Rastreamento da infecção latente por tuberculose em pacientes com artrite idiopática juvenil previamente à terapia anti‐TNF em um país de alto risco para tuberculose

ResumoObjetivoAvaliar, em um país endêmico, a eficácia em longo prazo do rastreamento à procura de infecção latente por tuberculose (ILTB) e profilaxia primária em pacientes com AIJ em uso de bloqueadores do TNF.MétodosTrata‐se de uma coorte retrospectiva que incluiu pacientes com AIJ elegíveis para a terapia anti‐TNF. Os pacientes foram rastreados à procura de ILTB previamente ao uso de anti‐TNF por meio do teste tuberculínico (TT), radiografia de tórax e história de exposição à TB. Os indivíduos foram acompanhados regularmente em intervalos de dois meses.ResultadosIncluíram‐se 69 pacientes com AIJ com idade atual de 17,4±5,8 anos, com média de duração da doença de 5±4,9 anos; 47 pacientes receberam um único anti‐TNF, enquanto 22 foram transferidos para outro anti‐TNF uma ou duas vezes: 57 foram tratados com etanercepte, 33 com adalimumabe e três com infliximabe. O rastreamento à procura de ILTB foi positivo em três pacientes: um era TT positivo e tinha história de exposição à TB e dois apenas eram TT positivo. Não foi diagnosticado caso de TB ativa durante o período de estudo (mediana de seguimento de 3,8 anos).ConclusãoA avaliação em longo prazo revelou que o rastreamento à procura de ILTB e a profilaxia primária antes do tratamento com anti‐TNF foram eficazes em um país de alto risco para TB e o TT foi o parâmetro mais sensível para identificar esses pacientes.AbstractObjectivesTo evaluate, in an endemic country, the long‐term efficacy of latent tuberculosis infection (LTBI) screening and primary prophylaxis in patients with JIA receiving TNF blockers.MethodsThis was a retrospective cohort that included JIA patients eligible to anti‐TNF therapy. Patients were screened for LTBI prior to anti‐TNF using tuberculin skin test (TST), chest X‐ray and history of exposure to TB. Subjects were regularly followed at 2‐month intervals.ResultsSixty‐nine JIA patients with current age of 17.4±5.8 years, mean disease duration of 5.0±4.9 years were included. Forty‐seven patients received a single anti‐TNF, while 22 patients switched to another anti‐TNF once or twice: 57 were treated with etanercepte, 33 patients with adalimumab and 3 infliximab. LTBI screening was positive in three patients: one had TST‐positive and history of TB exposure and two had solely TST‐positive. No active TB was diagnosed during the study period (median of follow‐up was 3.8 years).ConclusionLong‐term evaluation revealed that LTBI screening and primary prophylaxis before anti‐TNF treatment was effective in a high‐risk country and TST was the most sensitive parameter to identify these patients

Immunogenicity of influenza H1N1 vaccination in mixed connective tissue disease: effect of disease and therapy

OBJECTIVE: To assess the potential acute effects regarding the immunogenicity and safety of non-adjuvanted influenza A H1N1/2009 vaccine in patients with mixed connective tissue disease and healthy controls. METHODS: Sixty-nine mixed connective tissue disease patients that were confirmed by Kasukawa's classification criteria and 69 age- and gender-matched controls participated in the study; the participants were vaccinated with the non-adjuvanted influenza A/California/7/2009 (H1N1) virus-like strain. The percentages of seroprotec-tion, seroconversion, geometric mean titer and factor increase in the geometric mean titer were calculated. The patients were clinically evaluated, and blood samples were collected pre- and 21 days post-vaccination to evaluate C-reactive protein, muscle enzymes and autoantibodies. Anti-H1N1 titers were determined using an influenza hemagglutination inhibition assay. ClinicalTrials.gov: NCT01151644. RESULTS: Before vaccination, no difference was observed regarding the seroprotection rates (p = 1.0) and geometric mean titer (p = 0.83) between the patients and controls. After vaccination, seroprotection (75.4% vs. 71%, (p = 0.7), seroconversion (68.1% vs. 65.2%, (p = 1.00) and factor increase in the geometric mean titer (10.0 vs. 8.0, p = 0.40) were similar in the two groups. Further evaluation of seroconversion in patients with and without current or previous history of muscle disease (p = 0.20), skin ulcers (p = 0.48), lupus-like cutaneous disease (p = 0.74), secondary Sjogren syndrome (p = 0.78), scleroderma-pattern in the nailfold capillaroscopy (p = 1.0), lymphopenia #1000/mm³ on two or more occasions (p = 1.0), hypergammaglobulinemia $1.6 g/d (p = 0.60), pulmonary hypertension (p = 1.0) and pulmonary fibrosis (p = 0.80) revealed comparable rates. Seroconversion rates were also similar in patients with and without immunosuppressants. Disease parameters, such as C-reactive protein (p = 0.94), aldolase (p = 0.73), creatine phosphokinase (p = 0.40) and ribonucleoprotein antibody levels (p = 0.98), remained largely unchanged pre and post-vaccination. No severe side effects were reported. CONCLUSIONS: The non-adjuvanted influenza A/H1N1 vaccination immune response in mixed connective tissue disease patients is adequate and does not depend on the disease manifestations and therapy

Chronic spontaneous urticaria: a survey of 852 cases of childhood-onset systemic Lupus Erythematosus

Data regarding the prevalence of chronic spontaneous urticaria (CSU) in childhood-onset systemic lupus erythematosus (cSLE) patients and possible associated factors are limited to a few case reports. The objectives of this study were to assess CSU in a large cSLE population, in order to evaluate the demographic data, clinical manifestations, disease activity/damage, laboratory abnormalities and treatment. A retrospective multicenter cohort study (Brazilian cSLE group) was performed in 10 Pediatric Rheumatology services and included 852 cSLE patients. CSU was diagnosed according to the guidelines of the European Academy of Allergy and Clinical Immunology, the Global Allergy and Asthma European Network, the European Dermatology Forum and the World Allergy Organization. Patients with CSU (evaluated at urticaria diagnosis) and patients without CSU (evaluated at the last visit) were assessed for lupus clinical/laboratory features and treatment. CSU was observed in 10/852 cSLE patients (1.17%). The median of cSLE duration at urticaria diagnosis was 0 (-3 to 5) years. Comparison of cSLE patients with and without CSU revealed a greater frequency of constitutional symptoms (40 vs. 8%, p = 0.006), reticuloendothelial system involvement (30 vs. 3%, p = 0.003), mucocutaneous (90 vs. 28%, p < 0.0001) and musculoskeletal manifestations (50 vs. 6%, p < 0.0001) and methylprednisolone pulse therapy use (60 vs. 9%, p < 0.0001) in the former group. The frequency of immunosuppressive treatment was lower in patients with CSU (p = 0.018). The median SLE Disease Activity Index 2000 (12 vs. 2, p < 0.0001) and erythrocyte sedimentation rate (40 vs. 19 mm/1st hour, p = 0.024), was higher in patients with CSU. To our knowledge, this is the first study with evidence that CSU may be linked to cSLE. We also demonstrated that this particular skin manifestation occurs predominantly at disease onset and is associated with lupus moderate/high disease activity without major organ involvement1673186192CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ301805/2013-0; 2009/51897-5; 302724/2011-

Guidelines on Management of Human Infection with the Novel Virus Influenza A (H1N1) – A Report from the Hospital das Clínicas of the University of São Paulo

The pandemic novel influenza A (H1N1) infection was considered widespread in Brazil on July, 2009. Since then, 9.249 cases were confirmed in Brazil, most of them concentrated in São Paulo. The Hospital das Clínicas of the University of São Paulo is a reference center for H1N1 cases in São Paulo. The purpose of this review is to analyze the evidence concerning diagnosis, prevention, and treatment of novel influenza A (H1N1) infection. In addition, we propose guidelines for the management of this pandemic emphasizing Hospital das Clínicas “bundles” for the control of the pandemic novel influenza A (H1N1)

Epidemiology of Human Infection with the Novel Virus Influenza A (H1H1) in the Hospital das Clínicas, São Paulo, Brazil – June–September 2009

The pandemic novel influenza A (H1N1) infection was considered widespread in Brazil on July 16, 2009. Since then, 46,810 cases of acute respiratory syndrome have been reported in Brazil, most of them concentrated in São Paulo. Through September 16, we have confirmed 9,249 cases of novel influenza A H1N1in Brazil, including 699 deaths. The mortality rate observed in Brazil is 0.47/100,000 inhabitants and varies according to region. In this period, São Paulo registered 3733 cases (40.3% of the total) of novel influenza A (H1N1) infection and 327 deaths, reflecting a mortality rate of 0.79/100,000 inhabitants

Isogeometric analysis for fluid shear stress in cancer cells

Este trabalho foi financiado pelo Concurso Anual para Projetos de Investigação, Desenvolvimento, Inovação e Criação Artística (IDI&CA) 2018 do Instituto Politécnico de Lisboa. Código de referência IPL/2018/IGACFC_ISELThe microenvironment of the tumor is a key factor regulating tumor cell invasion and metastasis. The effects of physical factors in tumorigenesis is unclear. Shear stress, induced by liquid flow, plays a key role in proliferation, apoptosis, invasion, and metastasis of tumor cells. The mathematical models have the potential to elucidate the metastatic behavior of the cells’ membrane exposed to these microenvironment forces. Due to the shape configuration of the cancer cells, Non-uniform Rational B-splines (NURBS) lines are very adequate to define its geometric model. The Isogeometric Analysis allows a simplified transition of exact CAD models into the analysis avoiding the geometrical discontinuities of the traditional Galerkin traditional techniques. In this work, we use an isogeometric analysis to model the fluid-generated forces that tumor cells are exposed to in the vascular and tumor microenvironments, in the metastatic process. Using information provided by experimental tests in vitro, we present a suite of numerical experiments which indicate, for standard configurations, the metastatic behavior of cells exposed to such forces. The focus of this paper is strictly on geometrical sensitivities to the shear stress’ exhibition for the cell membrane, this being its innovation.info:eu-repo/semantics/publishedVersio

Anti-SARS-CoV-2 inactivated vaccine in patients with ANCA-associated vasculitis: Immunogenicity, safety, antibody decay and the booster dose

Objective: To evaluate inactivated CoronaVac prime vaccination, antibody decay, booster dose, and safety in ANCA-Associated Vasculitis (AAV) patients. Methods: Fifty-three AAV patients and 106 Controls (CG) received CoronaVac on days: D0 (first dose), D28(second dose), and D210 (booster dose, 32 AAV: 32 CG). The primary outcome was immunogenicity after the second vaccine dose (day 69) assessed by Seroconversion Rates (SC) of anti-SARS-CoV-2 S1/S2 IgG and Neutralizing Antibodies (NAb). Secondary outcomes were safety, immunogenicity (D28/D240), 6-months antibody decay (D210) and the booster dose response (D240). Results: At D69 SC (65.1% vs. 96.8%, p&nbsp;=&nbsp;0.0001), GMT (21.3&nbsp;UA/mL vs. 67.7&nbsp;UA/mL, p&nbsp;&lt;&nbsp;0.001) and NAb- positivity (53.7% vs. 80.6%, p&nbsp;=&nbsp;0.001) were moderate but lower in naïve-AAV patients than CG. Patients without SC used more often IS (93.3% vs. 53.3%, p&nbsp;=&nbsp;0.015), mycophenolate mofetil (20% vs. 0%, p&nbsp;=&nbsp;0.037) and prednisone (60.0% vs. 28.6%, p&nbsp;=&nbsp;0.057) than seroconverted. NAb negativity in AAV patients was associated with prednisone treatment (57.9% vs. 18.2%, p&nbsp;=&nbsp;0.015) and IS (84.2% vs. 55.0%, p&nbsp;=&nbsp;0.046). Logistic regression analysis models showed that only prednisone was associated with lower seroconversion (OR&nbsp;=&nbsp;0.2, 0,95% CI 0.05‒0.86, p&nbsp;=&nbsp;0.030) and with lower NAb positivity (OR&nbsp;=&nbsp;0.2, 0,95% CI 0.05‒0.88, p&nbsp;=&nbsp;0.034). After six months (D69‒D210) a decrease in IgG positivity occurred in 32 AAV patients (15.7%, p&nbsp;=&nbsp;0.074) and 32 CG (18.7%, p&nbsp;=&nbsp;0.041). For the NAb positivity, the 6-month decrease was not significant (p&nbsp;=&nbsp;0.114) whereas a major reduction occurred for CG (p&nbsp;&lt;&nbsp;0.001). A booster dose (D240) resulted in an increment in IgG-positivity (21.9%, p&nbsp;=&nbsp;0.023) and NAb-positivity (34.4%, p&nbsp;=&nbsp;0.006) in AAV patients. No moderate/severe adverse events attributable to the vaccine were observed. Conclusion: This study provides novel data on the excellent safety and moderate immunogenicity of CoronaVac in AAV patients. A six-month mild antibody waning was observed with a good response to the booster dose, although levels remained lower than CG (CoronavRheum-NCT04754698)

PReS-FINAL-2177: Safety and lack of autoantibody production following influenza H1N1 vaccination in patients with juvenile idiopathic arthritis (JIA)

Introduction Vaccination is an effective tool against several infectious agents including influenza. In 2010, the Advisory Committee on Immunization Practices (ACIP) recommended influenza A H1N1/2009 immunization for high risk groups, including juvenile idiopathic arthritis (JIA) patients and more recently the EULAR task force reinforced the importance of vaccination in immunosuppressed pediatric rheumatologic patients. We have recently shown that Influenza A H1N1/2009 vaccination generated protective antibody production with short-term safety profile among 93 JIA patients, but the possible impact of the vaccine in autoimmune response in JIA have not been studied. Therefore, we aimed to assess the production of some autoantibodies generated following influenza H1N1 vaccination in JIA patients. Objectives To assess the autoimmune response and H1N1 serology following influenza H1N1 vaccination in patients with JIA. Methods Cepa A/California/7/2009 (NYMC X-179A) anti-H1N1 was used to vaccinate JIA patients: 1 dose of immunization was given to all participants and those <9yrs of age received a second booster 3 weeks apart. Sera were analyzed before and 3 weeks following complete vaccination. Serology against H1N1 virus was performed by hemagglutination inhibition antibody assay, rheumatoid factor (RF) by latex fixation test, antinuclear antibodies (ANA) by IIF, IgM and IgG anticardiolipin (aCL) by ELISA.Results Among 98 JIA patients that were vaccinated, 58 sera were available for this study. Mean age of 58 JIA patients was 23.9 ± 9.5 yrs, 38 were females and 20 males with mean disease duration of 14.7 ± 10.1 yrs. JIA subtypes were: 33 (57%) poliarticular, 10 (17%) oligoarticular, 6 (10%) systemic and 9 (16%) other. Sixteen patients were off drugs while 42 (72%) were under different pharmacotherapy: 32 (55%) were on 1 DMARD/IS, 10 (17%) on 2 DMARDs/IS, 19 (33%) antimalarials, 29 (50%) MTX, 8(14%) sulfasalazine, 6 (10%) anti-TNFs, 4 (7%) abatacept; no patient was using prednisone >0.5 mg/kg/d. Seroprotection rates against H1N1 influenza increased from 23 to 83% and seroconversion rates were achieved in 78% JIA. Prior to vaccination, 31(53.4%) JIA patients were ANA+, 6(10.3%) RF+, and 4 (7%) IgM + IgG aCL+. After complete H1N1 vaccination, positivity for ANA remained the same whereas 1 patient became negative for IgG aCL, and another for RF, IgM and IgG aCL. One (1.7%) patient turned low titer IgG aCL+. Conclusion Vaccination of JIA patients against pandemic influenza A (H1N1) generated successful protective antibody production without the induction of autoantibody production, except for 1 patient that became positive for low titer IgG aCL, supporting its safety

Physical activity: a strategy to improve antibody response to a SARS-CoV-2 vaccine booster dose in patients with autoimmune rheumatic diseases.

Physical activity associates with improved immunogenicity following a 2-dose schedule of CoronaVac (Sinovac's inactivated SARS-CoV-2 vaccine) in patients with autoimmune rheumatic diseases (ARD). This study evaluates whether physical activity impacts vaccine-induced antibody responses to a booster dose in this population. This was a phase-4 trial conducted in Sao Paulo, Brazil. Patients with ARD underwent a 3-dose schedule of CoronaVac. One month after the booster, we assessed seroconversion rates of anti-SARS-CoV-2 S1/S2 IgG, geometric mean titers of anti-S1/S2 IgG, frequency of positive neutralizing antibodies, and neutralizing activity. Physical activity was assessed through questionnaire. Physically active (n = 362) and inactive (n = 278) patients were comparable for most characteristics; however, physically active patients were younger (P<.01) and had a lower frequency of chronic inflammatory arthritis (P<.01). Adjusted models showed that physically active patients had -2 times odds of seroconversion rates (OR: 2.09; 95% confidence interval, 1.22 to 3.61), -22% greater geometric mean titers of anti-S1/S2 IgG (22.09%; 95% confidence interval, 3.91 to 65.60), and -7% greater neutralizing activity (6.76%; 95% confidence interval, 2.80 to 10.72) than inactive patients. Patients with ARD who are physically active have greater odds of experiencing better immunogenicity to a booster dose of CoronaVac. These results support the recommendation of physical activity to improve vaccination responses, particularly for immunocompromised individuals