Israel Medical Association Journal

Background: The prevalence of pregestational diabetes mellitus (PGDM) in women of reproductive age has surged globally, contributing to increased rates of adverse pregnancy outcomes. Hemoglobin A1c (HbA1c) is a crucial marker for diagnosing and monitoring PGDM, with periconceptional levels influencing the risk of congenital anomalies and complications.

Objectives: To evaluate the association between periconceptional HbA1c levels and perinatal complications in pregnant women with poorly controlled PGDM.

Methods: We conducted a retrospective analysis of prospectively collected data of pregnancies between 2010 and 2019, HbA1c > 6% at 3 months prior to conception or during the first trimester. Outcomes of periconceptional HbA1c levels were compared.

Results: The cohort included 89 women: 49 with HbA1c 6–8%, 29 with HbA1c 8–10%, and 11 with HbA1c > 10%. Higher HbA1c levels were more prevalent in type 1 diabetics and were associated with increased end-organ damage risk. Women with elevated HbA1c levels tended toward unbalanced glucose levels during pregnancy. The cohort exhibited high rates of preterm delivery, hypertensive disorders, cesarean delivery, and neonatal intensive care unit admission. Overall live birth rate was 83%. While a significant correlation was found between HbA1c levels and preterm delivery, no consistent association was observed with other adverse outcomes.

Conclusions: Periconceptional glycemic control in PGDM pregnancies is important. Elevated HbA1c levels are associated with increased risks of adverse outcomes. Beyond a certain HbA1c level, risks of complications may not proportionally escalate.

Background: Cardiac amyloidosis (CA) is characterized by the extracellular deposition of misfolded protein in the heart. Precise identification of the amyloid type is often challenging, but critical, since the treatment and prognosis depend on the disease form and the type of deposited amyloid. Coexistence of clinical conditions such as old age, monoclonal gammopathy, chronic inflammation, or peripheral neuropathy in a patient with cardiomyopathy creates a differential diagnosis between the major types of CA: amyloidosis light chains (AL), amyloidosis transthyretin (ATTR) and amyloidosis A (AA).

Objectives: To demonstrate the utility of the Western blotting (WB)-based amyloid typing method in patients diagnosed with cardiac amyloidosis where the type of amyloid was not obvious based on the clinical context.

Methods: Congo red positive endomyocardial biopsy specimens were studied in patients where the type of amyloid was uncertain. Amyloid proteins were extracted and identified by WB. Mass spectrometry (MS) of the electrophoretically resolved protein-in-gel bands was used for confirmation of WB data.

Results: WB analysis allowed differentiation between AL, AA, and ATTR in cardiac biopsies based on specific immunoreactivity of the electrophoretically separated proteins and their characteristic molecular weight. The obtained results were confirmed by MS.

Conclusions: WB-based amyloid typing method is cheaper and more readily available than the complex and expensive gold standard techniques such as MS analysis or immunoelectron microscopy. Notably, it is more sensitive and specific than the commonly used immunohistochemical techniques and may provide an accessible diagnostic service to patients with amyloidosis in Israel.

Fetal hydrops is a life-threatening condition defined as abnormal accumulation of fluid in two or more fetal compartments: ascites, pleural effusion, pericardial effusion, or generalized skin edema [1]. Fetal hydrops may also be associated with polyhydramnios and placental edema [2].

Based on pathophysiology results, fetal hydrops is classified as either immune or non-immune. The frequency of immune fetal hydrops has decreased dramatically since the development of Rh (D) immunization given to mothers at risk. Nonimmune hydrops fetalis (NIHF) accounts for almost 90% of cases [1]. The etiology of NIHF is further classified as cardiovascular (17–35%), chromosomal (7–16%), hematologic (4–12%), infectious (5–7%), and unknown (15–25%). Inborn errors of metabolism account for only 1–2% of NIHF cases [1]. NIHF is commonly progressive. Complete resolution of NIHF before birth is rare.

Background: Acquired hepatocerebral degeneration (AHD) is a neurologic complication of severe chronic liver disease (CLD) with portosystemic shunts. The proposed etiology is manganese accumulation in the brain tissue, especially in the basal ganglia. Combination of clinical manifestation, mostly extrapyramidal movement disorders, and hyperintensities on T1-weighted brain magnetic resonance imaging (MRI) is diagnostic. Although liver transplantation controversial, it is suggested for AHD.

Objectives: To depict clinical and neuroimaging characteristics and response to treatments in patients diagnosed with AHD at Sheba Medical Center.

Methods: Review of patients with AHD diagnosis at the Liver Diseases Center at Sheba Medical Center between 2012 and 2017, data of clinical and neuroimaging, follow-up, and response to treatments, including liver transplantation were recorded.

Results: Five patients with diagnosis of AHD were identified, median age at diagnosis 55 years (range 45–64 years). Four patients had cirrhosis at the time of AHD diagnosis. The main risk factor for AHD was the presence of portosystemic shunts. The most prevalent clinical manifestations were movement disorders, specifically a combination of extrapyramidal and cerebellar signs including instability, rigidity, tremor, bradykinesia, and cognitive impairment. Brain MRI revealed hyperintensities on T1-weighted images in the basal ganglia in all patients. Administration of antiparkinsonian drugs showed clinical improvement, whereas liver transplantation performed in two patients was not associated to neurological improvement.

Conclusions: AHD is related to portosystemic shunts. The combination of Parkinsonism and cerebellar signs and MRI pallidal lesions should alert physicians to the diagnosis. The role of liver transplantation in AHD is still controversial.

Background: National registries for acromegaly and population-based data make an important contribution to disease understanding and management. Data concerning the epidemiology of acromegaly in Israel is scanty.

Objectives: To evaluate the epidemiology of acromegaly in different industrial areas in northern Israel.

Methods: Data from adult patients diagnosed with acromegaly from 2000 to 2020, living in Haifa and the western Galilee District were collected using the electronic database and medical records from Clalit Health Services. The prevalence of acromegaly in three distinct areas and overall were reported. In addition, other epidemiological data including associated co-morbidities, pituitary tumor size, and treatment modalities were collected.

Results: We identified 77 patients with a confirmed diagnosis of acromegaly. The overall prevalence was 155 cases/10⁶ inhabitants without statistically significant differences between the three areas. The mean age at diagnosis was 50 ± 1.8 years and the male to female ratio was 1.1. Macroadenoma and microadenoma were identified in 44 (57%) and 25 (33%), respectively. The frequency rate of acromegaly-associated co-morbidities such as diabetes, hypertension, carpal tunnel syndrome, and osteoporosis was similar to previously reported studies. The mean body mass index (BMI) was 29 ± 5.6 kg/m² .Obesity, with a BMI ≥ of 30 kg/m², was found in 29 patients (38%). The majority of patients underwent transsphenoidal surgery 67 (87%). Normalized insulin-like growth factor 1 was reported in 64 (83%).

Conclusions: A high prevalence of acromegaly was found in northern Israel. The pituitary microadenoma frequency rate is the highest reported.

Background: Whole-body integrated positron emission tomography / contrast-enhanced computed tomography (PET/CT) scan is increasingly used in cutaneous lymphomas. However, the value of PET/CT in the detection of cutaneous lesions in primary cutaneous B-cell lymphoma (PCBCL) has barely been investigated.

Objectives: To investigate the diagnostic accuracy of PET/CT in tracking cutaneous involvement in PCBCL.

Methods: A retrospective study was conducted on 35 consecutive patients diagnosed with cutaneous B-cell lymphoma according to the World Health Organization classification who were evaluated with PET/CT as the initial staging procedure before treatment.

Results: Thirty-five patients met the study criteria. In two patients extracutaneous disease was detected by PET/CT and CT and confirmed by biopsy. Of the 33 patients with PCBCL, 26 (79%) had small cell PCBCL (18 marginal-zone, 8 follicle-center lymphoma) and 7 (21%) had large cell PCBCL (3 follicle-center, 3 leg-type, 1 indeterminate). PET/CT detected skin lesions in 3 of 26 patients (12%) with small-cell PCBCL as compared to 6 of 7 patients with large-cell PCBLC (86%), a 7.4-fold detection risk (95% confidence interval, 2.4–22, P = 0.004). The PET-positive subgroup was characterized by larger lesion size (P < 0.001) and a higher Ki-67 proliferation index (P < 0.001).

Conclusions: The sensitivity of PET/CT for detecting cutaneous involvement of lymphomas is low for small-cell PCBCL but high for large-cell types, and thus may facilitate therapeutic strategies.

Objectives: To present our initial experience with MitraClip implantation in 20 high risk patients at Sheba Medical Center.

Methods: Twenty high surgical risk patients with symptomatic significant MR underwent MitraClip implantation. Clinical and echocardiographic parameters were recorded at baseline and at follow-up.

Results: The patients’ mean age was 76 years and 65% were male. Coronary artery disease was present in 85% and 45% had previous bypass surgery. Renal failure was present in 65%, atrial fibrillation in 60%, and 30% had an implantable cardioverter defibrillator/cardiac resynchronization therapy device. Mean left ventricular ejection fraction was 36%. Grade III-IV MR was present in all patients with the vast majority suffering from functional MR secondary to ventricular remodeling. New York Heart Association (NYHA) class was III-IV in 90%. Patients were followed for a mean of 231 days. Acute reduction of MR grade to ≤ 2 was accomplished in 19 of the 20 patients (95%) with a 30 day mortality of 5%. At follow-up MR was reduced to ≤ 2 in 64% of patients, and NYHA class improved in 70% of patients. An additional 2 patients (11%) died during follow-up.

Conclusions: MitraClip implantation is feasible and safe in high risk highly symptomatic patients with significant MR. Acute and mid-term results are comparable to similar high risk patient cohorts in the literature. Continued surveillance and longer follow-up are needed to elucidate which patients are most likely to benefit from the procedure.

Objectives: To investigate current smoking trends among Israeli physicians.

Methods: All practicing physicians at a tertiary university-affiliated medical center in central Israel were invited to complete a Web-based questionnaire on smoking habits and smoking-related issues via the institutional email. Findings were compared to those in the general population and between subgroups.

Results: Of the 90 responders (53 male, 88 Jewish), 54 (60%) had never smoked, 21 (23.3%) were past smokers, and 15 (16.7%) were current smokers. The rate of current smokers was lower than in the general population. The proportion of current smokers was higher among residents than attending physicians and among physicians in surgical compared to medical specialties. Past smokers accounted for 17.9% of the residents (average age at quitting 26.2 years) and 28.1% of the attending physicians (average age at quitting 33.0 years). Non-smokers more frequently supported harsh anti-smoking legislation.

Conclusions: The rate of smoking is lower in physicians than in the general population but has not changed over the last 15 years. Anti-smoking programs should particularly target physicians in surgical specialties. 

Background: Double balloon enteroscopy is a new technique that enables deep intubation of the endoscope into the small bowel lumen. Through a channel in the endoscope, invasive procedures such as biopsy, polypectomy and hemostasis can be performed, avoiding the need for surgery.

Objectives: To prospectively analyze our results of the first 124 DBEs[1] performed since February 2007.

Methods: The study group comprised all patients who underwent DBE at the Sheba Medical Center between February 2007 and February 2009. Recorded were the patients' demographic data, comorbidities, indications for the examination, results of previous non-invasive small bowel imaging (computed tomography enterography, capsule endoscopy, etc), investigation time, and results of the procedure including findings, endoscopic interventions, complications and pathological report.

Results: A total of 124 procedures were performed in 109 patients. Of the 124 examinations, 57 (46%) were normal and 67 (54%) showed pathology. The main pathologies detected on DBE were polyps (14%), vascular lesions (17.6%) and inflammation (12%). Endoscopic biopsies and therapeutic interventions were required in 58 examinations (46%). A new diagnosis was established in 15% of patients, diagnosis was confirmed in 29% and excluded or corrected in 12%. One complication was observed: a post-polypectomy syndrome that was treated conservatively.

Conclusions: DBE is a safe procedure and has a high diagnostic and therapeutic yield. Most of the examinations were performed under conscious sedation, and only a minority of patients required deeper sedation. 

Background: Infections with blood-borne viruses are a major health problem among illicit drug users. There is little information about infection rates and risk factors for hepatitis virus B, C or the human immunodeficiency virus in drug users in Israel.

Objectives: To determine the prevalence of HCV[1], HBV[2] and HIV[3] infections in a large cohort of drug users in Israel; to compare rates of HCV, HBV and HIV between injecting versus non-injecting drug users and between different origin countries; and to identify risk factors for HCV among illicit drug users.

Methods: We conducted a cross-sectional interviewer-administered questionnaire and serological screening for HCV, HBV and HIV in 1443 consecutive drug users diagnosed at the Israeli National Center for Diagnosis of Drug Addicts between January 2003 and December 2005.

Results: Fourteen (0.9%), 51 (3.5%) and 515 (35.7%) subjects tested positive for HIV, HBV and HCV, respectively. All three infections (HIV, HBV and HCV) were significantly more common among injecting drug users and immigrants from the former Soviet Union and other East European countries compared to native Israelis. Multivariate analysis showed that HCV infection was associated with age (> 40 years) (OR=2.06, 95% CI 1.40–3.03), immigration from East European countries and the former Soviet Union (OR=4.54, 95% CI 3.28–6.28), and injecting drug use (OR=16.44, 95% CI 10.79–25.05).

Conclusions: HIV, HBV and HCV prevalence among drug users in Israel is significantly lower than in North America and West Europe. Risk factors for HCV infection in this population include injecting drug use, older age, and immigration from the former Soviet Union.

Background: The Fibrotest-Actitest™ is a six-parameter scoring system that allows quantification of liver fibrosis and inflammation. This test has been validated by several studies in hepatitis B and C viruses and alcoholic liver disease, with a high correlation between the liver biopsy and the results of the FT-AT[1] (AUROC between 0.78 and 0.95).The FT-AT was introduced in Israel (Rambam Laboratory) in March 2005.

Objectives: To assess the results of HCV[2] patients who underwent the test during the period March 2005 to February 2006.

Methods: Serum was taken and brought to the central laboratory performing the tests within 4 hours. Six parameters were evaluated using commercial kits approved by the designer of the test (Biopredictive): total bilirubin, gamma-glutamyltransferase, alpha-2 macroglobulin, haptoglobin, alanine aminotransferase, and apolipoprotein-A1. The results were sent to the website of Biopredictive (France), which provided the FT-AT score online using a patented formula.

Results: Of the 325 patients tested, only 4 were not interpretable because of hemolysis. Patients' age ranged from 7 to 72 years (median 42); 54% were female. Liver biopsy was performed in 81 patients and was compared with the results of the Fibrotest. Findings were as follows: 27% of the patients were F0, 19% F1, 20% F2, 17% F3 and 17% F4; 18% were A0, 32% A1, 28% A2 and 22% A3. The AUROC curve comparing the Fibrotest with liver biopsy with a cutoff point at F2 and A2 for significant fibrosis and inflammation was 0.85 and 0.79 respectively.

Conclusion: Fibrotest is a simple and effective method to assess liver fibrosis and inflammation and can be considered an alternative to liver biopsy in most patients with HCV.

Background: Israeli youth lead 27 western countries in dieting. The prevalence of eating disorders has been rising in the last 30 years, causing social problems and medical complications.

Objectives: To examine the prevalence of eating disorders among high school students in a region in northern Israel (Misgav) and to examine the relationship between the parents' employment status and the subject’s eating disorder.

Methods: A structured questionnaire was administered to collect demographic data. The short version of the Eating Attitudes Test (EAT-26) was used to evaluate the subject’s attitudes toward and preoccupation with food, dieting, eating, physical appearance, and personal control over eating.

Results: Of 360 students approached, 283 (78%) completed the self-report EAT-26. One of every 5 females and one in every 20 males had an abnormal eating attitude. The rate of pathologic EAT-26[1] results, 20.8%, falls within the high range of similar community-based samples of female adolescents. There were no differences in EAT-26 score between students with an employed or unemployed mother; however, there was a trend for higher EAT-26 scores among those whose father was unemployed (21.4% vs. 12.7%, c²  = 0.14).

Conclusions: The findings support our hypothesis of a relatively high rate of abnormal eating attitudes (as reflected by high EAT-26 score) in this population. Another possible risk factor is having an unemployed father, which warrants further research and attention. Our next step is to introduce an intervention program in the school and to study its effect.

Objectives: To determine the effectiveness of a neuroreflexology-based screening test, specifically the Medex device (Medex Screen Ltd.), for diagnosing patients undergoing conventional internal organ assessment, in a hospital setting.

Methods: Patients admitted to an internal medicine department, who met the inclusion criteria and agreed to participate, underwent conventional medical evaluation that included past medical history and physical examination. Another examination was conducted by a second physician using the Medex device to determine internal organ pathologies. A third researcher compared the actual “conventional” diagnosis with the Medex device output using standard statistical analysis.   

Results: Overall, 150 patients participated in the study. Correlation was significant for all categories (P < 0.01) except for blood and lymphatic disease. A high sensitivity (>70%) was measured for cardiovascular, respiratory, gastrointestinal and genitourinary diseases. The highest measure of agreement, as represented by the Cohen-Kappa factor, was found for respiratory disease (0.57).

Conclusions: Although the exact mechanism is not entirely clear, measurement of electroskin impedance of dermal-visceral zones has the potential to serve as a screening tool for inner organ pathologies. Further research should be conducted to create more evidence to support or dispute the use of this technique as a reliable diagnostic tool.