Are obesity and rheumatoid arthritis interrelated

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

OP0098 SUICIDAL BEHAVIOUR IN FIBROMYALGIA PATIENTS: META-ANALYSIS AND SYSTEMATIC REVIEW OF THE LITERATURE

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Cannabis oil extracts for chronic pain: What else can be learned from another structured prospective cohort?

INTRODUCTION: The use of medicinal cannabis for managing pain expands, although its efficacy and safety have not been fully established through randomized controlled trials. OBJECTIVES: This structured, prospective questionnaire-based cohort was aimed to assess long-term effectiveness and safety of cannabis oil extracts in patients with chronic pain. METHODS: Adult Israeli patients licensed to use cannabis oil extracts for chronic pain were followed prospectively for 6 months. The primary outcome measure was change from baseline in average weekly pain intensity, and secondary outcomes were changes in related symptoms and quality of life, recorded before treatment initiation and 1, 3, and 6 months thereafter. Generalized linear mixed model was used to analyze changes over time. In addition, responders (≥30% reduction in weekly pain at any time point) were identified. RESULTS: The study included 218 patients at baseline, and 188, 154, and 131 at 1, 3, and 6 months, respectively. At 6 months, the mean daily doses of cannabidiol and Δ9-tetrahydrocannabinol were 22.4 ± 24.0 mg and 20.8 ± 30.1 mg, respectively. Pain decreased from 7.9 ± 1.7 at baseline to 6.6 ± 2.2 at 6 months ( CONCLUSION: This prospective cohort demonstrated a modest overall long-term improvement in chronic pain and related symptoms and a reasonable safety profile with the use of relatively low doses of individually titrated Δ9-tetrahydrocannabinol and cannabidiol

Folate and B12 Levels Correlate with Histological Severity in NASH Patients

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

Prediction of remission and low disease activity in disease-modifying anti-rheumatic drug-refractory patients with rheumatoid arthritis treated with golimumab

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 (R(2) = 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

Qual a Contribuiçao do Tilt Training (treinamento postural) na Prevençao da Síncope Vasovagal?

Histórico: A síncope vasovagal é um dos quadros clínicos mais comuns em adultos jovens. Estudos anteriores demonstram a eficiência do tilt training (treinamento postural) no tratamento desse transtorno clínico. Realizou-se um estudo prospectivo e randomizado com o objetivo de avaliar a contribuiçao do tilt training no tratamento de adultos jovens acometidos pela síncope vasovagal. Métodos: Quarenta e seis soldados, 25 dos quais do sexo masculino, média de idade de 19,4 ± 0,8 anos e diagnóstico clínico de síncope vasovagal pelo tilt test, foram divididos aleatoriamente em dois grupos: um grupo controle e outro submetido a tilt training diariamente, por três meses. Nos dois grupos, os participantes foram instruídos a aumentar a ingestao de líquidos e sal e evitar situaçoes indutoras da síncope, tais como permanecer em pé por períodos longos. Resultados: A adesao ao programa de treinamento, caracterizada pela realizaçao de 50% ou mais das sessoes diárias de tilt training, foi de 91% durante o primeiro mês, caindo para 58% nos três meses. Os que realizaram o treinamento apresentaram uma média (distância interquartílica) de 5,0 episódios de síncope (0,5 a 16,0) durante um ano de acompanhamento, enquanto o grupo controle apresentou média de 2,0 episódios (0 a 6,0; P = 0,737). Após a randomizaçao, nao houve diferença significativa no tempo de ocorrência do primeiro episódio de síncope entre os dois grupos: média de 1,0 por mês (0,5 a 2,0) no grupo em tratamento e 0,8 (0,5 a 2,0) no grupo controle (P = 0,336). Conclusoes: A realizaçao diária do tilt training, aliada às modificaçoes de estilo de vida, nao produziu melhora no resultado do tratamento de adultos jovens com síncope vasovagal. Verificou-se ainda a dificuldade de obter boa adesao ao programa de treinamento postural

Methotrexate enhances the anti-inflammatory effect of CF101 via up-regulation of the A(3 )adenosine receptor expression

Methotrexate (MTX) exerts an anti-inflammatory effect via its metabolite adenosine, which activates adenosine receptors. The A(3 )adenosine receptor (A(3)AR) was found to be highly expressed in inflammatory tissues and peripheral blood mononuclear cells (PBMCs) of rats with adjuvant-induced arthritis (AIA). CF101 (IB-MECA), an A(3)AR agonist, was previously found to inhibit the clinical and pathological manifestations of AIA. The aim of the present study was to examine the effect of MTX on A(3)AR expression level and the efficacy of combined treatment with CF101 and MTX in AIA rats. AIA rats were treated with MTX, CF101, or both agents combined. A(3)AR mRNA, protein expression and exhibition were tested in paw and PBMC extracts from AIA rats utilizing immunohistochemistry staining, RT-PCR and Western blot analysis. A(3)AR level was tested in PBMC extracts from patients chronically treated with MTX and healthy individuals. The effect of CF101, MTX and combined treatment on A(3)AR expression level was also tested in PHA-stimulated PBMCs from healthy individuals and from MTX-treated patients with rheumatoid arthritis (RA). Combined treatment with CF101 and MTX resulted in an additive anti-inflammatory effect in AIA rats. MTX induced A(2A)AR and A(3)AR over-expression in paw cells from treated animals. Moreover, increased A(3)AR expression level was detected in PBMCs from MTX-treated RA patients compared with cells from healthy individuals. MTX also increased the protein expression level of PHA-stimulated PBMCs from healthy individuals. The increase in A(3)AR level was counteracted in vitro by adenosine deaminase and mimicked in vivo by dipyridamole, demonstrating that receptor over-expression was mediated by adenosine. In conclusion, the data presented here indicate that MTX induces increased A(3)AR expression and exhibition, thereby potentiating the inhibitory effect of CF101 and supporting combined use of these drugs to treat RA

Methotrexate enhances the anti-inflammatory effect of CF101 via up-regulation of the A(3 )adenosine receptor expression

Methotrexate (MTX) exerts an anti-inflammatory effect via its metabolite adenosine, which activates adenosine receptors. The A(3 )adenosine receptor (A(3)AR) was found to be highly expressed in inflammatory tissues and peripheral blood mononuclear cells (PBMCs) of rats with adjuvant-induced arthritis (AIA). CF101 (IB-MECA), an A(3)AR agonist, was previously found to inhibit the clinical and pathological manifestations of AIA. The aim of the present study was to examine the effect of MTX on A(3)AR expression level and the efficacy of combined treatment with CF101 and MTX in AIA rats. AIA rats were treated with MTX, CF101, or both agents combined. A(3)AR mRNA, protein expression and exhibition were tested in paw and PBMC extracts from AIA rats utilizing immunohistochemistry staining, RT-PCR and Western blot analysis. A(3)AR level was tested in PBMC extracts from patients chronically treated with MTX and healthy individuals. The effect of CF101, MTX and combined treatment on A(3)AR expression level was also tested in PHA-stimulated PBMCs from healthy individuals and from MTX-treated patients with rheumatoid arthritis (RA). Combined treatment with CF101 and MTX resulted in an additive anti-inflammatory effect in AIA rats. MTX induced A(2A)AR and A(3)AR over-expression in paw cells from treated animals. Moreover, increased A(3)AR expression level was detected in PBMCs from MTX-treated RA patients compared with cells from healthy individuals. MTX also increased the protein expression level of PHA-stimulated PBMCs from healthy individuals. The increase in A(3)AR level was counteracted in vitro by adenosine deaminase and mimicked in vivo by dipyridamole, demonstrating that receptor over-expression was mediated by adenosine. In conclusion, the data presented here indicate that MTX induces increased A(3)AR expression and exhibition, thereby potentiating the inhibitory effect of CF101 and supporting combined use of these drugs to treat RA

Qual a Contribuiçao do Tilt Training (treinamento postural) na Prevençao da Síncope Vasovagal?

Histórico: A síncope vasovagal é um dos quadros clínicos mais comuns em adultos jovens. Estudos anteriores demonstram a eficiência do tilt training (treinamento postural) no tratamento desse transtorno clínico. Realizou-se um estudo prospectivo e randomizado com o objetivo de avaliar a contribuiçao do tilt training no tratamento de adultos jovens acometidos pela síncope vasovagal. Métodos: Quarenta e seis soldados, 25 dos quais do sexo masculino, média de idade de 19,4 ± 0,8 anos e diagnóstico clínico de síncope vasovagal pelo tilt test, foram divididos aleatoriamente em dois grupos: um grupo controle e outro submetido a tilt training diariamente, por três meses. Nos dois grupos, os participantes foram instruídos a aumentar a ingestao de líquidos e sal e evitar situaçoes indutoras da síncope, tais como permanecer em pé por períodos longos. Resultados: A adesao ao programa de treinamento, caracterizada pela realizaçao de 50% ou mais das sessoes diárias de tilt training, foi de 91% durante o primeiro mês, caindo para 58% nos três meses. Os que realizaram o treinamento apresentaram uma média (distância interquartílica) de 5,0 episódios de síncope (0,5 a 16,0) durante um ano de acompanhamento, enquanto o grupo controle apresentou média de 2,0 episódios (0 a 6,0; P = 0,737). Após a randomizaçao, nao houve diferença significativa no tempo de ocorrência do primeiro episódio de síncope entre os dois grupos: média de 1,0 por mês (0,5 a 2,0) no grupo em tratamento e 0,8 (0,5 a 2,0) no grupo controle (P = 0,336). Conclusoes: A realizaçao diária do tilt training, aliada às modificaçoes de estilo de vida, nao produziu melhora no resultado do tratamento de adultos jovens com síncope vasovagal. Verificou-se ainda a dificuldade de obter boa adesao ao programa de treinamento postural

Somatic Mutations and the Risk of Undifferentiated Autoinflammatory Disease in MDS: An Under-Recognized but Prognostically Important Complication

Objectives: We theorized that myelodysplastic syndrome (MDS) with somatic mutations and karyotype abnormalities are associated with autoinflammation, and that the presence of autoinflammatory disease affected prognosis in MDS.Methods: One hundred thirty-four MDS patients were assessed for the prevalence of autoinflammatory complications and its link with karyotypes and somatic mutation status. Autoinflammatory complications were described either as well-defined autoinflammatory diseases (AD) or undifferentiated “autoinflammatory disease” (UAD) (defined as CRP over 10.0 mg/L on five consecutive occasions, taken at separate times and not explained by infection). Several patient characteristics including demographic, clinical, laboratory, cytogenetics charts, and outcomes, were compared between different groups.Results: Sixty-two (46.3%) patients had an autoinflammatory complication manifesting as arthralgia (43.5% vs. 23.6%, p = 0.0146), arthritis (30.6% vs. 15.3%, p = 0.0340), skin rash (27.4% vs. 12.5%, p = 0.0301), pleuritis (14.5% vs. 4.2%, p = 0.0371) and unexplained fever (27.4% vs. 0%, p <0.0001). AD were found in 7.4% of MDS patients (with polymyalgia rheumatic being the most frequently one). Classical autoimmune diseases were found only in 4 MDS patients (3.0%). Transcription factor pathway mutations (RUNX1, BCOR, WTI, TP53) (OR 2.20 [95%CI 1.02–4.75], p = 0.0451) and abnormal karyotypes (OR 2.76 [95%CI 1.22–6.26], p = 0.0153) were associated with autoinflammatory complications. Acute leukaemic transformation was more frequent in MDS patients with autoinflammatory features than those without (27.4% vs. 9.7%, p = 0.0080).Conclusions: Autoinflammatory complications are common in MDS. Somatic mutations of transcription factor pathways and abnormal karyotypes are associated with greater risk of autoinflammatory complications, which are themselves linked to malignant transformation and a worse prognosis