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The association between uveitis and spondyloarthropathy (SpA)‐related conditions is well‐established. However, evidence describing the link between uveitis and psoriasis, and psoriasis without concomitant SpA‐related conditions is scarce and conflicting. This large‐scale population‐based study sought to describe the prevalence and features of uveitis among psoriasis patients in Israel as well as investigating the risk for uveitis in different subgroups of psoriasis patients compared to the general population. We conducted a retrospective study utilizing the electronic database of the Meuhedet Health Maintenance Organization. The study included all patients diagnosed with psoriasis between 2000 and 2020, each patient was matched with four controls based on age, sex, place of residence, and index date. Logistic regression models were employed to assess the association between psoriasis and uveitis while adjusting for the presence of SpA‐related conditions. A total of 61 003 psoriasis patients and 244 012 matched controls were included. The prevalence of uveitis was 1.3% versus 1.1% respectively (OR 1.12; 95% CI 1.10–1.30; p < 0.001). When adjusting to psoriasis severity, concurrent SpA, and psoriasis treatment no significant association was found. The rates of uveitis among psoriasis patients with concurrent SpA‐related conditions was 3.2% compared to 1.4% in controls without psoriasis or SpA (OR 2.38; 95% CI 2.00–2.83; p < 0.001), while in psoriasis patients without SpA, the rate of uveitis was 1.0% and was similar to controls. Although crude rates of uveitis were higher in patients with severe psoriasis compared to mild psoriasis (2.1% vs. 1.1%), after adjustment, no significant association compared to controls was found in either group. Our findings suggest that the positive association between psoriasis and uveitis is primarily mediated by the coexistence of other SpA‐related conditions. These findings imply the presence of a shared pathogenetic mechanism and set the direction for a phenotypic‐targeted screening strategy. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy and safety of ABBV‐3373, a novel antibody–drug conjugate (ADC) composed of the anti–tumor necrosis factor (anti‐TNF) monoclonal antibody adalimumab linked to a glucocorticoid receptor modulator (GRM), compared to adalimumab, in patients with rheumatoid arthritis (RA). Methods: In this randomized, double‐blind, active‐controlled, proof‐of‐concept trial (ClinicalTrials.gov identifier: NCT03823391), adults with moderate‐to‐severe RA receiving background methotrexate were administered intravenously (IV) ABBV‐3373 100 mg every other week for 12 weeks, followed by placebo for 12 weeks, or subcutaneous adalimumab 80 mg every other week for 24 weeks. The primary end point was change from baseline in the Disease Activity Score in 28 joints using C‐reactive protein (DAS28‐CRP) at week 12, with 2 prespecified primary comparisons of ABBV‐3373 versus historical adalimumab (80 mg every other week or equivalent dose) and versus combined in‐trial/historical adalimumab. Secondary end points included change from baseline in the Clinical Disease Activity Index, Simplified Disease Activity Index, and DAS28 using erythrocyte sedimentation rate, as well as the proportion of patients achieving a DAS28‐CRP of ≤3.2 and the American College of Rheumatology 50% improvement criteria. Results: Forty‐eight patients were randomized to receive either ABBV‐3373 (n = 31) or adalimumab (n = 17). At week 12, ABBV‐3373 demonstrated a reduction in DAS28‐CRP compared to historical adalimumab (−2.65 versus −2.13; P = 0.022) and compared to combined in‐trial/historical adalimumab (−2.65 versus −2.29; probability 89.9%), with numerically greater improvement than in‐trial adalimumab (−2.51). For secondary end points, greater efficacy was observed with ABBV‐3373 compared to historical adalimumab; ABBV‐3373 was predicted with 79.3–99.5% probability to be more effective than adalimumab based on combined in‐trial/historical adalimumab data. Of the ABBV‐3373–treated patients who achieved DAS28‐CRP ≤3.2 at week 12, 70.6% maintained this response at week 24 despite switching to placebo. Four serious adverse events (SAEs) were reported with ABBV‐3373 (noncardiac chest pain, pneumonia, upper respiratory tract infection, and anaphylactic shock) and 2 SAEs with adalimumab (breast abscess and bronchitis). After increasing the duration of IV ABBV‐3373 administration from 3 minutes to 15–30 minutes, no similar events of anaphylactic shock were reported. Conclusion: Data from this proof‐of‐concept trial support the continued development of a TNF–GRM ADC for the treatment of RA, with the potential to achieve superior outcomes compared to currently available therapies. [ABSTRACT FROM AUTHOR]

Objective: In this large population-based study we aimed: 1) to assess mortality in patients with ankylosing spondylitis (AS) compared to the general population, considering demographics, comorbidities, and treatment, and 2) to assess factors associated with mortality within patients with AS.Methods: This study was designed as a retrospective cohort study using the electronic database of the largest health maintenance organization in Israel. All patients with AS diagnosed between 2002 and 2018 were included. Controls were matched by age, sex, clinic, and enrollment time. Follow-up continued until death or the end of the study.Results: The study comprised 5,930 AS patients and 29,018 matched controls who were followed up for a median period of 7.5 years. There were 667 deaths within the AS cohort and 2,919 deaths within controls; the mean age at death was 76.9 years and 77.1 years, respectively (P = 0.74). A total of 3,249 AS patients (54.8%) were treated only with nonsteroidal antiinflammatory drugs, 1,760 (29.7%) were treated with tumor necrosis factor inhibitors (TNFi), and 1,687 (28.4%) with disease-modifying antirheumatic drugs (DMARDs). Mortality rates were increased among AS patients compared to controls, with an age- and sex-adjusted hazard ratio (HR) of 1.19 (95% confidence interval [95% CI] 1.10-1.30). The association was significant for men (HR 1.15 [95% CI 1.04-1.27]) and women (HR 1.32 [95% CI 1.13-1.54]), and after adjusting for background comorbidities (HR 1.14 [95% CI 1.05-1.24]). AS patients treated with TNFi or with a combination of TNFi and DMARDs did not have significant difference in mortality rates compared to controls (HR 0.67 [95% CI 0.38-1.18] and HR 0.93 [95% CI 0.69-1.25], respectively). Age, male sex, mean C-reactive protein (CRP) levels and general comorbidities were predictors of mortality within the AS cohort.Conclusion: AS patients had an increased mortality risk compared to the general population after adjusting for age, sex, and baseline comorbidities. AS patients treated with TNFi did not demonstrate excess mortality compared to matched controls. Within the AS cohort, age, male sex, background comorbidities, and higher CRP levels were identified as risk factors for mortality. [ABSTRACT FROM AUTHOR]

Background: Dermatomyositis (DM) and polymyositis (PM) are two rare autoimmune disorders occasionally described with dysthyroidism; however, no solid evidence still proves such an association. Aim: To evaluate the prevalence of dysthyroidism among DM/PM patients. Design and setting: A nation-wide case-control study was conducted. Methods: From the Clalit Health Services health records database, we extracted 2085 (DM = 1475 (70.7%), PM = 610 (29.3%)) PM/DM cases and 10 193 sex-age matched controls in the period 2000-2018. Both univariate and multivariate analyses were performed to evaluate the link dysthyroidism and PM/DM. Survival analysis was also performed. Results: The rate of hyperthyroidism was significantly (P = .0097) higher in cases (n = 40, 1.9%) with respect to controls (n = 123, 1.2%). Similarly, the rate of hypothyroidism was significantly (P < .0001) associated with cases (n = 234, 11.2%) when compared to controls (n = 853, 8.4%). At the multivariate logistic regression analysis, both DM (OR 1.31 [95%CI 1.07-1.60], P = .0087) and PM (OR 1.54 [95%CI 1.21-1.95], P = .004) were significantly associated with hypothyroidism, whereas DM (OR 1.70 [95%CI 1.10-2.61], P = .0165) but not PM (OR 1.45 [0.83- 2.55], P = .1947) was found to be associated with hyperthyroidism. Subjects with PM and positive for anti-Sjögren's syndrome-related antigen A (SSA) auto-antibody displayed a significant risk of developing hyperthyroidism (OR 5.85 [95%CI 1.02- 33.74], P = .0480), whereas individuals with DM and positive for antinuclear antibody (ANA) had a higher risk of developing hyperthyroidism (OR 2.65 [95%CI 1.00-7.03], P = .0498). Conclusions: Physicians treating PM/DM patients should consider screening for thyroid dysfunction on a regular basis. [ABSTRACT FROM AUTHOR]

Background: Although studied in a few randomized controlled trials, the efficacy of medical cannabis (MC) for chronic pain remains controversial. Using an alternative approach, this multicentre, questionnaire‐based prospective cohort was aimed to assess the long‐term effects of MC on chronic pain of various aetiologies and to identify predictors for MC treatment success. Methods: Patients with chronic pain, licensed to use MC in Israel, reported weekly average pain intensity (primary outcome) and related symptoms before and at 1, 3, 6, 9 and 12 months following MC treatment initiation. A general linear model was used to assess outcomes and identify predictors for treatment success (≥30% reduction in pain intensity). Results: A total of 1,045 patients completed the baseline questionnaires and initiated MC treatment, and 551 completed the 12‐month follow‐up. At 1 year, average pain intensity declined from baseline by 20% [−1.97 points (95%CI = −2.13 to −1.81; p < 0.001)]. All other parameters improved by 10%–30% (p < 0.001). A significant decrease of 42% [reduction of 27 mg; (95%CI = −34.89 to 18.56, p < 0.001)] from baseline in morphine equivalent daily dosage of opioids was also observed. Reported adverse effects were common but mostly non‐serious. Presence of normal to long sleep duration, lower body mass index and lower depression score predicted relatively higher treatment success, whereas presence of neuropathic pain predicted the opposite. Conclusions: This prospective study provides further evidence for the effects of MC on chronic pain and related symptoms, demonstrating an overall mild‐to‐modest long‐term improvement of the tested measures and identifying possible predictors for treatment success. [ABSTRACT FROM AUTHOR]

Problem: Antibody‐mediated autoimmune diseases, such as autoimmune thyroid diseases (ATD), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS), often are associated with recurrent fetal loss. One of the ATD is Hashimoto's thyroiditis which recently showed association with complications of pregnancy with increased levels of circulating autoantibodies reactive with epitopes on thyroid tissue such as thyroid peroxidase (anti‐TPO). In retrospective study of sera analyses in patients with Hashimoto's thyroiditis, all patients had mainly elevated circulating anti‐TPO autoantibodies. Aim: We assessed the potential of human anti‐TPO highly positive IgG, derived from patients with Hashimoto's thyroiditis sera associated with complications of pregnancy, to cause directly complications of pregnancy in murine model. Method of study: Naïve ICR female mice, infused intravenously with 100 μg of anti‐TPO‐positive IgG, showed increased fetal loss and embryo small for date (P <.001) in comparison with mice passively transferred with commercial IgG or PBS. Moreover, we observed embryos small for date in the mice passively transferred with anti‐TPO‐positive IgG, exemplified by reduced weight of embryos and placentae (P =.001). Histopathological examination revealed delay in fetal development in 50% cases of anti‐TPO‐positive IgG‐treated mice. Importantly, pathological changes in the transition zone, state of glycogen cells, and significant structural changes in the labyrinth part of placenta were observed in all anti‐TPO‐positive IgG samples. Conclusion: The current study shows in the first time, a direct proof of concept, on the association of human TPO‐positive IgG from Hashimoto's thyroiditis patients on fetal loss induction in murine model. [ABSTRACT FROM AUTHOR]

Background: Mood disorders, such as anxiety and depression, are extremely prevalent among patients with rheumatoid arthritis (RA). In this study, we assessed the impact of treatment with tocilizumab (TCZ), an IL‐6 antagonist, upon anxiety and depressive symptoms in a cohort of RA patients. Materials and Methods: Study participants were adults diagnosed with RA who received a weekly subcutaneous injection of tocilizumab for 24 weeks. We used the Hamilton Depression (HDRS) and Anxiety (HAMA) scores in order to assess the severity of depression and anxiety, respectively. RA disease activity indices and depression and anxiety levels were assessed at baseline, 4 weeks and study completion. Results: Ultimately, 91 patients were included in the study. The mean age was 54 years, and the majority were female (79%). The mean score in all disease activity indices as well as depression and anxiety levels decreased dramatically from baseline to study completion. Sixty patients (66%) demonstrated a significant decrease in anxiety and/or depression levels. When logistic regression was performed, an HDRS score indicative of depression at study baseline demonstrated an independent association with a significant psychiatric response whilst older age and increased baseline weight were negatively associated. HAMA and HDRA scores correlated with the following RA disease activity parameters, respectively; HAQ‐DI (r =.4,.42), DAS28 (r =.29,.32) and CDAI (0.28 and 0.33), all of them were statistically significant (P <.01). Conclusions: This study has demonstrated a favourable impact of TCZ therapy on parameters reflecting depression and anxiety severity in patients with RA. [ABSTRACT FROM AUTHOR]

As one facet of our study, we also evaluated the association between treatment exposure and death for nonsteroidal antiinflammatory drugs, so called conventional disease-modifying antirheumatic drugs, and TNFi. Their major concern was regarding the findings that demonstrated no excess mortality in AS patients treated with TNFi. These data are provided in Table 1, which demonstrates that overall and particularly in men, AS patients treated with TNFi, after adjusting for age, sex, and comorbidities, have decreased mortality compared to those treated otherwise. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Aims: Published data on long‐term adherence and persistence with adalimumab (Humira®) in clinical practice are scarce and often limited to selected patient populations. This study assessed adherence with adalimumab across different indications and identified correlates and outcomes of poor adherence. Methods: We analysed data originating from the electronic database of Maccabi Healthcare Services (MHS) that includes 2.1 million enrolees. We randomly selected patients with at least one dispense of adalimumab since it was included in the local health basket in Israel in 2008 until the end of 2013. Patients with the following indications (n = 1339) were included: Crohn's disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), psoriatic arthritis (PSA), ankylosing spondylitis (AS) and psoriasis. Adherence with therapy was assessed by the medication possession ratio (MPR) during the follow‐up period. Results: Good adherence (MPR ≥ 80%) was observed among 80% of study patients and was associated with lower risk for ≥1 hospitalization per year of follow‐up (adjusted‐OR = 1.94, 95% CI:1.15–3.28). Patients with AS and CD persisted on adalimumab therapy the most, reaching median use of 27.0 and 26.7 months, respectively. Half (52.4%) of the patients discontinued treatment during a mean (SD) follow‐up of 3.07 (1.71) years. High socioeconomic status was associated with lower risk for discontinuation (adjusted‐HR = 0.74; 0.60–0.91). UC and concomitant prednisolone use were associated with increased risk for treatment discontinuation (HR = 1.31; 1.00–1.72, and HR = 1.40; 1.17–1.68, respectively). Conclusion: Our results indicate encouraging persistence and adherence with adalimumab of patients with inflammatory conditions. [ABSTRACT FROM AUTHOR]

Objective: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting a wide range of systems including the peripheral and central nervous system. Cognitive impairment leading to dementia is one of the harmful central nervous system afflictions of SLE. The aim of this study was to investigate the association of SLE with dementia.Methods: A cross-sectional study was conducted using Clalit Health Care database, the largest health maintenance organization in Israel with more than 4.4 million enrollees. Systemic lupus erythematosus patients were compared in a 1:5 ratio to age- and sex-matched controls. Chi-square and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis.Results: The study included 4886 SLE patients and 24 430 age-frequency- and sex-frequency-matched controls without SLE. The proportion of dementia was higher among SLE patients compared to controls (1.56% and 0.51%, respectively; P < .001). This finding was consistent across all age groups by univariate analysis. In a multivariate logistic regression analysis, SLE was significantly associated with dementia (odds ratio = 1.51, 95% confidence interval, 1.11-2.04).Conclusion: Systemic lupus erythematosus is significantly associated with dementia. This finding should give rise to search for SLE in patients with an ambiguous cause for dementia, especially those with an early onset cognitive decline. [ABSTRACT FROM AUTHOR]

Problem The purpose of this study was to explore whether vitamin D might be a marker of female primary infertility in association with the presence of autoimmune diseases ( ADs). Methods The study was a cross-sectional descriptive study in consecutive outpatients of the Polymedical Center for Prevention of Recurrent Spontaneous Abortion ( RSA), in Rome, Italy. Women were eligible if they received a diagnosis of primary infertility or RSA. Serum vitamin D, calcium, and PTH were analyzed. Results Women with primary infertility (n=70) or RSA/non-infertile (n=105) were enrolled; controls (n=250) were included. Infertile women presented lower vitamin D ( P=0.03) and higher prevalence of AD ( P=0.007) than non-infertile women. In the multivariate analysis, the presence of ADs is associated with higher odds of infertility (OR=2.2), while normal vitamin D was a protective factor (OR=0.9). Conclusion We described that having vitamin D deficiency and suffering from an AD are independent risk factors for women primary infertility. Supplementation of vitamin D might be useful for pregnancy outcome. [ABSTRACT FROM AUTHOR]

Background Both smoking and obesity have been demonstrated as risk factors in several autoimmune diseases. Little is known about the relationship between systemic lupus erythematosus ( SLE) and both smoking and obesity. Objectives To investigate the association between SLE, tobacco consumption and body mass index ( BMI). Materials and methods Using data from the largest Health Maintenance Organization ( HMO) in Israel, the Clalit Health Services, we searched for an association between SLE, smoking and obesity. Chi-square and t-test were used for univariate analysis, and a logistic regression model was used for multivariate analysis. Data available from Clalit Health Services database included age, sex, BMI, smoking status, socioeconomic status ( SES) and diagnoses of chronic diseases. Results The study included 5018 patients with SLE and 25 090 age- and sex-matched controls. In multivariate analysis, we found a significant association between smoking and SLE ( OR = 1·91). Conversely, there was no association between BMI and SLE. Conclusion In this study, we have shown that smoking is independently associated with SLE, whereas BMI scores were not. [ABSTRACT FROM AUTHOR]

Background Association between antiphospholipid syndrome in systemic lupus erythematosus ( SLE) and valvular heart disease ( VHD) is well reported, but relatively few studies have been carried out to establish the linkage between VHD and SLE itself. We aimed to investigate link between VHD and SLE and to evaluate the association of diverse factors with VHD among these patients in a large-scale population-based study. Materials and methods We used the databases of the largest state-mandated health service organization in Israel. All SLE patients were included ( n = 5018) as well as their age and sex-matched controls ( n = 25 090), creating a cross-sectional population-based study. Medical records of all subjects were analysed for documented VHD and the presence of antiphospholipid antibodies ( aPLs). A logistic regression model was carried out to evaluate the diverse factors including SLE and aPLs as independent risk factors for VHD. Results Valvular heart disease were found to be more frequent among SLE group when compared to controls (aortic stenosis, 1·08% vs. 0·35% respectively, P < 0·001; aortic insufficiency, 1·32% vs. 0·29% respectively, P < 0·001; mitral stenosis, 0·74% vs. 0·21% respectively, P < 0·001; mitral insufficiency, 1·91% vs. 0·39% respectively, P < 0·001). Male sex, hypertension, aPLs and SLE were found to be significant independent risk factors for VHD. Conclusion All VHD are more prevalent among SLE patients when compared to controls. SLE and aPLs are independent risk factor for VHD ( OR of 2·46 and 1·7, respectively). Physicians must be aware of such significant association, and routine echocardiography should be considered in SLE patients regardless of their aPL status. [ABSTRACT FROM AUTHOR]

Infections are believed to often play a role in the immunopathogenesis of autoimmune disorders; such is the case in systemic sclerosis (SSc). In order to evaluate the potential role infections may have on the pathogenesis of SSc, we assessed serological reactivity against various infectious agents in patients with SSc and compared them with healthy controls. Serological samples obtained from 80 patients with SSc were compared with 296 compatible healthy controls. Both groups were of European origin. All samples were tested for the presence of antibodies directed against hepatitis B virus, hepatitis C virus, toxoplasmosis, rubella, CMV, EBV, and Treponema pallidum. We applied Bio-Rad commercial and experimental kits to assess most antigens and ELISA assays to complete the panel. Patients with SSc had elevated IgM and IgG against Toxoplasma gondii and against CMV. Higher titers were also detected against the hepatitis B virus core protein (recombinant HBc antigen) using MONOLISA anti-HBc Plus commercial kit (Bio-Rad). A significantly higher rate of IgM antibodies against the capsid antigen of the EBV was detected in SSc patients compared with healthy controls, as well. These data demonstrate that antibodies against CMV, HBV, and toxoplasmosis were detected more often in patients with SSc. This association implies that infectious agents may have a role in disease pathogenesis and expression. [ABSTRACT FROM AUTHOR]

Infectious agents have been implicated in the pathogenesis of many autoimmune diseases via various pathogenic mechanisms, such as molecular mimicry, resulting in modulation of the host's immune tolerance. In the following article we examine the association between serological evidence of past infection with Toxoplasma gondii, rubella virus, cytomegalovirus, Treponema pallidum, and Epstein–Barr virus, and the co-existence of celiac disease. Our results imply that certain infections may generate an immunological environment that disfavors future appearance of certain autoimmune conditions such as celiac disease. [ABSTRACT FROM AUTHOR]

Pneumatosis intestinalis (PI) is an uncommon condition characterized by the presence of gas within the wall of the gastrointestinal tract. PI is a physical or imaging finding that is the result of an underlying pathological process or a disease. This finding may present in diverse conditions, such as obstructive pulmonary disease and intestinal disease, including obstruction, inflammation, or ischemia. PI has also been reported in different autoimmune conditions, especially in systemic sclerosis and rarely with systemic lupus erythematosus. In this report we present PI occurring in three patients with different autoimmune conditions and review the literature. [ABSTRACT FROM AUTHOR]

Fibromyalgia is an ill-defined condition that causes pain and disability but still lacks effective treatment. The aim of this open-label study was to assess the efficacy of administering a food supplement, creatine monohydrate, in an “add on” to existing therapies in patients with fibromyalgia. This study included 30 patients with fibromyalgia. After 8 weeks of receiving creatine, we witnessed a significant improvement in parameters reflecting severity of fibromyalgia, quality of life and sleep, disability, and pain. These results deteriorated 4 weeks after stopping creatine therapy. The findings of this study are preliminary and limited due to the small sample and relatively high rate of dropouts. [ABSTRACT FROM AUTHOR]

Background: Vasovagal syncope is one of the most common medical conditions in young adults. Previous trials have shown effectiveness of tilt training in treating this condition. We conducted a prospective, randomized study in order to evaluate the role of tilt-training in young adults with vasovagal syncope. Methods: Forty-six soldiers (mean age 19.4 ± 0.8 years, 25 males), with a clinical diagnosis of vasovagal syncope supported by positive tilt test, were randomized to either three months of daily tilt training (treatment group), or no training (control group). Patients in both groups were instructed to increase fluid and salt intake, and to refrain from syncope-inducing situations, such as prolonged standing. Results: Compliance, defined as performing 50% or more of the tilt training daily sessions, was 91% during the first month, and declined to 58% during three months. Treatment group patients had a median (interquartile range) of 5.0 (0.5–16.0) syncope episodes during one-year follow up, compared to a median of 2.0 (0–6.0) episodes in the control group (P = 0.737). Also, there was no difference in time to first syncope after randomization between groups: a median of 1.0 (0.5–2.0) month in the treatment group, compared to 0.8 (0.5–2.0) month in the control group (P = 0.336). Conclusions: Adding daily three-month tilt training to modifications in lifestyle does not improve treatment results in young adults with vasovagal syncope. Good compliance is difficult to achieve in a tilt training program. [ABSTRACT FROM AUTHOR]

Probiotic fermented milk products have the capacity to modulate many immunological mechanisms. Several attempts have been made to alter the progression of various atopic and inflammatory disorders in which the immune system plays a major role. We studied this issue in an animal model of the antiphospholipid syndrome (APS) by supplementing the animals' daily intake with a probiotic mixture. We studied the effects of nutritional supplementation of a commercial product that consists of 108/ml Lactobacillus casei (Actimel) on Balb/c mice that were immunized with beta-2- glycoprotein (β2GPI) in order to induce a familiar murine model of APS. As controls, we used similar animals that were fed with either yogurt or sham solution as a supplement. We analyzed the effect of Actimel on the concentrations of interleukin (IL)-10 interferon gamma (IFNγ) as well as the extent of the primary T cell response to β2GPI, and the levels of autoantibodies to β2GPI determined by ELISA. Two weeks after priming (in the hind footpad) of Balb/c mice with β2GPI, we analyzed the cytokine profile of the animals by measuring the concentration of IL-10 and IFNγ in the supernatants of lymphocytes that were extracted from the popliteal lymph nodes. Following stimulation with 10 μg/mL of β2GPI, we noticed significant ( P < 0.05) suppression of IL-10 production by the stimulated lymphocytes in the animals fed with Actimel and yogurt in comparison to sham solution (73.42 ± 29.4, 84.7 ± 8, 196 ± 41.62 pg/mL, respectively). Both dairy products enhanced the secretion of IFNγ from 657 ± 47.09 pg/mL to 896 ± 78.1, and 933 ± 76.7 ( P < 0.01), respectively; similarly they also accelerated by a mild degree the level of the T cell primary response to β2GPI measured by [3H]thymidine incorporation. The level of autoantibodies to β2GPI was suppressed in mice fed with actimel and yogurt in a significant manner ( P < 0.05). Actimel as well as yogurt confer an immunological impact on Balb/c mice immunized with β2GPI. Actimel was able not only to enhance IFNγ secretion but also to inhibit IL-10 production. [ABSTRACT FROM AUTHOR]

This article analyzes the serum cytokine profile of a nonrandomized group of patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) who are destined to be treated with infliximab following failure after failure of different disease-modifiying antirheumatic drugs (DMARDs). Serial serum samples were collected from 11 patients with refractory RA, three with PsA and one with undifferentiated spondyloarthropathy. All were treated with the antitumor necrosis factor (TNF)α agent, infliximab, after failing to sustain a clinical remission with conventional DMARDs. Blood samples were obtained at different phases of their therapy. Serum levels of tumor necrosis factor (TNF)α, interferon (IFN)γ, interleukin (IL)-1β, IL-6, sIL-2R, IL-10, and IL-1 receptor antagonist (IL-1RA) were determined by commercial ELISA kits. Interestingly, only eight of the 11 patients with RA had elevated TNFα serum levels (at least once in their serial measurements). Only one was unresponsive to therapy and despite anti-TNFα therapy her serum TNFα levels remained extremely high. Two RA patients who responded to infliximab had normal TNFα serum levels prior to and following infliximab administration. One RA patient improved after infliximab therapy despite unrelenting high serum levels of TNFα, IL-6, and sIL-2R. Patients with active PsA who responded to infliximab therapy had sustained high serum TNFα levels. In an unselected population of RA and PsA patients, we noticed diverse patterns of serum cytokine profiles. These results imply that the cytokine profiles of RA and PsA are diverse and their pathogenesis is heterogeneous. [ABSTRACT FROM AUTHOR]

The development of autoimmune diseases may be influenced by hormonal, immunomodulatory, and metabolic pathways. Prolactin (PRL), ferritin, vitamin D, and the tumor marker tissue polypeptide antigen (TPA) were measured in autoimmune diseases: systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), polymyositis (PM), dermatomyositis (DM), multiple sclerosis (MS), autoimmune thyroid diseases, and antiphospholipid syndrome. Hyperprolactinemia (HPRL) was detected in 24% of PM patients, in 21% of SLE patients, in 6.7% of MS patients, 6% of RA patients, and in 3% of SSc patients. Hyperferritinemia was detected in 23% of SLE patients, 15% of DM patients, 8% of MS patients, and 4% of RA patients. The patients had relatively low levels of 25 OH Vitamin D: the average results (mean ± SD) were between 9.3 ± 4.4 to 13.7 ± 7.1 ng/mL in the different diseases, while the 25 OH Vitamin D concentrations less than 20 ng/mL are regarded as deficient. TPA levels were in the same range of the controls, elevated only in SLE. HPRL, hyperferritinemia, hypovitaminosis D, and TPA levels did not correlate with SLE activity elevated levels of rheumatoid factor or anti-CCP antibodies in RA. HPRL, hyperferritinemia, and hypovitaminosis D have different immunological implications in the pathogenesis of the autoimmune diseases. Preventive treatment with vitamin D or therapy for HPRL with dopamine agonists, may be considered in certain cases. Hyperferritinemia may be used as an acute-phase reactant marker in autoimmune diseases mainly SLE. TPA may be used to indicate the tendency for malignancies. [ABSTRACT FROM AUTHOR]

The aim of this study was to detect antibodies to vitamin D in systemic lupus erythematosus (SLE) and other autoimmune diseases. The results may shed light to a novel aspect of vitamin D deficiency in autoimmune diseases. Sera from 171 patients with SLE, 56 with antiphospholipid syndrome (APS), and 18 with pemphigus vulgaris (PV) were studied employing an enzyme-linked immunosorbent assay for anti-vitamin D antibodies along with 94 healthy blood donors. In parallel, vitamin D concentrations in the serum were determined by a DiaSorin commercial kit (LIAISON 25 OH vitamin D). Antibody-positive and antibody-negative individuals were compared with respect to demographic variables, SLE disease activity index (SLEDAI) score, autoantibodies profile, and serum vitamin D levels. Anti-vitamin D antibodies were detected in 7 (4%) of 171 patients with SLE, in 2 (3.5%) of 56 of sera from patients with APS, and in 2 (11%) of 18 sera from patients with PV. Vitamin D levels were similar in both SLE groups with and without anti-vitamin D antibodies. Demographic features, organ involvement, SLEDAI score, and autoantibodies did not differ between the groups. Except for anti-dsDNA antibodies, in which anti-vitamin D antibodies were strongly associated with these antibodies in sera from SLE patients ( P= 0.0004). Anti-vitamin D antibodies are observed in a subset of patients with SLE, APS, and PV, and are associated with anti-dsDNA antibodies in SLE. Further studies are required to explore the potential diagnostic and prognostic role of these novel antibodies in SLE. [ABSTRACT FROM AUTHOR]

Background: A high prevalence of thyroid disorders has been reported in patients with autoimmune diseases. The link between hyperthyroidism and systemic sclerosis (SSc) has been relatively overlooked, and only a few studies utilizing small samples or case reports have been reported so far. Objectives: To investigate the association between SSc and hyperthyroidism. Methods: We designed a case‐control study utilizing the medical database of the Clalit Health Services. Chi‐square and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. Results: The study included 2,431 SSc patients and 12,710 age‐ and sex‐matched controls. The mean age of the study population was 63.32 ± 18.06 years (median 66 years), and female‐to‐male ratio was 4.5:1. Age (P < .0001, OR 1.03 [95% CI 1.02‐1.04]), female sex (P = .0015, OR 1.86 [95% CI 1.27‐ 2.74]) and diagnosis of SSc (P = .0011, OR 1.81[95% CI 1.27‐2.58]) were all independently associated with hyperthyroidism. Patients with SSc and hyperthyroidism had 1.54‐fold increase of mortality rates during a mean follow‐up of 17 years than SSc patients without hyperthyroidism, even though at the Cox multivariate survival analysis, only age (HR 1.06 [95% CI 1.06‐1.07], P < .0001) and diagnosis of SSc (HR 2.35 [CI 2.06 to 2.69], P < .0001) resulted associated with a higher risk of mortality. Conclusions: Hyperthyroidism is highly prevalent among SSc patients and can negatively impact on their survival rates. Therefore, a pre‐emptive screening may be warranted in all SSc patients. Further studies are needed to evaluate whether tight control and optimal treatment for hyperthyroidism may lead to a reduction of all‐cause mortality in patients with SSc. [ABSTRACT FROM AUTHOR]

Background Numerous studies have shown that anxiety and depression are more prevalent among patients suffering from chronic skin disorders. Objectives The aims of this study were to assess the prevalences of depression and anxiety in patients suffering from chronic skin disorders, focusing particularly on allergic skin conditions. Additionally, we investigated resilience to disease progression using the Sense of Coherence Scale. Methods A total of 112 consecutive patients without known psychiatric disease were interviewed and asked to complete questionnaires in order to assess psychiatric symptomatology. The following scales were completed: the Mini International Neuropsychiatric Interview; the Hamilton Anxiety Scale (HAS); the Hamilton Depression Rating Scale (HDRS); and the self-administered questionnaire for the Sense of Coherence Scale (SoCS). Results Rates of anxiety and depression in patients with allergic and non-allergic conditions were considerably higher than those in the general population. This difference was notable in patients with allergic skin diseases, reaching 58.3 and 48.3%, compared with 15.4 and 23.1% for participants with non-allergic conditions, as measured by the HAS and HDRS, respectively ( P < 0.05). Statistically significant negative correlations between scores on the SoCS and scores on the HAS ( r = −0.45, P < 0.01) and HDRS ( r = −0.37, P < 0.01) were observed. Conclusions Our findings support the hypothesis that rates of anxiety and depression are higher among patients suffering from allergic chronic skin disorders. High SoCS scores may protect against the development of psychiatric illness in patients suffering from allergic skin disease. [ABSTRACT FROM AUTHOR]