Ultrasonographic assessment of enthesitis in HLA-B27 positive patients with rheumatoid arthritis, a matched case-only study

Introduction HLA-B27 has a modifier effect on the phenotype of multiple diseases, both associated and non-associated with it. Among these effects, an increased frequency of clinical enthesitis in patients with Rheumatoid Arthritis (RA) has been reported but never explored again. We aimed to replicate this study with a sensitive and quantitative assessment of enthesitis by using standardized ultrasonography (US). Methods The Madrid Sonography Enthesitis Index (MASEI) was applied to the US assessment of 41 HLA-B27 positive and 41 matched HLA-B27 negative patients with longstanding RA. Clinical characteristics including explorations aimed to evaluate spondyloarthrtitis and laboratory tests were also done. Results A significant degree of abnormalities in the entheses of the patients with RA were found, but the MASEI values, and each of its components including the Doppler signal, were similar in HLA-B27 positive and negative patients. An increase of the MASEI scores with age was identified. Differences in two clinical features were found: a lower prevalence of rheumatoid factor and a more common story of low back pain in the HLA-B27 positive patients than in the negative. The latter was accompanied by radiographic sacroiliitis in two HLA-B27 positive patients. No other differences were detected. Conclusion We have found that HLA-B27 positive patients with RA do not have more enthesitis as assessed with US than the patients lacking this HLA allele. However, HLA-B27 could be shaping the RA phenotype towards RF seronegativity and axial involvement.The study was supported by grants 10CSA918040PR from the Xunta de Galicia (http://www.sergas.e/MostrarContidos_N3_T01.aspx?IdPaxina=10142) and PI08/0744 of the Instituto de Salud Carlos III (http://www.isciii.es/) that are partially financed by the European Regional Development Fund of the European UnionS

Characteristics of the patients recruited for detailed analysis in function of the HLA-B27 subgroup.

a<p>Number with the feature/total number of patients with available information.</p>b<p>Including Etanercept, Adalimumab and Infliximab.</p

Positive power Doppler signal identifying tibial tuberosity enthesitis.

<p>The signal (in red) is detected in the tibial insertion of the patellar ligament in one of the studied patients.</p

Ultrasonographic evaluation of the entheses following the MASEI procedure.

*<p>The range between percentiles 10 and 90.</p

Representative images of features detected with US exploration.

<p>A) Example of analysis of the Achilles tendon thickness measured between the two yellow crosses in one patient, and B) Erosion detected in the superior pole of the calcaneous in a different patient.</p

Duration of post-vaccination immunity against yellow fever in adults

Submitted by Nuzia Santos ([email protected]) on 2015-06-22T17:37:43Z No. of bitstreams: 1 2014_152.pdf: 756403 bytes, checksum: c18d98237e29e19e785cf895a2a68ddc (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-06-22T17:37:52Z (GMT) No. of bitstreams: 1 2014_152.pdf: 756403 bytes, checksum: c18d98237e29e19e785cf895a2a68ddc (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-06-22T17:58:36Z (GMT) No. of bitstreams: 1 2014_152.pdf: 756403 bytes, checksum: c18d98237e29e19e785cf895a2a68ddc (MD5)Made available in DSpace on 2015-06-22T17:58:36Z (GMT). No. of bitstreams: 1 2014_152.pdf: 756403 bytes, checksum: c18d98237e29e19e785cf895a2a68ddc (MD5) Previous issue date: 2014Fundação Oswaldo Cruz. Brasilia, DF, BrasilFundação Oswaldo Cruz. Escola Nacional de Saúde Pública. Rio de Janeiro, RJ, BrazilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Biomarcadores Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicosde Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Biomarcadores. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Biomarcadores. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Imunopatologia .Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Esquistossomose. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Biomarcadores. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Biomarcadores. Belo Horizonte, MG, BrasilFood and Drug Administration Center for Biologics Evaluation and Research. Bethesda, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Fla-vivirus. Rio de JaneiroFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Fla-vivirus. Rio de JaneiroFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Fla-vivirus. Rio de JaneiroInstituto de Biologia do Exército. Rio de Janeiro, RJ, BrasilInstituto de Biologia do Exército. Rio de Janeiro, RJ, BrasilInstituto de Biologia do Exército. Rio de Janeiro, RJ, BrasilInstituto de Biologia do Exército. Rio de Janeiro, RJ, BrasilInstituto de Biologia do Exército. Rio de Janeiro, RJ, BrasilInstituto de Biologia do Exército. Rio de Janeiro, RJ, BrasilMinas Gerais. Secretaria Estadual de Saude. Belo Horizonte, MG, BrasilMinas Gerais. Secretaria Estadual de Saude. Belo Horizonte, MG, BrasilMinas Gerais. Secretaria Estadual de Saude. Belo Horizonte, MG, BrasilMinas Gerais. Secretaria Estadual de Saude. Belo Horizonte, MG, BrasilUniversidade Federal de Alfenas. Alfenas, MG, BrasilUniversidade de Brasília. Faculdade de Medicina. Brasilia, DF, BrasilFundação Oswaldo Cruz. Instituto Evandro Chagas. Ananindeua, PA, BrasilINTRODUCTION: Available scientific evidence to recommend or to advise against booster doses of yellow fever vaccine (YFV) is inconclusive. A study to estimate the seropositivity rate and geometric mean titres (GMT) of adults with varied times of vaccination was aimed to provide elements to revise the need and the timing of revaccination. METHODS: Adults from the cities of Rio de Janeiro and Alfenas located in non-endemic areas in the Southeast of Brazil, who had one dose of YFV, were tested for YF neutralising antibodies and dengue IgG. Time (in years) since vaccination was based on immunisation cards and other reliable records. RESULTS: From 2011 to 2012 we recruited 691 subjects (73% males), aged 18-83 years. Time since vaccination ranged from 30 days to 18 years. Seropositivity rates (95%C.I.) and GMT (International Units/mL; 95%C.I.) decreased with time since vaccination: 93% (88-96%), 8.8 (7.0-10.9) IU/mL for newly vaccinated; 94% (88-97), 3.0 (2.5-3.6) IU/mL after 1-4 years; 83% (74-90), 2.2 (1.7-2.8) IU/mL after 5-9 years; 76% (68-83), 1.7 (1.4-2.0) IU/mL after 10-11 years; and 85% (80-90), 2.1 (1.7-2.5) IU/mL after 12 years or more. YF seropositivity rates were not affected by previous dengue infection. CONCLUSIONS:Eventhough serological correlates of protection for yellow fever are unknown, seronegativity in vaccinated subjects may indicate primary immunisation failure, or waning of immunity to levels below the protection threshold. Immunogenicity of YFV under routine conditions of immunisation services is likely to be lower than in controlled studies. Moreover, infants and toddlers, who comprise the main target group in YF endemic regions, and populations with high HIV infection rates, respond to YFV with lower antibody levels. In those settings one booster dose, preferably sooner than currently recommended, seems to be necessary to ensure longer protection for all vaccinee

Booster dose after 10 years is recommended following 17DD-YF primary vaccination

Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiologicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiologicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Governo do Estado de Minas Gerais. Secretaria de Estado de Saúde. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiologicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiologicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiologicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Universidade Federal de Alfenas. Alfenas, MG, Brasil.Instituto de Biologia do Exercito. Rio de Janeiro, RJ, Brasil.Instituto de Biologia do Exercito. Rio de Janeiro, RJ, Brasil.Instituto de Biologia do Exercito. Rio de Janeiro, RJ, Brasil.Instituto de Biologia do Exercito. Rio de Janeiro, RJ, Brasil.Instituto de Biologia do Exercito. Rio de Janeiro, RJ, Brasil.Instituto de Biologia do Exercito. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Assessoria Clínica de Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiologicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiologicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Assessoria Clínica de Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Ministerio da Saude. Secretaria de Vigilancia em Saude. Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Brasil.Universidade de Brasília. Brasilia, DF, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.US Food and Drug Administration. Center for Biologics Evaluation and Research. Silver Spring, MD USAFundação Oswaldo Cruz. Diretoria Regional de Brasília. Brasília, DF, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Publica. Rio de Janeiro, DF, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.A single vaccination of Yellow Fever vaccines is believed to confer life-long protection. In this study, results of vaccinees who received a single dose of 17DD-YF immunization followed over 10 y challenge this premise. YF-neutralizing antibodies, subsets of memory T and B cells as well as cytokine-producing lymphocytes were evaluated in groups of adults before (NVday0) and after (PVday30-45, PVyear1-4, PVyear5-9, PVyear10-11, PVyear12-13) 17DD-YF primary vaccination. YF-neutralizing antibodies decrease significantly from PVyear1-4 to PVyear12-13 as compared to PVday30-45, and the seropositivity rates (PRNT≥2.9Log10mIU/mL) become critical (lower than 90%) beyond PVyear5-9. YF-specific memory phenotypes (effector T-cells and classical B-cells) significantly increase at PVday30-45 as compared to na've baseline. Moreover, these phenotypes tend to decrease at PVyear10-11 as compared to PVday30-45. Decreasing levels of TNF-α(+) and IFN-γ(+) produced by CD4(+) and CD8(+) T-cells along with increasing levels of IL-10(+)CD4(+)T-cells were characteristic of anti-YF response over time. Systems biology profiling represented by hierarchic networks revealed that while the na've baseline is characterized by independent micro-nets, primary vaccinees displayed an imbricate network with essential role of central and effector CD8(+) memory T-cell responses. Any putative limitations of this cross-sectional study will certainly be answered by the ongoing longitudinal population-based investigation. Overall, our data support the current Brazilian national immunization policy guidelines that recommend one booster dose 10 y after primary 17DD-YF vaccination

Clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in patients with ulcerative colitis treated with two consecutive anti-TNF agents: data from the ENEIDA registry

Background: Infliximab seems to be the most efficacious of the three available anti-TNF agents for ulcerative colitis (UC) but little is known when it is used as the second anti-TNF. Objectives: To compare the clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in UC patients. Design: Retrospective observational study. Methods: Patients from the ENEIDA registry treated consecutively with infliximab and a subcutaneous anti-TNF (or vice versa), naïve to other biological agents, were identified and grouped according to the administration route of the first anti-TNF into IVi (intravenous initially) or SCi (subcutaneous initially). Results: Overall, 473 UC patients were included (330 IVi and 143 SCi). Clinical response at week 14 was 42.7% and 48.3% in the IVi and SCi groups (non-statistically significant), respectively. Clinical remission rates at week 52 were 32.8% and 31.4% in the IVi and SCi groups (nonsignificant differences), respectively. A propensity-matched score analysis showed a higher clinical response rate at week 14 in the SCi group and higher treatment persistence in the IVi group. Regarding long-term outcomes, dose escalation and discontinuation due to the primary failure of the first anti-TNF and more severe disease activity at the beginning of the second anti-TNF were inversely associated with clinical remission. Conclusion: The use of a second anti-TNF for UC seems to be reasonable in terms of efficacy, although it is particularly reduced in the case of the primary failure of the first anti-TNF. Whether the second anti-TNF is infliximab or subcutaneous does not seem to affect efficacy