Israel Medical Association Journal

Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease mainly affecting exocrine glands. However, a subgroup of patients experiences extraglandular manifestations which worsens disease prognosis. To date evidence based guidelines for the management of pSS are lacking, hence the therapeutic approach is mainly based on expert opinion and data from other connective tissue diseases. In recent years, several studies have explored the efficacy and safety of biologic agents in pSS and after the failure of tumor necrosis factor inhibitors, the attention has been focused on compounds directly targeting B or T lymphocytes. The aim of this review article is to provide an overview of available data about B and T cell targeting in pSS and of future directions based on ongoing trials. 

Background: The prevalence of major malformations in the general population is estimated at 5% of all live births. Prenatal diagnosis is an important scientific tool that allows reliable consultation and improves pregnancy outcome. In 2008, congenital malformations were the leading cause of death in Muslim infants and the second cause of death in Jewish infants in Israel. It is known that folic acid consumption prior to pregnancy decreases the rate of several fetal malformations.

Objectives: To assess the folic acid consumption rate and to characterize variables associated with its use among pregnant women attending a rural medical center. 

Methods: A cross-sectional observational study was conducted at our institution. Pregnant women in the second or third trimester of pregnancy or within 3 days postpartum were interviewed. The main variable measured was the use of folic acid. Demographic variables and the rate of prenatal testing were assessed. A secondary analysis of the population that reported no consumption of folic acid was carried out. 

Results: Out of 382 women who participated in the study, 270 (71%) reported consumption of folic acid. Using a multivariate analysis model, we found that maternal education, planning of pregnancy, and low parity were independent predictors of folic acid consumption. Women who were not consuming folic acid tended to perform fewer prenatal tests during pregnancy.

Conclusions: High maternal educational level, planning of pregnancy, and low parity are related to high consumption rates of folic acid. Women who were not taking folic acid performed fewer prenatal tests during pregnancy. 

Background: Abatacept acts as a co-stimulation modulator preventing activation of T cells. Although it is approved for the treatment of rheumatoid arthritis (RA), its effects on adaptive immune response have not been fully elucidated. 

Objectives: To observe, in a cohort study, based on a clinical practice setting, the variation of peripheral blood T cells, immunoglobulin levels, and autoantibodies in the serum of RA patients during abatacept therapy. 

Methods: Our study comprised 48 RA patients treated with abatacept. All clinical data were collected at baseline and after 3 months of treatment. Clinical and laboratory tests included erythrocyte sedimentation rate, C-reactive protein, 28-joint disease activity score, RF, anti-citrullinated protein antibody, total immunoglobulins, immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), and lymphocyte sub-population. 

Results: Total immunoglobulin serum levels significantly decreased after 3 months of treatment and correlated positively with disease activity both at baseline and after 3 months of abatacept treatment. A reduction of serum IgM, IgG, IgA and RF was also demonstrated. The absolute number and percentage of cytotoxic (CD8+) T cells significantly decreased after 3 months of abatacept treatment, in particular the percentage of cytotoxic (CD8+) T cells significantly decreased only in patients responding to the treatment.

Conclusions: Our results highlight a different role of abatacept in the modulation of the adaptive immune response in RA by the reduction of polyclonal B-cell activation and cytotoxic T cells. 

 

Background: Patients with giant cell arteritis (GCA) suffer from inflammatory diseases often treated by large amounts of corticosteroids. Whether this inflammatory burden also carries an increased risk for cardiovascular morbidity, and especially ischemic heart disease, is not clearly established.

Objectives: To clarify the linkage between GCA and ischemic heart disease. 

Methods: In a cross-sectional study, we assessed the association between GCA and ischemic heart disease, adjusting for cardiovascular risk factors, among GCA patients and matched controls using the database of the largest healthcare provider in Israel.

Results: The study group was comprised of 5659 GCA patients and 28,261 age and gender matched controls. The proportion of ischemic heart disease was higher in the GCA group (27.5% vs. 12.5% among controls, odds ratio 2.65). Diabetes mellitus, hypertension, hyperlipidemia and smoking were also found to have higher concurrency in GCA. After stratifying for those cardiovascular co-morbidities using logistic regression, GCA remained independently associated with ischemic heart disease with an odds ratio of 1.247 (1.146–1.357 P < 0.001).

Conclusions: GCA is associated with both cardiovascular risk factors and ischemic heart disease. Healthcare professionals should not overlook this aspect of the disease when managing GCA patients. 

 

Background: Anti-glomerular basement membrane (GBM) antibody disease, or Goodpasture’s disease, is the clinical manifestation of the production of anti-GBM antibodies, which causes rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. Anti-GBM antibody detection is mandatory for the diagnosis of Goodpasture’s disease either from the serum or kidney biopsy. Renal biopsy is necessary for disease confirmation; however, in cases in which renal biopsy is not possible or is delayed, serum detection of anti-GBM antibody is the only way for diagnosis.

Objectives: To assess the predictive value of positive anti-GBM antibodies in a clinical setting. 

Methods: Data from anti-GBM antibody tests performed at one medical center between 2006 and 2016 were systematically and retrospectively retrieved. We recruited 1914 patients for the study. Continuous variables were computed as mean ± standard deviation, while categorical variables were recorded as percentages where appropriate. Sensitivity and specificity of anti-GBM titers were calculated. Kaplan–Meyer analysis was performed, stratifying survival according to the anti-GBM antibody titers.

Results: Of the 1914 anti-GBM test results detected, 42 were positive, 23 were borderline, 142 were excluded, and 1707 results were negative. Male-to-female ratio was 1:1.2. Sensitivity of anti-GBM test was 41.2% while specificity was 85.4%. Concerning the Kaplan–Meyer analysis, overall survival was 1163.36 ± 180.32 days (median 1058 days). 

Conclusions: Our study highlights the lack of sensitivity of serological testing of anti-GBM titers. Comparing survival curves, the survival correlated with anti-GBM titer only in a borderline way. Because highly sensitive bioassays are not routinely used in clinics, renal biopsy is still pivotal for Goodpasture’s disease diagnosis.

 

Background: Percutaneous dilatational tracheostomy (PDT) has become a standard technique for critically ill patients who require long-term ventilation. The most common early post-operative complication is bleeding related to anatomical variation in vasculature. The procedure is performed at the patient's bedside unless this is deemed unsafe and then the accepted alternative is open tracheostomy in the operating room. 

Objectives: To evaluate the use of pre-procedural ultrasound to aid in the decision of whether PDT in critical care patients should be performed at the patient's bedside or by open surgical tracheostomy.

Methods: Patients were jointly evaluated by a critical care physician and a head and neck surgeon. Based on this evaluation, the method of tracheostomy was determined. Subsequently, pre-procedural ultrasound examination of the anterior neck was performed. The final decision whether to perform PDT or open surgical tracheostomy was based on the ultrasound findings. Changes in management decisions following ultrasound were recorded. 

Results: We included 36 patients in this prospective study. Following ultrasound examination, the management decision was changed in nine patients (25%).

Conclusions: Pre-procedural ultrasound for critically ill patients undergoing tracheostomy can influence management decisions regarding the performance of tracheostomy. 

 

Obstetric antiphospholipid syndrome (Obs-APS) is one of the most commonly identified causes of recurrent pregnancy loss and its accurate diagnosis is a requirement for optimal treatment. Some patients do not fulfill the revised Sapporo classification criteria, the original APS classification criteria, and are considered to be non-criteria Obs-APS. In these patients with non-criteria, there is controversy about their inclusion within the spectrum of APS and eventually their treatment as having Obs-APS. A subset of patients may also have clinical characteristics of Obs-APS even though lupus anticoagulant (LA), anticardiolipin antibodies, and anti-β2-glycoprotein I (aβ2GPI) antibodies are consistently negative. These patients are recognized as seronegative Obs-APS.

We reviewed evidence of non-criteria Obs-APS and discuss a case of a woman with a diagnosis of active systemic lupus erythematosus (SLE) and non-criteria Obs-APS with four consecutive pregnancy losses. After an accurate diagnosis the patient received prenatal counseling and benefited from the optimal treatment of Obs-APS that led to a successful pregnancy. The applicability of this successful experience about outcomes in women with non-criteria, or seronegative, Obs-APS is also evaluated.

 

Taxanes are often used in the treatment of many types of cancers. Side effects of docetaxel are not as well documented as paclitaxel, but both can cause pulmonary injury. We present a dramatic case of a patient being treated for prostatic adenocarcinoma with docetaxel who presented with interstitial pneumonitis and responded dramatically to the early treatment with corticosteroids. This case is important as it reveals the side effects of docetaxel administration without administration of other chemotherapeutic agents, and it illustrates the importance of early diagnosis and treatment of docetaxel-induced interstitial pneumonitis. Further research into the mechanism of the side effects of docetaxel is warranted.

Background: Atrial fibrillation (AF) is the most common arrhythmia and a common cause of ischemic stroke. Stroke patients with AF have been shown to have a poorer neurological outcome than stroke patients without AF.

Objectives: To determine the impact of pre-existing AF on residual degree of disability in patients treated with IV thrombolysis.

Methods: In this case-control study, data of 214 stroke patients (63 with AF and 151 without AF) were collected from the National Acute Stroke Israeli Registry, a nationwide quadrennial stroke database. Stroke severity and outcome were compared using the National Institute of Health Stroke Scale (NIHSS) on admission and the modified Rankin Scale (mRS) on admission and discharge. Demographics and stroke characteristics were also compared between the groups.

Results: Stroke severity, as determined by NIHSS at admission, was higher in the AF group than the non-AF. In the group of patients who were treated with intravenous tissue plasminogen activator (tPA), more patients had favorable outcomes (mRS = 0–1 on discharge) in the non-AF group than in the AF group (P = 0.058, odds ratio = 2.217, confidence interval 0.973 to 5.05).

Conclusions: Our study suggests worse outcome in thrombolized patients with AF compared to non-AF stroke patients. Therefore, AF itself can be a poor prognostic factor for tPA sensitivity regarding the chance of revascularization and recovery after intravenous tPA.