Israel Medical Association Journal

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive death of motor neurons leading to fatal paralysis. The causes of ALS remain unknown; however, evidence supports the presence of autoimmune mechanisms contributing to pathogenesis. Although several environmental factors have been proposed, the only established risk factors are older age, male gender, and a family history of ALS. To date, there are no diagnostic test for ALS, and clinicians rely on the combination of upper motor neuron and lower motor neuron signs in the same body region. The aim of this paper was to provide a comprehensive review of current clinical literature with special focus on the role of autoimmunity in ALS, differential diagnosis, and available therapeutic approaches. Current evidence suggests a contribution of the innate immune system in ALS, with a role of microglial cell activation at the sites of neurodegeneration. The median time from symptom onset to diagnosis of ALS is 14 months, and this time estimate is mainly based on specific clinical signs and exclusion of ALS-like conditions. Several therapeutic approaches have been proposed, including immunosuppressive drugs, to reduce disease progression. Riluzole has been established as the only, although modestly effective, disease modifying therapy, extending mean patient survival by 3to 6 months. Recent advances in understanding the pathophysiology mechanisms of ALS encourage realistic hope for new treatment approaches. To date, the cornerstones of the management of patients with ALS are focused on symptom control, maintaining quality of life and improving survival.

Background: The MitraClip procedure is becoming an acceptable alternative for high-risk patients with mitral regurgitation (MR) due to functional (FMR) or degenerative (DMR) disease and suitable mitral anatomy.

Objectives: To evaluate the results of MitraClip at our institute in carefully selected patients.

Methods: We conducted a retrospective analysis of medical records and echocardiography data from January 2012 to December 2017.

Results: A total of 39 MitraClip procedures in 37 patients (aged 75 ± 12 years, 9 women) was performed. Twenty-four patients presented with FMR, 12 with DMR, and 1 with combined pathology. One-day post-procedure MR was moderate to low in 86.1% of patients, with immediate device success in 88.8%. MR at 1 year was moderate to low in 79% at 1 year. Survival at 1 year was 86% and at 2 years 69.4%. Peri-procedural (< 1 week) death and MitraClip failure occurred in one and three patients, respectively. New York Heart Association score improved to class 1 or 2 in 37% of patients at 1 year vs. one patient at baseline. Post-procedural systolic pulmonary pressure was reduced from 53 (range 48–65) to 43 (range 36–52) mmHg at 1 month with a subsequent plateau at follow-up, to 41 (34–57) mmHg at 6 months, and to 47 (38–50) at 12 months.

Conclusions: MitraClip in severe MR resulted in modest improvement in functional status and pulmonary pressure with a small risk of immediate procedural complications. Outcomes are encouraging considering the natural course of MR and the risks of surgical intervention.

Background: Gender differences in adolescent idiopathic scoliosis (AIS) have been documented in curve progression, response to bracing, and outcomes of surgical treatment. However, limited information is available about the relation between gender and scoliosis curve patterns and radiographical characteristics.

Objectives: To evaluate the effect of gender on curve pattern and compare clinical and radiographical characteristics between male and female patients with AIS.

Methods: We conducted a retrospective review of prospectively collected data that compared clinical and radiographical characteristics between male and female surgical candidates. Demographic and clinical data including age at presentation, gender, family history of scoliosis, brace treatment history, clinical coronal balance, shoulder asymmetry, and hump size were recorded. All patients graded their pain with the use of a visual analogue scale (VAS) on a scale from 0 to 10. Radiographs of the spine were reviewed to determine the type of curve according to the Lenke classification, Cobb angle, thoracic kyphosis angle, and the Risser sign. Radiologic coronal balance was recorded. Curve flexibility was determined by measuring the thoracic and lumbar curves magnitude on side bending radiographs

Results: The study included 163 patients with AIS including 35 males and 128 females patients. Although a trend toward more flexible major thoracic curves in females was noticed, there was no statistically significant difference between the 2 groups.

Conclusions: In this study we were not able to demonstrate any clinical nor radiological statistical differences between male and female patients who are candidate for surgical treatment.

Background: Dialysate purity contributes to the inflammatory response that afflicts hemodialysis patients.

Objectives: To compare the clinical and laboratory effects of using ultrapure water produced by a water treatment system including two reverse osmosis (RO) units in series, with a system that also includes an ultrapure filter (UPF).

Methods: We performed a retrospective study in 193 hemodialysis patients during two periods: period A (no UPF, 6 months) and period B (same patients, with addition of UPF, 18 months), and a historical cohort of patients treated in the same dialysis unit 2 years earlier, which served as a control group.

Results: Mean C-reactive protein, serum albumin and systolic blood pressure worsened in period B compared to period A and in the controls.

Conclusions: A double RO system to produce ultrapure water is not inferior to the use of ultrapure filters.

Background: The epidemiology of human brucellosis (HB) continues to evolve.

Objectives: To describe the current epidemiology of HB in Israel in general and in the population at risk.

Methods: We calculated the incidence of HB in Israel for the period 2009–2015, overall and for the Arab population. Data are based on mandatory reporting of HB in Israel, defined clinically with either laboratory confirmation or epidemiological linkage to a laboratory-confirmed case. We mapped the geographic distribution of HB throughout the study period according to localities. We specified localities with high incidence (≥ 10 per 100,000 population) and mapped the distribution of dense localities with time.

Results: The incidence of HB in the general population in Israel increased sharply from 1.9 per 100,000 in 2009 to a peak of 7.3 per 100,000 in 2014. Each year, 95–100% of cases occurred among Arabs, thus the incidence in the Arab population increased from 10 per 100,000 in 2009 to 33.5 per 100,000 in 2014. Throughout this period 133 different localities reported at least one case of HB, and of these 20 were high-incidence localities during one year at least. During the period 2009–2013 the number of affected localities ranged from 35 to 44 per year and the disease was local, while in 2014 there were 82 localities distributed across the country.

Conclusions: We demonstrate the importance of analyzing incidence in the population at risk for a disease. HB is an urgent public health issue in the Arab population in Israel, mandating an immediate and long-term eradication and control program.

Background: The lack of organs for liver transplantation has prompted transplant professionals to study potential solutions, such as the use of livers from donors older than 70 years. This strategy is not widely accepted because potential risks of vascular and biliary complications and recurrence of hepatitis C.

Objectives: To examine the efficacy and safety of liver grafts from older donors for transplantation.

Methods: A retrospective analysis of data on 310 adults who underwent deceased donor liver transplantation between 2005 and 2015 was conducted. We compared graft and recipient survival, as well as major complications, of transplants performed with grafts from donors younger than 70 years (n=265, control group) and those older than 70 years (n=45, older-donor group), followed by multivariate analysis, to identify risk factors.

Results: There was no significant difference between the control and older-donor group at 1, 5, and 10 years of recipient survival (79.5% vs. 73.3%, 68.3% vs. 73.3%, 59.2% vs. 66.7%, respectively) or graft survival (74.0% vs. 71.0%, 62.7% vs. 71.0%, 54.8% vs. 64.5%, respectively). The rate of biliary and vascular complications was similar in both groups. Significant risk factors for graft failure were hepatitis C (hazard ratio [HR] = 1.92, 95% confidence interval [95%CI] 1.16–2.63), older donor age (HR = 1.02, 95%CI 1.007–1.031), and male gender of the recipient (HR = 1.65, 95%CI 1.06–2.55).

Conclusion: Donor age affects liver graft survival. However, grafts from donors older than 70 years may be equally safe if cold ischemia is maintained for less than 8 hours.

Background: Contemporary data on clinical profiles and long-term outcomes of young adults with coronary artery disease (CAD) are limited.

Objectives: To determine the risk profile, presentation, and outcomes of young adults undergoing coronary angiography.

Methods: A retrospective analysis (2000–2017) of patients aged ≤ 35 years undergoing angiography for evaluation and/or treatment of CAD was conducted.

Results: Coronary angiography was performed in 108 patients (88% males): 67 acute coronary syndrome (ACS) and 41 non-ACS chest pain syndromes. Risk factors were similar: dyslipidemia (69%), positive family history (64%), smoking (61%), obesity (39%), hypertension (32%), and diabetes (22%). Eight of the ACS patients (12%) and 29 of the non-ACS (71%) had normal coronary arteries without subsequent cardiac events. Of the 71 with angiographic evidence of CAD, long-term outcomes (114 ± 60 months) were similar in ACS compared to non-ACS presentations: revascularization 41% vs. 58%, myocardial infarction 32% vs. 33%, and all-cause death 8.5% vs. 8.3%. Familial hypercholesterolemia (FH) was diagnosed in 25% of those with CAD, with higher rates of myocardial infarction (adjusted hazard ratio [HR] 2.62, 95% confidence interval [95%CI] 1.15–5.99) and revascularization (HR 4.30, 95%CI 2.01–9.18) during follow-up. Only 17% of patients with CAD attained a low-density lipoprotein cholesterol treatment goal < 70 mg/dl.

Conclusions: CAD in young adults is associated with marked burden of traditional risk factors and high rates of future adverse cardiac events, regardless of acuity of presentation, especially in patients with FH, emphasizing the importance of detecting cardiovascular risk factors and addressing atherosclerosis at young age.

Background: When a breast lesion is suspected based on a physical exam, mammography, or ultrasound, a stereotactic core needle biopsy (CNB) is usually performed to help establish a definitive diagnosis. CNBs are far less invasive than excisional biopsies, with no need for general anesthetics or hospitalization, and no recovery period. However, since only samples of the mass are removed in a CNB and not the whole mass, sampling errors can occur.

Objectives: To compare the degree of agreement between the pathological data from CNBs and excisional biopsies from a single tertiary referral hospital.

Methods: The concordance of pathological data was compared in patients who underwent CNBs and had their surgical procedures at the same medical center.

Results: From the 894 patients who underwent CNBs, 254 (28.4%) underwent subsequent excisional biopsies at our medical center. From the total of 894 patients, 227 (25.3%) who underwent a CNB were diagnosed with a malignancy, with the rest of the CNBs being diagnosed as benign pathologies. The pathological findings in the CNBs and in the excisional biopsies concurred in 232/254 (91.3%) of the cases.

Conclusions: A CNB to confirm mammographic or clinical findings of breast lesions is an accurate method to establish a pathological diagnosis of breast lesions. The accuracy is higher for invasive carcinomas than for non-invasive cancers. Excisional biopsies are necessary for lesions with anticipated sampling errors or when the core needle biopsy findings are discordant with clinical or mammographic findings.

Background: Limited information exists about detailed clinical characteristics and management of the small subset of Brugada syndrome (BrS) patients who had an arrhythmic event (AE).

Objectives: To conduct the first nationwide survey focused on BrS patients with documented AE.

Methods: Israeli electrophysiology units participated if they had treated BrS patients who had cardiac arrest (CA) (lethal/aborted; group 1) or experienced appropriate therapy for tachyarrhythmias after prophylactic implantable cardioverter defibrillator (ICD) implantation (group 2).

Results: The cohort comprised 31 patients: 25 in group 1, 6 in group 2. Group 1: 96% male, mean CA age 38 years (range 13–84). Nine patients (36%) presented with arrhythmic storm and three had a lethal outcome; 17 (68%) had spontaneous type 1 Brugada electrocardiography (ECG). An electrophysiology study (EPS) was performed on 11 patients with inducible ventricular fibrillation (VF) in 10, which was prevented by quinidine in 9/10 patients. During follow-up (143 ± 119 months) eight patients experienced appropriate shocks, none while on quinidine. Group 2: all male, age 30–53 years; 4/6 patients had familial history of sudden death age < 50 years. Five patients had spontaneous type 1 Brugada ECG and four were asymptomatic at ICD implantation. EPS was performed in four patients with inducible VF in three. During long-term follow-up, five patients received ≥ 1 appropriate shocks, one had ATP for sustained VT (none taking quinidine). No AE recurred in patients subsequently treated with quinidine.

Conclusions: CA from BrS is apparently a rare occurrence on a national scale and no AE occurred in any patient treated with quinidine.

Background: The recommendation of the U.S. Centers for Disease Control and Prevention regarding universal screening for Group B Streptococcus (GBS) at 35–37 weeks gestational age in pregnancy is not accepted in Israel. The National Council for Obstetrics, Neonatology and Genetics recommends intrapartum prophylaxis, mainly based on risk factors, to prevent early neonatal GBS infection. This policy is based on past studies demonstrating low colonization rates of the bacteria in Israeli pregnant women and very low neonatal sepsis rates.

Objectives: To determine the applicability of the high-risk group prophylaxis policy for Arab Israeli pregnant women.

Methods: Vaginorectal swabs from Arab Israeli pregnant women who attended the labor ward between October 2015 and February 2016, were obtained before any pelvic examination for GBS identification using Quidel’s AmpliVue® GBS assay. Women who tested positive received intrapartum antibiotic prophylaxis to prevent neonatal infection. Obstetric data were collected from each woman from a standardized questionnaire. Data regarding the delivery and neonates were collected as well.

Results: The study comprised 188 Arab pregnant women who met the inclusion criteria and signed a consent form to participate in the study. Of these, 59 had positive tests, and a carriage rate of 31%. No neonatal colonization of GBS was found.

Conclusions: The carrier rate in Arab pregnant women in northern Israel is higher than the national average, at least partially due to the more sensitive method of GBS detection used in the present study.

Background: Previous surveys demonstrated variations in the clinical practices relating to the treatment and screening of maternal thyroid dysfunction.

Objectives: To study the current practices in the management of subclinical hypothyroidism (SCH) and thyroid nodules during pregnancy of obstetricians/gynecologists (OB/GYNs) and endocrinologists in Israel.

Methods: An electronic questionnaire was sent by email to all members of the Israeli Endocrine Society and the Israel Society of Obstetrics and Gynecology. Questionnaires included demographic data and clinical scenarios with questions regarding the screening and management of pregnant women with SCH, hypothyroxinemia, and a palpable thyroid nodule. The questionnaire for OB/GYNs was slightly modified.

Results: We received 90 responses from endocrinologists and 42 responses from OB/GYNs. Among endocrinologists, 39% would repeat a thyroid-stimulating hormone (TSH) test of 2.9 mU/L with normal free thyroxine and treat with thyroxine if the second result was above 2.5 mU/L. Among OB/GYNs, 73% would manage a woman with SCH at the beginning of her pregnancy by themselves and only 22% would start thyroxine after a first TSH result above 2.5 mU/L. Concerning screening, 57% endocrinologists and 71% OB/GYNs recommended screening for thyroid dysfunction in every woman at the beginning of her pregnancy. Among endocrinologists, 54% would order an ultrasound for a palpable thyroid nodule and perform a fine needle aspiration only for suspicious lesions.

Conclusions: The medical approach to thyroid disease in pregnant women remains a matter of controversy. Our results support the need for larger and prospective clinical studies.