Abordagem da artroplastia total do joelho no Brasil: estudo transversal

CONTEXT AND OBJECTIVE: Total knee arthroplasty (TKA) has evolved particularly since the 1970s, with improvements in implants and surgical instruments, and has thus become an effective intervention for treating knee arthrosis. Many studies have presented rates of satisfactory clinical and radiological results greater than 90%, from follow-ups of over ten years. Nevertheless, despite scientific evidence showing the efficacy of TKA, the approaches taken present controversies in certain respects. The objective of this study was to evaluate how the Brazilian orthopedists deal with TKA, with investigation of the main aspects of this procedure. DESIGN AND SETTING: Cross-sectional survey conducted during the 39th Brazilian Congress of Orthopedics and Traumatology, in São Paulo, Brazil, in November 2007. METHODS: We applied a questionnaire to orthopedists registered at the congress. The questionnaire was randomly distributed and participation was voluntary; 858 completed questionnaires were included in the analysis. RESULTS: Most of the Brazilian orthopedists were members of SBOT and worked in the southeastern region. They used imported cemented implants through an anterior access route centered on the patella, with replacement of the joint surface of the patella and preservation of the posterior cruciate ligament. They did not have experience with simultaneous bilateral TKA. Postoperatively, they used antibiotics and suction drains for 48 hours. There was no consensus regarding prophylaxis for venous thromboembolism or the frequency of the main complications. CONCLUSION: The majority of Brazilian orthopedists work in the southeastern region of the country and agree about the main aspects of the approaches towards TKA.CONTEXTO E OBJETIVO: A artroplastia total do joelho (ATJ) evoluiu sobremaneira desde os anos 70, com melhora dos implantes e do instrumental cirúrgico, tornando-se uma intervenção efetiva para o tratamento da artrose do joelho. Muitos estudos apresentam resultados clínicos e radiológicos satisfatórios superiores a 90% no acompanhamento acima de 10 anos. Apesar das evidências científicas sobre sua eficácia da ATJ, a sua abordagem apresenta controvérsias em alguns aspectos. O objetivo do estudo foi avaliar como o ortopedista brasileiro aborda a ATJ e os principais aspectos técnicos na realização deste procedimento. TIPO DE ESTUDO E LOCAL: Estudo transversal, realizado durante o 39º Congresso Brasileiro de Ortopedia e Traumatologia em São Paulo, Brasil, em novembro de 2007. MÉTODOS: Aplicamos um questionário aos ortopedistas inscritos no congresso. A distribuição foi aleatória com adesão voluntária. Foram incluídos 858 questionários para análise. RESULTADOS: A maioria dos Ortopedistas Brasileiros são membros da SBOT e atua na região sudeste. Usam o implante importado, cimentado, por via de acesso anterior centrada na patela, com substituição da superfície articular da patela e preservação do ligamento cruzado posterior e não tem experiência com a artroplastia total bilateral simultânea. No pós-operatório utilizam antibióticos e dreno de sucção por 48 horas. Não houve consenso quanto à profilaxia para tromboembolismo venoso e frequência das principais complicações. CONCLUSÃO: A maioria dos ortopedistas brasileiros trabalha na região sudeste e concorda quanto aos principais aspectos da abordagem da ATJ.Universidade Federal de São Paulo (UNIFESP) Department of Orthopedics and TraumatologyUniversidade Federal de São Paulo (UNIFESP) Department of Orthopedics and Traumatology Orthopedist and Head of the Knee GroupUNIFESP, Department of Orthopedics and TraumatologyUNIFESP, Department of Orthopedics and Traumatology Orthopedist and Head of the Knee GroupSciEL

Causal Pathways from Enteropathogens to Environmental Enteropathy: Findings from the MAL-ED Birth Cohort Study

Background Environmental enteropathy (EE), the adverse impact of frequent and numerous enteric infections on the gut resulting in a state of persistent immune activation and altered permeability, has been proposed as a key determinant of growth failure in children in low- and middle-income populations. A theory-driven systems model to critically evaluate pathways through which enteropathogens, gut permeability, and intestinal and systemic inflammation affect child growth was conducted within the framework of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) birth cohort study that included children from eight countries. Methods Non-diarrheal stool samples (N = 22,846) from 1253 children from multiple sites were evaluated for a panel of 40 enteropathogens and fecal concentrations of myeloperoxidase, alpha-1-antitrypsin, and neopterin. Among these same children, urinary lactulose:mannitol (L:M) (N = 6363) and plasma alpha-1-acid glycoprotein (AGP) (N = 2797) were also measured. The temporal sampling design was used to create a directed acyclic graph of proposed mechanistic pathways between enteropathogen detection in non-diarrheal stools, biomarkers of intestinal permeability and inflammation, systemic inflammation and change in length- and weight- for age in children 0–2 years of age. Findings Children in these populations had frequent enteric infections and high levels of both intestinal and systemic inflammation. Higher burdens of enteropathogens, especially those categorized as being enteroinvasive or causing mucosal disruption, were associated with elevated biomarker concentrations of gut and systemic inflammation and, via these associations, indirectly associated with both reduced linear and ponderal growth. Evidence for the association with reduced linear growth was stronger for systemic inflammation than for gut inflammation; the opposite was true of reduced ponderal growth. Although Giardia was associated with reduced growth, the association was not mediated by any of the biomarkers evaluated. Interpretation The large quantity of empirical evidence contributing to this analysis supports the conceptual model of EE. The effects of EE on growth faltering in young children were small, but multiple mechanistic pathways underlying the attribution of growth failure to asymptomatic enteric infections had statistical support in the analysis. The strongest evidence for EE was the association between enteropathogens and linear growth mediated through systemic inflammation

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe