Israel Medical Association Journal

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.

Background: The human papillomavirus (HPV) test has proven to be efficient in triaging women with abnormal Pap findings in women with low cytological atypia, but there is no data about the accuracy for large loop excision of transformation zone in cases of recurrent atypia.

Objectives: To assess the clinical correlation between results of HPV typing and conization histology in women who had recurrent abnormal Pap test results with no colposcopy findings.

Methods: Our retrospective cohort study included 138 women enrolled in the Maccabi Healthcare Services who had consecutive atypical Pap test results for 2 years in which no abnormal colposcopic findings were detected. These women had an HPV typing and then conization.

Results: Among the total study population (n=138), 71.7% had negative histology, 19.6% had ≤ cervical intraepithelial neoplasia grade 1 (≤ CIN1), and 8.7% had CIN2+. With regard to HPV typing, 34.8% were negative and 65.2% were positive. Of those testing positive, 34.4% were positive for HPV 16 or 18. Sensitivity, specificity, positive predictive value, and negative predictive values of HPV typing for women were 89.7%, 44.4%, 38.9%, and 91.7%, respectively, and for HPV 16 or 18: 71.4%, 67.7%, 32.3%, and 100.0%, respectively. After stratification by cytological grades, for women with high-grade cervical cytology, the sensitivity and negative predictive values of the HPV typing were higher than among low-grade cervical cytology, while specificity and positive predictive values were lower.

Conclusions: HPV typing is a useful tool for the management of patients with persistently abnormal Pap test results.

Background: Coronary artery disease (CAD) has known risk factors. Individual risks related to specific ethnicities are complex and depend on genetic predisposition and lifestyle.

Objectives: To compare the nature and prevalence of risk factors in Arab and non-Arab ethnic patients with symptomatic obstructive CAD referred for coronary angiography.

Methods: CAD, defined as coronary angiography with a ≥ 50% narrowing in ≥ 1 vessel, was diagnosed in 1029 patients admitted to a medical center between April 2014 and October 2015. Patients were divided into two groups according to ethnic origin: Arab vs. non-Arab. Demographics, clinical presentation, and coronary risk profiles were compared.

Results: The diagnosis of CAD was made during ST-elevation myocardial infarction (STEMI) in 198 patients (19%) who arrived at the clinic, 620 (60%) with unstable angina/non-STEMI, and 211 (21%) with stable angina. Patients with symptomatic CAD and Arab ethnicity were 47% more prevalent than non-Arab patients presenting with CAD. The Arab patients were appoximately 5 years younger, 50% more likely to be active smokers, 25% more likely to be obese, and more likely to have a family history of CAD. Other coronary risk factors were similar between the two groups.

Conclusions: Smoking and obesity, which are potentially modifiable CAD risk factors, stood out as major risk factors, in addition to genetic disposition, among Arab and non-Arab patients with symptomatic CAD. Screening and educational interventions for smoking cessation, obesity control, and compliance to treatment of co-morbidities should be attempted in order to decrease CAD in the Arab population.

Background: Biological agents for anti-tumor necrosis factor-α therapy have revolutionized treatments for autoimmune diseases; however, approximately 20% of rheumatology and 40% of gastroenterology patients do not respond to the therapy, or they show reduced drug efficacy because of anti-drug antibody (ADA) formation.

Objectives: To evaluate laboratory tools for individual monitoring of infliximab therapy and the relationship between ADA and infliximab serum levels, ADA and clinical response, and ADA and autoantibodies.

Methods: Our study comprised patients treated with infliximab and affected by selected rheumatology and gastroenterology diseases. Sera were analyzed for infliximab, total-anti-drug antibodies (Total-ADA), and free-anti-drug antibodies (Free-ADA) serum levels and for the detection of specific autoantibodies.

Results: We analyzed 73 patients. Total-ADA were detected in 26 rheumatology and 21 gastroenterology patients. Serum infliximab levels were significantly lower in Total-ADA positive patients (P = 0.01 for rheumatology group, P = 0.02 for gastroenterology group). A lack of response was observed in 7 rheumatology and 15 gastroenterology samples. Total-ADA serum levels were statistically significantly higher in patients with treatment failure in both groups (P = 0.01 and P = 0.001, respectively). There was no significant association between the presence of Total-ADA and other autoantibodies. Free-ADA were detected in only 27 rheumatology patients. Results showed a significant correlation with clinical outcome (P = 0.006).

Conclusions: The correlation with clinical response suggests that the presence of ADA could interfere with efficacy of therapy. The tests for monitoring therapy may be an important tool to assist clinicians in early detection and prevention of therapy failure.

Background: Direct aspiration from suspected pathological tissue and rapid parathyroid hormone analysis may offer a reliable, cost effective alternative to currently used “gold standard” tests.

Objectives: To validate the accuracy of intraoperative measurements of parathyroid hormone levels in parathyroid adenomas.

Methods: A prospective study included 22 patients diagnosed with primary hyperparathyroidism who underwent parathyroidectomy due to an adenoma or hyperplasia. Aspirations of tissues extracted from three adjacent areas (the pathological parathyroid, thyroid, and muscle tissues) were sent for rapid parathyroid hormone analysis. The assay values of these tissue aspirates were compared to the results of the pathology report based on frozen section analysis and the final pathology report.

Results: All assay results were significantly higher for parathyroid tissue 16,800 to 1,097,986 pmol/L (median 26,600), than for either thyroid 1.7 to 415 pmol/L (median 6.5), P < 0.001, or muscle tissue 1.1 to 1230 pmol/L, (median 11.3), P < 0.001. All tissues showing high parathyroid assay values were also verified by pathology examinations: 7 had adenomas and 15 had a differential diagnosis of adenoma or hyperplasia. The frozen section identified all but one (false negative). Rapid intraoperative parathyroid levels > 1500 predicted parathyroid tissue with a 99% level of confidence, while levels between 1000 and 1500 predicted it with 95% confidence. The intraoperative parathyroid hormone assay showed > 70% decrease in 15/21 cases.

Conclusions: Rapid intraoperative parathyroid hormone analysis is a reliable and precise technique, equally accurate for frozen section analysis in predicting with high certainty intraoperative parathyroid tissue.

Background: Metal-on-metal total hip prostheses (MoM-THR) have been shown to produce hypersensitivity reactions and fluid collection (pseudotumor) by the hip as well as high blood metal ions levels (BMILs).

Objectives: To evaluate the magnetic resonance imaging (MRI) signal-to-noise ratio (S/N) in selected body tissues around the hip of patients who underwent MoM hip replacement and to correlate to BMILs.

Methods: Sixty-one MRI hip examinations in 54 post-MoM-THR patients (18 males, 36 females, mean age 65 years) were retrospectively evaluated independently by two readers. The mean S/N ratio in a region of interest was calculated for periprosthetic pseudotumor collection (PPC), the bladder, fat, and muscle on axial T1w, FSE-T2w, and short tau inversion recovery (STIR) sequences on the same location. BMILs were retrieved from patient files.

Results: PPC was detected in 32 patients (52%) with an average volume of 82.48 mm³. BMIL did not correlate with the presence of PPCs but positively correlated with the PPC's volume. A trend for positive correlation was found between BMILs and S/N levels of STIR images for muscle and bladder as well as for PPC and cobalt levels. A trend for correlation was also seen between BMIL with PPC's T1 w S/N.

Conclusions: Alteration of MRI S/N for different hip tissues showed a tendency for correlation with BMILs, possibly suggesting that metal deposition occurs in the PPC as well as in the surrounding tissues and bladder.

Background: Management of postoperative pain has become a growing concern, even for minor gynecological procedures. Proper postoperative pain management has been shown to lead to earlier mobilization, shortened hospital stay, and increased patient satisfaction. The optimal means of reducing the pain of pregnancy termination has not yet been determined.

Objectives: To compare the efficiency in pain management of two drugs, lornoxicam and paracetamol, given intravenously postoperatively to women who underwent abortion with dilation and curettage. 

Methods: The cohort comprised 80 women scheduled for dilation and curettage for pregnancy termination at 6–12 gestational weeks. The anesthesiologist gave 1000 mg paracetamol or 20 mg lornoxicam soon after starting the procedure, according to a randomization table. The medical staff and the patients were blinded to the drug that was administered. Pain levels were evaluated by a 10 cm visual analogue scale (VAS) at 15, 30, 60, 90, and 120 minutes following arrival at the postoperative care unit. 

Results: Mean levels of pain decreased from 60 minutes postoperative until the end of recording, reaching minimum levels at 120 minutes: 0.8 ± 0.19 and 1.5 ± 0.28, for lornoxicam and paracetamol, respectively. The differences between the groups were statistically significant (P < 0.05 from 60 minutes after the procedure until the time of discharge. 

Conclusions: Compared to women who received paracetamol, women who received lornoxicam after dilation and curettage for termination of pregnancy reported lower levels of pain, from 30 minutes postoperative until the time of discharge following the procedure. 

Background: Outcomes of patients with acute ST-elevation myocardial infarction (STEMI) are strongly correlated to the time interval from hospital entry to primary percutaneous coronary intervention (PPCI). Current guidelines recommend a door to balloon time of < 90 minutes. 

Objectives: To reduce the time from hospital admission to PPCI and to increase the proportion of patients treated within 90 minutes. 

Methods: In March 2013 the authors launched a seven-component intervention program: 

1. Direct patient evacuation by out-of-hospital emergency medical services to the coronary intensive care unit or catheterization laboratory


2. Education program for the emergency department staff


3. Dissemination of information regarding the urgency of the PPCI decision


4. Activation of the catheterization team by a single phone call


5. Reimbursement for transportation costs to on-call staff who use their own cars


6. Improvement in the quality of medical records


7. Investigation of failed cases and feedback 

Results: During the 14 months prior to the intervention, initiation of catheterization occurred within 90 minutes of hospital arrival in 88/133 patients(65%); during the 18 months following the start of the intervention, the rate was 181/200 (90%) (P < 0.01). The respective mean/median times to treatment were 126/67 minutes and 52/47 minutes (P < 0.01). Intervention also resulted in shortening of the time interval from hospital entry to PPCI on nights and weekends. 

Conclusions: Following implementation of a comprehensive intervention, the time from hospital admission to PPCI of STEMI patients shortened significantly, as did the proportion of patients treated within 90 minutes of hospital arrival.