Clalit Health Services

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.

To describe the clinical and laboratory findings, disease course, and treatment effectiveness of a large, genetically homogenous group of patients with deficiency of adenosine deaminase 2 (DADA2), and to identify factors associated with disease-related damage. We conducted a retrospective cohort study that included 45 patients with DADA2 vasculitis with long-term follow-up. Information was collected from patients' charts, including demographic information, clinical presentations, laboratory findings, and treatment. The extent of disease-related damage was determined based on the Vasculitis Damage Index. In this large homogenous cohort, we found that a young age at disease onset and periodic illness that included recurrent episodes of fever, myalgia, and abdominal pain were associated with disease-related damage. Patients with severe DADA2 disease responded favorably to tumor necrosis factor inhibitors (TNFi). Early age of onset and the periodic nature of the disease warrant prompt initiation of TNFi treatment to prevent later complications and severe disease progression.

Background/Objectives: An extensive body of data suggests that inflammation may contribute to the pathophysiological mechanisms of psychiatric illness. Circumstantial evidence implied that low-dose aspirin (LDA) may enhance the therapeutic efficacy of psychotropic drugs. We examined whether LDA administration with psychotropic medications is associated with medication regimen stability and other therapeutic effects in patients with bipolar disorder (BD), schizophrenia, and schizoaffective disorder (SAD). Methods: This retrospective study analyzed data from Clalit Health Services' Southern District database in Israel, including 1924 patients treated between 2017 and 2019. The Study Group consisted of patients treated with LDA plus psychotropic medications, whereas the Control Group included patients treated only with psychotropic medications. Study outcomes included suicide attempts and pharmacotherapy-related negative events, defined as psychotropic dose escalation, augmentation, or switching. Results: The study group included 137 patients (55% males, age 63.3 ± 12.3 years), and the control group included 1787 patients (60% males, age 47 ± 16.9 years). Significant differences were observed across nearly all outcomes, favoring the LDA co-treatment group. Patients in the study group exhibited lower rates of medication dosage increase (40 [29%] vs. 726 [40.5%], p = 0.01); fewer changes and/or additions of psychotropic medications (37 [26.9%] vs. 778 [43.5%], p < 0.001); and a non-significantly lower rate of suicide attempts (0 [0%] vs. 16 [0.9%], p = 0.53). Conclusions: Overall, LDA co-treatment was associated with better clinical outcomes among patients with BD, schizophrenia, and SAD. Follow-up large-scale epidemiological studies and prospective randomized clinical trials are needed to examine the therapeutic potential of add-on LDA to psychotropic medications.

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.

Abstract Background The integration of genomics into clinical care has created an urgent need for accurate, standardized variant interpretation. Variant scientists (VS) play a central role in translating sequencing results into clinically actionable findings, yet no formal framework currently supports their professional development. We surveyed practicing VS to identify training routes and knowledge gaps and used these insights to design a training program. Methods A national survey delivered to every practicing VS assessed training background, learning, access to interpretation tools, and professional challenges. A multidisciplinary committee defined core competencies and developed a phased training program. Results Thirty-eight respondents were included. Professional training was mostly acquired through observation of expert analysts (42.1%), followed by hands-on experience (39.5%). Only 18% participated in a dedicated VS course. Key challenges included keeping pace with evolving guidelines (55.2%) and copy number variant (CNV) analysis (47.3%). To help narrow these gaps and support more unified VS training, we developed a comprehensive framework combining theoretical modules, practical rotations, and assessment via a standardized proficiency test, supported by institutional forums and national meetings. Conclusion We deigned a unified, scalable VS training model to address core educational gaps and support standardization of variant interpretation training nationally and internationally.

The purpose of the present study was to examine and compare the attitudes of residents and seniors in family medicine from southern Israel toward transgender patients. It was a cross-sectional study based on a self-administered questionnaire. Attitudes toward transgender patients were assessed by the Transgender Attitudes and Beliefs Scale composed of "Interpersonal comfort," "Sex/gender beliefs", and "Human value" domains. The "Sex/gender beliefs" domain measures a person's belief about whether gender is a fixed, binary characteristic or a more fluid continuum. Fifty-five specialists (26; 47.3% males) and 56 residents (31; 56.4% males) took part in the study. Overall, family medicine physicians showed a favorable attitude toward transgender individuals on the "Human value" subscale with 82 (74%) giving favorable scores, but only 38 (34.2%) of the physicians demonstrated a favorable attitude on the "Sex/gender beliefs" scale. In the multivariable regression analysis, where age, sex, ethnicity, seniority, and level of religiosity were included as predictor variables, non-Jewish ethnicity and high level of religiosity were significantly associated with the "Interpersonal comfort" domain (adjusted odds ratio (95% confidence interval) (aOR (95% CI)) = 0.26 (0.09-0.78) and 0.34 (0.13-0.85), respectively). High level of religiosity was positively associated with the "Sex/gender beliefs" score (β = 0.11; 95% CI: 0.03-0.33). Female sex was positively associated with a favorable "Human value" attitude toward transgender patients at 4.03 (1.36-13.69), but residents had a negative aOR of 0.19 (0.04-0.85). In conclusion, our study identified physician characteristics associated with a less favorable attitude toward transgender patients. They should be the focus of interventions aimed at improving these attitudes.

Background: Shoulder arthroplasty is performed for various etiologies, including osteoarthritis, proximal humerus fractures (PHFs), and rotator cuff tears. While previous studies have focused on outcomes based on implant choice, less is known about the independent effects of surgery type, comorbidities, and fracture status on postoperative outcomes. This study evaluates their influence on length of stay (LOS), in-hospital mortality, and postoperative complications. Methods: A retrospective cohort analysis of 664,545 patients undergoing anatomic total shoulder arthroplasty (ATSA), reverse total shoulder arthroplasty (RTSA), or hemiarthroplasty (HA) was conducted. Multivariable Poisson and logistic regression models assessed predictors of LOS, mortality, and complications. Results: Among 132,909 patients, 63.3% underwent RTSA, 31.3% underwent ATSA, and 5.4% underwent HA. Mean hospitalization was longest for HA (2.56 days) and RTSA (1.82 days) compared to ATSA (1.39 days; p < 0.001). Poisson regression confirmed that RTSA increased LOS by 24.1% versus ATSA (IRR = 1.24, p < 0.001), while HA had the highest LOS (IRR = 1.58, p < 0.001). Postoperative complications were observed in 8.37% of ATSA, 13.81% of RTSA, and 17.81% of HA cases (overall ~12.3%). Compared with ATSA, RTSA increased the odds of complications (OR = 1.48, p < 0.001), while HA presented the greatest complication risk (OR = 1.51, p < 0.001). Among proximal humerus fracture (PHF) patients (9.9% of the cohort), 84.7% underwent RTSA. PHF independently increased LOS (IRR = 1.61, p < 0.001), mortality (OR = 1.62, p = 0.051), and complications (OR = 2.33, p < 0.001). Conclusions: RTSA is associated with longer hospitalization and higher complication rates, while PHF worsens LOS, mortality, and complication risk.

Temporal phenotyping of paroxysmal atrial fibrillation reveals prognostic circadian subtypes, Brimer Biton, Shany, Sobel, Jonathan, Reiner Benaim, Anat, Zvuloni, Eran, Almog, Ronit, Oster, Julien, Laufer, Izhar, Green, Ilan, Suleiman, Mahmoud, Tsutsui, Kenta, Sörnmo, Leif, Behar, Joachim A

The surgical procedure of the operative opening of the uterus and delivering the fetus known as cesarean section was probably practiced for thousands of years. Delivery of a living child after the death of its mother (the postmortem procedure) is referred to in the myths and folklore of many ancient societies. Some of the newborns so delivered survived, although their mothers did not. The current review describes ten anecdotes from about 3800 years of written history of cesarean section. These stories illustrate the evolution of cesarean section from postmortem to the lifesaving procedure of the parturient and her infant.