Are obesity and rheumatoid arthritis interrelated

OBJECTIVES In recent years, both the prevalence of obesity and the incidence of RA have been rising. Our aim was to assess the association between overweight or obesity and rheumatoid arthritis (RA). DESIGN Patients who were diagnosed with RA were compared with population-based controls, matched for age and sex (by a ratio of 1:5). Body measurements and smoking status were collected from medical records. Body mass index was classified in WHO categories of underweight, normal, overweight and obese (<18.5, 18.5-<25, 25-<30, ≥30 kg/m2 ). χ2 and t-tests and logistic regression models were used to compare the study groups and to assess the association between obesity and RA. SETTING A cross-sectional analysis performed utilizing the database of Clalit Health Services, the largest healthcare provider organisation in Israel. Data were collected from the beginning of computerised database usage (around year 2000) until 2015. PARTICIPANTS CHS covers over 4.4 million enrollees, of which all RA patients and matched controls were selected. MAIN OUTCOME MEASURES Proportion of obesity (BMI≥30.0 kg/m2 ) among RA patients and controls. RESULTS The study included 11 406 patients with RA and 54 701 controls. The proportion of obese subjects among RA patients was higher in comparison with controls, (33.4% vs 31.6%, respectively). In multivariate regression model, smoking and obesity were found to be associated with RA, whereas male gender was found as inversely related to RA. CONCLUSIONS Our findings demonstrate that obesity is significantly associated with RA. This finding underlines the role that obesity plays in inflammation and autoimmune conditions

The Incidence and Predictors of Solid- and Hematological Malignancies in Patients with Giant Cell Arteritis: A Large Real-World Database Study

Background: The association between giant cell arteritis (GCA) and malignancies had been widely investigated with studies reporting conflicting results. Therefore, in this study, we aimed to investigate this association using a large nationwide electronic database. Methods: This study was designed as a retrospective cohort study including GCA patients first diagnosed between 2002–2017 and age, sex and enrollment time-matched controls. Follow-up began at the date of first GCA-diagnosis and continued until first diagnosis of malignancy, death or end of study follow-up. Results: The study enrolled 7213 GCA patients and 32,987 age- and sex-matched controls. The mean age of GCA diagnosis was 72.3 (SD 9.9) years and 69.1% were women. During the follow-up period, 659 (9.1%) of GCA patients were diagnosed with solid malignancies and 144 (2.0%) were diagnosed with hematologic malignancies. In cox-multivariate-analysis the risk of solid- malignancies (HR = 1.12 [95%CI: 1.02–1.22]), specifically renal neoplasms (HR = 1.60 [95%CI: 1.15–2.23]) and sarcomas (HR = 2.14 [95%CI: 1.41–3.24]), and the risk of hematologic malignancies (HR = 2.02 [95%CI: 1.66–2.47]), specifically acute leukemias (HR = 1.81 [95%CI: 1.06–3.07]), chronic leukemias (HR = 1.82 [95%CI: 1.19–2.77]), Hodgkin’s lymphomas (HR = 2.42 [95%CI: 1.12–5.20]), non-Hodgkin’s-lymphomas (HR = 1.66: [95%CI 1.21–2.29]) and multiple myeloma(HR = 2.40 [95%CI: 1.63–3.53]) were significantly increased in GCA patients compared to controls. Older age at GCA-diagnosis (HR = 1.36 [95%CI: 1.25–1.47]), male-gender (HR = 1.46 [95%CI: 1.24–1.72]), smoking (HR = 1.25 [95%CI: 1.04–1.51]) and medium-high socioeconomic status (HR = 1.27 [95%CI: 1.07–1.50]) were independently associated with solid malignancy while age (HR = 1.47 [95%CI: 1.22–1.77]) and male-gender (HR = 1.61 [95%CI: 1.14–2.29]) alone were independently associated with hematologic- malignancies. Conclusion: our study demonstrated higher incidence of hematologic and solid malignancies in GCA patients. Specifically, leukemia, lymphoma, multiple myeloma, kidney malignancies, and sarcomas. Age and male gender were independent risk factors for hematological malignancies among GCA patients, while for solid malignancies, smoking and SES were risk factors as well

SCUBE3 loss-of-function causes a recognizable recessive developmental disorder due to defective bone morphogenetic protein signaling

Signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3) is a member of a small family of multifunctional cell surface-anchored glycoproteins functioning as co-receptors for a variety of growth factors. Here we report that bi-allelic inactivating variants in SCUBE3 have pleiotropic consequences on development and cause a previously unrecognized syndromic disorder. Eighteen affected individuals from nine unrelated families showed a consistent phenotype characterized by reduced growth, skeletal features, distinctive craniofacial appearance, and dental anomalies. In vitro functional validation studies demonstrated a variable impact of disease-causing variants on transcript processing, protein secretion and function, and their dysregulating effect on bone morphogenetic protein (BMP) signaling. We show that SCUBE3 acts as a BMP2/BMP4 co-receptor, recruits the BMP receptor complexes into raft microdomains, and positively modulates signaling possibly by augmenting the specific interactions between BMPs and BMP type I receptors. Scube3(-/-) mice showed craniofacial and dental defects, reduced body size, and defective endochondral bone growth due to impaired BMP-mediated chondrogenesis and osteogenesis, recapitulating the human disorder. Our findings identify a human disease caused by defective function of a member of the SCUBE family, and link SCUBE3 to processes controlling growth, morphogenesis, and bone and teeth development through modulation of BMP signaling.Genetics of disease, diagnosis and treatmen

Loss-of-function ENPP1 mutations cause both generalized arterial calcification of infancy and autosomal-recessive hypophosphatemic rickets.

The analysis of rare genetic disorders affecting phosphate homeostasis led to the identification of several proteins that are essential for the renal regulation of phosphate homeostasis; for example, fibroblast growth factor 23 (FGF23), which inhibits renal phosphate reabsorption and 1,25-dihydroxyvitamin D synthesis. Here, we report presumable loss-of-function mutations in the ENPP1 gene (ectonucleotide pyrophosphatase/phosphodiesterase) in members of four families affected with hypophosphatemic rickets. We provide evidence for the conclusion that ENPP1 is the fourth gene-in addition to PHEX, FGF23, and DMP1-that, if mutated, causes hypophosphatemic rickets resulting from elevated FGF23 levels. Surprisingly, ENPP1 loss-of-function mutations have previously been described in generalized arterial calcification of infancy, suggesting an as yet elusive mechanism that balances arterial calcification with bone mineralization

Autoantibody status in systemic sclerosis patients defines both cancer risk and survival with ANA negativity in cases with concomitant cancer having a worse survival

Background: A higher rate of cancer in systemic sclerosis (SSc) is recognized but the role of SSc-linked autoantibodies status (positive/negative and autoantibody specificities) in the survival of SSc-patients with cancer remains poorly understood. Methods: We utilized the Clalit-Health-Services medical database in a case-control study to evaluate the autoantibody status and specificities of SSc-patients with age- and sex-matched controls with regard to the prevalence of different cancer-subtypes and their impact on mortality. SSc-linked autoantibodies (ANA, anti-centromere, anti-RNP, anti-RNA polymerase III (RNAPIII) and anti-Scl-70) status was assessed in terms of cancer risk and outcome. Results: 2,431 SSc-patients and 12,377 age- and sex-matched controls were included. SSc-patients had a relative risk of cancer of 1.90 (95%CI 1.62-2.24, p < 0.0001) and tended to develop malignancies earlier than controls. RNAPIII and Scl-70 autoantibody were associated with an increased overall cancer risk and after SSc diagnosis risk of cancer, respectively. As expected, SSc-patients with cancer had a risk of death of 2.15 (1.65-2.79) in comparison to SSc-patients without cancer. ANA-positive SSc-patients with cancer had a better prognosis than ANA-negative cases (p = 0.0001). Despite the benefit of ANA-positive status on survival, the anti-Scl-70-positive subgroup with cancer had a significant negative impact on the survival compared to Scl-70-positive cases without cancer, whereas anti-RNAPIII and anti-centromere had no significant impact. Conclusion: ANA positivity is an independent predictor of favorable prognosis in SSc-patients with cancer, possibly suggesting that humoral autoimmunity in SSc with cancer may have some benefit. However, no survival benefit was discernible with the common autoantibodies

The Association between Sarcoidosis and Ischemic Heart Disease—A Healthcare Analysis of a Large Israeli Population

(1) Background: Inflammation plays a pivotal role in atherosclerosis, and the association between chronic inflammatory states and ischemic heart disease (IHD) has been shown in several rheumatic diseases. Persistent inflammation might also be a risk factor for IHD in sarcoidosis patients. (2) Methods: Demographic and clinical data of 3750 sarcoidosis patients and 18,139 age- and sex-matched controls were retrieved from the database of Clalit Health Services, Israel’s largest healthcare organization. Variables associated with IHD were assessed by a logistic regression model. To assess for variables that were related to increased risk of all-cause mortality, the Cox proportional hazards method was used, and a log-rank test was performed for survival analysis. (3) Results: Both groups were composed of 64% females with a median age of 56 years. An association between sarcoidosis and IHD was demonstrated by a multivariate analysis (adjusted odds ratio (OR) 1.5; 95% confidence interval (CI) 1.36–1.66). Long-term follow-up revealed increased mortality among sarcoidosis patients: 561 (15%) deaths compared to 1636 (9%) deaths among controls (p &lt; 0.001). Survival analysis demonstrated that sarcoidosis patients were also at increased risk for all-cause mortality compared to controls (multivariate model, adjusted HR 1.93; 95% CI 1.76–2.13)

"More Guts Than Brains?"-The Role of Gut Microbiota in Idiopathic Intracranial Hypertension

Idiopathic intracranial hypertension syndrome (IIH) is most common among obese women. Weight loss is an important factor in improving papilledema. Over the last decade, growing evidence has identified gut microbiota as a potential factor in the pathophysiology of obesity. Accordingly, we investigated whether the gut microbiome is modified in IIH patients compared with healthy controls, and provide possible new treatment venues