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18F-FDG PET/CT occupies a growing role in the diagnosis of large vessel vasculitis (LVV), illustrating enhanced uptake in the lining of large vessels. A retrospective single center study was conducted of patients who underwent 18F-FDG PET/CT scans between 2009 and 2019 at Sheba Medical Center, Israel. The imaging results were analyzed for evidence of LVV. We reviewed the PET/CT scans of 126 patients and identified 57 studies that either showed evidence of active LVV or that had been performed in patients previously treated for systemic vasculitis. In 6 patients with fevers of unknown origin and elevated inflammatory markers, PET/CT revealed LVV. Six of 13 patients previously treated for systemic vasculitis demonstrated persistent large vessel uptake. LVV was identified in 8 patients with other autoimmune diseases, and in 4 diagnosed with infectious aortitis. In 26 patients who underwent malignancy surveillance, PET/CT revealed more localized large vessel wall inflammation. Our results illustrate that PET/CT may identify large vessel wall inflammation in patients with a suspicion of LVV, and incidentally in patients who undergo malignancy surveillance. PET/CT may also help delineate the presence and extent of vessel inflammation in patients with LVV and in those with other autoimmune diseases. [ABSTRACT FROM AUTHOR]

Chronic pain is a common complaint among patients, and rheumatic diseases are a common cause for chronic pain. Current pharmacological interventions for chronic pain are not always useful or safe enough for long-term use. Cannabis and cannabinoids are currently being studied due to their potential as analgesics. In this review we will discuss current literature regarding cannabinoids and cannabis as treatment for rheumatic diseases. Fibromyalgia is a prevalent rheumatic disease that causes diffuse pain, fatigue, and sleep disturbances. Treatment of this syndrome is symptomatic, and it has been suggested that cannabis and cannabinoids could potentially alleviate some of the symptoms associated with fibromyalgia. In this review we cite some of the evidence that supports this claim. However, data on long-term efficacy and safety of cannabinoid and cannabis use are still lacking. Cannabinoids and cannabis are commonly investigated as analgesic agents, but in recent years more evidence has accumulated on their potential immune-modulatory effect, supported by results in animal models of certain rheumatic diseases. While results that demonstrate the same effect in humans are still lacking, cannabinoids and cannabis remain potential drugs to alleviate the pain associated with rheumatic diseases, as they were shown to be safe and to cause limited adverse effects. [ABSTRACT FROM AUTHOR]

Abstract Autoimmune diseases are a group of heterogeneous condition that occur secondary to the intrinsic loss of tolerance to self- antigens. In genetically susceptible individuals, the complex interplay of environmental factors and epigenetic deregulations have been proposed to drive disease etiopathogenesis. Various environmental variables have been identified including viral infections, exposure to pollutants, stress and dietary factors. Sodium, a major constituent of salt is essential for mammalian physiology. However, high salt intake may play a role in the development of autoimmune diseases. Several lines of evidence point toward the role of high sodium intake in reversing the suppressive effects of Regulatory T cells (Tregs) and instead promoting cellular shift toward T-helper (Th)-1 and Th17 pro-inflammatory phenotypes. These effects have been attributed to cascade of events that ultimately results in downstream activation of serum glucocorticoid kinase 1 (Sgk1). In vivo, various autoimmune animal models have confirmed the role of high sodium diet in the emergence and the exacerbation of autoimmune conditions including for instance Experimental Autoimmune Encephalomyelitis model for multiple sclerosis, MRL/lpr mouse model for lupus nephritis, collagen induced arthritis model for rheumatoid arthritis, and dextran sulfate sodium induced colitis, and TNBS-induced colitis models for Crohn's disease. Clinical epidemiological studies are scarce. High sodium intake was associated with increased risk of rheumatoid arthritis disease emergence. In multiple sclerosis, some studies suggest a relation to clinical exacerbation rates however other studies did not corroborate these results. Taken together, high dietary salt intake plays a role in the spectrum of autoimmune disease etiology. Further research is warranted to better characterize such relationship and assist in identifying individuals that would benefit from dietary salt restriction. [ABSTRACT FROM AUTHOR]

Fibromyalgia is a chronic disease, characterized by pain, fatigue, and poor sleep quality. Patients and mainly those with chronic diseases tend to search for health-related material online. Google Trends (GT), an online tracking system of Internet hit-search volumes that recently merged with its sister project Google Insights for Search (Google Inc.), was used to explore Internet activity related to fibromyalgia. Digital interest in fibromyalgia and related topics searched worldwide has been reported in the last 13 years. A slight decline in this interest has been observed through the years, remaining stable in the last 5 years. Fibromyalgia web behavior exhibited a regular, cyclic pattern, even though no seasonality could be detected. Similar findings have been reported among rheumatoid arthritis and depression. However, differently from rheumatoid arthritis and depression, the focus of the fibromyalgia-related queries was more concentrated on drug side effects and the 'elusive' nature of fibromyalgia: is it a real or imaginary condition? Does it really exist or is it all in your head? A tremendous amount of information on fibromyalgia and related topics exist online. Still many queries have been raised and repeated constantly by fibromyalgia patients in the last 13 years. Therefore, physicians should be aware of the common concerns of people or patients regarding fibromyalgia in order to give a proper answers and education. [ABSTRACT FROM AUTHOR]

Background: Previous studies demonstrated unclear and vast variability in the association between Ankylosing Spondylitis (AS) and the risk of cancer. Objectives: To assess the risk of overall and site-specific malignancies for AS patients in Israel, while examining the role of comorbidities and immunomodulatory therapy. Methods: We conducted a retrospective electronic data-based study including all AS patients diagnosed between 2002 and 2018, with no history of cancer prior to enrollment, with 5:1 ratio matched-control by age, gender, and place of residence. The odds Ratios (OR) for site-specific malignancies, comparing AS patients and controls, were calculated using logistic regression. Risk factors for malignancies within the AS cohort were evaluated in the same manner. Results: This study comprised 5825 AS patients and 28,356 matched controls. There was a higher overall risk of cancer in AS patients compared to controls (OR = 1.4, 95% CI 1.24–1.6), specifically for solid malignancies (OR = 1.5, 95% CI 1.3–1.7), CNS (OR = 3.72, 95% CI 1.29–10.7), kidney (OR = 2.06, 95% CI 1.12–3.8), and malignancy of unknown primary (OR = 3.06, 95% CI 2.35–3.98). Regarding predictors for malignancy within AS patients, older age at diagnosis (OR = 1.31, 95%,CI 1.25–2.36), diabetes (OR = 1.52, 95% CI 1.18–1.97), IBD (OR = 2.61, 95% CI 1.75–3.89), and treatment with DMARDs (OR = 2.17, 95% CI 1.65–2.83) were associated with a higher risk of solid malignancies, while NSAIDs treatment alone had a protective effect for solid malignancies (OR = 0.78, 95% CI 0.61–0.99). No significant association was found between anti-TNF therapy and the risk of solid or hematologic malignancies within the AS group. Conclusion: AS is associated with an increased risk of overall and site-specific malignancies, with independently higher risk for older age, comorbidity of DM, IBD, and treatment with DMARDs. [ABSTRACT FROM AUTHOR]

Anti-citrullinated protein autoantibodies (ACPAs) are the major autoantibodies in rheumatoid arthritis (RA). Anti-citrullinated protein autoantibodies are directed against different citrullinated antigens, including filaggrin, fibrinogen, vimentin, and collagen. Presence of ACPA is associated with joint damage and extra-articular manifestations, suggesting that ACPAs are most likely pathogenic autoantibodies in RA. In vitro, ACPAs induce macrophage tumor necrosis factor alpha (TNF-α) production, osteoclastogenesis, and complement activation. These autoantibodies also induce the formation of neutrophil extracellular traps (NETs). Additionally, ACPAs induce pathogenic cytokines expression and oxidative stress in immune cells derived from RA patients. The aim of this review is to show the pathogenic roles of these autoantibodies in RA. [ABSTRACT FROM AUTHOR]

Objective. To assess the adherence and persistence with allopurinol therapy among gout patients and to identify risk factors for therapy discontinuation.Methods. The study population included adults in Maccabi Healthcare Services, a 2-million member health maintenance organization in Israel, who were diagnosed with gout between 2002 and 2008. Adherence with allopurinol was retrospectively assessed by calculating the proportion of days covered of dispensed prescriptions. Persistence was assessed by calculating the mean proportion of follow-up days covered with allopurinol for every study participant.Results. A total of 7644 patients were identified. Among men, the incidence of gout was strongly associated with age, ranging from 0.5 per 1000 among adults younger than 45 years to more than 36 per 1000 among elderly men aged 85 or older). A total of 1331 gout patients (17% of the study population) were adherent to allopurinol therapy, 36% and 47% had partial and poor adherence, respectively. Persistence analysis indicated that the average duration until therapy was discontinued was similar among men (358 days) and women (379 days). Women aged 45–64 years, non-married individuals, those of low socioeconomic status and those with lower body weight were more likely to discontinue therapy. Logistic regression (n = 2471, 32% of the study sample) showed a 4.5 risk of non-compliance among 45- to 65-year-old women. Better compliance was achieved among those with comorbidities, particularly among patients with concomitant cardiovascular disease.Conclusion. Only one out of six gout patients is adherent with allopurinol. Intervention programmes to increase adherence with treatment should focus on high-risk populations. [ABSTRACT FROM PUBLISHER]

Abstract: Rheumatoid arthritis (RA) therapy has been revolutionized in recent years following the introduction of three main anti-tumor necrosis factor-alpha inhibitors (anti-TNF) agents, infliximab, adalimumab and etanercept. Evidence in the literature indicates that patients treated with anti-TNF agents are at increased risk for bacterial infections, but it is not clear if this is a result of the treatment or of disease severity. The treatment has been recognized as a clear risk factor for reactivation of latent TB infections. So far, observational studies have not indicated any increased overall risk of cancer in RA patients treated with anti-TNF. The overall risk of lymphoma in these patients does not appear to differ greatly from that recorded among untreated patients, but rather is associated with the degree of disease activity rather than the type of therapy. There is a consensus in the literature that the likelihood of drug survival with infliximab is inferior to both adalimumab and etanercept, mostly due to increased risk of infection or allergic reactions. Due to the lack of head to head studies, there is no agreement as to which agent has the highest rates of treatment response and disease remission. [Copyright &y& Elsevier]

Abstract: Low vitamin D serum concentrations have been reported in several autoimmune conditions. The study''s aim was to explore such a relationship in a large multinational population of patients with systemic sclerosis (SSc) and to pursue possible clinical and laboratory correlates with vitamin D concentrations. 327 sera samples of European patients with SSc and 141 samples of compatible healthy controls were studied for vitamin D concentrations using the commercial kit LIAISON 25-OH vitamin D assay (Diasorin). Additionally, clinical parameters including the Rodnan skin score, diffusing lung capacity for carbon monoxide (DLCO), systolic pulmonary artery pressure (sPAP), forced vital capacity (FVC), and nailfold video capillaroscopic, erythrocyte sedimentation rate (ESR), anti-nuclear antibodies (ANA and scl70), rheumatoid factor (RF) were investigated. Vitamin D serum concentration was 13.5±9.0ng/ml (mean±standard deviation) in patients with SSc compared to 21.6±9.7ng/ml in a control group (p<0.001). A negative correlation between patients'' age and vitamin D concentration (r=−0.2, p<0.05, n=96) was observed. An inverse relationship was found between skin involvement and vitamin D serum concentrations; Patients with a Rodnan skin score of 10 or lower (n=11) had a mean vitamin D concentration of 17.7±10.4ng/ml compared to patients with a score above 10 (n=28) 8±10.1ng/ml (p=0.02, by the Mann–Whitney test). In conclusion, Patients with SSc have significantly lower serum vitamin D concentrations compared to healthy controls; moreover fibrosis of the cutaneous tissue is inversely related to the vitamin D concentration. [Copyright &y& Elsevier]

Background: The beneficial effects of statins in rheumatoid arthritis (RA) have been suggested previously, but it is unclear whether statins may prevent its development. The aim of this retrospective cohort study was to explore whether persistent use of statins is associated with onset of RA. Methods and Findings: The computerized medical databases of a large health organization in Israel were used to identify diagnosed RA cases among adults who began statin therapy between 1998 and 2007. Persistence with statins was assessed by calculating the mean proportion of follow-up days covered (PDC) with statins for every study participant. To assess the possible effects of healthy user bias, we also examined the risk of osteoarthritis (OA), a common degenerative joint disease that is unlikely to be affected by use of statins. A total of 211,627 and 193,770 individuals were eligible for the RA and OA cohort analyses, respectively. During the study follow-up period, there were 2,578 incident RA cases (3.07 per 1,000 personyears) and 17,878 incident OA cases (24.34 per 1,000 person-years). The crude incidence density rate of RA among nonpersistent patients (PDC level of ,20%) was 51% higher (3.89 per 1,000 person-years) compared to highly persistent patients who were covered with statins for at least 80% of the follow-up period. After adjustment for potential confounders, highly persistent patients had a hazard ratio of 0.58 (95% confidence interval 0.52-0.65) for RA compared with nonpersistent patients. Larger differences were observed in younger patients and in patients initiating treatment with high efficacy statins. In the OA cohort analysis, high persistence with statins was associated only with a modest decrement in risk ratio (hazard ratio = 0.85; 0.81-0.88) compared to nonadherent patients. Conclusions: The present study demonstrates an association between persistence with statin therapy and reduced risk of developing RA. The relationship between continuation of statin use and OA onset was weak and limited to patients with short-term follow-up. [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]

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]

Melanin has several physiological roles in maintaining health, but, notably, it affects the synthesis of vitamin D. Melanin is the primary determinant of the degree of skin pigmentation and protects the body from harmful ultraviolet radiation. Synthesis of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) in the skin, however, is dependent on ultraviolet B light. Highly pigmented skin, to the level found in people of African origin, abrogates almost all ultraviolet-induced 1,25(OH)2D3 synthesis. Numerous animal models and clinical studies have underlined the essential role of vitamin D as a modulator of the different processes of the immune system. Evidence indicates that serum concentrations of 1,25(OH)2D3 and the prevalence of autoimmune diseases in a certain population are associated with the latitude at which that population resides. This article explores the relationship between skin pigmentation, vitamin D and the prevalence of autoimmune disease. [ABSTRACT FROM AUTHOR]

Abstract: Infectious agents have been implicated in the pathogenesis of many autoimmune diseases. Celiac disease (CD) is an autoimmune disorder affecting patients with a specific genetic predisposition (HLA-DQ2, HLA-DQ8) who are exposed to gluten, the major storage protein of wheat and similar grains. An environmental factor, such as an infectious agent, is thought to precipitate the disease via various pathogenic mechanisms, such as molecular mimicry, resulting in modulation of the host''s immune tolerance. There is evidence that CD is related to perinatal infections, and that maternal-milk may have a protective role. Observations imply that there is a relationship between viral infections such as Adenovirus 12 and Hepatitis C virus and the development of CD. Understanding the relationship between infectious agents and autoimmunity may assist in prediction, early diagnosis and perhaps also the prevention of CD. [Copyright &y& Elsevier]

Abstract: Autoimmune disorders carry significant morbidity and mortality. Reduction–oxygenation reactions and their byproduct reactive oxygen species have been suspected to influence the initiation and outcome of these disorders. It stands to reason that inhibition of these negative influences by the use of antioxidants would help control these entities. We reviewed the published works in relation to several autoimmune disorders and attempted to conclude what benefit can be achieved with the use of antioxidants. There are several reports which strengthen this notion. However, the number of interventional works is still to low for this to be unequivocal. Cigarette smoking, with its multitude of biological effects, is also implicated in the pathogenesis and course of these diseases. We tried to surmise what is the extent of its effect on the clinical and pathological course of these illnesses. Smoking was shown to increase morbidity and levels of markers for disease activity. It was also found to increase the risk of manifesting these diseases. The number of works needs to be expanded, though. [Copyright &y& Elsevier]

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]

Study objective: To explore the causes of sudden and unexpected death in a young and healthy military population, to examine the various patterns of diseases associated with these tragic events, and to investigate the factors found to be associated with this grave outcome. Design: We retrospectively investigated 151 cases of Israeli military personnel who died unexpectedly over a 30-year period. We collected all the available medical records, autopsy results, and investigation committee reports. Results: A total of 151 cases of sudden and unexpected death occurred among enlisted military personnel during the period. Cardiac disorders caused 47% of deaths, followed by neurologic causes (17%) and pulmonary causes (11%). In 30 events (20%), the cause of death remained undetermined. Symptoms (eg, syncope, chest pain, palpitations, and others) occurred prior to death in 52 cases (34%). Asthma was the most common risk factor in our study population having been previously recognized in 10 cases (6.7%). Eight of the 13 subjects with asthma died following an acute asthmatic attack. Conclusion: Cardiac events are the leading cause of unexpected death in young healthy people. The frequency of subjects with asthma was found to be higher than that in the general age-adjusted population. [ABSTRACT FROM AUTHOR]

Background: Axial spondyloarthropathy(AS) is a chronic inflammatory disease primarily affecting the axial skeleton, often characterized by sacroiliitis. While pulmonary embolism (PE), a potentially lethal condition, has been linked to several autoimmune diseases, limited data exist regarding PE risk among patients with AS. Methods: This retrospective cohort study utilized the Clalit Healthcare Services (CHS) database, including 5825 patients with AS and 28,356 matched controls. Follow-up began at the date of first AS diagnosis for patients and at the matched patient's diagnosis date for controls and continued until PE diagnosis, death, or study end date. Results: Prevalence of PE before AS diagnosis in patients compared to controls was 0.4% vs. 0.2% (p < 0.01). The incidence rate of PE was 11.6 per 10,000 person-years for patients with AS and 6.8 per 10,000 person-years for controls. The adjusted hazard ratio (HR) for PE in patients with AS was 1.70 (p < 0.001). Subgroup analysis demonstrated excess risk for PE in patients with AS regardless of gender and age, with variations among AS treatment categories. Discussion: Our findings highlight a significant association between AS and PE, indicating an increased risk in patients with AS independent of age and sex and suggests a subclinical level of inflammation. Preliminary results suggest a protective role of immunosuppressing drugs. Further research into the impact of treatment strategies should be conducted and could inform clinical management and reduce the life-threatening risk of PE in Patients with AS. [ABSTRACT FROM AUTHOR]

Some disease-modifying agents commonly used to treat patients with rheumatic diseases/autoimmune disorders, such as hydroxychloroquine and colchicine, are under investigation as potential therapies for the "coronavirus disease 2019" (COVID-19). However, the role of such agents as prophylactic tools is still not clear. This is a retrospective study based on a large healthcare computerized database including all patients that were screened for the "Severe Acute Respiratory Syndrome Coronavirus type 2" (SARS-CoV-2) in the study period from February 23rd 2020 to March 31st 2020. A comparison was conducted between subjects tested positive for SARS-CoV-2 and those found negative in terms of rate of administration of hydroxychloroquine/colchicine therapy. An overall sample of 14,520 subjects were screened for SARS-CoV-2 infection and 1317 resulted positive. No significant difference was found in terms of rates of usage of hydroxychloroquine or colchicine between those who were found positive for SARS-CoV-2 and those who were found negative (0.23% versus 0.25% for hydroxychloroquine, and 0.53% versus 0.48% for colchicine, respectively). These findings raise doubts regarding the protective role of these medications in the battle against SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

This case presents a patient with hypertrophic osteoarthropathy of the lower extremities that developed secondary to congenital cyanotic heart disease. The major clinical manifestation was severe bilateral leg pain. The pain that was debilitating in nature completely resolved following a single administration of 60 mg pamidronate. Hypertrophic osteoarthropathy (HOA) is an acquired, uncommon disorder of obscure etiology. It has been described mainly in association with chronic suppurative pulmonary diseases, bronchogenic carcinoma and lung metastases, cystic fibrosis, and cyanotic congenital malformations of the heart. [ABSTRACT FROM AUTHOR]

Objective: To identify predicators of patients with fibromyalgia (FM) that are associated with a severe COVID-19 disease course. Methods: We utilized the data base of the Clalit Health Services (CHS); the largest public organization in Israel, and extracted data concerning patients with FM. We matched two subjects without FM to each subject with FM by sex and age and geographic location. Baseline characteristics were evaluated by t-test for continuous variables and chi-square for categorical variables. Predictors of COVID-19 associated hospitalization were identified using univariable logistic regression model, significant variables were selected and analyzed by a multivariable logistic regression model. Results: The initial cohort comprised 18,598 patients with FM and 36,985 matched controls. The mean age was 57.5± 14.5(SD), with a female dominance of 91%. Out of this cohort we extracted the study population, which included all patients contracted with COVID-19, and consisted of 571 patients with FM and 1008 controls. By multivariable analysis, the following variables were found to predict COVID-19 associated hospitalization in patients with FM: older age (OR, 1.25; CI, 1.13–1.39; p<0.001), male sex (OR, 2.63; CI, 1.18–5.88; p<0.05) and hypertension (OR, 1.75; CI, 1.04–2.95; p<0.05). Conclusion: The current population-based study revealed that FM per se was not directly associated with COVID-19 hospitalization or related mortality. Yet classical risk factors endangering the general population were also relevant among patients with FM. [ABSTRACT FROM AUTHOR]

Fibromyalgia Syndrome (FMS) is a highly prevalent condition, that causes chronic pain and severe reduction in quality of life and productivity, as well as social isolation. Despite the significant morbidity and economic burden of FMS, current treatments are scarce. To investigate whether stimulation of ACC -mPFC activity by dTMS enhances a pain-directed psychotherapeutic intervention. 19 FMS patients were randomised to receive either 20 sessions of dTMS or sham stimulation, each followed by a pain-directed psychotherapeutic intervention. With the H7 HAC coil or sham stimulation, we targeted the ACC -mPFC; specific brain areas that play a central role in pain processing. Clinical response to treatment was assessed with the McGill Pain Questionnaire Short Form (SF-MPQ), the Visual Analogue Fibromyalgia Impact Questionnaire, the Brief Pain Inventory questionnaire, and the Hamilton Depression Rating Scale. DTMS treatment was safe and well tolerated by FMS patients. A significant decrease in the combined sensory and affective pain dimensions was specifically demonstrated in the dTMS cohort, as measured by the SF-MPQ (Significant group × time interaction [ F(2, 32) = 3.51 , p <.05 , η p 2 = 0.18]; No significant changes were found in depressive symptoms in both the dTMS and sham groups. Our results suggest that a course of dTMS combined with a pain-directed psychotherapeutic intervention can alleviate pain symptoms in FMS patients. Beyond clinical possibilities, future studies are needed to substantiate the innovative hypothesis that it is not dTMS alone, but rather dTMS-induced plasticity of pain-related networks, that enables the efficacy of pain-directed psychotherapeutic interventions. • Current treatments for fibromyalgia syndrome (FMS) are scarce. • DTMS or sham were followed by a pain-directed psychotherapeutic intervention. • DTMS directed to the ACC and mPFC was safe and well tolerated by FMS patients. • The psychotherapeutic intervention alleviated pain specifically in the dTMS cohort. [ABSTRACT FROM AUTHOR]

Background: The skin–gut axis, characterized by bidirectional communication between the skin and gut, plays a crucial role in the pathogenesis of psoriasis and inflammatory bowel diseases (IBD). Objectives: We aimed to explore the association between psoriasis and IBD and identify predictors associated with IBD development among patients with psoriasis. Design: Retrospective cohort study. Methods: A retrospective study which utilized an electronic database from the Meuhedet Health Maintenance Organization (MHMO) in Israel. Psoriasis was categorized as severe if any systemic agent or phototherapy was administered. Univariate and multivariate logistic regressions were used to identify specific predictors for IBD, with adjustments made for potential confounders. The study received approval from the Ethical Committee of the MHMO. Results: In total, 61,003 adult patients who were diagnosed with psoriasis between 2000 and 2022 were included. Among them, 1495/61,003 patients (2.4%) were diagnosed with IBD, as compared to 3834/244,012 patients (1.6%) in the non-psoriasis group [adjusted odds ratio (OR): 1.47; 95% confidence interval (CI): 1.37–1.56; p < 0.001]. Increased age (OR: 1.01; 95% CI: 1.01–1.02; p < 0.001), male gender (OR: 1.22; 95% CI: 1.03–1.45; p = 0.024), and Jewish ethnicity (OR: 2.5; 95% CI: 1.2–4.1; p < 0.001) were identified as significant risk factors for IBD. Spondyloarthropathies, including psoriatic arthritis (OR: 2.27; 95% CI: 1.86–2.77; p < 0.001) and ankylosing spondylitis (OR: 2.82; 95% CI: 1.5–5.32; p < 0.05), were associated with a higher prevalence of IBD. Furthermore, severe psoriasis was significantly associated with a higher likelihood of IBD, compared to mild psoriasis (OR: 16.03; 95% CI: 11.02–23.34; p < 0.001). Conclusion: A significant association between psoriasis and IBD was demonstrated, including its subtypes: Crohn's disease and ulcerative colitis. Moreover, such association may depend on psoriasis severity as determined by the treatment used. This association warrants further investigation and implies a potential need for closer monitoring of patients with severe psoriasis. Plain language summary: Association between psoriatic disease severity and risk of inflammatory bowel diseases 1- Gut and skin barrier play an integral role in psoriasis and inflammatory bowel disease (IBD) development. 2- Shared genetic and environmental factors could explain the association between both diseases. 3- We report increased association between psoriasis and IBD, a relationship that is more pronounced in patients with severe psoriasis. 4- Patients with spondyloarthritis related diseases have a stronger association with IBD. [ABSTRACT FROM AUTHOR]

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]

Introduction: Active metabolite of vitamin D has neuro-immunomodulatory and neuroprotective properties. However, there is still a debate about the potential association between low serum levels of hydroxy-vitamin D and increased risk for dementia. Objectives: To determine an association between hypovitaminosis D and dementia for different 25-hydroxyvitamin-D (25(OH)D) serum level cutoffs. Methods: Patients were identified utilizing the database of Clalit Health Services (CHS), the largest healthcare provider in Israel. For each subject, all available values of 25(OH)D during the study period, which lasted from 2002 to 2019, were obtained. Rates of dementia were compared across different cutoffs of 25(OH)D levels. Results: Cohort included 4278 patients, of whom 2454 (57%) were women. The mean age at the beginning of follow-up was 53 (±17). During the 17-year study period, a total of 133 patients (3%) were diagnosed with dementia. In a fully adjusted multivariate analysis, the risk for dementia was almost 2-fold higher in patients with an average of vitamin D insufficiency (<75 nmol/l) measurements (OR = 1.8, 95% C.I. = 1.0-3.2) compared to reference values (≥75 nmol/l). Patients with vitamin D deficiency (<50 nmol/l) demonstrated higher rates of dementia (OR = 2.6, 95% C.I. = 1.4-4.8). In our cohort, patients were diagnosed with dementia at a younger age in the deficiency (77 vs. 81 P -value = 0.05) and the insufficiency groups (77 vs. 81 P -value = 0.05) compared to the reference values (≥75 nmol/l). Conclusion: Insufficient levels of vitamin D are associated with dementia. Dementia is diagnosed at a younger age in patients with insufficient and deficient vitamin D levels. [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]

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.

This report presents the case of a young woman with seropositive rheumatoid arthritis in whom bilateral septic arthritis of the hip developed after four months of therapy with etanercept alone. Staphylococcus aureus infection was found unexpectedly during exposure of the hips at the beginning of an elective total hip arthroplasty. This report highlights a possible association between tumor necrosis factor TNF-α blockade therapy and multifocal septic arthritis. Several studies have demonstrated that both etanercept and infliximab are highly effective in the treatment of patients who have inadequate responses to conventional diseasemodifying antirheumatic drugs such as methotrexate.

The association between the clinical picture of symptomatic women with silicone breast implants (SBI) and dysregulated immunity was in dispute for decades. In the current study, we describe for the first time the functional activity of purified IgG antibodies derived from symptomatic women with SBIs (suffering from subjective/autonomic-related symptoms), both in vitro and in vivo. We found that IgGs, derived from symptomatic women with SBIs, dysregulate inflammatory cytokines (TNFα, IL-6) in activated human peripheral blood mononuclear cells, compared to healthy-women-derived IgGs. Importantly, behavioral studies conducted following intracerebroventricular injection of IgGs derived from symptomatic women with SBIs (who have dysregulated circulating level of IgG autoantibodies directed against autonomic nervous system receptors) into mice brains demonstrated a specific and transient significant increment (about 60%) in the time spent at the center of the open field arena compared with mice injected with IgG from healthy women (without SBIs). This effect was accompanied with a strong trend of reduction of the locomotor activity of the SBI-IgG treated mice, indicating an overall apathic-like behavior. Our study is the first to show the potential pathogenic activity of IgG autoantibodies in symptomatic women with SBIs, emphasizing the importance of these antibodies in SBI-related illness. [ABSTRACT FROM AUTHOR]

COVID-19 vaccine circulation approval was a turning point for the coronavirus pandemic. The current approved COVID-19 vaccines, including messenger ribonucleic acid (mRNA)-based and adenovirus vector-based vaccines, were shown to significantly reduce the disease mortality and severity, and its adverse reactions are mainly mild ones. However, few cases of autoimmune conditions, both flare-ups and new-onset, were described in association with these vaccines. Susac vasculitis (SaS) is a rare autoimmune disease characterized by the clinical triad of encephalopathy, visual disturbances, and sensorineural hearing loss. Its pathogenesis is still not fully understood but is believed to be related to autoimmune processes, including autoantibodies to anti-endothelial cells and cellular immune processes that lead to microvascular damage and, consequently, micro-occlusions of the cerebral, inner ear, and retinal vessels. It has been previously described following vaccination and, most recently, few cases following coronavirus vaccines. We here describe a case of a previously healthy 49-year-old man diagnosed with SaS 5 days following the first dose of the BNT162b2 COVID-19 vaccine. [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]

Anti-PLA2R antibodies (Ab) are a diagnostic and prognostic biomarker in primary membranous nephropathy (PMN). We assessed the relationship between the levels of anti-PLA2R Ab at diagnosis and different variables related to disease activity and prognosis in a western population of PMN patients. Forty-one patients with positive anti-PLA2R Ab from three nephrology departments in Israel were enrolled. Clinical and laboratory data were collected at diagnosis and after one year of follow-up, including serum anti-PLA2R Ab levels (ELISA) and glomerular PLA2R deposits on biopsy. Univariable statistical analysis and permutation-based ANOVA and ANCOVA tests were performed. The median [(interquartile range (IQR)) age of the patients was 63 [50–71], with 28 (68%) males. At the time of diagnosis, 38 (93%) of the patients had nephrotic range proteinuria, and 19 (46%) had heavy proteinuria (≥8 gr/24 h). The median [IQR] level of anti-PLA2R at diagnosis was 78 [35–183] RU/mL. Anti-PLA2R levels at diagnosis were correlated with 24 h proteinuria, hypoalbuminemia and remission after one year (p = 0.017, p = 0.003 and p = 0.034, respectively). The correlations for 24 h proteinuria and hypoalbuminemia remained significant after adjustment for immunosuppressive treatment (p = 0.003 and p = 0.034, respectively). Higher levels of anti-PLA2R Ab at diagnosis in patients with active PMN from a western population are associated with higher proteinuria, lower serum albumin and remission one year after the diagnosis. This finding supports the prognostic value of anti-PLA2R Ab levels and their possible use in stratifying PMN patients. [ABSTRACT FROM AUTHOR]

The induction of autoantibodies is common following therapy with anti-TNF-α agents. However, anti-TNF-α-induced lupus (ATIL) is rare. We assessed the clinical characteristics of three patients with inflammatory bowel disease (IBD) who were treated with infliximab and developed distinct subsets of ATIL. Also, we searched for similar cases in the published literature. We describe three patients with ATIL. The first patient had a classical drug-induced lupus (DIL) presented by thrombocytopenia that resolved after infliximab discontinuation. The second case experienced symmetric polyarthritis of 14 joints in rheumatoid arthritis (RA)-like distribution accompanied by lymphopenia. The third one had a severe serositis including ascites and pleural and pericardial effusions along with pancytopenia. In this patient, ATIL coexisted with anti-TNF-α-induced hepatitis. The second and third patients met the American College of Rheumatology classification criteria for SLE. Nevertheless, all three cases exhibited ANA and anti-dsDNA positivity, and only the second patient had anticardiolipin (aCL IgG) and anti-histone antibodies. The coexistence of both lupus-like syndrome and hepatitis following anti-TNF-α therapy in the same patient is very rare, and to the best of our knowledge, only four such case reports are mentioned in literature. Patients with mild ATIL may tolerate another anti-TNF-α agent without recurrence of the disease. Rheumatologists should be aware of the distinct clinical presentations of ATIL and its coexistence with other rare anti-TNF-alpha complications such as hepatitis. [ABSTRACT FROM AUTHOR]

Since Jenner, vaccines and vaccinations have stirred a hot, highly polarized debate, leading to contrasting positions and feelings, ranging from acritical enthusiasm to blind denial. On the one hand, we find anti-vaccination movements which divulge and disseminate misleading information, myths, prejudices, and even frauds, with the main aim of denying that vaccination practices represent a major public health measure, being effective in controlling infectious diseases and safeguarding the wellbeing of entire communities. Recently, the authors of many vaccine safety investigations are being personally criticized rather than the actual science being methodologically assessed and critiqued. Unfortunately, this could result in making vaccine safety science a “hazardous occupation”. Critiques should focus on the science and not on the authors and on the scientists that publish reasonably high-quality science suggesting a problem with a given vaccine. These scientists require adequate professional protection so there are not disincentives to publish and to carry out researches in the field. The issues for vaccine safety are not dissimilar to other areas such as medical errors and drug safety. [ABSTRACT FROM AUTHOR]

Background: COVID-19 is a heterogenous disease resulting in long-term sequela in predisposed individuals. It is not uncommon that recovering patients endure non-respiratory ill-defined manifestations, including anosmia, and neurological and cognitive deficit persisting beyond recovery—a constellation of conditions that are grouped under the umbrella of long-term COVID-19 syndrome. Association between COVID-19 and autoimmune responses in predisposed individuals was shown in several studies. Aim and methods: To investigate autoimmune responses against neuronal and CNS autoantigens in SARS-CoV-2-infected patients, we performed a cross-sectional study with 246 participants, including 169 COVID-19 patients and 77 controls. Levels of antibodies against the acetylcholine receptor, glutamate receptor, amyloid β peptide, alpha-synucleins, dopamine 1 receptor, dopamine 2 receptor, tau protein, GAD-65, N-methyl D-aspartate (NMDA) receptor, BDNF, cerebellar, ganglioside, myelin basic protein, myelin oligodendrocyte glycoprotein, S100-B, glial fibrillary acidic protein, and enteric nerve were measured using an Enzyme-Linked Immunosorbent Assay (ELISA). Circulating levels of autoantibodies were compared between healthy controls and COVID-19 patients and then classified by disease severity (mild [n = 74], severe [n = 65], and requiring supplemental oxygen [n = 32]). Results: COVID-19 patients were found to have dysregulated autoantibody levels correlating with the disease severity, e.g., IgG to dopamine 1 receptor, NMDA receptors, brain-derived neurotrophic factor, and myelin oligodendrocyte glycoprotein. Elevated levels of IgA autoantibodies against amyloid β peptide, acetylcholine receptor, dopamine 2 receptor, myelin basic protein, and α-synuclein were detected in COVID-19 patients compared with healthy controls. Lower IgA autoantibody levels against NMDA receptors, and IgG autoantibodies against glutamic acid decarboxylase 65, amyloid β peptide, tau protein, enteric nerve, and S100-B were detected in COVID-19 patients versus healthy controls. Some of these antibodies have known clinical correlations with symptoms commonly reported in the long COVID-19 syndrome. Conclusions: Overall, our study shows a widespread dysregulation in the titer of various autoantibodies against neuronal and CNS-related autoantigens in convalescent COVID-19 patients. Further research is needed to provide insight into the association between these neuronal autoantibodies and the enigmatic neurological and psychological symptoms reported in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Ankylosing spondylitis (AS) is an inflammatory rheumatic disease involving the axial skeleton ultimately resulting in physical disability and psychological sequalae. The current study aims to evaluate the link between AS and psychiatric disorders, and to investigate the impact of different disease modifying drugs on such link. A large retrospective, population-based, cross-sectional study utilizing the Clalit-Health-Service (CHS) database was conducted on 5825 AS patients and 25,984 age- and sex-matched control individuals. The prevalence of psychiatric morbidity was compared between AS patients and age- and gender-matched controls. Predictors for psychiatric disorders in AS patients were also investigated. The prevalence of psychiatric morbidity was higher in AS patients compared to controls (13.8 % vs. 9.8 %, p < 0.001). Similarly, major depression was positively associated with AS (OR 1.60, 95 % CI 1.43–1.79, p < 0.001), however, schizophrenia was negatively associated with AS (OR 0.60, 95 % CI 0.42–0.89, p < 0.011). Conventional DMARDs (cDMARDs) and anti-TNF used for management of AS were not shown to be predictors for psychiatric illnesses in AS patients. Patients with AS are at a higher risk of developing psychiatric disorders, with increased risk of depression and lower risk of schizophrenia. cDMARDs and TNF-inhibitors are not predictors of psychiatric disorders in AS patients. • Ankylosing spondylitis (AS) patients are at higher risk of psychiatric comorbidities • Depression is higher in patients with AS • AS patients have lower rates of schizophrenia • Inflammatory milieu of AS could be related to psychiatric comorbidity [ABSTRACT FROM AUTHOR]

Introduction: The exact pathogenesis of fibromyalgia (FM) syndrome is unclear. However, various infectious have been implicated with the development of FM after their acute phase. We aimed to investigate the incidence of FM syndrome among convalesced individuals following hospitalization for Acute Coronavirus Disease-2019 (COVID-19). Methods: We performed a cross-sectional study on patients who were discharged after COVID-19 hospitalization from the Sheba Medical Center, Israel, between July 2020 to November 2020. A phone interview was performed consisting of the following questionnaires: the Fibromyalgia Survey Diagnostic Criteria Questionnaire, Sense of Coherence Questionnaire to evaluate resilience, and the Subjective Traumatic Outlook Questionnaire to assess the associated psychological aspects of the trauma. The incidence of post-COVID FM was calculated and regression models were performed to identify predictors. Results: The study population consisted of 198 eligible patients who completed the phone interview. The median age was 64 (52–72) and 37% were women. The median follow-up was 5.2 months (IQR 4.4–5.8). The incidence of FM was 15% (30 patients) and 87% (172 patients) had at least one FM-related symptom. Female gender was significantly associated with post-COVID FM (OR 3.65, p = 0.002). In addition, high median Subjective Traumatic Outlook scores and low median Sense of Coherence scores were both significantly associated with post-COVID FM (OR 1.19, p<0.001 and OR 0.92, p<0.001, respectively). Conclusions: FM is highly prevalent among COVID-19 convalescent patients. Our finding suggests that a significant subjective traumatic experience and a low resilience are highly associated with post-COVID FM. [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]

BACKGROUNDS: It has been hypothesized that ankylosing spondylitis is associated with an increased risk of incident hip fractures due to osteoporosis and risk of falls but the supporting evidence is limited and mixed. OBJECTIVES: To assess the risk of hip fractures in a large cohort of patients with ankylosing spondylitis compared to a matched cohort. DESIGN: A retrospective cohort study. SUBJECTS: Men and women diagnosed with ankylosing spondylitis from 1 January 2002 to 31 December 2018. Matching in a 5:1 ratio was based on age and sex. Follow-up ended on 23 June 2019. MAIN MEASURES: Cox regression models adjusting for confounders defined in a causal inference framework were used to determine the hazard ratio for hip fractures. KEY RESULT: The final cohorts included 5,909 ankylosing spondylitis patients and 28,671 matched patients. The ankylosing spondylitis cohort had a mean age of 49 (17) years and was composed of 3,762 (64%) men, 3,638 (62%) patients born in Israel, and 1,532 (26%) patients of low residential socioeconomic status. During 45,388 and 224,192 cumulative person-years of follow-up, the ankylosing spondylitis and matched cohorts had 2.47 and 1.63 cases of hip fractures per 1,000 person-years, respectively. Ankylosing spondylitis patients also developed hip fractures earlier (74 [13] vs. 79 [10] years, p = 0.002). Ankylosing spondylitis was associated with hip fractures in the unadjusted (HR = 1.52, 95% CI [1.23–1.88]) and adjusted (HR = 1.56, 95% CI [1.27–1.93]) models. The association was evident in men (HR = 1.65, 95% CI [1.25–2.18]) and women (HR = 1.48, 95% CI [1.07–2.05]). CONCLUSION: This study found that ankylosing spondylitis patients developed hip fractures earlier and more often compared to a matched cohort. This study suggests that ankylosing spondylitis patients might benefit from more proactive screening, mitigation, and prevention of risk factors for hip fractures. [ABSTRACT FROM AUTHOR]

Introduction: Biologic therapies are licensed for both psoriasis (PsO) and psoriatic arthritis (PsA) with some electronic medical record data suggest that IL (Interleukin)-23 blockers might be more protective in PsA prevention than TNF blockers; however, the findings have been inconsistent. Higher Psoriasis Area and Severity Index (PASI) scores have also been linked to an increased PsA risk. To clarify these unresolved issues we investigated biologic agents, methotrexate, phototherapy, and topical therapy for PsA prevention in patients with psoriasis.This retrospective cohort study analyzed data from 58,671 patients with psoriasis from the Israeli Meuhedet Health Services Organization database was evaluated for incident PsA. Patients were categorized on the basis of treatment: group 1, topical therapy; group 2, phototherapy; group 3, conventional disease-modifying antirheumatic drugs (cDMARDs; methotrexate); group 4, biologic DMARDs which was also stratified according to biologic class.The PsA incidence rate was lower in the biologic agents’ group versus the methotrexate group (HR 0.46 [95% CI 0.35–0.62]). The incidence rates per 100 person-years varied across biologic treatment groups, with the anti‑IL‑12/23 or anti‑IL‑23p19 group at 4.57, the anti-IL-17 group at 4.35, and the TNF inhibitor group at 2.55. No differences were found between various biological agents in terms of preventing PsA. The phototherapy group exhibited a higher PsA development rate than the topical therapy group (HR 1.85 [95% CI 1.65–2.07]).Biological agents are more effective than methotrexate in reducing incident PsA in patients with psoriasis. This lower rate of PsA on topical therapy compared to phototherapy supports the importance of psoriasis severity as a risk factor.Methods: Biologic therapies are licensed for both psoriasis (PsO) and psoriatic arthritis (PsA) with some electronic medical record data suggest that IL (Interleukin)-23 blockers might be more protective in PsA prevention than TNF blockers; however, the findings have been inconsistent. Higher Psoriasis Area and Severity Index (PASI) scores have also been linked to an increased PsA risk. To clarify these unresolved issues we investigated biologic agents, methotrexate, phototherapy, and topical therapy for PsA prevention in patients with psoriasis.This retrospective cohort study analyzed data from 58,671 patients with psoriasis from the Israeli Meuhedet Health Services Organization database was evaluated for incident PsA. Patients were categorized on the basis of treatment: group 1, topical therapy; group 2, phototherapy; group 3, conventional disease-modifying antirheumatic drugs (cDMARDs; methotrexate); group 4, biologic DMARDs which was also stratified according to biologic class.The PsA incidence rate was lower in the biologic agents’ group versus the methotrexate group (HR 0.46 [95% CI 0.35–0.62]). The incidence rates per 100 person-years varied across biologic treatment groups, with the anti‑IL‑12/23 or anti‑IL‑23p19 group at 4.57, the anti-IL-17 group at 4.35, and the TNF inhibitor group at 2.55. No differences were found between various biological agents in terms of preventing PsA. The phototherapy group exhibited a higher PsA development rate than the topical therapy group (HR 1.85 [95% CI 1.65–2.07]).Biological agents are more effective than methotrexate in reducing incident PsA in patients with psoriasis. This lower rate of PsA on topical therapy compared to phototherapy supports the importance of psoriasis severity as a risk factor.Results: Biologic therapies are licensed for both psoriasis (PsO) and psoriatic arthritis (PsA) with some electronic medical record data suggest that IL (Interleukin)-23 blockers might be more protective in PsA prevention than TNF blockers; however, the findings have been inconsistent. Higher Psoriasis Area and Severity Index (PASI) scores have also been linked to an increased PsA risk. To clarify these unresolved issues we investigated biologic agents, methotrexate, phototherapy, and topical therapy for PsA prevention in patients with psoriasis.This retrospective cohort study analyzed data from 58,671 patients with psoriasis from the Israeli Meuhedet Health Services Organization database was evaluated for incident PsA. Patients were categorized on the basis of treatment: group 1, topical therapy; group 2, phototherapy; group 3, conventional disease-modifying antirheumatic drugs (cDMARDs; methotrexate); group 4, biologic DMARDs which was also stratified according to biologic class.The PsA incidence rate was lower in the biologic agents’ group versus the methotrexate group (HR 0.46 [95% CI 0.35–0.62]). The incidence rates per 100 person-years varied across biologic treatment groups, with the anti‑IL‑12/23 or anti‑IL‑23p19 group at 4.57, the anti-IL-17 group at 4.35, and the TNF inhibitor group at 2.55. No differences were found between various biological agents in terms of preventing PsA. The phototherapy group exhibited a higher PsA development rate than the topical therapy group (HR 1.85 [95% CI 1.65–2.07]).Biological agents are more effective than methotrexate in reducing incident PsA in patients with psoriasis. This lower rate of PsA on topical therapy compared to phototherapy supports the importance of psoriasis severity as a risk factor.Conclusion: Biologic therapies are licensed for both psoriasis (PsO) and psoriatic arthritis (PsA) with some electronic medical record data suggest that IL (Interleukin)-23 blockers might be more protective in PsA prevention than TNF blockers; however, the findings have been inconsistent. Higher Psoriasis Area and Severity Index (PASI) scores have also been linked to an increased PsA risk. To clarify these unresolved issues we investigated biologic agents, methotrexate, phototherapy, and topical therapy for PsA prevention in patients with psoriasis.This retrospective cohort study analyzed data from 58,671 patients with psoriasis from the Israeli Meuhedet Health Services Organization database was evaluated for incident PsA. Patients were categorized on the basis of treatment: group 1, topical therapy; group 2, phototherapy; group 3, conventional disease-modifying antirheumatic drugs (cDMARDs; methotrexate); group 4, biologic DMARDs which was also stratified according to biologic class.The PsA incidence rate was lower in the biologic agents’ group versus the methotrexate group (HR 0.46 [95% CI 0.35–0.62]). The incidence rates per 100 person-years varied across biologic treatment groups, with the anti‑IL‑12/23 or anti‑IL‑23p19 group at 4.57, the anti-IL-17 group at 4.35, and the TNF inhibitor group at 2.55. No differences were found between various biological agents in terms of preventing PsA. The phototherapy group exhibited a higher PsA development rate than the topical therapy group (HR 1.85 [95% CI 1.65–2.07]).Biological agents are more effective than methotrexate in reducing incident PsA in patients with psoriasis. This lower rate of PsA on topical therapy compared to phototherapy supports the importance of psoriasis severity as a risk factor. [ABSTRACT FROM AUTHOR]

Background: Personality disorders are prevalent in 6–10% of the population, but their risk for cause-specific mortality is unclear. The aim of the study was to assess the association between personality disorders diagnosed in late adolescence and all-cause as well as cause-specific (cardiovascular-related, external-related) mortality. Methods: We performed a longitudinal study on a historical prospective cohort based on nationwide screening prior to recruitment to the Israeli army. The study participants were 16–19-year-old persons who attended the army screening (medical and cognitive, including screening for psychiatric disorders) between 1967 and 2006. Participants were followed from 1967 till 2011. Results: The study included 2 051 606 subjects, of whom 1 229 252 (59.9%) were men and 822 354 (40.1%) were women, mean age 17.36 years. There were 55 508 (4.5%) men and 8237 (1.0%) women diagnosed with personality disorders. The adjusted hazard ratio (HRs) for coronary, stroke, cardiovascular, external-related causes and all-cause mortality among men with personality disorders were 1.34 (1.03–1.74), 1.82 (1.20–2.76), 1.45 (1.23–1.71), 1.41 (1.30–1.53) and 1.44 (1.36–1.51), respectively. The absolute rate difference for all-cause mortality was 56.07 and 13.19 per 105 person-years among men and women, respectively. Among women with personality disorders, the adjusted HRs for external-related causes and all-cause mortality were 2.74 (1.87–4.00) and 2.01 (1.56–2.58). Associations were already evident within 10 years of follow-up. Conclusions: Personality disorder in late adolescence is associated with increased risk of cardiovascular, external- and all-cause mortality. Increased cardiovascular mortality is evident before the age of 40 years and may point to the importance of lifestyle education already in youth. [ABSTRACT FROM AUTHOR]

Background: Silicone breast implants (SBIs) has been shown to be associated with an increased risk of autoimmune diseases. In the current study, we aimed to explore the potential association between circulating autoantibodies against the autonomic nervous system and cognitive impairment, memory deficit, and depressive symptoms reported by women with SBIs. Methods: ELISA assays were used to quantify anti-adrenergic receptors (α1, α2, β1, β2), anti-muscarinic receptors (M1-M5), anti-endothelin receptor type A, and anti-angiotensin II type 1 receptor titers in the sera of 93 symptomatic female subjects with SBIs and 36 age-matched healthy female controls. Results: A significant difference was detected in the level of autoantibodies against the autonomic nervous system receptors in women with SBIs who reported memory impairment, cognitive impairment, and sleep disturbance as compared with both women with SBIs who did not complain of these symptoms or with healthy individuals without SBIs. Conclusions: Clinical symptoms such as depression, cognitive impairment, and sleep disturbances were found to be associated with dysregulation of the levels of circulating autoantibodies targeting the autonomous nervous system receptors in women with SBIs. These autoantibodies may have diagnostic significance in diseases associated with breast implants. [ABSTRACT FROM AUTHOR]