Journal of Clinical Medicine

16 pages, 992 KB

Open AccessArticle

The Clinical, Histological, and Genetic Spectrum of RYR1 Variants—A Multi-Center Israeli Cohort Study

by Mira Ginsberg, Marina Michelson, Sharon Aharoni, Liora Sagie, Yael Michaeli, Ditza Rotenberg, Vitaly Finkelshtein, Keren Yosovich, Zohar Argov, Andrea Nissenkorn, Dorit Lev, Menachem Sadeh and Ron Dabby

J. Clin. Med. 2026, 15(4), 1388; https://doi.org/10.3390/jcm15041388 (registering DOI) - 10 Feb 2026

Abstract

Background: Variants in the ryanodine receptor 1 (RYR1) gene have been linked to a range of disorders, from congenital myopathy to adult-onset manifestations, with phenotypes varying from mild to severe. Methods: A retrospective review was conducted on an Israeli [...] Read more.

Background: Variants in the ryanodine receptor 1 (RYR1) gene have been linked to a range of disorders, from congenital myopathy to adult-onset manifestations, with phenotypes varying from mild to severe. Methods: A retrospective review was conducted on an Israeli cohort of 36 individuals with RYR1 variants, identified through genetic testing as part of a national collaboration among multiple pediatric and adult neuromuscular clinics. Clinical features, molecular data, laboratory results, electromyographic findings, and muscle histology were analyzed. Each variant was classified according to its respective domain within the RYR1 gene. Results: Thirty-six cases were included in the analysis; 31 were from 11 unrelated families, and 5 were sporadic. Nine individuals were asymptomatic with normal CK levels. Most of the 27 affected patients presented with variable degrees of perinatal weakness, often accompanied by respiratory impairment or arthrogryposis. Weakness was predominantly proximal, with clinical courses that included deterioration, improvement, or stabilization. Three cases of King–Denborough syndrome were identified. Additional presentations included malignant hyperthermia and, in isolated cases, periodic paralysis. Muscle biopsies demonstrated considerable histologic heterogeneity, including fiber-size variation, internal nuclei, multiminicores, and fibrosis or dystrophic features. The pathogenic RYR1 variants included five compound-heterozygous genotypes, two homozygous variants, and two heterozygous variants. There was a positive correlation between variants located in the Bsol domain and disease severity. Conclusions: This cohort confirms and expands the clinical and histological diversity associated with RYR1 variants in Israel. Variants in the Bsol domain appear to be indicative of disease severity. Full article

(This article belongs to the Section Clinical Neurology)

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12 pages, 340 KB

Open AccessArticle

Five-Year Persistence of Vedolizumab in Crohn’s Disease: Results from a Real-World Cohort

by Marc Harb, Vinciane Muls, Alice Hoyois and Jennifer Aoun

J. Clin. Med. 2026, 15(4), 1387; https://doi.org/10.3390/jcm15041387 (registering DOI) - 10 Feb 2026

Abstract

Background: Vedolizumab (VDZ) is an α4β7 anti-integrin monoclonal antibody effective in Crohn’s disease (CD). While its short- and mid-term efficacy is well established, real-world data on long-term outcomes beyond 3 years are scarce. Recent studies suggest a progressive decline in persistence rates [...] Read more.

Background: Vedolizumab (VDZ) is an α4β7 anti-integrin monoclonal antibody effective in Crohn’s disease (CD). While its short- and mid-term efficacy is well established, real-world data on long-term outcomes beyond 3 years are scarce. Recent studies suggest a progressive decline in persistence rates after 2 to 3 years, with very limited data beyond this period. The primary objective of this study was to evaluate the 5-year persistence of VDZ. Secondary objectives were to describe clinical, biological, and endoscopic responses at 2 years among patients remaining on treatment, and to identify predictors of long-term persistence, including the baseline Clinical Decision Support Tool (CDST) score. Methods: We conducted a retrospective observational study which included 60 adult patients with CD treated with VDZ before April 2025. Collected baseline variables included age, sex, BMI, smoking status, disease duration and location, prior biologic exposure, and CDST score. Treatment persistence was evaluated at 5 years. Clinical, biological, and endoscopic responses were assessed at 2 years. A global response was then defined as the achievement of a clinically significant improvement, normalization or marked reduction in inflammatory biomarkers, and endoscopic improvement. Predictors of persistence were also analyzed. Results: The mean age of this cohort was 45.4 ± 15.2 years, mean disease duration was 12.7 ± 10.1 years, and mean CDST score was calculated at 20.6 ± 2.7. At 5 years, 23/41 patients (56.1%) remained on VDZ therapy. Persistence was significantly associated with male sex (65.2% vs. 27.8%), longer disease duration (215 vs. 106 months), absence of rheumatologic manifestations (13.0% vs. 44.4%), and clinico-biological response at 12 months (65.2% vs. 30.8%). At 24 months, a global response was observed in all patients persisting at 5 years compared to 22.2% of those who discontinued (p < 0.001). At 2 years, 39/51 patients (76.5%) remained on VDZ. Persistence was associated with longer disease duration (189 vs. 75 months), male sex (61.5% vs. 25.0%), and absence of isolated colonic disease (0% vs. 16.7%). A global response at 2 years was achieved by 89.7% of persistent patients compared with none of the non-persistent group (p < 0.001). The CDST, uniformly elevated in this cohort, did not discriminate between persistent and non-persistent patients, but reflected appropriate initial patient selection. Conclusions: This real-world study documents 5-year outcome data on VDZ persistence in Crohn’s disease, a duration infrequently studied, with 56% of patients maintaining treatment. Early response at 12 and 24 months emerged as a key determinant of long-term persistence, highlighting the value of assessing 2-year outcomes to identify durable responders. Although not discriminatory in this homogeneous cohort, the CDST score emphasizes the potential role of predictive tools in guiding personalized therapeutic strategies. These results contribute to defining the long-term role of VDZ in the management of CD. Full article

(This article belongs to the Special Issue Inflammatory Bowel Disease: Clinical Pathogenesis and Management Strategies)

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15 pages, 690 KB

Open AccessArticle

Impact of Physiotherapy Based on the Rigo Concept and Whole-Body Vibration on Sagittal Spinal Curvatures, Trunk Symmetry, and the Angle of Trunk Rotation in Adolescents with Idiopathic Scoliosis

by Paulina Ewertowska, Marta Flis, Joanna Kujałowicz, Borislav Chongov and Dariusz Czaprowski

J. Clin. Med. 2026, 15(4), 1386; https://doi.org/10.3390/jcm15041386 (registering DOI) - 10 Feb 2026

Abstract

Background: Conservative treatment for adolescent idiopathic scoliosis (AIS) includes physiotherapeutic scoliosis-specific exercises (PSSE) and bracing. One PSSE-based approach is the Rigo Concept, which emphasizes three-dimensional (3D) postural correction, expansion techniques, muscle activation, and postural integration. Recently, increasing interest has been directed toward incorporating [...] Read more.

Background: Conservative treatment for adolescent idiopathic scoliosis (AIS) includes physiotherapeutic scoliosis-specific exercises (PSSE) and bracing. One PSSE-based approach is the Rigo Concept, which emphasizes three-dimensional (3D) postural correction, expansion techniques, muscle activation, and postural integration. Recently, increasing interest has been directed toward incorporating whole-body vibration (WBV) into physiotherapy. WBV is a reflex-based neuromuscular training method shown to improve muscle strength and power and enhance proprioception, which may be beneficial in the treatment of AIS. Objectives: This study aimed to assess the effects of physiotherapy based on the Rigo Concept combined with WBV on sagittal spinal curvatures, trunk symmetry, and the angle of trunk rotation (ATR) in girls with AIS. Methods: This prospective controlled experimental study included 45 girls (12.8 ± 1.7 years) with AIS who participated in a 5-day physiotherapy session based on the Rigo Concept. Of these, 22 participants additionally received WBV using a Galileo Med 35 platform (3 × 3 min/day, frequency 25 Hz, peak-to-peak displacement 2 mm), forming the Rigo–WBV group. The remaining participants received the Rigo Concept alone (Rigo–ONLY). Participants were allocated to the study groups using a quasi-random method based on the order of enrollment. ATR was defined as the primary endpoint, while thoracic kyphosis, lumbar lordosis, sacral slope, coronal balance, and scapular position were considered secondary outcomes. All outcomes were assessed before and after the intervention. Results: Neither the Rigo–WBV nor the Rigo–ONLY intervention affected sagittal spinal curvatures (p > 0.05). Coronal balance improved in both the Rigo–WBV (Δ 0.5 cm, p < 0.001) and Rigo–ONLY groups (Δ 0.4 cm, p = 0.005). In the Rigo–ONLY group, an improvement in scapular height asymmetry was observed (Δ 1.1°, p = 0.010). Following the Rigo–WBV intervention, ATR decreased in the main thoracic (Δ 1.9°, p < 0.001), thoracolumbar (Δ 1.9°, p < 0.001), lumbar curve (Δ 2.1°, p < 0.001), and pelvis (Δ 1.0°, p < 0.001). In the Rigo–ONLY group, a reduction in ATR was observed only in the thoracolumbar curve (Δ 1.9°, p < 0.001). Conclusions: In terms of clinical and postural changes, five-day physiotherapy based on the Rigo Concept, with or without WBV, does not influence sagittal spinal curvatures in girls with AIS. Both interventions may improve coronal balance. Moreover, the Rigo Concept combined with WBV may reduce ATR. Full article

(This article belongs to the Section Clinical Rehabilitation)

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10 pages, 492 KB

Open AccessArticle

Undiagnosed Diabetes in Metabolically Unhealthy Normal Weight Adults: A Cross-Sectional Analysis of National Health and Nutrition Examination Survey Cycle 2017–2020 in the United States

by Sándor Pál and Annamária Sepsey

J. Clin. Med. 2026, 15(4), 1385; https://doi.org/10.3390/jcm15041385 (registering DOI) - 10 Feb 2026

Abstract

Background/Objectives: Although body mass index (BMI) is a conventional screening tool for type 2 diabetes mellitus (T2D), its reliability as a sole indicator of metabolic health is controversial, and the metabolic profile of a subset of individuals with normal BMI is indicative [...] Read more.

Background/Objectives: Although body mass index (BMI) is a conventional screening tool for type 2 diabetes mellitus (T2D), its reliability as a sole indicator of metabolic health is controversial, and the metabolic profile of a subset of individuals with normal BMI is indicative of obesity-related complications. This study aimed to estimate the prevalence and predictors of undiagnosed diabetes among Metabolically Unhealthy Normal Weight (MUNW) adults. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2017–March 2020 were analyzed. Normal weight adults (BMI 18.5–24.9 kg/m²) were categorized into Metabolically Healthy (MHNW) and Unhealthy (MUNW) phenotypes based on the presence of ≥2 metabolic risk factors, including elevated blood pressure, triglycerides, waist circumference, or low HDL cholesterol. The primary outcome was undiagnosed diabetes, defined as HbA1c ≥ 6.5% or Fasting Plasma Glucose ≥ 126 mg/dL. Results: The study population represented approximately 60 million US adults. The prevalence of undiagnosed diabetes was nearly four times higher in the MUNW group (4.84%) compared to the MHNW group (1.28%). In multivariable logistic regression analysis, age and race emerged as significant predictors. Notably, Asian adults exhibited a significantly higher risk of undiagnosed diabetes (OR 6.10; 95% CI: 1.32–28.2) compared to White adults, independent of metabolic phenotype. Conclusions: Reliance solely on BMI may overlook undiagnosed diabetes in normal-weight adults, particularly those with metabolic clustering or of Asian descent. These findings underscore the importance of multidimensional risk assessment integration into preventive care, optimizing clinical management. Full article

(This article belongs to the Special Issue Obesity-Related Metabolic and Cardiovascular Disorders)

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17 pages, 1887 KB

Open AccessArticle

Automated Joint Space Width Assessment in Patients Treated for Juvenile Osteochondritis Dissecans of the Distal Femur: A Cross-Sectional Study and Systematic Review of the Literature

by Matthias Pallamar, Kaveh Same, Jennyfer Angel Mitterer, Sebastian Simon, Jan Philipp Nolte, Sebastian Farr, Jochen Hofstaetter and Catharina Chiari

J. Clin. Med. 2026, 15(4), 1384; https://doi.org/10.3390/jcm15041384 (registering DOI) - 10 Feb 2026

Abstract

Background/Objectives: Juvenile osteochondritis dissecans (JOCD) of the knee is commonly treated using conservative or joint-preserving surgical techniques. While clinical outcomes are generally favorable, the risk of early cartilage degeneration remains unclear. Joint space width (JSW) on weight-bearing radiographs serves as an indirect marker [...] Read more.

Background/Objectives: Juvenile osteochondritis dissecans (JOCD) of the knee is commonly treated using conservative or joint-preserving surgical techniques. While clinical outcomes are generally favorable, the risk of early cartilage degeneration remains unclear. Joint space width (JSW) on weight-bearing radiographs serves as an indirect marker of cartilage health. Artificial intelligence (AI)-based JSW assessment may enable sensitive and reproducible detection of early degenerative changes. Methods: This cross-sectional feasibility study included 21 skeletally immature patients treated for JOCD of the distal femur between 2002 and 2017. Treatment modalities comprised conservative management, retrograde drilling, and fragment refixation. Fully automated JSW measurements were performed on standardized anteroposterior knee radiographs using a validated AI-based software IB Lab KOALA™, Version 2.4. JSW of the affected compartment was compared with the contralateral knee and between treatment groups. Clinical outcomes were assessed using the Lysholm Knee Scoring Scale and the International Knee Documentation Committee (IKDC) score. Additionally, a systematic review of the literature on post-treatment degenerative changes following OCD therapy was conducted according to PRISMA guidelines. Results: Compared with manually reviewing images, the software IB Lab KOALA™, Version 2.4 as easy to implement. AI-based analysis revealed no significant differences in JSW between the affected and contralateral knees, nor between treatment modalities. Average JSW exceeded 6 mm in all groups after a median follow-up of 64 (min. 27, max. 177) months. Clinical scores were high and comparable across treatments. A moderate positive correlation was observed between the JSW and Lysholm score, while increasing age and longer follow-up were associated with a reduced JSW. The systematic review identified ten relevant studies, reporting generally favorable long-term clinical outcomes with a low but present risk of osteoarthritis progression. Conclusions: Our AI-based analysis showed no differences in JSW between conservative and joint-preserving surgical treatments of JOCD in the follow-up. This technology can provide a valuable tool for standardized and sensitive radiographic monitoring in young patients. Full article

(This article belongs to the Section Clinical Pediatrics)

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22 pages, 4820 KB

Open AccessArticle

Machine Learning-Identified Potential Interaction Between Clazosentan and Nicardipine in Patients with Subarachnoid Hemorrhage

by Yusuke Inoue, Masahito Katsuki, Toshikazu Hidaka, Junichiro Ochiai, Yuichiro Kawamoto, Daizo Ishii, Katsumi Takizawa, Hirofumi Nakatomi, Masaki Chin, Motohiro Morioka, Hiroki Kurita, Kaima Suzuki, Takatoshi Sorimachi, Koreaki Irie, Ichiro Nakahara, Nobutaka Horie and Fusao Ikawa

J. Clin. Med. 2026, 15(4), 1383; https://doi.org/10.3390/jcm15041383 (registering DOI) - 10 Feb 2026

Abstract

Background/Objectives: Subarachnoid hemorrhage (SAH) is frequently complicated by cerebral vasospasm (VS). Clazosentan has reduced VS in Japanese studies but shown inconsistent efficacy in Western trials. We hypothesized that clinical and pharmacologic interactions may influence its effectiveness. Methods: We analyzed the multicenter [...] Read more.

Background/Objectives: Subarachnoid hemorrhage (SAH) is frequently complicated by cerebral vasospasm (VS). Clazosentan has reduced VS in Japanese studies but shown inconsistent efficacy in Western trials. We hypothesized that clinical and pharmacologic interactions may influence its effectiveness. Methods: We analyzed the multicenter “Database of Cohort Study for Outcome of SAH In Japan” (DCI Japan) registry, prospectively collected from 2020 to 2023, to assess associations between clazosentan use, VS prevention, functional outcomes, and potential interactions in adults with aneurysmal SAH (aSAH) treated by surgical clipping or endovascular coiling within 4 days of onset. Outcomes included angiographic VS (AVS), symptomatic VS (SVS), cerebral infarction, and modified Rankin Scale (mRS) scores at discharge and at 6 months. Predictors and interactions were first screened using univariable analysis and Light Gradient Boosting Machine, then evaluated via multivariable logistic regression. Results: Among 544 patients (mean age 65.2 ± 14.2 years; 71.5% female), 34.0% received clazosentan. AVS, SVS, and cerebral infarction occurred in 20.6%, 16.0%, and 22.4%, respectively. Poor outcomes (mRS 3–6) were observed in 48.8% at discharge and 33.7% (137/406) at 6 months. Clazosentan use was associated with reduced odds of AVS (OR 0.27, 95% CI [0.11–0.69]), SVS (OR 0.15 [0.04–0.64]), and poor 6-month outcome (OR 0.08 [0.01–0.68]). A potential interaction with nicardipine was linked to higher odds of AVS (OR 1.85 [1.43–2.65]). Conclusions: Clazosentan was associated with reduced VS and improved 6-month outcomes after aSAH, although concomitant nicardipine may attenuate its prophylactic effectiveness against AVS. Full article

(This article belongs to the Special Issue Clinical Updates and Perspectives on Subarachnoid Hemorrhage: 2nd Edition)

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10 pages, 331 KB

Open AccessArticle

Diagnostic Utility of Skin Prick Test Ratios and Specific IgE in Predicting Egg White Allergy: Reducing the Need for Oral Food Challenges in Children

by Filiz Demir Şahin, Ozan Kapçay, Mehmet Kılıç and Hilal Şahin Sindi

J. Clin. Med. 2026, 15(4), 1382; https://doi.org/10.3390/jcm15041382 (registering DOI) - 10 Feb 2026

Abstract

Background: Skin prick testing (SPT) and serum egg white–specific IgE (sIgE) support oral food challenge (OFC) decisions in suspected egg allergy, but the incremental value of histamine-normalized SPT indices remains uncertain. Methods: In this single-center retrospective study, 105 egg-sensitized children underwent [...] Read more.

Background: Skin prick testing (SPT) and serum egg white–specific IgE (sIgE) support oral food challenge (OFC) decisions in suspected egg allergy, but the incremental value of histamine-normalized SPT indices remains uncertain. Methods: In this single-center retrospective study, 105 egg-sensitized children underwent clinically indicated OFC. Commercial egg white SPT, prick-to-prick testing with fresh egg white, histamine controls, and serum egg white–specific IgE were assessed. Discriminatory performance was evaluated by ROC analysis, and independent predictors of OFC positivity were identified using multivariable logistic regression. Results: OFC was positive in 23 of 105 children (21.9%). Egg white SPT wheal diameter, the prick-to-histamine ratio, and serum egg white–specific IgE (sIgE) levels were significantly higher in OFC-positive patients (all p < 0.001). ROC analysis demonstrated moderate-to-good discrimination for both sIgE (AUC = 0.767) and the prick-to-histamine ratio (AUC = 0.786), without clear superiority of normalized indices. In multivariable logistic regression analysis, only absolute egg white SPT wheal diameter (adjusted OR 1.41 per 1 mm increase; 95% CI 1.13–1.77) and serum egg white–specific IgE level (adjusted OR 31.86 per 100 kUA/L increase; 95% CI 1.60–636.15) remained independent predictors of OFC positivity. Conclusions: Absolute egg white SPT wheal diameter and serum sIgE independently predict OFC outcomes in egg-sensitized children. Histamine-normalized indices did not provide added value over wheal size alone. These findings support a probabilistic, context-based use of test results to inform selective OFC planning rather than replace OFC. Full article

(This article belongs to the Section Immunology & Rheumatology)

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12 pages, 1567 KB

Open AccessArticle

Clinical Outcomes of Injectable Porcine Collagen in Diabetic Patients with Achilles Tendinopathy: A Retrospective Study

by Giacomo Placella, Niccolò Biavardi, Mattia Alessio Mazzola and Vincenzo Salini

J. Clin. Med. 2026, 15(4), 1381; https://doi.org/10.3390/jcm15041381 (registering DOI) - 10 Feb 2026

Abstract

Background/Objective: Achilles tendinopathy (AT) is a disabling condition, and treatment options are limited in patients in whom corticosteroid injections are discouraged or contraindicated, including individuals with diabetes. Collagen injections have been proposed as a conservative option; however, clinical evidence in diabetic populations [...] Read more.

Background/Objective: Achilles tendinopathy (AT) is a disabling condition, and treatment options are limited in patients in whom corticosteroid injections are discouraged or contraindicated, including individuals with diabetes. Collagen injections have been proposed as a conservative option; however, clinical evidence in diabetic populations remains limited. This study aims to describe pain and functional outcomes after peritendinous collagen injections in diabetic patients with chronic Achilles tendinopathy. Methods: Twenty-two diabetic patients with ultrasound-confirmed degenerative Achilles tendinopathy refractory to conservative management were retrospectively included and split into two groups according to AT type: insertional (IAT) and non-insertional/midportion (NIAT). All patients received five weekly ultrasound-guided peritendinous collagen injections. Outcomes included VAS assessed at baseline, after the second injection, at 1 month, and at 6 months; VISA-A at baseline and 6 months; return-to-work (RTW) time; and adverse events. Baseline variables included BMI, HbA1c, symptom duration, and previous treatments. Analyses were based on descriptive statistics and within-group comparisons over time. Results: All patients completed the treatment protocol, and no adverse events were recorded. Pain significantly improved over follow-up in both subgroups. Mean VAS decreased from baseline to 6 months (mean ΔVAS: 5.1 in IAT and 4.4 in NIAT; p = 0.001 for within-group change). VISA-A also improved at 6 months (mean ΔVISA-A: 32.78 in IAT and 38.97 in NIAT; p < 0.0001). Median RTW was 37 days in IAT and 35 days in NIAT (p > 0.05). No significant between-group differences were observed for VAS or VISA-A changes (p > 0.05). Conclusions: In this uncontrolled retrospective case series, peritendinous collagen injections were feasible and well-tolerated in diabetic patients with Achilles tendinopathy and were associated with clinically relevant improvements in pain and functional outcomes at 6 months. These findings are hypothesis-generating and warrant confirmation in prospective controlled studies. Full article

(This article belongs to the Special Issue Molecular Injection Therapy in Orthopedic and Musculoskeletal Disorders: Conservative Approaches and Innovative Treatments)

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17 pages, 1088 KB

Open AccessArticle

Forecasting Stone-Free Status Following Percutaneous Nephrolithotomy Utilizing Explainable Machine Learning

by Resul Çiçek, İbrahim Topçu, Bulut Dural, İpek Balıkçı Çiçek, Murat Yılmaz and Cemil Çolak

J. Clin. Med. 2026, 15(4), 1380; https://doi.org/10.3390/jcm15041380 (registering DOI) - 10 Feb 2026

Abstract

Background: This study aimed to create and evaluate explainable machine learning models for forecasting postoperative stone-free status following percutaneous nephrolithotomy (PNL) utilizing a substantial clinical cohort. Methods: This retrospective single-center analysis encompassed 2144 adult patients who received PNL from 2010 to 2024. We [...] Read more.

Background: This study aimed to create and evaluate explainable machine learning models for forecasting postoperative stone-free status following percutaneous nephrolithotomy (PNL) utilizing a substantial clinical cohort. Methods: This retrospective single-center analysis encompassed 2144 adult patients who received PNL from 2010 to 2024. We employed clinical, radiographic, stone-related, and surgical data to train four supervised machine learning models: Extreme Gradient Boosting (XGBoost), Random Forest, Light Gradient Boosting Machine (LightGBM), and Adaptive Boosting (AdaBoost). We used the Synthetic Minority Oversampling Technique exclusively on the training set to fix the class imbalance. We assessed the model’s accuracy, precision, recall, F1-score, and area under the receiver operating characteristic curve (ROC–AUC) to see how well it worked. SHapley Additive exPlanations (SHAP) were used to measure explainability. Results: The total stone-free rate was 84.8%. XGBoost had the best predictive performance of the models tested, with an accuracy of 0.916 and a ROC–AUC of 0.975. LightGBM was close behind. Random Forest and AdaBoost had relatively inferior performance. SHAP analysis identified anatomical anomalies as demonstrated the strongest association with stone-free outcomes. The size of the access sheath and the number of stones were next. Other parameters that were identified by SHAP as important contributors to model predictions were the placement of the stone, Guy’s Stone Score, the length of the operation, and the density of the stone. These feature associations demonstrated clinical coherence with established knowledge in surgical practice. Conclusions: Explainable machine learning algorithms, especially XGBoost, can accurately predict stone-free outcomes following PNL in a way that makes sense to doctors. The incorporation of SHAP improves transparency and facilitates the prospective application of these models as decision-support instruments in personalized surgical planning. Full article

(This article belongs to the Topic The Use of New Technologies, Artificial Intelligence and Digital Twin in Health and Clinical Practice)

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43 pages, 1343 KB

Open AccessReview

Curative Approach to the Treatment of Beta-Thalassemia and Sickle Cell Disease with Hematopoietic Stem Cell Transplantation

by Ugo Testa, Germana Castelli and Elvira Pelosi

J. Clin. Med. 2026, 15(4), 1379; https://doi.org/10.3390/jcm15041379 (registering DOI) - 10 Feb 2026

Abstract

β-thalassemia and sickle cell disease are two inherited hematological diseases due to defective hemoglobin synthesis or to the production of hemoglobin with altered properties. These two conditions have prolonged survival with modern support therapies, albeit life-long, complex, expensive and resource-consuming. Studies carried out [...] Read more.

β-thalassemia and sickle cell disease are two inherited hematological diseases due to defective hemoglobin synthesis or to the production of hemoglobin with altered properties. These two conditions have prolonged survival with modern support therapies, albeit life-long, complex, expensive and resource-consuming. Studies carried out in the last three decades have shown that allogeneic hematopoietic stem cell transplantation (allo-HSCT) and gene therapy may offer a curative approach for these diseases. Allo-HSCT should be performed early in life to reduce disease-related complications like irreversible tissue damage due to iron overload in patients with transfusion-dependent β-thalassemia (TDT) and systemic vasculopathy in patients with sickle cell disease (SCD). HSCTs from a matched-sibling donor or a matched-unrelated donor represent the best therapeutic option; however, haploidentical HSCT in both TDT and SCD is now increasingly performed as a valuable and viable option for a larger number of these patients. An alternative curative strategy is based on gene therapy. These curative approaches, particularly those of gene therapy, are available only in a part of the world. Gene therapy diffusion is strongly limited by its high technological and infrastructure requirements and its very high cost. Criteria must be defined for the optimal selection of TDT and SCD patients for allo-HSCT or gene therapy. Full article

(This article belongs to the Section Hematology)

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12 pages, 1326 KB

Open AccessSystematic Review

Neuropathic Pain in Neuromyelitis Optica Spectrum Disorders: Prevalence and Management Strategies—A Systematic Review and Meta-Analysis

by Alexandra Akrivaki, Vasileios Giannopapas, Evangelia-Makrina Dimitriadou, Dimitrios Tzanetakos, Dimitrios Kitsos, Konstantina Stavrogianni, Athanasios K. Chasiotis, Georgios Tsivgoulis, John S. Tzartos and Sotirios Giannopoulos

J. Clin. Med. 2026, 15(4), 1378; https://doi.org/10.3390/jcm15041378 (registering DOI) - 10 Feb 2026

Abstract

Introduction: Neuropathic pain (NP) in neuromyelitis optica spectrum disorder (NMOSD) represents a significant and often under-recognized complication arising from central nervous system (CNS) lesions. Unlike other demyelinating disorders, NMOSD involves a distinct immunopathogenesis primarily driven by aquaporin-4 antibodies (AQP4-IgG), leading to severe inflammatory [...] Read more.

Introduction: Neuropathic pain (NP) in neuromyelitis optica spectrum disorder (NMOSD) represents a significant and often under-recognized complication arising from central nervous system (CNS) lesions. Unlike other demyelinating disorders, NMOSD involves a distinct immunopathogenesis primarily driven by aquaporin-4 antibodies (AQP4-IgG), leading to severe inflammatory damage. NP is typically the consequence of inflammatory damage to the spinothalamic tract or dorsal columns, resulting in both acute and chronic pain syndromes. Methods: A systematic review and meta-analysis were conducted following a comprehensive search of Medline and Scopus, identifying nine eligible studies reporting on NP in NMOSD. Results: Pooled prevalence was estimated using a random-effects metaprop meta-analysis with Freeman–Tukey transformation and REML-based heterogeneity estimation. The pooled prevalence of NP among patients with NMOSD was 56.2% (95% CI: 41.7–70.1%; I² = 95.3%, p < 0.001). Sensitivity analysis including only AQP4-IgG⁺ cohorts revealed a prevalence of 63.2% (95% CI: 23.4–94.7%; I² = 98.1%, p < 0.001). No significant difference was found between mixed and AQP4-IgG⁺-only populations (53.05% vs. 63.27%, p = 0.63). Meta-regression showed no significant associations between NP prevalence and age (β = 0.01, p = 0.33) or disability (β = 0.08, p = 0.18). Qualitative synthesis demonstrated an association between thoracic spinal cord lesions and NP, and also indicated that NP was often resistant and refractory to standard pharmacologic therapies. Conclusions: NP affects one in two NMOSD patients, and is associated with thoracic spinal cord lesions. In comparison with multiple sclerosis, NP in NMOSD is primarily structural and immunopathological in origin. Treatment strategies remain inadequate, emphasizing the need for early recognition and a disease-specific therapeutic approach. Full article

(This article belongs to the Special Issue Multiple Sclerosis and Demyelinating Disease: Clinical Treatment and Management)

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17 pages, 7580 KB

Open AccessArticle

Morphogenesis and Topography of the Mesorectal Fascia

by Iulian Alexandru Dogaru, Adrian Daniel Tulin, Iulian Mirel Slavu, Daniela Elena Gheoca Mutu, Mihaly Enyedi, Răzvan Stănciulescu, Cosmin Marian Panțu and Zoran Florin Filipoiu

J. Clin. Med. 2026, 15(4), 1377; https://doi.org/10.3390/jcm15041377 (registering DOI) - 10 Feb 2026

Abstract

Background: First described by Carl Toldt in the late 19th century, the mesorectum has since been a topic of anatomical and surgical debate. Its clinical importance was redefined by Heald’s introduction of Total Mesorectal Excision (TME), nowadays the golden standard in oncologic [...] Read more.

Background: First described by Carl Toldt in the late 19th century, the mesorectum has since been a topic of anatomical and surgical debate. Its clinical importance was redefined by Heald’s introduction of Total Mesorectal Excision (TME), nowadays the golden standard in oncologic rectal surgery. This study aims to elucidate the embryological development and adult anatomy of the mesorectum and the mesorectal fascia, with a focus on clinically significant relations, particularly the peritoneum, and components of the hypogastric plexuses. Methods: We performed anatomical dissections on four 12–15-week-old human fetuses and eight formalin-fixed adult cadavers. In addition, a transverse pelvic section was examined to assess the spatial organization of mesorectal and fascial structures. Results: Our findings confirm the presence of a dorsal mesentery at the rectal level during fetal development, illustrating its transformation into the adult mesorectum. We identified the mesorectal contents in the fetus and examined the course and relations of the superior rectal vessels, hypogastric nerves, and pelvic splanchnic nerves, in both fetal and adult specimens. Conclusions: The observed fetal and adult configurations provide a continuous morphological description of the mesorectum and its compartmental organization within the pelvis. This study enhances the understanding of the mesorectum’s embryology, structure, and vital surgical landmarks. By delineating the so-called ‘Holy plane’ of Heald (the natural avascular plane between the mesorectal and presacral fasciae used during total mesorectal excision) and the delicate connective fibers known surgically as ‘angel’s hair’, which become visible when this plane is correctly entered, rectal and presacral fasciae, and neurovascular elements, provides a comprehensive anatomical framework that may inform surgical plane identification and support future clinical investigations into nerve-sparing rectal surgery. Full article

(This article belongs to the Section General Surgery)

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13 pages, 1280 KB

Open AccessArticle

Association of A1 Segment Morphology with the Rupture Risk and Morphology of Anterior Communicating Artery Aneurysms: A Retrospective, Single-Center Study

by Ilhan Aydin, Neslihan Cavusoglu, Berkay Kef, Asya Gokceli, Efecan Cekic, Sahin Hanalioglu, Egemen Gok, Murad Asilturk and Bulent Timur Demirgil

J. Clin. Med. 2026, 15(4), 1376; https://doi.org/10.3390/jcm15041376 (registering DOI) - 10 Feb 2026

Abstract

Background/Objectives: A1 segment asymmetry, including hypoplasia and aplasia, is a well-recognized anatomical variation associated with altered hemodynamic stress and anterior communicating artery (ACoA) aneurysm formation. However, its influence on subsequent aneurysm rupture risk remains controversial. This study aimed to evaluate the relationship between [...] Read more.

Background/Objectives: A1 segment asymmetry, including hypoplasia and aplasia, is a well-recognized anatomical variation associated with altered hemodynamic stress and anterior communicating artery (ACoA) aneurysm formation. However, its influence on subsequent aneurysm rupture risk remains controversial. This study aimed to evaluate the relationship between A1 segment morphology and aneurysm rupture risk, as well as its association with aneurysm size and morphological complexity. Methods: A retrospective single-institution analysis was conducted on 211 patients treated for ACoA aneurysms between June 2016 and March 2025. A1 segment morphology was assessed using digital subtraction angiography and categorized as symmetric, hypoplastic (diameter < 1 mm or <50% of the contralateral vessel), or aplastic. Demographic, clinical, and radiological variables were recorded. Statistical analyses included univariate comparisons with Bonferroni correction for multiple testing and multivariable logistic regression to identify independent predictors of aneurysm rupture. Results: The study population had a mean age of 54.72 ± 10.97 years, with a male-to-female ratio of 1.24:1 (55.5% male, 44.5% female). Symmetric A1 segments were observed in 49.3% of patients, hypoplastic segments in 31.3%, and aplastic segments in 19.4%. No statistically significant association was identified between A1 morphology and aneurysm rupture rates (p = 0.251) or mean aneurysm diameter (p = 0.996). Univariate analysis demonstrated that younger age (p = 0.006), male sex (p = 0.016), and smoking (p = 0.033) were associated with rupture. However, none of these factors, including A1 morphology, remained independent predictors of rupture in the multivariable logistic regression model. Conclusions: Although A1 segment asymmetry is common in patients with ACoA aneurysms, it does not independently influence rupture risk or aneurysm morphology. Our findings suggest that rupture behavior is driven primarily by dynamic hemodynamic factors rather than static anatomical variations. Full article

(This article belongs to the Special Issue Intracranial Aneurysms: Diagnostics and Current Treatment)

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15 pages, 1204 KB

Open AccessArticle

Evaluation of the Relationship Between Adenomyosis and Cervical Elastography Parameters

by Dilara Sarikaya Kurt, Ahmet Kurt, Sümeyya Duran Kaymak, Berna Turhan, İzzet Özgürlük, Hüseyin Levent Keskin and Kadriye Erdoğan

J. Clin. Med. 2026, 15(4), 1375; https://doi.org/10.3390/jcm15041375 (registering DOI) - 10 Feb 2026

Abstract

Objectives: We aim to investigate cervical biomechanical alterations associated with adenomyosis using shear-wave elastography (SWE), and to explore the discriminative potential of cervical SWE parameters. Methods: In this prospective study, 84 patients with adenomyosis, diagnosed both clinically and by ultrasonography according to the [...] Read more.

Objectives: We aim to investigate cervical biomechanical alterations associated with adenomyosis using shear-wave elastography (SWE), and to explore the discriminative potential of cervical SWE parameters. Methods: In this prospective study, 84 patients with adenomyosis, diagnosed both clinically and by ultrasonography according to the MUSA parameters, and 65 healthy women underwent elastography to the cervix with SWE. Six areas of the cervix were evaluated: anterior and posterior internal os, middle part of the cervix, and external os. Results: The adenomyosis group showed a significantly higher cervical length (27.3 ± 5.5 mm vs. 23.8 ± 4.6 mm), as well as greater anterior (11.3 ± 2.4 mm vs. 9.9 ± 1.3 mm) and posterior (11.3 ± 2.2 mm vs. 10.5 ± 1.8 mm) cervical measurements compared with the controls (p < 0.001). SWE showed higher stiffness measurements for the anterior and posterior internal os (22.3 ± 5.4 kPa and 22.2 ± 4.9 kPa) compared with the controls (15.5 ± 5.8 kPa and 15.7 ± 5.6 kPa, respectively; p < 0.001). Receiver operating characteristic analysis demonstrated high discrimination for these measurements, with area under curve values of 0.804 for the anterior internal os and 0.808 of posterior internal os. Optimal cut-offs were 17.5 kPa (sensitivity 82%, specificity 70%) and 18.5 kPa (sensitivity 81%, specificity 74%). Conclusions: Cervical elastography may serve as a non-invasive adjunctive tool for exploring disease-related biomechanical changes and for supporting imaging-based assessment of adenomyosis. Full article

(This article belongs to the Section Obstetrics & Gynecology)

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18 pages, 1887 KB

Open AccessArticle

Depressive Symptoms, Functional Status, and Cardiovascular Parameters in Patients with Major Depressive Disorder Undergoing Cardiac Rehabilitation While Treated with Vortioxetine: A Prospective Observational Study

by Iván Hoditx Martín-Costa, Rafael Colman, Álvaro García-Amador, Cristian García-Caballero, Jerónimo Acosta-Rueda, Marta Fontán-Esteban and Yerika Martín-Quero

J. Clin. Med. 2026, 15(4), 1374; https://doi.org/10.3390/jcm15041374 (registering DOI) - 10 Feb 2026

Abstract

Background/Objectives: Real-world evidence on the use of vortioxetine within cardiac rehabilitation (CR) programs among patients with major depressive disorder (MDD) remains limited. We aimed to describe the evolution of depressive symptoms, functional status, and selected cardiovascular and biometric parameters in patients with MDD [...] Read more.

Background/Objectives: Real-world evidence on the use of vortioxetine within cardiac rehabilitation (CR) programs among patients with major depressive disorder (MDD) remains limited. We aimed to describe the evolution of depressive symptoms, functional status, and selected cardiovascular and biometric parameters in patients with MDD undergoing CR while receiving vortioxetine in routine clinical practice. Methods: This was a 12-week, prospective, observational study conducted at Clínica Colman (Cádiz, Spain) between July 2022 and July 2024. Adults diagnosed with MDD who were undergoing CR and receiving vortioxetine as part of routine care were included. Depressive symptoms (Hamilton Depression Rating Scale, HAM-D) and functional impairment (Sheehan Disability Scale, SDS) were assessed at baseline and at weeks 3, 7, and 12. Cardiovascular and biometric parameters were measured at baseline and at week 12. Repeated-measures ANOVA and paired t-tests were used for statistical analysis. Results: Forty-nine patients were included (mean age 65.6 years; 41% women). Over the 12-week follow-up period, mean HAM-D and SDS scores decreased over time (both p < 0.001). Changes were also observed in VO₂ max, body weight, body mass index, and waist circumference (all p < 0.05). Left ventricular ejection fraction, blood pressure, and QTc interval showed no relevant variation during follow-up. Mild adverse effects were reported in 6.1% of patients. Conclusions: In patients with MDD and undergoing CR while receiving vortioxetine, longitudinal changes were observed in psychological, functional, and selected cardiovascular measures. These real-world data describe clinical trajectories within integrated rehabilitation settings and provide hypothesis-generating evidence for future controlled studies. Full article

(This article belongs to the Section Cardiovascular Medicine)

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12 pages, 432 KB

Open AccessArticle

Effectiveness and Safety of Dupilumab in Patients with Chronic Rhinosinusitis with Nasal Polyps and Associated T2 Comorbidities: One-Year Real Life Round

by Eustachio Nettis, Rossella Casella, Elisabetta Di Leo, Ippolita Zaza, Fabio Lodi Rizzini, Alessandro Vrenna, Luisa Brussino, Irene Ridolfi, Laura Bonzano, Lia Ginaldi, Ernesto Aitella, Vincenzo Patella, Roberta Zunno, Massimo Triggiani, Isabella Carrieri, Nicola Antonio Adolfo Quaranta, Lucia Iannuzzi, Francesca Serena Romano, Erminia Ridolo, Alessandro Barone, Angela Maria D’Uggento, Valentina D’Aiuto and Aikaterini Detoraki Show full author list Hide full author list

J. Clin. Med. 2026, 15(4), 1373; https://doi.org/10.3390/jcm15041373 (registering DOI) - 10 Feb 2026

Abstract

Background/Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) represents a common and debilitating inflammatory disorder primarily driven by type 2 immune mechanisms. Its frequent overlap with asthma, allergic rhinoconjunctivitis and atopic dermatitis highlights the need for therapeutic strategies able to address multimorbidity within the [...] Read more.

Background/Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) represents a common and debilitating inflammatory disorder primarily driven by type 2 immune mechanisms. Its frequent overlap with asthma, allergic rhinoconjunctivitis and atopic dermatitis highlights the need for therapeutic strategies able to address multimorbidity within the same pathogenic spectrum. The development of monoclonal antibodies targeting signaling pathways provides an effective and well-tolerated option that addresses common comorbidities. Targeting the IL-4 receptor alpha subunit, dupilumab is a completely human IgG4 monoclonal antibody that reduces type 2 inflammation in many organ systems by blocking IL-4 and IL-13 signaling. This study aimed to assess the long-term effectiveness and safety of dupilumab in a real-world cohort of patients with severe CRSwNP, stratified according to the presence of common type 2 comorbidities, over a 52-week treatment period. Methods: We conducted a prospective, multicenter, observational study across ten Italian secondary care centers for Allergy and Clinical Immunology and Otolaryngology. All participating centers were affiliated with the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC). Enrolled adult subjects with severe CRSwNP received dupilumab treatment in the context of standard care for 52 weeks. Several efficacy parameters were used. Results: A significant improvement was detected for all the applied efficacy parameters, i.e., 22-item Sinonasal Outcome Test (SNOT-22) and bilateral endoscopic nasal polyp (NPS) scores for CRSwNP, Rhinitis Control Scoring System (RCSS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores for allergic perennial rhinitis, Forced Expiratory Volume in the first second (FEV1) and Asthma Quality of Life Questionnaire (AQLQ) scores for asthma, Eczema Area and Severity Index (EASI), Atopic Dermatitis Control Toll (ADCT) and Dermatology Life Quality Index (DLQI) scores for AD. Dupilumab was well-tolerated, with no new safety signals. Conclusions: This multicenter real-world study demonstrates that dupilumab provides sustained, clinically meaningful, and safe benefits for patients with severe CRSwNP and coexisting type 2 comorbidities, supporting its role as an integrated therapeutic option in precision management of type 2 inflammatory diseases. Full article

(This article belongs to the Special Issue Allergic and Eosinophilic Diseases: Diagnosis, Treatment and Management (Second Edition))

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11 pages, 863 KB

Open AccessReview

Transaxillary Robotic Thyroidectomy: A Novel Technique and Update

by Barbara Mullineris, Alice Francescato, Giovanni Colli, Davide Gozzo, Silvia Traficante and Micaela Piccoli

J. Clin. Med. 2026, 15(4), 1372; https://doi.org/10.3390/jcm15041372 - 9 Feb 2026

Abstract

Gasless Transaxillary Robotic Thyroidectomy (G-TART) has undergone significant refinement through the adoption of novel strategies to enhance surgical precision and safety. In this paper, we describe a novel technique that integrates dynamic endoscope repositioning, called the “swing technique”, with the use of a [...] Read more.

Gasless Transaxillary Robotic Thyroidectomy (G-TART) has undergone significant refinement through the adoption of novel strategies to enhance surgical precision and safety. In this paper, we describe a novel technique that integrates dynamic endoscope repositioning, called the “swing technique”, with the use of a specialized intraoperative neuromonitoring (IONM) probe—Modena Robotic Probe—designed for robotic applications. The procedure, performed using the Da Vinci Xi system (Intuitive Surgical, Sunnyvale, CA, USA), incorporates intermittent IONM during recurrent laryngeal nerve (RLN) dissection. The swing technique involves real-time adjustment of the 30° endoscope between robotic ports to improve visualization within the confined transaxillary (TA) surgical field, particularly during contralateral dissection. Simultaneously, the Modena Robotic Probe, a custom monopolar stimulation probe developed in collaboration with Dr. Langer Medical GmbH for connection to the AVALANCHE^® SI2 neuromonitor, allows precise RLN mapping and verification throughout the operation. This approach could facilitate accurate anatomical tracking, minimize the risk of thermal or mechanical nerve injury, and enable safe navigation in a narrow operative TA tunnel. The adoption of advanced imaging techniques in conjunction with specialized robotic instrumentation may contribute to enhanced surgical safety and accuracy, emphasizing the importance of procedure-specific robotic approaches in thyroid surgery. Full article

(This article belongs to the Special Issue Endocrine Surgery: Current Developments and Trends)

24 pages, 4957 KB

Open AccessReview

Mitigating Blue-Light Risk in Display-Based Digital Therapeutics: A Practical Framework to Support Clinical Efficacy

by Wonki Hong

J. Clin. Med. 2026, 15(4), 1371; https://doi.org/10.3390/jcm15041371 - 9 Feb 2026

Abstract

Display-driven optical stimuli underpin a major class of clinically validated digital therapeutics (DTx) now expanding from neuropsychiatric disorders to chronic diseases. The display’s optical characteristics—spectral power distribution, luminance, contrast, and temporal modulation—therefore define the delivered dose of these software-based interventions. In this context, [...] Read more.

Display-driven optical stimuli underpin a major class of clinically validated digital therapeutics (DTx) now expanding from neuropsychiatric disorders to chronic diseases. The display’s optical characteristics—spectral power distribution, luminance, contrast, and temporal modulation—therefore define the delivered dose of these software-based interventions. In this context, blue-rich emission in the 450–480 nm band, particularly with evening exposure, can suppress melatonin via melanopsin-mediated intrinsically photo-sensitive retinal ganglion cell (ipRGC) pathways and perturb circadian timing, potentially attenuating therapeutic efficacy. This review summarizes clinical evidence for display-enabled DTx across major indications and synthesizes mechanistic and experimental data linking blue light to sleep and circadian disruption, with downstream mood, cognitive, cardiovascular, and metabolic effects, as well as increased risk of cancer and skin damage. This review distinguishes wavelength-dependent hazards by separating retinal photochemical risk in the roughly 415–450 nm range from circadian-disruptive melanopic effects in the 450–480 nm range, informing spectrum optimization for therapeutic use. It then synthesizes mitigation strategies spanning display emitter spectrum engineering, optical filtering or conversion films, and software controls such as color temperature tuning, high-frequency dimming, metameric spectrum design, and personalized circadian lighting. The review concludes with design, prescription, and standards considerations to align display output with therapeutic intent. Full article

(This article belongs to the Special Issue Applications of Artificial Intelligence and Digital Therapeutics in Clinical Medicine: 2nd Edition)

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22 pages, 1279 KB

Open AccessSystematic Review

Erector Spinae Plane Block Versus Thoracic Paravertebral Block for Postoperative Analgesia in Thoracic Surgery: A Systematic Review and Meta-Analysis of Randomized and Observational Studies

by Yoon Ji Choi, Hyun Kang and Sang Hun Kim

J. Clin. Med. 2026, 15(4), 1370; https://doi.org/10.3390/jcm15041370 - 9 Feb 2026

Abstract

Background/Objectives: Both erector spinae plane block (ESPB) and thoracic paravertebral block (TPVB) are widely used for thoracic surgery analgesia, but comparative evidence remains inconsistent. This meta-analysis compared their analgesic efficacy and safety with time-stratified analyses and trial sequential analysis (TSA). Methods: We searched [...] Read more.

Background/Objectives: Both erector spinae plane block (ESPB) and thoracic paravertebral block (TPVB) are widely used for thoracic surgery analgesia, but comparative evidence remains inconsistent. This meta-analysis compared their analgesic efficacy and safety with time-stratified analyses and trial sequential analysis (TSA). Methods: We searched MEDLINE, Embase, Web of Science, and CENTRAL (inception to January 2026) for randomized controlled trials (RCTs) and observational studies comparing ESPB with TPVB in adults undergoing thoracic surgery. Primary outcomes were pain scores at rest and during coughing at 0–6 h, 24 h, and 48 h postoperatively. Secondary outcomes included opioid consumption and adverse events. Random-effects meta-analyses were performed. Evidence certainty was assessed using GRADE. Results: Twenty-five studies (22 RCTs, 3 observational studies; 1847 patients) were included. TPVB provided superior early analgesia (0–6 h) at rest (SMD 0.25, 95% CI 0.03–0.47) and during coughing (SMD 0.28, 95% CI 0.02–0.54); TSA confirmed firm evidence for early pain at rest. Pain scores at 24 h and 48 h were comparable between techniques. TPVB reduced 24 h opioid consumption (SMD 0.42, 95% CI 0.11–0.73), but evidence certainty was low due to heterogeneity and insufficient information size by TSA. No differences were observed in postoperative nausea and vomiting or hypotension. Conclusions: ESPB and TPVB provide comparable analgesia beyond the early postoperative period. TPVB demonstrates superior early analgesia (0–6 h) with firm evidence, but opioid-sparing effects remain uncertain. Both techniques are safe. ESPB represents a practical alternative to TPVB, particularly where technical simplicity is prioritized. Full article

(This article belongs to the Special Issue Advances and Clinical Comparisons in Analgesia: Pharmacological, Non-Pharmacological, and Device-Based Approaches)

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