Σάββατο 17 Μαρτίου 2018
BIOIMPEDANCE: NEW APPROACH TO NON-INVASIVE DETECTION OF LIVER FIBROSIS - A PILOT STUDY
ABSTRACT BACKGROUND: Fibrosis are common structural hepatic change in patients with chronic hepatitis. Liver biopsy is the gold standard for determining the extent of liver fibrosis. Considering the technical difficulties and cost, improvements in non-invasive screening tools are greatly needed. Bioimpedance have been shown to be safe to evaluate tissue fibrosis. OBJECTIVE: To assess the utility of using monofrequential bipolar bioimpedance for the detection of severity of liver fibrosis consistent with chronic viral hepatitis C infections. METHODS: One hundred and ten patients were studied prospectively and formed two groups according to the lab tests results for the detection of HCV, ALT and AST: Group 1 Control (n=50 healthy patients with HCV negative and with ALT and AST values within the normal clinical range) and Group 2 Positive (n=60 patients positive for anti-HCV positive) which were biopsied. All patients underwent an examination with an Electro Sensor Complex, bioimpedance technology. To compare the groups 1 and 2, the ROC curves was used to determine the specificity and sensitivity of the bioimpedance to detect liver fibrosis. To identify liver fibrosis severity the Group 2 Positive was subdivided according to the liver biopsy results (Metavir fibrosis score) into: Sub Group 2A (F0-F1 n=25) - patients without or with minimal portal fibrosis and Sub Group 2B (F3-F4 n=20) patients with numerous septa/cirrhosis. A statistical analysis was conducted to analyze the bioimpedance data differences in delta of the conductance. RESULTS: From the comparison between Groups 1 and 2: 1) The delta value for conductance in the pathway representing the right foot-left hand minus left hand-right foot demonstrated a sensitivity of 85% and a specificity of 78% with a cutoff value ≤5 and P=0.0001. 2) For the comparison between Sub Group 2A (Metavir F0+F1) and Sub Group 2B (Metavir F3+F4), the neural network for the Electro Sensor Complex data demonstrated a sensitivity of 85% and a specificity of 72% with a cutoff probability >50% and P=0.001. AUCROC=0.81. CONCLUSION: Bioimpedance technology had good level sensitivity and acceptable specificity for detecting liver fibrosis using delta of the conductance. There is a potential for the use of bioimpedance technology as non-invasive approaches for screening of liver fibrosis.
RESUMO CONTEXTO: A fibrose é uma alteração hepática estrutural comum em pacientes com hepatite crônica. A biópsia hepática é o padrão ouro para determinar a extensão da fibrose hepática. Considerando as dificuldades técnicas e os custos, melhorias em ferramentas de rastreio não-invasivas são bastante necessárias. A tecnologia bioimpedância tem se mostrado ser segura para avaliar fibrose tecidual. OBJETIVO: Avaliar a utilidade do uso da bioimpedância bipolar para detectar a severidade da fibrose hepática compatível com a hepatite viral B e C. MÉTODOS: Cento e dez pacientes foram estudados, prospectivamente e dois grupos foram formados de acordo com os resultados dos testes laboratoriais para a detecção de HCV, ALT e AST: Grupo 1 Controle (n=50 pacientes saudáveis com HCV negativos e com valores de ALT e AST dentro do padrão de normalidade) e Grupo 2 Positivo (n=60 pacientes positivos para a infecção viral anti-VHC ou HBsAg positiva) que foram biopsiados. Todos os pacientes foram submetidos a um exame com o Electro Sensor Complex, que utiliza a bioimpedância bipolar. Para comparar os Grupos 1 e 2, a curva ROC foi utilizada para determinar a especificidade e sensibilidade da bioimpedância em detectar a fibrose hepática. Para identificar a severidade da fibrose hepática, o Grupo 2 Positivo foi subdividido de acordo com os resultados da biópsia (escore Metavir) em: Sub Grupo 2A (F0-F1 n=25 ) - pacientes sem ou com fibrose portal mínima e Sub Grupo 2B (F3-F4 n=20) pacientes com numerosos septos/cirrose. A análise estatística foi realizada para analisar as diferenças dos valores delta de condutância da bioimpedância. RESULTADOS: A comparação entre os Grupos 1 e 2 mostrou: 1) O valor delta de condutância na via do pé direito à mão esquerda menos o valor do delta da mão esquerda ao pé direito demonstrou uma sensibilidade de 85% e uma especificidade de 78%, com um valor de corte ≤5 e P=0,0001. 2). Na comparação entre o Sub Grupo 2A (Metavir F0+F1) e o Sub Grupo 2B (Metavir F3 + F4), a rede neural para os dados aferidos pelo Electro Sensor Complex demonstrou uma sensibilidade de 85% e uma especificidade de 72%, com um corte de probabilidade >50% P=0,001 e AUCROC=0,81. CONCLUSÃO: Bioimpedância apresentou boa sensibilidade e aceitável especificidade para a detecção da fibrose hepática utilizando o delta da condutância da bioimpedância. Existe um potencial para o uso da bioimpedância como abordagens não-invasivas para o rastreamento da fibrose hepática.
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MEASUREMENT OF CONTROLLED ATTENUATION PARAMETER: A SURROGATE MARKER OF HEPATIC STEATOSIS IN PATIENTS OF NONALCOHOLIC FATTY LIVER DISEASE ON LIFESTYLE MODIFICATION - A PROSPECTIVE FOLLOW-UP STUDY
ABSTRACT BACKGROUND: Liver biopsy is a gold standard method for hepatic steatosis assessment. However, liver biopsy is an invasive and painful procedure and can cause severe complications therefore it cannot be frequently used in case of follow-up of patients. Non-invasive assessment of steatosis and fibrosis is of growing relevance in non-alcoholic fatty liver disease (NAFLD). To evaluate hepatic steatosis, transient elastography with controlled attenuation parameter (CAP) measurement is an option now days. OBJECTIVE: Aim of this study is to evaluate role of measurement of controlled attenuation parameter, a surrogate marker of hepatic steatosis in patients of nonalcoholic fatty liver disease on lifestyle modification. METHODS: In this study, initially 37 participants were included who were followed up after 6 months with transient elastography, blood biochemical tests and anthropometric measurements. The results were analyzed by Multivariate linear regression analysis and paired samples t-test (Dependent t-test) with 95% confidence interval. Correlation is calculated by Pearson correlation coefficients. RESULTS: Mean CAP value for assessing hepatic steatosis during 1st consultation (278.57±49.13 dB/m) was significantly improved (P=0.03) after 6 months of lifestyle modification (252.91±62.02 dB/m). Only fasting blood sugar (P=0.008), weight (P=0.000), body mass index (BMI) (P=0.000) showed significant positive correlation with CAP. Only BMI (P=0.034) and weight (P=0.035) were the independent predictor of CAP value in NAFLD patients. CONCLUSION: Lifestyle modification improves the hepatic steatosis, and CAP can be used to detect the improvement of hepatic steatosis during follow-up in patients with NAFLD on lifestyle modification. There is no relation between CAP and Fibroscan score in NAFLD patients. Only BMI and weight can predict CAP value independently.
RESUMO CONTEXTO: A biópsia hepática é o método padrão-ouro para avaliação de esteatose hepática. No entanto, é um procedimento invasivo e doloroso que pode causar complicações graves e, portanto, não pode ser usado com frequência em caso de acompanhamento dos pacientes. A avaliação não invasiva de esteatose e fibrose é de crescente relevância na doença hepática gordurosa não alcoólica (DHGNA). Para avaliar a esteatose hepática, a elastografia transitória com parâmetro de atenuação controlada (PAC) é uma opção atual. OBJETIVO: O objetivo deste estudo foi de avaliar o papel da medição do PAC, um marcador substituto da esteatose hepática em pacientes da doença hepática gordurosa não alcoólica, com modificação do estilo de vida. MÉTODOS: Foram incluídos inicialmente neste estudo 37 participantes acompanhados por 6 meses com elastografia transitória, testes bioquímicos no sangue, e medidas antropométricas. Os resultados foram analisados por análise de regressão linear multivariada e emparelhado em amostras-teste t (teste t-dependente) com intervalo de confiança de 95%. A correlação foi calculada pelos coeficientes de correlação de Pearson. RESULTADOS: O valor do PAC para avaliar esteatose hepática durante a primeira consulta (278,57±49,13 dB/m) foi significativamente melhorado (P=0,03) após 6 meses de modificação do estilo de vida (252,91±62,02 dB/m). Somente a glicemia de jejum (P=0,008), o peso (valor de P=0,000), o índice de massa corporal (IMC) (P=0,000) mostraram correlação positiva significativa com PAC. Apenas o IMC (P=0,034) e o peso (P=0,035) foram o preditores independentes de valor de PAC em pacientes com DHGNA. CONCLUSÃO: A modificação do estilo de vida melhora a esteatose hepática, e o PAC pode ser usado para detectar a melhoria da esteatose hepática durante o seguimento em pacientes com DHGNA. Não existe relação entre o PAC e o escore do Fibroscan em pacientes com DHGNA. Só o IMC e o peso podem prever o valor do PAC independentemente.
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LIVER TRANSPLANTATION IN HEPATITIS DELTA: SOUTH AMERICA EXPERIENCE
ABSTRACT BACKGROUND: The Amazon region is one of the main endemic areas of hepatitis delta in the world and the only one related to the presence of genotype 3 of the delta virus. OBJECTIVE: To analyze the profile, mortality and survival of cirrhotic patients submitted to liver transplantation for chronic hepatitis delta virus and compare with those transplanted by hepatitis B virus monoinfection. METHODS: Retrospective, observational and descriptive study. From May 2002 to December 2011, 629 liver transplants were performed at the Walter Cantídio University Hospital, of which 29 patients were transplanted due to cirrhosis caused by chronic delta virus infection and 40 by hepatitis B chronic monoinfection. The variables analyzed were: age, sex, MELD score, Child-Pugh score, upper gastrointestinal bleeding and hepatocellular carcinoma occurrence before the transplantation, perioperative platelet count, mortality and survival. RESULTS: The Delta Group was younger and all came from the Brazilian Amazon Region. Group B presented a higher proportion of male patients (92.5%) compared to Group D (58.6%). The occurrence of upper gastrointestinal bleeding before transplantation, MELD score, and Child-Pugh score did not show statistical differences between groups. The occurrence of hepatocellular carcinoma and mortality were higher in the hepatitis B Group. The survival in 4 years was 95% in the Delta Group and 75% in the B Group, with a statistically significant difference (P=0.034). Patients with hepatitis delta presented more evident thrombocytopenia in the pre-transplantation and in the immediate postoperative period. CONCLUSION: The hepatitis by delta virus patients who underwent liver transplantation were predominantly male, coming from the Brazilian Amazon region and with similar liver function to the hepatitis B virus patients. They had a lower incidence of hepatocellular carcinoma, more marked perioperative thrombocytopenia levels and frequent episodes of upper gastrointestinal bleeding. Patients with hepatitis by delta virus had lower mortality and higher survival than patients with hepatitis B virus.
RESUMO CONTEXTO: A região Amazônica é uma das principais áreas endêmicas da hepatite delta no mundo e a única relacionada com a presença do genótipo 3 do vírus delta. OBJETIVO: Analisar o perfil, mortalidade e sobrevida dos pacientes cirróticos submetidos a transplante hepático por hepatite crônica pelo vírus delta e comparar com os transplantados pela monoinfecção do vírus da hepatite B. MÉTODOS: Estudo retrospectivo, observacional e descritivo. Entre maio de 2002 a dezembro de 2011, foram realizados 629 transplantes de fígado no Hospital Universitário Walter Cantídio, dos quais 29 pacientes foram transplantados por cirrose causada pela infecção crônica do vírus delta e 40 pela monoinfecção crônica da hepatite B. As variáveis analisadas foram: origem, idade, sexo, escore de MELD, classificação de Child-Pugh, ocorrência de hemorragia digestiva alta e carcinoma hepatocelular antes do transplante, número de plaquetas perioperatória, mortalidade e sobrevida. RESULTADOS: O Grupo Delta foi mais jovem e todos oriundos da região Amazônica Brasileira. O Grupo B apresentou maior proporção de pacientes do sexo masculino (92,5%) em relação ao Grupo D (58,6%). A ocorrência de hemorragia digestiva alta antes do transplante, escore de MELD e classificação de Child-Pugh não obtiveram diferenças estatísticas entre os grupos. A ocorrência de carcinoma hepatocelular e a mortalidade foram maiores no grupo com hepatite B. A sobrevida em 4 anos foi de 95% no Grupo delta e 75% no Grupo B com diferença estatisticamente significante (P=0,034). Pacientes com hepatite delta, apresentaram mais acentuada plaquetopenia no pré-transplante e no pós-operatório imediato. CONCLUSÃO: Os pacientes com hepatite por vírus delta submetidos ao transplante hepático eram predominantemente homens, vindos da região da Amazônia brasileira e com função hepática semelhante a dos pacientes com vírus da hepatite B. Apresentavam menor incidência de carcinoma hepatocelular, níveis de trombocitopenia perioperatória mais acentuados e episódios frequentes de hemorragia digestiva alta. Os pacientes com hepatite por vírus delta apresentaram menor mortalidade e maior sobrevida que os pacientes com vírus da hepatite B.
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PREOPERATIVE RISK FACTORS FOR ACUTE KIDNEY INJURY AFTER LIVER TRANSPLANTATION: RESULTS FROM A CROSS-SECTIONAL STUDY IN NORTHEAST OF BRAZIL
ABSTRACT BACKGROUND: Acute kidney injury (AKI) is a common complication in the immediate postoperative period of patients undergoing liver transplantation. OBJECTIVE: The aim of this study was to evaluate preoperative risk factors for AKI after liver transplantation. METHODS: A cross-sectional study was conducted with adults submitted to orthotopic liver transplantation at a reference hospital in Fortaleza, Northeast of Brazil, from January to December 2016. Preoperative risk factors were evaluated for AKI development in the immediate postoperative period. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. RESULTS: A total of 40 patients were included in the study. AKI was found in 85% of patients in the first 24 hours after transplantation, most of them (40%) classified in KDIGO stage 1. Preoperative data indicate that serum albumin levels were lower in the KDIGO stage 3 group compared to the non-AKI group, as well as the hematocrit levels. Direct bilirubin (DB) was higher in the KDIGO stage 3 group compared to the group without AKI, as well as alkaline phosphatase (AP) and gamma-glutamiltransferase (GGT). In a logistic regression analysis independent risk factors for AKI were increase levels of AP, GGT and DB and decrease level of serum albumin. CONCLUSION: Low levels of serum albumin, and elevated levels of DB, AP and GGT in the preoperative period are risk factors for AKI development after liver transplantation.
RESUMO CONTEXTO: Lesão renal aguda (LRA) é uma complicação comum no pós-operatório imediato do transplante hepático. OBJETIVO: O objetivo foi avaliar os fatores de risco pré-operatórios para LRA após o transplante hepático. MÉTODOS: Foi realizado estudo transversal com adultos submetidos a transplante hepático ortotópico em um hospital de referência em Fortaleza, Nordeste do Brasil, de janeiro a dezembro de 2016. Foram avaliados os fatores de risco pré-operatórios para o desenvolvimento de LRA no pós-operatório. LRA foi definida de acordo com os critérios do Kidney Disease: Improving Global Outcomes (KDIGO). RESULTADOS: Foram incluídos 40 pacientes no estudo. LRA foi encontrada em 85% dos casos nas primeiras 24 horas após o transplante, sendo a maioria deles (40%) classificados no estágio KDIGO 1. Os dados pré-operatórios indicaram que os níveis séricos de albumina eram menores nos pacientes no estágio KDIGO 3, em comparação com o grupo sem LRA, bem como os níveis de hematócrito. Os níveis de bilirrubina direta (BD) eram maiores nos pacientes no estágio KDIGO 3 em comparação ao grupo sem LRA, bem como os níveis de fosfatase alcalina (FA) e gama-glutamiltransferase (GGT). Em um modelo de regressão logística, os fatores de risco independentes para LRA foram: níveis elevados de FA, GGT e BD e níveis reduzidos de albumina. CONCLUSÃO: Níveis reduzidos de albumina sérica, e níveis elevados de BD, FA e GGT no período pré-operatório são fatores de risco para o desenvolvimento de LRA após o transplante hepático.
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IMPACT OF MICROBIOLOGICAL CHANGES ON SPONTANEOUS BACTERIAL PERITONITIS IN THREE DIFFERENT PERIODS OVER 17 YEARS
ABSTRACT BACKGROUND: Spontaneous bacterial peritonitis is a serious complication in cirrhotic patients, and changes in the microbiological characteristics reported in the last years are impacting the choice of antibiotic used for treatment. OBJECTIVE: The aim of the present study is to evaluate the changes in the epidemiology and bacterial resistance of the germs causing spontaneous bacterial peritonitis over three different periods over 17 years. METHODS: All cirrhotic patients with spontaneous bacterial peritonitis and positive culture of ascites fluid were retrospectively studied in a reference Hospital in Southern Brazil. Three periods were ramdomly evaluated: 1997-1998, 2002-2003 and 2014-2015. The most frequent infecting organisms and the sensitivity in vitro to antibiotics were registered. RESULTS: In the first period (1997-1998) there were 33 cases, the most common were: E. coli in 13 (36.11%), Staphylococcus coagulase-negative in 6 (16.66%), K. pneumoniae in 5 (13.88%), S. aureus in 4 (11.11%) and S. faecalis in 3 (8.33%). In the second period (2002-2003), there were 43 cases, the most frequent were: Staphylococus coagulase-negative in 16 (35.55%), S. aureus in 8 (17.77%), E. coli in 7 (15.55%) and K. pneumoniae in 3 (6.66%). In the third period (2014-2015) there were 58 cases (seven with two bacteria), the most frequent were: E. coli in 15 (23.1%), S. viridans in 12 (18.5%), K. pneumoniae in 10 (15.4%) and E. faecium 5 (7.7%). No one was using antibiotic prophylaxis. Considering all staphylococci, the prevalence increased to rates of the order of 50% in the second period, with a reduction in the third period evaluated. Likewise, the prevalence of resistant E. coli increased, reaching 14%. CONCLUSION: There was a modification of the bacterial population causing spontaneous bacterial peritonitis, with high frequency of gram-positive organisms, as well as an increase in the resistance to the traditionally recommended antibiotics. This study suggests a probable imminent inclusion of a drug against gram-positive organisms in the empiric treatment of spontaneous bacterial peritonitis.
RESUMO CONTEXTO: A peritonite bacteriana espontânea é uma complicação séria em pacientes cirróticos e as alterações nas características microbiológicas relatadas nos últimos anos podem afetar a escolha do antibiótico utilizado no tratamento. OBJETIVO: Os objetivos do presente estudo são avaliar as mudanças na epidemiologia e perfil de resistência bacteriana dos germes causadores de peritonite bacteriana espontânea em três períodos diferentes ao longo de 17 anos. MÉTODOS: Todos os pacientes cirróticos com peritonite bacteriana espontânea e cultura positiva de fluido ascítico foram estudados retrospectivamente em um hospital de referência no Sul do Brasil. Foram avaliados três diferentes períodos selecionados de forma randômica: 1997-1998, 2002-2003 e 2014-2015. Os organismos infecciosos mais frequentes e a sensibilidade in vitro a antibióticos foram registados. RESULTADOS: No primeiro período (1997-1998) houve 33 casos; os mais comuns foram: E. coli em 13 (36,1%), Staphylococcus coagulase-negativo em 6 (16,7%), K. pneumoniae em 5 (13,9%), S. aureus em 4 (11,1%) e S. faecalis em 3 (8,3%). No segundo período (2002-2003), houve 43 casos, os mais frequentes foram: Staphylococus coagulase-negativo em 16 (35,5%), S. aureus em 8 (17,8%), E. coli em 7 (15,5%) e K. pneumoniae em 3 (6,7%). No terceiro período (2014-2015), houve 58 casos (sete com duas bactérias), os mais frequentes foram: E. coli em 15 (23,1%), S. viridans em 12 (18,5%), K. pneumoniae em 10 (15,4%) e E. faecium 5 (7,7%). Nenhum paciente estava usando profilaxia antibiótica. Quando considerados todos os estafilococos, a prevalência aumentou para taxas da ordem de 50% no segundo período, apresentando redução no terceiro período avaliado. Do mesmo modo, a prevalência de E coli resistente aumentou, chegando a 14%. CONCLUSÃO: Houve modificação da população bacteriana causadora de peritonite bacteriana espontânea, com alta frequência de organismos gram-positivos, bem como aumento da resistência aos antibióticos tradicionalmente recomendados. Este estudo sugere uma provável inclusão iminente de um medicamento contra organismos gram-positivos no tratamento empírico da peritonite bacteriana espontânea.
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PROTON PUMP INHIBITORS INCREASE THE OVERALL RISK OF DEVELOPING BACTERIAL INFECTIONS IN PATIENTS WITH CIRRHOSIS
ABSTRACT BACKGROUND: Acid suppression has been associated with adverse events; such as, enteric infections. Proton pump inhibitors (PPI) are frequently prescribed in patients with cirrhosis, but is unclear if PPI are associated with the development of bacterial infections in these patients. OBJECTIVE: To assess the impact of PPI intake on the development of bacterial, viral and fungal infections in patients with cirrhosis. METHODS: An observational, retrospective, historic cohort study. The exposed cohort included patients with cirrhosis with chronic use of PPI. The non-exposed cohort had not been using PPI. The follow-up period was 3 years, searching in the medical records for any events of bacterial infection confirmed by bacteriological culture. RESULTS: One hundred and thirteen patients met the selection criteria, 44 (39%) had chronic use of PPI; of them, 28 (63.6%) patients had not a clear clinical indication to justify the prescription of PPI. Twenty four (21.2%) patients developed bacterial infections during the follow-up period. In the univariate analysis, decompensated cirrhosis (Child B/C), presence of ascites, history of variceal bleeding, and chronic consumption of PPI were risk factors related to the development of infections. But, in the adjusted multivariate analysis only the chronic use of PPI was associated with development of infections (RR=3.6; 95% CI=1.1-12.3; P=0.04). CONCLUSION: There is an over-prescription of PPI without a justified clinical indication. The long-term consumption of PPI in patients with cirrhosis is associated with the development of bacterial infections; therefore these drugs must be carefully prescribed in this specific population.
RESUMO CONTEXTO: A supressão de ácido tem sido associada a efeitos adversos, tais como infecções entéricas. Inibidores da bomba protônica são frequentemente prescritos em pacientes com cirrose, mas não está claro se o inibidor de bomba de próton (IBP) está associado ao desenvolvimento de infecções bacterianas nesses pacientes. OBJETIVO: Avaliar o impacto da ingestão de IBP no desenvolvimento de infecção bacteriana, viral e fúngica em pacientes com cirrose. MÉTODOS: Foi realizado estudo de coorte observacional, retrospectivo, histórico. A coorte exposta incluiu pacientes com cirrose e com uso crônico de IBP. A coorte de não expostos não estava usando IBP. O período de seguimento foi de 3 anos, procurando-se nos registros médicos qualquer evento de infecção bacteriana, confirmada pela cultura bacteriológica. RESULTADOS: Cento e treze pacientes preencheram os critérios de seleção, 44 (39%) pacientes faziam uso crônico de IBP; deles, 28 (63,6%) não tinham uma indicação clínica clara para justificar a prescrição de IBP. Vinte e quatro (21,2%) pacientes desenvolveram infecções bacterianas durante o período de seguimento. Na análise univariada, cirrose descompensada (Child B/C), presença de ascite, história de hemorragia varicosa e consumo crônico de IBP foram fatores de risco relacionados ao desenvolvimento de infecções. Porém, na análise multivariada ajustada, somente o uso crônico de IBP foi associado ao desenvolvimento de infecções (RR=3,6; 95% CI = 1.1-12.3; P=0,04). CONCLUSÃO: Há uma prescrição excessiva de PPI sem uma indicação clínica justificada. O consumo de longo prazo do IBP em pacientes com cirrose é associado ao desenvolvimento de infecções bacterianas. Portanto, essas drogas devem ser cuidadosamente prescritas nesta população específica.
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ASSOCIATION OF INTERLEUKIN-10 -1082 A/G (RS1800896) POLYMORPHISM WITH SUSCEPTIBILITY TO GASTRIC CANCER: META-ANALYSIS OF 6,101 CASES AND 8,557 CONTROLS
ABSTRACT BACKGROUND: The promoter -1082 A/G (rs1800896) polymorphism of Interleukin-10 (IL-10) gene have been widely reported and considered to have a significant role on gastric cancer risk, but the results are inconsistent. OBJECTIVE: To clarify the association, we conducted a meta-analysis to investigate the associations IL-10 -1082 A/G polymorphism with gastric cancer. METHODS: Eligible articles were identified by searching databases including PubMed, Web of Science, and Google Scholar up to August 03, 2017. Odds ratios (OR) with corresponding 95% confidence intervals (CIs) were used to assess the association. RESULTS: A total of 30 case-control studies with 6,101 cases and 8,557 controls were included in this meta-analysis. Overall, a significant association between IL-10 -1082 A/G polymorphism and gastric cancer risk was observed under the allele model (G vs A: OR=1.305, 95% CI=1.076-1.584; P=0.007), heterozygote model and (GA vs AA: OR=1.252, 95% CI=1.252-1.054; P=0.011) and dominant model (GG+GA vs AA: OR=1.264, 95% CI=1.053-1.516; P=0.012). In the subgroup analysis by ethnicity, increased gastric cancer risk were found in Asians under the allele model (G vs A: OR=1.520, 95% CI=1.172-1.973; P=0.002), homozygote model (GG+GA vs AA: OR=1.571, 95% CI=1.023-2.414; P= 0.039), heterozygote model (GA vs AA: OR=1.465, 95% CI=1.192-1.801; P≤0.001) and dominant model (GG+GA vs AA: OR=1.448, 95% CI=1.152-1.821; P=0.002), but not among Caucasian and Latinos populations. CONCLUSION: These results suggested that the IL-10 -1082 A/G (rs1800896) polymorphism might contribute to the gastric cancer susceptibility, especially among Asians.
RESUMO CONTEXTO: O promotor-1082 A/polimorfismo G (rs1800896) do gene da interleucina-10 (IL-10) é amplamente relatado e considerado por ter um papel significativo no risco de câncer gástrico, porém os resultados são inconsistentes. OBJETIVO: Para esclarecer melhor esta associação, realizou-se uma meta-análise para investigar as associações de IL-10-1082 A/polimorfismo G com câncer gástrico. MÉTODOS: Artigos elegíveis foram identificados através de pesquisa de bases de dados PubMed, Web of Science e Google Scholar até 3 de agosto de 2017. Razões de possibilidades (OR) com intervalo de confiança de 95% correspondente (CIs) foram usados para avaliar a associação. RESULTADOS: Um total de 30 estudos de caso-controle, 6.101 casos e com 8.557 controles foram incluídos nesta meta-análise. Em geral, uma associação significativa entre IL-10-1082 A/G polimorfismo e risco de câncer gástrico foi observada sob o modelo de alelo (G vs A: OR=1.305, 95% CI=1.076-1.584; P=0.007), no modelo heterozigoto (GA vs AA: OR=1.252, 95% CI=1.252-1.054; P=0.011) e modelo dominante (GG+GA vs AA: OR=1.264, 95% CI=1.053-1.516; P=0.012). Na análise de subgrupo pela etnia, foi encontrado risco aumentado de câncer gástrico em asiáticos sob o modelo de alelo (G vs A: OR=1.520, 95% CI=1.172-1.973; P=0.002), modelo heterozigoto (GG+GA vs AA: OR=1.571, 95% CI=1.023-2.414; P= 0.039), e modelo dominante (GG+GA vs AA: OR=1.448, 95% CI=1.152-1.821; P=0.002), mas não entre a população caucasiana e latina. CONCLUSÃO: Estes resultados sugeriram que a IL-10-1082 A/polimorfismo G (rs1800896) pode contribuir para a suscetibilidade de câncer gástrico, especialmente entre os asiáticos.
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SERUM ELECTROLYTES AND OUTCOME IN PATIENTS UNDERGOING ENDOSCOPIC GASTROSTOMY
ABSTRACT BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a gold standard for long term enteral feeding. Neurologic dysphagia and head/neck cancer are the most common indications for PEG as they can lead to protein-energy malnutrition and serum electrolyte abnormalities, with potential negative impact on metabolic balance. Refeeding syndrome may also be related with severe electrolyte changes in PEG-fed patients and contribute to poor prognosis. OBJECTIVE: This study aims to evaluate the changes in serum concentrations of the main electrolytes and its possible association with the outcome. METHODS: Retrospective study of patients followed in our Artificial Nutrition Clinic, submitted to PEG from 2010 to 2016, having head/neck cancer or neurologic dysphagia, who died under PEG feeding. Serum electrolytes (sodium, potassium, chlorine, magnesium, calcium and phosphorus) were evaluated immediately before the gastrostomy procedure. Survival after PEG until death was recorded in months. RESULTS: We evaluated 101 patients, 59 with electrolyte alterations at the moment of the gastrostomy. Sodium was altered in 32 (31.7%), magnesium in 21 (20.8%), chlorine in 21 (20.8%), potassium in 14 (13.8%), calcium in 11 (10.9 %) and phosphorus in 11 (10.9%). The survival of patients with low sodium (<135 mmol/L) was significantly lower when compared to patients with normal/high values, 2.76 months vs 7.80 months, respectively (P=0.007). CONCLUSION: Changes in serum electrolytes of patients undergoing PEG were very common. More than half showed at least one abnormality, at the time of the procedure. The most frequent was hyponatremia, which was associated with significantly shorter survival, probably reflecting severe systemic metabolic distress.
RESUMO CONTEXTO: A gastrostomia endoscópica percutânea (PEG) é a via de eleição preferencial para a nutrição entérica de longa duração. A disfagia neurológica e as neoplasias cervico-faciais constituem as principais indicações para PEG por poderem conduzir a desnutrição energético-proteica e alterações hidroeletrolíticas, com potencial impacto negativo no equilíbrio metabólico. A síndrome de realimentação pode também estar associada a alterações hidroeletrolíticas graves em doentes alimentados por PEG e contribuir para um mau prognóstico. OBJETIVO: Avaliar as alterações das concentrações séricas dos principais eletrólitos e a eventual associação entre os valores séricos alterados e o prognóstico dos doentes gastrostomizados. Métodos - Estudo retrospetivo realizado em doentes seguidos na Consulta de Nutrição Artificial do Hospital Garcia de Orta, propostos e submetidos a PEG, de 2010 a 2016 e que faleceram sob nutrição por PEG. Consideraram-se os valores séricos dos iões em estudo avaliados imediatamente antes do procedimento endoscópico de gastrostomia, obtidos por consulta do processo clínico. A sobrevida, após a realização da PEG até à morte foi registrada em meses. RESULTADOS: Avaliaram-se 101 doentes. A sobrevida média pós-gastrostomia foi 6,55 meses. Destes, 59 apresentaram alterações de alguns iões no momento da realização da PEG. O sódio estava alterado em 31 (30,6%), magnésio em 20 (19,8%), cloro em 19 (18,8%), potássio em 14 (13,8%), cálcio em 10 (9,9%) e o fósforo em 9 (8,9%). Quando comparada a sobrevida dos doentes com valores de sódio baixo (<135 mmol/L) com a dos doentes com valores normais/elevados, esta foi 2,76 meses vs 7,80 meses, respectivamente (P=0,007). CONCLUSÃO: As alterações dos eletrólitos séricos nos doentes submetidos a PEG foram muito frequentes, com mais de metade dos doentes a apresentarem pelo menos uma alteração aquando da realização do procedimento. A alteração mais frequente foi a hiponatrémia, associando-se a pior prognóstico com sobrevida significativamente mais curta, refletindo provavelmente um grave compromisso metabólico sistêmico.
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THE USE OF THE FORCEPS BIOPSY AS AN AUXILIARY TECHNIQUE FOR THE VISUALIZATION OF THE MAJOR DUODENAL PAPILLA USING THE FOWARD-VIEWING UPPER ENDOSCOPY
ABSTRACT BACKGROUND: - Conventional esophagogastroduodenoscopy is the best method for evaluation of the upper gastrointestinal tract, but it has limitations for the identification of the major duodenal papilla, even after the use of the straightening maneuver. Side-viewing duodenoscope is recommended for optimal examination of major duodenal papilla in patients at high risk for lesions in this region. OBJECTIVE: To evaluate the use of the biopsy forceps during conventional esophagogastroduodenoscopy as an additional tool to the straightening maneuver, in the evaluation of the major duodenal papilla. METHODS: A total of 671 patients were studied between 2013 and 2015, with active major duodenal papilla search in three endoscope steps: not straightened, straightened and use of the biopsy forceps after straightening. In all of them it was recorded whether: major duodenal papilla was fully visualized (position A), partially visualized (position B) or not visualized (position C). If major duodenal papilla was not fully visualized, patients continued to the next step. RESULTS: A total of 341 were female (50.8%) with mean age of 49 years. Of the 671 patients, 324 (48.3%) major duodenal papilla was identified in position A, 112 (16.7%) in position B and 235 (35%) in position C. In the 347 patients who underwent the straightening maneuver, position A was found in 186 (53.6%), position B in 51 (14.7%) and position C in 110 (31.7%). Of the 161 remaining patients and after biopsy forceps use, position A was seen in 94 (58.4%), position B in 14 (8.7%) and position C in 53 (32.9%). The overall rate of complete visualization of major duodenal papilla was 90%. CONCLUSION: The use of the biopsy forceps significantly increased the total major duodenal papilla visualization rate by 14%, reaching 604/671 (90%) of the patients (P<0.01) and it can be easily incorporated into the routine endoscopic examination of the upper gastrointestinal tract.
RESUMO CONTEXTO: Esofagogastroduodenoscopia convencional é o melhor método para avaliação do trato gastrointestinal superior, mas apresenta limitações para identificação da papila duodenal maior, mesmo após emprego da manobra de retificação. Exame completo da papila duodenal maior está indicado para pacientes de alto risco para adenocarcinoma da papila duodenal maior. OBJETIVO: Avaliar a utilização da pinça de biópsia durante esofagogastroduodenoscopia convencional como ferramenta adicional à manobra de retificação na avaliação da papila duodenal maior. MÉTODOS: Foram estudados 671 pacientes entre 2013-2015 com busca ativa da papila duodenal maior em três etapas: endoscópio não retificado, endoscópio retificado e uso da pinça de biópsia após retificação. Em todas se registrou: se a papila duodenal maior foi totalmente visualizada (posição A), se parcialmente visualizada (posição B) ou se não visualizada (posição C). Caso a papila duodenal maior não tenha sido completamente visualizada, o paciente foi direcionado para a etapa seguinte. RESULTADOS: Um total de 341 era do sexo feminino (50,8%) com idade média de 49 anos. Dos 671 pacientes, em 324 (48,3%) a papila duodenal maior foi identificada na posição A, 112 (16,7%) em posição B e, 235 (35%) em posição C. Dos 347 pacientes submetidos à manobra de retificação, posição A foi encontrada em 186 (53,6%), posição B em 51 (14,7%) e posição C em 110 (31,7%). Dos 161 pacientes restantes que utilizaram a pinça de biópsia, posição A foi vista em 94 (58,4%), posição B em 14 (8,7%) e posição C em 53 (32,9%). A taxa acumulativa de visualização completa da papila duodenal maior foi de 90%. CONCLUSÃO: O uso da pinça de biópsia aumentou a taxa de visualização completa da papila duodenal maior em 14%, alcançando 604/671 (90%) dos pacientes (P<0,01) avaliados e pode ser facilmente incorporada aos exames endoscópicos de rotina do trato gastrointestinal superior.
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SWALLOWING IN PATIENTS WITH LARYNGITIS
ABSTRACT BACKGROUND: Dysphagia is described as a complaint in 32% of patients with laryngitis. OBJECTIVE: The objective of this investigation was to evaluate oral and pharyngeal transit of patients with laryngitis, with the hypothesis that alteration in oral-pharyngeal bolus transit may be involved with dysphagia. METHODS: Videofluoroscopic evaluation of the swallowing of liquid, paste and solid boluses was performed in 21 patients with laryngitis, 10 of them with dysphagia, and 21 normal volunteers of the same age and sex. Two swallows of 5 mL liquid bolus, two swallows of 5 mL paste bolus and two swallows of a solid bolus were evaluated in a random sequence. The liquid bolus was 100% liquid barium sulfate and the paste bolus was prepared with 50 mL of liquid barium and 4 g of food thickener (starch and maltodextrin). The solid bolus was a soft 2.2 g cookie coated with liquid barium. Durations of oral preparation, oral transit, pharyngeal transit, pharyngeal clearance, upper esophageal sphincter opening, hyoid movement and oral-pharyngeal transit were measured. All patients performed 24-hour distal esophageal pH evaluation previous to videofluoroscopy. RESULTS: The evaluation of 24-hour distal esophageal pH showed abnormal gastroesophageal acid reflux in 10 patients. Patients showed longer oral preparation for paste bolus and a faster oral transit time for solid bolus than normal volunteers. Patients with laryngitis and dysphagia had longer preparation for paste and solid boluses, and a faster oral transit time with liquid, paste and solid boluses. CONCLUSION: A longer oral preparation for paste and solid boluses and a faster transit through the mouth are associated with dysphagia in patients with laryngitis.
RESUMO CONTEXTO: Disfagia é uma queixa presente em 32% dos pacientes com laringite. OBJETIVO: O objetivo desta investigação foi avaliar o trânsito oral e faríngeo de pacientes com laringite, com a hipótese de que a alteração no trânsito do bolo pela boca e faringe pode estar envolvida com a queixa de disfagia. MÉTODOS: A avaliação videofluoroscópica da deglutição de bolos líquido, pastoso e sólido foi realizada em 21 pacientes com laringite, 10 deles com disfagia e 21 voluntários normais da mesma idade e sexo. Duas deglutições de 5 mL de bolo líquido, duas deglutições de bolo pastoso e duas deglutições de bolo sólido foram avaliadas em sequência casual definida por sorteio. Bolo líquido foi sulfato de bário 100%, e o bolo pastoso foi preparado com 50 mL de bário líquido e 4 g de espessante alimentar (amido e maltodextrina). O bolo sólido foi 2,2 g de uma bolacha macia embebida em bário líquido. A duração da preparação oral, trânsito oral, trânsito faríngeo, depuração da faringe, abertura do esfíncter superior do esôfago, movimento do hióide e do trânsito oral-faríngeo foram medidas. Precedendo a videofluoroscopia todos pacientes realizaram exame de pHmetria de 24 horas. RESULTADOS: O registro do pH intraesofágico distal revelou resultado anormal em 10 pacientes. Pacientes com laringite apresentaram maior duração da preparação oral para bolo pastoso e um tempo de trânsito oral mais rápido para bolo sólido. Os pacientes com laringite e disfagia tiveram uma preparação oral mais longa para bolo pastoso e sólido e tempo de trânsito oral menor com bolos líquido, pastoso e sólido. CONCLUSÃO: Preparação oral mais longa para bolos pastoso e sólido e trânsito mais rápido através da boca são situações associadas com a presença de disfagia em pacientes com laringite.
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RENZI SCORE FOR OBSTRUCTED DEFECATION SYNDROME - VALIDATION OF THE PORTUGUESE VERSION ACCORDING TO THE COSMIN CHECKLIST
ABSTRACT BACKGROUND: Recently, the Obstructed Defecation Syndrome score (ODS score) was developed and validated by Renzi to assess clinical staging and to allow evaluation and comparison of the efficacy of treatment of this disorder. OBJECTIVE: Our goal is to validate the Portuguese version of Renzi ODS score, according to the Consensus based Standards for the selection of the Health Measurement Instruments (COSMIN) checklist. METHODS: Following guidelines for cross-cultural validity, Renzi ODS score was translated into the Portuguese language. Then, a group of patients and healthy controls were invited to fill in the Renzi ODS score at baseline, after 2 weeks and 3 months, respectively. We assessed internal consistency, reliability and measurement error, content and construct validity, responsiveness and interpretability. RESULTS: A total of 113 individuals (77 patients; 36 healthy controls) completed the questionnaire. Seventy and 30 patients repeated the Renzi ODS score after 2 weeks and 3 months respectively. Factor analysis confirmed the unidimensionality of the scale. Cronbach's α coefficient of 0.77 supported item's homogeneity. Weighted quadratic kappa of 0.89 established test-retest reliability. The smallest detectable change at the individual level was 2.66 and at the group level was 0.30. Renzi ODS score and the total (-0.32) and physical (-0.43) SF-36 scores correlated negatively. Patient and control's groups significantly differed (11 points). The change score of Renzi ODS score between baseline and 3 months correlated negatively with the clinical evolution (-0.86). ROC analysis showed minimal important change of 2.00 with AUC 0.97. Neither floor nor ceiling effects were observed. CONCLUSION: This work validated the Portuguese version of Renzi ODS score. We can now use this reliable, responsive, and interpretable (at the group level) tool to evaluate Portuguese ODS patients.
RESUMO CONTEXTO: Recentemente, o Score de Distúrbios Evacuatórios (SDE) foi desenvolvido e validado por Renzi para avaliação e comparação da eficácia do tratamento dos doentes com esta patologia. Objetivo - O nosso objetivo é validar uma versão portuguesa do SDE de acordo com as orientações da checklist de COSMIN. MÉTODOS: O SDE foi traduzido para o português, cumprindo as orientações para validação cultural. Indivíduos com distúrbio evacuatório e controlos saudáveis foram convidados a responder ao SDE numa fase inicial, 2 semanas e 3 meses depois, respetivamente. Foi avaliada a consistência interna, confiabilidade, erro de medição, validade de conteúdo e constructo, responsividade e interpretabilidade. RESULTADOS: Foram entrevistados 113 indivíduos (77 doentes; 36 controlos saudáveis) na fase inicial. O SDE foi aplicado novamente aos 77 doentes, 2 semanas depois, e a 30 doentes, 3 meses depois. Relativamente à consistência interna, a análise fatorial confirmou a unidimensionalidade e o coeficiente α de Cronbach foi 0,77, suportando homogeneidade dos itens. O kappa quadrático ponderado de 0,89 estabeleceu a reprodutibilidade teste-reteste. Considerando o erro de medição, a mudança mínima detectável a nível individual foi 2,66 e a nível de grupo foi 0,30. A validade do constructo foi avaliada através do coeficiente de correlação de Spearman entre o SDE e o score total (-0,32) e físico (-0,43) do SF-36. Em termos de validação clínica, verificou-se uma diferença significativa de 11 pontos entre as médias dos doentes e controlos. A responsividade foi confirmada pelo coeficiente de correlação de -0,86 entre a mudança do score e a evolução clínica, avaliados após 3 meses. Através da curva ROC, a mudança mínima importante foi 2,00 e a AUC foi 0,97. Não foram observados efeito-chão efeito-tecto. CONCLUSÃO: Este projeto permitiu validar a versão portuguesa do SDE de Renzi. É possível agora utilizar esta ferramenta na avaliação de distúrbios evacuatórios em doentes falantes de língua portuguesa.
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EVOLUTION OF MORTALITY FOR COLORECTAL CANCER IN BRAZIL AND REGIONS, BY SEX, 1996-2015
ABSTRACT BACKGROUND: Colorectal cancer is among the three most frequent neoplasms in Brazil, being a public health problem. OBJECTIVE: To describe distribution pattern of colorectal cancer mortality in Brazil and regions, according to sex, between 1996 and 2015. METHODS: Values of standardized and stratified mortality rates by sex between 1996 and 2015 were used, through polynomial regression models and joinpoint analysis. RESULTS: It was observed that, for linear trends in mortality rates, for both sexes, there is a statistically significant trend increasing in both models, with rates and trends, and higher for men than for women, respectively, 7.3% per year (R2=0.95, P<0.001) and 6.5% per year (R2=0.87, P<0.001). It is observed a difference in magnitude and behavior of trend between the regions. CONCLUSION: It is understood that it is important to know the trend of rates in order to define priority populations for early interventions that increase survival and reduce mortality.
RESUMO CONTEXTO: O câncer de cólon e reto está entre as três neoplasias mais frequentes no Brasil, sendo um problema de saúde pública. OBJETIVO: Descrever o padrão de distribuição da mortalidade por câncer de cólon e reto no Brasil e regiões, por sexo, no período de 1996 a 2015. MÉTODOS: Utilizou-se os valores de taxas de mortalidade padronizadas e estratificadas por sexo entre 1996 e 2015, através dos modelos de regressão polinomial e análise por joinpoints. RESULTADOS: Foi observado que, para as tendências lineares das taxas de mortalidade, para ambos os sexos, há tendência de aumento linear estatisticamente significativa em ambos os modelos, sendo as taxas e as tendências maiores para homens do que para mulheres, respectivamente, 7,3% ao ano (R2=0,95; P<0,001) e 6,5% ao ano (R2=0,87; P<0,001). Observa-se diferença na magnitude e comportamento da tendência entre as regiões. CONCLUSÃO: Entende-se que é importante conhecer a tendência das taxas de forma a definir populações prioritárias para intervenções precoces que aumentem a sobrevida e reduzam a mortalidade.
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DRAIN AMYLASE LEVELS MAY INDICATE GASTROJEJUNOSTOMY LEAKS AFTER ROUX-EN-Y GASTRIC BYPASS
ABSTRACT BACKGROUND: Although the incidence of leaks after Roux-en-Y gastric bypass (RYGB) significantly decreased over time, their detection still remains challenging. OBJECTIVE: This study aimed to determine the usefulness of drain amylase levels to detect leaks after RYGB. METHODS: This is a population-based study which enrolled 170 individuals who underwent RYGB. Drain amylase levels were determined on the first and fourth postoperative days. Two thresholds were evaluated: three times higher than the serum levels (parameter I) and higher than 250 IU/L (parameter II). The main outcomes evaluated were perioperative morbidity, the occurrence of leaks, 30-day readmissions and reoperations, hospital stay, and mortality. RESULTS: Considering the parameter I, high drain amylase levels were significantly associated with leaks (12.5% vs 0; P<0.00001). Considering the parameter II, high drain amylase levels were significantly associated with longer hospital stay (8±5.7 vs 4.5±1.3 days; P=0.00032), 30-day reoperations (50% vs 3%; P=0.000285), and leaks (50% vs 0; P<0.00001). The parameter I presented a sensitivity of 100% and specificity of 95.9%, whereas the parameter II presented a sensitivity of 100% and a specificity of 99.4%. CONCLUSION: The determination of drain amylase levels after RYGB was a significant indicator of leaks, hospital stay, and 30-day reoperations. This finding reinforces the importance of abdominal drainage in the RYGB within this context.
RESUMO CONTEÚDO: Embora a incidência de fistulas após o bypass gástrico em Y de Roux (BGRY) tenha diminuído significativamente com a evolução da técnica, sua detecção continua desafiadora. OBJETIVO: Determinar a acurácia dos níveis de amilase no dreno abdominal para detector fístulas após o BGYR. MÉTODOS: Este é um estudo populacional que avaliou 170 indivíduos submetidos ao BGYR. Os níveis de amilase no dreno foram determinados no primeiro e quarto dias de pós-operatório. Dois pontos de corte foram avaliados: três vezes maior que os níveis séricos (parâmetro I) e acima de 250 UI/L (parâmetro II). Os principais desfechos estudados foram: morbidade perioperatória, ocorrência de fístulas, reinternações e reoperações nos primeiros 30 dias, permanência hospitalar e mortalidade. RESULTADOS: Considerando o parâmetro I, altos níveis de amilase do dreno foram indicadores significativos de fístulas (12,5% vs 0; P<0,00001). Considerando o parâmetro II, altos níveis de amilse no dreno estiveram significativamente associados a maior permanência hospitalar (8±5,7 vs 4,5±1,3 dias; P=0,00032), frequência de reoperações (50% vs 3%; P=0,000285) e ocorrência de fístulas (50% vs 0; P<0,00001). O parâmetro I apresentou sensibilidade de 100% e especificidade de 95,9%, enquanto o parâmetro II apresentou sensibilidade de 100% e especificidade de 99,4%. CONCLUSÃO: A determinação dos níveis de amilase no dreno após o BGYR foi um indicador significativo de fístulas, permanência hospitalar e reoperações. Este achado reforça a importância da drenagem abdominal no BGYR dentro deste contexto.
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COMPARISON OF THE LEVELS OF C-REACTIVE PROTEIN, GLP-1 AND GLP-2 AMONG INDIVIDUALS WITH DIABETES, MORBID OBESITY AND HEALTHY CONTROLS: AN EXPLORATORY STUDY
ABSTRACT BACKGROUND: The glucagon-like peptides 1 and 2 (GLP-1/GLP-2) are gut hormones that may directly affect the glucose homeostasis and their activity seems to be significantly affected by chronic inflammation. OBJECTIVE: To evaluate the postprandial levels of glucagon-like peptides 1 and 2 (GLP-1/GLP-2), C-reactive protein (CRP), and the postprandial glucose and insulin levels among individuals with obesity, type 2 diabetes, and healthy controls. METHODS: An exploratory cross-sectional study, which involved individuals awaiting for bariatric/metabolic surgery and healthy controls. Postprandial levels of GLP-1, GLP-2, glucose, and insulin were obtained after a standard meal tolerance test. Inflammation was assessed by means of CRP. RESULTS: There were 30 individuals enrolled in the study, divided into three groups: non-diabetic with morbid obesity (NDO; n=11 individuals), diabetic with mild obesity (T2D; n=12 individuals), and healthy controls (C; n=7 individuals). The mean CRP levels were significantly higher in the NDO group (6.6±4.7 mg/dL) than in the T2D (3.3±2.2 mg/dL) and C groups (2.5±3.2 mg/dL) (P=0.038). The GLP-1 levels following standard meal tolerance test and the area under the curve of GLP-1 did not differ among the three groups. The GLP-2 levels were significantly lower in the NDO and T2D than in the C group following standard meal tolerance test at all the times evaluated. The area under the curve of the GLP-2 was significantly lower in the NDO and T2D groups than in the C group (P=0.05 and P=0.01, respectively). CONCLUSION: GLP-2 levels were impaired in the individuals with obesity and diabetes. This mechanism seems to be enrolled in preventing the worsening of the glucose homeostasis in these individuals.
RESUMO CONTEXTO: Os peptídeos semelhantes ao glucagon 1 e 2 (GLP-1/GLP-2) são hormônios gastrointestinais que podem afetar diretamente a homeostase glicêmica; a atividade de ambos parece ser significativamente afetada pela inflamação crônica. OBJETIVO: Avaliar os níveis pós-prandiais dos peptídeos semelhantes ao glucagon 1 e 2 (GLP-1/GLP-2), proteína C reativa (PCR) e as curvas pós-prandiais de glucose e insulina entre indivíduos com obesidade, diabetes tipo 2 e controles saudáveis. MÉTODOS: Estudo piloto transversal, que envolveu indivíduos aguardando a realização de cirurgia bariátrica/metabólica e controles saudáveis. Os níveis de GLP-1, GLP-2, glucose e insulina foram obtidos após um teste de refeição padrão. A inflamação foi avaliada através dos níveis de PCR. RESULTADOS: Houve 30 indivíduos avaliados no estudo, divididos em três grupos: obesos mórbidos sem diabetes (NDO; n=11 pacientes), diabéticos com obesidade leve (T2D; n=12 pacientes) e controles (C; n=7 pacientes). Os níveis médios de PCR foram significativamente maiores no grupo NDO (6,6±4,7 mg/dL) do que nos grupos T2D (3,3±2,2 mg/dL) e C (2,5±3,2 mg/ dL) (P=0,038). Os níveis de GLP-1 após o teste de refeição padrão e a área sob a curva do GLP-1 não diferiram significativamente entre os grupos. Os níveis de GLP-2 foram significativamente mais baixos nos grupos NDO e T2D do que no grupo C em todos os tempos avaliados. A área sob a curva do GLP-2 foi significativamente menor nos grupos NDO e T2D do que no grupo C (P=0,05 and P=0,01, respectivamente). CONCLUSÃO: Os níveis de GLP-2 encontram-se alterados em indivíduos com obesidade e diabetes. Este mecanismo parece estar envolvido na prevenção da piora da homeostase glicêmica nestes indivíduos.
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ASSOCIATION OF POTENTIAL CELIAC DISEASE AND REFRACTORY IRON DEFICIENCY ANEMIA IN CHILDREN AND ADOLESCENTS
ABSTRACT BACKGROUND: Celiac disease is an enteropathy caused by dietary gluten. The combination of serologic, genetic and histologic data has led to description of other categories of this disease. OBJECTIVE: There are a number of patients with iron deficiency anemia (IDA) that do not respond to iron treatment and may be repeated for many times, Therefore, we aimed to investigate celiac disease in this group. METHODS: In this cross sectional transverse prospective study from August 2011 to February 2013, in a Pediatric care clinic affiliated to Shiraz University of Medical Sciences, 184 children including 92 IDA patients who responded to treatment using iron supplement, 45 non-responding iron deficient patients, and 47 healthy individuals, with the maximum age of 18 years, with written consent from their parents, participated in serologic screening (with Anti-TTG antibody and anti-Endomysial antibody) for celiac disease. Patients with at least one positive serology test underwent multiple mucosal biopsy from bulb and duodenum. RESULTS: Among 184 participants, 19 (10.3%) subjects had positive serologic test for celiac disease, including 13 (28.9%) patients in the group with refractory IDA, 5 (5.4%) patients in the group with treated IDA, and 1 patient in the healthy group. The frequency of positive serologic test in the group with IDA resistant to treatment was prominently higher than the other two groups (P<0.001). Among the patients with positive serologic celiac test who underwent endoscopy and biopsy, no histologic evidence of celiac disease was seen. They were diagnosed as potential celiac disease. CONCLUSION: Frequency of potential celiac disease in patients with refractory IDA was higher than control the subjects. Therefore, we recommend serologic screening for early detection and minimizing the complications of celiac disease and repeated iron therapy for this group.
RESUMO CONTEXTO: A doença celíaca é uma enteropatia causada pelo glúten na dieta. A combinação de dados sorológicos, genéticos e histológicos proporcionou a descrição de outras categorias desta doença. OBJETIVO: Há pacientes com anemia por deficiência de ferro que não respondem ao tratamento com ferro mesmo que repetido por muitas vezes. O objetivo deste trabalho foi investigar a presença de doença celíaca nestes indivíduos. MÉTODOS: Realizado estudo prospectivo com cruzamento secional transversal, de agosto de 2011 a fevereiro de 2013, em uma clínica de cuidados pediátricos afiliados a Shiraz University Medical Sciences, com 184 crianças incluindo 92 pacientes com anemia por deficiência de ferro que responderam ao tratamento com ferro suplementar, 45 não respondedores e 47 indivíduos sadios, com idade máxima de 18 anos, todos com consentimento informado dos pais. Todos participaram da triagem sorológica (com anticorpos anti-TTG e anticorpo antiendomísio) para doença celíaca. Pacientes com pelo menos um teste de sorologia positiva foram submetidos a biópsia da mucosa múltipla do bulbo e duodeno. RESULTADOS: Entre os 184 participantes, 19 (10,3%) tinham teste sorológico positivo para doença celíaca, incluindo 13 (28,9%) pacientes no grupo com a anemia por deficiência de ferro refratária, 5 (5,4%) pacientes no grupo com anemia por deficiência de ferro tratados e respondedores e 1 paciente do grupo saudável. A frequência de teste sorológico positivo no grupo com anemia por deficiência de ferro resistente ao tratamento foi destacadamente maior do que os outros dois grupos (P<0,001). Entre os pacientes com teste sorológico positivo para doença celíaca submetidos a endoscopia e biópsia, não foi vista nenhuma evidência histológica de doença celíaca. Foram diagnosticados como potencial doença celíaca. CONCLUSÃO: Potencial frequência de doença celíaca em pacientes com anemia por deficiência de ferro refratária foi maior do que nos controles. Portanto, recomendamos testes sorológicos de triagem para a detecção precoce, minimizando as complicações da terapia de ferro repetidas para este grupo.
http://ift.tt/2pmrKl9
PREVALENCE OF CELIAC DISEASE PREDISPOSING GENOTYPES, INCLUDING HLA-DQ2.2 VARIANT, IN BRAZILIAN CHILDREN
ABSTRACT BACKGROUND: Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Almost all celiac patients carry immune recognition genes coding for HLA-DQ2.5 and DQ8 heterodimers. Over the last few years, great importance has been given to HLA-DQ2.2 as probable predisposing variant, although controversies still exist regarding its relevance. OBJECTIVE: The aim of our study was to determine the possible existence of an association between HLA-DQ2.2 and celiac disease in Brazilian children by analyzing the prevalence of the predisposing variants for celiac disease in a representative group of children of a population in which this determination is still missing. METHODS: HLA-DQ typing was performed in samples from a group of celiac (n=100) and non-celiac children (n=110). All samples were tested for the presence of the following variants: DQA1*05-DQB1*02 (DQ2.5), DQA1*03-DQB1*03:02 (DQ8) and DQA1*02:01-DQB1*02:02 (DQ2.2). Fisher`s exact test was used for statistical analysis. RESULTS: In the group of 100 celiac children, 78 (78%) were positive for DQ2, 13 (13 %) were DQ2/DQ8 and 6 (6%) were DQ8 positives. The HLA-DQ pattern in the 110 non-celiac children was as follows: positive for DQ2 in 33 (29.9%) samples, in 2 (1.8 %) was positive for DQ2/DQ8 and in 15 (13.6%) was positive for DQ8. We found significant differences between the distribution of some but not all of the analyzed alleles when comparing celiac and non-celiac children. CONCLUSION: The genotyping of celiac disease HLA-DQ predisposing alleles showed similarities with HLA-DQ patterns found in both European and non-European populations, which may be a reflection of the miscegenation, which gave origin to the current Brazilian population. No significant association was found between DQ2.2 variant and celiac disease in the studied population.
RESUMO CONTEXTO: A doença celíaca é uma enteropatia autoimune, desencadeada pela ingestão do glúten em indivíduos geneticamente predispostos. Quase todos os pacientes celíacos possuem genes que codificam os heterodímeros HLA-DQ2.5 e DQ8. Nos últimos anos, mesmo com algumas controvérsias a respeito, tem se dado grande importância ao HLA-DQ2.2 como outra provável variante predisponente para doença celíaca. OBJETIVO: O objetivo do nosso trabalho foi determinar a provável associação entre HLA-DQ2.2 e a doença celíaca em crianças brasileiras, mediante a análise da prevalência das variantes predisponentes para doença celíaca em um grupo representativo desta população que ainda carece de dita informação. MÉTODOS: A genotipagem das variantes HLA-DQ foi realizada em populações de crianças celíacas (n=100) e não celíacas (n=110). A presença das seguintes variantes foi testada em todas as amostras: DQA1*05-DQB1*02 (DQ2.5), DQA1*03-DQB1*03:02 (DQ8) e DQA1*02:01-DQB1*02:02 (DQ2.2). A análise estatística foi realizada utilizando o teste exato de Fisher. RESULTADOS: No grupo de 100 crianças celíacas, 78 (78%) foram positivas para DQ2, 13 (13%) para DQ2/DQ8 e 6 (6%) foram DQ8 positivas. O padrão de variantes predisponentes no grupo de 110 crianças não celíacas foi: 33 (29.9%) amostras positivas para DQ2, 2 (1.8%) DQ2/DQ8 positivas e 15 (13.6%) DQ8 positivas. Quando as prevalências de ambos grupos foram compradas, foram achadas diferenças significativas entre algumas, mas não todas as variantes predisponentes. CONCLUSÃO: A genotipagem das variantes HLA-DQ predisponentes para doença celíaca mostrou um padrão similar ao achado em populações europeias e não-europeias, o qual pode ser resultado da miscigenação que deu origem à população brasileira atual. Nosso trabalho não mostrou associação significativa entre a variante DQ2.2 e a doença celíaca na população estudada.
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REVIEW OF CELIAC DISEASE PRESENTATION IN A PEDIATRIC TERTIARY CENTRE
ABSTRACT BACKGROUND: Celiac disease is an immune-mediated disorder with a multiform presentation and therefore a challenging diagnosis. OBJECTIVE: Our purpose is to identify the epidemiological, clinical, laboratory and histologic characteristics of children with celiac disease at diagnosis and on follow-up. METHODS: Children with previously established or newly diagnosed celiac disease, admitted in a tertiary centre in a two-year period (2014-2016) were recruited. Data was collected retrospectively from electronic medical records and clinical notes, and subsequently analysed with SPSS version 20.0. RESULTS: A total of 159 patients, out of 312, were included. Age ranged from 1 to 17 years (mean ± SD: 8.5±4.5 years, 69% girls). Disease presentation was classical in 60%, non-classical in 25%, subclinical in 10% and 5% classified as potential celiac disease. Non-classical and subclinical profiles had a higher mean age at presentation but not statistically significant (P-value 0.24). The most frequent gastrointestinal features at presentation were abdominal pain (58%), diarrhea (43%) and bloating (27%). A positive family history for celiac disease was present in 24% (n=35). We found anaemia in 23%, low ferritin in 63% and a moderate to severe deficiency of 25-hydroxyvitamin D in 62%. celiac disease -specific serologic testing and esophagogastroduodenoscopy were performed in 99%. Histology revealed modified Marsh 2 or 3 enteropathy in 94%, the remaining had normal histology but positive human leukocyte antigen typing. Clinical improvement at 12 months of gluten-free diet was complete in 51% and partial in 49%. IgA tTG normalized after 12-30 months of gluten-free diet in 45%. On growth assessment at diagnosis and after 12-28 months of gluten-free diet, 100% had height increase (mean ±SD: 7.11±4.43 cm) and 96% weight gain (mean ±SD: 5.60±4.91 kg). CONCLUSION: Our findings outline the diverse clinical presentations of pediatric celiac disease that should be considered irrespective of age. Increased clinician's awareness will enable an early diagnosis and treatment, with subsequent symptom and nutritional status improvement.
RESUMO CONTEXTO: A doença celíaca é uma doença imuno-mediada com uma apresentação multiforme constituindo, por isso, um desafio diagnóstico. OBJETIVO: O objetivo deste trabalho foi identificar as características epidemiológicas, clínicas, laboratoriais e histológicas ao diagnóstico e no seguimento de crianças com doença celíaca. MÉTODOS: Foram incluídas crianças com doença celíaca admitidas num hospital pediátrico terciário ao longo de 2 anos (2014-2016). A recolha da informação clínica foi retrospetiva a partir dos processos clínicos eletrônicos ou em papel e analisada com o software SPSS versão 20.0. RESULTADOS: Foram incluídos 159 doentes, a partir de uma amostra de 312. A idade variou entre 1 e 17 anos (média ± desvio padrão: 8,5±4,5 anos, 69% do sexo feminino). A apresentação da doença foi clássica em 60%, não clássica em 25%, subclínica em 10% e classificada como doença celíaca potencial em 5%. Os doentes com apresentações não clássica e subclínica, tiveram uma idade média de apresentação superior, mas sem significância estatística (P=0,24). Ao diagnóstico, as manifestações gastrointestinais mais frequentes foram dor abdominal (58%), diarreia (43%) e distensão abdominal (27%). Havia história familiar de doença celíaca em 24% (n=35) dos doentes. Foi detetada anemia em 23%, níveis baixos de ferritina em 63% e um défice moderado a grave de 25-hidroxivitamina D em 62%. Foram realizados testes serológicos para a doença celíaca e a esofagogastroduodenoscopia em 99%. Os achados histológicos revelaram enteropatia nos estágios de Marsh modificado tipo 2 ou 3 em 94%, os restantes apresentavam histologia normal mas tipagem do antigénio leucocitário humano positiva. Aos 12 meses de dieta sem glúten a melhoria clínica foi completa em 51% e parcial em 49%. O valor de IgA tTG normalizou em 45% após 12-30 meses de dieta sem glúten. Na avaliação do crescimento, ao diagnóstico e após 12-28 meses de dieta sem glúten, 100% teve evolução estatural positiva (média ±DP: 7,11±4,43 cm) e 96% aumentaram de peso (média ±DP: 5,60±4,91 kg). CONCLUSÃO: Os resultados do estudo evidenciam a diversidade da apresentação clínica da doença celíaca em pediatria, devendo ser considerada em todas as idades. Um maior reconhecimento da doença pelos médicos permitirá um diagnóstico e tratamento atempados, com subsequente melhoria sintomática e do estado nutricional.
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Ion homeostasis and ion channels in NLRP3 inflammasome activation and regulation
Iva Hafner-Bratkovic | Pablo Pelegrín
http://ift.tt/2pkkJSE
Immune-based identification of cancer patients at high risk of progression
Yann-Alexandre Vano | Florent Petitprez | Nicolas A Giraldo | Wolf H Fridman | Catherine Sautès-Fridman
http://ift.tt/2HHr1Ct
Driving CARs on the uneven road of antigen heterogeneity in solid tumors
Nan Chen | Xiaoyu Li | Navin K Chintala | Zachary E Tano | Prasad S Adusumilli
http://ift.tt/2pndAko
Cancer vaccines: translation from mice to human clinical trials
Hoyoung Maeng | Masaki Terabe | Jay A Berzofsky
http://ift.tt/2HHr3u5
Oncolytic viruses and immunity
Shyambabu Chaurasiya | Nanhai G Chen | Yuman Fong
http://ift.tt/2FLQ9f2
Allelic frequencies of 60 pharmacogene variants assessed within a Burmese population residing in northeast Indiana, USA
Pharmacogenomics, Ahead of Print.
http://ift.tt/2pkehLh
SNPs affecting the clinical outcomes of regularly used immunosuppressants
Pharmacogenomics, Ahead of Print.
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Genetic predictors of efficacy and toxicity of iguratimod in patients with rheumatoid arthritis
Pharmacogenomics, Ahead of Print.
http://ift.tt/2FZ55Wx
A nationwide cross-sectional survey of pharmacy students on pharmacogenetic testing in The Netherlands
Pharmacogenomics, Volume 19, Issue 4, Page 311-319, March 2018.
http://ift.tt/2DEW1Ru
Patient perspectives following pharmacogenomics results disclosure in an integrated health system
Pharmacogenomics, Volume 19, Issue 4, Page 321-331, March 2018.
http://ift.tt/2G0jOjU
Role of miRNAs in treatment response and toxicity of childhood acute lymphoblastic leukemia
Pharmacogenomics, Volume 19, Issue 4, Page 361-373, March 2018.
http://ift.tt/2tXNDg8
BCL11A and MDR1 expressions have prognostic impact in patients with acute myeloid leukemia treated with chemotherapy
Pharmacogenomics, Volume 19, Issue 4, Page 343-348, March 2018.
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Detection of a rare CYP3A4 variant in a transplant patient characterized by a tacrolimus poor metabolizer phenotype
Pharmacogenomics, Volume 19, Issue 4, Page 305-310, March 2018.
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Genetic variations in genes of the stress response pathway are associated with prolonged abstinence from heroin
Pharmacogenomics, Volume 19, Issue 4, Page 333-341, March 2018.
http://ift.tt/2G2YuKo
Novel approach for CES1 genotyping: integrating single nucleotide variants and structural variation
Pharmacogenomics, Volume 19, Issue 4, Page 349-359, March 2018.
http://ift.tt/2DAGy4T
New Research From Psychological Science
Read about the latest research published in Psychological Science:
Hair and Salivary Testosterone, Hair Cortisol, and Externalizing Behaviors in Adolescents
Andrew D. Grotzinger, Frank D. Mann, Megan W. Patterson, Jennifer L. Tackett, Elliot M. Tucker-Drob, and K. Paige Harden
Experiments in humans and animals suggest that testosterone plays a role in aggressive and status-seeking behavior. However, one meta-analysis suggests that endogenous testosterone in humans has a small effect on such behaviors and findings vary widely across individual studies. The authors hypothesized that inconsistent findings may be due, at least in part, to moderating variables. A large sample of adolescent participants provided saliva and hair samples and completed measures of rule breaking and aggression, pubertal development, peer deviance and prosociality, callous-unemotional traits, and parental monitoring. Hair testosterone was associated with aggression, particularly when hair cortisol was low; salivary testosterone was not associated with aggression. The data provided little evidence in support of nonhormonal factors as moderators. Analyses revealed one interaction in the opposite direction from that hypothesized and two three-way interactions; these findings should be explored in future work to determine whether they are replicable. The findings suggest that the neuroendocrine bases of externalizing behavior are more complex than previously thought.
Is Source Information Automatically Available in Working Memory?
Hui Chen, Richard A. Carlson, and Brad Wyble
We often remember bits of information without remembering how or where we encountered them, a phenomenon that has been explored extensively in the context of long-term memory. The authors investigated whether source amnesia also occurs with short-term memory, which would suggest an encoding failure as opposed to forgetting. In one experiment, participants saw a series of color words; each was printed in one of four colors. After each word, they had to indicate whether the word and the ink were congruent or incongruent. On a surprise test, a substantial proportion of participants misreported the color of the ink they had identified as incongruent on the previous trial. Some selected the color indicated by the word, suggesting that they had memories of the semantic representations for word and ink color but could not tie the representations to their sources. Additional experiments produced further evidence of source-memory errors, indicating that source information is not automatically stored in working memory.
Rachel R. Romeo, Julia A. Leonard, Sydney T. Robinson, Martin R. West, Allyson P. Mackey, Meredith L. Rowe, and John D. E. Gabrieli
The quantity and quality of language that children hear affects later linguistic, cognitive, academic, and social skills, and research has shown that language exposure varies widely according to family socioeconomic status (SES). To investigate the neural mechanisms underlying this relationship, the authors analyzed home audio recordings, behavioral data, and functional MRI data from 36 4- to 6-year-old children. Children who experienced more conversational turns with adults in the home recordings showed greater verbal ability and relatively greater activation in Broca's area during a passive-listening task, independently of other covariates such as SES, cognitive ability, and number of words spoken in the home. Activation in Broca's area mediated the relationship between conversational turns and children's verbal ability. Furthermore, conversational turns and Broca's area activation jointly mediated the relationship between parental education and children's verbal ability. The findings suggest both an environmental and a neural mechanism that may underlie SES-related disparities in children's language skills.
The Gender-Equality Paradox in Science, Technology, Engineering, and Mathematics Education
Gijsbert Stoet and David C. Geary
Women and girls continue to be underrepresented in science, technology, engineering, and mathematics (STEM) fields, even in countries with high levels of gender equality. Drawing from expectancy-value theory, the authors hypothesized that students' perceptions about how they perform relative to their peers may inform their educational and occupational choices. Data from an international survey of 15-year-olds showed that girls had scientific literacy similar to or greater than that of boys in a majority of countries. In countries such as Finland, where girls outperformed boys in science, girls generally performed even better in reading. Sex differences in personal academic strengths and pursuit of STEM degrees were greater in more gender-equal countries. A mediation analysis suggested that life-quality pressures may lead girls and women to engage more with STEM subjects in less gender-equal countries. Investigating individual competencies and expectancies in the context of broader social factors is important to understanding the gender gap in STEM fields, the authors conclude.
http://ift.tt/2FIXzj7
Recurrent Pneumonia due to Fibrosing Mediastinitis in a Teenage Girl: A Case Report with Long-Term Follow-Up
A teenage girl was evaluated for recurrent right pneumonia. The evaluation revealed a calcified mediastinal mass that compressed the right intermediate and middle lobar bronchi, as well as the right pulmonary artery and veins. The clinical picture together with imaging studies and borderline positive serology testing suggested a diagnosis of fibrosing mediastinitis associated with histoplasmosis. This rare condition is characterized by the local proliferation of invasive fibrous tissue within the mediastinum due to a hyperimmune reaction to Histoplasma capsulatum. Antifungal and anti-inflammatory therapies are usually ineffective, and surgical intervention contains a high morbidity risk. Palliative surgery and stenting of the compressed airway have been suggested. In the past, the prognosis was thought to be poor, but recent studies demonstrate a more positive outcome. Our patient had been radiologically and functionally stable under follow-up for over thirteen years and has married and delivered two healthy children, both following an uneventful pregnancy.
http://ift.tt/2DAxWv5
Successful Treatment of High-Level Aminoglycoside-Resistant Enterococcus faecalis Bacteremia in a Preterm Infant with Ampicillin and Cefotaxime
Enterococcal bloodstream infections are usually treated with single-agent antibiotics. In persistent infections, synergistic combination therapy is often required with a beta-lactam and an aminoglycoside antibiotic. High-level aminoglycoside-resistant (HLAR) enterococci are increasingly prevalent and preclude the use of this combination. The use of ampicillin with a third-generation cephalosporin to treat endovascular HLAR Enterococcus infections is becoming more established in the adult population; however, the literature on treatment of such infections in children remains scarce. We report a preterm neonate with persistent HLAR Enterococcus faecalis bacteremia from day of life 9 to 17 despite treatment with ampicillin and vancomycin. On day of life 17, antibiotic treatment was switched to ampicillin and cefotaxime, with subsequent clearance of blood cultures on day of life 20. To our knowledge, this is the first report illustrating the use of ampicillin and cefotaxime for an HLAR E. faecalis infection in a neonate.
http://ift.tt/2pjoiIC
Peer Inclusion in Interventions for Children with ADHD: A Systematic Review and Meta-Analysis
Objective. To assess the effectiveness of peer inclusion in interventions to improve the social functioning of children with ADHD. Methods. We searched four electronic databases for randomized controlled trials and controlled quasi-experimental studies that investigated peer inclusion interventions alone or combined with pharmacological treatment. Data were collected from the included studies and methodologically assessed. Meta-analyses were conducted using a random-effects model. Results. Seventeen studies met eligibility criteria. Studies investigated interventions consisting of peer involvement and peer proximity; no study included peer mediation. Most included studies had an unclear or high risk of bias regarding inadequate reporting of randomization, blinding, and control for confounders. Meta-analyses indicated improvements in pre-post measures of social functioning for participants in peer-inclusive treatment groups. Peer inclusion was advantageous compared to treatment as usual. The benefits of peer inclusion over other therapies or medication only could not be determined. Using parents as raters for outcome measurement significantly mediated the intervention effect. Conclusions. The evidence to support or contest the efficacy of peer inclusion interventions for children with ADHD is lacking. Future studies need to reduce risks of bias, use appropriate sample sizes, and provide detailed results to investigate the efficacy of peer inclusion interventions for children with ADHD.
http://ift.tt/2pjQ9YA
Routine histologic features in complex atypical hyperplasia can predict the presence of endometrial carcinoma: a clinicopathologic study of 222 cases
There is a wide range of finding endometrial adenocarcinoma (ADCA) in the uterus following a diagnosis of complex atypical hyperplasia (CAH), likely due to a poor diagnostic reproducibility and an inherent heterogeneity in CAH. We evaluated whether histologic subtyping of CAH would help predict ADCA. Our study consisted of 222 cases of CAH diagnosed by endometrial biopsy or curettage. ADCA was seen in 38.3% of these cases at hysterectomy. We divided CAH into two subtypes: type A was defined as back-to-back glands in a focus smaller than 2.1 mm, and type B as crowded glands with cytologic atypia but there was still intervening stroma regardless of lesional size.
http://ift.tt/2FHuTH3
Mesenchymal Chondrosarcomas Showing Immunohistochemical Evidence of Rhabdomyoblastic Differentiation: A Potential Diagnostic Pitfall
The diagnosis of mesenchymal chondrosarcoma, a distinctive biphasic malignant neoplasm harboring the HEY1-NCOA2 gene fusion and consisting of primitive round to spindled cells admixed with foci of relatively mature hyaline cartilage, is usually straightforward by morphological evaluation alone. However, in the setting of a limited biopsy, specimens lacking cartilage generate a broad differential diagnosis, encompassing a variety of other primitive sarcomas, including spindle cell/ sclerosing rhabdomyosarcoma.
http://ift.tt/2DAoM1F
A four-microRNA signature predicts lymph node metastasis and prognosis in breast cancer
Recent findings have reported that human microRNAs (miRNAs) could serve as prognostic biomarkers in various cancers. We aimed to identify miRNAs that were associated with lymph node metastasis (LNM) and prognosis in breast cancer patients. A miRNA microarray covering 2019 mature miRNAs was used to identify differentially-expressed miRNAs in nine patients with LNM and three patients without LNM. Thirty-five differentially expressed miRNAs were identified, of which 10 significantly were up-regulated while the other 25 were down-regulated in tissues with LNM compared to those without LNM.
http://ift.tt/2FKsknK
Whole-exome sequencing identified mutational profiles of squamous cell carcinomas of anus
Anal squamous cell carcinoma (ASCC), either with human papillomavirus (HPV) (+) or (−), is a neoplastic disease with frequent recurrence and metastasis. To characterize ASCC genomes, we attempted to disclose novel alterations of ASCC genomes as well as other genetic features including mutation signatures. We performed whole-exome sequencing and copy number alteration (CNA) profiling for 8 ASCC samples from 6 patients (2 cases with primary and recurrent/metastatic tumors). We found known ASCC mutations (TP53, CDKN2A and PIK3CA) and CNAs (gains on 3q and 19q and losses on 11q and 13q).
http://ift.tt/2FOuAq5
ACOT1 expression is associated with poor prognosis in gastric adenocarcinoma
Acyl-CoA thioesterase 1 (ACOT1) is an important isoform of the ACOT family that catalyzes the reaction of fatty acyl-CoAs to CoA-SH and free fatty acids. Recent studies of gastrointestinal tumor metabolism suggest that there is abnormal metabolism of lipids and fatty acids during tumor progression. However, the function and contribution of ACOT1 in gastric cancer development are still poorly understood. Additionally, GLI3 is a major transcription factor in the regulation of hedgehog (Hh) signaling.
http://ift.tt/2GE3bbB
Model for Identifying Individuals at Risk for Esophageal Adenocarcinoma
The prognosis for most patients with esophageal adenocarcinoma (EAC) is poor because they present with advanced disease. Models developed to identify patients at risk for EAC and increase early detection have been developed based on data from case–control studies. We analyzed data from a prospective study to identify factors available to clinicians that identify individuals with a high absolute risk of EAC.
http://ift.tt/2G103sC
Houston Consensus Conference on Testing for Helicobacter pylori Infection in the United States
Despite guidelines for detection and treatment of Helicobacter pylori infection, recommendations to test patients before and after therapy are commonly not followed in the United States (US). At the Houston Consensus Conference, 11 experts on management of adult and pediatric patients with H pylori, from different geographic regions of the US, met to discuss key factors in diagnosis of H pylori infection, including identification of appropriate patients for testing, effects of antibiotic susceptibility on testing and treatment, appropriate methods for confirmation of infection and eradication, and relevant health system considerations.
http://ift.tt/2G3nP7i
Smoking Cessation After Treatment of Squamous Cell Head and Neck Cancer: The Impact of Survivorship Counseling
Continued tobacco abuse after diagnosis and treatment of squamous cell head and neck cancer (SCHNC) is associated with an increased risk of treatment failure and second primary malignancies. The purpose of this study is to characterize patients more likely to stop smoking after head and neck cancer treatment and explore the impact of survivorship counseling on tobacco cessation.
http://ift.tt/2Iwl2Ss
A pilot single-center prospective randomized trial to assess the short-term effect of a flashing warning light on reducing fluoroscopy time and radiation exposure during ERCP
ERCP has the risk of exposure to ionizing radiation. Performers may unconsciously increase fluoroscopy time (FT) due to lack of radiation protection awareness. This study investigates whether a flashing warning light adopted as a behavioral intervention for performers reduces FT and radiation exposure during ERCP.
http://ift.tt/2FQbhMV
A Novel In Vitro Wound Healing Assay to Evaluate Cell Migration
Here, we present a protocol to evaluate the effect of peptides on the migration of bronchial epithelial cells. This method allows for the rapid and highly reproducible obtainment of quantitative data on the speed of cell migration and wound closure.
http://ift.tt/2HJI1s3
Markers of non-coeliac wheat sensitivity in patients with myalgic encephalomyelitis/chronic fatigue syndrome
We recently reported in Gut that non-coeliac wheat sensitivity (NCWS) is associated with a state of systemic immune activation in conjunction with a compromised intestinal epithelium.1 Patients with NCWS experience GI symptoms, most commonly including abdominal pain and bloating, as well as extraintestinal symptoms, among which fatigue, headache and cognitive difficulties feature prominently.1 2 A principal component analysis of the generated data from our study, including markers of antibody reactivity to wheat gluten, intestinal cell damage and systemic innate and adaptive immune responses to microbial components, found clustering of the patients and controls into discernible groups and demonstrated the potential utility of the identified biomarkers for identifying patients with NCWS.1
Extreme fatigue, in particular one that does not improve with rest, is a hallmark of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).3 Immune system abnormalities have been found to be associated with symptoms...
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Kinematics and postural muscular activity during continuous oscillating platform movement in children and adolescents
Abstract
The aims of this study were to (1) characterize anticipatory and reactive postural strategies in typically developing (TD) children and adolescents; (2) determine if TD youth shift from reactive to anticipatory mechanisms based on knowledge of platform movement; and (3) determine whether TD youth further modify postural strategies when additional information about the perturbation is provided. Sixteen typically developing youth aged 7–17 years stood with eyes open on a movable platform that progressively translated anteroposteriorly (20 cm peak-to-peak) through four speeds (0.1, 0.25, 0.5, and 0.61 Hz). Participants performed two trials each of experimenter-triggered and self-triggered perturbations. Postural muscle activity (1000 Hz) of the tibialis anterior, gastrocnemius, quadriceps and hamstrings and 3D whole body kinematics (100 Hz) were recorded. The Anchoring Index and marker-pair trajectory cross-correlations were calculated as indications of body stabilization. The number of steps taken to regain balance/avoid falling were counted. Transition states and steady states were analyzed separately. Generally, the higher frequencies resulted in more steps being taken, lower correlations coupled with greater temporal lags between marker trajectories, and postural muscle activity similar to older adults. The provision of self-triggered perturbations allowed participants to make the appropriate changes to their balance by use of anticipatory postural control mechanisms.
http://ift.tt/2pk9TMB
Immunohistochemical ATRX expression is not a surrogate for 1p19q codeletion
Abstract
The IDH-mutant and 1p/19q co-deletion (1p19q codel) provides significant diagnostic and prognostic value in lower-grade gliomas. As ATRX mutation and 1p19q codel are mutually exclusive, ATRX immunohistochemistry (IHC) may substitute for 1p19q codel, but this has not been comprehensively examined. In the current study, we performed ATRX-IHC in 78 gliomas whose ATRX statuses were comprehensively determined by whole exome sequencing. Among the 60 IHC-positive and 18 IHC-negative cases, 86.7 and 77.8% were ATRX-wildtype and ATRX-mutant, respectively. ATRX mutational patterns were not consistent with ATRX-IHC. If our cohort had only used IDH status and IHC-based ATRX expression for diagnosis, 78 tumors would have been subtyped as 48 oligodendroglial tumors, 16 IDH-mutant astrocytic tumors, and 14 IDH-wildtype astrocytic tumors. However, when the 1p19q codel test was performed following ATRX-IHC, 8 of 48 ATRX-IHC-positive tumors were classified as "1p19q non-codel" and 3 of 16 ATRX-IHC-negative tumors were classified as "1p19q codel"; a total of 11 tumors (14%) were incorrectly classified. In summary, we observed dissociation between ATRX-IHC and actual 1p19q codel in 11 of 64 IDH-mutant LGGs. In describing the complex IHC expression of ATRX somatic mutations, our results indicate the need for caution when using ATRX-IHC as a surrogate of 1p19q status.
http://ift.tt/2FTwLsg
Study protocol for the SMART2D adaptive implementation trial: a cluster randomised trial comparing facility-only care with integrated facility and community care to improve type 2 diabetes outcomes in Uganda, South Africa and Sweden
Introduction
Type 2 diabetes (T2D) is increasingly contributing to the global burden of disease. Health systems in most parts of the world are struggling to diagnose and manage T2D, especially in low-income and middle-income countries, and among disadvantaged populations in high-income countries. The aim of this study is to determine the added benefit of community interventions onto health facility interventions, towards glycaemic control among persons with diabetes, and towards reduction in plasma glucose among persons with prediabetes.
Methods and analysisAn adaptive implementation cluster randomised trial is being implemented in two rural districts in Uganda with three clusters per study arm, in an urban township in South Africa with one cluster per study arm, and in socially disadvantaged suburbs in Stockholm, Sweden with one cluster per study arm. Clusters are communities within the catchment areas of participating primary healthcare facilities. There are two study arms comprising a facility plus community interventions arm and a facility-only interventions arm. Uganda has a third arm comprising usual care. Intervention strategies focus on organisation of care, linkage between health facility and the community, and strengthening patient role in self-management, community mobilisation and a supportive environment. Among T2D participants, the primary outcome is controlled plasma glucose; whereas among prediabetes participants the primary outcome is reduction in plasma glucose.
Ethics and disseminationThe study has received approval in Uganda from the Higher Degrees, Research and Ethics Committee of Makerere University School of Public Health and from the Uganda National Council for Science and Technology; in South Africa from the Biomedical Science Research Ethics Committee of the University of the Western Cape; and in Sweden from the Regional Ethical Board in Stockholm. Findings will be disseminated through peer-reviewed publications and scientific meetings.
Trial registration numberISRCTN11913581; Pre-results.
http://ift.tt/2FQU0n5
Prevalence and causes of visual impairment amongst older adults in a rural area of North India: a cross-sectional study
Objectives
To determine the prevalence, causes and associated factors for visual impairment (VI) in rural population of Jhajjar district, Haryana, north India.
MethodsA community-based, cross-sectional study was conducted in two blocks of Jhajjar district. A total of 34 villages were selected using probability proportionate to size sampling method. Adults aged 50 years and above were selected using compact segment cluster sampling approach. Presenting visual acuity using LogMAR E chart was measured along with collection of other demographic details as part of the house-to-house survey. Subjective refraction and torch light examination were performed at a clinic site within the village to ascertain VI and its cause. VI was considered when presenting visual acuity was less than 6/18 in the better eye. Common causes of VI viz uncorrected refractive errors, cataract, central corneal opacity and others were noted by optometrists. Descriptive analysis was undertaken. Multivariate logistic regression analysis was performed for determining associated factors with VI.
ResultsOut of 2025 enumerated adults, 1690 (83.5%) were examined at the household level and 1575 (78%) completed all study procedures. The prevalence of VI was found to be 24.5% (95% CI 21.1 to 26.3) and blindness was 5% (95% CI 3.9 to 6.1). The most common causes of VI were uncorrected refractive errors (50%) and cataract (37%). The VI in study participants was found to be associated with age, gender, marital and educational status.
ConclusionsVI is still a public health problem in rural population of Jhajjar district, Haryana. Provision of spectacles and cataract surgical services are simple interventions to address this issue.
http://ift.tt/2FHnsj9
Assessing the impact of care farms on quality of life and offending: a pilot study among probation service users in England
Objectives
To assess the feasibility of conducting a cost-effectiveness study of using care farms (CFs) to improve quality of life and reduce reoffending among offenders undertaking community orders (COs). To pilot questionnaires to assess quality of life, connection to nature, lifestyle behaviours, health and social-care use. To assess recruitment and retention at 6 months and feasibility of data linkage to Police National Computer (PNC) reconvictions data and data held by probation services.
DesignPilot study using questionnaires to assess quality of life, individually linked to police and probation data.
SettingThe pilot study was conducted in three probation service regions in England. Each site included a CF and at least one comparator CO project. CFs are working farms used with a range of clients, including offenders, for therapeutic purposes. The three CFs included one aquaponics and horticulture social enterprise, a religious charity focusing on horticulture and a family-run cattle farm. Comparator projects included sorting secondhand clothes and activities to address alcohol misuse and anger management.
ParticipantsWe recruited 134 adults (over 18) serving COs in England, 29% female.
Results52% of participants completed follow-up questionnaires. Privatisation of UK probation trusts in 2014 negatively impacted on recruitment and retention. Linkage to PNC data was a more successful means of follow-up, with 90% consenting to access their probation and PNC data. Collection of health and social-care costs and quality-adjusted life year derivation were feasible. Propensity score adjustment provided a viable comparison method despite differences between comparators. We found worse health and higher reoffending risk among CF participants due to allocation of challenging offenders to CFs, making risk of reoffending a confounder.
ConclusionsRecruitment would be feasible in a more stable probation environment. Follow-up was challenging; however, assessing reconvictions from PNC data is feasible and a potential primary outcome for future studies.
http://ift.tt/2DzunVX
Nineteen and Up study (19Up): understanding pathways to mental health disorders in young Australian twins
Purpose
The Nineteen and Up study (19Up) assessed a range of mental health and behavioural problems and associated risk factors in a genetically informative Australian cohort of young adult twins and their non-twin siblings. As such, 19Up enables detailed investigation of genetic and environmental pathways to mental illness and substance misuse within the Brisbane Longitudinal Twin Sample (BLTS).
ParticipantsTwins and their non-twin siblings from Queensland, Australia; mostly from European ancestry. Data were collected between 2009 and 2016 on 2773 participants (age range 18–38, 57.8% female, 372 complete monozygotic pairs, 493 dizygotic pairs, 640 non-twin siblings, 403 singleton twins).
Findings to dateA structured clinical assessment (Composite International Diagnostic Interview) was used to collect lifetime prevalence of diagnostic statistical manual (4th edition) (DSM-IV) diagnoses of major depressive disorder, (hypo)mania, social anxiety, cannabis use disorder, alcohol use disorder, panic disorder and psychotic symptoms. Here, we further describe the comorbidities and ages of onset for these mental disorders. Notably, two-thirds of the sample reported one or more lifetime mental disorder.
In addition, the 19Up study assessed general health, drug use, work activity, education level, personality, migraine/headaches, suicidal thoughts, attention deficit hyperactivity disorder (ADHD) symptomatology, sleep–wake patterns, romantic preferences, friendships, familial environment, stress, anorexia and bulimia as well as baldness, acne, asthma, endometriosis, joint flexibility and internet use.
The overlap with previous waves of the BLTS means that 84% of the 19Up participants are genotyped, 36% imaged using multimodal MRI and most have been assessed for psychological symptoms at up to four time points. Furthermore, IQ is available for 57%, parental report of ADHD symptomatology for 100% and electroencephalography for 30%.
Future plansThe 19Up study complements a phenotypically rich, longitudinal collection of environmental and psychological risk factors. Future publications will explore hypotheses related to disease onset and development across the waves of the cohort. A follow-up study at 25+years is ongoing.
http://ift.tt/2GBX083
Dementia case-finding in hospitals: a qualitative study exploring the views of healthcare professionals in English primary care and secondary care
Objectives
In 2012–2013, the English National Health Service mandated hospitals to conduct systematic case-finding of people with dementia among older people with unplanned admissions. The method was not defined. The aim of this study was to understand current approaches to dementia case-finding in acute hospitals in England and explore the views of healthcare professionals on perceived benefits and challenges.
DesignQualitative study involving interviews, focus groups and thematic content analysis.
SettingPrimary care and secondary care across six counties in the East of England.
ParticipantsHospital staff involved in dementia case-finding and primary care staff in the catchment areas of those hospitals.
ResultsWe recruited 23 hospital staff and 36 primary care staff, including 30 general practitioners (GPs). Analysis resulted in three themes: (1) lack of consistent approaches in case-finding processes, (2) barriers between primary care and secondary care which impact on case-finding outcomes and (3) perceptions of rationale, aims and impacts of case-finding. The study shows that there were variations in how well hospitals recorded and reported outcomes to GPs. Barriers between primary care and secondary care, including GPs' lack of access to hospital investigations and lack of clarity about roles and responsibilities, impacted case-finding outcomes. Staff in secondary care were more positive about the initiative than primary care staff, and there were conflicting priorities for primary care and secondary care regarding case-finding.
ConclusionsThe study suggests a more evidence-based approach was needed to justify approaches to dementia case-finding. Information communicated to primary care from hospitals needs to be comprehensive, appropriate and consistent before GPs can effectively plan further investigation, treatment or care. Follow-up in primary care further requires access to options for postdiagnostic support. There is a need to evaluate the outcomes for patients and the economic impact on health and care services across settings.
http://ift.tt/2DywitO
Impact of a multifactorial treatment programme on clinical outcomes and cardiovascular risk estimates: a retrospective cohort study from a specialised diabetes centre in Denmark
Objectives
To investigate the impact of a multifactorial treatment programme in a real-life setting on clinical outcomes and estimated cardiovascular disease (CVD) risk.
DesignA retrospective observational cohort study, using data from the electronic medical records and national registers.
SettingTertiary diabetes centre in Denmark.
ParticipantsPatients with type 2 diabetes (n=4299) referred to a programme with focus on treatment of hyperglycaemia, hypertension and dyslipidaemia between 1 January 2001 and 1 April 2016.
OutcomesPrimary outcomes were changes in haemoglobin A1c (HbA1c), blood pressure (BP) and low-density lipoprotein (LDL) cholesterol as well as proportion reaching treatment targets. Our secondary outcome was to investigate changes in antidiabetic, antihypertensive and lipid-lowering treatment, together with the impact on estimated CVD risk. Linear mixed model for repeated measurements were used for continuous variables and logistic regression for dichotomous variables.
ResultsThe patients achieved a mean±SD decrease in HbA1c, systolic and diastolic BP and LDL cholesterol of 1.0%±0.04% (10.6±0.4 mmol/mol), 6.3±0.4 mm Hg, 2.7±0.2 mm Hg and 0.32±0.02 mmol/L, respectively (p<0.0001). The proportion of patients who met the treatment goal for HbA1c (<7% (<53 mmol/mol)) increased from 31% to 58% (p<0.0001); for BP (<130/80 mm Hg) from 24% to 34% (p<0.0001), and for LDL cholesterol (<2.5 mmol/L (patients without previous CVD) or <1.8 mmol/L (patients with previous CVD)) from 52% to 65%. Those reaching all three guideline treatment targets increased from 4% to 15% (p<0.0001), and when relaxing the BP target to <140/85 from 8% to 24%. The estimated CVD risk was relatively reduced by 15.2% using the Swedish National Diabetes Register risk engine and 30.9% using the UK Prospective Diabetes Study risk engine.
ConclusionsOur data support that short-term multifactorial treatment of patients with glycaemic dysregulation in a specialist outpatient setting is both achievable and effective, and associated with a clinically meaningful improvement in CVD risk.
http://ift.tt/2GAauRu
Protocol for a pragmatic randomised controlled trial of Body Brain Life--General Practice and a Lifestyle Modification Programme to decrease dementia risk exposure in a primary care setting
Introduction
It has been estimated that a 10%–25% reduction in seven key risk factors could potentially prevent 1.1–3.0 million Alzheimer's disease cases globally. In addition, as dementia is preceded by more subtle cognitive deficits which have substantial social and economic impact, effective preventative interventions would likely have more extensive benefits. The current study evaluates in primary care a multidomain risk-reduction intervention targeting adults with high risk of developing dementia.
Methods and analysisA randomised controlled trial (RCT) is being conducted to evaluate three intervention programmes using a pragmatic approach suitable to the clinic: (1) a 12-week online and face-to-face dementia risk-reduction intervention (Body Brain Life—General Practice (BBL-GP)); (2) a 6-week face-to-face group lifestyle modification programme (LMP); and (3) a 12-week email-only programme providing general health information. We aim to recruit 240 participants, aged 18 and over, to undergo a comprehensive cognitive and physical assessment at baseline and follow-ups (postintervention, 18, 36 and 62 weeks). The primary outcome is dementia risk measured with the modified version of the Australian National University—Alzheimer's Disease Risk Index Short Form. Secondary outcomes are cognitive function measured with Trails A and B, and the Digit Symbol Modalities Test; physical activity with moderate-vigorous physical activity and the International Physical Activity Questionnaire; depression with the Centre for Epidemiological Studies Depression; cost evaluation with the 12-item Short Form Health Survey, Framingham Coronary Heart Disease Risk Score and Australian Type 2 Diabetes Risk Assessment Tool; diet quality with the Australian Recommended Food Score; and sleep quality with the Pittsburgh Sleep Quality Index.
Ethics and disseminationThis RCT is a novel pragmatic intervention applied in a primary care setting to reduce the dementia risk exposure in adults at high risk. If successful, BBL-GP and LMP will provide a versatile, evidence-based package that can be easily and quickly rolled out to other primary care settings and which can be scaled up at relatively low cost compared with other strategies involving intensive interventions.
Trial registration numberACTRN12616000868482
http://ift.tt/2FNVazv
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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