Rebecca Sieff Hospital

This cross-sectional study investigated the relationship between depressive symptoms and creative personality through the lens of epigenetic modifications within Hypothalamic-Pituitary-Adrenal (HPA) axis genes. By analyzing DNA methylation patterns in key HPA axis genes-including corticotropin-releasing hormone (CRH), its receptor (CRHR1), CRH binding protein (CRHBP), melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (STAR), FK506 binding protein 5 (FKBP5), and the glucocorticoid receptor (NR3C1), we examined how methylation variation was associated with the depressive symptoms-creativity link in 371 participants (190 women, 181 men). Our findings revealed that among individuals with methylation patterns putatively associated with reduced HPA axis activity, higher depressive symptoms were positively associated with creative personality, suggesting that in this biological context, introspective aspects of depressive symptoms may coincide with creative propensities. Conversely, among individuals with methylation patterns putatively associated with heightened HPA axis activity, higher depressive symptoms were negatively associated with creative personality. These results suggest that the association between depressive symptoms and creativity is not uniform but differs based on methylation variation in genes involved in stress response regulation. The findings highlight the potential role of HPA axis-related biological factors in understanding individual differences in the depression-creativity relationship, though the cross-sectional design precludes causal inference.

ABSTRACTDespite the global expansion of medical cannabis, limited empirical attention has been given to the sociocultural and religious factors shaping patient attitudes, particularly in multi‐faith societies. Israel provides a distinctive context for such examination, combining advanced medical cannabis regulation with substantial religious diversity. This cross‐sectional study examined how religious affiliation and trust in the medical profession influence attitudes toward medical and recreational cannabis among patients in Northern Israel. A survey was administered to 374 hospitalized patients from four religious groups—Jewish, Muslim, Christian, and Druze—using validated measures of cannabis‐related attitudes and trust in the medical profession. Exploratory factor analyses supported scale validity and reliability. Analyses included ANCOVA and correlations, controlling for age, religiosity, and prior exposure to medical cannabis. Attitudes toward cannabis differed significantly by religious affiliation. Christian participants reported the most favorable views toward both medical and recreational cannabis, followed by Jewish respondents, while Muslim and Druze participants expressed more conservative attitudes. Contrary to prior literature, higher trust in the medical profession was associated with more negative cannabis attitudes overall. A mixed‐design ANCOVA revealed a significant interaction between religious affiliation, trust level, and cannabis type, indicating religion‐specific patterns in how trust shapes cannabis attitudes. These findings underscore the importance of culturally and religiously informed health communication and policy approaches in pluralistic healthcare settings.

The prevalence of autoimmune diseases (AIDs) in Ethiopian patients with type 1 diabetes (T1D) is mainly unknown. This study aimed to determine the co-occurrence of AIDs in T1D Ethiopian patients and to compare their prevalence to non-Ethiopian Israeli patients. A retrospective cohort analysis of 12,759 T1D patients, of whom 672 (5.3%) were of Ethiopian descent, aged ≥ 18 years, registered in the Clalit Health Services database was conducted. The AID cases were identified by ICD-10 codes from 2000 to 2023. Additionally, data on thyroid peroxidase antibody (TPO) and tissue transglutaminase (TTG) antibodies were extracted and analyzed. The mean age of the entire cohort was 30.4 ± 18.9 years, 54% were male, and the mean follow-up was 10.9 ± 6.1 years. An additional AID was diagnosed among 14% of the Ethiopian and 26% of the non-Ethiopian populations (p < 0.001), respectively. Although the prevalence of coexisting autoimmune conditions was approximately half in the Ethiopian group, the relative distribution pattern of common and less common AIDs remained similar to that observed in the non-Ethiopian population. The prevalence of AIDs in Ethiopians is lower than in non-Ethiopian patients with T1D, indicating the existence of ethnic differences in susceptibility to AIDs. Nevertheless, the low screening rates highlight the need for greater vigilance and adherence to guidelines by medical staff.

Intraoperative radiotherapy (IORT) offers single-session treatment during breast-conserving surgery (BCS). Outcomes depend heavily on patient selection and tumor characteristics. To assess local recurrence (LR) and prognosis using the 2024 American Society for Radiation Oncology (ASTRO) risk classification in IORT-treated patients. This multicenter retrospective study analyzed 358 IORT cases (356 patients) treated between 2014 and 2018 using the Zeiss INTRABEAM system. Cases were classified per the 2024 ASTRO partial-breast irradiation guidelines. The primary endpoint was local recurrence-free survival (LRFS); secondary endpoints included overall survival (OS) and mastectomy-free survival (MFS). The median age was 66 years (range 48-80); all tumors were invasive with a median tumor size of 10 mm. At a median follow-up of 7.1 years, LR occurred in 14/358 cases (3.9%) at a median of 5.2 years post-diagnosis. Five- and 8-year LRFS were 98.3% and 94.8%, respectively; 5- and 8-year OS were 99.4% and 97.7%; MFS at 8 years was 98.2%. Cases that were classified as "conditionally recommended" or "conditionally not recommended" had significantly higher LR than the "suitable" group (8.5% vs. 2.7%; HR 3.25, 95% CI 1.05-10.08, p = 0.041). Exploratory analysis showed that cases with ≥2 conditional criteria carried a markedly higher risk than those with 0-1 (21.4% vs. 3.2%; Firth-penalized Cox HR 8.26, 95% CI 2.06-26.06, p = 0.005). In appropriately selected patients, IORT achieves local control consistent with contemporary series. The 2024 ASTRO risk classification effectively identifies high-risk cases, supporting its use for risk-adapted candidate selection.

ABSTRACTBackgroundBotulinum toxin type A (BoNT‐A) is widely recognized as the leading nonsurgical cosmetic treatment worldwide for diminishing dynamic wrinkles in the glabellar, forehead, and periorbital areas. While BoNT‐A is widely acknowledged for its effectiveness and popularity, there are notable inconsistencies in results, methodologies, and safety reporting across clinical studies, highlighting the necessity for the careful development of strong, evidence‐driven guidelines.ObjectivesThis study aimed to compile and evaluate data from clinical research focusing on upper‐face BoNT‐A injections, specifically regarding safety outcomes, effectiveness, patient satisfaction, and response rates. This investigation concentrated on the outcomes of the clinical trials conducted.MethodsThis analysis includes prospective cohorts, randomized controlled trials, and observational studies that report on BoNT‐A cosmetic treatments specifically in the upper face area. A thorough examination of MEDLINE, EMBASE, Cochrane Library, and Web of Science studies was conducted, covering literature up to May 2025. The assessment included response rates, levels of patient satisfaction, and the extent of wrinkle reduction. The analysis employed a random‐effects model to produce combined estimates, followed by an assessment of heterogeneity utilizing τ2, I2, and Cochran's Q. Forest diagrams and Egger's test were utilized to evaluate publication bias and the effects of small studies when applicable.ResultsAfter the administration of BoNT‐A therapy, a notable decrease in the severity ratings of wrinkles was observed, as indicated by the synthesis of ten clinical trials examining this aspect (Cohen's d = 1.93; 95% CI: 1.60–2.25; p = 0.001). However, the data also revealed a considerable degree of variability (I2 = 90%). The findings indicated substantial variability in effect sizes related to patient satisfaction across four distinct trials (Cohen's d = 22.54; 95% CI: −2.07–47.15; p = 0.07), accompanied by significant heterogeneity (I2 = 99.9%) and potential indications of publication bias. The findings revealed significant variability (I2 = 100%) and wide prediction intervals, indicating substantial inconsistency and limited applicability of the response outcomes in future research. Analysis of five studies regarding response rates revealed a significant overall effect (Cohen's d = 34.30; 95% CI: 3.65–64.94; p = 0.28). The overall impact was determined to be noteworthy.ConclusionsBoNT‐A injections contribute to a decrease in wrinkle severity and improve clinical results for rejuvenating the upper face. Research indicates notable variability and susceptibility to bias regarding patient satisfaction and response rates. The findings emphasize the necessity for subgroup analyses, enhanced reporting methodologies, and uniform outcome evaluations to identify factors contributing to variability in responses to BoNT‐A therapy.Trial RegistrationThis study was conducted in accordance with PROSPERO guidelines

The long-term impact of COVID-19 vaccination on post-acute COVID-19 symptoms and associated quality of life (QoL) changes remains incompletely described. This study aimed to explore the impact of the timing of COVID-19 priming and booster doses, on reporting long COVID symptoms and associated QoL changes. Individuals who had PCR testing for SARS-CoV-2 processed in government hospitals in Northern Israel between 15th March 2021 and 15th June 2022 were invited to answer serial online surveys collecting information on SARS-CoV-2 infection, vaccination status and post-acute symptoms every 3-4 months for two years. Participants were categorized into groups based on the number of doses received prior to infection. We compared these groups over time in terms of reporting post-COVID symptom clusters and QoL, using population-average and mixed-effects regression models, respectively. A total of 4809 individuals are enrolled and respond to up to five follow-up surveys. Of these, 1377 (28.61%) report a positive SARS-CoV-2 test, while 3432 (71.39%) report a negative result. After adjustment for potential confounders, receiving at least three COVID-19 vaccine doses prior to infection is associated with a 34% reduction in the likelihood of reporting at least one long COVID symptom cluster compared to being unvaccinated (adjusted odds ratio [aOR] = 0.66, p = 0.022). Pre-infection vaccination is also associated with higher quality of life (QoL) scores (β = 0.07, p < 0.001). The estimated vaccine effectiveness of three pre-infection doses against long COVID over a two-year period is 26.5% (95% CI: 10.8-39.4). This protective effect remains stable over time. In contrast, vaccination received after infection shows no association with long COVID symptoms or QoL outcomes. Receiving at least three COVID-19 vaccine doses prior to SARS-CoV-2 infection provides a sustained protective effect against long COVID and its negative impact on quality of life for at least two years. The longer-term durability of this protection, the role of reinfection, and the influence of emerging viral variants remains to be investigated.

Disclosure: L.C. Gregory: None. S. Rath: None. H. Mandel: None. G. Elias-Assad: None. N.N. Samra: None. M.J. Parker: None. P. Dimitri: None. N.K. Hanchate: None. M.T. Dattani: None.Background: Congenital Hypopituitarism (CH) is a life-threatening developmental disorder ranging in severity, characterized by a variable combination of pituitary hormone deficiencies. These include GH deficiency (GHD) (most predominant), gonadotropin, ACTH, TSH, prolactin and vasopressin deficiencies respectively. To date, pathogenic variants have been identified in ∼10-15 % of patients, however the majority do not have a molecular diagnosis. Methods: Whole exome sequencing was performed in two unrelated kindreds including three patients with GHD, hypogonadotropic hypogonadism, and developmental delay/autism. Magnetic resonance imaging (MRI) was performed on the three patients to analyse their pituitary gland anatomy and visualize any structural brain defects. In situ hybridisation was conducted on embryonic human brain tissue sections at different Carnegie stages (CS) of development to generate a developmental expression profile of CCDC149. A null Ccdc149 mouse model was generated for phenotypic characterization. Results: Severe scoliosis was present in two out of the three patients, the two siblings from Pedigree 1 had a normal pituitary, with the third unrelated patient having a small anterior pituitary on MRI. Two novel homozygous CCDC149 frameshifts, c.832G>T p.G278* and c.665T>A, p.L222* respectively, were identified in the two unrelated kindreds with CH. Human embryonic expression of CCDC149 was specific to the developing hypothalamo-pituitary (HP) region at CS16, 19, 20 and 23. Preliminary murine data suggest that Ccdc149-knockout mice exhibit growth impairment and reduced fertility compared to their wildtype littermates. Conclusion: We report the first genetic variant in CCDC149, a novel gene associated with CH, scoliosis and learning difficulties/autism. CCDC149 variants have not been reported in any human disease previously. We present clinical and molecular data in two kindreds with CH, as well as gene expression in human embryonic brain and murine data, to confirm the association between CH and CCDC149 variations. Our study demonstrates that CCDC149 is a novel candidate gene for this disorder, and should be considered as a potential cause in patients with unsolved CH. Previous studies in C.elegans have identified expression of the CCDC149 orthologue in the basal bodies of ciliated neurons, suggesting that impaired cilia function may be an underlying mechanism in this complex disorder. Further functional investigations in patient fibroblasts in this context are currently underway.Presentation: Saturday, July 12, 2025

Background/Objectives: Cholesteatoma is a destructive middle ear pathology that can cause chronic infection, ossicular erosion, and hearing loss. While surgical excision is the standard treatment, recurrence remains a major clinical challenge, and comprehensive data on long-term outcomes are limited. This meta-analysis evaluated cholesteatoma recurrence rates following surgery, identified clinical and surgical predictors of recurrence, and assessed trends across follow-up durations, techniques, and patient demographics. Methods: We searched PubMed, Scopus, Web of Science, CENTRAL, and Google Scholar for relevant studies (CRD42024550351). Studies reporting postoperative recurrence were included. Data on demographics, surgical approach, cholesteatoma type, and outcomes were extracted. Risk of bias was assessed using the Newcastle–Ottawa Scale. Pooled recurrence rates were calculated using random-effects models, and subgroup and meta-regression analyses were performed to identify predictors. Results: Eighty-four studies comprising 12,819 patients were included. The cholesteatoma recurrence rate showed geographic variability. Recurrence was higher in children (13%) than adults (10%), and in acquired (12%) versus congenital (7%) cholesteatoma. Advanced-stage disease, left-sided lesions, and revision surgeries increased recurrence risk. Canal wall down had lower recurrence (7%) than canal wall up techniques (16%). Adjuncts such as mastoid obliteration, ossicular reconstruction, and planned second-look surgeries reduced recurrence. Cumulative recurrence reached 39% at 15 years and 33% at 25 years. Meta-regression identified age, staged procedures, and second-look surgeries as independent predictors. Conclusions: Cholesteatoma recurrence is influenced by age, surgical approach, and disease severity. CWD procedures and comprehensive surgical planning reduce recurrence risk. Long-term follow-up and standardized outcome definitions are essential to improve monitoring and disease control.

Background and Clinical Significance: Zoledronic acid (ZA) is a widely used bisphosphonate for the prevention of skeletal-related events in patients with metastatic bone disease. While it is generally well tolerated, rare immune-mediated complications may be underrecognized. To date, myocarditis has not been reported in association with ZA. Case Presentation: A 35-year-old woman with metastatic pheochromocytoma developed acute, non-exertional chest pain approximately 36 h after receiving her first intravenous ZA infusion. Laboratory testing revealed elevated high-sensitivity troponin T, peaking at 1182 ng/L. Cardiac magnetic resonance imaging (CMR) demonstrated myocardial edema and subepicardial late gadolinium enhancement, consistent with acute myocarditis per the 2018 revised Lake Louise criteria. An extensive diagnostic workup excluded infectious, autoimmune, and ischemic causes. Symptoms and troponin levels improved following ZA discontinuation and supportive care. In the absence of alternative etiologies, and given the close temporal association with ZA administration, the diagnosis of presumed ZA-associated myocarditis was supported by clinical presentation, biochemical markers, and CMR findings, recognizing that histopathological confirmation is rarely pursued in clinically stable patients. Conclusions: To our knowledge, this is the first reported case of presumed zoledronic acid–associated myocarditis confirmed by cardiac MRI. This report highlights the diagnostic utility of CMR in suspected drug-related cardiac inflammation and the importance of considering myocarditis in patients presenting with unexplained chest pain following ZA infusion, particularly when other causes have been excluded.