Yarden Yavne

Investigating the link between ischemic heart disease and Behcet's disease: A cross-sectional analysis

BACKGROUND Behcets disease (BD) is a multi-systemic chronic inflammatory disorder which involves the vasculature tree of all sizes. The current studys aim was to examine the association between BD and the development of ischemic heart disease (IHD) and its potential impact as a cardiovascular risk factor. METHODS This study was conducted as a case-control study utilizing the database of Clalit Health Services. The proportion of IHD was compared between patients diagnosed with BD and age- and gender-matched controls. Univariate analysis was performed using Chi-square and Student t-test and a multivariable analysis was performed using a logistic regression model. RESULTS 871 BD patients and 4439 age- and gender-matched controls were included in this study. The proportion of IHD amongst BD patients was increased in comparison with controls (10.9% vs. 7.52% respectively, p-value=0.001). BD was associated with IHD on multivariable analysis (odds ratio 1.485, 95% confidence interval 1.106-1.982). When the comparison between BD patients with IHD and controls with IHD was stratified according to risk factors, age younger than 70 and male gender were both found to be significantly elevated in the BD group. CONCLUSIONS BD patients have an increased proportion of IHD in comparison with matched controls. Our findings demonstrate that the population of BD patients with IHD has a higher proportion of younger males in comparison with controls with IHD.

Patients With Vasculitides Admitted to the Intensive Care Unit: Implications From a Single-Center Retrospective Study:

Background: Vasculitides are a group of disorders characterized by inflammation of vessels. Vasculitides may have life-threatening complications with significant morbidity and mortality; however, information regarding the outcome and prognosis of patients with vasculitides requiring intensive care unit (ICU) is scarce. Methods: Data of patients with vasculitides admitted to the ICU of the Sheba Medical Center between the years 2000 and 2014 were retrieved retrospectively. Continuous variables were computed as mean (standard deviation), whereas categorical variables were recorded as percentages. In order to investigate the impact of clinical variables on mortality, Student t test and χ2 analyses were performed. Results: Twenty-five patients with vasculitides were admitted to the ICU during the study period with mean age of 52 ± 14 years and sex ratio of male/female: 12/13. The mortality rate among these patients was 48%. Leading causes for ICU admission were infection (64%), disease exacerbation (34%), and hemorrhage (16%), while respiratory or cardiovascular involvement accounted for the majority of mortality during admission. An elevated Sequential Organ Failure Assessment (SOFA) score was significantly associated with mortality (P = .041). Conclusion: Our study confirms the high mortality rate among patients with vasculitides who require ICU care as well as the roles of infection and disease flare-up as causes for admission. An elevated SOFA score was found to be predictive of mortality.

A systematic review of precipitating physical and psychological traumatic events in the development of fibromyalgia

The role of physical and psychological trauma precipitating fibromyalgia is often encountered by physicians, yet a proper systematical review of this association is lacking. Literature searches identified 51 studies which examined the association of fibromyalgia with a preceding traumatic event of physical or emotional nature. The overall quality of evidence of studies included, as assessed by the GRADE criteria, was low, however the majority of studies described a significant association between prior physically traumatic events and the onset of chronic widespread pain or fibromyalgia. Elevated rates of psychological trauma in fibromyalgia patients were demonstrated across the literature and several studies indicate a mediating effect of post-traumatic stress disorder. Potential biological mechanisms for conversion of traumatic events into a chronic pain syndrome, such as fibromyalgia, are discussed.

Borderline positive antineutrophil cytoplasmic antibodies (ANCA)-PR3/MPO detection in a large cohort tertiary center: lessons learnt from a real-life experience

Abstract Background: Enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence (IIF) are the best strategies for antineutrophil cytoplasmic antibodies (ANCA) detection. In a minority of subjects, ELISA-based ANCA testing may result in a borderline positive titre. Therefore, we assessed the clinical significance of such a result. Methods: This is a retrospective study, which included all subjects screened for ANCA subtypes (myeloperoxidase (MPO) or proteinase-3 (PR3)) with subsequent identification of borderline positive results, as determined by ELISA and retested using IIF. The demographic, clinical and laboratory data of subjects with borderline positive ANCA test results were extracted from their medical records. Results: A total of 14,555 PR3/MPO-ANCA tests were performed with ELISA during the study period (2006–2016). Of the 14,555 PR3-ANCA antibody tests that were performed, 94 were borderline positive (titre 0.9–1.1), and of 14,555 MPO-ANCA antibody tests, 43 were borderline positive (titre 0.9–1.1). The male-to-female ratio was 1:1.08 and the mean age was 50.95±21.79 years. Four MPO-ANCA (9.30%) and 11 PR3-ANCA (11.70%) antibody borderline samples resulted positive on IIF testing. Subjects with borderline positive MPO-ANCA were found to have a poorer outcome in terms of renal failure and the requirement of dialysis. Conclusions: Subjects with borderline positive MPO-ANCA and positive p-ANCA (IIF) seem to have a less favorable outcome. Physicians should be aware of these findings and possibly perform a closer follow-up and routine screening for these subjects.

Stroke among Rheumatoid Arthritis Patients: Does Age Matter? A Real-Life Study

Background/Aims: Rheumatoid arthritis (RA) is a chronic, debilitating autoimmune disease that affects the joints and it is known to be associated with cardiovascular morbidity. However, the association between RA and stroke among different age groups has not been explored. The objective of our study was to evaluate the association between RA and stroke in different age strata. Methods: Cross-sectional study, utilizing the database of Israel’s largest healthcare provider. The proportion of stroke was compared between patients diagnosed with RA and age- and gender-matched controls. The study sample was divided into 2 age groups: young (≤65 years) and elderly (>65 years). Multivariable analysis was performed using logistic regression. Results: The study included 11,782 RA patients and 57,973 age- and gender-matched controls. RA patients, primarily young, had more cardiovascular risk factors than controls. Stroke rates were significantly elevated among young RA patients in comparison with controls (3.74 vs. 2.20%, respectively, p < 0.001). In multivariate analysis, RA was found to be independently associated with stroke (OR 1.18, 95% CI 1.09–1.28). Conclusion: RA is independently associated with stroke, especially among RA patients under 65 years, for whom cardiovascular risk factors were more prominent. Physicians should advise RA patients to manage their risk factors strictly.

Association between giant cell arteritis and thyroid dysfunction in a “real life” population

PurposeGiant cell arteritis is a systemic autoimmune disorder which involves inflammation of medium to large vessels. The association between giant cell arteritis and autoimmune thyroid disorders has been investigated numerous times in the literature with inconsistent results. Our objective was to evaluate whether a genuine association exists between giant cell arteritis and thyroid dysfunction, which is often due to immune-mediated thyroid disease.MethodsUtilizing the medical database of Clalit Health Services, we compared the proportion of hypo and hyperthyroidisim between patients with giant cell arteritis and age-matched and gender-matched controls in a cross-sectional study. Univariate analysis was performed using Chi-square and student t-test and a multivariate analysis was performed using a logistic regression model.ResultsFive thousand six hundred and sixty three giant cell arteritis patients and 23,308 age-matched and gender-matched controls were included in the study. The proportion of hypothyroidism amongst giant cell arteritis patients was increased in comparison with controls (18.2 vs. 6.91%, respectively, p-value < 0.001), as was hyperthyroidism (2.56 and 1.19% respectively, p-value < 0.001). Giant cell arteritis demonstrated an independent association with hypothyroidism on multivariate analysis (Odd Ratios 1.297, 95% Confidence Intervals 1.19–1.42), yet not with hyperthyroidism.ConclusionsGiant cell arteritis patients have a higher proportion of hypothyroidism in comparison with matched controls. Physicians treating giant cell arteritis patients should consider screening for thyroid dysfunction on a regular basis.

Folate and B12 Levels Correlate with Histological Severity in NASH Patients

Background: The correlation between abnormal vitamin serum levels and chronic liver disease has been previously described in literature. However, the association between the severity of folate serum levels (B9), vitamin B12 and nonalcoholic steatohepatitis (NASH) has not been widely evaluated. Therefore, the aim of this study was to investigate the existence of such a correlation in a cohort of NASH patients. Methods: All patients aged 18 years and older who were diagnosed with biopsy-proven NASH at the EMMS hospital in Nazareth during the years 2015–2017 were enrolled in this study. Data regarding demographic, clinical and laboratory parameters was collected. Patients with other liver diseases were excluded. Results: Eighty-three NASH patients were enrolled during the study period. The mean age was 41 ± 11 years and the majority of patients were male. Mean values of folate and B12 were 9.85 ± 10.90 ng/mL and 387.53 ± 205.50 pg/mL, respectively. Half of the patients were presented with a grade 1 steatosis (43.4%), a grade 2 fibrosis (50.6%) and a grade 3 activity score (55.4%). The fibrosis grade was significantly correlated with low folate levels on multivariate analysis (p-value < 0.01). Similarly, low B12 levels were significantly associated with a higher fibrosis grade and NASH activity (p-value < 0.001 and p-value < 0.05 respectively). Conclusion: Our study demonstrated a statistically significant correlation between low levels of folate and vitamin B12 with the histological severity of NASH. These findings could have diagnostic and therapeutic implications for patient management and follow-up.

The link between COPD and ankylosing spondylitis: A population based study

BACKGROUND Ankylosing spondylitis (AS) is one of the most common and severe subtypes of the spondyloarthropathies. Extra-articular involvement among AS patients, including lung disease, has been described widely. Chronic obstructive pulmonary disease (COPD) has been linked to several autoimmune diseases, however, very few studies have investigated the association between AS and COPD. OBJECTIVE To assess whether an association exists between AS and COPD. MATERIAL AND METHODS A population-based cross-sectional study was conducted using data retrieved from the largest electronic medical records database in Israel, the Clalit Health Services (CHS). Patients were defined as having AS or COPD when there was at least one such documented diagnosis in their medical records. The proportion of COPD was compared between AS patients and controls. A logistic regression model was used to estimate the association between AS and COPD in a multivariate analysis adjusted for age, gender and smoking status. RESULTS The study included 4076 patients with AS and 20,290 age- and sex-frequency matched controls. The proportion of COPD in AS patients was higher than in controls (46% vs. 18%, respectively, p < .001). Multivariate logistic regression demonstrated a robust independent association between AS and COPD (OR 1.225, p = .031). CONCLUSION Our study supports an association between AS and COPD, further extending the link between COPD and autoimmune diseases. This finding highlights the importance of smoking cessation in AS patients and raises the question of whether COPD screening may be warranted.

Vitamin D, autoimmunity and recurrent pregnancy loss: More than an association

Recurrent pregnancy loss (RPL) affects close to 1% of couples; however, the etiology is known in only about 50% of the cases. Recent studies show that autoimmune dysregulation is a probable cause of RPL, which in some cases may be overlooked. In order for a pregnancy to proceed to term, early modulation of immunologic response is required to induce tolerance to the semi‐allogenic fetus. Certain subsets of both the innate and adaptive immune responses play a role in the induction of fetomaternal tolerance. A relatively predominant T‐cell helper (Th) 2 and T regulatory (Treg) cell population seem to favor a better pregnancy outcome, whereas Th1 and Th17 cell populations appear to have an opposite effect. Lately, the role of vitamin D in the modulation of immune response was established. Vitamin D has been shown to promote a more favorable environment for pregnancy through various mechanisms, such as enhancement of the shift toward Th2 cells and regulation of immune cell differentiation and cytokine secretion. Therefore, it seems that vitamin D deficiency sways the balance toward a worse outcome and may play a part in recurrent pregnancy loss. This review sheds light on the immunologic changes, which occur in early pregnancy and the regulatory role vitamin D has in the maintenance of this delicate balance.

Silicone breast implants and the risk of autoimmune/rheumatic disorders: a real-world analysis

Objectives Several epidemiological studies have investigated the link between silicone breast implants (SBIs) and autoimmune/rheumatic disorders, reporting inconsistent results. We aimed to evaluate the association between SBIs and the most clinically relevant autoimmune/rheumatic disorders using a large, population-based database. Methods In this cross-sectional study, we used the computerized databases of Maccabi Healthcare Services (MHS), which include up to 20 years of data on 2 million members. Women with SBIs were identified by procedure and diagnosis codes, clinical breast examinations and mammography referrals. Autoimmune/rheumatic disorders were identified using the International Classification of Diseases 9th revision (ICD-9) codes. Multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). A Coxs proportional hazards model was used to calculate the hazard ratios (HRs) and 95% CIs among a subgroup of SBI recipients for whom the year of SBIs insertion was available. Results We included 24 651 SBI recipients and 98 604 matched SBI-free women. The adjusted OR between SBIs and being diagnosed with any autoimmune/rheumatic disorders was 1.22 (95% CI 1.18-1.26). The strongest association with SBIs (OR > 1.5, p < 0.001) was recorded for Sjögrens syndrome, systemic sclerosis (SSc) and sarcoidosis (OR of 1.58, 1.63 and 1.98, respectively). Similar results were calculated when analysis was limited to women with no breast cancer history. A multivariable Cox regression model yielded a HR of 1.45 (95% CI 1.21-1.73) for being diagnosed with at least one autoimmune/rheumatic disorder in women with SBI compared with those without. Conclusions SBIs seem to be associated with higher likelihood of autoimmune/rheumatic disorders diagnosis.