Sheba Medical Center Research Articles

The effect of Covid-19 mRNA vaccine on serum anti-Müllerian hormone levels.

Does the administration of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine have an association with ovarian reserve as expressed by circulating anti-Müllerian hormone (AMH) levels? Ovarian reserve as assessed by serum AMH levels is not altered at 3 months following mRNA SARS-CoV-2 vaccination. A possible impact of SARS-CoV-2 infection or vaccination through an interaction between the oocyte and the somatic cells could not be ruled out, however, data are limited. This is a prospective study conducted at a university affiliated tertiary medical center between February and March 2021. Study population included reproductive aged women (18-42 years) that were vaccinated by two Pfizer-BioNTech Covid-19 vaccines (21 days apart). Women with ovarian failure, under fertility treatments, during pregnancy, previous Covid-19 infection or vaccinated were excluded from the study. Blood samples were collected for AMH levels before the first mRNA vaccine administration. Additional blood samples after 3 months were collected for AMH and anti-Covid-19 antibody levels. Primary outcome was defined as the absolute and percentage change in AMH levels. The study group consisted of 129 women who received two mRNA vaccinations. Mean AMH levels were 5.3 (±SD 4.29) µg/l and 5.3 (±SD 4.50) µg/l at baseline and after 3 months, respectively (P = 0.11). To account for possible age-specific changes of AMH, sub-analyses were performed for three age groups: <30, 30-35 and >35 years. AMH levels were significantly lower for women older than 35 years at all times (P = 0.001 for pre and post vaccination AMH levels versus younger women). However, no significant differences for the changes in AMH levels before and after vaccinations (Delta AMH) were observed for the three age groups (P = 0.46). Additionally, after controlling for age, no association was found between the degree of immunity response and AMH levels. Although it was prospectively designed, for ethical reasons we could not assign a priori a randomized unvaccinated control group. This study examined plasma AMH levels at 3 months after the first vaccination. It could be argued that possible deleterious ovarian and AMH changes caused by the SARS-CoV-2 mRNA vaccinations might take effect only at a later time. Only longer-term studies will be able to examine this issue. The results of the study provide reassurance for women hesitant to complete vaccination against Covid 19 due to concerns regarding its effect on future fertility. This information could be of significant value to physicians and patients alike. The study was supported by Sheba Medical Center institutional sources. All authors have nothing to disclose. The study protocol was approved by the 'Sheba Medical Center' Ethical Committee Review Board (ID 8121-21-SMC) on 8 February 2021 and was registered at the National Institutes of Health (NCT04748172).

The urologist\u2019s learning curve of \u201cin-bore\u201d magnetic resonance-guided prostate biopsy

BackgroundThe combination of multi-parametric MRI to locate and define suspected lesions together with their being targeted by an MRI-guided prostate biopsy has succeeded in increasing the detection rate of clinically significant disease and lowering the detection rate of non-significant prostate cancer. In this work we investigate the urologist’s learning curve of in-bore MRI-guided prostate biopsy which is considered to be a superior biopsy technique.Materials and methodsFollowing Helsinki approval by The Chaim Sheba Medical Center ethics committee in accordance with The Sheba Medical Center institutional guidelines (5366-28-SMC) we retrospectively reviewed 110 IB-MRGpBs performed from 6/2016 to 1/2019 in a single tertiary center. All patients had a prostate multi-parametric MRI finding of at least 1 target lesion (prostate imaging reporting and data system [PI-RADS] score ≥ 3). We analyzed biopsy duration and clinically significant prostate cancer detection of targeted sampling in 2 groups of 55 patients each, once by a urologist highly trained in IB-MRGpBs and again by a urologist untrained in IB-MRGpBs. These two parameters were compared according to operating urologist and chronologic order.ResultsThe patients’ median age was 68 years (interquartile range 62–72). The mean prostate-specific antigen level and prostate size were 8.6 ± 9.1 ng/d and 53 ± 27 cc, respectively. The mean number of target lesions was 1.47 ± 0.6. Baseline parameters did not differ significantly between the 2 urologists’ cohorts. Overall detection rates of clinically significant prostate cancer were 19%, 55%, and 69% for PI-RADS 3, 4 and 5, respectively. Clinically significant cancer detection rates did not differ significantly along the timeline or between the 2 urologists. The average duration of IB-MRGpB targeted sampling was 28 ± 15.8 min, correlating with the number of target lesions (p < 0.0001), and independent of the urologist’s expertise. Eighteen cases defined the cutoff for the procedure duration learning curve (p < 0.05).ConclusionsOur data suggest a very short learning curve for IB-MRGpB-targeted sampling duration, and that clinically significant cancer detection rates are not influenced by the learning curve of this technique.

The Sheba Medical Center Protocol for Bedside Evaluation of Swallowing Disorders Among Tracheotomized Patients.

The Sheba Blue Dye Test Protocol (SBDTP) is a swallowing bedside evaluation for tracheotomized patients (TP). It is based on the Modified Evans' Blue Dye Test (MEBDT), but includes several modifications that aim to overcome previously described caveats of the traditional MEBDT. These modifications include evaluating the patient three times, with increasing quantities of bolus. The purpose of this study was to examine the rates of positive and negative results of TP undergoing the SBDTP, in comparison to the MEBDT, which, generally, consists of a single evaluation. The study included a cohort of 39 TP admitted to the Sheba general hospital with various background diseases. Findings indicated that the percentage of positive results increased significantly from the first (18%) to the last stage (46.2%) of the SBDTP. This result demonstrated the advantage of the SBDTP as a more reliable evaluation for tracing aspiration among TP, especially in cases where access to instrumental examination is limited.

NCOG-50. CHARACTERIZING MENINGIOMA IN YOUNG PATIENTS UNDER 40

Abstract BACKGROUND Meningiomas are the most common primary CNS tumor in adults, with a median age at diagnosis of 65 years. Younger patients usually have a genetic background or history of prior radiation exposure. Population-level studies suggest 80-85% of meningiomas are WHO grade I (benign), 15-18% grade II (atypical), and 1-3% grade III (anaplastic). This case series describes a single center experience of meningiomas in patients under 40. METHODS We reviewed the Sheba Medical Center Neurosurgery and radiotherapy databases containing patients operated on for meningioma between 2011-2020. Digital medical records were retrieved, including pathology reports, surgical reports, clinical and radiological data, and use of radiotherapy or medical treatments. RESULTS Of 600 patients in the database, 47 patients under 40 (7.8%) were identified and 54 tumors were reviewed (five patients had multiple operation). 32 patients were female (68%) ; 2 were under 20 years old, 17 were age 20-30 and 28 were age 31-39 at first presentation. Seven patients had received prior radiation therapy for a childhood malignancy. 28 meningiomas were histology confirmed grade I (52%), 22 were grade II (41%), 2 were grade III (4%), and 2 (4%) were grade undetermined. 22 tumors were located in the skull base (41%) and 32 (59%) in the brain convexity. 16 skull base tumors were grade I, five were grade II, and one was grade III. 12 convexity tumors were grade I, 16 were grade II, and two were grade III. Median follow-up was 35 months (range 1 - 98 months). CONCLUSION Our experience with meningioma patients under 40 revealed a different grade segregation than the older population, with younger patients showing a higher incidence of grade II tumors. These tumors are generally more aggressive, and require careful resection and consideration for post-surgical radiotherapy. Further validation with population based databases is required.

The effect of the Covid-19 pandemic on patient visits to the emergency department and hospitalizations in medical wards in an Israeli medical center

BackgroundThe Covid-19 pandemic began in Israel on February 2020. Between February and October 2020, 2 periods of lockdown were imposed on Israeli population.ObjectiveTo assess the effect of the Covid-19 pandemic on visits to the emergency department (ED) and on hospitalizations in medical wards in Israel’s Chaim Sheba Medical Center, and to compare the effect during the first and second lockdowns.MethodsData regarding the number of visits of non-Covid-19 patients to the ED and the number of admissions to the medical wards, were extracted from the computerized system of the hospital. Data were analyzed for patients' characteristics, length of stay in the medical wards, in hospital mortality and the rate of 7 and 30 days re-hospitalization, and compared to the same period during 2019.ResultsTotal visits to the Sheba ED during March-October decreased by 18.5%. The most dramatic decrease occurred during the first lockdown. The number of patients admitted to the Sheba medical wards decreased by 28% (P < 0.05). The length of stay decreased from 3.69 days during 2019 to 3.42 days during 2020 (P < 0.01). The most pronounced decrease in the length of stay was observed during the second month of the first lockdown. During the pandemic, hospitalized patients at Sheba were older and were less likely to be males. The in-hospital absolute non-COVID mortality decreased from 913 to 858 respectively.ConclusionsThe Covid-19 crisis emphasizes the role of medical wards in the care of complex patients. Medical wards in Israel were at the frontline of Israel's battle against this pandemic, while continuing to treat very complex non-Covid patients. To avoid burnout of the medical staff who treat very intensively complex patients, we believe these wards should be strengthen with specialists having expertise in treating these patients. Due to our insights, the Sheba medical Center is now redesigning the concept of how intensive care beds should be managed in a big tertiary center.

BNT162b2 mRNA COVID-19 vaccination in immunocompromised patients: A prospective cohort study.

BackgroundTrials of the Pfizer-BioNTech BNT162b2 mRNA vaccine showed 95% efficacy in preventing symptomatic disease; however, the trials excluded immunocompromised patients (ICPs). We aim at analyzing antibody response in ICPs.MethodsA prospective cohort study was conducted at Sheba Medical Center, Israel, between January and April 2020, in 1274 participants who received the vaccine, including 1002 ICPs and 272 immunocompetent healthcare workers (HCWs). Antibodies were measured two-four weeks after vaccination by SARS-CoV-2 anti–receptor binding domain IgG antibodies (RBD IgG) and pseudo-virus neutralization assays. Multivariable logistic regression analyses were used to identify factors associated with vaccine-induced antibody response. Adverse events (AEs) were monitored.FindingsRBD-IgG antibodies were detected in 154/156 (98.7%) of patients with HIV, 75/90 (83.3%) with solid malignancies, 149/187 (79.7%) with myeloma, 83/111 (74.8%) following hematopoietic stem cell transplants, 25/36 (69.4%) following liver transplantation, 26/43 (60.5%) with myelodysplastic syndrome, 96/188 (51.0%) with chronic lymphocytic leukemia/non-Hodgkin's lymphoma, 50/110 (45.5%) following kidney transplantation, 15/80 (18.8%) following heart transplantation, and 269/272 (98.9%) in controls. There was a significant correlation r = 0.74 (95%CI 0.69,0.78) between RBD-binding IgG and neutralizing antibodies in all groups. Multivariate logistic regression analysis showed that age > 65 years (OR 0.41,95%CI 0.30,0.57) and underlying immunosuppression (OR 0.02,95%CI 0.01,0.07) were significantly associated with a non-reactive response of IgG antibodies. HIV patients showed a similar immunological response as healthy adults. The vaccine was safe without any episodes of rejection, graft-versus-host disease (GVHD) or allergy. Immunocompetent HCWs experienced significantly more AEs than ICPs.InterpretationAntibody response to the Pfizer-BioNTech vaccine was highly variable among different ICPs; thus, individual recommendations should be provided for the different immunosuppression states.

Study and modulation of cardiac electroporation with a novel model utilizing human induced pluripotent stem cells

Abstract Background Cardiac electroporation is a promising novel non-thermal ablation method, gaining significant interest with recent first-in-man data suggesting effective cardiac lesion generation with no collateral damage. Nevertheless, significant knowledge gaps exist regarding its electrophysiological consequences in cardiomyocytes, including; cell specificity, protocol optimization, irreversibility threshold, recovery time-constants, and the mechanistic nature of its cytolytic and anti-arrhythmic properties. Purpose Establishing an innovative in-vitro model for the study of cardiac electroporation-ablation, utilizing human induced pluripotent stem cells (hiPSCs). Methods and results Healthy-control hiPSC-derived cardiomyocytes were enzymatically dissociated and seeded as circular cell sheets (hiPSC-CCSs). Electroporation-ablation experiments were performed using a custom designed high-frequency electroporation (HF-EP) generator. Two needle-shaped electrodes were used for HF-EP delivery (Figure 1). Subsequently, detailed voltage- and Ca2+-mapping studies of the hiPSC-CCSs were conducted (Figure 2). HF-EP application resulted in the generation of electrically isolated lesions within the hiPSC-CCSs (Figure 3). Further characterization of the temporal changes and electrophysiological properties following electroporation revealed that; (1) lesions persisted over prolonged periods of time (days), indicating irreversible electroporation, (2) a temporal decrease in lesion dimensions was noted, consistent with a significant reversible electroporation component (Figures 3–5), (3) most tissue recovery had occurred within the first 15 minutes following electroporation, with little recovery beyond that time-frame, (4) increasing pulse-number augmented lesion area as well as the proportion of irreversible damage, and (5) electroporation sensitization was achieved by increasing extracellular Ca2+, indicating its crucial role in electroporation cytolysis, potentially via direct cellular toxicity and apoptosis facilitation (Figures 5–6). Finally, evaluating for HF-EP anti-arrhythmic properties, we targeted multiple rotors or focal triggered-activity generated in the hiPSC-CCSs. HF-EP application generated sustained line-blocks, isolating arrhythmogenic substrates within the hiPSC-CCSs while blocking the propagation of arrhythmic wavefronts (Figure 7). Conclusion Our results demonstrate the ability to study cardiac electroporation utilizing hiPSC-derived cardiomyocytes, provide novel insights into its temporal and electrophysiological characteristics, facilitate electroporation protocol optimization, screen for potential electroporation sensitizers, and to study its mechanistic nature and anti-arrhythmic properties. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Division of Cardiology, and Tamman Cardiovascular Research Institute, Leviev Heart Center, Sheba Medical Center - Tel Hashomer, Ramat-Gan, Israel Figures 1–4Figures 5–7

Ocular Surface Temperature: Characterization in a Large Cohort of Healthy Human Eyes and Correlations to Systemic Cardiovascular Risk Factors.

Purpose: To characterize ocular surface temperature (OST) in healthy eyes and its association with systemic risk factors of cardiovascular and ischemic heart disease. Methods: This prospective cross-sectional study included consenting subjects who were examined at the Institute for Medical Screening in Sheba Medical Center. A Therm-App™ thermal imaging camera (Opgal LTD, Israel) was used for OST acquisition, and the mean OST of the medial canthal, lateral canthal, and central cornea regions were measured. Room and body temperatures were also recorded. Past medical and ocular history as well as data from various clinical examinations performed at the same visit were obtained. Results: Thermographic images were obtained from 186 subjects, 150 of which were included in the final analysis. OST was significantly higher in the medial canthal, central cornea, and lateral canthal regions in people with a history of ischemic heart disease (p = 0.02, p = 0.02, and p = 0.03, respectively). There were no significant OST differences (ANOVA test) associated with the presence of hypertension, diabetes mellitus, or active smoking status. Conclusions: OST correlated positively with the presence of ischemic heart disease. This correlation, its pathophysiological base, and its clinical application warrants further investigation.

Subcutaneous ICD combined with VT ablation for the secondary prevention of sudden cardiac death: pilot data from the prospective multinational SICD-VTAbl study

Abstract Background The aim of the Subcutaneous ICD Combined with Ventricular Tachycardia Ablation (SICD-VTAbl) Study is to provide preliminary data on the safety and efficacy of a management strategy that incorporates S-ICD implantation and VT ablation among patients with a secondary prevention indication for an ICD. We hypothesize that VT ablation for the prevention of monomorphic VT recurrence combined with S-ICD implantation for termination of life-threatening VT/VF is safe, while reducing the need for device interventions and systemic complications associated with conventional transvenous ICD implantation for secondary prevention. Methods SICD-VTAbl is an uncontrolled, prospective, multinational observational study, conducted in France, Germany, US (Rochester NY, and Rochester MN) and coordinated in Israel. We aim to prospectively enroll 30 patients presenting with scar-related VT/VF who will undergo VT ablation/substrate modification followed by S-ICD implantation. The primary endpoint is the first occurrence of S-ICD therapy (appropriate and inappropriate). Secondary endpoints include separate occurrence of appropriate and inappropriate ICD therapies, peri-procedural complications, and adverse clinical outcomes. Results We provide clinical, arrhythmia, and outcome data on the first 15 patients enrolled in the SICD-VTAbl Study through February 2021. Mean age was 59±12 years, 78% were males, 60% had New York Heart Association (NYHA) Class ≥II symptoms, 20% had renal insufficiency, and 33% were treated with an antiarrhythmic medication (all amiodarone). Periprocedural, arrhythmia, and long-term outcome data are provided in Table 1. There were no major complications associated with the VT ablation and the S-ICD implantation procedures. During a median follow-up of 6 months (interquartile range: 2–12 months), 2 patients (13%) received S-ICD therapy: one patient (7%) experienced VF terminated by the S-ICD and one patient experienced a single episode of inappropriate S-ICD therapy. Adverse events during follow-up, unrelated to study procedures, occurred in 3 patients (20%): hospitalization for heart failure exacerbation (N=1) and non-cardiovascular hospitalizations (N=2). None of the patients died during follow-up (Table 1). Conclusions Our preliminary data from the SICD-VTAbl Study suggest that a management approach that incorporates VT ablation followed by S-ICD implantation is safe and may lead to improved arrhythmia and clinical outcomes in patients presenting with a secondary prevention indication for an ICD. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Research grant to Sheba Medical Center from Boston Scientific

Effect of interleukin-1 inhibition in a cohort of patients with colchicine-resistant familial Mediterranean fever treated consecutively with anakinra and canakinumab

To evaluate the efficacy of IL-1 blockers in a cohort of patients with colchicine-resistant familial Mediterranean fever (crFMF) treated consecutively with anakinra and canakinumab. Patients with crFMF treated with anakinra and canakinumab in any order were identified using the computerised database of Sheba Medical Centre. Background characteristics of the patients, reason for switching IL-1 inhibitor, and frequency of attacks under colchicine only, anakinra, and canakinumab were extracted from the computerised patient files. Patients were then interviewed for patient-reported outcomes. A total of 46 patients in our clinic were prescribed canakinumab for crFMF after previous anakinra treatment, whereas no patients who switched treatment from canakinumab to anakinra were identified. Of those, 23/46 patients (50%) discontinued anakinra due to inadequate response (11 of them with secondary failure after a good initial response). Frequency of flares was significantly decreased following switch to canakinumab from anakinra treatment (p<0.01). After the switch to canakinumab, the median duration of flares, the severity of pain during a flare, and the patient's global assessment of disease activity were all significantly decreased (p≤0.01), according to the reports from the patients. Canakinumab is an effective treatment for FMF after failure of anakinra due to any cause.

Real-World Data Show Patients With Schizophrenia Adhere Better to Clozapine and LAIs

Back to table of contents Previous article Next article Clinical & ResearchFull AccessReal-World Data Show Patients With Schizophrenia Adhere Better to Clozapine and LAIsNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:8 Oct 2021https://doi.org/10.1176/appi.pn.2021.9.32AbstractAn analysis of national VA health databases shows clozapine along with long-acting formulas of aripiprazole and paliperidone have lower discontinuation rates than oral olanzapine, while oral quetiapine and ziprasidone have higher discontinuation rates.Patients with schizophrenia may be less likely to discontinue treatment if prescribed clozapine or long-acting injectable (LAI) formulations of second-generation antipsychotics, according to a report in AJP in Advance. The findings, which also revealed that patients who were taking multiple antipsychotics (polypharmacy) had lower discontinuation rates, were based on data from the U.S. Department of Veterans Affairs (VA).Though the data was limited to veterans, lead author Marc Weiser, M.D., head of the Division of Psychiatry at Sheba Medical Center in Ramat Gan, Israel, noted the findings mirrored those of a 2017 study that used Swedish medical data. “Replicating research findings is difficult,” Weiser noted. “When you have nearly identical outcomes from two studies done by different investigators in different countries using different patient populations, it points to the results being broadly applicable.”Weiser and colleagues compiled VA clinical and pharmacy data from all patients who received a schizophrenia diagnosis and at least one antipsychotic prescription lasting 60 days or more between October 2010 and September 2015. To keep the data robust, the investigators focused on antipsychotics with at least 150 prescriptions during the analysis period. The final sample included 37,368 patients with 62,056 antipsychotic prescriptions among 15 categories: nine oral medications (aripiprazole, clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone, and all first-generation antipsychotics), five LAI formulations (first-generation drugs fluphenazine and haloperidol and second-generation aripiprazole, paliperidone, and risperidone), and patients receiving polypharmacy.The investigators compared the treatment discontinuation rates and hospital admission rates associated with all the medications relative to olanzapine. Weiser noted olanzapine was chosen as the reference since it is considered the most well-tolerated oral antipsychotic and it was used as the reference drug in the 2017 Swedish study.After adjusting for patient sociodemographic factors, Weiser and colleagues found that five groups had a lower risk of treatment discontinuation than olanzapine. These included patients taking clozapine (with nearly 60% less discontinuation risk than olanzapine), a trio of second-generation LAIs (aripiprazole, paliperidone, and risperidone), and patients on polypharmacy. Patients taking oral quetiapine, oral ziprasidone, oral aripiprazole, oral risperidone, and oral first-generation antipsychotics all had higher risks of discontinuation than those taking olanzapine. In a secondary analysis, the investigators found that all three second-generation LAIs were associated with lower risks of discontinuation with the oral formulations of the medications.Weiser told Psychiatric News that he was not surprised by the findings that clozapine was associated with a lower risk of treatment discontinuation than the other antipsychotics. “Since clozapine requires patients to check in regularly, physicians tend to prescribe it to patients who they believe will be compliant; there is a pre-screening process built in.”The polypharmacy findings were a bit more surprising, he noted. “Giving patients multiple antipsychotics is considered a no-no in clinical settings, but this finding supports that giving the right combination of drugs can boost their effectiveness,” he said. Future studies should look at which combinations may offer the most symptom improvement along with lowest risks of side effects.In contrast to the discontinuation findings, none of the medications were found to reduce the risk of psychiatric hospitalization compared with olanzapine. Weiser noted this was the one of the few divergences from the Swedish study, which found clozapine to be superior to olanzapine.While no antipsychotics were superior to olanzapine in terms of hospitalizations, several were associated with increased hospitalization risk: these included oral and LAI first-generation antipsychotics, as well as oral lurasidone, quetiapine, and ziprasidone.Weiser noted that he was particularly concerned about the quetiapine finding, being that this was the second most-prescribed medication in the sample (behind oral risperidone) and this medication was associated with a 36% increased risk of hospitalization. “It is interesting since in the general population, quetiapine is not used that extensively for schizophrenia,” he said. Rather, quetiapine is more commonly prescribed off-label for conditions like anxiety or insomnia.This study was supported by the Stanley Medical Research Institute. Weiser also serves on the staff of the Stanley Institute. ■“Differences in Antipsychotic Treatment Discontinuation Among Veterans With Schizophrenia in the U.S. Department of Veterans Affairs” is posted here.The 2017 analysis, “Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29 823 Patients With Schizophrenia” is posted here. ISSUES NewArchived

An impact of lipid profile and lipid lowering drugs on \u226570\u2009year olds of an upper socioeconomic class: a retrospective cohort study

BackgroundLife expectancy has greatly increased, generating an improvement in screening programs for disease prevention, lifesaving drugs and medical devices. The impact of lowering low-density lipoprotein cholesterol (LDL-C) in the very elderly is not well-established. Our aim was to explore the association of LDL-C, high density lipoprotein cholesterol (HDL-C) and lipid lowering drugs (LLDs) on cognitive decline, malignancies and overall survival.MethodsThis was a retrospective cohort study. Our study comprised 1498 (72.7%) males and 561 (27.3%) females, aged ≥70 who had attended the Institute for Medical Screening (IMS), Sheba Medical Center, Israel at least twice during 2013–2019. Data were obtained from the computerized database of the IMS. A manual quality control to identify potential discrepancies was performed.ResultsOverall, 6.3% of the subjects treated with LLDs (95/1421) versus 4.2% not treated (28/638), cognitively declined during the study years. No statistically significant effects of LDL-C, HDL-C and LLDs on cognitive decline were observed after correcting for age, prior stroke and other vascular risk factors. With regard to cancer, after adjusting for confounders and multiple inferences, no definite relationships were found.ConclusionsThis analysis of an elderly, high socioeconomic status cohort suggests several relationships between the use of LLDs and health outcomes, some beneficial, especially, with regard to certain types of cancer, but with a higher risk of cognitive decline. Further studies are warranted to clarify the health effects of these medications in the elderly.

Kidney and urinary tract findings among patients with Kabuki (make-up) syndrome.

Kabuki syndrome (KS) is a genetic disorder caused mainly by de novo pathogenic variants in KMT2D or KDM6A, characterized by recognizable facial features, intellectual disability, and multi-systemic involvement, including short stature, microcephaly, hearing loss, cardiac defects, and additional congenital anomalies. While congenital anomalies of the kidneys and urinary tract (CAKUT) are known manifestations of this disorder, studies focused solely on kidney involvement are scarce, and its prevalence is most likely underestimated. This study aimed to describe the prevalence and nature of CAKUT and other renal manifestations, in a cohort of KS patients followed at a single tertiary center. All patients who were evaluated at the Sheba Medical Center and received a clinical and/or molecular diagnosis of KS, over a 16-year period (2004-2020), were included. Digital medical records, including ultrasound studies, were reviewed by a team of pediatric nephrologists. Thirteen patients were included in the study, at ages ranging from the neonatal period to 20years. In eight patients, a pathogenic variant in KMT2D was established. CAKUT were detected in 8/13 (61.5%) of patients and varied from hypospadias, hydronephrosis, or double collecting systems to pelvic kidney, kidney asymmetry, horseshoe kidney, or kidney agenesis. One patient experienced kidney failure necessitating transplantation at 20years of age. Our findings underscore the high prevalence of CAKUT and genitourinary involvement in patients with KS and suggest that assessment by pediatric nephrology specialists is warranted as part of the routine multidisciplinary evaluation of newly diagnosed patients. A higher resolution version of the Graphical abstract is available as Supplementary information.

Coronavirus disease 2019 (COVID-19) vaccination uptake among healthcare workers.

To assess reasons for noncompliance with COVID-19 vaccination among healthcare workers (HCWs). Cohort observational and surveillance study. Sheba Medical Center, a 1,600-bed tertiary-care medical center in Israel. The study included 10,888 HCWs including all employees, students, and volunteers. The BNT162b2 mRNA COVID-19 vaccine was offered to all HCWs of the hospital. Noncompliance was assessed, and pre-rollout and post-rollout surveys were conducted. Data regarding uptake of the vaccine as well as demographic data and compliance with prior influenza vaccination were collected, and 2 surveys were distributed. The survey before the rollout pertained to the intention to receive the vaccine, and the survey after the rollout pertained to all unvaccinated HCWs regarding causes of hesitancy. In the pre-rollout survey, 1,673 (47%) of 3,563 HCWs declared their intent to receive the vaccine. Overall, 8,108 (79%) HCWs received the COVID-19 vaccine within 40 days of rollout. In a multivariate logistic regression model, the factors that were significant predictors of vaccine uptake were male sex, age 40-59 years, occupation (paramedical professionals and doctors), high socioeconomic level, and compliance with flu vaccine. Among 425 unvaccinated HCWs who answered the second survey, the most common cause for hesitancy was the risk during pregnancy (31%). Although vaccine uptake among HCWs was higher than expected, relatively low uptake was observed among young women and those from lower socioeconomic levels and educational backgrounds. Concerns regarding vaccine safety during pregnancy were common and more data about vaccine safety, especially during pregnancy, might improve compliance.

Association of Infliximab and Vedolizumab Trough Levels with Reported Rates of Adverse Events: A Cross-Sectional Study.

Infliximab and vedolizumab are effective treatments for inflammatory bowel disease (IBD), although associated with adverse events (AE). While low or non-existent drug levels and positive antidrug antibodies have been associated with therapeutic failure, there is no clear association between higher drug levels and AE. A cross-sectional study consisting of Crohn’s disease (CD) and ulcerative colitis (UC) patients receiving infliximab or vedolizumab at the Sheba Medical Center was performed. Patients completed a questionnaire regarding AEs related to biological therapy. Serum trough levels obtained on the same day were analyzed. Objective measures of outcomes were retrieved from medical records. Questionnaires were completed by infliximab (n = 169) and vedolizumab (n = 88)-treated therapy patients. Higher infliximab levels were only numerically associated with the occurrence of at least one AE (p = 0.08). When excluding fatigue and abdominal pain, higher infliximab levels were statistically associated with the occurrence of at least one AE (p = 0.03). Vedolizumab drug levels > 18 μg/mL were also linked with the occurrence of more AEs. No specific association was observed between the increased levels of either infliximab or vedolizumab and specific AEs (neurological symptoms, upper GI symptoms, infectious complications, and musculoskeletal symptoms). As significant AEs are very rare, additional multi-center studies are required.

P14.36 Characterising Meningiomas in young patients under 40

Abstract BACKGROUND Meningiomas are the most common primary CNS tumor in adults, with a median age at diagnosis of 65 years and a female to male ratio of 2–3:1 (except in grade II, III meningiomas). Younger patients usually have a genetic background or history of prior radiation exposure. Based on population-level studies, approximately 80–85% of meningiomas are WHO grade I (benign), 15–18% grade II (atypical), and 1–3% grade III (anaplastic). This case series describes a single center experience of the presentation and pathology of meningiomas in patients under the age of 40. MATERIALS AND METHODS We reviewed the Sheba Medical Center Neurosurgery and radiotherapy databases containing patients who were operated on for meningioma between the years 2011–2020. Patients under 40 were selected and information from digital medical records was gathered on these patients, including pathology reports, surgical reports, clinical and radiological data, and the use of radiotherapy or medical treatments. RESULTS Of 600 patients in the database, 49 patients under 40 (8.3%) were identified and 54 tumors were reviewed (five patients were operated on for multiple meningiomas). 31 patients were female (63%); 2 were under 20 years old, 15 were age 20–29 and 32 were age 30–39 at first presentation. Seven patients had received prior radiation therapy for a childhood malignancy. 28 meningiomas were histology confirmed grade I (52%), 22 were grade II (41%), 2 were grade III (4%), and 2 (4%) were grade undetermined. 22 tumors were located in the skull base (41%) and 32 (59%) in the brain convexity. Of the skull base tumors, 16 were grade I, 5 were grade II, and one was grade III. Of the convexity tumors, 12 were grade I, 16 were grade II, and 2 were grade III. Median follow-up was 35 months, and longest follow-up time was 98 months. Six patients were treated with additional radiotherapy after surgery. CONCLUSION Our experience with meningioma patients under 40 revealed a different grade segregation than the older population, with younger patients showing a higher incidence of grade II tumors. These tumors are generally more aggressive, and require careful resection and consideration for post-surgical radiotherapy. Further validation with population based databases is required.

Prevalence of Allergic Reactions After Pfizer-BioNTech COVID-19 Vaccination Among Adults With High Allergy Risk

Allergic reactions among some individuals who received the Pfizer-BioNTech (BNT162b2) COVID-19 vaccine discourage patients with allergic conditions from receiving this vaccine and physicians from recommending the vaccine. To describe the assessment and immunization of highly allergic individuals with the BNT162b2 vaccine. In a prospective cohort study from December 27, 2020, to February 22, 2021, 8102 patients with allergies who applied to the COVID 19 vaccine referral center at the Sheba Medical Center underwent risk assessment using an algorithm that included a detailed questionnaire. High-risk patients (n = 429) were considered "highly allergic" and were immunized under medical supervision. Pfizer-BioNTech (BNT162b2) COVID-19 vaccine. Allergic and anaphylactic reactions after the first and second doses of BNT162b2 vaccine among highly allergic patients. Of the 429 individuals who applied to the COVID-19 referral center and were defined as highly allergic, 304 (70.9%) were women and the mean (SD) age was 52 (16) years. This highly allergic group was referred to receive immunization under medical supervision. After the first dose of the BNT162b2 vaccine, 420 patients (97.9%) had no immediate allergic event, 6 (1.4%) developed minor allergic responses, and 3 (0.7%) had anaphylactic reactions. During the study period, 218 highly allergic patients (50.8%) received the second BNT162b2 vaccine dose, of which 214 (98.2%) had no allergic reactions and 4 patients (1.8%) had minor allergic reactions. Other immediate and late reactions were comparable with those seen in the general population, except for delayed itch and skin eruption, which were more common among allergic patients. The rate of allergic reactions to BNT162b2 vaccine, is higher among patients with allergies, particularly among a subgroup with a history of high-risk allergies. This study suggests that most patients with a history of allergic diseases and, particularly, highly allergic patients can be safely immunized by using an algorithm that can be implemented in different medical facilities and includes a referral center, a risk assessment questionnaire, and a setting for immunization under medical supervision of highly allergic patients. Further studies are required to define more specific risk factors for allergic reactions to the BNT162b2 vaccine.

Neuro-ophthalmologic outcomes of standard versus hypo-fractionated stereotactic radiotherapy of AVPM

BackgroundMost anterior visual pathway meningiomas (AVPM) are benign and slow-growing, but these tumors may affect visual functions, including visual acuity (VA) and visual field (VF). Due to location, most are treated non-surgically by fractionated stereotactic radiotherapy (FSRT), aiming to prevent tumor progression and visual functions deterioration. Unfortunately, FSRT in itself may affect visual functions. The current preferred treatment regimen (in terms of safety and effectiveness) is undetermined. While most cases are treated with conventional fractionation (cFSRT)—50.4–54 Gy in 28–30 fractions of 1.8–2 Gy, advances in technology have allowed shortening of total treatment length to hypofractionation (hSRT)—25-27 Gy in 3–5 fractions of 5–9 Gy. Our aim was to evaluate the association of radiotherapy regimen for treating AVPM (cFSRT vs. hSRT) with visual function outcomes (VA, VF) at the last neuro-ophthalmologic evaluation.MethodsWe conducted a retrospective cohort study of AVPM cases treated at Sheba Medical Center during 2004–2015. We compared cFSRT and hSRT regimens regarding visual function (VA, VF) outcomes at the last neuro-ophthalmologic evaluation. VA was determined by the logarithm of the minimum angle of resolution (LogMAR). VF was determined by the mean deviation (MD). A clinically relevant change in VA was defined as 0.2 LogMAR.Results48 patients (13 receiving hSRT, 35 receiving cFSRT) were included, with a median follow-up of 55 months. No significant difference was evident regarding LogMAR or MD of involved eyes at the last evaluation. Six (17%) patients in the cFSRT group experienced clinically relevant VA deterioration in the involved eye, compared with six (46%) in hSRT (p = 0.06).ConclusionOur findings, using comprehensive and meticulous investigation of visual outcomes, suggest that hSRT may be associated with higher risk for VA and VF deterioration in AVPM especially in ONSM. We recommend the use of cFSRT for ONSM.

Patterns of Cone-Beam Computed Tomography (CBCT) Utilization by Various Dental Specialties: A 4-Year Retrospective Analysis from a Dental and Maxillofacial Specialty Center.

The study aimed to analyze the uses of cone-beam computed tomography (CBCT) in the diagnosis and treatment in various dental specialties. This 4-year cross-sectional study analyzed the records of 1409 individuals who underwent a CBCT at the Oral and Maxillofacial Center at Sheba Medical Center, Israel. The average age of the patients was 27.9 ± 11.5 (range: 9–86 years). Patients were referred for CBCT by the following departments: Oral and Maxillofacial Surgery (1063; 75.5%), Endodontics (182; 12.9%), Periodontology (122; 8.6%) and Orthodontics (42; 3.0%). Most CBCT radiographs evaluated the maxilla (774; 55.0%), followed by the mandible (481; 34.1%) and both (154; 10.9%). The target anatomical structures included: bone (694; 49.3%), teeth (307; 21.7%), and both jaws (408; 29.0%). The main indications for CBCT use were: assessment of anatomical structures and implant sites (787; 55.9%), determine root canals morphology (182; 12.9%), visualization of impacted teeth, tooth alignment, and localization (177; 12.6%), suspected cysts or tumors (148; 10.5%), evaluation of Temporomandibular joint disorders (106; 7.5%) and other reasons (9; 0.6%). In 279 (19.8%) of cases, the diagnosis changed following CBCT, mainly in Orthodontics tooth analysis (28 (66.7%); p < 0.001). Practitioners and health authorities should be aware of this baseline information regarding CBCT use in the diagnosis and assessment of various oral and maxillofacial pathologies, anomalies and tooth position relative to anatomic structures. Continuing research and publications of CBCT utilization and guidelines are recommended.

Inpatient Telemedicine and New Models of Care during COVID-19: Hospital Design Strategies to Enhance Patient and Staff Safety.

The challenges of the COVID-19 pandemic have led to the development of new hospital design strategies and models of care. To enhance staff safety while preserving patient safety and quality of care, hospitals have created a new model of remote inpatient care using telemedicine technologies. The design of the COVID-19 units divided the space into contaminated and clean zones and integrated a control room with audio-visual technologies to remotely supervise, communicate, and support the care being provided in the contaminated zone. The research is based on semi-structured interviews and observations of care processes that implemented a new model of inpatient telemedicine at Sheba Medical Center in Israel in different COVID-19 units, including an intensive care unit (ICU) and internal medicine unit (IMU). The study examines the impact of the diverse design layouts of the different units associated with the implementation of digital technologies for remote care on patient and staff safety. The results demonstrate the challenges and opportunities of integrating inpatient telemedicine for critical and intermediate care to enhance patient and staff safety. We contribute insights into the design of hospital units to support new models of remote care and suggest implications for Evidence-based Design (EBD), which will guide much needed future research.