O marcapasso definitivo como alternativa terapêutica na doença aterosclerótica coronariana com bloqueio AV total e síncope. Apresentaçao de caso

Homem com 52 anos de idade, portador de diabetes mellitus, hipertensao arterial sistêmica e doença aterosclerótica coronariana. Apresentava episódios de síncope precedidos por angina, durante os quais o eletrocardiograma mostrava ritmo sinusal e bloqueio AV total, com corrente de lesao subepicárdica. A cineangiocoronariografia revelou lesoes ateroscleróticas significativas nas três artérias coronárias. A terapêutica proposta foi a cirurgia de revascularizaçao do miocárdio, recusada pelo paciente. As opçoes farmacológicas foram exploradas sem sucesso. O implante de marca passo definitivo tipo VVI foi realizado como a única e razoável opçao terapêutica. No seguimento de um ano o paciente nao mais apresentou síncopes

A induçao de fibrilaçao atrial nao sustentada pré-implante constitui-se em critério para a nao utilizaçao da estimulaçao atrial definitiva?

Este trabalho visa correlacionar a incidência de fibrilaçao atrial (FA) com os critérios para escolha do modo de estimulaçao cardíaca definitiva. Foi realizado um estudo prospectivo de 44 pacientes consecutivos, submetidos a implante de marcapasso com a estimulaçao atrial definitiva (EAD). As indicaçoes para o implante foram: disfunçao do nó sinusal em 20 pacientes, BAV 3º grau em 11 pacientes, BAV de 2º grau em 7 pacientes, taquicardia paroxística supra-ventricular em 3 pacientes, hipersensibilidade do seio carotídeo em 2 pacientes e síncope vaso-vagal em 1 paciente. O modo de estimulaçao utilizado foi AAI (47,7%) e DDD (48,7%) e, em todos os casos, a estimulaçao foi feita com cabo-eletrodo de fixaçao ativa. O tempo médio de seguimento foi de 47,8 meses. Antes do implante do marcapasso os pacientes foram submetidos a testes de avaliaçao do sistema juncional AV (determinaçao do ponto de Wenckebach) e estabilidade atrial, com estimulaçao atrial transesofágica ou intra-cavitária, sendo selecionados para implante com EAD apenas apacientes que apresentaram fibrilaçao atrial nao sustentada (FANS) ou átrio estável. Dos 44 pacientes estudados, 4 apresentaram FANS durante os testes. Destes, 1 paciente desenvolveu FA crônica, tornando desnecessária a EAD, e outro apresentou episódios repetidos de FA, revertidos ao ritmo sinusal com amiodarona. Os outros 2 pacientes ainda estao em seguimento sem apresentar fibrilaçao atrial. Considerase que: 1 - o marcapasso com EAD associa-se a uma baixa incidência de FA no pós-operatório; 2 - a necessidade de alterar o modo de estimulaçao é mínima quando sao observados os resultados dos testes pré-operatórios; 3 - a induçao da FANS no pré-operatório parece indicar que o paciente irá desenvolver FA durante a evoluçao, o que nao impede que se proceda a EAD, mesmo que por um período de tempo limitado

Safety and efficacy of factor IX gene transfer to skeletal muscle in murine and canine hemophilia B models by adeno-associated viral vector serotype 1

Adeno-associated viral (AAV) vectors (serotype 2) efficiently transduce skeletal muscle, and have been used as gene delivery vehicles for hemophilia B and for muscular dystrophies in experimental animals and humans. Recent reports suggest that AAV vectors based on serotypes 1, 5, and 7 transduce murine skeletal muscle much more efficiently than AAV-2, with reported increases in expression ranging from 2-fold to 1000-fold. We sought to determine whether this increased efficacy could be observed in species other than mice. In immunodeficient mice we saw 10- to 20-fold higher levels of human factor IX (hF.IX) expression at a range of doses, and in hemophilic dogs we observed approximately 50-fold higher levels of expression. The increase in transgene expression was due partly to higher gene copy number and a larger number of cells transduced at each injection site. In all immunocompetent animals injected withAAV-1, inhibitory antibodies to F.IX developed, but in immunocompetent mice treated with high doses of vector, inhibitory antibodies eventually disappeared. These studies emphasize that the increased efficacy of AAV-1 vectors carries a risk of inhibitor formation, and that further studies will be required to define doses and treatment regimens that result in tolerance rather than immunity to F.IX

Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length

Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) 350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.Peer reviewe

A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways

Measuring routine childhood vaccination coverage in 204 countries and territories, 1980-2019 : a systematic analysis for the Global Burden of Disease Study 2020, Release 1

Background Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time. Methods For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dosespecific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in countryreported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development. Findings By 2019, global coverage of third-dose DTP (DTP3; 81.6% [95% uncertainty interval 80.4-82 .7]) more than doubled from levels estimated in 1980 (39.9% [37.5-42.1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38.5% [35.4-41.3] in 1980 to 83.6% [82.3-84.8] in 2019). Third- dose polio vaccine (Pol3) coverage also increased, from 42.6% (41.4-44.1) in 1980 to 79.8% (78.4-81.1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56.8 million (52.6-60. 9) to 14.5 million (13.4-15.9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019. Interpretation After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe