Journal of Clinical Medicine

11 pages, 1541 KB

Open AccessArticle

Artificial Intelligence and FLIP Panometry—Automated Classification of Esophageal Motility Patterns

by Miguel Mascarenhas, Francisco Mendes, João Rala Cordeiro, Joana Mota, Miguel Martins, Maria João Almeida, Catarina Araujo, Joana Frias, Pedro Cardoso, Ismael El Hajra, António Pinto da Costa, Virginia Matallana, Constanza Ciriza de Los Rios, João Ferreira, Miguel Mascarenhas Saraiva, Guilherme Macedo, Benjamin Niland and Cecilio Santander

J. Clin. Med. 2026, 15(1), 401; https://doi.org/10.3390/jcm15010401 - 5 Jan 2026

Viewed by 596

Abstract

Background/Objectives: Functional lumen imaging probe (FLIP) panometry allows real-time assessment of the esophagogastric junction opening and esophageal body contractile activity during an endoscopic procedure. Despite the development of the Dallas Consensus, FLIP panometry analysis remains complex. Artificial intelligence (AI) models have proven [...] Read more.

Background/Objectives: Functional lumen imaging probe (FLIP) panometry allows real-time assessment of the esophagogastric junction opening and esophageal body contractile activity during an endoscopic procedure. Despite the development of the Dallas Consensus, FLIP panometry analysis remains complex. Artificial intelligence (AI) models have proven their benefit in high-resolution esophageal manometry; however, data on their role in FLIP panometry are scarce. This study aims to develop an AI model for automatic classification of motility patterns during a FLIP panometry exam. Methods: A total of 105 exams from five centers from both the European and American continents were included. Several machine learning models were trained and evaluated for detection of FLIP panometry patterns. Each exam was classified with an expert consensus-based decision according to the Dallas Consensus, with division into a training and testing dataset in a patient-split design. Models’ performance was evaluated through their accuracy and area under the receiver-operating characteristic curve (AUC-ROC). Results: Pathological planimetry patterns were identified by an AdaBoost Classifier with 84.9% accuracy and a mean AUC-ROC of 0.92. Random Forest identified disorders of the esophagogastric junction opening with 86.7% accuracy and an AUC-ROC of 0.973. The Gradient Boosting Classifier identified disorders of the contractile response with 86.0% accuracy and an AUC-ROC of 0.933. Conclusions: In this study, integrating exams with different probe sizes and demographic contexts, a machine learning model accurately classified FLIP panometry exams according to the Dallas Consensus. AI-driven FLIP panometry could revolutionize the approach to this exam during an endoscopic procedure, optimizing exam accuracy, standardization, and accessibility, and transforming patient management. Full article

(This article belongs to the Special Issue Artificial Intelligence in Gastrointestinal Disorders: Current Updates from Theory to Clinical Practice)

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19 pages, 525 KB

Open AccessSystematic Review

Electromyography After Total Hip Arthroplasty: A Systematic Review of Neuromuscular Alterations and Functional Movement Patterns

by Maria Cesarina May, Andrea Zanirato, Luca Puce, Eugenio Giannarelli, Carlo Trompetto, Lucio Marinelli and Matteo Formica

J. Clin. Med. 2026, 15(1), 400; https://doi.org/10.3390/jcm15010400 - 5 Jan 2026

Viewed by 700

Abstract

Background: Electromyography (EMG) is increasingly used to characterize neuromuscular alterations after total hip arthroplasty (THA), yet available evidence remains fragmented and inconsistent. This systematic review synthesizes postoperative EMG findings during gait, functional tasks, and static assessments, highlighting clinical implications and future research [...] Read more.

Background: Electromyography (EMG) is increasingly used to characterize neuromuscular alterations after total hip arthroplasty (THA), yet available evidence remains fragmented and inconsistent. This systematic review synthesizes postoperative EMG findings during gait, functional tasks, and static assessments, highlighting clinical implications and future research needs. Methods: Peer-reviewed studies employing surface, needle, or high-density EMG after THA were systematically examined. Extracted variables included activation amplitude, timing (onset, offset, burst duration), co-activation patterns, and the influence of surgical approach. Methodological rigor, normalization procedures, and the extractability of quantitative EMG metrics were also assessed. Results: Across studies, postoperative EMG consistently revealed non-physiological activation patterns, including delayed or prolonged gluteus medius activity and excessive recruitment of posterior chain muscles. These abnormalities persisted for up to 12 months and, in isolated cases, beyond a decade. Comparisons of surgical approaches demonstrated early denervation signs and impaired recruitment following lateral-based incisions, whereas later adaptations differed between lateral and posterior approaches but remained abnormal in both. Needle EMG studies confirmed transient involvement of muscles innervated by the superior gluteal nerve, while high-density EMG identified persistent deficits in spatial and temporal organization despite clinical improvement. Load-bearing and assisted-task studies showed that cane use and balance challenges modulate abductor demand yet continue to expose asymmetries and elevated stabilization requirements. Nonetheless, comparability across investigations remains limited because few studies adopted standardized normalization procedures or reproducible locomotor tasks. Conclusions: Neuromuscular recovery after THA appears incomplete and asymmetric, characterized by compensatory strategies not detectable through clinical or kinematic assessments alone. Improved diagnostic sensitivity and clinical applicability will require protocol standardization and the broader adoption of advanced EMG approaches. Full article

(This article belongs to the Special Issue Total Hip Arthroplasty Today: Trends, Challenges, and Future Directions)

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17 pages, 1215 KB

Open AccessReview

Maternal–Fetal Implications of Mpox Infection: Current Evidence

by Stefany Silva Pereira, Antonio Braga, Beatriz Bussi Rosolen, Talita Almeida Durães, Marcela Fermoselle de Vita Silva, Giovanna Alves de Britto, Giuliana Augustinelli Sales, Gustavo Yano Callado, Camilla Martins dos Santos Maia, Evelyn Traina, Edward Araujo Júnior, Gabriele Tonni and Roberta Granese

J. Clin. Med. 2026, 15(1), 399; https://doi.org/10.3390/jcm15010399 - 5 Jan 2026

Viewed by 694

Abstract

Mpox is an emerging zoonotic infection caused by the Monkeypox virus, an Orthopoxvirus with increasing global relevance following the 2022 multinational outbreak. Historically endemic to Central and West Africa, the disease has evolved from sporadic zoonotic transmission to sustained human-to-human spread, particularly through [...] Read more.

Mpox is an emerging zoonotic infection caused by the Monkeypox virus, an Orthopoxvirus with increasing global relevance following the 2022 multinational outbreak. Historically endemic to Central and West Africa, the disease has evolved from sporadic zoonotic transmission to sustained human-to-human spread, particularly through close physical and intimate contact. Clinical manifestations typically include fever, lymphadenopathy, and progressive mucocutaneous lesions, although severity varies according to viral clade, immune status, and comorbidities. The 2022 outbreak, predominantly associated with the Clade IIb variant, was characterized by milder disease, localized lesions, and reduced mortality compared with the more virulent Clade I variant. Despite this, severe outcomes remain possible, particularly in vulnerable groups such as children, pregnant individuals, immunocompromised patients, and persons with extensive dermatological disorders. Diagnosis relies primarily on polymerase chain reaction testing from lesion-derived samples, with genomic sequencing serving as a complementary tool for epidemiological surveillance. Management is largely supportive, though antivirals such as tecovirimat may be considered in severe cases or in high-risk populations. Data regarding therapeutic safety in pregnancy are limited; however, tecovirimat appears to have the most favorable profile, whereas cidofovir and brincidofovir remain contraindicated. Prevention strategies include targeted vaccination with the non-replicating Modified Vaccinia Ankara–Bavarian Nordic vaccine, used for both pre- and post-exposure prophylaxis, particularly in individuals at elevated risk. Given the evolving epidemiological profile, the potential for vertical transmission, and the risk of adverse perinatal outcomes, Mpox infection during pregnancy poses unique clinical challenges. This review synthesizes current evidence on virology, clinical presentation, diagnosis, prevention, and management, with an emphasis on obstetric considerations and public health implications. Full article

(This article belongs to the Special Issue Clinical Updates on Maternal Fetal Medicine: 2nd Edition)

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18 pages, 1613 KB

Open AccessArticle

Electrical Evoked Potentials After Perioperative Pain Neuroscience Education or Back School Education: A Subgroup Analysis of a Randomized Controlled Trial

by Lisa Goudman, Eva Huysmans, Wouter Van Bogaert, Iris Coppieters, Kelly Ickmans, Jo Nijs, Ronald Buyl and Maarten Moens

J. Clin. Med. 2026, 15(1), 398; https://doi.org/10.3390/jcm15010398 - 5 Jan 2026

Viewed by 493

Abstract

Background/Objectives: Biopsychosocial pain neuroscience education (PNE) has recently gained attention in preparing patients for surgery. PNE is expected to influence pain coping strategies and descending nociceptive inhibition. The goal of this study was to compare cortical evoked responses during experimental pain processing [...] Read more.

Background/Objectives: Biopsychosocial pain neuroscience education (PNE) has recently gained attention in preparing patients for surgery. PNE is expected to influence pain coping strategies and descending nociceptive inhibition. The goal of this study was to compare cortical evoked responses during experimental pain processing using a conditioned pain modulation (CPM) paradigm between patients receiving perioperative PNE (PPNE) or perioperative biomedical back school education (PBSE). Methods: This predefined EEG subgroup analysis included only participants with complete EEG recordings at baseline and 6 weeks. Of these, twenty-three patients with low back-related leg pain, scheduled for lumbar spine surgery, were randomized to either two sessions of PPNE or two sessions of PBSE. All patients were stimulated electrically at the median nerve of the symptomatic side and the sural nerve of the symptomatic and non-symptomatic side before and 6 weeks after the educational sessions, while evoked potentials were recorded by electroencephalography (EEG). Subsequently, this protocol was repeated during the application of the CPM paradigm by immersing the hand contralateral to the symptomatic side into cold water. Results: A significant decrease in the amplitude of the waveforms during CPM was found compared to the waveforms before CPM at the non-symptomatic sural nerve. No significant differences were found at the other test locations. For the waveforms of the CPM effect (subtracted waveforms), no significant treatment effects were revealed between the PPNE and PBSE groups. Conclusions: These exploratory findings suggest that PPNE was not associated with differential modulation of EEG evoked potentials during CPM compared with PBSE at 6 weeks post-surgery. Full article

(This article belongs to the Section Anesthesiology)

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21 pages, 560 KB

Open AccessReview

Male Infertility: A Comprehensive Review of Urological Causes and Contemporary Management

by Biagio Barone, Ugo Amicuzi, Simone Tammaro, Michelangelo Olivetta, Marco Stizzo, Michele Musone, Luigi Napolitano, Luigi De Luca, Pasquale Reccia, Federico Capone, Arturo Lecce, Giovanni Pagano, Silvestro Imperatore, Stefano Chianese, Salvatore Papi, Giampiero Della Rosa, Fabrizio Dinacci, Mariano Coppola, Antonio Madonna, Marco Grillo, Dante Di Domenico, Francesco Del Giudice, Vincenzo Francesco Caputo, Dario Del Biondo, Roberto Falabella and Felice Crocetto Show full author list Hide full author list

J. Clin. Med. 2026, 15(1), 397; https://doi.org/10.3390/jcm15010397 - 5 Jan 2026

Cited by 1 | Viewed by 2216

Abstract

Male infertility is a prevalent global health issue, with urological disorders representing some of the most common and correctable causes. Key conditions such as varicocele, obstructive azoospermia, erectile dysfunction and Peyronie’s disease impair fertility through distinct pathophysiological mechanisms, including disrupted spermatogenesis, reproductive tract [...] Read more.

Male infertility is a prevalent global health issue, with urological disorders representing some of the most common and correctable causes. Key conditions such as varicocele, obstructive azoospermia, erectile dysfunction and Peyronie’s disease impair fertility through distinct pathophysiological mechanisms, including disrupted spermatogenesis, reproductive tract obstruction and failed sperm delivery. The effective management of these conditions hinges on a systematic diagnostic evaluation, which integrates clinical history, physical examination, semen analysis and specialized imaging. Modern management follows a logical progression, beginning with foundational lifestyle modifications, advancing to targeted medical or surgical interventions, and culminating, when necessary, in assisted reproductive technologies. Treatment strategies are therefore highly targeted, ranging from medical management and surgical correction—such as varicocelectomy or microsurgical reconstruction—to sperm retrieval techniques. Furthermore, evidence-based lifestyle modifications and a multidisciplinary clinical approach are fundamental to optimizing reproductive outcomes for affected couples. A comprehensive understanding of these urological etiologies is therefore essential for guiding appropriate intervention and improving the prospects of achieving pregnancy. Full article

(This article belongs to the Special Issue Latest Research on Male Infertility)

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10 pages, 215 KB

Open AccessArticle

Systemic Inflammation Marker Alterations in Severe Alopecia Areata Patients Treated with Janus Kinase Inhibitors

by Gokhan Sahin, Fatma Aydin and Esra Pancar Yuksel

J. Clin. Med. 2026, 15(1), 396; https://doi.org/10.3390/jcm15010396 - 5 Jan 2026

Viewed by 720

Abstract

Background/Objectives: Alopecia areata is an autoimmune disorder characterized by nonscarring hair loss and systemic immune dysregulation. Hematological indices such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), mean platelet volume (MPV), systemic immune-inflammation index (SII), erythrocyte sedimentation rate (ESR), and [...] Read more.

Background/Objectives: Alopecia areata is an autoimmune disorder characterized by nonscarring hair loss and systemic immune dysregulation. Hematological indices such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), mean platelet volume (MPV), systemic immune-inflammation index (SII), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) have been associated with inflammatory activity in dermatologic diseases. This study aimed to compare systemic inflammatory markers among patients with severe and mild alopecia areata and healthy controls, and to explore longitudinal changes in these markers in patients with severe disease who achieved clinical improvement following Janus kinase (JAK) inhibitor therapy. Methods: This retrospective cohort study included 129 participants: 43 patients with severe alopecia areata (SALT ≥ 50) treated with JAK inhibitors who achieved documented clinical improvement, 43 patients with mild disease (SALT ≤ 20), and 43 age- and sex-matched healthy controls. Hematological inflammatory markers, including red cell distribution width (RDW), MPV, MLR, NLR, PLR, SII, ESR, and CRP, were compared across groups. In patients with severe disease, longitudinal changes were assessed at baseline, three months after treatment initiation, and at the time of documented clinical improvement. Results: MLR, NLR, PLR, SII, and ESR levels were significantly higher in the severe group compared with mild cases and controls, while RDW, MPV, and CRP showed no significant differences. Among patients with severe alopecia areata who achieved clinical improvement following JAK inhibitor therapy, NLR and SII decreased significantly over time. MLR, PLR, and CRP also showed reductions during follow-up, while ESR and RDW remained unchanged. Conclusions: Systemic inflammatory markers are elevated in severe alopecia areata compared with mild disease and healthy controls. In patients who achieved clinical improvement with JAK inhibitor therapy, several inflammatory indices demonstrated longitudinal changes. These findings are exploratory and suggest an association between systemic inflammation, disease severity, and clinical improvement rather than definitive predictive biomarkers. Full article

(This article belongs to the Section Dermatology)

11 pages, 569 KB

Open AccessArticle

Preeclampsia as an Independent and Major Risk Factor for Significant Postpartum Depression Symptomatology: Results from a Prospective Cohort Study

by Larisa-Mihaela Holbanel, Adina Turcu-Stiolica, Daniela Gabriela Glavan, Sebastian Constantin Toma and Nicolae Cernea

J. Clin. Med. 2026, 15(1), 395; https://doi.org/10.3390/jcm15010395 - 5 Jan 2026

Viewed by 574

Abstract

Background/Objectives: Preeclampsia is a severe hypertensive disorder that has been linked to increased maternal psychiatric morbidity. However, existing literature remains inconsistent regarding whether this association is independent of underlying medical co-morbidities such as chronic hypertension and diabetes. Our objective was to precisely [...] Read more.

Background/Objectives: Preeclampsia is a severe hypertensive disorder that has been linked to increased maternal psychiatric morbidity. However, existing literature remains inconsistent regarding whether this association is independent of underlying medical co-morbidities such as chronic hypertension and diabetes. Our objective was to precisely evaluate the Adjusted Odds Ratio (AOR) of developing Postpartum Depression symptomatology (probable PPD) following a diagnosis of preeclampsia in a prospectively tracked cohort, controlling for essential confounders. Methods: This prospective cohort study included 180 women (33 in the Preeclampsia group, 147 in the Normotensive reference group), with stringent exclusion of women with prior psychiatric history to reduce confounding. PPD was assessed postpartum using the Edinburgh Postnatal Depression Scale (EPDS ≥ 13 cutoff). Multivariable logistic regression was employed to calculate the AOR, adjusting for maternal age, chronic hypertension, and prepregnancy diabetes. Results: The multivariable analysis demonstrated a highly significant and independent association between the primary exposure and the outcome. Preeclampsia was associated with 12.7-fold increased odds of developing PPD (AOR: 12.7; 95% CI: 5.1–31.7; p < 0.001). In contrast, none of the included confounders—chronic hypertension (AOR: 1.96, p = 0.182), prepregnancy diabetes (AOR: 1.8, p = 0.372), or age (AOR: 0.99, p = 0.759)—showed a statistically significant independent association with PPD risk. The model achieved strong explanatory power (Nagelkerke R² = 0.327; Omnibus Test p < 0.001). Conclusions: Preeclampsia represents a powerful and independent determinant of the risk for significant PPD symptomatology, substantially increasing the adjusted odds of the condition. These findings mandate that women with a history of preeclampsia be designated a high-risk group and receive immediate, mandatory, and intensified postpartum mental health surveillance and preferential access to specialized psychological support. Full article

(This article belongs to the Special Issue Perinatal Mental Health Management)

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12 pages, 1706 KB

Open AccessArticle

Increasing Obesity Rates Worldwide from 1976 to 2016: The Obesity Epidemic

by Karsten Keller, Volker H. Schmitt, Omar Hahad, Christine Espinola-Klein and Lukas Hobohm

J. Clin. Med. 2026, 15(1), 394; https://doi.org/10.3390/jcm15010394 - 5 Jan 2026

Viewed by 1757

Abstract

Background: Obesity is a major health concern worldwide and the World Health Organization (WHO) has declared it a global epidemic. We aimed to analyze temporal trends of obesity prevalence worldwide. Methods: We used data of “The Global Health Observatory” of the WHO and [...] Read more.

Background: Obesity is a major health concern worldwide and the World Health Organization (WHO) has declared it a global epidemic. We aimed to analyze temporal trends of obesity prevalence worldwide. Methods: We used data of “The Global Health Observatory” of the WHO and analyzed data from the Global Burden of Disease (GBD) Study 2023. Obesity prevalence (crude estimates) among adults in different worldwide WHO regions and temporal trends from 1976 and 2016 were analyzed. Results: Obesity prevalence showed large regional differences. In 2016, obesity prevalence was highest in the WHO European region and the region of the Americas, at more than 20%, whereas prevalence was lower in the WHO African region, the WHO Western Pacific region and the WHO South-East Asia region, at less than 10%. The absolute increase from 1976 to 2016 comprised an increase of 19.7% in the region of the Americas, of 14.8% and 14.2% in the WHO European region and the WHO Eastern Mediterranean region, followed by 7.3% in the WHO African region, 6.0% in the WHO Western Pacific region, and 4.2% in the WHO South-East Asia region. We observed a substantially higher prevalence of obesity in females. High BMI has risen sharply in rank worldwide, now ranging among the top six global risk factors for death. Major BMI-related causes include ischemic heart disease, type 2 diabetes mellitus, hypertensive heart disease, and ischemic stroke. Conclusions: Obesity prevalence showed large regional differences and was highest in Europe and America. The prevalence of obesity increased worldwide between 1976 and 2016. Obesity prevalence was higher in females than in males. The importance of obesity for premature death increased between 1990 and 2023. Full article

(This article belongs to the Section Epidemiology & Public Health)

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12 pages, 632 KB

Open AccessArticle

CLR (CRP to Lymphocytes) Score for Differentiating Simple and Complicated Appendicitis in Pediatric Patients

by Adir Alper, Ariel Galor, Mathias Lerner, Omer Levy and Osnat Zmora

J. Clin. Med. 2026, 15(1), 393; https://doi.org/10.3390/jcm15010393 - 5 Jan 2026

Viewed by 820

Abstract

Background: Acute appendicitis, a frequent pediatric surgical emergency, requires distinguishing simple from complicated cases for treatment decisions. Current tools, such as clinical scores and ultrasound, are sometimes ineffective. This study evaluates the biomarkers: neutrophils to lymphocytes ratio (NLR), monocytes to lymphocytes ratio [...] Read more.

Background: Acute appendicitis, a frequent pediatric surgical emergency, requires distinguishing simple from complicated cases for treatment decisions. Current tools, such as clinical scores and ultrasound, are sometimes ineffective. This study evaluates the biomarkers: neutrophils to lymphocytes ratio (NLR), monocytes to lymphocytes ratio (MLR), platelet-to-lymphocyte ratio (PLR), neutrophils to monocytes ratio (NMR), neutrophils to platelet ratio (NPR), pan-immune-inflammation value (PIV) ratio, and C-Reactive Protein (CRP) to lymphocytes ratio (CLR) for differentiation between simple and complicated appendicitis. Methods: A retrospective study of 878 pediatric patients (<18 years) who underwent appendectomy (2018–2024) at a tertiary medical center, with appendicitis classified as simple (SA, n = 696) or complicated (CA, n = 182) using intraoperative findings. Biomarkers were calculated from preoperative blood counts and CRP. Diagnostic accuracy was assessed using Mann–Whitney U tests, ROC curves, and logarithmic regression. Results: Patients with CA had higher neutrophils counts (13.61 ± 4.92 vs. 11.39 ± 4.29 K/μL), monocytes counts (1.23 ± 1.41 vs. 0.95 ± 0.48 K/μL), platelet counts (294.31 ± 72.73 vs. 270.15 ± 72.08 K/μL), CRP levels (88.55 ± 97.75 vs. 27.15 ± 44.74 mg/L), and elevated biomarker ratios as compared to those with SA: NLR (≥10.15, OR = 2.45), MLR (≥0.645, OR = 2.78), PLR (≥224.38, OR = 2.502), NMR (≥6.38, OR = 2.34), NPR (≥0.0405, OR = 1.876), PIV (≥2433.85, OR = 3.348), and CLR (≥11.77, OR = 5.935), all at p < 0.01. CLR demonstrated the highest accuracy (AUC = 0.772, sensitivity 78%, specificity 62.6%), outperforming established biomarkers, followed by PIV (AUC = 0.679). NPR was the least effective marker (AUC = 0.569). Conclusions: CLR, a promising biomarker, can aid in distinguishing complicated from simple appendicitis in children, and may offer accessible tools for resource-limited settings. Full article

(This article belongs to the Section Clinical Laboratory Medicine)

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10 pages, 257 KB

Open AccessArticle

Performance of Routine MRI Reporting for Parapharyngeal Space Tumors: A Retrospective Radiologic–Pathologic Comparison

by Mohammed Alshahrani, Mohammed Almayouf, Aseel Doubi, Omar Alotaibi, Sharif Almatrafi, Khalid AlQahtani, Saleh Aldhahri, Majed Albarrak, Mohammed Alessa, Ahmed Albosaily and Faisal Alzahrani

J. Clin. Med. 2026, 15(1), 392; https://doi.org/10.3390/jcm15010392 - 5 Jan 2026

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Abstract

Background/Objectives: The parapharyngeal space is a complex anatomical region that houses critical neurovascular structures and serves as the origin of rare tumors, which account for 0.5–1% of head and neck neoplasms. Magnetic resonance imaging (MRI) is useful for their preoperative assessment. However, its [...] Read more.

Background/Objectives: The parapharyngeal space is a complex anatomical region that houses critical neurovascular structures and serves as the origin of rare tumors, which account for 0.5–1% of head and neck neoplasms. Magnetic resonance imaging (MRI) is useful for their preoperative assessment. However, its accuracy in real-world clinical settings remains underexplored. This study aimed to investigate the diagnostic accuracy of MRI for parapharyngeal tumors at two tertiary centers. Methods: This retrospective study included patients who underwent MRI and surgical excision at two tertiary centers in Saudi Arabia between 2018 and 2024. Two reviewers independently extracted their MRI data and compared them with the final pathological data to determine the diagnostic performance of MRI. Results: Of the 31 patients (58.1% female; median age, 37.5 years), 90.3% had benign tumors. Neurogenic (41.9%) and salivary (25.8%) tumors were most common; 61.3% were located within the pre-styloid space. The benign and malignant groups had comparable baseline characteristics. MRI demonstrated moderate overall diagnostic agreement (κ = 0.525) and near-perfect concordance for schwannomas (κ = 0.912) and paragangliomas (κ = 0.839) but poor agreement for hemangiopericytomas (κ = −0.051). It had high accuracy (90.3%), specificity (92.9%), and negative predictive value (96.3%) for detecting malignancy but limited sensitivity (66.7%) or positive predictive value (50.0%). Nonetheless, cautious interpretation is required due to the limited prevalence of malignancy in the cohort (n = 3). Conclusions: MRI demonstrated high specificity for benign parapharyngeal space lesions in routine clinical reporting within this retrospective cohort, reflecting strong radiologic–pathologic agreement. Estimates of sensitivity and positive predictive value for malignancy were influenced by the limited number of malignant cases. Accordingly, the reported diagnostic performance measures should be interpreted as descriptive and exploratory, characterizing real-world MRI performance rather than definitive diagnostic accuracy. Full article

(This article belongs to the Section Otolaryngology)

13 pages, 1370 KB

Open AccessSystematic Review

Acquired Reactive Perforating Collagenosis—A Rare Entity Occurring Within Common Disorders: A Systematic Review and Our Personal Experience

by Maria Alexandra Junghetu, Cristina Violeta Tutunaru, Simona Laura Ianoși, Claudia Valentina Georgescu and Olguța Anca Orzan

J. Clin. Med. 2026, 15(1), 391; https://doi.org/10.3390/jcm15010391 - 5 Jan 2026

Viewed by 1096

Abstract

Background/Objectives: Acquired reactive perforating collagenosis (ARPC) is a rare entity usually occurring in adults with systemic diseases such as diabetes mellitus, chronic kidney disease (CKD), cardiovascular diseases, and malignancies, although drug-related and trauma-induced cases have also been reported. Given its rarity and [...] Read more.

Background/Objectives: Acquired reactive perforating collagenosis (ARPC) is a rare entity usually occurring in adults with systemic diseases such as diabetes mellitus, chronic kidney disease (CKD), cardiovascular diseases, and malignancies, although drug-related and trauma-induced cases have also been reported. Given its rarity and the lack of consensus on optimal management, we conducted a systematic review to summarize updated diagnostic and therapeutic insights into ARPC. Additionally, we report a case of ARPC associated with CKD. Methods: This study was conducted in accordance with the PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A literature search was performed in the PubMed database between May–September 2025. The search strategy targeted open-access, primary human studies, published within the last 15 years, available in English, and including adult patients with histopathologically confirmed ARPC. Results: Twenty-seven studies, predominantly case reports and case series, were included. The mean patient age was 60.8 ± 14.4 years. Only one case occurred in the absence of comorbidities, while most subjects had underlying systemic diseases. Drug-induced cases were also described. Clinically, ARPC should be suspected in patients presenting with pruritic papules/nodules with central keratotic plugs. Additional diagnostic tools include dermoscopy and reflectance confocal microscopy. However, histopathological evidence of transepidermal elimination of altered collagen fibers is mandatory. The current treatments of ARPC include antihistamines, keratolytics, topical/intralesional/oral corticosteroids, topical/systemic retinoids, phototherapy, dupilumab and allopurinol. Other therapies have been reported across the literature, including emerging ones. Conclusions: Once ARPC is diagnosed, a thorough evaluation for underlying diseases, including malignancies, is essential. Clinical trials are warranted to define optimal therapeutic strategies. Full article

(This article belongs to the Section Dermatology)

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21 pages, 1614 KB

Open AccessReview

The Prone-Position Whole Breast Irradiation Paradox: Where Do We Stand? A Comprehensive Review

by Chris Monten, Ilaria Benevento, Antonietta Montagna, Edy Ippolito, Paola Anselmo, Luciana Rago, Barbara D’Andrea, Angela Solazzo, Antonella Bianculli, Raffaele Tucciariello, Giammaria Fiorentini, Vito Metallo, Simone Salvago, Carmen Santoro, Anna Vallario and Grazia Lazzari

J. Clin. Med. 2026, 15(1), 390; https://doi.org/10.3390/jcm15010390 - 5 Jan 2026

Viewed by 716

Abstract

Over the past two decades, interest in prone-position whole breast irradiation (WBI) as an effective and practical alternative to supine treatment has been growing a lot. Although solid scientific data has provided evidence of substantial dosimetric benefit with decreased toxicity, there is still [...] Read more.

Over the past two decades, interest in prone-position whole breast irradiation (WBI) as an effective and practical alternative to supine treatment has been growing a lot. Although solid scientific data has provided evidence of substantial dosimetric benefit with decreased toxicity, there is still conflict in the radiotherapy community over whether to adopt prone-position WBI as a valid alternative to supine radiotherapy (RT) in routine clinical practice. A large number of prone trials have been conducted to assess and address concerns related to prone treatment in large and pendulous breasts and in left and right breast cancer (BC), nodal irradiation, and its reproducibility with deep inspiration breath hold (DIBH) delivery with photons or protons. Appropriate atlases have been defined to improve prone nodal irradiation. Additionally, more comfortable customized immobilization couches have been constructed to permit IMRT beams and VMAT arrangements with modern LINACs. Although our search in literature databases shows a growing body of evidence from the past two decades on this issue, prone WBI is still underused. Given the paradox of the advances and benefits of this positioning and the lack of drive in the radiotherapy community towards its clinical implementation, the purpose of this comprehensive review is to evaluate the true advantages of this position in real life and contextualize it in scenarios like large breasts, left-sided breast cancer, and nodal irradiation to encourage its implementation in clinical practice. Full article

(This article belongs to the Special Issue The State of the Art in Adjuvant Breast Irradiation: Technical, Clinical, and Genomic Advances in the Adjuvant and Neo-Adjuvant Fields)

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17 pages, 296 KB

Open AccessArticle

Lifestyle Habits and Alternative Tobacco and Nicotine Products: Results from the MINERVA Project

by Giulia Lorenzoni, Honoria Ocagli, Danila Azzolina, Noor Muhammad Khan, Francesca Angioletti, Kostantina-Thaleia Pilali, Aslihan Şentürk Acar, Paola Berchialla, Matteo Martinato and Dario Gregori

J. Clin. Med. 2026, 15(1), 389; https://doi.org/10.3390/jcm15010389 - 5 Jan 2026

Viewed by 619

Abstract

Background/Objectives: Alternative Tobacco and Nicotine Products (ATNPs) have gained widespread popularity. Although they are often promoted as lower-risk alternatives to traditional tobacco products, concerns remain regarding their association with risky behaviors among adolescents and young adults. This study examines the relationship between dietary [...] Read more.

Background/Objectives: Alternative Tobacco and Nicotine Products (ATNPs) have gained widespread popularity. Although they are often promoted as lower-risk alternatives to traditional tobacco products, concerns remain regarding their association with risky behaviors among adolescents and young adults. This study examines the relationship between dietary and lifestyle habits and both ATNP use and intention to use ATNP among Italian participants in the MINERVA (My changINg lifEstyles our Research and eVeryone heAlth) international project. Methods: MINERVA is an observational, international, prospective cohort study. A study-specific questionnaire was administered to participants, who were recruited through informal snowball sampling. The questionnaire collected information on sociodemographic characteristics, lifestyle factors, dietary habits, and the use of both traditional tobacco products and ATNPs. Predictors of ATNP use and intention to use were assessed using logistic regression models. Results: Data from 7535 Italian participants were analyzed. Overall, 48% reported having ever used ATNP, and 14% of non-smokers and non-users expressed an intention to try these products. Significant predictors of ATNP use and intention to use included prior smoking, lower age, and having family members who smoke. Lifestyle factors such as frequent consumption of fast food, junk food, and alcoholic beverages were positively associated with both ATNP use and intention to use. Conversely, daily fruit and vegetable consumption was inversely associated with these outcomes. Conclusions: ATNP use and intention to use were associated with unhealthy dietary and lifestyle patterns. These findings highlight the importance of integrated public health strategies addressing substance use alongside broader lifestyle behaviors among adolescents and young adults. Full article

(This article belongs to the Section Epidemiology & Public Health)

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10 pages, 855 KB

Open AccessArticle

Aesthetic Rehabilitation of Patients with Central and Peripheral Facial Palsy with Injectables (BNT-A, HA-Fillers and CaHa)

by Athanasios Tsivgoulis, Eleftherios Stefas, Georgios Galatas, Georgia Papagiannopoulou, Stella Fanouraki, Maria-Ioanna Stefanou, Pinelopi Vlotinou, Christina Zompola, Georgios Tsivgoulis and Aikaterini Theodorou

J. Clin. Med. 2026, 15(1), 388; https://doi.org/10.3390/jcm15010388 - 5 Jan 2026

Viewed by 786

Abstract

Background: Facial palsy constitutes a profoundly disabling condition, often leading to marked functional deficits and a decline in facial appearance, which substantially reduces the patient’s quality of life. A combined therapy of botulinum toxin (BoNTA), hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) appears [...] Read more.

Background: Facial palsy constitutes a profoundly disabling condition, often leading to marked functional deficits and a decline in facial appearance, which substantially reduces the patient’s quality of life. A combined therapy of botulinum toxin (BoNTA), hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) appears promising in the pharmacological approach of these patients. Methods: We reported our single center experience of patients with facial palsy, either of central or peripheral etiology who were treated with the combination of BoNTA, HA and CaHA, during a 6-month period (January 2025–June 2025). Results: Eight consecutive adult patients [mean age: 49.50 ± 7.95 years, 6 (75%) female] with facial palsy, either of central (4 patients) or peripheral (4 patients) etiology, received the combination of BoNTA, HA and CaHA. No serious adverse reactions were documented. Localized bruising and swelling at injection sites resolved without requiring any additional intervention. Facial Disability Index (FDI) was assessed both prior to and following treatment. The functional subscale increased from 65.63 ± 16.13 to 80.63 ± 10.50 (improvement rate = 24.4%, p-value = 0.002), while the psychosocial subscale increased from 63.00 ± 17.34 to 74.50 ± 10.89 (improvement rate = 18.3%, p-value = 0.004). Consequently, the total FDI score improved from 128.63 ± 28.92 to 155.13 ± 17.96 (overall improvement = 20.6%, p-value = 0.001). Conclusions: The present case series underscores the potential therapeutic role of CaHA as an adjunct to BoNTA and HA injections in patients with central or peripheral facial palsy. Full article

(This article belongs to the Special Issue Stroke Care: From Acute Interventions to Long-Term Recovery)

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17 pages, 272 KB

Open AccessArticle

Validation and Psychometric Evaluation of the Polish Language Version of the Sleep Disturbance Scale for Children (SDSC)

by Małgorzata Jączak-Goździak, Oliviero Bruni and Marcin Żarowski

J. Clin. Med. 2026, 15(1), 387; https://doi.org/10.3390/jcm15010387 - 5 Jan 2026

Viewed by 563

Abstract

Background/Objectives: In this study, we aimed to validate and psychometrically evaluate a tool for examining sleep disorders in Polish children. Methods: This study involved a randomly selected sample of 348 children aged 6 to 15 years, sourced from preschools, primary schools, [...] Read more.

Background/Objectives: In this study, we aimed to validate and psychometrically evaluate a tool for examining sleep disorders in Polish children. Methods: This study involved a randomly selected sample of 348 children aged 6 to 15 years, sourced from preschools, primary schools, and secondary schools in a city with a population exceeding 100,000, in addition to two smaller towns in Poland. Parents were asked to complete the Sleep Disorders Scale for Children (SDSC) in conjunction with a sociodemographic survey. The tool’s reliability was assessed using Cronbach’s alpha (α), and correlations among various domains were evaluated using Spearman’s rank correlation coefficient (Rs). Results: The study demonstrated excellent internal consistency for the SDSC, with a Cronbach’s α value of 0.9. The individual subscales also exhibited acceptable reliability values, ranging from 0.69 to 0.83. Considering T-scores over 70 as indicative of a problem, we identified at least one sleep disorder in 65 participants (18.68%). The most common issues included sleep hyperhidrosis (SHY; 7.47%), disorders of excessive somnolence (DOES; 7.18%), and sleep–wake transition disorders (SWTDs; 5.75%). Students in secondary education were more likely to experience disorders of initiating and maintaining sleep (DIMS), disorders of arousal (DA), and DOES. Conclusions: Based on our findings, the Polish version of the SDSC may be considered a reliable and effective tool for assessing sleep disturbances in school-age children and adolescents. Full article

(This article belongs to the Special Issue Advances in Child Neurology)

15 pages, 1894 KB

Open AccessArticle

Association Between Time to PSA Nadir, Radiologic Progression, and PSA Progression in mHSPC Patients Treated with Abiraterone or Enzalutamide

by Ugur Ozkerim, Oguzcan Kinikoglu, Deniz Isik, Yunus Emre Altintas, Seval Ay Ersoy, Heves Surmeli, Hatice Odabas, Tugba Basoglu and Nedim Turan

J. Clin. Med. 2026, 15(1), 386; https://doi.org/10.3390/jcm15010386 - 5 Jan 2026

Viewed by 803

Abstract

Background: Time to prostate-specific antigen (PSA) nadir (TTN) has been proposed as an early indicator of treatment responsiveness in metastatic hormone-sensitive prostate cancer (mHSPC). However, its prognostic relevance in patients treated with next-generation androgen receptor pathway inhibitors (ARPIs), such as abiraterone or [...] Read more.

Background: Time to prostate-specific antigen (PSA) nadir (TTN) has been proposed as an early indicator of treatment responsiveness in metastatic hormone-sensitive prostate cancer (mHSPC). However, its prognostic relevance in patients treated with next-generation androgen receptor pathway inhibitors (ARPIs), such as abiraterone or enzalutamide, remains incompletely defined. Methods: This retrospective cohort study included 147 patients with mHSPC treated with abiraterone or enzalutamide between 2019 and 2024. TTN, PSA kinetics, radiologic progression-free survival (rPFS), and PSA progression-free survival (PSA-PFS) were analyzed using Kaplan–Meier methods and multivariable Cox regression. TTN was evaluated both as a continuous variable and dichotomized at the cohort median (≤9 vs. >9 months). Results: TTN distributions were comparable between treatment groups (median 9.0 vs. 6.0 months, p = 0.197). Patients with a shorter TTN (≤9 months) experienced significantly longer median rPFS compared with those with longer TTN (>9 months) (10.7 vs. 7.95 months; p = 0.036). No significant association was observed between TTN and PSA-PFS (9.3 vs. 10.75 months; p = 0.34). In multivariable analysis, enzalutamide was independently associated with a reduced risk of radiologic progression compared with abiraterone (HR 0.622; 95% CI 0.441–0.877), whereas TTN was not an independent predictor. Conclusions: A shorter TTN was associated with improved radiologic outcomes, suggesting that rapid PSA suppression may reflect more favorable disease biology in patients receiving ARPI therapy. Although TTN showed limited value in predicting biochemical progression, it may serve as a simple and accessible biomarker for early risk stratification and tailoring follow-up intensity in mHSPC. Validation in larger, multicenter cohorts is warranted. Full article

(This article belongs to the Section Pharmacology)

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11 pages, 1713 KB

Open AccessReview

Feasibility of Laparoscopic Radical Colpectomy in Locally Advanced Vaginal Cancer: A Case Report and Literature Review

by Davut Dayan, Hannes Endres, Stefan Lukac, Wolfgang Janni, Florian Ebner, Mandana Shirin Khodawandi and Jasmina Veta Darkovski

J. Clin. Med. 2026, 15(1), 385; https://doi.org/10.3390/jcm15010385 - 5 Jan 2026

Viewed by 544

Abstract

Objectives: Due to the rarity of primary vaginal carcinoma, standardized treatment approaches are limited. Radical surgery is rare, especially in advanced stages. This report evaluates the feasibility, technical aspects and outcomes of laparoscopic en bloc resection in advanced vaginal carcinoma. Case presentation [...] Read more.

Objectives: Due to the rarity of primary vaginal carcinoma, standardized treatment approaches are limited. Radical surgery is rare, especially in advanced stages. This report evaluates the feasibility, technical aspects and outcomes of laparoscopic en bloc resection in advanced vaginal carcinoma. Case presentation: A 67-year-old woman presented with pain and vaginal bleeding. Clinical examination revealed a stenosing vaginal tumour up to 2 cm above the introitus, extending to the urethra and right vulva. Biopsies confirmed invasive squamous cell carcinoma with VAIN/VIN III. Imaging revealed enlarged pelvic lymph nodes, but no distant metastases. Methods: The surgical procedure comprised laparoscopic en bloc resection, including bilateral pelvic lymphadenectomy, radical hysterectomy with bilateral salpingo-oophorectomy, and total vaginal excision down to the pelvic floor. Additionally, inguinal bilateral ICG-guided sentinel lymph node dissection, vulvectomy with clitoral preservation, and partial urethral resection were performed, followed by transvaginal specimen removal. Vaginal closure was achieved via combined transvaginal and laparoscopic pelvic floor reconstruction. The postoperative course was uneventful, with early recovery of urinary and bowel function. Final histology confirmed complete tumor resection with clear margins (pT3, pN0, L0, V0, Pn0, R0). Functional outcomes remained excellent, with no recurrence or functional impairment at one-year follow-up. Conclusions: Laparoscopic en bloc resection appears to be a feasible option for selected patients with locally advanced vaginal carcinoma, enabling complete tumour removal with preservation of pelvic floor function and resulting in favourable postoperative and oncological outcomes. Full article

(This article belongs to the Section Oncology)

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10 pages, 703 KB

Open AccessCase Report

Inferior Vena Cava-Atrial Anastomosis in Liver Transplant Recipient with Inferior Vena Cava Occlusion: A Case Report and Literature Review

by Jakub Rochoń, Piotr Kalinowski, Joanna Marczak, Krzysztof Gibiński and Michał Grąt

J. Clin. Med. 2026, 15(1), 384; https://doi.org/10.3390/jcm15010384 - 5 Jan 2026

Viewed by 742

Abstract

A 25-year-old woman with decompensated liver cirrhosis and complete inferior vena cava (IVC) occlusion was referred to our department for liver transplantation. The etiology of cirrhosis was Budd-Chiari syndrome (BCS) related to systemic lupus erythematosus, autoimmune hepatitis, and primary biliary cholangitis (AIH-PBC) overlap [...] Read more.

A 25-year-old woman with decompensated liver cirrhosis and complete inferior vena cava (IVC) occlusion was referred to our department for liver transplantation. The etiology of cirrhosis was Budd-Chiari syndrome (BCS) related to systemic lupus erythematosus, autoimmune hepatitis, and primary biliary cholangitis (AIH-PBC) overlap syndrome. Transplantation was feasible due to an extensive collateral circulation of pre-vertebral veins that drained blood from the lower extremities and both kidneys to the azygos-hemiazygos veins. This venous anomaly enabled the excision of the obstructed retrohepatic IVC, followed by an alternative anastomosis of the suprahepatic IVC to the right atrium without reconstruction of the infrahepatic IVC. Despite good venous patency and normalization of liver graft function, the patient developed cecum perforation, cardiovascular and respiratory insufficiency, which led to the patient’s death two months after transplantation. This case report supports an individual approach and highlights the feasibility of liver transplantation despite an extensive IVC thrombosis. To our knowledge, it is the first description of the application of a deceased donor liver transplantation in patients with AIH-PBC overlap syndrome and lupus-related BCS. A concise review of published literature on IVC-atrial anastomosis in adult liver transplant recipients is provided, and the technique is discussed based on our recent experience. Full article

(This article belongs to the Section General Surgery)

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8 pages, 3970 KB

Open AccessCase Report

Massive Hemoperitoneum Caused by Spontaneous Rupture of a Superficial Uterine Fundal Vein During Preterm Labor: A Case Report

by Won-Kyu Jang and Hyun Mi Kim

J. Clin. Med. 2026, 15(1), 383; https://doi.org/10.3390/jcm15010383 - 5 Jan 2026

Cited by 1 | Viewed by 554

Abstract

Spontaneous hemoperitoneum in pregnancy is rare, and rupture of a superficial uterine fundal vein in an unscarred uterus is exceptionally uncommon. A 37-year-old woman at 27 + 0 weeks presented with left upper quadrant abdominal pain, and imaging revealed a localized hematoma adjacent [...] Read more.

Spontaneous hemoperitoneum in pregnancy is rare, and rupture of a superficial uterine fundal vein in an unscarred uterus is exceptionally uncommon. A 37-year-old woman at 27 + 0 weeks presented with left upper quadrant abdominal pain, and imaging revealed a localized hematoma adjacent to the left uterine fundus without active bleeding. During conservative management, she developed sudden severe pain with fetal heart rate decelerations at 27 + 6 weeks, prompting emergency cesarean delivery. Intraoperative findings showed approximately 2400 mL of hemoperitoneum caused by rupture of a superficial fundal vein, with the uterus otherwise intact, and bleeding was controlled with a fibrin sealant patch. Maternal recovery and neonatal outcome were favorable. This case underscores that rupture of superficial uterine veins should be considered in pregnant patients presenting with unexplained hemoperitoneum during pregnancy. Full article

(This article belongs to the Section Reproductive Medicine & Andrology)

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10 pages, 885 KB

Open AccessBrief Report

Cardioneuroablation Acutely Affects the Amplitude and Efficiency of Respiratory Heart Rate Variability

by Piotr Niewinski, Stanislaw Tubek, Krzysztof Nowak, Krystian Josiak and Bartłomiej Paleczny

J. Clin. Med. 2026, 15(1), 382; https://doi.org/10.3390/jcm15010382 - 5 Jan 2026

Viewed by 509

Abstract

Background/Objectives: Cardioneuroablation (CNA) is used to treat reflex syncope by parasympathetic denervation of the cardiac conduction system. Respiratory heart rate variability (RespHRV) constitutes an important physiological mechanism that optimizes lung perfusion. The impact of CNA on various components of RespHRV remains unclear. [...] Read more.

Background/Objectives: Cardioneuroablation (CNA) is used to treat reflex syncope by parasympathetic denervation of the cardiac conduction system. Respiratory heart rate variability (RespHRV) constitutes an important physiological mechanism that optimizes lung perfusion. The impact of CNA on various components of RespHRV remains unclear. Methods: Eleven subjects (36.8 ± 14.1 years) undergoing CNA for the treatment of cardioinhibitory, vagally mediated syncope were enrolled. For the RespHRV assessment, we used continuous respiratory flow measurement and an electrocardiogram. RespHRV analysis included the following: (a) amplitude, reflecting the overall magnitude of changes in RR interval during the respiratory cycle (RespHRVpv, ms); and (b) efficiency, defined as the percentage of inspirations accompanied by RR shortening (short-RRi inspirations, %), and expirations accompanied by RR prolongation (long-RRi expirations, %). Baroreflex sensitivity (BRS, ms/mmHg) was assessed with a sequential method using a noninvasive hemodynamic monitor. Both RespHRV and BRS were captured 48 h apart, before and after CNA. Results: A significant reduction was observed in RespHRVpv (57 [30–131] vs. 13 [7–16] ms, p = 0.003), short-RRi inspirations (97.0 [77.8–100.0] vs. 36.0 [14.3–63.2] %, p = 0.003), and long-RRi expirations (88.0 [78.1–97.6] vs. 31.1 [21.4–65.8] %, p = 0.008). Moreover, we found a strong relationship between ΔBRS and ΔRespHRVpv (r = 0.77, p = 0.005) following CNA. Conclusions: Our results indicate a substantial role of the cardiac parasympathetic system in RespHRV development, including both its amplitude and efficiency. The marked decrease in key RespHRV measures after CNA highlights the need for further research into its long-term clinical effects. Full article

(This article belongs to the Special Issue Understanding Syncope: Multidisciplinary Approaches to Diagnosis and Management)

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13 pages, 549 KB

Open AccessSystematic Review

The Role of Biological Effective Dose in Gamma Knife Radiosurgery: A Systematic Review Across Multiple Indications

by Hao Deng, Xinyuejia Huang, Qian Wang, Yuan Gao, Mengqi Wang, Yang Wu, Xiaoman Shi, Maoyu Wang, Wei Pan, Senlin Yin and Wei Wang

J. Clin. Med. 2026, 15(1), 381; https://doi.org/10.3390/jcm15010381 - 5 Jan 2026

Viewed by 578

Abstract

Background: Gamma Knife radiosurgery (GKS) is widely used for the management of intracranial disorders. Emerging evidence suggests that incorporating the biological effective dose (BED) into GKS planning may improve the prediction of treatment efficacy and toxicity. This review aims to evaluate the role [...] Read more.

Background: Gamma Knife radiosurgery (GKS) is widely used for the management of intracranial disorders. Emerging evidence suggests that incorporating the biological effective dose (BED) into GKS planning may improve the prediction of treatment efficacy and toxicity. This review aims to evaluate the role of BED in GKS across multiple intracranial indications. Methods: A qualitative review of published clinical studies was performed to assess the application of BED models in GKS for pituitary adenomas, vestibular schwannomas, meningiomas, arteriovenous malformations (AVMs), trigeminal neuralgia, and other disorders. The relationships between BED, treatment outcomes, and adverse effects were compared across indications. Results: The association between BED and clinical outcomes was most consistent in AVMs, where higher BED correlated closely with obliteration rates. In other diseases, BED-based analyses showed promising but variable predictive value. Notably, BED-derived parameters demonstrated improved prediction of post-GKS hypopituitarism in pituitary adenomas and AVM obliteration compared with physical dose alone. However, most available evidence was derived from retrospective studies. Conclusions: BED may serve as a valuable complement to conventional physical dose metrics in GKS planning, but its ability to replace physical dose remains uncertain. Prospective studies and histology-specific radiobiological parameter validation are required to establish the routine clinical utility of BED. Full article

(This article belongs to the Section Nuclear Medicine & Radiology)

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19 pages, 310 KB

Open AccessReview

Endometriosis and Reproductive Sparing Surgery: A Narrative Review and AGREE II-S-Based Evaluation of International Guidelines

by Giovanni Pecorella, Andrea Morciano, Radmila Sparic, Gernot Hudelist, Ertan Saridogan, Marta Stojković and Andrea Tinelli

J. Clin. Med. 2026, 15(1), 380; https://doi.org/10.3390/jcm15010380 - 4 Jan 2026

Cited by 1 | Viewed by 1101

Abstract

Endometriosis is a complex disease that may affect a woman’s fertility and quality of life. Owing to substantial variations in symptom severity, lesion distribution, and reproductive impact, its management presents considerable clinical challenges. The most recent internationally recognized guidelines include those issued by [...] Read more.

Endometriosis is a complex disease that may affect a woman’s fertility and quality of life. Owing to substantial variations in symptom severity, lesion distribution, and reproductive impact, its management presents considerable clinical challenges. The most recent internationally recognized guidelines include those issued by the European Society of Human Reproduction and Embryology (ESHRE, 2022), the German Society of Gynecology and Obstetrics (DGGG/SGGG/OEGGG S2k, 2025), the World Endometriosis Society (WES), the National Institute for Health and Care Excellence (NICE, 2024), and the American College of Obstetricians and Gynecologists (ACOG, reaffirmed 2022). To provide a comprehensive overview of these recommendations, we critically compared these guidelines, with particular emphasis on the recently updated German S2k guideline. Searches were conducted through PubMed and institutional repositories using selected key terms, and the AGREE II tool (Appraisal of Guidelines for Research and Evaluation) was employed to assess methodological quality. Key clinical domains examined included indications for conservative and radical surgery, management of endometriomas and deep infiltrating endometriosis (DIE), the role of surgery before Assisted Reproductive Technology (ART), the impact of second-look procedures, and integration of psychosocial dimensions via Patient-Reported Outcome Measures (PROMs). The results show a general trend toward interdisciplinary treatment models, cautious use of radical resection techniques, and customized, symptom-based surgical interventions. Despite ongoing disagreements, there is general agreement on collaborative decision-making, preserving fertility, and adjusting surgery time and technique between the guidelines to meet the requirements of individual patients. Full article

(This article belongs to the Section Obstetrics & Gynecology)

14 pages, 1588 KB

Open AccessArticle

A Proposed Model of a Pragmatic Surgical Approach in Women Affected by Uterine Fibroids Undergoing IVF: A “Real Practice” Experience

by Domenico Antonaci, Francesco Galanti, Roberta Dall’Alba, Eleonora Benedetti, Andrea Rago, Laura Antonaci, Donatella Miriello and Rocco Rago

J. Clin. Med. 2026, 15(1), 379; https://doi.org/10.3390/jcm15010379 - 4 Jan 2026

Viewed by 653

Abstract

Background/Objectives: Uterine fibroids are the most common benign neoplasms of the female genital tract, with a prevalence of 20% to 40% among women of reproductive age. Their management in the context of Assisted Reproductive Technologies (ART) represents a major clinical challenge, characterized [...] Read more.

Background/Objectives: Uterine fibroids are the most common benign neoplasms of the female genital tract, with a prevalence of 20% to 40% among women of reproductive age. Their management in the context of Assisted Reproductive Technologies (ART) represents a major clinical challenge, characterized by controversies, contrasting approaches, and a lack of shared guidelines. Indeed, the detrimental effects of fibroid treatments are not well known and may be influenced by the size, location, and number of fibroids. The impact of hysteroscopic myomectomy in women affected by submucosal myomas (FIGO classification type: G0–G2) is well documented in the current literature; however, the impact of intramural and subserosal myoma removal (FIGO types 3–8), in particular those <4/5 cm in diameter, remains controversial. The aim of the present study is to introduce and share a pragmatic surgical approach to uterine fibroid management prior to In Vitro Fertilization (IVF), to reduce the knowledge gap regarding uterine fibroid treatment. Methods: We conducted a retrospective observationally study that included 94 cases of infertile women, who underwent myomectomy at our IVF centre at Sandro Pertini Hospital, Rome, Italy, between 2020 and 2025. These patients met the inclusion criterion of having an idiopathic/tubal factor of infertility and were aged < 40. We evaluated a group of 17 women (group A) who underwent hysteroscopic myomectomy for submucosal fibroids (FIGO types 0–2) and a group of 39 women (group B) who underwent open (laparotomic) myomectomy for intramural/subserosal fibroids (FIGO types 3–8). Group B was compared with a control group of 38 women who were similar in terms of all demographic and clinical parameters and myoma features (group C) and did not want to undergo a myomectomy procedure. All surgical procedures were executed by the same expert surgeon following our proposed model: submucosal fibroids were always removed by operative hysteroscopy, while intramural/subserosal fibroids were removed if there were three or more and if they were at least 1 ≥ 3 cm in size. All enrolled patients subsequently underwent IVF treatment at our centre, which consisted of an antagonist protocol for ovarian stimulation, and all transferred embryos were of good quality according to the recent European Society of Human Reproduction and Embryology (ESHRE) classification. Results: In group A, we observed an implantation rate of 41% and a clinical pregnancy rate of 35.2%, and these results are consistent with the current literature. In group B, we obtained statistically significant differences in the implantation (31% vs. 12.9%) and pregnancy rates (28.1% vs. 7.8%) compared to group C (p = 0.02 and p = 0.03, respectively). In addition, the live birth rate was statistically higher compared to that in group C (p < 0.01). Miscarriage and preterm delivery rates were lower in group B, although the differences were not statistically significant. No severe post-surgical complications, such as uterine rupture, were observed during subsequent pregnancies. Conclusions: Despite the limited patient sample size, the monocentric experience, and the retrospective design, we emphasize the effectiveness of our proposed surgical model in women affected by myomas. Indeed, the surgical treatment of submucosal, intramural, and subserosal lesions may improve ART and pregnancy outcomes (through a higher implantation rate, pregnancy rate, and live birth rate, as well as a lower miscarriage/preterm rate). Full article

(This article belongs to the Special Issue Modern Gynecological Surgery: Clinical Updates and Perspectives)

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24 pages, 2703 KB

Open AccessSystematic Review

Effects of SGLT2 Inhibitors on Clinical Outcomes, Symptoms, Functional Capacity, and Cardiac Remodeling in Heart Failure: A Comprehensive Systematic Review and Multidomain Meta-Analysis of Randomized Trials

by Olivia-Maria Bodea, Stefania Serban, Maria-Laura Craciun, Diana-Maria Mateescu, Eduard Florescu, Camelia-Oana Muresan, Ioana-Georgiana Cotet, Marius Badalica-Petrescu, Andreea Munteanu, Dana Velimirovici, Nilima Rajpal Kundnani and Simona Ruxanda Dragan

J. Clin. Med. 2026, 15(1), 378; https://doi.org/10.3390/jcm15010378 - 4 Jan 2026

Viewed by 1200

Abstract

Background: SGLT2 inhibitors are key therapies in heart failure (HF), but their combined multidomain effects have not been analyzed together. Methods: We conducted a PROSPERO-registered (CRD420251235850) systematic review and meta-analysis of all randomized controlled trials (RCTs) comparing SGLT2i (dapagliflozin, empagliflozin, canagliflozin, [...] Read more.

Background: SGLT2 inhibitors are key therapies in heart failure (HF), but their combined multidomain effects have not been analyzed together. Methods: We conducted a PROSPERO-registered (CRD420251235850) systematic review and meta-analysis of all randomized controlled trials (RCTs) comparing SGLT2i (dapagliflozin, empagliflozin, canagliflozin, sotagliflozin) with placebo in adults with HF, regardless of ejection fraction or diabetes status. We searched PubMed/MEDLINE, Embase, Cochrane CENTRAL, and Web of Science through 1 February 2025. Outcomes were grouped into four domains: (1) clinical events, (2) symptoms/health status (Kansas City Cardiomyopathy Questionnaire, KCCQ), (3) functional capacity (6 min walk distance, peak VO₂), and (4) cardiac remodeling/energetics (cardiac MRI, 31P-MRS). We used random-effects models with Hartung–Knapp adjustment and assessed heterogeneity by I² and prediction intervals. Results: Eleven RCTs with 23,812 patients (HFrEF, HFmrEF, HFpEF, and acute or recently decompensated HF) were included. SGLT2i lowered the risk of cardiovascular death or first HF hospitalization by 23% (HR 0.77, 95% CI 0.72–0.82; p < 0.0001; I² = 28%; prediction interval 0.68–0.87), with similar effects across ejection fraction, diabetes status, and presentation type. All-cause and cardiovascular mortality dropped by 12% (HR 0.88, 95% CI 0.81–0.96) and 14% (HR 0.86, 95% CI 0.78–0.95), respectively. SGLT2i improved KCCQ—Clinical Summary Score by 4.6 points (95% CI 3.4–5.8; p < 0.0001) and increased the odds of a ≥5-point improvement (OR 1.49, 95% CI 1.32–1.68; NNT = 12). Six-minute walk distance increased by 21.8 m (95% CI 9.4–34.2; p = 0.001), and mechanistic trials showed significant reverse remodeling (ΔLVEDV −19.8 mL, ΔLVEF +6.1%; both p < 0.001). No improvement was observed in myocardial PCr/ATP ratio. Safety was favorable, with no excess ketoacidosis or severe hypoglycemia. Conclusions: This multidomain synthesis demonstrates that SGLT2 inhibitors provide consistent, robust reductions in mortality and hospitalizations, while also delivering early, clinically meaningful improvements across multiple patient-centered domains. These results establish SGLT2i as a foundational component of contemporary HF management. Full article

(This article belongs to the Special Issue Therapies for Heart Failure: Clinical Updates and Perspectives)

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11 pages, 242 KB

Open AccessArticle

Noninvasive BCL6 Preoperative Screening and Anatomic Patterns of Endometriosis in Patients with Unexplained Infertility

by Farrah Khoyloo, Camran Nezhat, Zahra Najmi, Quincy Harding, Dahnia Zarroug, Angie Tsuei and Farr Nezhat

J. Clin. Med. 2026, 15(1), 377; https://doi.org/10.3390/jcm15010377 - 4 Jan 2026

Viewed by 537

Abstract

Background/Objectives: Endometriosis is a chronic, inflammatory, estrogen-dependent disease that has historically been underdiagnosed, especially in patients with unexplained infertility. On average, diagnosis is delayed by 11 years, underscoring the need for precision medicine to improve outcomes. To compare disease severity and anatomical distribution [...] Read more.

Background/Objectives: Endometriosis is a chronic, inflammatory, estrogen-dependent disease that has historically been underdiagnosed, especially in patients with unexplained infertility. On average, diagnosis is delayed by 11 years, underscoring the need for precision medicine to improve outcomes. To compare disease severity and anatomical distribution of endometriosis between patients with unexplained infertility who underwent noninvasive Receptiva BCL6 testing before surgery and those who did not. Methods: A cross-sectional analysis was conducted on 195 women with unexplained infertility and histologically confirmed endometriosis following diagnostic video laparoscopy, with or without robotic assistance. Disease severity was staged using updated guidelines. Anatomical sites of endometriosis were documented. Patients were grouped based on whether they had undergone the Receptiva BCL6 overexpression test prior to surgery. Results: Of the 195 patients, 43 underwent Receptiva testing; 41 of them tested positive and were confirmed to have endometriosis during surgery. These patients had fewer affected anatomical regions (3.14 ± 2.09) compared to those without testing (3.93 ± 2.26; p = 0.04). The No Receptiva group also had more high-stage cases (70.39% vs. 65.12%, p-value: 0.038). In both groups, endometriosis most frequently involved the periureteral region, rectovaginal septum, and ovaries, though ovarian tissue was rarely excised to preserve fertility. Conclusions: Among patients with unexplained infertility and confirmed endometriosis, those who had preoperative Receptiva testing showed lower disease burden and severity. These findings support the potential utility of noninvasive testing to enrich diagnostic accuracy and guide earlier, more targeted intervention. Full article

(This article belongs to the Section Obstetrics & Gynecology)

19 pages, 548 KB

Open AccessArticle

by Noriko Takeuchi, Takayuki Maruyama, Naoki Toyama, Yuzuki Katsube, Takahiro Tabuchi and Daisuke Ekuni

J. Clin. Med. 2026, 15(1), 376; https://doi.org/10.3390/jcm15010376 - 4 Jan 2026

Viewed by 1006

Abstract

Background/Objectives: Oral health-related quality of life (OHRQoL) may influence mental health outcomes, yet longitudinal evidence on its association with depression remains limited. This study aimed to examine whether oral health status and OHRQoL are associated with a change in self-reported depression status [...] Read more.

Background/Objectives: Oral health-related quality of life (OHRQoL) may influence mental health outcomes, yet longitudinal evidence on its association with depression remains limited. This study aimed to examine whether oral health status and OHRQoL are associated with a change in self-reported depression status among adults in Japan. Methods: We analyzed data from the Japan COVID-19 and Society Internet Survey (JACSIS), conducted in 2022 and 2023. A total of 15,068 participants aged ≥20 years without depression at baseline were included. Depression status was identified by self-reported measures between the two survey waves. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for change in self-reported depression status in relation to OHRQoL and oral health status, adjusting for sociodemographic and behavioral factors. Results: During follow-up, 218 participants (1.45%) reported a change in self-reported depression status. Poorer OHRQoL was significantly associated with a change in self-reported depression status (OR: 1.018; 95% CI: 1.001–1.036; p = 0.039). Additional risk factors included younger age (OR: 0.974; 95% CI: 0.964–0.985), participation in hobbies and cultural activities (OR: 2.224; 95% CI: 1.498–3.302), habitual use of sleeping pills or anxiolytics (current use OR: 3.512; 95% CI: 2.267–5.442), increased loneliness (OR: 1.217; 95% CI: 1.140–1.299), lower life satisfaction (OR: 0.900; 95% CI: 0.836–0.969), and poor self-rated health (OR: 2.921; 95% CI: 1.810–4.715). Conclusions: Impaired OHRQoL was associated with a change in self-reported depression status, potentially through psychosocial mechanisms. These findings suggest that oral health and OHRQoL may be relevant factors to consider in integrated oral and mental health approaches in clinical practice. Full article

(This article belongs to the Section Mental Health)

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12 pages, 3262 KB

Open AccessFeature PaperArticle

Impact of Contralateral Implant Placement in Unilateral Implant-Based Postmastectomy Breast Reconstruction: A Single Center Retrospective Cohort Study

by Salvatore D’Arpa, Giuseppe Antonio D’Amico, Giulio Jad Jaber, Michele Rosario Colonna and Massimo David

J. Clin. Med. 2026, 15(1), 375; https://doi.org/10.3390/jcm15010375 - 4 Jan 2026

Viewed by 469

Abstract

Background/Objectives: Investigating how placement of a contralateral breast implant in the context of unilateral implant-based breast reconstruction influences aesthetic and patient-reported outcomes. Methods: A retrospective analysis was performed on a single-center prospectively maintained database (January 2021–March 2025) including patients who underwent [...] Read more.

Background/Objectives: Investigating how placement of a contralateral breast implant in the context of unilateral implant-based breast reconstruction influences aesthetic and patient-reported outcomes. Methods: A retrospective analysis was performed on a single-center prospectively maintained database (January 2021–March 2025) including patients who underwent unilateral implant-based breast reconstruction in association with a contralateral implant placement or not. Exclusion criteria were bilateral implant-based reconstruction or autologous reconstruction, follow-up of less than 6 months and missing data. Demographics and complications were analyzed. Aesthetic outcomes were evaluated by independent blinded surgeons using the Kroll Scale, patient satisfaction was investigated with the BREAST-Q Reconstruction Module v2.0. Statistical analysis used the Student’s t-test, Multivariate regression analysis and Mann–Whitney U test with significance set at p < 0.05. Results: The study group included 21 patients (40.4%) who received a contralateral implant, while the control group included 31 patients (59.6%) who did not receive a contralateral implant. Patients who received contralateral implants showed a significant improvement in cosmetic outcomes evaluated with the Kroll Scale and a raw increment, without statistical significance, in BREAST-Q scores in all subsections investigated (Psychosocial well-being, Sexual well-being and Satisfaction with breasts). Conclusions: Placing a contralateral breast implant in the context of unilateral implant-based breast reconstruction significantly improves aesthetic outcomes and correlates with higher patient satisfaction scores for the reconstructed breast, compared to placing no contralateral implant, without increasing the overall complication rate. Full article

(This article belongs to the Special Issue Clinical Advances of Breast Surgery and Reconstruction)

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13 pages, 962 KB

Open AccessArticle

Diagnostic Performance of HbA1c for Detecting OGTT-Diagnosed Diabetes in Obese Individuals with Suspected Prediabetes

by Abdullah Budak, Ihsan Solmaz, Ömer Faruk Alakuş and Bilgin Bahadır Başgöz

J. Clin. Med. 2026, 15(1), 374; https://doi.org/10.3390/jcm15010374 - 4 Jan 2026

Viewed by 673

Abstract

Background: We aimed to investigate the diagnostic performance between the oral glucose tolerance test (OGTT) and HbA1c in diagnosing prediabetes and diabetes among obese individuals, and to evaluate the diagnostic performance of HbA1c for detecting OGTT-defined diabetes in obese individuals referred for evaluation [...] Read more.

Background: We aimed to investigate the diagnostic performance between the oral glucose tolerance test (OGTT) and HbA1c in diagnosing prediabetes and diabetes among obese individuals, and to evaluate the diagnostic performance of HbA1c for detecting OGTT-defined diabetes in obese individuals referred for evaluation of suspected prediabetes. Methods: Individuals with prediabetes were included between 1 January 2020 and 31 December 2022. Participants were categorized as mildly, moderately, morbidly, or super obese based on body mass index (BMI). According to the 75 g OGTT results, patients were classified into three groups: isolated impaired fasting glucose (IFG), combined IFG + impaired glucose tolerance (IGT), and overt type 2 diabetes mellitus (T2DM). The threshold HbA1c value for T2DM diagnosis in obese patients was determined based on OGTT outcomes. Results: Of the 139 prediabetic obese patients included, 115 (82.7%) were female, with a mean age of 45.18 ± 11.74 years. Based on BMI, 34 patients (24.5%) were mildly obese, 41 (29.5%) moderately obese, 49 (35.3%) morbidly obese, and 15 (10.8%) super obese. According to the 75 g OGTT results, 37.4% (n = 52) had isolated IFG, 45.3% (n = 63) had combined IFG + IGT, and 17.3% (n = 24) had overt T2DM. A weak–moderate positive correlation was observed between HbA1c and fasting blood glucose (Spearman’s rho = 0.263, p = 0.002). ROC–AUC analysis showed that HbA1c had significant discriminatory power in detecting T2DM diagnosed by the 75 g OGTT (AUC = 0.881, 95% CI: 0.816–0.946, p < 0.001). The optimal HbA1c cut-off was 6.15%, with 83.3% sensitivity and 80% specificity. The positive predictive value was 46.1%, and the negative predictive value was 95.8%. Conclusions: An HbA1c threshold of 6.15% demonstrated optimal performance for detecting OGTT-defined diabetes in obese individuals with suspected prediabetes. This value should not be interpreted as a population-wide diagnostic threshold. These findings indicate that HbA1c may serve as a useful screening tool to identify obese individuals who warrant confirmatory OGTT testing, rather than as a stand-alone diagnostic criterion. Further large-scale studies are warranted to confirm these results and support future clinical guidelines. Full article

(This article belongs to the Special Issue Clinical Advances in Diabetes, Obesity, and Hypertension)

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16 pages, 675 KB

Open AccessSystematic Review

Clinical and Laboratory Performance of ACTIVA BioACTIVE Restorative in Primary Teeth: A Systematic Review of Pediatric Evidence

by Malina Popa, Stefania Dinu, Magda Mihaela Luca, Bogdan Andrei Bumbu, Edita Maghet and Romina Georgiana Bita

J. Clin. Med. 2026, 15(1), 373; https://doi.org/10.3390/jcm15010373 - 4 Jan 2026

Cited by 2 | Viewed by 767

Abstract

Background and Objectives: ACTIVA BioACTIVE Restorative is a resin–ionomer hybrid marketed as a bioactive material for pediatric restorations, yet its specific performance in primary teeth has not been systematically synthesized. The study aim was to evaluate clinical and laboratory outcomes of ACTIVA in [...] Read more.

Background and Objectives: ACTIVA BioACTIVE Restorative is a resin–ionomer hybrid marketed as a bioactive material for pediatric restorations, yet its specific performance in primary teeth has not been systematically synthesized. The study aim was to evaluate clinical and laboratory outcomes of ACTIVA in primary dentition compared with established restorative materials. Methods: Following a PRISMA-aligned, OSF-registered protocol, PubMed, Scopus, and Web of Science were searched to 18 October 2025 for full-text clinical trials and in vitro studies involving ACTIVA in primary teeth or primary dentin. Eligible designs included randomized or prospective clinical studies and standardized in vitro experiments. Primary outcomes were clinical and radiographic success; secondary outcomes included placement time, shear bond strength, and calcium-ion release. Results: Three randomized clinical trials (86 children, 305 restorations) and one in vitro study met the inclusion criteria. At 12 months, clinical success with ACTIVA ranged from 97.5 to 97.8% versus 95.0–97.8% for bulk-fill and conventional composites. At 24 months, a split-mouth trial reported clinical success of 93.0% for ACTIVA and 95.3% for compomer, with radiographic success of 86.0% and 88.3%, respectively, remaining within the predefined non-inferiority margin. ACTIVA required a mean of 2.4 ± 0.6 min less placement time than compomer. In vitro, shear bond strength to primary dentin was higher for ACTIVA than for an RMGIC (4.29 ± 0.65 vs. 2.47 ± 0.32 MPa), with greater calcium-ion release at 21 days (0.77 ± 0.13 vs. 0.53 ± 0.12 ppm). Conclusions: Within 1–2 years of follow-up, ACTIVA shows clinical performance in primary molars comparable to compomer, bulk-fill, and conventional composites, while offering shorter placement time and favorable bio-interactive behavior. Full article

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

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21 pages, 2571 KB

Open AccessArticle

Propranolol Reduces Epistaxis in Hereditary Hemorrhagic Telangiectasia: A Large Retrospective Study

by Marcelo Martín Serra, Vanina Pagotto, Luisa Maria Botella and Carmelo Bernabeu

J. Clin. Med. 2026, 15(1), 372; https://doi.org/10.3390/jcm15010372 - 4 Jan 2026

Viewed by 630

Abstract

Background/Objectives: Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular dysplasia characterized by recurrent epistaxis, anemia, and visceral arteriovenous malformations. Epistaxis is the most frequent and disabling manifestation, with limited effective pharmacological options. Propranolol, a non-selective beta-blocker with vasoconstrictive and antiangiogenic properties, has [...] Read more.

Background/Objectives: Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular dysplasia characterized by recurrent epistaxis, anemia, and visceral arteriovenous malformations. Epistaxis is the most frequent and disabling manifestation, with limited effective pharmacological options. Propranolol, a non-selective beta-blocker with vasoconstrictive and antiangiogenic properties, has shown benefit in other vascular anomalies but remains scarcely studied in HHT. This study aimed to evaluate the effect of oral propranolol on nasal bleeding in patients with HHT. Methods: A retrospective observational study including 151 adults with HHT (44 treated with propranolol, 107 untreated) was conducted using data from an Institutional HHT Registry from a referral center. Baseline demographic and clinical variables were recorded. Outcomes at 6 months included changes in hemoglobin, adherence to nasal hygiene, use of bleeding-related therapies, and improvement in epistaxis frequency and intensity according to the Sadick–Bergler scale. Logistic regression models were adjusted for confounders and indication bias using inverse probability of treatment weighting (IPTW). Results: After IPTW adjustment, propranolol was significantly associated with reduced frequency of epistaxis (adjusted OR: 3.8; 95% CI: 1.3–11.2; p = 0.016), while no effect was observed on intensity. Hemoglobin levels increased modestly in both groups without a significant difference. Patients without propranolol showed greater antifibrinolytic use, whereas adherence to nasal care remained stable among treated patients. Conclusions: Oral propranolol reduced nasal bleeding frequency in HHT, even among patients with greater baseline severity. Given its accessibility, safety, and potential to lessen treatment burden, it may represent a valuable adjunct therapy. This study represents the largest cohort of HHT patients treated with propranolol reported to date. Randomized trials including standardized bleeding scores and patient-reported outcomes are warranted to confirm clinical and quality-of-life benefits. Full article

(This article belongs to the Special Issue Hereditary Hemorrhagic Telangiectasia: Recent Advances and Future Challenges—2nd Edition)

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