Israel Medical Association Journal

Backgrounds: Behçet's disease (BD) is a chronic vasculitic multi-systemic disease of unknown etiology. BD is characterized by recurrent attacks of oral aphthae, genital ulcers, and uveitis. BD is a multisystemic disorder and as such it may provoke various psychiatric manifestations, including depression.

Objectives: To evaluate the association between BD and depression, adjusting for established risk factors for depression.

Methods: We executed a cross-sectional study based on the Clalit Health Services database, the largest healthcare organization in Israel, serving over 4.4 million members. For this study 873 BD patients were detected and matched with 4369 controls by age and sex.

Results: The rate of depression was higher among the BD patients compared with the control group (9.39% vs 5.49%, respectively, odds ratio [OR] 1.79, 95% confidence interval [95%CI] 1.37–2.31, P < 0.001). An association between BD and depression was also observed on multivariable analysis (OR 1.83, 95%CI 1.39–2.39, P < 0.001). When stratifying the data, according to established risk factors, the association between BD and depression was prominent in the youngest age group (18–39 years of age), low and high socioeconomical status, and non-smokers.

Conclusions: Establishing the association between BD and depression should influence the attitude and the treatment of BD patients, as this relationship requires a more holistic approach and a multidisciplinary treatment regimen for all patient needs.

Background: Fibromyalgia syndrome (FMS) is characterized by widespread musculoskeletal pain and tenderness with associated neuropsychological symptoms such as fatigue, unrefreshing sleep, cognitive dysfunction, anxiety, and depression. Osteoporosis is defined as a reduction of bone density. Previous studies to determine an association of FMS with osteoporosis showed mixed results, partially due to small sample sizes and lack of statistical power.

Objectives: To evaluate the association of FMS with osteoporosis.

Methods: We conducted a case-control study utilizing the database from Israel’s largest health maintenance organization. FMS patients were compared to age- and sex-matched controls. Data were analyzed using chi-square and t-tests. Multivariable logistic regression models assessed the association between osteoporosis and FMS. Spearman’s rho test was used for correlation.

Results: We utilized data from 14,296 FMS patients and 71,324 age- and sex-matched controls. Spearman's rho test showed a significant correlation between FMS and osteoporosis (correlation coefficient 0.55, P < 0.001). A logistic regression for osteoporosis showed an odds ratio [OR] of 1.94 (95% confidence interval [95%CI] 1.83–2.06, P < 0.001) for FMS compared to controls and found higher body mass index to be slight protective (OR 0.926, 95%CI 0.92–0.93, P < 0.001).

Conclusions: There is a significant correlation between FMS and osteoporosis. Early detection of predisposing factors for osteoporosis in FMS patients and implementation of suitable treatments and prevention measures (such as dietary supplements, resistance or weight bearing exercise, and bone-mineral enhancing pharmacological therapy) may reduce both occurrence rate and severity of osteoporosis and its complications, such as fractures.

Background: Patients with type 2 diabetes mellitus (T2DM) have a high rate of cardiovascular disease (CVD). The Mediterranean diet is preferred for CVD prevention. Endothelial dysfunction is demonstrated early in T2DM.

Objectives: To study the effects of dietary intervention of T2DM patients without known CVD on endothelial function and vascular inflammation.

Methods: A prospective study enrolled 22 patients with T2DM. Patients were divided randomly into two groups: an intervention group with 12 patients (55 ± 7 years old, 6 women) and a control group with 10 patients (59 ± 10 years old, 5 women). Clinical evaluation included body mass index (BMI) and endothelial function measured by the flow mediated percent change (FMD%). Fasting blood was drawn on entry to the study and 3 months later, measuring C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), total cholesterol, triglycerides, and glycosylated hemoglobin (HbA1C%). The intervention was based on weekly telephone calls by a clinical dietitian for 3 months.

Results: In the intervention group CRP and ICAM-1 were reduced (from 4.2 ± 3.3 mg/dl to 0.4 ± 0.5 mg/dl, P = 0.01 and from 258.6 ± 98.3 ng/ml to 171.6 ± 47.7 ng/ml, P = 0.004). Endothelial function (FMD%) was improved (from 0.5 ± 8.0% to 9.5 ± 11.5%, P = 0.014). No change was observed in BMI, HbA1C%, total cholesterol, and triglycerides levels in either group.

Conclusions: Patients with T2DM on the Mediterranean diet who received a weekly telephone call for 3 months improved their endothelial function with reduction of markers of inflammation.

Background: An association was shown between thrombocytosis and future development of several cancers.

Objectives: To investigate whether pre-treatment platelet counts correlated with clinical outcomes of patients with breast cancer.

Methods: This retrospective study included 22 patients who had been diagnosed with stage I breast cancer and were 66.8 ± 13.2 years of age. Of these, 22 with stage II were 61.6 ± 12.3 years old and 9 with stage III and IV were 64.4 ± 15.3 years old. Clinical and hematological data from the first visit to the oncology clinic were collected. The follow-up period was 12 months to 5 years.

Results: A significant difference in platelet counts was found between patients who died (187,000 ± 4000 µ/L) and those who were disease free for 5 years (248,000 ± 83,000 µ/L, P = 0.0001). A significant difference in platelet-to-lymphocyte ratio was found between patients who died and those with recurrence (192 ± 81 vs. 124 ± 71, P = 0.01). A negative correlation was found between age and lymph nodes (Ps = -0.305, P = 0.02) and staging and white blood cells count (Ps = -0.280, P = 0.04). A positive correlation was found between clinical staging and lymph nodes (Ps = 0.443, P = 0.001) and clinical staging and metastases (P = 0.308, P = 0.02).

Conclusions: Platelet counts may be a prognostic marker for breast cancer. Patients who died within 1 year had lower pre-treatment platelet count, which could represent an insidious disseminated intravascular coagulopathy cancer related consumption process.

Background: Sheba Medical Center, Tel Hashomer, is a tertiary hospital located in the center of Israel. It is the largest hospital in Israel and was the first to face coronavirus disease-2019 (COVID-19) patients in the country at the beginning of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic.

Objectives: To describe our experience with the COVID-19 pandemic, focusing on our triage method in the emergency department (ED). Our goal was to keep the main hospitalization buildings clean of infection by separating COVID-19 positive patients from COVID-19 negative patients.

Methods: We divided our ED into two separate sections: a regular non-COVID-19 ED and an advanced biological ED. We created clear protocols of triage for suspected and confirmed COVID-19 patients. We reviewed the data of patients admitted to our ED during the month of March and analyzed the results of our triage method in separating COVID-19 positive from negative patients.

Results: During the month of March 2020, 7957 patients were referred to our ED. Among them 2004 were referred to the biological ED and 5953 were referred to the regular ED. Of the 2004 patients referred to the biological ED, 1641 (81.8%) were sampled for SARS-CoV-2 polymerase chain reaction of whom 143 (8.7%) were positive. Only two COVID-19 positive patients unintentionally entered the main clean hospital, making our triage almost full proof.

Conclusions: Our triage method was successful in separating COVID-19 positive from negative patients and maintained the regular hospital clean of COVID-19 allowing treatment continuation of regular non-COVID-19 patients.

Background: Cardiovascular disease (CVD) is more frequent in patients with systemic lupus erythematosus (SLE) compared with age- and sex-matched healthy subjects. SLE is an autoimmune disease that is more prevalent in women (9:1). Women tend to develop CVD in post-menopausal years; however, women with SLE may develop endothelial dysfunction and CVD at a younger age in the pre-menopausal years.

Objectives: To study the endothelial function of adult-onset SLE patients from the north of Israel (the Galilee region) and to determine whether modern management (including biological treatments) changes the risk of developing CVD.

Methods: Thirteen females with adult-onset SLE without renal involvement were recruited to this prospective study. Clinical parameters (age, height, body mass index [BMI]), laboratory parameters (C-reactive protein [CRP] and hemoglobin level), and vascular responsiveness (flow mediated diameter percent change [FMD%]) were evaluated and compared to 11 age-matched healthy females. Student's t-test was used to find differences between the two groups.

Results: No difference was observed in adult-onset SLE female patients and their age- and sex-matched controls with regard to age (42.1 ± 11.8 years vs. 36.6 ± 10.8 years, P = NS), BMI (25 ± 1.8 kg/m² vs. 25 ± 2.5 kg/m², P = NS), and hemoglobin level (11.9 ± 0.9 gr% vs. 12.7 ± 1.2 gr%, P = NS). However, a significant difference was found in CRP (2.57 ± 2.2 mg vs. 0.60 ± 0.37 mg, P = 0.001), vascular responsiveness (0.94 ± 6.6 FMD% vs. 9.2 ± 8.1 FMD%, P = 0.012), and height (165.7 ± 4.5 cm vs. 171.6 ± 5.8 cm, P = 0.009).

Conclusions: Adult-onset SLE females had impaired endothelial function even though they were treated by modern protocols.

Inflammation is the basic mechanism leading to many pathological processes, including degenerative diseases, atherosclerosis, and cancer. We found an interesting link connecting rheumatoid arthritis and atherosclerosis that may explain the high cardiovascular event rate among patients with rheumatoid arthritis, but also may lead to a new way of thinking and a better understanding of atherosclerosis. Rheumatoid arthritis could serve as a model of accelerated atherosclerosis. Understanding the basic mechanisms of rheumatoid arthritis may solve some of the complexity of atherosclerosis.

Erectile dysfunction (ED) is a syndrome associated with endothelial dysfunction, which may predict cardiovascular events in men presenting with this syndrome. It has been shown to be associated with a higher rate of acute myocardial infarction and cardiovascular mortality, vascular inflammation, and impaired endothelial function. In this review we present the literature findings and describe the mechanistic pathways that are known to be involved in this syndrome and its related clinical consequences.

Background: With the widespread use of antifungal agents, the frequency of non-albicans Candida (NAC) blood-stream infections (BSI) is increasing.

Objectives: To describe the epidemiology, clinical manifestations, and risk factors for NAC BSI, focusing on prior antifungal and immunosuppressive therapy.

Methods: The authors conducted an observational, retrospective cohort study among adult patients with candidemia at the Rambam Health Care Campus, a tertiary medical center in Israel, between 2009 and 2015. Comparisons between patients with Candidemia albicans and NAC candidemia were performed. Regression analysis, with NAC BSI as the dependent variable and significant risk factors for NAC as independent variables, was performed.

Results: A total of 308 episodes of candidemia were included. C. albicans was isolated in 30.8% of patients (95/308), while NAC spp. were isolated in the rest. Significant independent risk factors for NAC included immunosuppression therapy (odds ratio [OR] 0.38, 95% confidence interval [95%CI] 0.19–0.76) and previous azole use (OR 0.2, 95%CI 0.06–0.710). The interaction between prior azole and immunosuppression therapy in the model was not significant, and after its inclusion in the model only immunosuppression remained significantly associated with NAC. In the subgroup of patients who did not receive prior azoles, immunosuppression therapy, neutropenia, and bone marrow transplantation were significantly associated with NAC.

Conclusions: Independent of previous azole treatment, immunosuppressive therapy was a significant risk factor for NAC in our cohort.