Objectives: Gene-environment interactions increase the risk of psychosis. The objective of this study was to investigate gene-gene and gene-environment interactions in psychosis, including single nucleotide variants (SNVs) of dopamine-2 receptor (D2R), N-methyl-d-aspartate receptor (NMDAR), and cannabinoid receptor type 1 (CB1R), lifetime cannabis use, and childhood trauma. Methods: Twenty-three SNVs of genes encoding D2R (DRD2: rs1799978, rs7131056, rs6275), NMDAR (GRIN1: rs4880213, rs11146020; GRIN2A: rs1420040, rs11866328; GRIN2B: rs890, rs2098469, rs7298664), and CB1R (CNR1: rs806380, rs806379, rs1049353, rs6454674, rs1535255, rs2023239, rs12720071, rs6928499, rs806374, rs7766029, rs806378, rs10485170, rs9450898) were genotyped in 143 first-episode psychosis patients (FEPp) and 286 community-based controls by Illumina HumanCoreExome-24 BeadChip. Gene-gene and gene-environment associations were assessed using nonparametric Multifactor Dimensionality Reduction software. Results: Single-locus analyses among the 23 SNVs for psychosis and gene-gene interactions were not significant (p > 0.05 for all comparisons); however, both environmental risk factors showed an association with psychosis (p < 0.001). Moreover, gene-environment interactions were significant for an SNV in CNR1 and cannabis use. The best-performing model was the combination of CNR1 rs12720071 and lifetime cannabis use (p < 0.001), suggesting an increased risk of psychosis. Conclusion: Our study supports the hypothesis of gene-environment interactions for psychosis involving T-allele carriers of CNR1 SNVs, childhood trauma, and cannabis use. Objectives Geneenvironment Gene environment genegene gene geneenvironment (SNVs dopamine2 dopamine 2 dopamine- D2R, DR , D R (D2R) Nmethyldaspartate N methyl d aspartate NMDAR, (NMDAR) CB1R, CBR CB (CB1R) trauma Methods Twentythree Twenty three DRD2 DRD (DRD2 rs1799978 rs rs7131056 rs6275, rs6275 rs6275) GRIN1 GRIN (GRIN1 rs4880213 rs11146020 GRIN2A GRINA A rs1420040 rs11866328 GRIN2B GRINB B rs890 rs2098469 rs7298664, rs7298664 rs7298664) CNR (CNR1 rs806380 rs806379 rs1049353 rs6454674 rs1535255 rs2023239 rs6928499 rs806374 rs7766029 rs806378 rs10485170 rs9450898 14 firstepisode first episode FEPp (FEPp 28 communitybased community based HumanCoreExome24 HumanCoreExome 24 HumanCoreExome-2 BeadChip Genegene software Results Singlelocus Single locus p 005 0 05 0.0 comparisons comparisons) however 0.001. 0001 0.001 . 001 0.001) Moreover bestperforming best performing rs1272007 0.001, Conclusion Tallele T allele (D2R (NMDAR (CB1R (DRD rs179997 rs713105 rs627 (GRIN rs488021 rs1114602 rs142004 rs1186632 rs89 rs209846 rs729866 (CNR rs80638 rs80637 rs104935 rs645467 rs153525 rs202323 rs692849 rs776602 rs1048517 rs945089 HumanCoreExome2 HumanCoreExome- 00 0. 000 0.00 rs127200 rs17999 rs71310 rs62 rs48802 rs111460 rs14200 rs118663 rs8 rs20984 rs72986 rs8063 rs10493 rs64546 rs15352 rs20232 rs69284 rs77660 rs104851 rs94508 rs12720 rs1799 rs7131 rs6 rs4880 rs11146 rs1420 rs11866 rs2098 rs7298 rs806 rs1049 rs6454 rs1535 rs2023 rs6928 rs7766 rs10485 rs9450 rs1272 rs179 rs713 rs488 rs1114 rs142 rs1186 rs209 rs729 rs80 rs104 rs645 rs153 rs202 rs692 rs776 rs1048 rs945 rs127 rs17 rs71 rs48 rs111 rs14 rs118 rs20 rs72 rs10 rs64 rs15 rs69 rs77 rs94 rs12 rs1 rs7 rs4 rs11 rs2 rs9

Resumo Nós investigamos a viabilidade de incluir a pesquisa de anticorpos anti-NMDAR na avaliação de pacientes em primeiro episódio psicótico em um programa de intervenção precoce no Hemisfério Sul. Anticorpos IgG anti-NMDAR foram avaliados por ELISA em 166 pacientes (64,0% homens), 166 controles de base populacional pareados e 76 irmãos (30,3% homens). Foram realizados teste exato de Fisher e ANOVA. Os anticorpos anti-NMDAR positivos foram mais observados no transtorno afetivo bipolar (10,0%) do que na esquizofrenia (2,4%) ou depressão psicótica (3,1%), embora não tenham sido observadas diferenças significativas. Nossos resultados não são conclusivos quanto à inclusão de anticorpos IgG anti-NMDAR no plasma em protocolos de diagnósticos diferenciais para psicose.

Abstract We investigated the feasibility of including plasma anti-NMDAR antibody screening in the assessment of first-episode psychosis patients in an early intervention programme in the Southern hemisphere. Anti-NMDAR IgG antibodies were assessed by ELISA in 166 patients (64.0% men), 166 matched population-based controls and 76 patients’ siblings (30.3% men). Fisher’s exact test and ANOVA were performed. Positive anti-NMDAR antibody patients were more often observed in bipolar disorder (10.0%) than schizophrenia (2.4%) or psychotic depression (3.1%), although no significant differences were observed. Our results are not conclusive regarding the inclusion of plasma anti-NMDAR IgG antibodies in differential diagnostic protocols for psychosis.

Resumo Nós investigamos a viabilidade de incluir a pesquisa de anticorpos anti-NMDAR na avaliação de pacientes em primeiro episódio psicótico em um programa de intervenção precoce no Hemisfério Sul. Anticorpos IgG anti-NMDAR foram avaliados por ELISA em 166 pacientes (64,0% homens), 166 controles de base populacional pareados e 76 irmãos (30,3% homens). Foram realizados teste exato de Fisher e ANOVA. Os anticorpos anti-NMDAR positivos foram mais observados no transtorno afetivo bipolar (10,0%) do que na esquizofrenia (2,4%) ou depressão psicótica (3,1%), embora não tenham sido observadas diferenças significativas. Nossos resultados não são conclusivos quanto à inclusão de anticorpos IgG anti-NMDAR no plasma em protocolos de diagnósticos diferenciais para psicose.

Abstract We investigated the feasibility of including plasma anti-NMDAR antibody screening in the assessment of first-episode psychosis patients in an early intervention programme in the Southern hemisphere. Anti-NMDAR IgG antibodies were assessed by ELISA in 166 patients (64.0% men), 166 matched population-based controls and 76 patients’ siblings (30.3% men). Fisher’s exact test and ANOVA were performed. Positive anti-NMDAR antibody patients were more often observed in bipolar disorder (10.0%) than schizophrenia (2.4%) or psychotic depression (3.1%), although no significant differences were observed. Our results are not conclusive regarding the inclusion of plasma anti-NMDAR IgG antibodies in differential diagnostic protocols for psychosis.

Resumo Objetivo: O objetivo deste estudo foi comparar a qualidade da imagem das técnicas de saturação de gordura T2 SPAIR e STIR e, adicionalmente, comparar o desempenho diagnóstico das duas sequências para detecção de inflamação ativa nas imagens de ressonância magnética (RM) das sacroilíacas. Materiais e Métodos: Foram incluídos 69 pacientes consecutivos que realizaram RM das articulações sacroilíacas no período de 2012 a 2014. O cálculo da relação sinal/ruído (RSR) foi realizado pelo método do Colégio Americano de Radiologia. O desempenho diagnóstico foi realizado utilizando os resultados da leitura das imagens da sequência T1 SPIR Gd+ como referência. Resultados: A avaliação da RSR mostrou média de 72,8 para a sequência T1 SPIR Gd+. A sensibilidade e a especificidade das sequências STIR e SPAIR 2 para o diagnóstico de sacroiliite com inflamação ativa não apresentaram diferenças estatisticamente significantes. Conclusão: Nossos resultados reforçam a literatura recente sugerindo que não há superioridade da sequência STIR em relação à sequência SPAIR T2 para a avaliação das sacroilíacas em pacientes com espondiloartrite. A sequência SPAIR T2 apresenta melhor RSR em relação à sequência STIR em imagens de RM de 1,5 T, o que reforça que a sequência SPAIR T2 possa ser utilizada como opção vantajosa na avaliação da sacroiliite inflamatória.

Abstract Objective: To compare two different fat-saturated magnetic resonance imaging (MRI) techniques-STIR and T2 SPAIR-in terms of image quality, as well as in terms of their diagnostic performance in detecting sacroiliac joints (SIJ) active inflammation. Materials and Methods: We included 69 consecutive patients with suspected spondyloarthritis undergoing MRI between 2012 and 2014. The signal-to-noise ratio (SNR) was calculated with the method recommended by the American College of Radiology. Two readers evaluated SIJ MRI following ASAS criteria to assess diagnostic performance regarding the detection of active SIJ inflammation. T1 SPIR Gd+ sequence was used as the reference standard. Results: The mean SNR was 72.8 for the T1 SPIR Gd+ sequence, compared with 14.1 and 37.6 for the STIR and T2 SPAIR sequences, respectively. The sensitivity and specificity of STIR and SPAIR T2 sequences did not show any statistically significant differences, for the diagnosis of sacroiliitis with active inflammation. Conclusion: Our results corroborate those in the recent literature suggesting that STIR sequences are not superior to T2 SPAIR sequences for SIJ evaluation in patients with suspected spondyloarthritis. On 1.5-T MRI, T2-weighted SPAIR sequences provide better SNRs than do STIR sequences, which reinforces that T2 SPAIR sequences may be an advantageous option for the evaluation of sacroiliitis.

Abstract Background: Currently, magnetic resonance imaging (MRI) is used to evaluate active inflammatory sacroiliitis related to axial spondyloarthritis (axSpA). The qualitative and semiquantitative diagnosis performed by expert radiologists and rheumatologists remains subject to significant intrapersonal and interpersonal variation. This encouraged us to use machine-learning methods for this task. Methods: In this retrospective study including 56 sacroiliac joint MRI exams, 24 patients had positive and 32 had negative findings for inflammatory sacroiliitis according to the ASAS group criteria. The dataset was randomly split with ∼ 80% (46 samples, 20 positive and 26 negative) as training and ∼ 20% as external test (10 samples, 4 positive and 6 negative). After manual segmentation of the images by a musculoskeletal radiologist, multiple features were extracted. The classifiers used were the Support Vector Machine, the Multilayer Perceptron (MLP), and the Instance-Based Algorithm, combined with the Relief and Wrapper methods for feature selection. Results: Based on 10-fold cross-validation using the training dataset, the MLP classifier obtained the best performance with sensitivity = 100%, specificity = 95.6% and accuracy = 84.7%, using 6 features selected by the Wrapper method. Using the test dataset (external validation) the same MLP classifier obtained sensitivity = 100%, specificity = 66.7% and accuracy = 80%. Conclusions: Our results show the potential of machine learning methods to identify SIJ subchondral bone marrow edema in axSpA patients and are promising to aid in the detection of active inflammatory sacroiliitis on MRI STIR sequences. Multilayer Perceptron (MLP) achieved the best results.

Abstract INTRODUCTION Corticosteroids and/or thalidomides have been associated with thromboembolism events (TBE) in multibacillary (MB) leprosy. This report aimed to determine genetic and laboratory profiles associated with leprosy and TBE. METHODS Antiphospholipid antibodies (aPL), coagulation-related exams, prothrombin and Leiden’s factor V mutations, and ß2-glycoprotein-I (ß2GPI) Val247Leu polymorphism were assessed. RESULTS Six out of seven patients with leprosy were treated with prednisone and/or thalidomide during TBE and presented at least one positive aPL. All patients presented ß2GPI polymorphism, and one showed prothrombin mutation. CONCLUSIONS Corticosteroid or thalidomide adverse effects and aPL and ß2GPI polymorphisms may cause TBE in patients with MB leprosy.

Resumo A síndrome de Sjögren (SS) é uma doença autoimune crônica sistêmica que afeta as glândulas lacrimal e salivar. A SS pode se manifestar como SS primária (SSp) ou SS secundária (SSs), a última ocorrendo em conjunto com outra desordem autoimune. Em ambos os casos, os olhos secos e a boca seca afetam a qualidade de vida do paciente. As complicações tardias podem incluir cegueira, destruição dos tecidos dentários, candidíase oral e linfoma. Este artigo relata dois casos de SS, cada um apresentando lesão nodular oral incomum diagnosticada como linfoma MALT reincidente e mucocele. A importância do diagnóstico, tratamento e manejo das lesões orais por um cirurgião-dentista durante o atendimento de pacientes com SS é enfatizada, pois as manifestações orais da SS podem comprometer a qualidade de vida do paciente.

Abstract Sjögren’s syndrome (SS) is a systemic chronic autoimmune disorder affecting the lacrimal and salivary glands. SS may manifest as primary SS (pSS) or secondary SS (sSS), the latter occurring in the context of another autoimmune disorder. In both cases, the dry eyes and mouth affect the patient’s quality of life. Late complications may include blindness, dental tissue destruction, oral candidiasis and lymphoma. This paper reports two cases of SS, each of them presenting unusual oral nodular lesion diagnosed as relapsed MALT lymphoma and mucocele. The importance of the diagnosis, treatment and management of the oral lesions by a dentist during the care of SS patients is emphasized, as the oral manifestations of SS may compromise the patient’s quality of life.

Resumo Objetivos Avaliar incidência de tuberculose e triagem para tuberculose latente em brasileiros com artrite reumatoide em uso de agentes biológicos na prática clinica. Pacientes e métodos Estudo de coorte com dados do Registro Brasileiro de Monitoração de Terapias Biológicas (BiobadaBrasil), de 01/2009 a 05/2013, abrangeu 1.552 tratamentos, 415 somente com drogas modificadoras do curso da doença (MMCDs) sintéticas, 942 MMCDs sintéticas em associação com anti-TNF (etanercepte, infliximabe, adalimumabe) e 195 MMCDs sintéticas em associação com outros biológicos (abatacepte, rituximabe e tocilizumabe). Avaliaram-se ocorrência de tuberculose, tempo de exposição às drogas e triagem para TB. Análise estatística: teste t não pareado e teste de Fisher bicaudal; p < 0,05. Resultados O tempo de exposição dos controles foi de 981 pacientes-ano, do grupo de anti-TNF foi de 1.744 pacientes-ano (adalimumabe = 676, infliximabe = 547 e etanercepte = 521 pacientes-ano) e o de outros biológicos de 336 pacientes-ano. A incidência de TB foi de 1,01/1.000 pacientes-ano nos controles e de 2,87 pacientes-ano nos usuários de anti-TNF (adalimumabe = 4,43/1.000 pacientes-ano; etanercepte = 1,92/1.000 pacientes-ano e infliximabe = 1,82/1.000 pacientes-ano). Não houve casos de tuberculose no grupo de outros biológicos. O tempo médio de exposição até a ocorrência de tuberculose foi de 27(11) meses para o grupo anti-TNF. Conclusões A incidência de tuberculose foi maior nos usuários de MMCDs sintéticas e anti-TNF do que nos usuários de MMCDs sintéticas e de MMCDs sintéticas e biológicos não anti-TNF, e também mais tardia, sugerindo infecção durante o tratamento, e não falha na triagem.

Abstract Objectives To assess the incidence of tuberculosis and to screen for latent tuberculosis infection among Brazilians with rheumatoid arthritis using biologics in clinical practice. Patients and methods This cohort study used data from the Brazilian Registry of Biological Therapies in Rheumatic Diseases (Registro Brasileiro de Monitoração de Terapias Biológicas - BiobadaBrasil), from 01/2009 to 05/2013, encompassing 1552 treatments, including 415 with only synthetic disease-modifying anti-rheumatic drugs, 942 synthetic DMARDs combined with anti-tumor necrosis factor (etanercept, infliximab, adalimumab) and 195 synthetic DMARDs combined with other biologics (abatacept, rituximab and tocilizumab). The occurrence of tuberculosis and the drug exposure time were assessed, and screening for tuberculosis was performed. Statistical analysis: Unpaired t-test and Fisher's two-tailed test; p < 0.05. Results The exposure times were 981 patient-years in the controls, 1744 patient-years in the anti-TNF group (adalimumab = 676, infliximab = 547 and etanercept = 521 patient-years) and 336 patient-years in the other biologics group. The incidence rates of tuberculosis were 1.01/1000 patient-years in the controls and 2.87 patient-years among anti-TNF users (adalimumab = 4.43/1000 patient-years; etanercept = 1.92/1000 patient-years and infliximab = 1.82/1000 patient-years). No cases of tuberculosis occurred in the other biologics group. The mean drug exposure time until the occurrence of tuberculosis was 27(11) months for the anti-TNF group. Conclusions The incidence of tuberculosis was higher among users of synthetic DMARDs and anti-TNF than among users of synthetic DMARDs and synthetic DMARDs and non-anti-TNF biologics and also occurred later, suggesting infection during treatment and no screening failure.

Resumo Em 2014, o tofacitinibe, um medicamento modificador do curso da doença (MMCD) sintético, alvo-específico, inibidor seletivo das Janus quinases (JAK), foi aprovado para uso no Brasil. Este documento de posicionamento tem o objetivo de atualizar as recomendações da Sociedade Brasileira de Reumatologia (SBR) sobre o tratamento da artrite reumatoide (AR) no Brasil, especificamente com relação ao uso de MMCD sintéticos alvo-específicos. O método dessa recomendação incluiu revisão bibliográfica de artigos científicos, feita na base de dados Medline. Após a revisão, foi produzido um texto, que responde a perguntas na estrutura Pico, e considera questões de eficácia e segurança do uso do tofacitinibe para tratamento de AR em diferentes situações (como primeira linha de tratamento, após falha ao metotrexato [MTX] ou outros MMCD sintéticos convencionais, após falha da terapia biológica). Com base nas evidências existentes, e considerando os dados disponíveis sobre eficácia, segurança e custo das medicações disponíveis para tratamento da doença no Brasil, a Comissão de AR da SBR, após processo de discussão e votação de propostas, estabeleceu o seguinte posicionamento sobre o uso de tofacitinibe para o tratamento da AR no Brasil: “Tofacitinibe, em monoterapia ou em associação ao MTX, é uma opção para os pacientes com AR em atividade moderada ou alta, após falha de pelo menos dois esquemas com diferentes MMCD sintéticos e um esquema de MMCD biológico”. O grau de concordância com essa recomendação foi 7,5. Esse posicionamento poderá ser revisto nos próximos anos, com a maior experiência adquirida com o uso do medicamento.

Abstract In 2014, tofacitinib, a target-specific, synthetic disease modifying anti rheumatic drug (DMARD) and a selective inhibitor of Janus kinase (JAK) was approved for use in Brazil. This position paper aims to update the recommendations of the Brazilian Society of Rheumatology (SBR) on the treatment of rheumatoid arthritis (RA) in Brazil, specifically regarding the use of target-specific synthetic DMARDs. The method of this recommendation consisted of a literature review of scientific papers held on the Medline database. After this review, a text was produced, answering questions in Pico structure, considering efficacy and safety issues of tofacitinib use for RA treatment in different scenarios (such as first-line treatment after failure with methotrexate [MTX] or other conventional synthetic DMARDs after failure with biological therapy). Based on existing evidence, and considering the available data on efficacy, safety and cost of medications available to treat the disease in Brazil, the RA Commission of SBR, after a process of discussion and voting on proposals, established the following position on the use of tofacitinib for treatment of RA in Brazil: “Tofacitinib, alone or in combination with MTX, is an alternative for RA patients with moderate or high activity after failure of at least two different synthetic DMARDs and one biological DMARD.” The level of agreement with this recommendation was 7.5. This position may be reviewed in the coming years, in the face of a greater experience with the use of this medication.

OBJETIVO: Elaborar recomendações para a vacinação em pacientes com artrite reumatoide (AR) no Brasil. MÉTODO: Revisão da literatura e opinião de especialistas membros da Comissão de AR da Sociedade Brasileira de Reumatologia e um pediatra reumatologista. RESULTADOS E CONCLUSÕES: Foram estabelecidas 12 recomendações: 1) Antes de iniciar drogas modificadoras do curso de doença, deve-se revisar e atualizar o cartão vacinal; 2) As vacinas contra influenza sazonal e contra H1N1 estão indicadas anualmente para pacientes portadores de AR; 3) A vacina antipneumocócica deve ser indicada para todos os pacientes; 4) A vacina contra varicela deve ser indicada para pacientes com história negativa ou duvidosa de infecção prévia por varicela; 5) A vacina contra HPV deve ser considerada em adolescentes e mulheres jovens; 6) A vacina antimeningocócica é indicada para pacientes portadores de AR apenas em casos de asplenia ou deficiência de complemento; 7) Existe orientação de imunização contra o Haemophilus influenzae tipo B de pacientes adultos asplênicos; 8) Não há indicação de uma vacina adicional contra BCG em pacientes com AR; 9) A vacina contra hepatite B é indicada para pacientes com anticorpos contra HBsAg negativos; considerar a vacina contra hepatite A em combinação com a hepatite B; 10) Pacientes com grande risco de contrair tétano que receberam rituximabe nas últimas 24 semanas devem utilizar imunização passiva com imunoglobulina antitetânica; 11) A vacina contra febre amarela é contraindicada nos pacientes com AR em uso de imunossupressores; 12) As recomendações acima descritas devem ser revisadas ao longo da evolução da AR.

OBJECTIVE: To elaborate recommendations to the vaccination of patients with rheumatoid arthritis (RA) in Brazil. METHOD: Literature review and opinion of expert members of the Brazilian Society of Rheumatology Committee of Rheumatoid Arthritis and of an invited pediatric rheumatologist. RESULTS AND CONCLUSIONS: The following 12 recommendations were established: 1) Before starting disease-modifying anti-rheumatic drugs, the vaccine card should be reviewed and updated; 2) Vaccines against seasonal influenza and against H1N1 are indicated annually for patients with RA; 3) The pneumococcal vaccine should be indicated for all patients with RA; 4) The vaccine against varicella should be indicated for patients with RA and a negative or dubious history for that disease; 5) The HPV vaccine should be considered for adolescent and young females with RA; 6) The meningococcal vaccine is indicated for patients with RA only in the presence of asplenia or complement deficiency; 7) Asplenic adults with RA should be immunized against Haemophilus influenzae type B; 8) An additional BCG vaccine is not indicated for patients diagnosed with RA; 9) Hepatitis B vaccine is indicated for patients with RA who are negative for antibodies against HBsAg; the combined hepatitis A and B vaccine should be considered; 10) Patients with RA and at high risk for tetanus, who received rituximab in the preceding 24 weeks, should undergo passive immunization with tetanus immunoglobulin in case of exposure; 11) The YF vaccine is contraindicated to patients with RA on immunosuppressive drugs; 12) The above described recommendations should be reviewed over the course of RA.