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Aim: Following the Hamas terror attack on Israeli towns on October 2023, 250 individuals were taken into captivity. On November-December 2023, during the cease-fire deal, 26 women and children were released. This study is the first to describe the physical and behavioural findings in children and their mothers in the immediate phase of returning home from captivity., Methods: This is a retrospective study describing the clinical characteristics of the returnees after 49-53 days in captivity. Patients were admitted to a designated unit in the Schnieder Children's Medical Center of Israel on November-December 2023. The hospitalisation duration was 1-9 days. All patients were evaluated according to a detailed protocol and were treated respectively., Results: Patient population included 19 children (ranged 2-18 years old) and 7 women (ranged 34-78 years old). The most common clinical findings upon return included significant weight loss, psychological trauma, complications of poor hygiene and complications of recent shrapnel injuries. Microbiology tests were positive for multiple gastrointestinal pathogens. Serologic screening tests were positive for various infectious diseases., Conclusion: Clinical findings in this time period were diverse and required the attention of a multidisciplinary team. Long term clinical and psychological effects are yet to be known., (© 2024 The Author(s). Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Background: While the number of female medical graduates continues to increase, only a few pursue an orthopaedic career. This is related to challenges regarding pregnancy and the peripartum period during orthopaedic training., Aims: To evaluate fertility, pregnancy-related complications and attitudes towards female orthopaedic surgeons in Israel., Methods: An electronic anonymous 34-question electronic web-based survey was sent to all Israeli female orthopaedic surgeons. Participation was voluntary. Questions were formulated to determine demographics, obstetrics medical history, teratogenic exposure, medical leave and breastfeeding parameters along with attitude towards pregnancy., Results: Twenty-six orthopaedic surgeons complied with the survey, 68% of all registered female orthopaedic surgeons. Participants age was 39.5 (±8.8). The average number of children for a female orthopaedic surgeon was 2.2 (±1.4), with an average of 1.3 (±1.1) deliveries during residency. The average age for a first child was 31.1 (±3.7) years. Four surgeons required fertility treatments and six had abortions. Thirty-eight per cent experienced pregnancy complications. Most surgeons were exposed to radiation and bone cement during pregnancy. The average duration of maternity leave was 19.4 (±9.9) weeks and return to work was associated with cessation of breastfeeding. Seventy-six per cent of surgeons felt that pregnancy had negatively influenced their training, and 12% reported negative attitudes from colleagues and supervisors., Conclusions: Orthopaedic surgeons in Israel experience a delay in childbirth and higher rates of pregnancy complications. Most feel that their training is harmed by pregnancy. Programme directors should design a personalized support programme for female surgeons during pregnancy and the peripartum period., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Cancer incidence in patients with endogenous Cushing's syndrome (CS) has never been established. Here, we aimed to assess the cancer risk in patients with CS as compared with individually matched controls., Design: A nationwide retrospective matched cohort study of patients with endogenous CS diagnosed between 2000 and 2023 using the database of Clalit Health Services in Israel., Methods: Patients with adrenal carcinoma or ectopic CS were excluded. Patients with CS were matched in a 1:5 ratio, with controls individually matched for age, sex, socioeconomic status, and body mass index. The primary outcome was defined as the first diagnosis of any malignancy following a CS diagnosis. Risk of malignancy was calculated using the Cox proportional hazard model, with death as a competing event., Results: A total of 609 patients with CS and 3018 controls were included [mean age at diagnosis, 48.0 ± 17.2 years; 2371 (65.4%) women]. The median follow-up was 14.7 years (IQR, 9.9-20.2 years). Patients with CS had an increased cancer risk, with a hazard ratio (HR) of 1.78 (95% CI 1.44-2.20) compared with their matched controls. The risk of malignancy was elevated in patients with Cushing's disease (251 cases and 1246 controls; HR 1.65, 95% CI 1.15-2.36) and in patients with adrenal CS (200 cases and 991 controls; HR 2.36, 95% CI 1.70-3.29). The increased cancer risk in patients with CS persists after exclusion of thyroid malignancies., Conclusion: Endogenous CS is associated with increased malignancy risk. These findings underscore the need for further research to establish recommendations for cancer screening in this population., Competing Interests: Conflict of Interest: Yaron Rudman, Laura Dery, Hiba Masr-Iraqi, Liat Sasson, Tzipora Shochat, and Shiri Kushnir do not have any financial or personal relationships with other people or organizations to disclose. Amit Akirov has received occasional scientific fee for scientific consulting and advisory boards from Medison, CTS Pharma, and Neopharm. Maria Fleseriu has been a PI with research funding from the university and has received occasional scientific fee for scientific consulting and advisory boards from Crinetics, Recordati, Sparrow, and Xeris. Ilan Shimon has been an investigator for Xeris Biopharma and has received occasional scientific fee for scientific consulting and advisory boards from Medison, CTS Pharma, and Neopharm., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Examining the safety of theBNT162b2 mRNA vaccine in multiple sclerosis (MS) patients remains inconclusive, particularly regarding the potential for disease exacerbations. This study aims to assess the effects of BNT162b2 COVID-19 vaccination on disease activity in MS patients through sequential MRI imaging., Methods: A retrospective study of 84 MS patients from five Israeli hospitals was conducted. MS lesion load was determined from three brain MRI scans, one postvaccination and two prevaccination scans. A post hoc analysis compared subgroups featuring vaccinated and unvaccinated patients respectively, with early onset MS., Results: The cohort included 70 women with early onset (mean age 16.4 ± 0.8 years) and adult onset (mean age 34.9 ± 1.1 years) MS. Among the early onset group, vaccinated patients showed an increased risk of new lesions (p = .00026), while there was no increased risk among adult-onset patients. Additionally, a comparison between early onset vaccinated and nonvaccinated groups revealed a higher risk of increased lesions in the vaccinated group (p = .024)., Discussion: Overall, the study suggests that the BNT162b2 vaccine is generally safe in MS patients, with no association found between vaccination and new lesions in most patients. However, close MRI follow-up is recommended for early-onset MS cases to monitor lesion development., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Objectives: No data are available regarding glycemic management of individuals with type 1 diabetes (T1D) during Passover. Our aim in this study was to assess the effect of Passover on diabetes management and glycemic management in adults with T1D with nutritional changes during Passover (observant) compared with those who did not change their dietary habits during Passover (nonobservant)., Methods: We conducted an observational pre-post study of adults with T1D, followed in a diabetes clinic in Israel. Data were downloaded from insulin pumps and continuous glucose monitoring for 37 days: 2 weeks before Passover, 9 days of Passover, and 2 weeks thereafter. Differences in percentage of time spent above target (>10.0 to >13.9 mmol/L), at target (3.9 to 10.0 mmol/L), and below target (<3.9 to <3.0 mmol/L) were compared using paired t tests or paired signed rank tests., Results: The study cohort included 43 individuals with T1D (23 observant, 20 nonobservant). The average blood glucose was significantly higher during Passover compared with the period before Passover---in nonobservant patients 8.2±1.5 mmol/L and 7.9±1.3 mmol/L (p=0.043), respectively, and in observant patients 8.7±1.6 mmol/L and 8.4±1.6 mmol/L (p=0.048), respectively. Time above range 10 to 13.9 mmol/L was increased in observant individuals during Passover, as compared with the period before Passover, at 24.9±16.2% and 20.6±12.4% (p=0.04), respectively. The dose of bolus insulin had increased significantly in observant individuals: 27.4±13.9 units during Passover, as compared with 24.2±11.2 units before Passover (p=0.02)., Conclusions: Passover alters glycemic management and insulin needs in Jewish adults with T1D. It is advisable to make specific adjustments to maintain the recommended glycemic management., (Copyright © 2024 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Purpose: We evaluated hearing loss and general intelligence among persons with auricle anomalies and cleft lip and/or alveolus and/or cleft palate (CLAP)., Methods: A nationwide cross-sectional study of data recorded during 1966-2019, as mandatory pre-military recruitment of individuals., Results: Of 3 182 892 adolescents, 548 were diagnosed with auricle anomalies and 2072 with CLAP. For the latter, the adjusted odds ratios for the low, low to medium and medium general intelligence categories compared to the highest category were 1.4 [95% CI 1.5-1.2], 1.2 [95% CI 1.4-1.1] and 1.1 [95% CI 1.2-0.9] respectively. The corresponding values for the auricle anomalies were not significant., Conclusions: General intelligence was impaired among individuals with CLAP, but no significant correlation was found among individuals suffering from auricle anomalies., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Living kidney donations in Israel come from 2 sources: family members and individuals who volunteer to donate their kidney to patients with whom they do not have personal acquaintance. We refer to the first group as directed living donors (DLDs) and the second as semidirected living donors (SDLDs). The incidence of SDLD in Israel is ∼60%, the highest in the world. We introduce results of a survey among 749 living donors (349 SDLDs and 400 DLDs). Our data illustrate the sociodemographic profile of the 2 groups and their answers to a series of questions regarding spirituality and social tolerance. We find SDLDs to be sectorial: they are mainly married middle-class religious men who reside in small communities. However, we found no significant difference between SDLDs and DLDs in their social tolerance. Both groups ranked high and expressed tolerance toward different social groups. Semidirected living donation enables donors to express general preferences as to the sociodemographic features of their respected recipients. This stirs a heated debate on the ethics of semidirected living donation. Our study discloses a comprehensive picture of the profile and attitudes of SDLDs in Israel, which adds valuable data to the ongoing debate on the legitimacy of semidirected living donation., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Using immunotherapy to fight cancer, and specifically, the use of engineered T-cells expressing a chimeric receptor against an antigen found on malignant cells (chimeric antigen receptor, CAR-T cells) constitutes a significant breakthrough in the treatment of the disease. In recent years, several CAR-T therapies have been approved in Europe and the USA, and some are already approved and funded through the national health basket in Israel, for the indications of diffuse large B-cell lymphoma, mantle cell lymphoma and B-cell acute lymphoblastic leukemia, after the failure of at least two lines of treatment. The treatment with CAR-T cells achieves prolonged remissions and even long-term cure of patients who had a very poor prognosis. However, the treatment involves significant side effects, and requires specific expertise in the management of patients both during the period of preparation for cell transplantation, and following the treatment. During the immediate post-infusion period, the most common adverse reactions are cytokine release syndrome (CRS) which stems from the activation of the immune system, and neurological toxicity that can accompany CRS. These effects require close monitoring, grading their severity, and providing anti-cytokine therapy or steroid therapy until control of symptoms is achieved. Later effects can be persistent cytopenias, immune over-activation, and prolonged immune deficiency. Treatments for additional indications and new CAR-T constructs are being developed and will allow more effective and safer treatment. This article summarizes the principles for CAR-T administration that, as currently provided in Israel, include the short- and long-term follow-up of the patients.

Background: The leading causes of maternal mortality include respiratory failure, cardiovascular events, infections, and hemorrhages. The use of extracorporeal membrane oxygenation (ECMO) as rescue therapy in the peripartum period for cardiopulmonary failure is expanding in critical care medicine., Methods: This retrospective observational study was conducted on a nationwide cohort in Israel. During the 3-year period, between September 1, 2019, and August 31, 2022, all women in the peripartum period who had been supported by ECMO for respiratory or circulatory failure at 10 large Israeli hospitals were identified. Indications for ECMO, maternal and neonatal outcomes, details of ECMO support, and complications were collected., Results: During the 3-year study period, in Israel, there were 540 234 live births, and 28 obstetric patients were supported by ECMO, with an incidence of 5.2 cases per 100 000 or 1 case per 19 000 births (when excluding patients with COVID-19, the incidence will be 2.5 cases per 100 000 births). Of these, 25 were during the postpartum period, of which 16 (64%) were connected in the PPD1, and 3 were during pregnancy. Eighteen patients (64.3%) were supported by V-V ECMO, 9 (32.1%) by V-A ECMO, and one (3.6%) by a VV-A configuration. Hypoxic respiratory failure (ARDS) was the most common indication for ECMO, observed in 21 patients (75%). COVID-19 was the cause of ARDS in 15 (53.7%) patients. The indications for the V-A configuration were cardiomyopathy (3 patients), amniotic fluid embolism (2 patients), sepsis, and pulmonary hypertension. The maternal and fetal survival rates were 89.3% (n = 25) and 100% (n = 28). The average ECMO duration was 17.6 ± 18.6 days and the ICU stay was 29.8 ± 23.8 days. Major bleeding complications requiring surgical intervention were observed in one patient., Conclusions: The incidence of using ECMO in the peripartum period is low. The maternal and neonatal survival rates in patients treated with ECMO are high. These results show that ECMO remains an important treatment option for obstetric patients with respiratory and/or cardiopulmonary failure., (© 2023 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

The COVID-19 pandemic posed a major challenge in cancer care worldwide which might have an impact on the management of diffuse large B-cell lymphoma (DLBCL). We conducted a retrospective study comparing characteristics, management, and outcomes of DLBCL patients diagnosed during the first year of the COVID-19 pandemic (1/3/2020-28/2/2021) to those diagnosed in the previous year (1/3/2019-28/2/2020) in two tertiary centers in Italy and Israel. 182 patients were diagnosed with DLBCL during the study period. More patients were diagnosed during the pandemic compared to the year before: 60 vs. 29 and 54 vs. 39 in Italy and in Israel, respectively. Trends towards older age and higher transformation rates were shown during the pandemic. The interval between the initiation of symptoms and diagnosis was longer during the pandemic. Five and four patients were diagnosed with COVID-19 during treatment in Italy and in Israel, respectively. there was no difference in dose density and intensity of treatment, before and during the pandemic. The median follow-up during and before the pandemic was 15.2 and 25.5 months, respectively. Progression-free survival (PFS) was slightly shorter during the pandemic compared to the year before (64.9% vs. 70.6%; p = 0.0499). In multivariate analysis, older age and transformed disease were independently related to PFS, while diagnosis of DLBCL during the pandemic was not. Despite the challenges caused by COVID-19 pandemic, the management of DLBCL patients remained unchanged including dose density and intensity. Nevertheless, a shorter PFS during the outbreak might be attributed to differences in patients' characteristics., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Banking of frozen spermatozoa by single men opens the possibility of procreation long after their death. Requests for posthumous reproduction by the families of the deceased are growing, raising an ethical debate, especially when written instructions were not left by the patients and in cases of unplanned perimortem collection. The issue of the progenitors' intention to procreate after death is the key to ethically based decision-making in these cases., Objectives: To evaluate the attitude of single men cryopreserving spermatozoa before life-threatening medical situations towards post-mortem usage of their cryopreserved spermatozoa., Materials & Methods: Adult single men prior to sperm cryopreservation before cytotoxic therapy were asked to sign a structured form declaring their will and instructions for the usage of their cryopreserved spermatozoa in case of their demise., Results: Four hundred fifty-two men of diverse ethnicity, religious and cultural backgrounds signed the form providing instructions for the use of their cryopreserved spermatozoa in case of mortality. Their age was 27.4 ± 8.06 years. Seven (1.5%) patients willed their spermatozoa for posthumous reproduction to a sibling, 22 (4.9%) to parents, and 26 (5.7%) to their informal female partners. The significant majority (n = 397; 87.8 %) of the single men were ordered to destroy their cryopreserved spermatozoa in case of their expiry. Note that, 26-39 years old men were less likely (81.8% vs. >90% in other ages) to order sperm destruction, as well as men with a poorer prognosis (83% vs. 90%)., Discussion: In this study group, most single men cryopreserving spermatozoa in the face of future life-threatening morbidity do so for their own future live parenthood, and are not interested in posthumous reproduction., Conclusion: Our results doubt the claim that single men who had an unplanned perimortem sperm collection can be universally presumed to have wished to father a child posthumously. Any claimed assumed consent in these cases should be considered for each case individually based on its specific circumstances., (© 2023 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Objective: Multiple cases and case series reported Graves' disease (GD) following coronavirus disease 2019 (COVID-19) vaccination. We aimed to determine whether COVID-19 vaccination was associated with the incidence of GD., Methods: We analyzed data from Clalit Health Services, the largest healthcare organization in Israel, which insures 4.7 million patients. A population-based, matched, case-control study was performed. Cases were defined as adult patients diagnosed with GD between December 2020 and November 2022. Each case was matched with controls in a 1:2 ratio. Each control was assigned an index date, which was identical to that of their matched case, defined as the date of GD diagnosis. Time between vaccination date and the diagnosis of GD or index date was assessed., Results: A total of 726 patients with GD were matched with 1452 controls. The study patients and controls have received similar proportions of the COVID-19 vaccine [at least 1 dose: 80% (581/726) vs 77.8% (1129/1452), P = .22, respectively]. In a univariate analysis, at least 1 dose of the COVID-19 vaccine was not associated with the incidence of GD [odds ratio 95% confidence interval: 1.15 (.92-1.43)]. The mean time between first COVID-19 vaccination and the diagnosis of GD for cases or index date for controls was not significantly different [275.69 days (SD 144.37) for cases compared to 275.45 days (SD 145.76) for controls]., Conclusion: Our study found no association between COVID-19 vaccination and the incidence of GD., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Wilson disease is caused by pathogenic variants in the ATP7B gene which encodes a copper-transporting ATPase., Aims: Describe a common founder pathogenic variant among Bukharan Jews and to assess its prevalence, clinical features, and outcome., Methods: The cohort consisted of patients of Bukharan Jewish descent diagnosed with Wilson disease at a tertiary pediatric medical center in 2013-2018. Clinical and genetic data were collected and analyzed., Results: Six patients from 4 unrelated families who were homozygous for the c.3784G > T p.(Val1262Phe) pathogenic variant in ATP7B were identified. Five presented with elevated aminotransferase levels, and one, with acute liver failure. Mean age at diagnosis was 8.7 years (5-12.5). Serum ceruloplasmin level was extremely low in all patients (1.9-7 mg/dL; mean 3.2(. The variant was identified in a heterozygous state in 5/153 Bukharan Jews; 2/33 from our local exome database and 3/120 healthy unrelated Bukharan Jews in another cohort, for an estimated carrier frequency of ∼1:30., Conclusions: We report a common founder pathogenic variant in the ATP7B gene among Bukharan Jews associated with severe early-onset Wilson disease. Given the clinical severity, high frequency of the variant, and being a treatable disease, its inclusion in pre-symptomatic screening in the Bukharan Jewish community should be considered. Furthermore, WD should be part of future genetic newborn screening programs in Israel and worldwide, to enable early treatment and prevention of future life-threatening complications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Polygenic risk score (PRS), calculated based on genome-wide association studies (GWASs), can improve breast cancer (BC) risk assessment. To date, most BC GWASs have been performed in individuals of European (EUR) ancestry, and the generalisation of EUR-based PRS to other populations is a major challenge. In this study, we examined the performance of EUR-based BC PRS models in Ashkenazi Jewish (AJ) women., Methods: We generated PRSs based on data on EUR women from the Breast Cancer Association Consortium (BCAC). We tested the performance of the PRSs in a cohort of 2161 AJ women from Israel (1437 cases and 724 controls) from BCAC (BCAC cohort from Israel (BCAC-IL)). In addition, we tested the performance of these EUR-based BC PRSs, as well as the established 313-SNP EUR BC PRS, in an independent cohort of 181 AJ women from Hadassah Medical Center (HMC) in Israel., Results: In the BCAC-IL cohort, the highest OR per 1 SD was 1.56 (±0.09). The OR for AJ women at the top 10% of the PRS distribution compared with the middle quintile was 2.10 (±0.24). In the HMC cohort, the OR per 1 SD of the EUR-based PRS that performed best in the BCAC-IL cohort was 1.58±0.27. The OR per 1 SD of the commonly used 313-SNP BC PRS was 1.64 (±0.28)., Conclusions: Extant EUR GWAS data can be used for generating PRSs that identify AJ women with markedly elevated risk of BC and therefore hold promise for improving BC risk assessment in AJ women., Competing Interests: Competing interests: BCAC conflict of interest: MWB conducts research funded by Amgen, Novartis and Pfizer. PAF conducts research funded by Amgen, Novartis and Pfizer. He received Honoraria from Roche, Novartis and Pfizer. JV is one ofthe inventors of diagnosis and treatment of ERCC3-mutant cancer. AWK has a research funding for his institution from Myriad Genetics for an unrelated project (funding dates 2017–2019). UM has research collaborations with Mercy BioAnalytics, RNA Guardian, Dana Farber and iLOF (Intelligent Lab on Fiber). RAM is a consultant for Pharmavite., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objective: To determine genealogical, clinical and pathological characteristics of a cohort with Cys618Arg mutation from an Israeli multicenter MTC study., Methods: Retrospective database analysis examining RET mutations and comparing Cys618Arg and Cys634Arg/Thr/Tyr subgroups., Results: Genetic testing was performed in 131/275 MTC patients (47.6%). RET mutations were found in 50/131 (38.2%), including Cys618Arg (28/50 cases,56%), and Cys634Arg/Thr/Tyr (15/50,30%). Through genealogical study, 31 MTC patients were found descendants of one family of Jewish Moroccan descent, accounting for 27/28 patients with documented Cys618Arg mutation and 4 patients without available genetic testing. Familial Cys618Arg cases (n=31) and Cys634Arg/Thr/Tyr cases (n=15, from 6 families) were compared. Although surgical age was similar (25.7 vs 31.3 years, p=0.19), the Cys618Arg group had smaller tumors (8.9mm vs 18.5mm, p=0.004) and lower calcitonin levels (33.9 vs 84.5 X/ULN, p=0.03). Youngest ages at MTC diagnosis were 8 and 3 years in Cys618Arg and Cys634Arg/Thr/Tyr cohorts, respectively. Long-term outcome was similar between groups. The Cys618Arg cohort had lower rates of pheochromocytoma (6.5% vs 53.3%, p=0.001) and primary hyperparathyroidism (3.2% vs 33.3%, p=0.01)., Conclusion: This is the first description of RET mutation distribution in Israel. Of 131 tested MTC patients, Cys618Arg was the predominant mutation. To the best of our knowledge, this is the largest cohort of Cys618Arg mutation described. For Cys618Arg and Cys634Arg/Thr/Tyr cohorts, MTC was diagnosed earlier than expected, likely due to familial genetic screening, and MTC outcomes were similar between groups. International studies are necessary to further characterize the clinical features of Cys618 mutations due to their relative rarity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rosenblum, Hirsch, Grozinsky-Glasberg, Benbassat, Yoel, Ishay, Zolotov, Bachar, Banne, Levy and Twito.)

Introduction: Initiation of global vaccination significantly reduced the morbidity and mortality of COVID-19. During the Omicron wave, approximately 70% of the Israeli adult population was fully vaccinated, but the efficacy of the vaccine was questioned., Methods: We conducted a retrospective cohort study of all adult patients admitted to the COVID-19 departments in Rabin Medical Center, during the Delta wave and the Omicron wave. Patients were matched in the 2 waves using the inverse probability of treatment weighting (IPTW) method and risk for mechanical ventilation and 30-day all-cause mortality was assessed., Results: Vaccination had a significant effect on 30-day mortality in the Delta and Omicron waves with adjusted OR of 0.35 (0.17-0.70) and 0.5 (0.27-0.95) respectively. Nonetheless, the rate of mechanical ventilation was similar between the groups with OR of 0.75 (0.52-1.09) and 0.64 (0.40-1.01). Vaccination status did not change the length of admission in both waves., Conclusion: We observed a decreased risk for 30-day mortality among vaccinated patients during the Delta and Omicron waves in Israel. This association, even though consistent, was of a lesser magnitude during the Omicron wave., (Copyright © 2023 Elsevier España, S.L.U. All rights reserved.)

Background: Previous studies demonstrated a 'weekend effect' and a 'night effect' of increased mortality among patients admitted during weekends or night shifts, presumably due to understaffing., Aims: To examine whether death during hospitalisation follows a similar effect regardless of admission time., Methods: A retrospective cohort study among deceased patients hospitalised in the internal medicine wing of a tertiary medical centre in Israel, between 2019 and 2020. Demographic and medical data were retrieved from electronic medical charts. Causes of death were specifically categorised. We applied statistical models to test for differences in mortality using incidence rate ratio (IRR) according to the day, time and cause of death., Results: One thousand, two hundred and seventy-eight deceased patients were included. All-cause mortality was similar between weekends and weekdays. When sepsis was the cause of death, higher IRR were demonstrated on Fridays in comparison with weekdays (IRR 1.4; 95% confidence interval (CI) 1.1-1.9; P < 0.05). Other causes of death were not consistent with a 'weekend effect'. Mortality during night shifts was higher in comparison with the afternoon (IRR 1.5; 95% CI 1.3-4.7) and similar to the morning (IRR 1; 95% CI 0.9-1.2)., Conclusion: Our study did not find a pattern of 'weekend effect' or 'night effect' on all-cause mortality among hospitalised patients in internal medicine wards. Our findings suggest that perhaps specifically death from sepsis, and not all-cause mortality, can be used as a surrogate for the measurement of understaffing or quality of care in the internal ward., (© 2022 Royal Australasian College of Physicians.)

Background: Thyroid cancer (TC) is one of the most common carcinomas in young women. Concerns have been raised regarding the impact of the disease and its treatment on reproductive function. The aim of the study was to investigate the association of TC diagnosis and radioactive iodine (RAI) treatment on infertility and pregnancy rates in women. Methods: The comprehensive computerized database of a health management organization in Israel was screened for all female patients who were diagnosed with TC at age ≤40 years in 2000-2020. Rates of infertility (based on a documented diagnosis or purchase of fertility medications in the patient files) and pregnancy were compared with healthy age-matched controls. Results: The cohort included 1164 patients with TC (median age at diagnosis 31.6 years; interquartile range [IQR]: 26.7-35.4) and 5030 controls, followed for a median period of 10 years (IQR: 5.0-15.0). The infertility rate was higher in the TC group than in the control group (23.9% vs. 20.4%, p  = 0.008). Still, the postdiagnosis/referent date pregnancy rates were comparable in the whole cohort (46.9/47.7%, p  = 0.625) and across all age quartiles. The median time to the first pregnancy postdiagnosis/referent date was longer in TC patients than in controls (37 vs. 31 months, p  < 0.001). Within the TC group, women who received repeated radioactive iodine treatment ( n  = 611, 52.5%) had comparable rates of infertility and pregnancy as those who did not. However, their time to the first postdiagnosis pregnancy was longer (median 45 vs. 29 months, p  = 0.020). Conclusions: Our study provides reassuring evidence about the reproductive characteristics of women treated for TC. Pregnancy rates in TC survivors were comparable with controls. However, a higher infertility rate and a longer time to conceive were observed in the TC group compared with the control group. These findings were consistent in women who received single or repeated RAI treatments.

Objective: We aimed to characterize the course of COVID-19 in autoimmune inflammatory rheumatic disease (AIIRD) patients in Israel, taking into consideration several remarkable aspects, including the outcomes of the different outbreaks, the effect of vaccination campaigns, and AIIRD activity post-recovery., Methods: We established a national registry of AIIRD patients diagnosed with COVID-19, including demographic data, AIIRD diagnosis, duration and systemic involvement, comorbidities, date of COVID-19 diagnosis, clinical course, and dates of vaccinations. COVID-19 was diagnosed by a positive SARS-CoV-2 polymerase chain reaction., Results: Israel experienced 4 outbreaks of COVID-19 until 30.11.2021. The first three outbreaks (1.3.2020 - 30.4.2021) comprised 298 AIIRD patients. 64.9% had a mild disease and 24.2% had a severe course; 161 (53.3%) patients were hospitalized, 27 (8.9%) died. The 4 th outbreak (delta variant), starting 6 months after the beginning of the vaccination campaign comprised 110 patients. Despite similar demographic and clinical characteristics, a smaller proportion of AIIRD patients had negative outcomes as compared to the first 3 outbreaks, with regards to severity (16 patients,14.5%), hospitalization (29 patients, 26.4%) and death (7 patients, 6.4%). COVID-19 did not seem to influence the AIIRD activity 1-3 months post-recovery., Conclusions: COVID-19 is more severe and has an increased mortality in active AIIRD patients with systemic involvement, older age and comorbidities. Vaccination with 3 doses of the mRNA vaccine against SARS-CoV-2 protected from severe COVID-19, hospitalization and death during the 4 th outbreak. The pattern of spread of COVID-19 in AIIRD patients was similar to the general population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kharouf, Eviatar, Braun, Pokroy-Shapira, Brodavka, Zloof, Agmon-Levin, Toledano, Oren, Lidar, Zisman, Tavor, Amit-Vazina, Sabbah, Breuer, Dagan, Beshara-Garzuzi, Markovits, Elias, Feld, Tayer-Shifman, Gazitt, Reitblatt, Rubin, Haddad, Giryes, Paran, Peleg, Molad, Elkayam, Mevorach, Balbir-Gurman and Braun-Moscovici.)

Background: The Israeli physician workforce faces multiple challenges. These include planned policies reducing physician on-call from 26 to 18 h and, from 2026, allowing only graduates of Ministry of Health approved foreign medical schools to take the Israeli licensing examination and an ongoing physician shortage (2019: Israel had 3.19 physicians/1000 persons vs. OECD average of 3.49 physicians/1000 persons). This study examines the potential impact of these planned policies on the Israeli anesthesiology workforce., Methods: Surveys conducted among 34 public and private Israeli hospital anesthesiology department chairs collected data on their department's number of weekday on-call anesthesiologists and current shortage of anesthesiologists. A subsequent survey collected data on each anesthesiologist in the workforce, including the country where they studied medicine., Results: Each weekday night there were 114 on-call anesthesiologists; 72 residents and 42 attendings. Using productive work coefficients, this translates to 104 resident and 51 attending anesthesiologists. Furthermore, 21 departments had existing anesthesia workforce shortages totaling 110 anesthesiologists. There were 873 anesthesiologists from non-OECD countries whose medical schools are not accredited by the World Federation for Medical Education, of whom 332 were residents (61.9% of residents). Only 20.1% of anesthesiology residents were Israeli medical school graduates., Conclusions: Descriptive survey data assessed the immediate and long-term consequences for the healthcare system and anesthesiology workforce of two new Health Ministry policies. Implementing the 18-h policy will immediately remove from the daytime workforce 155 anesthesiologists and who will be unavailable to staff elective surgery operating rooms. This will compound the current national shortage of 110 anesthesiologists. It is unclear how to replace this shortfall since there are no surplus Israeli physicians and very few Israeli graduates choose anesthesiology as a specialty. This situation will be exacerbated after 2026 when graduates of certain foreign medical schools will be unable to enter the medical workforce, further reducing the pool of potential anesthesiology residents. Both policies were promulgated without adequate operational and budgetary planning or fiscal or workforce resources; implementation of the 18-h on-call policy has already been postponed. Therefore, new or updated policies must be accompanied by specific operational plans, budgetary allocations and funds for additional workforce., (© 2023. The Author(s).)

The current monkeypox virus global spread and lack of data regarding clinical specimens' infectivity call for examining virus infectivity, and whether this correlates with results from PCR, the available diagnostic tool. We show strong correlation between viral DNA amount in clinical specimens and virus infectivity toward BSC-1 cell line. Moreover, we define a PCR threshold value (Cq ≥ 35, ≤ 4,300 DNA copies/mL), corresponding to negative viral cultures, which may assist risk-assessment and decision-making regarding protective-measures and guidelines for patients with monkeypox.

Background: Neuraxial protocols for cesarean delivery differ among institutions, with various means of assessing the block prior to incision and managing breakthrough intra-operative pain. The different approaches used to deal with these issues in Israel have not been assessed., Methods: Questionnaires were distributed to all anesthesiologists working in obstetric units in Israeli hospitals. The survey included several non-identifying respondent details intended to allow a description of the study population as a whole and multiple-choice questions addressing neuraxial techniques, method of pre-operative block assessment and medications used to treat intra-operative pain., Results: Three hundred and sixty-one doctors completed the survey in 24 medical centers, an 81.1% response rate. Thirteen different protocols for spinal anesthesia and 20 different protocols for epidural anesthesia were described. Nine different protocols for assessment of the block prior to incision were identified, with significant inter-institutional differences (P <0.001). For treatment of intra-operative pain prior to delivery, 35.7% of spinals given and 40% of epidurals given were converted to general anesthesia whereas, after delivery, conversion of spinal to general anesthesia was 18% and epidural to general anesthesia was 18.6%., Conclusions: There were a variety of spinal and epidural regimens used as well as different methods for assessing the block and managing intra-operative pain. Further studies should be performed to identify optimal techniques for neuraxial anesthesia for pre-operative block assessment and for management of intra-operative pain., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Most studies estimate hepatitis C virus (HCV) disease prevalence from convenience samples. Consequently, screening policies may not include those at the highest risk for a new diagnosis., Methods: Clalit Health Services members aged 25-74 as of 31 December 2009 were included in the study. Rates of testing and new diagnoses of HCV were calculated, and potential risk groups were examined., Results: Of the 2 029 501 included members, those aged 45-54 and immigrants had lower rates of testing (12.5% and 15.6%, respectively), higher rates of testing positive (0.8% and 1.1%, respectively), as well as the highest rates of testing positive among tested (6.1% and 6.9%, respectively)., Discussion: In this population-level study, groups more likely to test positive for HCV also had lower rates of testing. Policy makers and clinicians worldwide should consider creating screening policies using on population-based data to maximize the ability to detect and treat incident cases., (© The Author(s) 2020. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Reports have suggested an association between the development of myocarditis and the receipt of messenger RNA (mRNA) vaccines against coronavirus disease 2019 (Covid-19), but the frequency and severity of myocarditis after vaccination have not been extensively explored., Methods: We searched the database of Clalit Health Services, the largest health care organization (HCO) in Israel, for diagnoses of myocarditis in patients who had received at least one dose of the BNT162b2 mRNA vaccine (Pfizer-BioNTech). The diagnosis of myocarditis was adjudicated by cardiologists using the case definition used by the Centers for Disease Control and Prevention. We abstracted the presentation, clinical course, and outcome from the patient's electronic health record. We performed a Kaplan-Meier analysis of the incidence of myocarditis up to 42 days after the first vaccine dose., Results: Among more than 2.5 million vaccinated HCO members who were 16 years of age or older, 54 cases met the criteria for myocarditis. The estimated incidence per 100,000 persons who had received at least one dose of vaccine was 2.13 cases (95% confidence interval [CI], 1.56 to 2.70). The highest incidence of myocarditis (10.69 cases per 100,000 persons; 95% CI, 6.93 to 14.46) was reported in male patients between the ages of 16 and 29 years. A total of 76% of cases of myocarditis were described as mild and 22% as intermediate; 1 case was associated with cardiogenic shock. After a median follow-up of 83 days after the onset of myocarditis, 1 patient had been readmitted to the hospital, and 1 had died of an unknown cause after discharge. Of 14 patients who had left ventricular dysfunction on echocardiography during admission, 10 still had such dysfunction at the time of hospital discharge. Of these patients, 5 underwent subsequent testing that revealed normal heart function., Conclusions: Among patients in a large Israeli health care system who had received at least one dose of the BNT162b2 mRNA vaccine, the estimated incidence of myocarditis was 2.13 cases per 100,000 persons; the highest incidence was among male patients between the ages of 16 and 29 years. Most cases of myocarditis were mild or moderate in severity. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.)., (Copyright © 2021 Massachusetts Medical Society.)

Objectives: To evaluate the sex-specific effects of stimulants in children with attention-deficit/hyperactivity disorder (ADHD) on body mass index (BMI) z and height z trajectories., Study Design: A retrospective cohort study using the database of Israel Clalit Health Services was performed. Participants included 5- to 18-year-old insured patients with documentation of at least 2 consecutive prescriptions of stimulant drugs for ADHD. Participants were further compared with sex- and age-matched insured control patients without ADHD., Results: A total of 4561 (66% boys) participants with ADHD were included. Of these, 2151 (70% boys) had follow-up data for ≥2 years of treatment. A decline of ≥1 SD in height and BMI z score was observed in 10.1% and 13.2% of the cohort, respectively. During ≥2 years follow-up, boys had a greater decline in height z score (~0.2 SD) than girls (~0.06 SD). Boys' height z score continued to decline after 1 and ≥2 years, and girls' height z score declined after 1 year, and then stabilized. The trajectory of BMI z score of boys and girls was similar, showing a greater decline after 1 year, followed by an incline after ≥2 years. Younger age at stimulants initiation, better adherence, longer treatment duration, and lower socioeconomic status were correlated with a greater impact on growth attenuation. The non-ADHD group (n = 4561, 66% boys) had baseline height z score and BMI z score similar to those in children with ADHD before treatment initiation. Height z score and BMI z score were greater in children without ADHD compared with children with ADHD following 1 year of treatment (P < .001)., Conclusions: These findings highlight the importance of growth monitoring accompanied with dietary counseling in children with ADHD treated with stimulants., (Copyright © 2021. Published by Elsevier Inc.)

Background: Gliomas manifest in a variety of histological phenotypes with varying aggressiveness. The etiology of glioma remains largely unknown. Taller stature in adulthood has been linked with glioma risk. The aim of this study was to discern whether this association can be detected in adolescence., Methods: The cohort included 2 223 168 adolescents between the ages of 16 and 19 years. Anthropometric measurements were collected at baseline. Incident cases of glioma were extracted from the Israel National Cancer Registry over a follow-up period spanning 47 635 745 person-years. Cox proportional hazard models were used to estimate the hazard ratio (HR) for glioma and glioma subtypes according to height, body mass index (BMI), and sex., Results: A total of 1195 patients were diagnosed with glioma during the study period. Mean (SD) age at diagnosis was 38.1 (11.7) years. Taller adolescent height (per 10-cm increase) was positively associated with the risk for glioma of any type (HR: 1.15; P = .002). The association was retained in subgroup analyses for low-grade glioma (HR: 1.17; P = .031), high-grade glioma (HR: 1.15; P = .025), oligodendroglioma (HR: 1.31; P = .015), astrocytoma (HR: 1.12; P = .049), and a category of presumed IDH-mutated glioma (HR: 1.17; P = .013). There was a trend toward a positive association between height and glioblastoma, however this had borderline statistical significance (HR: 1.15; P = .07). After stratification of the cohort by sex, height remained a risk factor for men but not for women., Conclusions: The previously established association between taller stature in adulthood and glioma risk can be traced back to adolescence. The magnitude of association differs by glioma subtype., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Patients with cancer undergoing treatment are at high risk of COVID-19 following SARS-CoV-2 infection; however, their ability to produce an adequate antibody response to messenger RNA SARS-CoV-2 vaccines is unclear., Objective: To evaluate rates of antispike (anti-S) antibody response to a BNT162b2 vaccine in patients with cancer who are undergoing systemic treatment vs healthy controls., Design, Setting, and Participants: This prospective cohort study included 102 adult patients with solid tumors undergoing active intravenous anticancer treatment and 78 controls who received the second dose of the BNT162b2 vaccine at least 12 days before enrollment. The controls were taken from a convenience sample of the patients' family/caregivers who accompanied them to treatment. The study was conducted between February 22, 2021, and March 15, 2021 at Davidoff Cancer Center at Beilinson Hospital (Petah Tikva, Israel)., Interventions: Blood samples were drawn from the study participants. Serum samples were analyzed and the titers of the IgG antibodies against SARS-CoV-2 spike receptor-binding domain were determined using a commercially available immunoassay. Seropositivity was defined as 50 or greater AU/mL., Main Outcomes and Measures: The primary outcome was the rate of seropositivity. Secondary outcomes included comparisons of IgG titers and identifying factors that were associated with seropositivity using univariate/multivariable analyses., Results: The analysis included 180 participants, which comprised 102 patients with cancer (median [interquartile range (IQR)] age, 66 [56-72] years; 58 men [57%]) and 78 healthy controls (median [IQR] age, 62 [49-70] years; 25 men [32%]). The most common tumor type was gastrointestinal (29 [28%]). In the patient group, 92 (90%) were seropositive for SARS-CoV 2 antispike IgG antibodies after the second vaccine dose, whereas in the control group, all were seropositive. The median IgG titer in the patients with cancer was significantly lower than that in the controls (1931 [IQR, 509-4386] AU/mL vs 7160 [IQR, 3129-11 241] AU/mL; P < .001). In a multivariable analysis, the only variable that was significantly associated with lower IgG titers was treatment with chemotherapy plus immunotherapy (β, -3.5; 95% CI, -5.6 to -1.5)., Conclusions and Relevance: In this cohort study of patients with cancer who were receiving active systemic therapy, 90% of patients exhibited adequate antibody response to the BNT162b2 vaccine, although their antibody titers were significantly lower than those of healthy controls. Further research into the clinical relevance of lower titers and their durability is required. Nonetheless, the data support vaccinating patients with cancer as a high priority, even during therapy.

Obesity is associated with an increased susceptibility to infections. Several studies have reported adverse clinical outcomes of influenza among obese individuals. Our aim was to examine the association between obesity and the clinical outcomes of hospitalized adult patients ill with seasonal influenza. Consecutive hospitalized adult patients between 10/2017 and 4/2018 with laboratory confirmed influenza A and B were divided into an obese group (body mass index (BMI) ≥ 30 kg/m 2 ) and controls. The primary outcome was a composite endpoint of 30-day all-cause mortality, vasopressor use, mechanical ventilation, ICU admission, and severe influenza complication (myocarditis and encephalitis). Secondary outcomes encompassed all the components of the primary outcome, 90-day all-cause mortality, occurrence of pneumonia, length of hospital stay, and 90-day readmission rates. The study comprised 512 hospitalized adults diagnosed with laboratory-confirmed influenza A (195/512) and B (317/512). Within this group, 17% (86/512) were classified obese; the remaining 83% (426/512) were controls. Results of the composite outcome (7/85, 8% vs. 45/422, 11%; p=0.5) and the crude 30-day all-cause mortality rate (5/86, 6% vs. 34/426, 8%, p=0.5) were similar between the two groups. The multivariate analysis demonstrated that obesity was not a significant risk factor for influenza adverse events (OR=1.3, CI 95% 0.3-3.3; p=0.5), whereas advanced age, chronic kidney disease, and hypoalbuminemia were significant risk factors (OR=1.03, OR=2.7, and OR=5.4, respectively). Obesity was not associated with influenza-related morbidity and mortality among the hospitalized adults during the 2017-2018 influenza season. Further studies researching different influenza seasons are essential.

Abstract: Radioiodine-refractory thyroid cancers (IRTCs) are uncommon and have a poor prognosis. Treatment options for radioiodine-refractory and anaplastic tumors (ATCs) are limited. Although the genomic landscape of thyroid cancer has been studied, there is little evidence on whether next-generation sequencing (NGS) findings translate to tumor control.We analyzed all patients with IRTC and ATC who underwent commercially available NGS in 3 cancer centers.Twenty-two patients were identified, 16 patients with IRTCs and 6 patients with ATCs. Eighteen (82%) had targetable findings in NGS, nine patients were treated accordingly. Median progression-free survival for targeted treatment was 50 months [95% confidence interval (CI95%) 9.8-66.6] and2 months (CI95% 0.2-16.5) for IRTC and ATC, respectively. Of 4 patients who achieved durable responses of 7 to 50 months, 2 are ongoing. The estimated median OS of IRTC receiving targeted treatment was not reached (CI95% 89.7-111.4 months) and was 77.8 months (CI95% 52.5-114.6) for patients treated conventionally (P = .3).NGS may detect clinically significant genetic alterations and benefit patients with advanced thyroid cancers., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Secondary bacterial infections are a potentially fatal complication of influenza infection. We aimed to define the impact of secondary bacterial infections on the clinical course and mortality in coronavirus disease 2019 (COVID-19) patients by comparison with influenza patients. COVID-19 (n = 642) and influenza (n = 742) patients, admitted to a large tertiary center in Israel and for whom blood or sputum culture had been taken were selected for this study. Bacterial culture results, clinical parameters, and death rates were compared. COVID-19 patients had higher rates of bacterial infections than influenza patients (12.6% vs. 8.7%). Notably, the time from admission to bacterial growth was longer in COVID-19 compared to influenza patients (4 (1-8) vs. 1 (1-3) days). Late infections (> 48 h after admission) with gram-positive bacteria were more common in COVID-19 patients (28% vs. 9.5%). Secondary infection was associated with a higher risk of death in both patient groups 2.7-fold (1.22-5.83) for COVID-19, and 3.09-fold (1.11-7.38) for Influenza). The association with death remained significant upon adjustment to age and clinical parameters in COVID-19 but not in influenza infection. Secondary bacterial infection is a notable complication associated with worse outcomes in COVID-19 than influenza patients. Careful surveillance and prompt antibiotic treatment may benefit selected patients.

Objectives: The effectiveness of remdesivir, a Food and Drug Administration-approved drug for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been repeatedly questioned during the current coronavirus disease 2019 (COVID-19) pandemic. Most of the recently reported studies were randomized controlled multicentre clinical trials. Our goal was to test the efficiency of remdesivir in reducing nasopharyngeal viral load and hospitalization length in a real-life setting in patients admitted to a large tertiary centre in Israel., Methods: A total of 142 COVID-19 patients found to have at least three reported SARS-CoV-2 quantitative RT-PCR tests during hospitalization were selected for this study. Of these, 29 patients received remdesivir, while the remaining non-treated 113 patients served as controls., Results: Among the tested parameters, the control and remdesivir groups differed significantly only in the intubation rates. Remdesivir treatment did not significantly affect nasopharyngeal viral load, as determined by comparing the differences between the first and last cycle threshold values of the SARS-CoV-2 quantitative RT-PCR tests performed during hospitalization (cycle threshold 7.07 ± 6.85 vs. 7.08 ± 7.27, p 0.977 in the control and treated groups, respectively). Remdesivir treatment shortened hospitalization length by less than a day compared with non-treated controls and by 3.1 days when non-intubated patients from both groups were compared. These differences, however, were not statistically significant, possibly because of the small size of the remdesivir group., Discussion: Remdesivir was not associated with nasopharyngeal viral load changes, but our study had a significant disease severity baseline imbalance and was not powered to detect viral load or clinical differences., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Endocrine and metabolic associations have been recently reported in patients with hidradenitis suppurativa (HS); however, fertility was only rarely investigated in women and not at all in men., Objective: To evaluate the association of HS with male and female infertility., Methods: A cross-sectional, matched controlled, population-based study was designed. The association between HS and male and female infertility was evaluated in patients with HS (n = 4191) and age- and gender-matched controls (n = 20 941), while utilising the Clalit Health Services databases, the largest community-based health maintenance organisation in Israel., Results: Hidradenitis suppurativa was associated with infertility in males and females over all reproductive-age groups, especially among individuals aged 36-45 years (OR 4.50, 95%CI 2.55-7.93, P < 0.001), and in female patients (OR 3.10, 95%CI 2.57-3.74, P < 0.001). After adjustment for demographic and clinical factors, the association remained significant only in females (OR 1.26 95%CI 1.04-1.55, P < 0.05)., Conclusion: Patients with HS are at increased risk of infertility, particularly females and patients in the 36- to 45-year age group. Physicians should take the additional physiological and psychological burden of infertility among HS patients into account, primarily among female patients at procreative age., (© 2021 The Australasian College of Dermatologists.)

Objectives: While highly effective in preventing SARS-CoV-2 spread, national lockdowns come with an enormous economic price. Few countries have adopted an alternative "testing, tracing, and isolation" approach to selectively isolate people at high exposure risk, thereby minimizing the economic impact. To assist policy makers, we performed a cost-effectiveness analysis of these 2 strategies., Methods: A modified Susceptible, Exposed, Infectious, Recovered, and Deceased (SEIRD) model was employed to assess the situation in Israel, a small country with ∼9 million people. The incremental cost-effectiveness ratio (ICER) of these strategies as well as the expected number of infected individuals and deaths were calculated., Results: A nationwide lockdown is expected to save, on average, 274 (median 124, interquartile range: 71-221) lives compared to the "testing, tracing, and isolation" approach. However, the ICER will be, on average, $45 104 156 (median $49.6 million, interquartile range: 22.7-220.1) to prevent 1 case of death., Conclusion: A national lockdown has a moderate advantage in saving lives with tremendous costs and possible overwhelming economic effects. These findings should assist decision makers dealing with additional waves of this pandemic., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: There are three major types of genetic cutaneous porphyrias (GCP): erythropoietic protoporphyria (EPP), variegate porphyria (VP), and hereditary coproporphyria (HCP). Scarce data are available regarding their impact on patients' quality of life in the Mediterranean region., Purpose: To describe the cutaneous features of GCP in Israel., Methods: An established nationwide cohort of patients with GCP diagnosed during 1988-2019 was surveyed by telephone for cutaneous features of GCP. Impact on quality of life was assessed using the Dermatology Life Quality Index., Results: Of the 95 patients with GCP, 71 (75%) completed the survey (21 HCP; 40 VP; 10 EPP). All EPP patients reported cutaneous symptoms compared with 58% of VP and 5% of HCP (P < .001). Mean age at symptom onset was 7 ± 6 years in EPP and 25 ± 15 years in VP (P < .001). Photosensitivity was the most common symptom in EPP (90%). In VP photosensitivity (52%), blistering (52%) and scarring (74%) were all common symptoms. In both VP and EPP, the dorsal hands/forearms were the most affected regions (≥96%), and in ≥ 78%, symptoms occurred on an almost daily basis. All EPP patients changed their lifestyle due to cutaneous symptoms vs 57% in VP. Major effect on quality of life was observed among EPP patients compared with a moderate effect in VP. No treatment was effective in EPP, while phototherapy and moisturizers were effective in 5 of 7 (71%) VP patients., Conclusion: This study sheds light on the cutaneous features of the GCP, which have a substantial effect on patients' quality of life., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Few studies have addressed external validity of randomized controlled trials in infectious diseases. We aimed to assess the external validity of an investigator-initiated trial on treatment for uncomplicated urinary tract infection., Methods: In the original study, women ( n  = 513) with urinary tract infection were randomized to nitrofurantoin or fosfomycin treatment in three countries between 2013 and 2017. In the present study we compared women who were screened for enrolment but excluded to women who participated in the trial, both groups in Israel. The primary outcome was the rate of emergency department index visits resulting in hospitalization within 28 days., Results: We compared 127 included to 110 excluded patients. The most common reasons for exclusion were logistic difficulties in recruitment and antibiotic use in the preceding month. Included patients tended to be older [39 (IQR 29-59) vs. 35.5 (IQR 24-56.25 years)], more likely to have history of recurrent infection and had more urinary symptoms. Among excluded patients, 13.6% (15/110) had initial visits resulting in hospitalization compared to 3.1% (4/127) of included participants ( p  = .003). The rate of emergency department visits within 28 days was similar in both groups. Clinical and microbiological failures were significantly more common in included patients [26% (33/127) vs. 1.8% (2/110), p  < .001; 7.9% (10/127) vs. 0% (0/110), p  = .003; respectively]., Conclusions: While differences were observed between included and excluded patients, the excluded group did not represent a more 'complicated' population. The present study shows the importance of collecting data on patients excluded from randomized controlled trials.

Background: Population external validity is the extent to which an experimental study results can be generalized from a specific sample to a defined population. In order to apply the results of a study, we should be able to assess its population external validity. We performed an investigator-initiated randomized controlled trial (RCT) (AIDA study), which compared colistin-meropenem combination therapy to colistin monotherapy in the treatment of patients infected with carbapenem-resistant Gram-negative bacteria. In order to examine the study's population external validity and to substantiate the use of AIDA study results in clinical practice, we performed a concomitant observational trial., Methods: The study was conducted between October 1st, 2013 and January 31st, 2017 (during the RCTs recruitment period) in Greece, Israel and Italy. Patients included in the observational arm of the study have fulfilled clinical and microbiological inclusion criteria but were excluded from the RCT due to receipt of colistin for > 96 h, refusal to participate, or prior inclusion in the RCT. Non-randomized cases were compared to randomized patients. The primary outcome was clinical failure at 14 days of infection onset., Results: Analysis included 701 patients. Patients were infected mainly with Acinetobacter baumannii [78.2% (548/701)]. The most common reason for exclusion was refusal to participate [62% (183/295)]. Non-randomized and randomized patients were similar in most of the demographic and background parameters, though randomized patients showed minor differences towards a more severe infection. Combination therapy was less common in non-randomized patients [31.9% (53/166) vs. 51.2% (208/406), p = 0.000]. Randomized patients received longer treatment of colistin [13 days (IQR 10-16) vs. 8.5 days (IQR 0-15), p = 0.000]. Univariate analysis showed that non-randomized patients were more inclined to clinical failure on day 14 from infection onset [82% (242/295) vs. 75.5% (307/406), p = 0.042]. After adjusting for other variables, non-inclusion was not an independent risk factor for clinical failure at day 14., Conclusion: The similarity between the observational arm and RCT patients has strengthened our confidence in the population external validity of the AIDA trial. Adding an observational arm to intervention studies can help increase the population external validity and improve implementation of study results in clinical practice., Trial Registration: The trial was registered with ClinicalTrials.gov, number NCT01732250 on November 22, 2012.

Importance: Chronic kidney disease (CKD) is prevalent in the population of patients undergoing transcatheter aortic valve replacement (TAVR). Data on the association of TAVR with kidney function are scarce, as are data on the relationship between changes in kidney function after TAVR and mortality., Objective: To describe the changes in kidney function (both periprocedural and at steady state) after TAVR and to explore the association of TAVR with midterm mortality., Design, Setting, and Participants: This single-center, retrospective cohort study was conducted at a public, tertiary academic medical center, which serves as a regional referral center for valvular heart interventions. Consecutive cases of patients undergoing TAVR from November 5, 2008, to December 31, 2019, were included in the study, with available baseline and post-TAVR data on kidney function., Exposures: Steady state (1 month) change in kidney function after TAVR. Significant improvement or deterioration in renal function was defined as a greater than or equal to 10% change in estimated glomerular filtration rate (eGFR)., Main Outcomes and Measures: Overall mortality at 2-year follow-up., Results: A total of 894 patients (mean [SD] age, 82.2 [7.1] years; 452 women ([51.2%]) were evaluated. A total of 362 patients (40.5%) were treated from 2017 to 2019, 348 patients (38.9%) were treated from 2013 to 2016, and 184 patients (20.5%) were treated from 2008 and 2012. Patients had a mean (SD) Society of Thoracic Surgeons (STS) score of 5.2% (4.0%) and a mean (SD) eGFR of 65.1 (23.1) mL/min/1.73 m2. Acute kidney injury occurred in 115 (11.1%) patients by 48 hours, of whom 73 (63.5%) resolved by discharge. One month after TAVR, eGFR improved by at least 10% in 329 patients (36.8%) and deteriorated by at least 10% in 233 patients (26.1%). Overall, CKD stage remained stable or improved in 720 patients (80.6%), and only 5 patients (0.97%) progressed to stage 5 CKD 1 month after TAVR. A deterioration of 10% or greater in eGFR 1 month after TAVR was associated with a hazard ratio of 2.16 (95% CI, 1.24-5.24; P = .04) at 2-year mortality. Patients who showed CKD status resolution (eGFR improvement to >60 mL/min/1.73 m2 after TAVR) had a similar 2-year mortality to those with baseline eGFR greater than 60 mL/min/1.73 m2 and vice versa. Factors associated with steady state CKD status resolution after TAVR included lower STS score, higher left ventricular ejection fraction, higher baseline eGFR, no acute kidney injury at discharge from the TAVR admission, and lower contrast-eGFR ratio., Conclusions and Relevance: In this cohort study, kidney outcomes after TAVR were reassuring; greater than 80% of patients showed stable or improved kidney function 1 month after the procedure. Improvement in kidney function was associated with a lower 2-year mortality, whereas deterioration in kidney function was associated with increased mortality. Our data suggest that cardiorenal syndrome was a possible cause of CKD in patients in need of TAVR and that there was potential for improvement in both renal and cardiac function after this procedure.

Objective: Carbapenems are considered treatment of choice for bacteremia caused by potential AmpC-producing bacteria, including Enterobacter spp. We aimed to compare mortality following carbapenem vs. alternative antibiotics for the treatment of Enterobacter spp. bacteremia. Patients and Methods: We conducted a retrospective study in two centers in Israel. We included hospitalized patients with Enterobacter bacteremia treated with third-generation cephalosporins (3GC), piperacillin/tazobactam, quinolones, or carbapenem monotherapy as the main antibiotic in the first week of treatment, between 2010 and 2017. Cefepime was excluded due to nonavailability during study years. The primary outcome was 30-day all-cause mortality. Univariate and multivariate analyses were conducted, introducing the main antibiotic as an independent variable. Results: Two hundred seventy-seven consecutive patients were included in the analyses. Of these, 73 were treated with 3GC, 39 with piperacillin/tazobactam, 104 with quinolones, and 61 with carbapenems. All-cause 30-day mortality was 16% (45 patients). The type of antibiotics was not significantly associated with mortality on univariate or multivariate analyses. With carbapenems as reference, adjusted odds ratios (ORs) for mortality were 0.708, 95% confidence interval (CI) 0.231-2.176 with 3GC; OR 1.172, 95% CI 0.388-3.537 with piperacillin/tazobactam; and OR 0.586, 95% CI 0.229-1.4 with quinolones. The main antibiotic was not associated with repeated growth of Entrobacter spp. in blood cultures or other clinical specimens. Resistance development was observed with 3GC and piperacillin/tazobactam. Conclusions: Carbapenem treatment was not advantageous to alternative antibiotics, including 3GC, among patients with Enterobacter spp. bacteremia in an observational study.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disease involving the skin bearing apocrine glands. There are numerous comorbidities and associated diseases among patients with HS. The association of HS and thyroid abnormalities is equivocal. We aimed to explore whether HS is associated with thyroid disorders., Methods: In this cross-sectional large-scale population-based study in Israel, patients with a validated diagnosis of HS were matched at a proportion of 1:5 with age- and gender-matched healthy controls without HS. A cross-checking for HS diagnosis by International Classification of Diseases, ninth revision (ICD-9) coding, and hyperthyroidism and hypothyroidism by ICD-9 coding was performed. Demographic and exposure covariates were identified. Univariate and multivariate logistic regressions were utilized to establish the association of HS with thyroid disorders., Results: Study participants included 4,191 HS patients and 20,941 controls. The average age of patients was 39.7 years old, and 61.8% were female. 53.4% of HS patients and 13.5% of controls (P < 0.001) were smokers. Odds ratios (ORs) for hypothyroidism and hyperthyroidism in HS were 2.91 (95% confidence interval [CI] 2.48-3.40) and 2.25 (95% CI 1.55-3.28), respectively (P < 0.001 for both). While the association of HS with hypothyroidism was maintained across genders and all age groups, and remained positive after controlling for smoking status, the association with hyperthyroidism remained positive only among females, middle-aged patients, and nonsmokers., Conclusion: HS is independently associated with hypothyroidism. The association of HS with hyperthyroidism held significance only in limited subgroups. Smoking status is a major modifier, mainly in the association of HS with hyperthyroidism., (© 2020 the International Society of Dermatology.)

Acute hepatic porphyria (AHP) attacks begin with abdominal pain and can progress to severe life-threatening conditions. Early diagnosis and treatment may prevent these complications. We investigated the difference between the severity of porphyria attacks before and after porphyria diagnosis. A retrospective study including AHP patients hospitalized for an acute attack in Israel during a 15-year period. Diagnosis of an attack was based on typical clinical symptoms accompanied by at least one documented elevated urinary porphobilinogen above fourfold of normal values. The primary outcome was intensive care unit (ICU) admissions. Secondary outcomes included the length of hospital stay, severe hyponatremia, seizures, and psychiatric symptoms. 42 attacks in 9 patients were included. Most attacks occurred in women (78.6%) and in acute intermittent porphyria patients (76.2%). The mean age of attack was 26.5 (± 6.3) years. Attacks following porphyria diagnosis had a lower prevalence of ICU admission (3.3% versus 75.0%, p < 0.001), seizures (0% versus 50.0%, p < 0.001), psychiatric symptoms (23.3% versus 66.7%, p = 0.01), severe hyponatremia (16.7% versus 83.3%, p < 0.001), and median length of hospital stay (5 versus 11.0 days, p < 0.001). These results remained significant after simple univariate logistic regression for ICU admission [odds ratio (OR) 0.01, 95% confidence interval (CI) 0.00-0.12], prolonged hospital stay (OR 0.08, 95% CI 0.01-0.41), seizures or neurological symptoms (OR 0.06, 95% CI 0.01-0.30), and severe hyponatremia (OR 0.02, 95% CI 0.00-0.20). Previously diagnosed AHP patients have a significantly milder attack course as compared to previously undiagnosed patients. Family screening following sentinel cases might prevent severe AHP attacks.

Background: Fever of unknown origin (FUO) is a rare manifestation of cat scratch disease (CSD). Data regarding CSD-associated FUO (CSD-FUO), particularly in adults, are limited. We aimed to study disease manifestations and long-term clinical outcome., Methods: A national CSD surveillance study has been conducted in Israel since 1991. Data are obtained using questionnaires, review of medical records, and telephone interviews. FUO was defined as fever of ≥14 days without an identifiable cause. CSD-FUO patients were identified in the 2004-2017 CSD national registry. Follow-up included outpatient clinic visits and telephone/e-mail surveys., Results: The study included 66 CSD-FUO patients. Median age was 35.5 years (range, 3-88). Median fever duration was 4 weeks (range, 2-9). Relapsing fever pattern was reported in 52% of patients, weight loss in 57%, and night sweats in 48%. Involvement of ≥1 organs occurred in 59% of patients; hepatosplenic space-occupying lesions (35%), abdominal/mediastinal lymphadenopathy (20%), ocular disease (18%), and multifocal osteomyelitis (6%) were the most common. Malignancy, particularly lymphoma, was the initial radiological interpretation in 21% of patients; 32% underwent invasive diagnostic procedures. Of the 59 patients available for follow-up (median duration, 31 weeks; range, 4-445), 95% had complete recovery; 3 patients remained with ocular sequelae., Conclusion: This is the first attempt to characterize CSD-FUO as a unique syndrome that may be severe and debilitating and often mimics malignancy. Relapsing fever is a common clinical phenotype. Multiorgan involvement is common. Recovery was complete in all patients except in those with ocular disease., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: To evaluate the ethnic distribution of Israeli patients with the syndrome of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA)., Study Design: The medical records of patients with PFAPA attending 2 pediatric tertiary medical centers in Israel from March 2014 to March 2019 were retrospectively reviewed. Patients with concomitant familial Mediterranean fever were excluded. Ethnicity was categorized as Mediterranean, non-Mediterranean, and multiethnic. Findings were compared with patients with asthma under treatment at the same medical centers during the same period., Results: The cohort included 303 patients with PFAPA and 475 with asthma. Among the patients with PFAPA, 178 (58.7%) were of Mediterranean descent (Sephardic Jews or Israeli Arabs), 96 (33.0%) were multiethnic, and 17 (5.8%) were of non-Mediterranean descent (all Ashkenazi Jews). Patients with PFAPA had a significantly higher likelihood of being of Mediterranean descent than the patients with asthma (58.7% vs 35.8%; P < .0001). The Mediterranean PFAPA subgroup had a significantly earlier disease onset than the non-Mediterranean subgroup (2.75 ± 1.7 vs 3.78 ± 1.9 years, P < .04) and were younger at disease diagnosis (4.77 ± 2.3 vs 6.27 ± 2.9 years, P < .04)., Conclusions: PFAPA was significantly more common in patients of Mediterranean than non-Mediterranean descent. Further studies are needed to determine the genetic background of these findings., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cutaneous leishmaniasis poses a therapeutic challenge in the paediatric population. The aim of this study was to assess the efficacy and safety of miltefosine treatment for Old World cutaneous leishmaniasis in paediatric patients. A multicentre retrospective review of 10 children (≤ 18 years of age) with cutaneous leishmaniasis treated with miltefosine in Israel was performed. Mean ± standard deviation age at diagnosis was 9.1 ± 5.0 years. The Leishmania species diagnosed was L. tropica in 8 cases and Leishmania major in 2 cases. Mean ± standard deviation duration of treatment was 44.8 ± 20.6 days, with a mean follow-up period of 12.1 ± 17.1 months. Complete response was noted in 8 (80%) patients. Treatment failure was noted in 2 (20%) cases. Side-effects related to the medication were minimal. In conclusion, oral miltefosine may be an effective and safe treatment for Old World cutaneous leishmaniasis caused by Leishmania tropica or Leishmania major in children. However, further studies are warranted to draw a definite conclusion.

Background: This retrospective study compared perioperative measures, costs, quality of life and survival after open vs. robotic surgery, among obese women diagnosed with low-grade endometrial cancer., Methods: Obese women (body mass index (BMI) ≥ 30) who underwent open or robotic surgery for endometrial cancer, in one of two tertiary medical centers in the center of Israel, 2013-2016, postoperative grade 1-2, were included. Costs per patient, including 30-days post-surgery were calculated. Quality of life was evaluated by Physical and Mental Components of the SF-36 and a recovery from surgery questionnaire. Overall survival outcomes were obtained from patients' files. Surgical outcomes, including operating and anesthesia times, length of hospital stay, and intraoperative and postoperative complications according to the Clavien-Dindo classification scale were reviewed., Results: In all, 138 women with BMI ≥30 underwent open (n = 61) or robotic surgery (n = 77) during the study period. The groups had similar BMI, comorbidities, demographics and tumor characteristics. Robotic surgery was associated with shorter hospital stays (mean 1.7 vs. 4.8 days; P < .0001) and fewer postoperative complications (Clavien-Dindo > 2, 5.2% vs. 19.7%; P = .0008), but longer operating theater time (3.8 vs. 2.8 h; P < .001). Costs are equivalent when at least 350 robotic surgeries are performed annually, not including the initial system costs. Quality of life measures were better after robotic surgery. SF-36 showed better measures for robotic surgery (Physical 56 vs. 39 and Mental 73 vs. 56; P < .01). After robotic surgery, patients tended to recover quicker when compared to open surgery, as they returned to normal activities earlier, with less need for family and governmental assistance (mean recovery time, 23 vs. 70 days; P < 0.006 and mean change in preoperative total functioning score, - 1.5 vs. -3.9: P < 0.05, respectively). Overall, 5-year survival was 89.8% for the open surgery group vs. 94% for the robotic surgery group (log rank, P = 0.330)., Conclusions: Obese women with low-grade endometrial cancer had better quality of life after robotic vs. open surgery. They also had shorter hospital stays and fewer postoperative complications. Centers with high volumes of robotic surgery can achieve similar costs when comparing both methods. These results were achieved without jeopardizing survival. Our results further emphasize the need for the Israeli healthcare system to include specific reimbursement for robotic procedures in the population we studied.

Objective: To evaluate current real-life experience with medical treatment for active acromegaly in a large cohort., Methods: Data on demographic parameters, blood tests, imaging studies, and treatments were extracted from the medical records., Results: The cohort included 87 patients (43 male) with active acromegaly. The mean age at diagnosis was 40.2±11.4 years, and the mean duration of follow-up was 7.9±5.8 years. Seventy patients presented with a macroadenoma. Mean baseline insulin growth factor 1 (IGF-1) (n = 67) was 3.2±1.9 × upper limit of normal (ULN). Surgery and radiotherapy were performed in 75 and 10 patients, respectively. Currently, 38 subjects receive somatostatin analogues, pegvisomant as a monotherapy is given to 8 patients, pasireotide is given to 17 patients, cabegoline to 4 patients, estrogen to 2 females, and SSAs combined with pegvisomant to 10 patients. Eight patients are not being actively treated, including 4 following radiotherapy. Good biochemical control (IGF-1 <1.3 × ULN) was achieved in 76 patients (87%), and 11 patients (13%) are currently uncontrolled (IGF-1 >1.3 × ULN). Seventy-eight percent of controlled patients are being given 1 medication; 11% are on combination therapy; 4 patients are well controlled after radiotherapy and 2 are partially controlled without any treatment. The main adverse effects of treatment were diabetes mellitus in 7 patients (on pasireotide) and symptomatic cholelithiasis in 5 patients., Conclusion: Active acromegaly can be controlled medically in most patients, with a low rate of adverse effects. This study displays the characteristic variety of treatment options available for active acromegaly., (© 2020 American Association of Clinical Endocrinologists. Published by Elsevier, Inc. All rights reserved.)

Cutaneous leishmaniasis poses a therapeutic challenge in the paediatric population. The aim of this study was to assess the efficacy and safety of miltefosine treatment for Old World cutaneous leishmaniasis in paediatric patients. A multicentre retrospective review of 10 children (≤ 18 years of age) with cutaneous leishmaniasis treated with miltefosine in Israel was performed. Mean ± standard deviation age at diagnosis was 9.1 ± 5.0 years. The Leishmania species diagnosed was L. tropica in 8 cases and Leishmania major in 2 cases. Mean ± standard deviation duration of treatment was 44.8 ± 20.6 days, with a mean follow-up period of 12.1 ± 17.1 months. Complete response was noted in 8 (80%) patients. Treatment failure was noted in 2 (20%) cases. Side-effects related to the medication were minimal. In conclusion, oral miltefosine may be an effective and safe treatment for Old World cutaneous leishmaniasis caused by Leishmania tropica or Leishmania major in children. However, further studies are warranted to draw a definite conclusion.

Mutations in more than 150 genes are responsible for inherited hearing loss, with thousands of different, severe causal alleles that vary among populations. The Israeli Jewish population includes communities of diverse geographic origins, revealing a wide range of deafness-associated variants and enabling clinical characterization of the associated phenotypes. Our goal was to identify the genetic causes of inherited hearing loss in this population, and to determine relationships among genotype, phenotype, and ethnicity. Genomic DNA samples from informative relatives of 88 multiplex families, all of self-identified Jewish ancestry, with either non-syndromic or syndromic hearing loss, were sequenced for known and candidate deafness genes using the HEar-Seq gene panel. The genetic causes of hearing loss were identified for 60% of the families. One gene was encountered for the first time in human hearing loss: ATOH1 (Atonal), a basic helix-loop-helix transcription factor responsible for autosomal dominant progressive hearing loss in a five-generation family. Our results show that genomic sequencing with a gene panel dedicated to hearing loss is effective for genetic diagnoses in a diverse population. Comprehensive sequencing enables well-informed genetic counseling and clinical management by medical geneticists, otolaryngologists, audiologists, and speech therapists and can be integrated into newborn screening for deafness., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Background: In adults, post-liver transplantation anemia (PLTA) is common, but its characteristics and long-term influence on major outcomes have yet to be elucidated., Aim: We aimed to assess prevalence, characteristics, predictors, and outcomes of PLTA at 6 months (early PLTA) and at 2 years (late PLTA)., Methods: A single-center retrospective cohort study using prospectively collected data from liver transplantations in adults during January 2007-December 2015. PLTA impact on various long-term outcomes was assessed, including mortality, composites of mortality or graft failure, cardiovascular outcomes, and malignancy occurrences., Results: Hundred and fifty liver transplanted individuals were included. There was a 79% prevalence of anemia pre-transplantation, whereas early and late PLTA were evident in 58% and 40% of patients, respectively. Pre-transplantation anemia was associated with development of early PLTA which was associated with late PLTA. In a multivariate analysis, early PLTA was significantly associated with mortality or graft failure at a follow-up of 3 years (odds ratio 3.838, 95% CI 1.114-13.226). Late PLTA was not significantly associated with worse long-term outcomes., Conclusions: Early and late PLTA are prevalent among liver transplanted patients. Early PLTA is associated with long-term mortality or graft failure.