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Objective The association between chronic inflammatory conditions and cardiovascular disease is well established. Considering FMF, few studies exist investigating the risk of ischaemic heart disease, and none address the risk of stroke. We aimed to evaluate the incidence and risk for stroke in FMF patients compared with the general population. Methods A retrospective cohort study using the electronic database of Clalit Health Services (CHS), the largest health organization in Israel. All FMF patients diagnosed between 2000 and 2016 were included and matched with control according to age, gender and place of residence. Follow-up continued until the first diagnosis of stroke or death. The incidence of stroke was compared between the groups using univariate and multivariate models adjusting for cardiovascular risk-factors. Results A total of 9769 FMF patients and a similar number of controls were followed up for a median period of 12.5 years. The mean age at the beginning of the follow-up was 25.7 years. In total, 208 FMF patients were diagnosed with stroke compared with 148 controls, resulting in an incidence rate (per 10 000 persons-years) of 19.8 (95% CI 17.2, 22.7) and 13.9 (95% CI 11.8, 16.4), respectively, and a crude HR of 1.42 (95% CI 1.15–1.76; P  < 0.001). In a multivariate analysis, FMF patients who developed amyloidosis with related or non-related renal failure demonstrated significant stroke risk (HR = 2.16; 95% CI 1.38, 3.38; P  < 0.001), as well as for those who did not develop these complications (HR = 1.32; 95% CI 1.04, 1.67; P  < 0.05). Conclusion FMF patients are at increased risk for stroke regardless of known complications. [ABSTRACT FROM AUTHOR]

Passive transfer of antithyroid antibodies in mice leads to reproductive disorders. The purpose was to assess the placental tissue of experimental animals under the influence of the circulating thyroperoxidase antibodies. We performed an immunohistochemical examination of murine placentae after a passive transfer of thyroperoxidase antibodies. Placentae of mice that passively transferred IgG from healthy donors were used as control samples. For histological examination, 30 placental samples were selected from mice from the anti-TPO group and 40 placental samples were taken from mice from the IgG group. Immunostaining for VEGFR1, THBS 1, Laminin, CD31, CD34, FGF-β, CD56, CD14, TNF-α, kisspeptin, MCL 1, and Annexin V was performed. There is a significant decrease in the relative area of the expression of VEGFR1 (23.42 ± 0.85 vs. 33.44 ± 0.35, P < 0.01), thrombospondin 1 (31.29 ± 0.83 vs. 34.51 ± 0.75, P < 0.01), CD14 (25.80 ± 0.57 vs. 32.07 ± 0.36, P <.01), CD56 (30.08 ± 0.90 vs. 34.92 ± 0.15, P < 0.01), kisspeptin (25.94 ± 0.47 vs. 31.27 ± 0.57, P < 0.01), MCL 1 (29.24 ± 1.06 vs. 38.57 ± 0.79, P < 0.01) in the labyrinth zone of the placentae of mice from the anti-TPO group compared with control group. A significant increase in the relative expression of laminin and FGF-β was noted in the group of mice to which antibodies to thyroperoxidase were transferred, compared with the control group (36.73 ± 1.38 vs. 29.83 ± 0.94, P < 0.01 and 23.26 ± 0.61 vs. 16.38 ± 1.01, P < 0.01respectively). Our study exposed an imbalance of pro- and anti-angiogenic factors, decreased representation of placental macrophages and NK cells, abnormal trophoblast invasion processes, and insufficient expression of antiapoptotic factors in the placentae of mice in which anti-TPO antibodies were passively transferred. We performed an immunohistochemical examination of murine placentae after a passive transfer of thyroperoxidase antibodies. Our study exposed an imbalance of pro- and anti-angiogenic factors, decreased representation of placental macrophages and NK cells, abnormal trophoblast invasion processes, and insufficient expression of antiapoptotic factors in the placentae of mice in which anti-TPO antibodies were passively transferred. [ABSTRACT FROM AUTHOR]

Aims Anti-Ro/La autoantibodies are especially prevalent in autoimmune diseases but are also relatively frequent in healthy adults. Their arrhythmogenic effect on the immature cardiac conductive system is well established, with substantial evidence demonstrating an increased risk for congenital atrioventricular block in neonates of seropositive mothers. Despite their wide distribution and their arrhythmogenic potential effect, there are no large population studies conducted in seropositive adults. Thus, this is the first large population-based study to examine the association of anti-Ro/La seropositivity with cardiac rhythm and conduction disturbances. Methods and results This cross-sectional designed study involved the electronic health records of the largest health maintenance organization in Israel. All subjects that were tested positive for anti-Ro/anti-La antibodies between the years 2002 and 2019 were included and were matched by age, gender, and place of residence, with controls. Rates of different cardiac rhythm and conduction disturbances were compared between groups. Sensitivity analyses were performed using propensity score matching. The study population included 17 231 anti-Ro/La seropositive subjects and 84 368 controls. Anti-Ro seropositive patients had higher rates of conduction disturbances (3.0 vs. 1.7%, P < 0.001) and rhythm disturbances (10.5 vs. 7.0%, P < 0.001). Patients who tested positive for anti-La alone did not demonstrate a significant association with arrhythmias. Multivariate logistic regression analysis, controlling for possible confounders, showed an increased risk for cardiac conduction disturbances [odds ratio (OR) 1.44, 95% confidence interval (CI) 1.25–1.66, P < 0.001], as well as for cardiac rhythm disturbances (OR 1.21, 95% CI 1.11–1.31, P < 0.001) among anti-Ro seropositive patients. However, the association with rhythm disturbances was more robust in certain subgroup analyses. Conclusions Anti-Ro seropositivity is positively associated with adult cardiac conduction disturbances and, to a lesser extent, cardiac rhythm disturbances, regardless of the presence of concurrent autoimmune disease. [ABSTRACT FROM AUTHOR]

Objectives The risk of amyloidosis during the course of AS is yet to be firmly established. We aimed to evaluate the risks, predictors and prognostic outcomes of amyloidosis among patients with AS. Methods A population-based cohort study was conducted comparing AS patients (n  = 5911) with age-, sex- and ethnicity-matched control subjects (n  = 29 007) with regard to incident cases of amyloidosis. Hazard ratios (HRs) and odds ratios (ORs) were estimated by Cox regression and logistic regression analyses, respectively. Results The incidence rate of amyloidosis was 2.15 (95% CI 1.09, 2.82) and 0.35 (95% CI 0.16, 0.66) per 10 000 person-years among patients with AS and controls, respectively. The risk of incident amyloidosis was >6-fold higher among patients with AS relative to control subjects [adjusted HR 6.16 (95% CI 2.43, 15.62); P  < 0.001]. A higher comorbidity burden [OR 1.36 (95% CI 1.08, 1.73); P  = 0.010] was found to predict an increased susceptibility to amyloidosis in AS patients. Compared with other patients with AS, those with AS and comorbid amyloidosis had a 14-fold increased risk of end-stage renal disease necessitating dialysis [adjusted HR 14.7 (95% CI 2.0, 107.2); P  = 0.008], but comparable risk of all-cause mortality [adjusted HR 2.16 (95% CI 0.69, 6.71); P  = 0.174]. Conclusions Patients with AS are at an increased risk of amyloidosis. AS-associated amyloidosis is associated with an elevated risk of dialysis dependence. Awareness of the burden and consequences of this complication may be of help for rheumatologists managing patients with AS. [ABSTRACT FROM AUTHOR]

Objective To assess the association between FMF and asthma. Methods This study was designed as a cross-sectional study. All patients diagnosed with FMF between 1 January 2000 and 31 December 2016 who were prescribed colchicine were included in the study. Controls were matched by sex, date of birth, residential socioeconomic status and country of birth. Logistic regression models were used to determine the odds ratio for asthma in FMF patients and controls. Results A total of 7098 FMF patients who were prescribed colchicine were identified. Of them, 3547 (50%) were females, 3632 (51%) were of low residential socioeconomic status and 6160 (87%) were born in Israel. Their median age at the end of follow-up was 37 years (23–54). In an unadjusted logistic regression, FMF was associated with asthma [odds ratio (OR)=1.33, 95% CI: 1.17, 1.51; P  <0.001]. The association persisted after adjusting for sex, socioeconomic status and country of birth (OR=1.33, 95% CI: 1.18, 1.52; P  <0.001) Conclusion FMF is positively associated with asthma. Further research is required to validate our results and explore possible explanations of this association. These findings cast doubt on previous studies implying FMF to be a protective factor from asthma. [ABSTRACT FROM AUTHOR]

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 Cox's 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 Sjögren's 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. [ABSTRACT FROM AUTHOR]

Objective. To create a tool to predict probability of remission and low disease activity (LDA) in patients with RA being considered for anti-TNF treatment in clinical practice. Methods. We analysed data from GO-MORE, an open-label, multinational, prospective study in biologic naïve patients with active RA (DAS28-ESR ≥3.2) despite DMARD therapy. Patients received 50 mg s.c. golimumab (GLM) once monthly for 6 months. In secondary analyses, regression models were used to determine the best set of baseline factors to predict remission (DAS28-ESR<2.6) at month 6 and LDA (DAS28-ESR ≤3.2) at month 1. Results. In 3280 efficacy-evaluable patients, of 12 factors included in initial regression models predicting remission or LDA, six were retained in final multivariable models. Greater likelihood of LDA and remission was associated with being male; younger age; lower HAQ, ESR (or CRP) and tender joint count (or swollen joint count) scores; and absence of comorbidities. In models predicting 1-, 3- and 6-month LDA or remission, area under the receiver operating curve was 0.648-0.809 (R²=0.0397-0.1078). The models also predicted 6-month HAQ and EuroQoL-5-dimension scores. A series of matrices were developed to easily show predicted rates of remission and LDA. Conclusion. A matrix tool was developed to show predicted GLM treatment outcomes in patients with RA, based on a combination of six baseline characteristics. The tool could help provide practical guidance in selection of candidates for anti-TNF therapy. [ABSTRACT FROM AUTHOR]

Objective. MTX hepatotoxicity is considered to occur more frequently in patients with psoriasis than in patients with RA. However, toxicity guidelines are based on reports from studies with small sample sizes and limited follow-up periods. The current study's objective was to examine the long-term risk of MTX hepatotoxicity based on a database review of patients with RA or psoriasis, and to examine whether the two populations differed.Methods. We conducted a retrospective cohort review among members of a large health maintenance organization (HMO) in Israel who were diagnosed with either RA (n = 119) or psoriasis (n = 690) and who had purchased at least one dose of MTX. Liver function analyses were performed serially in these patients during the follow-up. All abnormal assays were recorded in the computerized database of the HMO.Results. Both groups had hepatic enzyme elevation; the pre-disposing factors predictive of liver damage were female gender and a higher cumulative dose of MTX (hazard ratios, 1.46 and 1.07, respectively, P < 0.001). Age, concurrent diseases and type of disease had no influence on susceptibility to liver damage. No statistically significant difference was detected in any abnormal liver function test among patients with either RA or psoriasis.Conclusion. Our study did not corroborate previous findings of significant differences between psoriasis patients and RA patients concerning susceptibility to hepatotoxicity from MTX therapy. The only significant factor predicting a higher risk of hepatic damage was female gender. [ABSTRACT FROM PUBLISHER]

A response from the author of the article "Hepatotoxicity rates do not differ in patients with rheumatoid arthritis and psoriasis treated with methotrexate" in the 2009 issue is presented.