Rabin Medical Center

Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) lower LDL cholesterol and may influence cancer through immunomodulatory pathways. However, their effect on human cancer incidence remains unknown. We conducted a retrospective, propensity score-matched study (Clalit Health Services, Israel, 2010-2023) comparing PCSK9 mAbs to ezetimibe. Adults prescribed PCSK9 mAbs for 6 months or more were matched 1:3 to ezetimibe-treated patients without prior cancer, applying a 1-year latency. The cohort included 9,876 patients (2,469 PCSK9 mAb; 7,407 ezetimibe; mean age 65). During a median 4.6-year follow-up, cancer occurred in 12% of PCSK9 mAb users and 11% of ezetimibe users (HR 1.09 [95% CI, 0.95-1.25]). In sex-stratified analysis, men on PCSK9 mAbs had a higher cancer incidence (12.5% vs. 10.3%, P = 0.03); no difference was observed in women. All-cause mortality was significantly lower in the PCSK9 mAb group (3% vs. 5%; HR 0.65 [95% CI, 0.54-0.80]). Post-cancer-diagnosis mortality did not differ. In this large cohort, PCSK9 mAb therapy appeared safe regarding overall cancer risk and was associated with a significant reduction in all-cause mortality; the slightly higher cancer incidence in men may likely be attributed to a higher prevalence of baseline risk factors.

Large Language Models (LLMs) demonstrate increasing capabilities in medical knowledge assessment, yet limitations remain in cross-population validation, direct human-AI comparisons, and evaluation of newer models in anesthesiology contexts. This study addresses these gaps by conducting a head-to-head comparison between newer LLMs and human examinees on official Israeli multiple-choice board examinations. We evaluated two LLMs (Claude 3.7 Sonnet and ChatGPT-4) against anonymized aggregate data from 381 examinees on three consecutive official Israeli anesthesiology board examinations (2023–2024), comprising 450 multiple-choice questions stratified by difficulty, discrimination ability, and topic. Each model was tested twice per exam. Claude 3.7 Sonnet achieved 73.67% accuracy, significantly outperforming both human examinees (62.77%, P < 0.001) and ChatGPT-4 (64.44%, P < 0.001). However, both LLMs performed below the upper quartile of human performance (78.05%). While LLMs excelled on easy questions and theoretical domains like cardiac physiology (Claude: 96.88%, ChatGPT-4: 81.25%), they showed lower performance in areas such as ambulatory (Claude: 30.00%, ChatGPT-4: 10.00%) and regional anesthesia (Claude: 44.44%, ChatGPT-4: 38.89%). Human examinees demonstrated consistent performance across all domains, whereas LLMs showed extreme variability. Self-consistency was substantial for both LLMs (κ = 0.66–0.68), but agreement with human responses was moderate (κ = 0.34–0.39). While advanced LLMs currently exceed average examinee performance on anesthesiology board examinations, they fall short of top-quartile examinees at present and demonstrate significant performance variability across different topic areas.

Prenatal education improves maternal and neonatal outcomes. Ultrasound-guided visual biofeedback provides real-time visualization of fetal head movement, enabling expectant mothers to refine their pushing techniques. Pelvic floor muscle training may improve the ability to contract and relax the pelvic floor during labor. When used during the second stage of labor, US-BF has been shown to confer obstetrical benefits. Implementing prelabor ultrasound-guided visual biofeedback can further improve motor learning and optimize pushing effectiveness during the second stage of labor. This study aimed to evaluate the feasibility and effectiveness of pelvic floor physiotherapist-led prelabor ultrasound-guided visual biofeedback for improving obstetrical outcomes. A single-blinded randomized controlled trial was conducted in a community clinic. The study was approved by the Ariel University Human Ethics Committee (20211128) and registered on ClinicalTrials.gov (ID: NCT05258786). Nulliparous women at term with singleton pregnancies in vertex presentation were randomized into three groups: (1) Intervention: Prelabor transperineal and transabdominal ultrasound-guided visual biofeedback for pelvic floor muscle training and second-stage pushing training, (2) Control: Verbal instructions for pelvic floor muscle training and second-stage pushing, and (3) Routine Care: Standard prenatal education. In-person training sessions were held at an outpatient physiotherapy clinic between 37 and 39 weeks of gestation. Within the intervention group, pushing efficacy was assessed using the angle of progression, and pelvic floor muscle contraction efficacy was assessed using bladder base displacement across the pre-, during-, and post-biofeedback phases. Obstetric outcomes, including second-stage duration, mode of delivery, perineal integrity, and postpartum urinary retention, were retrieved from medical records. Stress urinary incontinence was assessed using the International Consultation on Incontinence Questionnaire–Short Form before delivery and at two and eight weeks postpartum. Out of 161 randomized women, 120 completed the study. In the intervention group, pushing efficacy showed a significant quadratic pattern, improving during biofeedback and declining after visual feedback was withdrawn (p = 0.007), while pelvic floor muscle contraction efficacy remained largely unchanged. Compared to the combined control and routine care groups, the intervention group had significantly lower rates of operative vaginal delivery (p = 0.050), higher rates of an intact perineum (p = 0.025), and lower rates of postpartum urinary retention requiring catheterization (p = 0.039). No significant differences were found in second-stage duration, cesarean delivery rates, or stress urinary incontinence outcomes. Physiotherapist-led prelabor ultrasound-guided visual biofeedback for second-stage pushing and pelvic floor muscle training was feasible and associated with improved obstetrical outcomes. These findings suggest a promising direction for enhancing prelabor education and maternal preparation. The study was approved by the ethical review board (Ariel University Human Ethics Committee Noa Ben Ami − 20211128, Ariel University, Israel) and registered on ClinicalTrials.gov on February 18, 2022 (ID: NCT05258786). Prior to enrolment, informed consent was obtained from all participants. All procedures were conducted in accordance with the ethical standards of the institutional research committee, and the 1964 Declaration of Helsinki and its subsequent amendments.

To evaluate the technical feasibility of a standardized, sclerotomy-free method for injecting viscoelastic material into the suprachoroidal space using a novel mechanical injector, and to evaluate an upgraded injector version in an ex vivo porcine model. This laboratory investigation was conducted at a central medical research center using thirteen freshly enucleated pig eyes obtained from a local farm. All eyes underwent a 360-degree peritomy and were fixed to a Styrofoam platform. In cohort 1 (n = 5), a custom mechanical injector (Supra SEG) with a 30-gauge needle and selectable penetration depths (0.7 mm and 0.9 mm) was used to inject saline or viscoelastic materials (Biolon Prime, Healon 5 Pro, and Healon EndoCoat) into the suprachoroidal space (SCS). In cohort 2 (n = 8), an upgraded injector (27-gauge needle and larger-diameter tubing) was evaluated using the 0.9 mm depth. Ultrasound biomicroscopy (UBM) was performed before and after each injection to confirm SCS localization. The primary outcome was successful UBM-verified delivery into the SCS. In cohort 1, injections at 0.7 mm were unsuccessful in all attempts, whereas 0.9 mm enabled correct SCS delivery in all eyes. In cohort 2, successful UBM-confirmed suprachoroidal delivery was achieved in all eight eyes across multiple viscoelastic materials, including sequential and repeat injections that produced a larger, merged suprachoroidal bleb. UBM demonstrated characteristic echogenic appearances for each material. Injection resistance in cohort 2 was consistently mild to moderate. A sclerotomy-free, image-guided, tangential suprachoroidal injection technique using a purpose-built injector is technically feasible in ex vivo porcine eyes. Because this post-mortem model cannot adequately assess hemorrhagic complications, procedural safety and clinical performance require further in vivo evaluation.

Mitral regurgitation (MR) is the most common valvular disease in developed countries. Many patients with functional MR (FMR) are inoperable due to high surgical risk, and effective transcatheter options are limited. Radiofrequency (RF) ablation can contract connective tissue. To assess the feasibility, safety, and efficacy of Biorefine, a novel transcatheter RF ablation system for mitral annulus remodeling without implants, in a preclinical ovine model. Twelve sheep underwent transseptal RF ablation of the posterior mitral annulus under 3D echocardiographic and fluoroscopic guidance. Mitral geometry and coaptation were evaluated acutely (n = 4), at 58days (n = 4), and 178days (n = 4). Histology assessed tissue effects. All procedures were complication-free. Eleven of 12 animals showed ≥ 15% annular area reduction (mean 21.8%), ≥ 10% A-P diameter reduction (mean 15%), and 71.9% mean coaptation increase. Histology confirmed localized fibrosis (≤ 3mm) without off-target injury. Biorefine appears safe, durable, and implant-free for FMR.

Background: Limb-salvage surgery using extendable distal femoral endoprostheses has become the standard reconstruction following tumor resection in skeletally immature patients, allowing continued growth and improved function. However, mechanical complications, particularly tibial pain, remain challenging and poorly understood. This study aimed to identify radiographic predictors of tibial pain and evaluate their potential utility in early risk detection. Methods: A retrospective cohort study was conducted of 29 skeletally immature patients (mean age 10.4 years) who underwent expandable distal femoral endoprosthetic replacement between 2008 and 2018 at a tertiary orthopedic oncology center. Standardized radiographs were analyzed at 6 months and final follow-up (mean 75 months) to assess cortical thickness, stem-to-cortex distances, stem migration, stress shielding, pedestal formation, and periosteal reaction. Associations between radiographic parameters and tibial pain were assessed using multivariable logistic regression, t-tests, and chi-square analyses. Results: Seventeen patients (58.6%) developed activity-limiting tibial pain requiring analgesics, as documented during follow-up. Mean medial and lateral cortical thickness increased from 3.0 mm and 3.4 mm to 4.1 mm and 5.1 mm, respectively. The logistic regression model demonstrated strong explanatory power (Pseudo R2 = 0.57, p = 0.004). Medial cortical thickness at last follow-up was the only significant independent predictor of tibial pain (p = 0.042), and was significantly associated with tibial pain. Patients with tibial pain exhibited greater medial cortical thickening (p &lt; 0.001). Stem migration (φ = 0.421, p = 0.065), stress shielding (φ = 0.476, p = 0.044), pedestal formation (φ = 0.608, p = 0.004), and periosteal reaction (φ = 0.569, p = 0.008) were also associated with pain. Conclusions: Medial cortical hypertrophy emerged as a potential radiographic biomarker for tibial pain. after expandable distal femoral endoprosthesis in growing patients. The findings suggest that cortical remodeling, stress shielding, and pedestal formation collectively reflect stem micromotion and bone adaptation. Early radiographic surveillance of these parameters warrants further investigation in prospective studies to determine their clinical utility. Larger multicenter studies are warranted to validate these predictors and refine postoperative monitoring protocols.