Journal of Clinical Medicine

112 pages, 3368 KB

Open AccessSystematic Review

Evidence-Based Clinical Recommendations for the Appropriate Use of Diagnostic Tests in Pediatric Allergology: Focus on Asthma, Rhinoconjunctivitis, and Keratoconjunctivitis Vernal

by Valentina Fainardi, Matteo Riccò, Rachele Antignani, Simona Bellodi, Claudia Borrelli, Tommaso Carretta, Mauro Calvani, Fabio Cardinale, Elena Chiappini, Maria Angiola Crivellaro, Massimiliano Esposito, Roberto Grandinetti, Amelia Licari, Michele Miraglia Del Giudice, Maria Marsella, Alberto Martelli, Iria Neri, Rita Nocerino, Diego Peroni, Cristina Piersantelli, Giuseppe Pingitore, Arianna Rossi, Giuseppe Squazzini, Mariangela Tosca, Carlo Caffarelli and Susanna Esposito Show full author list Hide full author list

J. Clin. Med. 2026, 15(12), 4848; https://doi.org/10.3390/jcm15124848 - 22 Jun 2026

Cited by 1 | Viewed by 603

Abstract

Background: Appropriateness of diagnostic test prescriptions represents a critical component of quality care in pediatric allergology, directly influencing diagnostic accuracy, therapeutic decisions, healthcare resource utilization, and patient outcomes. A multidisciplinary expert panel was convened to develop evidence-based clinical recommendations addressing the appropriate use [...] Read more.

Background: Appropriateness of diagnostic test prescriptions represents a critical component of quality care in pediatric allergology, directly influencing diagnostic accuracy, therapeutic decisions, healthcare resource utilization, and patient outcomes. A multidisciplinary expert panel was convened to develop evidence-based clinical recommendations addressing the appropriate use of specialist consultations and diagnostic investigations in children with asthma, allergic rhinoconjunctivitis, and vernal keratoconjunctivitis (VKC). Methods: Clinical questions were formulated using the PICO framework and prioritized through structured expert consensus. Systematic literature reviews were conducted across major databases, and the certainty of evidence was assessed using the GRADE methodology. Results: Specialist evaluation emerged as a key determinant of improved diagnostic precision, optimization of treatment strategies, and reduction of inappropriate therapies. In asthma, spirometry, FeNO measurement, and allergy testing contributed to enhanced diagnostic accuracy and better control. In allergic rhinoconjunctivitis, allergological assessment supported diagnosis and the selection of immunotherapy, with demonstrated benefits on symptoms and quality of life. For VKC, multidisciplinary specialist involvement facilitated early diagnosis, personalized management, and prevention of complications. Conclusions: Although the overall certainty of evidence ranged from moderate to low, consistent clinical benefits supported consensus-based recommendations. Implementation of these recommendations may improve care quality, promote equitable access to diagnostic resources, and reduce unnecessary healthcare utilization. Full article

(This article belongs to the Section Clinical Pediatrics)

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17 pages, 948 KB

Open AccessReview

Surgical and Transcatheter Approach of a Failed Mitral Valve Repair: A Comprehensive Review on Selecting the Most Suitable Approach

by Roberto Nerla, Martina Mandas, Gianluca Pillitteri, Elisa Mikus, Niki Bernardoni, Angelo Squeri, Davide Pacini, Carlo Savini and Fausto Castriota

J. Clin. Med. 2026, 15(12), 4847; https://doi.org/10.3390/jcm15124847 - 22 Jun 2026

Viewed by 574

Abstract

Mitral valve regurgitation is the second most common valvular heart disease in Europe, and an estimated 10% of individuals older than 75 years have severe mitral regurgitation. Mitral valve repair is the preferred strategy to treat mitral regurgitation and is associated with better [...] Read more.

Mitral valve regurgitation is the second most common valvular heart disease in Europe, and an estimated 10% of individuals older than 75 years have severe mitral regurgitation. Mitral valve repair is the preferred strategy to treat mitral regurgitation and is associated with better outcomes than mitral valve replacement. Despite the proven efficacy of surgical repair, available data in functional aetiologies reported a non-negligible rate of echocardiographically detected severe mitral regurgitation within ten years of the index procedure, in some cases resulting in redo interventions. Data on the optimal management of patients with failed mitral repair remain limited. The aim of this review is to present the available approaches for treating failed mitral valve repair and to describe criteria for selecting the most appropriate strategy on the basis of the underlying mechanism of repair failure, with respect to possible surgical re-repair and novel transcatheter edge-to-edge repair techniques in the presence of favourable mitral valve anatomies. Full article

(This article belongs to the Special Issue Clinical Therapeutic Advances of Mitral Regurgitation)

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15 pages, 1311 KB

Open AccessArticle

Hybrid Metaheuristic Feature Selection for Breast Cancer Detection in Digital Mammography: A Feasibility Study with Nested Validation, Benchmarking, and External Stress Testing

by Bandar S. Alshreef and Yousif A. Kariri

J. Clin. Med. 2026, 15(12), 4846; https://doi.org/10.3390/jcm15124846 - 22 Jun 2026

Viewed by 504

Abstract

Background/Objectives: The “small-n-large-p” dilemma in mammography artificial intelligence (AI)—where the number of candidate imaging features far exceeds the number of labeled cases—commonly results in model overfitting, unstable feature selection, and poor generalization across clinical settings. This study aims to reassess the internal performance [...] Read more.

Background/Objectives: The “small-n-large-p” dilemma in mammography artificial intelligence (AI)—where the number of candidate imaging features far exceeds the number of labeled cases—commonly results in model overfitting, unstable feature selection, and poor generalization across clinical settings. This study aims to reassess the internal performance of the HiTopology-GOA-CSA (Grasshopper Optimization Algorithm–Crow Search Algorithm) feature-selection framework for mammography using a larger real Curated Breast Imaging Subset of Digital Database for Screening Mammography (CBIS-DDSM) cohort and a stricter leakage-aware evaluation strategy. Methods: In this retrospective computational study using public anonymized datasets, an expanded internal cohort of 98 CBIS-DDSM mass cases (49 benign, 49 malignant) was assembled from digital imaging and communications in medicine (DICOM) region of interest (ROI) series. A total of 1074 features were extracted per case, including 88 handcrafted radiomic descriptors and 986 EfficientNet-B5 deep features. HiTopology-GOA-CSA selected 102 features, corresponding to 91% feature reduction. Two internal evaluation modes were compared: Mode A, which matched the original pilot methodology by performing feature selection once on the full cohort before cross-validation, and Mode B, which used strict nested feature selection within training folds. Performance was assessed with 5-fold stratified cross-validation using a multilayer perceptron (MLP) classifier. Results: On the expanded cohort, Mode A achieved an area under the receiver operating characteristic curve (AUC) of 0.726 (95% CI: 0.594–0.858), sensitivity of 0.658, specificity of 0.651, and F1-score of 0.644. Under the stricter nested evaluation, Mode B achieved AUC of 0.683 (95% CI: 0.549–0.817), sensitivity of 0.598, specificity of 0.631, and F1-score of 0.595. Mean pairwise Jaccard similarity across nested folds was 0.604, indicating moderate feature stability. Benchmark comparisons showed that the proposed method was competitive but did not outperform standard baselines; LASSO logistic regression achieved the highest AUC of 0.739, while the proposed HiTopology-GOA-CSA + MLP achieved an AUC of 0.683. Real external validation on the locked VinDr-Mammo subset (n = 25) remained near-random (AUC of 0.500 [95% CI: 0.304–0.696]), with complete prediction collapse (sensitivity of 1.000, specificity of 0.000). Conclusions: The framework demonstrated feasibility for structured feature selection and stress testing in a small-cohort mammography AI setting; however, external validation revealed near-random discrimination and prediction collapse, indicating limited generalizability. These findings emphasize the need for benchmark comparisons, transparent uncertainty reporting, patient-level validation, and larger multicenter datasets before clinical translation. Full article

(This article belongs to the Special Issue Clinical Advances in Cancer Imaging)

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23 pages, 422 KB

Open AccessArticle

Identity Transformation and the Role of Accountability in Recovery from Problematic Pornography Use: A Phenomenological-Hermeneutical Study

by Luís Lorente-Corral, David Sancho-Cantus, Samuel Asensio, Cristina Cunha-Pérez and Jorge Casaña-Mohedo

J. Clin. Med. 2026, 15(12), 4845; https://doi.org/10.3390/jcm15124845 - 22 Jun 2026

Viewed by 819

Abstract

Background: Problematic pornography use (PPU) has emerged as a clinically significant phenomenon with severe repercussions for mental health and interpersonal relationships. Despite advances in prevalence studies, a gap remains in understanding the subjective processes of recovery and personal transformation. Objective: To [...] Read more.

Background: Problematic pornography use (PPU) has emerged as a clinically significant phenomenon with severe repercussions for mental health and interpersonal relationships. Despite advances in prevalence studies, a gap remains in understanding the subjective processes of recovery and personal transformation. Objective: To describe the lived experience of individuals in recovery from PPU and compulsive sexual behavior and to analyze the perceived factors and dynamics of group support within their process of change. Methods: A qualitative study was conducted following Van Manen’s phenomenological-hermeneutical approach. In-depth semi-structured interviews were held with 27 individuals (26 men, 1 woman) engaged in structured recovery. Data analysis was performed through thematic analysis supported by ATLAS.ti Scientific Software Development GmbH, 2026. Results: A structured trajectory was identified across three phases: personal collapse, group engagement, and transformative mechanisms. Accountability emerged as a salient perceived mechanism of change, fostering sincerity (35.7%) and relapse prevention (19.1%). The “mirror effect” and “rational hope” within the support group facilitate a profound identity shift from a “spoiled identity” to a state of personal authenticity. Conclusions: For individuals engaged in structured support groups, recovery from PPU transcends mere abstinence, requiring a profound identity transformation facilitated by collective connection and honesty. These findings suggest the potential utility of integrating group-based accountability into therapeutic interventions for behavioral addictions tailored to the patient’s experiential profile. Full article

(This article belongs to the Special Issue Current Therapeutic Approaches to Addictive Disorders)

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15 pages, 914 KB

Open AccessArticle

Does Early Surgical Treatment in Degenerative Cervical Myelopathy Have a Favorable Clinical Outcome and Impact on Quality of Life?

by Michele Incerti, Paola M. F. Cristaldi, Andrea Parlangeli, Vittorio Ricciuti, Federica Balletti, Daniele Nicoli, Clarissa Cavadoli and Franco Servadei

J. Clin. Med. 2026, 15(12), 4844; https://doi.org/10.3390/jcm15124844 - 22 Jun 2026

Viewed by 489

Abstract

Background/Objectives: degenerative cervical myelopathy (DCM) is the leading cause of spinal cord impairment in adults, often resulting in disability and reduced quality of life (QoL). Surgery is recommended for moderate and severe cases, while its role in mild DCM remains debated. Emerging evidence [...] Read more.

Background/Objectives: degenerative cervical myelopathy (DCM) is the leading cause of spinal cord impairment in adults, often resulting in disability and reduced quality of life (QoL). Surgery is recommended for moderate and severe cases, while its role in mild DCM remains debated. Emerging evidence suggests that early surgery may improve outcomes, particularly QoL. Methods: We conducted a retrospective, single-center observational study of a cohort of patients undergoing cervical spine surgery for DCM between January 2020 and August 2023 at a single institution (Policlinico di Monza, Italy). Demographic, clinical, radiological and surgical data, as well as complications and outcomes, were analyzed. Neurological status was assessed using the modified Japanese Orthopedic Association (mJOA) score and QoL was evaluated using the Short Form-36 (SF-36) questionnaire preoperatively, at discharge, and at follow-up. Results: 51 patients were included (mean age 58.1 years; 41% female), with anterior surgery performed in 67%. Mild preoperative mJOA score was observed in 74% of patients. At follow-up, 65% achieved complete recovery, 29% improved, and 6% remained stable. No neurological deterioration was recorded. Univariate analysis identified age, anterior cervical discectomy and fusion (ACDF), and mild preoperative mJOA score as significant predictors of recovery. Multivariate logistic regression analysis identified mild preoperative mJOA score as a strong independent predictor of complete clinical recovery (OR = 240.64, 95% CI: 6.82–8496.22, p = 0.002). SF-36 showed significant improvements in emotional well-being, social functioning, pain, and general health, particularly in mild cases. Complications were low (5.8%) and limited to transient dysphagia. Conclusions: early surgical treatment in selected patients with mild DCM may be associated with favorable neurological and quality-of-life outcomes, although larger prospective studies are needed. Full article

(This article belongs to the Special Issue Novel Insights into Clinical Diagnosis and Management of Degenerative Cervical Myelopathy)

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28 pages, 612 KB

Open AccessReview

Shear Wave Elastography in Musculoskeletal Imaging: A Narrative Review

by Enes Gurun, Mesut Ozturk, Mustafa Basaran and Ahmet Emin Okutan

J. Clin. Med. 2026, 15(12), 4843; https://doi.org/10.3390/jcm15124843 - 22 Jun 2026

Cited by 4 | Viewed by 1009

Abstract

Shear wave elastography (SWE) is an increasingly investigated ultrasound-based technique in musculoskeletal imaging that provides quantitative information on tissue stiffness and biomechanical properties. This narrative review aims to summarize the basic principles, technical considerations, current clinical applications, limitations, and future perspectives of SWE [...] Read more.

Shear wave elastography (SWE) is an increasingly investigated ultrasound-based technique in musculoskeletal imaging that provides quantitative information on tissue stiffness and biomechanical properties. This narrative review aims to summarize the basic principles, technical considerations, current clinical applications, limitations, and future perspectives of SWE in musculoskeletal imaging. Unlike conventional grayscale and Doppler ultrasonography, which mainly assess morphology and vascularity, SWE may provide additional functional information in major musculoskeletal tissues, including tendons and ligaments, skeletal muscles, peripheral nerves, fibrocartilaginous structures, plantar fascia, and selected soft tissue lesions. Current evidence suggests potential roles for SWE in detecting early biomechanical alterations, assessing disease severity, differentiating symptomatic from asymptomatic tissues, and monitoring response to treatment or rehabilitation. However, musculoskeletal tissues are anisotropic, viscoelastic, and position-dependent; as a result, SWE measurements are influenced by acquisition-related factors, tissue biomechanics, positioning and loading conditions, region of interest (ROI) placement, tissue depth, and device-related variability. For this reason, SWE findings should not be interpreted as standalone diagnostic criteria but should be considered together with clinical findings, conventional ultrasonography, MRI, electrophysiology, histopathology, and patient-centered outcomes when appropriate. This review highlights the need for tissue-specific measurement protocols, standardized reporting, normative reference data, inter-vendor harmonization, and longitudinal validation against clinically meaningful outcomes before SWE can be more reliably integrated into routine musculoskeletal imaging and rehabilitation practice. Full article

(This article belongs to the Special Issue Imaging in Diagnosis and Treatment of Musculoskeletal Disorders)

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20 pages, 5463 KB

Open AccessArticle

Associations Between Lower Extremity Myotonic Properties, Strength, and Balance in American Football Players: An Exploratory LASSO-Based Study

by Derya Azim, Ömer Özer, Ahmet Kurtoğlu and Safaa M. Elkholi

J. Clin. Med. 2026, 15(12), 4842; https://doi.org/10.3390/jcm15124842 - 22 Jun 2026

Viewed by 430

Abstract

Background/Objectives: Evidence on the role of muscle mechanical (myotonic) properties in athletic performance remains limited in young adult and sub-elite populations, particularly in American football, and sex-specific patterns of association are not well understood. This study aimed to investigate the associations between lower [...] Read more.

Background/Objectives: Evidence on the role of muscle mechanical (myotonic) properties in athletic performance remains limited in young adult and sub-elite populations, particularly in American football, and sex-specific patterns of association are not well understood. This study aimed to investigate the associations between lower extremity myotonic properties and performance outcomes (strength and balance) in American football athletes, with a specific focus on sex-related differences and candidate predictors. Methods: A cross-sectional design was implemented involving 35 American football athletes (17 female, 18 male). Lower extremity muscle tone, stiffness, and elasticity were assessed using MyotonPRO. Strength parameters (lower limb, handgrip, back, and shoulder internal rotation) and balance performance (static and dynamic under eyes-open and eyes-closed conditions) were evaluated using standardized measurement protocols. Pearson correlation analysis was conducted to examine bivariate associations, followed by Least Absolute Shrinkage and Selection Operator (LASSO) regression to determine candidate predictors while addressing multicollinearity. Results: Male athletes exhibited significantly greater height, body mass, and BMI (p < 0.001), alongside elevated myotonic values compared to females. Correlation analyses indicated distinct sex-specific association patterns between myotonic properties and performance metrics. LASSO regression revealed a distinct sex-specific divergence in strength prediction: female strength was predominantly driven by proximal musculature (quadriceps and hamstring elasticity/stiffness), whereas male strength was anchored by distal musculature (gastrocnemius tone/stiffness). Furthermore, rigorous penalization shrunk nearly all balance coefficients to zero in both sexes, indicating that resting myotonic properties do not independently predict dynamic or static postural control. Conclusions: While lower extremity myotonic properties are candidate predictors of multi-regional strength via sex-specific proximal and distal strategies, they do not independently predict balance performance, suggesting postural control relies primarily on active motor recruitment rather than passive resting mechanics. Given the cross-sectional design of this study, causal inferences cannot be drawn, and these findings should be interpreted accordingly. The observed sex-specific differences may support consideration of individualized, sex-informed training strategies in American football athletes. Full article

(This article belongs to the Special Issue New Insights into Physical Therapy)

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33 pages, 518 KB

Open AccessArticle

Sharp-Wave EEG Activity and Cytomegalovirus Exposure in Schizophrenia Spectrum Disorders: A Neuroimmune Perspective

by Mădălina Georgeta Sighencea, Marius Cornițescu and Simona Corina Trifu

J. Clin. Med. 2026, 15(12), 4841; https://doi.org/10.3390/jcm15124841 - 22 Jun 2026

Viewed by 476

Abstract

Background: Immune mechanisms are increasingly implicated in the heterogeneity of schizophrenia spectrum disorders. Cytomegalovirus (CMV), a latent immunomodulatory herpesvirus, is linked to cognitive and immunological alterations, but its electrophysiological correlates remain largely unexplored. This study investigates the relationships among CMV serostatus, EEG [...] Read more.

Background: Immune mechanisms are increasingly implicated in the heterogeneity of schizophrenia spectrum disorders. Cytomegalovirus (CMV), a latent immunomodulatory herpesvirus, is linked to cognitive and immunological alterations, but its electrophysiological correlates remain largely unexplored. This study investigates the relationships among CMV serostatus, EEG features, inflammatory markers, and clinical–cognitive variables. Methods: In this prospective cross-sectional study, 123 patients with schizophrenia spectrum disorders underwent integrated clinical, cognitive, laboratory, and qualitative visual EEG assessments. CMV exposure was determined via IgG serology. Results: Global electroencephalographic EEG organization did not differ by CMV serostatus. However, a descriptive increase in resting-state sharp-wave discharges was observed in CMV-seronegative patients, independent of baseline cortical rhythms. Immunologically, CMV-seropositive individuals exhibited significantly higher total leukocyte counts, consistent with latent viral immune remodeling rather than overt systemic inflammation. Clinically, CMV-seropositive patients demonstrated descriptively higher scores on the disorganization dimension derived from the PANSS (Positive and Negative Syndrome Scale) five-factor consensus model. While these variations did not retain statistical significance after multiple testing correction, separate dimensional analyses revealed that patients exhibiting sharp waves demonstrated better overall cognitive functioning and superior performance within a memory-related item grouping. Notably, the presence of sharp-wave activity was independent of both peripheral inflammatory profiles and treatment-resistant status, underscoring a distinct electrophysiological phenotype. Conclusions: CMV exposure represents a modulating biological background associated with corrected leukocyte elevations and subtle electrophysiological variability, rather than a direct determinant of global clinical severity. The nominal EEG variations and their independent link to better-preserved memory performance highlight non-linear neuroimmune interactions. Given the cross-sectional design, these exploratory patterns warrant a non-causal interpretation but outline a foundation for future longitudinal investigations. Full article

(This article belongs to the Special Issue Clinical Advances and New Perspectives in the Diagnosis and Treatment of Schizophrenia)

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13 pages, 1304 KB

Open AccessArticle

Bias in the Composite Outcomes of Kidney-Cardio Protective Trials in Chronic Kidney Disease: A Meta-Epidemiological Study

by Ioannis Bellos, Smaragdi Marinaki and Vassiliki Benetou

J. Clin. Med. 2026, 15(12), 4840; https://doi.org/10.3390/jcm15124840 - 22 Jun 2026

Viewed by 424

Abstract

Background/Objectives: Composite endpoints are commonly used in chronic kidney disease (CKD) trials to enhance statistical efficiency but may not reflect clinically meaningful outcomes. We assessed agreement between composite endpoints and key components using the bias attributable to composite outcome (BACO) index and [...] Read more.

Background/Objectives: Composite endpoints are commonly used in chronic kidney disease (CKD) trials to enhance statistical efficiency but may not reflect clinically meaningful outcomes. We assessed agreement between composite endpoints and key components using the bias attributable to composite outcome (BACO) index and explored determinants of variability. Methods: We performed a meta-epidemiological analysis of randomized controlled trials evaluating sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and non-steroidal mineralocorticoid receptor antagonists in CKD. BACO was defined as the ratio of the log-hazard ratio for the composite endpoint to that of the reference outcome (kidney failure or cardiovascular death), with variance estimated using the delta method. Determinants were analyzed using inverse-variance weighted mixed-effects meta-regression. Results: Eight trials comprising 38 composite endpoints were included. Higher reference-event rates were associated with higher BACO values overall (β: 0.06, 95% CI: 0.02; 0.10) and in kidney failure-referenced analyses (β: 0.07, 95% CI: 0.02; 0.12). Stronger composite treatment effects correlated with higher BACO (β: −1.07, 95% CI: −1.84; −0.30). The number of components and follow-up duration showed no significant association. In cardiovascular death-referenced models, BACO was associated with trial size (β: 0.12 per 1000 participants), mean age (β: −0.04 per 10 years), and female proportion (β: 0.09 per 10% increase). Conclusions: Agreement between composite endpoints and clinically relevant outcomes is driven by the relative frequency and treatment responsiveness of component events rather than endpoint complexity. Composite endpoints in which clinically important outcomes are infrequent may not reliably reflect treatment effects, underscoring need for clinically aligned endpoint strategies. Full article

(This article belongs to the Special Issue Chronic Kidney Disease Management: Integrating Pharmacotherapy, Biomarkers, and Lifestyle Interventions for Improved Outcomes)

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26 pages, 2512 KB

Open AccessArticle

Diagnostic Performance of AI-Based Cloud Software Regarding the Detection of Endodontic Findings on CBCT: A Single-Centre Cross-Sectional Validation Study

by Maythem Al Fartousi, Arthur Buscot and Christian Ralf Gernhardt

J. Clin. Med. 2026, 15(12), 4839; https://doi.org/10.3390/jcm15124839 - 22 Jun 2026

Viewed by 581

Abstract

Background/Objectives: The aim of the present investigation was to validate the diagnostic performance of the AI-based dental cloud software Diagnocat^® AIS (Version 1.0 (UDI: 860010268018), DGNCT LLC, Miami, FL, USA) regarding the detection possibilities of seven different endodontic findings on cone-beam [...] Read more.

Background/Objectives: The aim of the present investigation was to validate the diagnostic performance of the AI-based dental cloud software Diagnocat^® AIS (Version 1.0 (UDI: 860010268018), DGNCT LLC, Miami, FL, USA) regarding the detection possibilities of seven different endodontic findings on cone-beam computed tomography (CBCT) against a multi-rater consensus reference standard, and to characterize its calibration, threshold-optimized performance and clinical utility. Methods: 358 root-canal-treated teeth from 167 CBCT scans (167 patients) were retrospectively evaluated at a single private dental practice. From initially included 383 root-canal-treated teeth from 177 patients, 358 (93.5%) were recognized by the AI tool and entered the primary analysis. Two experienced dentists with a clinical focus on endodontics independently graded each tooth and disagreements were adjudicated by a senior expert. Seven different endodontic findings were evaluated: (i) apical (periapical) lesion; (ii) short root-canal filling (apical filling end >2 mm short of the radiographic apex); (iii) voids/lacunae in the root-canal filling; (iv) missed (un-instrumented/un-filled) canal; (v) overfilled root-canal filling (apical extrusion); (vi) apicoectomy (resected root apex with or without retrograde filling); and (vii) coronal restoration with a full-coverage crown. Diagnocat^® output was binarized at the manufacturer-fixed 0.50 probability threshold; sensitivity, specificity, predictive values, accuracy, area under the curve AUC (ROC), Cohen κ and Gwet AC1 were computed with 95% cluster-bootstrap confidence intervals (cluster = scan). Threshold optimization, probability calibration, GEE-based subgroup analyses, and decision-curve analysis were pre-specified. Results: Diagnostic performance varied by finding. AUCs were 0.984 for missed canal, 0.917 for overfilled root canal, 0.902 for short root filling, 0.893 for crown, 0.864 for apical lesion, 0.857 for apicoectomy and 0.761 for voids in the root filling. Apical-lesion sensitivity rose from 33.6% for sub-millimeter lesions to ≥80% for lesion measuring 1–5 mm. Re-tuning the decision threshold raised missed-canal sensitivity from 69.6% to 97.5%. Decision-curve analysis confirmed positive benefits for missed canal and root-filling-quality findings. Conclusions: The AI tool Diagnocat^® can be recommended as a focused screening adjunct in CBCT-based endodontic interpretation for missed canals, crowns, and gross root-filling-quality flaws. Sub-millimeter apical lesions and several less common findings (resorption, instrument fragment, retrograde filling) remain outside the reliable performance envelope of the current platform. Full article

(This article belongs to the Special Issue Clinical Research and Application of Artificial Intelligence and Deep Learning in Dentistry and Oral and Maxillofacial Surgery)

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39 pages, 33856 KB

Open AccessReview

Cosmetic Principles and Contemporary Techniques: Achieving Aesthetic Outcomes in DIEP Flap Breast Reconstruction

by Christodoulos Kaoutzanis, Bilal F. Hamzeh, Markos Mardourian, David W. Mathes and Julian Winocour

J. Clin. Med. 2026, 15(12), 4838; https://doi.org/10.3390/jcm15124838 - 22 Jun 2026

Viewed by 772

Abstract

The deep inferior epigastric perforator (DIEP) flap holds its place as the gold standard approach for autologous tissue breast reconstruction given the strong durability, favorable donor site morbidity, and high patient satisfaction overall. With the reliability and safety of microsurgical reconstruction of the [...] Read more.

The deep inferior epigastric perforator (DIEP) flap holds its place as the gold standard approach for autologous tissue breast reconstruction given the strong durability, favorable donor site morbidity, and high patient satisfaction overall. With the reliability and safety of microsurgical reconstruction of the breasts being well-established over these last decades, the goals of DIEP flap reconstruction have expanded beyond flap survival toward optimization of aesthetic, patient-reported, and quality-of-life outcomes. Achieving ideal cosmesis requires thoughtful decision-making across the reconstructive continuum, including of radiation timing, mastectomy incision design, nipple–areolar complex management, reconstructive sequencing, flap shaping and inset, abdominal closure, neurotization, and the potential role of any revision or adjunctive procedures. Modern techniques including delayed-immediate reconstruction, nipple delay, free nipple grafting, fat grafting, and abdominal wall reinforcement have expanded the availability of personalized care in breast reconstruction. This narrative review integrates a targeted literature search with consensus-driven expert opinion informed by our senior authors’ extensive cumulative experience performing DIEP flap breast reconstruction. It discusses principles, technical strategies, and evolving evidence for optimizing aesthetic outcomes in DIEP flap breast reconstruction while preserving safety and minimizing morbidity. Full article

(This article belongs to the Special Issue Evolution of Breast Reconstruction: Current Techniques, Advances and Future Directions)

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19 pages, 285 KB

Open AccessArticle

Diagnostic Performance and Error Patterns of a Large Language Model and Neural Network in Periodontitis Classification: A Comparative Study

by Agata Ossowska, Aida Kusiak, Albert Camlet and Dariusz Świetlik

J. Clin. Med. 2026, 15(12), 4837; https://doi.org/10.3390/jcm15124837 - 22 Jun 2026

Viewed by 450

Abstract

Background/Objectives: Periodontitis is a highly prevalent chronic disease requiring accurate diagnosis for effective treatment planning. Artificial intelligence (AI) has emerged as a potential tool to support clinical decision-making. This study aimed to compare the diagnostic performance and classification error patterns of a [...] Read more.

Background/Objectives: Periodontitis is a highly prevalent chronic disease requiring accurate diagnosis for effective treatment planning. Artificial intelligence (AI) has emerged as a potential tool to support clinical decision-making. This study aimed to compare the diagnostic performance and classification error patterns of a large language model (LLM) and a neural network (NN) in periodontitis classification according to the current staging and grading system. Methods: This retrospective study included 110 patients with periodontal disease. Clinical and demographic variables (age, sex, smoking status, number of teeth, API, BOP, PPD, and CAL) were analyzed. Reference diagnoses were established by two experts. Cases were evaluated using an LLM and a neural network. Model performance was assessed using accuracy, confusion matrices, and Cohen’s kappa coefficient, along with error analysis. Results: The LLM achieved 62% accuracy for stage and 63% for grade classification (κ = 0.48). The neural network showed higher performance, with 85% accuracy for stage and 79% for grade (κ = 0.79 and κ = 0.67, respectively). The LLM more often underestimated disease severity, whereas the neural network tended to overestimate progression. Differences between models were statistically significant (p < 0.0001). Conclusions: In this dataset and classification task, the task-specific neural network demonstrated higher diagnostic performance than the evaluated large language model. However, the findings should be interpreted in light of the fundamentally different training paradigms and intended applications of these AI systems. Further research is required to optimize and validate AI-based approaches for clinical use. Full article

(This article belongs to the Special Issue Clinical Research and Application of Artificial Intelligence and Deep Learning in Dentistry and Oral and Maxillofacial Surgery)

16 pages, 8305 KB

Open AccessArticle

Direct Maxillary Sinus Tissue Analysis for TAS2R38 Polymorphisms: Establishing a Tissue-Based Translational Framework in Odontogenic Rhinosinusitis

by Andra-Lavinia Greța-Oanță, Alexandra Roman, Ioana Berindan-Neagoe, Ștefan Strilciuc, Ștefan Cristian Vesa, Laura Ancuța Pop, Veronica Elena Trombitaș and Silviu Albu

J. Clin. Med. 2026, 15(12), 4836; https://doi.org/10.3390/jcm15124836 - 22 Jun 2026

Viewed by 541

Abstract

Background/Objectives: Bitter taste receptors (T2Rs), specifically T2R38, are present in the respiratory epithelium and react with bacterial quorum-sensing molecules to induce an innate immunity response. Although TAS2R38 polymorphisms have been correlated with susceptibility to chronic rhinosinusitis (CRS), they have not yet been explored [...] Read more.

Background/Objectives: Bitter taste receptors (T2Rs), specifically T2R38, are present in the respiratory epithelium and react with bacterial quorum-sensing molecules to induce an innate immunity response. Although TAS2R38 polymorphisms have been correlated with susceptibility to chronic rhinosinusitis (CRS), they have not yet been explored in odontogenic rhinosinusitis (ORS), a distinct form of CRS with particular microbial and inflammatory features. We aim to establish a proof-of-concept methodology for investigating TAS2R38 genetic variants in ORS using direct maxillary sinus tissue analysis and demonstrate the feasibility of this translational approach. Methods: We conducted a prospective pilot case–control study of 36 ORS patients and 37 controls undergoing septoplasty without sinonasal disease. Maxillary sinus mucosal biopsies were obtained intraoperatively with informed consent. Genomic DNA was extracted using the PureLink Genomic DNA Mini Kit and quantified via NanoDrop spectrophotometry. TAS2R38 haplotypes were determined and classified as taster (PAV/PAV), non-taster (AVI/AVI), or intermediate (PAV/AVI) phenotype. Results: Among fully classifiable canonical TAS2R38 phenotypes (32 ORS patients, 28 controls), distributions were: tasters 12.5% vs. 25.0%, non-tasters 31.3% vs. 25.0%, and intermediate 56.3% vs. 50.0%. AVI/AVI non-taster status was not significantly associated with ORS susceptibility (OR = 1.36, 95% CI: 0.44–4.25; Fisher’s exact p = 0.775). Conclusions: This proof-of-concept study demonstrates that genotyping-grade genomic DNA can be recovered from acutely inflamed maxillary sinus mucosa, validating this substrate for future tissue-based expression, functional, and microbiome analyses not obtainable from peripheral samples; germline genotyping itself does not require sinus tissue. The observed difference in non-taster prevalence (31.3% vs. 25.0%) did not reach statistical significance and is reported descriptively. This directional trend is hypothesis-generating only and, given the limited statistical power, does not constitute evidence for an association. The demonstrated feasibility, together with the established biological rationale, supports an adequately powered confirmatory study and lays the foundation for future investigation of taste receptor genetics in ORS pathogenesis, and potentially personalized therapeutic strategies. Full article

(This article belongs to the Special Issue Clinical Advances in Rhinitis and Sinusitis: Diagnosis, Therapy and Multimorbidity Management)

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30 pages, 2427 KB

Open AccessReview

Multimorbidity in Chronic Overlapping Pain Conditions: From Burden to Integrated Care

by Emmanuel d’Incau, Chelsea Marie Kaplan, Jean-Arthur Micoulaud-Franchi, Christin Veasley and Richard Ohrbach

J. Clin. Med. 2026, 15(12), 4835; https://doi.org/10.3390/jcm15124835 - 22 Jun 2026

Cited by 2 | Viewed by 1115

Abstract

Chronic overlapping pain conditions (COPCs) refer to a set of chronic pain disorders that frequently co-occur and may involve partially overlapping mechanisms. The U.S. National Institutes of Health currently recognizes ten COPCs: fibromyalgia, painful temporomandibular disorders, chronic low back pain, chronic migraine headache, [...] Read more.

Chronic overlapping pain conditions (COPCs) refer to a set of chronic pain disorders that frequently co-occur and may involve partially overlapping mechanisms. The U.S. National Institutes of Health currently recognizes ten COPCs: fibromyalgia, painful temporomandibular disorders, chronic low back pain, chronic migraine headache, chronic tension-type headache, irritable bowel syndrome, endometriosis, interstitial cystitis/bladder pain syndrome, vulvodynia, and myalgic encephalomyelitis/chronic fatigue syndrome. When multiple COPCs coexist, they are associated with a disproportionate multimorbidity burden, including greater pain, poorer psychological well-being, functional limitations, disability, fatigue, sleep disturbances, diminished quality of life, and increased healthcare utilization. Despite their impact, COPCs remain under-recognized, underdiagnosed, and undertreated. Combining structured literature searches and citation tracking with narrative syntheses, this review examines comorbid relationships, the burden of multimorbidity, and potentially overlapping nociplastic mechanisms. By adopting a multimorbidity-based perspective rather than a one-disease, one-treatment approach, it highlights barriers to care—including limited clinical awareness, under-recognition of additional COPCs, limited mechanistic understanding, and fragmented care—and proposes integrated strategies emphasizing prevention, systematic screening, mechanism-informed assessment, and coordinated, patient-centered multimodal management. Full article

(This article belongs to the Section Clinical Neurology)

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17 pages, 615 KB

Open AccessArticle

Prognostic Value of Bronchoalveolar Lavage in Systemic Autoimmune Rheumatic Diseases-Associated Interstitial Lung Disease

by Maximilian Robert Gysan, Kastriot Kastrati, Svitlana Pochepnia, Helmut Prosch, Antje Lehmann, Silvia Lee, Andreas Renner, Christina Bal, Anastasia Papaporfyriou, Christopher Milacek, Lukasz Antoniewicz, Seda Metekol, Markus Kramer, Lisa John, Zahra Kargarpour, Iris Aykara, Peter Weber, Karolina Anderle, Hans Peter Kiener, Michael Bonelli, Daniel Mrak, Daniel Aletaha, Ahmed El-Gazzar, Daniela Gompelmann, Marco Idzko and Helga Lechner-Radner Show full author list Hide full author list

J. Clin. Med. 2026, 15(12), 4834; https://doi.org/10.3390/jcm15124834 - 22 Jun 2026

Viewed by 587

Abstract

Background: Systemic autoimmune rheumatic diseases-associated interstitial lung disease (SARD-ILD) presents with varied disease courses, emphasizing the need for reliable predictors of progression. The prognostic utility of bronchoalveolar lavage (BAL) in SARD-ILD remains underexplored. The objective of this study was to evaluate the role [...] Read more.

Background: Systemic autoimmune rheumatic diseases-associated interstitial lung disease (SARD-ILD) presents with varied disease courses, emphasizing the need for reliable predictors of progression. The prognostic utility of bronchoalveolar lavage (BAL) in SARD-ILD remains underexplored. The objective of this study was to evaluate the role of BAL fluid lymphocyte count in predicting disease progression in patients with SARD-ILD. Methods: This observational study included patients with SARD-ILD undergoing BAL as part of their diagnostic workup. Disease progression was defined as either Forced vital capacity (FVC) decrease >10%, two out of the following three criteria within two years: FVC decrease of 5–10%, worsening symptoms, increased fibrosis on imaging, or any of the following: escalation of treatment, Interstitial lung disease (ILD) exacerbation, lung transplantation, or disease-specific mortality. Logistic regression identified predictors of progression. Time-to-progression was assessed using Kaplan–Meier survival curves. The optimal BAL lymphocyte threshold for predicting progression was identified using the Youden Index and the Wilcoxon method. Results: We identified 89 patients, of whom 30 (33.7%) had progressive disease. Progressors had a significantly higher BAL lymphocyte count compared to non-progressors (31.6 ± 24.8% vs. 14.3 ± 16.5%, p < 0.001). BAL lymphocyte proportion was significantly and independently associated with disease progression (odds ratio, 1.05; 95% confidence interval 1.02–1.07; p < 0.01). A lymphocyte count above 9 percent was associated with a markedly increased risk of disease progression (odds ratio, 13.14; 95% confidence interval, 4.20–51.98; p < 0.01). Conclusions: BAL lymphocyte count was associated with a higher likelihood of progression in SARD-ILD. BAL assessment may help identify patients at increased risk of disease progression. However, these findings should be considered exploratory and require validation in larger prospective studies and across individual SARD-ILD subtypes. Full article

(This article belongs to the Section Respiratory Medicine)

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17 pages, 8255 KB

Open AccessArticle

Global Postural Re-Education Versus Deep Neck Flexor Activation on Chronic Nonspecific Neck Pain with Forward Head Posture

by Huda B. Abd Elhamed, Esraa Ahmed Mohamed Ahmed, Enas Fawzy Youssif, Amr M. Yehia, Mohamed A. Abdel Ghafar, Safaa M. Elkholi and Shahesta Ahmed Osama

J. Clin. Med. 2026, 15(12), 4833; https://doi.org/10.3390/jcm15124833 - 22 Jun 2026

Viewed by 718

Abstract

Background and Objectives: Chronic nonspecific neck pain (NSNP) is among the most common musculoskeletal disorders. Global postural re-education (GPR) might be effective in decreasing neck pain (NP) and dysfunction and improving forward head posture (FHP) by recovering muscle chains and reducing postural [...] Read more.

Background and Objectives: Chronic nonspecific neck pain (NSNP) is among the most common musculoskeletal disorders. Global postural re-education (GPR) might be effective in decreasing neck pain (NP) and dysfunction and improving forward head posture (FHP) by recovering muscle chains and reducing postural alteration. Deep neck flexor activation (DNF) might also decrease NP and improve FHP by improving DNF endurance. This study aimed to compare the effects of GPR versus DNF activation on pain, dysfunction, FHP, and DNF endurance. Materials and Methods: Forty-six physiotherapy students with chronic NSNP participated in this non-randomized comparative study and were allocated into two equal groups based on their availability and preference regarding session duration. Group A underwent GPR exercises combined with active neck exercises, whereas group B received DNF activation in addition to active neck exercises. All participants were assessed pre- and post-intervention for pain intensity using a visual analog scale (VAS), neck disability using the Arabic version of the neck disability index (NDI), FHP via a photometric method with Kinovea software, and DNF endurance using pressure biofeedback. Results: A significant effect of both treatments was reported on reducing pain intensity, improving the FHP and enhancing the neck functional status with no substantial differences between both groups. A significant improvement in DNF endurance was observed in both groups, with substantially higher values between groups in favor of the DNF group. Conclusions: Both GPR and DNF activation exercises were associated with reductions in pain and improvements in neck disability among physiotherapy students with chronic NSNP and FHP. Also, both CVA and DNF endurance improved, with more improvement observed in DNF endurance in the DNF group compared with the GPR group. Full article

(This article belongs to the Special Issue Physical Therapy in Musculoskeletal Disorders: Prevention, Diagnosis, Clinical Management and Treatment—2nd Edition)

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12 pages, 235 KB

Open AccessArticle

Predictors of Heart Rate Depression During Carotid Artery Stenting in Presumed Low-Risk Patients: A Retrospective Single-Center Observational Study

by Itamar Gothelf, Farouq Alguayn, Galia Karp, Krestina Shihada, Yair Zlotnik, Yana Mechnik Steen and Anat Horev

J. Clin. Med. 2026, 15(12), 4832; https://doi.org/10.3390/jcm15124832 - 22 Jun 2026

Viewed by 480

Abstract

Background: Hemodynamic depression, characterized by bradycardia and hypotension, is a common complication of carotid artery stenting (CAS) and is primarily attributed to carotid sinus baroreceptor stimulation. While prophylactic atropine is often used in high-risk patients, predictors of unexpected hemodynamic depression among patients initially [...] Read more.

Background: Hemodynamic depression, characterized by bradycardia and hypotension, is a common complication of carotid artery stenting (CAS) and is primarily attributed to carotid sinus baroreceptor stimulation. While prophylactic atropine is often used in high-risk patients, predictors of unexpected hemodynamic depression among patients initially deemed low-risk remain incompletely defined. Objective: To identify clinical, anatomical, and procedural predictors of hemodynamic depression in patients undergoing CAS without prophylactic atropine. Methods: We performed a retrospective, single-center observational study of consecutive patients undergoing CAS between January 2015 and May 2024. Patients who received prophylactic atropine for low baseline heart rate (HR) were excluded. Hemodynamic depression was defined as a >20% reduction in HR from baseline. Absolute bradycardia (HR <50 bpm) and hypotension (>40% reduction in systolic blood pressure) were recorded descriptively. Results: A total of 158 patients underwent CAS, of whom 33 (20.9%) were excluded due to prophylactic atropine administration for low pre-procedural heart rates (<60 bpm). Among 125 included patients, 62 (49.6%) experienced significant HR reduction during CAS. In multivariable analysis, a shorter distance between the stenotic lesion and the carotid bifurcation was independently associated with hemodynamic depression (OR 0.90 per mm increase; 95% CI 0.82–0.99; p = 0.023). Greater intraprocedural reductions in systolic and mean arterial pressure were also associated with HR depression. Traditional clinical risk factors, including age, sex, comorbidities, degree of stenosis, calcification severity, anesthesia type, and procedure urgency, were not independently predictive. Conclusions: Hemodynamic depression remains frequent during CAS even among patients classified as low risk. Lesion proximity to the carotid bifurcation is a key anatomical predictor of autonomic instability, highlighting the limitations of standard risk stratification and supporting a lesion-specific approach to periprocedural hemodynamic management. Full article

(This article belongs to the Special Issue Carotid Artery Disease (CAD) and Its Complications: A Comprehensive Update)

13 pages, 555 KB

Open AccessArticle

Clinical Impact of Semaglutide in Patients with Heart Failure and Preserved Ejection Fraction

by Yuki Hida, Teruhiko Imamura and Koichiro Kinugawa

J. Clin. Med. 2026, 15(12), 4831; https://doi.org/10.3390/jcm15124831 - 22 Jun 2026

Viewed by 517

Abstract

Background: The clinical impact of oral semaglutide on cardiac biomarkers in real-world patients with heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus (T2DM) remains unclear. We evaluated whether initiation of oral semaglutide was associated with a reduction in [...] Read more.

Background: The clinical impact of oral semaglutide on cardiac biomarkers in real-world patients with heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus (T2DM) remains unclear. We evaluated whether initiation of oral semaglutide was associated with a reduction in B-type natriuretic peptide (BNP) levels and explored factors associated with this response. Methods: We retrospectively enrolled 27 patients with HFpEF who initiated oral semaglutide for T2DM management at a single academic center. Clinical data were collected at three time points: three months before treatment initiation (pre-treatment period), at initiation (baseline), and three months after semaglutide initiation (on-treatment period). The primary outcome was the change in the common logarithm of BNP levels (log BNP) during the on-treatment versus pre-treatment period. Results: Median age was 67 (59, 78) years and 21 (77.8%) were men. Log BNP remained stable during the pre-treatment period (p = 0.34) but decreased significantly during the on-treatment period (p < 0.001). The reduction in log BNP during the on-treatment period was significantly greater than during the pre-treatment period (mean difference −0.35, 95% confidence interval −0.44 to −0.11, p < 0.001). Concomitant reductions were observed in HbA1c, body weight, C-reactive protein, left atrial volume index, and left ventricular mass index. Changes in C-reactive protein levels were significantly correlated with those in log BNP (r = 0.46, p = 0.015). Conclusions: In patients with HFpEF and T2DM, three-month oral semaglutide therapy was associated with reductions in BNP, as well as improvements in glycemic control, systemic inflammation, left atrial volume index, and left ventricular mass index. Full article

(This article belongs to the Section Cardiology)

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31 pages, 2460 KB

Open AccessReview

Beyond DSM Categories: Criteria for Biologically Valid Disease Axes in Psychiatry

by Lukasz Szarpak, Bernard Rybczynski, Michal Pruc, Bartosz W. Maj, Maciej Maslyk, Iwona Niewiadomska and Wieslaw J. Cubala

J. Clin. Med. 2026, 15(12), 4830; https://doi.org/10.3390/jcm15124830 - 22 Jun 2026

Viewed by 634

Abstract

Dimensional and transdiagnostic models have become central to contemporary efforts to move psychiatric nosology beyond DSM/ICD categories. This shift reflects persistent limitations of categorical syndromes as final biological targets, including within-diagnosis heterogeneity, cross-diagnostic comorbidity, developmental instability, and incomplete alignment with underlying mechanisms. This [...] Read more.

Dimensional and transdiagnostic models have become central to contemporary efforts to move psychiatric nosology beyond DSM/ICD categories. This shift reflects persistent limitations of categorical syndromes as final biological targets, including within-diagnosis heterogeneity, cross-diagnostic comorbidity, developmental instability, and incomplete alignment with underlying mechanisms. This article examines a central unresolved problem in this transition: when, if ever, a descriptive or predictive psychiatric dimension can be interpreted as a candidate disease axis. We conducted a conceptual synthesis of major dimensional and transdiagnostic frameworks, including Research Domain Criteria (RDoC), Hierarchical Taxonomy of Psychopathology (HiTOP), the general psychopathology factor, cross-disorder genomic models, clinical staging approaches, and data-driven subtyping. The analysis separates three levels of inference that are often conflated in psychiatric research: descriptive structure, predictive utility, and disease-level biological validity. The synthesis identifies a recurrent inferential error in which reproducible factors, clusters, or classifiers are prematurely treated as evidence of disease architecture. Such constructs may describe real covariance patterns or improve prognostic prediction without establishing biological validity. We propose an eight-domain hierarchical framework for promotion to candidate disease-axis status, organized into four core gatekeepers—replication across cohorts, ascertainment, and methods, developmental coherence, incremental prognostic value beyond diagnosis and nonspecific severity, and discriminability from nonspecific severity—and four supporting/disciplining domains: cross-level convergence, mechanistic constraint, clinical leverage, and explicit falsifiability/boundary conditions. On this basis, middle-level transdiagnostic spectra and selected cross-disorder genomic liabilities appear more defensible as candidate disease axes than highly global or weakly specified constructs. Psychiatry was justified in turning toward dimensional models, but dimensionality alone does not confer biological validity. The key task is not to choose between categories and dimensions, but to define the evidential thresholds under which dimensional constructs warrant ontological promotion. Full article

(This article belongs to the Special Issue Clinical Advances in Personalized Psychiatry)

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19 pages, 2136 KB

Open AccessArticle

Beyond Ocular Toxicity: Cerebrovascular Events After Intra-Arterial Chemotherapy for Retinoblastoma

by Yacoub A. Yousef, Alaa Tarazi, Mona Mohammad, Hadeel Halalsheh, Qusai F. Abu Salim, Dima Abu Laban, Reem AlJabari, Mustafa Mehyar, Hazem Haboob and Ibrahim AlNawaiseh

J. Clin. Med. 2026, 15(12), 4829; https://doi.org/10.3390/jcm15124829 - 22 Jun 2026

Viewed by 482

Abstract

Background: Cerebrovascular accidents (CVAs) are among the most serious complications of intra-arterial chemotherapy (IAC) for retinoblastoma (RB). This study evaluated the incidence and potential risk factors of this rare event. Methods: A retrospective cohort study included RB patients who received IAC [...] Read more.

Background: Cerebrovascular accidents (CVAs) are among the most serious complications of intra-arterial chemotherapy (IAC) for retinoblastoma (RB). This study evaluated the incidence and potential risk factors of this rare event. Methods: A retrospective cohort study included RB patients who received IAC at a tertiary cancer center. Diagnosis of CVAs was based on clinical and/or neuroimaging findings. Data included demographics, tumor features, complications, and outcomes. Meta-analysis was not feasible due to heterogeneity. A systematic review following PRISMA guidelines was conducted across major databases up to December 2025, including studies reporting CVA after IAC. Results: The cohort included 33 children who underwent 104 IAC procedures (Melphalan). CVA occurred in three patients (3/33 (9%) of patients, and 3/104 (2.9%) of procedures). Two were confirmed by neuroimaging, while one was a transient ischemic attack. Two patients (67%) were girls, and 2 of 3 (67%) were younger than 1 year. All events occurred during the IAC procedure and were ipsilateral to the treated eye. Two patients had no residual neurological deficits, while one showed improvement with only a minor residual deficit. The systematic review included 14 studies with 932 patients and identified 11 CVA events (1.2%; Range 0–9.1% per patient and 0–2.2% per IAC procedure). All were ischemic with variable presentations. Younger age, repeated catheterization, vasospasm, and embolic events were common risk factors. Outcomes were generally favorable. Conclusions: CVA after IAC, though rare, may be underreported. Events are likely procedure-related and influenced by age, treatment intensity, and vascular toxicity. Careful technique, close monitoring, and standardized reporting are needed to recognize/reduce the real risk. Full article

(This article belongs to the Special Issue Pediatric Ophthalmology: Current Progress and Future Options)

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15 pages, 1999 KB

Open AccessSystematic Review

Efficacy of Vitamin D Supplementation to Alleviate Premenstrual Syndrome Symptoms: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

by Amani Zainab, Reem Samir Tageldin, Rumaysah Patel, Mohamed Abdulrahim Hassan, Lama Atef Aburas, Marya Alkahily, Layan Shamsan, Salma Salman Al-Olaimat, Ashaz Sayeed and Ahmed Abu-Zaid

J. Clin. Med. 2026, 15(12), 4828; https://doi.org/10.3390/jcm15124828 - 22 Jun 2026

Viewed by 789

Abstract

Aim: Premenstrual Syndrome (PMS) substantially impairs quality of life, while standard pharmacologic treatments are often limited by adverse effects or contraindications. This systematic review and meta-analysis evaluated the efficacy of vitamin D supplementation compared to passive control (placebo or standard care) for [...] Read more.

Aim: Premenstrual Syndrome (PMS) substantially impairs quality of life, while standard pharmacologic treatments are often limited by adverse effects or contraindications. This systematic review and meta-analysis evaluated the efficacy of vitamin D supplementation compared to passive control (placebo or standard care) for PMS symptom relief. Methods: PubMed, Web of Science, Scopus, Google Scholar, and CENTRAL were searched for randomized controlled trials (RCTs) up to January 2026. The primary outcome was change in total PMS severity scores. Secondary outcomes included depression, anxiety, physical symptoms, craving, and water retention. Standardized mean differences (SMDs) with 95% confidence intervals (CI) were pooled using a random-effects model. Heterogeneity was assessed using the I² statistic. Results: Five RCTs including 436 participants were reviewed. The overall risk of bias was rated as “some concerns” in four RCTs and “low risk” in one trial. Vitamin D significantly reduced total PMS severity (SMD: −0.78, 95% CI: −1.30, −0.26, I² = 58.22%) as well as physical symptoms (SMD: −1.00, 95% CI: −1.99, −0.01, I² = 90.53%) and depression (SMD: −0.78, 95% CI: −1.53, −0.02, I² = 84.56%). No significant effects were observed for anxiety, craving, or water retention. Vitamin D was well tolerated with no reported adverse events. Conclusions: Vitamin D supplementation may reduce overall PMS severity, particularly physical and depressive symptoms. However, results show substantial heterogeneity across outcomes, and the certainty of evidence remains “very low”, underscoring the need for further high-quality, well-powered RCTs. Full article

(This article belongs to the Section Obstetrics & Gynecology)

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10 pages, 10616 KB

Open AccessComment

Comment on Maga et al. The Effect of Selective Occlusal Adjustment on the Disclusion Time Reduction and Symmetry of Occlusal Contacts of the Own Dentition Using Digital Occlusion Analysis in Patients with Temporomandibular Disorders. J. Clin. Med. 2025, 14, 7007

by Robert B. Kerstein

J. Clin. Med. 2026, 15(12), 4827; https://doi.org/10.3390/jcm15124827 - 22 Jun 2026

Viewed by 1163

Abstract

The authors of The Effect of Selective Occlusal Adjustment on the Disclusion Time Reduction and Symmetry of Occlusal Contacts of the Own Dentition Using Digital Occlusion Analysis in Patients with Temporomandibular Disorders, J [...] Full article

(This article belongs to the Special Issue Multidisciplinary Approach to the Diagnosis and Treatment of Temporomandibular Disorders: Patient Care Challenges—2nd Edition)

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11 pages, 498 KB

Open AccessArticle

Outcomes of Salvage Trabeculectomy in Japanese Patients with Open-Angle Glaucoma and Persistent Intraocular Pressure Elevation Following Trabectome or Microhook Ab Interno Trabeculotomy

by Toshiki Oka, Mari Sakamoto, Sotaro Mori, Kaori Ueda, Yuko Yamada-Nakanishi and Makoto Nakamura

J. Clin. Med. 2026, 15(12), 4826; https://doi.org/10.3390/jcm15124826 - 21 Jun 2026

Viewed by 418

Abstract

Background/Objectives: The objective was to describe the one-year outcomes of salvage trabeculectomy (TLE) in eyes with persistent elevation of intraocular pressure (IOP) requiring early surgical intervention after failed minimally invasive glaucoma surgery (MIGS). Methods: This retrospective observational study included 38 eyes of [...] Read more.

Background/Objectives: The objective was to describe the one-year outcomes of salvage trabeculectomy (TLE) in eyes with persistent elevation of intraocular pressure (IOP) requiring early surgical intervention after failed minimally invasive glaucoma surgery (MIGS). Methods: This retrospective observational study included 38 eyes of 38 consecutive Japanese patients who underwent TLE within 100 days after Trabectome (TOM) or microhook ab interno trabeculotomy (μTLO) because of uncontrolled IOP despite maximally tolerated medical therapy. Surgical success was defined as (1) IOP reduction ≥30% from baseline, (2) 5 < IOP < 18 mmHg, (3) no additional glaucoma surgery, and (4) no loss of light perception. The Kaplan–Meier method was used to estimate the one-year success rate. Changes in IOP, medication use, best-corrected visual acuity (BCVA), and mean deviation (MD) were analyzed using the Wilcoxon matched-pairs signed-rank test and a linear mixed-effects model. Results: The median interval between MIGS and TLE was 41.5 days (interquartile range, 28–70 days). The one-year surgical success rate was 86.8% (Kaplan–Meier estimate). IOP and medication use were significantly reduced after TLE (p < 0.0001) and remained stable throughout the 12-month follow-up. BCVA did not differ significantly between baseline and 12 months after TLE, whereas a small but statistically significant difference in MD was observed. No serious vision-threatening complications were encountered. Conclusions: TLE performed shortly after failed MIGS achieved substantial IOP reduction with acceptable safety over a one-year follow-up period. TLE may be considered as one of the surgical options in cases where sufficient IOP reduction cannot be achieved after failed MIGS, and no effective alternative treatments are available. Full article

(This article belongs to the Section Ophthalmology)

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13 pages, 1670 KB

Open AccessArticle

Metabolic Improvements Following Upper Airway Surgery in Obstructive Sleep Apnea: Association of Airway Improvement with Insulin Resistance

by Chia-Chen Lin, Wan-Ni Lin, Li-Jen Hsin, Ming-Shao Tsai, Li-Ang Lee and Hsueh-Yu Li

J. Clin. Med. 2026, 15(12), 4825; https://doi.org/10.3390/jcm15124825 - 21 Jun 2026

Viewed by 502

Abstract

Background: Obstructive sleep apnea (OSA) is increasingly recognized as a systemic disorder associated with insulin resistance and elevated risk of type 2 diabetes. While continuous positive airway pressure (CPAP) is the standard therapy, its long-term metabolic benefits remain inconsistent. The metabolic impact of [...] Read more.

Background: Obstructive sleep apnea (OSA) is increasingly recognized as a systemic disorder associated with insulin resistance and elevated risk of type 2 diabetes. While continuous positive airway pressure (CPAP) is the standard therapy, its long-term metabolic benefits remain inconsistent. The metabolic impact of upper airway surgery is less well defined. Methods: In this retrospective study, 49 patients with polysomnography-confirmed OSA who underwent upper airway surgery were evaluated. Respiratory and metabolic parameters—including apnea–hypopnea index (AHI), fasting plasma glucose, fasting insulin, glycated hemoglobin (HbA1c), and homeostatic model assessment for insulin resistance (HOMA-IR)—were assessed preoperatively and at 6 months postoperatively. Associations between changes in AHI (ΔAHI) and insulin resistance (ΔHOMA-IR) were analyzed using correlation and receiver operating characteristic (ROC) analyses. Results: Significant improvements were observed in both respiratory and metabolic parameters. AHI decreased from 46.6 ± 25.8 to 20.7 ± 14.1 events/h (p < 0.001). Fasting plasma glucose, insulin levels, and HOMA-IR were significantly reduced postoperatively (all p < 0.05), while HbA1c showed a downward trend. Reduction in AHI was moderately correlated with improvement in insulin resistance (r = 0.527, p < 0.001). ROC analysis demonstrated modest discriminative ability of ΔAHI for identifying normalization of insulin resistance (AUC = 0.62). Conclusions: Upper airway surgery was associated with significant improvements in insulin resistance and glycemic parameters in patients with OSA. The correlation between airway improvement and metabolic change supports a physiological link between upper airway obstruction and insulin sensitivity. These findings suggest that upper airway surgery may represent a clinically relevant adjunct within multimodal strategies for metabolic risk reduction, particularly in patients unable to tolerate CPAP therapy. Full article

(This article belongs to the Section Otolaryngology)

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12 pages, 260 KB

Open AccessArticle

Association Between Pain Self-Efficacy and Adherence to Hemodialysis Regimen

by Ioanna Mitsia, Vasiliki Matziou, Maria Polikandrioti, Sofia Zyga and Victoria Alikari

J. Clin. Med. 2026, 15(12), 4824; https://doi.org/10.3390/jcm15124824 - 21 Jun 2026

Viewed by 442

Abstract

Background/Objectives: Pain is a common symptom in patients undergoing hemodialysis (HD) and may influence their quality of life. Pain self-efficacy may play an important role in self-management and adherence behaviors. This study aimed to examine the association between pain self-efficacy and adherence [...] Read more.

Background/Objectives: Pain is a common symptom in patients undergoing hemodialysis (HD) and may influence their quality of life. Pain self-efficacy may play an important role in self-management and adherence behaviors. This study aimed to examine the association between pain self-efficacy and adherence to the HD regimen in patients undergoing HD. Methods: In this descriptive and cross-sectional study, 199 patients undergoing HD from a single private hospital (convenience sample) in Athens, Greece, completed the Greek-Simplified Adherence Questionnaire-HD (GR-SMAQ-HD) to assess adherence and the Pain Self-efficacy Questionnaire (PSEQ) to assess pain self-efficacy. Sociodemographic and clinical data were also recorded. Bivariate analyses and multiple linear regression were performed to identify factors associated with adherence. Statistical significance was set at p < 0.05. Results: Patients demonstrated moderate levels of pain self-efficacy (mean PSEQ = 33.96 ± 9.74) and moderate adherence to the HD regimen (mean GR-SMAQ-HD = 4.78 ± 2.54). No significant correlation was found between pain self-efficacy and adherence in bivariate analysis (rho = 0.125, p = 0.221). However, in multivariate analysis, pain self-efficacy was a significant independent predictor of adherence (β = 0.056, p = 0.032). Longer duration of End-Stage Renal Disease (ESRD) (β = −0.158, p < 0.001), higher pill burden (rho = −0.237, p = 0.030) were associated with lower adherence. Marital status was also a significant predictor of adherence (β = 1.631, p = 0.016). The model explained 24% of the variance in adherence (Adjusted R² = 0.24). Conclusions: Pain self-efficacy may indirectly affect adherence to the HD regimen, although its direct effect is modest. Adherence appears to be negatively influenced by pill burden and ESRD duration, while social support may play an important role. Full article

(This article belongs to the Special Issue A Holistic Approach to Management of Complications in Hemodialysis)

18 pages, 4571 KB

Open AccessSystematic Review

Comparative Efficacy and Safety of 0.05% Cyclosporine A and 3% Diquafosol Sodium in Dry Eye Disease: A Systematic Review and Meta-Analysis with Trial Sequential Analysis

by Abdullah Y. Alsuhail, Abdullah M Alkandari, Ahmed Mohammad, Sara Almutawtah, Yaqoub AlFoudari, Fatmah S. Semairan, Fahad Mohammad, Abdullah AlOtaibi, Omar Almutairi, Rashed A. Alasoosi, Shahad T. Ahmad and Abdullah M. Alharran

J. Clin. Med. 2026, 15(12), 4823; https://doi.org/10.3390/jcm15124823 - 21 Jun 2026

Viewed by 725

Abstract

Background: Dry Eye Disease (DED) is a multifactorial ocular surface disorder characterized by tear film instability and inflammation. Cyclosporine A, an immunomodulator, and Diquafosol sodium, a mucin secretagogue, represent two distinct therapeutic pathways. However, current evidence directly comparing their clinical efficacy is inconsistent. [...] Read more.

Background: Dry Eye Disease (DED) is a multifactorial ocular surface disorder characterized by tear film instability and inflammation. Cyclosporine A, an immunomodulator, and Diquafosol sodium, a mucin secretagogue, represent two distinct therapeutic pathways. However, current evidence directly comparing their clinical efficacy is inconsistent. This meta-analysis aimed to compare treatment outcomes and efficacy between 0.05% Cyclosporine A and 3% Diquafosol sodium in patients with moderate-to-severe DED. Methods: In January 2026, we conducted a systematic search of PubMed, Scopus, Web of Science, and the Cochrane Library for randomized controlled trials directly comparing 0.05% Cyclosporine A to 3% Diquafosol sodium in adult patients with moderate-to-severe DED. For the meta-analysis, we used R 4.5.0 with R Studio 2024.12.1+563. Results: We included six RCTs with a total of 859 patients. No significant differences were found between Cyclosporine A and Diquafosol sodium in Tear Break-Up Time (TBUT) at 4, 8, or 12 weeks. Cyclosporine A showed a suggestive greater improvement in Schirmer test scores at 4 weeks (SMD = 0.35, 95% CI 0.07 to 0.63). A modest benefit in symptom scores favoring Diquafosol sodium was observed at 12 weeks (SMD = 0.23, 95% CI 0.06 to 0.41). Subgroup analysis suggested this symptomatic benefit may be more pronounced in patients with severe disease, although subgroup interaction tests were not statistically significant. There were no significant differences in corneal or conjunctival staining at any time point. The risk of adverse events did not differ significantly between treatments. Conclusions: Early improvement in tear production showed a potential benefit for Cyclosporine A, while longer-term symptomatic relief showed a potential benefit for Diquafosol sodium, with suggestive evidence in severe disease. However, these findings should be interpreted cautiously, given the methodological limitations and inconclusive TSA evidence for several outcomes. Future large-scale, standardized trials with extended follow-up are warranted to confirm these findings. Full article

(This article belongs to the Section Ophthalmology)

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13 pages, 1118 KB

Open AccessArticle

Remaining Root Filling Material in Oval Canals After Retreatment Using MicroMega Remover and Reciproc Blue Systems with and Without Passive Ultrasonic Irrigation: A Micro-CT Study

by Furkan Konus and Faruk Oztekin

J. Clin. Med. 2026, 15(12), 4822; https://doi.org/10.3390/jcm15124822 - 21 Jun 2026

Viewed by 451

Abstract

Background/Objectives: The aim of this study was to compare the effectiveness of the Reciproc Blue (RB) and MicroMega Remover (MR) systems in removing root canal filling material and to evaluate the effect of passive ultrasonic irrigation (PUI) on remaining filling material (RFM) [...] Read more.

Background/Objectives: The aim of this study was to compare the effectiveness of the Reciproc Blue (RB) and MicroMega Remover (MR) systems in removing root canal filling material and to evaluate the effect of passive ultrasonic irrigation (PUI) on remaining filling material (RFM) using micro-computed tomography (micro-CT)-based three-dimensional (3D) analysis. Methods: Forty single-rooted mandibular premolar teeth were included in the study. The root canals were prepared up to size F2 using the ProTaper Gold rotary file system and obturated with the lateral compaction technique. After the initial micro-CT scan, the teeth were randomly divided into four groups: Group RB, Group MR, Group RB + PUI, and Group MR + PUI (n = 10). Following retreatment, a second micro-CT scan was performed. The percentage of RFM was calculated, and statistical analyses were performed using Kruskal–Wallis and Mann–Whitney U tests with Bonferroni correction. A rank-based factorial analysis was additionally performed (p < 0.05). Results: RFM was observed in all groups. No significant difference was found between the RB (7.37%) and MR (7.31%) systems (p > 0.05). However, the groups treated with PUI (RB + PUI and MR + PUI) showed significantly lower RFM values than the groups without PUI (p = 0.001). Factorial analysis revealed no significant effect of file system or file system × PUI interaction, whereas PUI significantly reduced RFM (p < 0.001). Conclusions: The RB and MR systems demonstrated similar effectiveness in removing root canal filling material. Although complete canal cleanliness could not be achieved, under the in vitro conditions of the present study, PUI significantly reduced the amount of micro-CT-measured RFM. Full article

(This article belongs to the Special Issue New Clinical Advancements in Endodontics)

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19 pages, 720 KB

Open AccessArticle

The Association of G Protein-Coupled Estrogen Receptor (GPER) Polymorphisms with Ionizing Radiation Exposure in Healthcare Workers

by Ünal Öztürk, Ergül Belge Kurutaş, Nuray Üremiş, Muhammed Mehdi Üremiş and Fatma Nur Özkömeç

J. Clin. Med. 2026, 15(12), 4821; https://doi.org/10.3390/jcm15124821 - 21 Jun 2026

Viewed by 478

Abstract

Background/Objectives: The G protein-coupled estrogen receptor (GPER) is known to interact with cellular stress responses and DNA damage pathways. Therefore, exposure to ionizing radiation may modulate the biological consequences of single-nucleotide polymorphisms in the GPR30 gene. This study aims to evaluate the association [...] Read more.

Background/Objectives: The G protein-coupled estrogen receptor (GPER) is known to interact with cellular stress responses and DNA damage pathways. Therefore, exposure to ionizing radiation may modulate the biological consequences of single-nucleotide polymorphisms in the GPR30 gene. This study aims to evaluate the association between GPER polymorphisms and radiation sensitivity. Methods: The study included 50 healthcare workers exposed to ionizing radiation and 36 healthy individuals with no known occupational exposure to radiation. Genomic DNA was isolated and PCR products were purified using GeneAll kits. Genomic regions encompassing three GPER single-nucleotide polymorphisms (rs3808350, rs3808351, and rs11544331) were amplified by polymerase chain reaction (PCR), followed by DNA sequencing analysis using the BigDye Cycle Sequencing Kit. In addition, an in silico functional and clinical annotation of rs11544331 was performed using Ensembl VEP, SIFT, PolyPhen-2, AlphaMissense, CADD, UniProt, and ClinVar. Results: Genotypic, dominant, and allelic analyses revealed no significant association between radiation exposure and the rs3808350 or rs3808351 polymorphisms. In contrast, a statistically significant association was observed for rs11544331. The frequency of individuals carrying the CT and TT genotypes (CT + TT) was significantly higher in the ionizing radiation-exposed group compared with the control group (OR = 2.981; 95% CI: 1.106–7.904; p = 0.0241). In allelic analysis, the T allele was more prevalent in the exposed group and was significantly associated with radiation exposure (OR = 2.959; 95% CI: 1.282–6.606; p = 0.0110). In silico analysis confirmed that rs11544331 corresponds to the p.Pro16Leu substitution in GPER1; however, SIFT, PolyPhen-2, AlphaMissense, CADD, and ClinVar consistently indicated a tolerated, benign, likely benign, or low-deleteriousness profile. Conclusions: GPER-mediated stress responses and genetic polymorphisms may play a potential role in determining genetic susceptibility following exposure to ionizing radiation. Full article

(This article belongs to the Section Clinical Guidelines)

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11 pages, 237 KB

Open AccessArticle

Reduced Indocyanine Green Clearance Is Associated with Enteral Feeding Intolerance in Septic Patients Without Overt Liver Injury

by Yingying Hao, Ming Yan, Rujing Bai, Chenyu Li, Chen Qu, Zhuxi Yu, Wenkui Yu, Ning Liu, Tao Gao and Ying Xu

J. Clin. Med. 2026, 15(12), 4820; https://doi.org/10.3390/jcm15124820 - 21 Jun 2026

Viewed by 353

Abstract

Background/Objectives: The gut–liver axis is central to sepsis, but assessing mesenteric perfusion remains challenging. Indocyanine green (ICG) clearance reflects hepatic blood flow. Since portal flow is derived from mesenteric circulation and supplies most of the liver, reduced ICG clearance may indicate mesenteric [...] Read more.

Background/Objectives: The gut–liver axis is central to sepsis, but assessing mesenteric perfusion remains challenging. Indocyanine green (ICG) clearance reflects hepatic blood flow. Since portal flow is derived from mesenteric circulation and supplies most of the liver, reduced ICG clearance may indicate mesenteric hypoperfusion, which can lead to enteral feeding intolerance (EFI). This study examines whether reduced ICG clearance in septic patients without overt liver injury is associated with EFI. Methods: This study is a secondary analysis of a prospective cohort study (March–May 2024, 20-bed ICU). Septic patients without sepsis-related liver injury or recent abdominal surgery were included. ICG plasma disappearance rate (ICG-PDR) was measured at admission; patients were grouped by ICG-PDR (≤18%/min vs. >18%/min). The primary outcome was EFI within 7 days. Multivariate logistic regression and correlation analyses were performed. Results: Among 77 patients (44 with ICG-PDR > 18%/min, 33 with ≤18%/min), the decreased ICG-PDR group had higher SOFA scores (8.4 ± 4.2 vs. 5.4 ± 3.5, p = 0.001) and higher EFI rates (66.7% vs. 43.1%, p = 0.041). Univariate analysis showed ICG-PDR ≤ 18%/min associated with EFI (OR = 2.632, p = 0.043), but this was attenuated after SOFA adjustment (OR = 2.247, p = 0.171). Reduced ICG-PDR correlated with central venous pressure (CVP) (r = 0.626, p < 0.001) but not with mean arterial pressure (r = −0.175, p = 0.129). Conclusions: In septic patients with preserved hepatocyte function, reduced ICG clearance is associated with EFI, but this relationship is largely explained by disease severity (SOFA). Reduced ICG clearance correlates with CVP; however, ICG-PDR cannot distinguish between portal venous and arterial inflow components. The exact mechanism remains speculative. Full article

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

20 pages, 848 KB

Open AccessReview

Small Hearts, Big Clues: A Narrative Review on Sex-Related Disparities in the Diagnosis and Management of Cardiac Amyloidosis in Women

by Ilenia Monaco, Mounia Sedrati, Insaf Chouarfia, Fatima Zahra Samet Bouhaik, Valeria Trivelloni, Yassine Bencharef, Mohammed Fouad Sekkal and Dario Bottigliero

J. Clin. Med. 2026, 15(12), 4819; https://doi.org/10.3390/jcm15124819 - 21 Jun 2026

Viewed by 1159

Abstract

Background: Amyloidosis is an infiltrative cardiomyopathy caused by amyloid deposition into the myocardium. In recent years, recognition of this treatable cause of heart failure has increased. There are striking sex differences in the diagnosis, clinical course and outcome of the disease. Notably, women [...] Read more.

Background: Amyloidosis is an infiltrative cardiomyopathy caused by amyloid deposition into the myocardium. In recent years, recognition of this treatable cause of heart failure has increased. There are striking sex differences in the diagnosis, clinical course and outcome of the disease. Notably, women have a worse prognosis than men with similar amounts of cardiac involvement. Methods: This review provides an overview of the current state of knowledge regarding the epidemiology, clinical features, diagnosis and treatment of amyloid heart disease. The differences observed between men and women are discussed, and recent advances in the field are highlighted. Results: Compared to men, women are generally older at diagnosis, appear to have less severe cardiac disease at the time of impairment and are more frequently diagnosed late. The less apparent disease manifestations in women may be responsible for the delay in diagnosis. Moreover, women may be underdiagnosed when sex-neutral diagnostic criteria are used. Conclusions: Addressing diagnostic disparities may require the use of sex-specific diagnostic thresholds, as well as a more expansive use of multimodality imaging. Future clinical trials should aim to enroll a greater number of female participants to inform optimal therapeutic approaches and to define the sex-specific disease phenotype for this increasingly treatable disease. Full article

(This article belongs to the Section Cardiovascular Medicine)

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J. Clin. Med., Volume 15, Issue 12 (June-2 2026) – 450 articles

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