-based tools and reveal the limitations of such tools for automated ICH detection and their impact on clinical workflow and outcomes of patients. Full article

(This article belongs to the Special Issue Neurocritical Care: Clinical Advances and Practice Updates)

► Show Figures

Graphical abstract

16 pages, 3002 KB

Open AccessEditor’s ChoiceReview

Pregnancy-Associated Takotsubo Syndrome: A Narrative Review of the Literature

by Panagiotis Iliakis, Anna Pitsillidi, Nikolaos Pyrpyris, Christos Fragkoulis, Ioannis Leontsinis, Georgios Koutsopoulos, Emmanouil Mantzouranis, Stergios Soulaidopoulos, Alexandros Kasiakogias, Kyriakos Dimitriadis, Günter Karl Noé and Konstantinos Tsioufis

J. Clin. Med. 2025, 14(7), 2356; https://doi.org/10.3390/jcm14072356 - 29 Mar 2025

Cited by 7 | Viewed by 2553

Abstract

Takotsubo syndrome (TTS) is a clinical syndrome defined most typically by transient systolic dysfunction and dilatation of the apex of the left ventricle or other regional areas in the documented absence of obstructive coronary artery disease. Although more commonly presented in postmenopausal women, [...] Read more.

Takotsubo syndrome (TTS) is a clinical syndrome defined most typically by transient systolic dysfunction and dilatation of the apex of the left ventricle or other regional areas in the documented absence of obstructive coronary artery disease. Although more commonly presented in postmenopausal women, there are reports in the literature of TTS during the peripartum and postpartum periods. Early TTS diagnosis in pregnancy is of great importance in improving both maternal and fetal mortality. Although TTS involves many pathogenetic pathways, the imbalance between declining estrogen and arising sympathetic nervous system tone plays an important role. This review aims to provide recent published evidence of TTS in pregnancy and delve into the epidemiology of TTS in pregnancy, the pathophysiological mechanisms involved, the prognosis of TTS for the mother and the fetus, and its therapeutic multi-disciplinary management. Full article

(This article belongs to the Special Issue Diagnosis and Management of Complications During Pregnancy)

► Show Figures

Figure 1

16 pages, 987 KB

Open AccessEditor’s ChoiceArticle

The Ability of the Triglyceride-Glucose (TyG) Index and Modified TyG Indexes to Predict the Presence of Metabolic-Associated Fatty Liver Disease and Metabolic Syndrome in a Pediatric Population with Obesity

by Sofia Tamini, Adele Bondesan, Diana Caroli, Nicoletta Marazzi and Alessandro Sartorio

J. Clin. Med. 2025, 14(7), 2341; https://doi.org/10.3390/jcm14072341 - 28 Mar 2025

Cited by 7 | Viewed by 1689

Abstract

Background: Metabolic-associated fatty liver disease (MASLD) and metabolic syndrome (MetS) are increasingly prevalent among children and adolescents with obesity, posing significant long-term metabolic and cardiovascular risks. Non-invasive identification of at-risk individuals is crucial for a timely intervention. This study aimed to evaluate [...] Read more.

Background: Metabolic-associated fatty liver disease (MASLD) and metabolic syndrome (MetS) are increasingly prevalent among children and adolescents with obesity, posing significant long-term metabolic and cardiovascular risks. Non-invasive identification of at-risk individuals is crucial for a timely intervention. This study aimed to evaluate the diagnostic performance of the triglyceride-glucose (TyG) index and its modified versions, TyG-body mass index (TyG-BMI) and TyG-waist circumference (TyG-WC), in predicting MASLD and MetS in a large cohort of children and adolescents with obesity. Methods: A total of 758 children and adolescents with obesity (454 females, 304 males; mean age 14.8 ± 2.1 years; mean BMI 37.9 ± 6.2 kg/m²) were included. MASLD was diagnosed via ultrasonography, while MetS was defined using International Diabetes Federation criteria. TyG, TyG-WC, and TyG-BMI were calculated for all participants. Receiver operating characteristic (ROC) curves were generated to assess the diagnostic accuracy of these indexes, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: MASLD was detected in 38.9% of participants, with a higher prevalence in males (p < 0.0001). MetS was present in 27.8% of the cohort, with higher prevalence in males (p < 0.0001). Among the indexes, TyG-WC exhibited the highest sensitivity for MASLD (77.6%), whereas TyG-BMI had the highest specificity (63.3%). In predicting MetS, all three indexes performed better than for MASLD, with TyG demonstrating the highest PPV (54.5%) and TyG-BMI the highest NPV (87.5%). Predictive performance was lower in males than females, potentially due to sex-specific differences in fat distribution and metabolic response. Conclusions: TyG, TyG-WC, and TyG-BMI are promising, non-invasive tools for identifying children and adolescents with obesity at risk for MASLD and MetS. The superior sensitivity of TyG-WC and the high specificity of TyG-BMI highlight the value of incorporating anthropometric parameters into metabolic screening. Integrating these indexes into routine clinical practice may enhance early detection, allowing for timely intervention and personalized management strategies, ultimately reducing the long-term burden of metabolic and liver diseases in pediatric populations. Full article

(This article belongs to the Section Clinical Pediatrics)

► Show Figures

Figure 1

14 pages, 651 KB

Open AccessEditor’s ChoiceArticle

Long-Term Outcomes and Prognostic Factors of Medial Open Wedge High Tibial Osteotomy for Medial Compartment Knee Osteoarthritis or Osteonecrosis

by Yuji Arai, Shuji Nakagawa, Atsuo Inoue, Yuta Fujii, Ryota Cha, Kei Nakamura and Kenji Takahashi

J. Clin. Med. 2025, 14(7), 2294; https://doi.org/10.3390/jcm14072294 - 27 Mar 2025

Cited by 7 | Viewed by 2876

Abstract

Background/Objectives: Medial open wedge high tibial osteotomy (MOWHTO) has led to favorable clinical results since the introduction of locking plates. Surgical indications, techniques, and postoperative alignment are crucial for achieving favorable clinical outcomes. This study analyzed the clinical outcomes of patients after >5 [...] Read more.

Background/Objectives: Medial open wedge high tibial osteotomy (MOWHTO) has led to favorable clinical results since the introduction of locking plates. Surgical indications, techniques, and postoperative alignment are crucial for achieving favorable clinical outcomes. This study analyzed the clinical outcomes of patients after >5 years of post-MOWHTO follow-up to identify the influential factors. Methods: Thirty-nine patients (48 knees) underwent MOWHTO for medial compartment knee osteoarthritis or -necrosis and were followed up for >5 years. The targeted postoperative % mechanical axis (%MA) was 62.5% (Fujisawa point). The Japanese Orthopaedic Association (JOA) Knee Disease Outcome Criteria score; Kellgren–Lawrence classification; hip-knee-ankle, medial proximal tibial, mechanical lateral distal femoral, and joint line convergence angles (JLCA); and %MA were evaluated preoperatively, at implant removal, and at the final follow-up. Total knee arthroplasty (TKA) was the survival endpoint. Uni- and multivariate analyses were performed to identify the factors influencing survival rates. Results: The mean JOA score improved from preoperative to implant removal and was sustained at 102 months. Four of the 48 knees required TKA, resulting in a 10-year survival rate of 82%. Body mass index, preoperative JLCA, and Δ%MA influenced the post-MOWHTO survival rate. The Δ%MA was significantly greater in the group with a %MA < 62.5% at implant removal. Conclusions: MOWHTO with a target %MA of 62.5% yielded favorable long-term outcomes. Additionally, preoperative obesity and high joint instability negatively influenced post-MOWHTO survival. Furthermore, a postoperative %MA of < 62.5% is associated with difficulty maintaining stable alignment and an increased risk of conversion to TKA. Full article

(This article belongs to the Section Orthopedics)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Editor’s Choice Articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI