ABSTRACT The increase of H. pylori resistance to clarithromycin is a concern. This study evaluated the prevalence of H. pylori’s primary resistance to clarithromycin and its association with virulence factors in adult dyspeptic patients and asymptomatic children. The gastric mucosa from patients (153 gastritis, 24 gastric cancer, 21 peptic ulcer) and gastric juice obtained by string test from 24 H. pylori and 23S rRNA positive asymptomatic children were included. The clarithromycin resistance was assessed by TaqMan RT-PCR 23S rRNA point mutations, A2142G and/or A2143G, and H. pylori virulence markers by PCR. Overall, the clarithromycin resistance was 14.4% (32/222), 14.2% in adults, and 12% in children, whereas origin, gender, and disease were not distinctive factors. The most prevalent point mutation was A2143G (62.5%). The point mutation was significantly less frequent in cagA-positive (11.4%) than in cagA-negative (23.6%) strains (p=0.03 OR = 0.4 95%CI = 0.19 - 0.91) as well as in cagE-positive (10.2%), cagE-negative (21.2%) (p=0.03 OR: 0.4 I.C:0.20-0.91). No difference was found in iceA or vacA alleles genotypes. Primary resistance to clarithromycin was lower than that reported in Southeast Brazil. The cagA and cagE positive H. pylori samples have few point mutations suggesting that individuals infected with virulent strains may be more susceptible to anti-H. pylori treatment.

RESUMO Objetivo. Identificar tendências temporais e padrões espaciais de mortalidade relacionada ao câncer gástrico em todo o Brasil. Métodos. Realizou-se um estudo ecológico a partir de declarações de óbito registradas de 2000 a 2019 em que o câncer gástrico foi indicado como qualquer causa de morte (causa básica ou associada). As tendências ao longo do tempo foram avaliadas a partir de modelos de regressão por pontos de inflexão (joinpoint). Os aglomerados espaciais e espaço-temporais foram identificados por estatística de varredura espaço-temporal de Kulldorff para detectar áreas de alto risco. Resultados. O câncer gástrico foi registrado como qualquer causa de morte em 276.897/22.663.091 (1,22%) declarações de óbito. A mortalidade relacionada ao câncer gástrico ajustada por idade aumentou significativamente ao longo do tempo [variação percentual anual (VPA): 0,7, intervalo de confiança (IC) de 95%: 0,5 a 0,8]. O aumento da mortalidade foi mais acentuado no Norte e Nordeste, regiões menos desenvolvidas (região Norte, VPA: 3,1, IC 95%: 2,7 a 3,5; região Nordeste, VPA: 3,1, IC 95%: 2,5 a 3,7). Identificaram-se oito aglomerados de alto risco de mortalidade relacionada ao câncer gástrico em associação espaço-temporal nas regiões Norte, Sul, Nordeste e Centro-Oeste, além de um grande aglomerado que abrangia uma larga faixa geográfica nas regiões Sul e Sudeste do Brasil durante os primeiros anos do período de estudo (2000 a 2009). Conclusões. Mais recentemente, no período de 2010 a 2019, identificaram-se aglomerados de câncer gástrico na região Nordeste. O aumento da mortalidade em todo o país nesta análise de dados relativos a 20 anos evidencia a persistência da alta carga de câncer gástrico no Brasil, sobretudo em regiões desfavorecidas do ponto de vista socioeconômico. A identificação dessas áreas em que a população corre alto risco de morte relacionada ao câncer gástrico enfatiza a necessidade de desenvolver medidas de controle efetivas e intersetoriais.

ABSTRACT Objective. To identify nationwide temporal trends and spatial patterns of gastric cancer–related mortality in Brazil. Methods. An ecological study was performed using death certificates registered from 2000 to 2019 in which gastric cancer was recorded as any cause of death (an underlying or associated cause). Trends over time were assessed using joinpoint regression models. Spatial and spatiotemporal clusters were identified by Kulldorff’s space–time scan statistics to identify high-risk areas. Results. In 276 897/22 663 091 (1.22%) death certificates gastric cancer was recorded as any cause of death. Age-adjusted gastric cancer–related mortality increased significantly over time (annual percentage change [APC]: 0.7, 95% confidence interval [CI]: 0.5 to 0.8). The increase in mortality was more pronounced in the less-developed North and Northeast Regions (North Region, APC: 3.1, 95% CI: 2.7 to 3.5; Northeast Region, APC: 3.1, 95% CI: 2.5 to 3.7). Eight spatiotemporally associated high-risk clusters of gastric cancer–related mortality were identified in the North, South, Northeast and Central–West Regions, as well as a major cluster covering a wide geographical range in the South and Southeast Regions of Brazil during the first years of the study period (2000 to 2009). Conclusions. More recently, during 2010 to 2019, clusters of gastric cancer have been identified in the Northeast Region. The nationwide increase in mortality in this analysis of 20 years of data highlights the persistently high burden of gastric cancer in Brazil, especially in socioeconomically disadvantaged regions. The identification of these areas where the population is at high risk for gastric cancer–related mortality emphasizes the need to develop effective and intersectoral control measures.

RESUMEN Objetivo. Identificar las tendencias temporales y los patrones espaciales de la mortalidad relacionada con el cáncer gástrico a nivel nacional en Brasil. Métodos. Se realizó un estudio ecológico, empleando certificados de defunción registrados entre los años 2000 y 2019 en los que se notificó cáncer gástrico como cualquier causa de muerte (subyacente o asociada). Se evaluaron las tendencias con el transcurso del tiempo mediante modelos de regresión de punto de inflexión (joinpoint). Se identificaron los conglomerados espaciales y espaciotemporales mediante la técnica estadística de exploración espaciotemporal de Kulldorff para determinar cuáles eran las áreas de alto riesgo. Resultados. En 276 897 de 22 663 091 certificados de defunción (1,22%), se registró cáncer gástrico como cualquier causa de muerte. La mortalidad relacionada con el cáncer gástrico ajustada por edad aumentó significativamente con el tiempo (cambio porcentual anual: 0,7; intervalo de confianza [IC] del 95%: 0,5 a 0,8). El aumento de la mortalidad fue más acusado en la regiones Norte y Noreste, menos desarrolladas, (región Norte, cambio porcentual anual: 3,1, IC del 95%: 2,7 a 3,5; región Noreste, cambio porcentual anual: 3,1, IC del 95%: 2,5 a 3,7). Durante los primeros años del período de estudio (del 2000 al 2009), se identificaron ocho conglomerados de alto riesgo de mortalidad relacionada con el cáncer gástrico y con asociación espacial y temporal en las regiones Norte, Sur, Noreste y Centro-Oeste, así como un conglomerado importante que cubría un amplio rango geográfico en las regiones Sur y Sureste de Brasil. Conclusiones. Más recientemente, del 2010 al 2019, se han identificado conglomerados de cáncer gástrico en la región noreste. El aumento nacional de la mortalidad en este análisis de veinte años de datos destaca la carga persistentemente alta del cáncer gástrico en Brasil, especialmente en las regiones socioeconómicamente desfavorecidas. La identificación de estas áreas en que la población presenta un alto riesgo de mortalidad relacionada con el cáncer gástrico subraya la necesidad de elaborar medidas de control intersectoriales y efectivas.

ContextoO tratamento da infecção do vírus da hepatite C pós-transplante é um desafio devido à baixa tolerância dos pacientes e às baixas taxas de resposta.ObjetivoDeterminar a taxa de resposta ao interferon peguilado e ribavirina no tratamento da recorrência da hepatite C após transplante de fígado.MétodosEntre 18 de maio de 2002 e 18 de dezembro de 2011, 601 pacientes realizaram transplante hepático no Hospital Universitário Walter Cantídio, 176 (29,2%) desses eram infectados pelo vírus da hepatite C. Quarenta pacientes receberam terapia antiviral e foram incluídos nesse estudo. Vinte e sete (70%) completaram o protocolo de tratamento, que consistia de interferon peguilado e ribavirina por 48 semanas.ResultadosA taxa de resposta virológica sustentada foi de 55% de acordo com a análise por intenção de tratar. A idade dos receptores e a exposição prévia ao transplante de antivirais foram fatores associados com a resposta virológica sustentada na análise multivariada. Pacientes foram acompanhados por 57 meses em média. A sobrevida em 1 e 5 anos foi de 100% em respondedores, enquanto que em não respondedores foi de 100% e 78% respectivamente.ConclusãoA resposta virológica sustentada foi satisfatória na série de pacientes transplantados e diminuiu com o aumento da idade. A não exposição prévia ao transplante a drogas antivirais teve impacto positivo na chance de resposta virológica sustentada. A sobrevida global foi similar em respondedores e não respondedores.

BackgroundTreatment of hepatitis C virus infection in post-transplantation patients is a challenge due to poor tolerance and low success rates.ObjectiveTo determine the response rate to pegylated interferon and ribavirin in post-liver transplant patients with hepatitis C recurrence.MethodsBetween 18 May 2002 and 18 December 2011, 601 patients underwent liver transplantation at our service (Hospital Universitário Walter Cantídio, University of Ceará), 176 (29.2%) of whom were hepatitis C virus positive. Forty received antiviral therapy and were included in this cohort study. Twenty-eight (70%) completed the treatment protocol, which consisted of pegylated interferon and ribavirin for 48 weeks.ResultsThe sustained virological response rate was 55% according to intention-to-treat analysis. Recipient age and exposure to antiviral drugs prior to liver transplantation were associated with sustained virological response in the multivariate analysis. Patients were followed for 57 months on the average. Survival at 1 and 5 years was 100% in responders, versus 100% and 78%, respectively, in non-responders.ConclusionSustained virological response rates were satisfactory in our series of liver transplantation patients, and decreased with increasing recipient age. Non-exposure to antiviral drugs prior to liver transplantation was positively associated with sustained virological response. The overall survival of responders and non-responders was similar.

Helicobacter pylori infection is one of the most common infections worldwide and is associated with gastric diseases. Virulence factors such as VacA and CagA have been shown to increase the risk of these diseases. Studies have suggested a causal role of CagA EPIYA-C in gastric carcinogenesis and this factor has been shown to be geographically diverse. We investigated the number of CagA EPIYA motifs and the vacA i genotypes in H. pylori strains from asymptomatic children. We included samples from 40 infected children (18 females and 22 males), extracted DNA directly from the gastric mucus/juice (obtained using the string procedure) and analysed the DNA using polymerase chain reaction and DNA sequencing. The vacA i1 genotype was present in 30 (75%) samples, the i2 allele was present in nine (22.5%) samples and both alleles were present in one (2.5%) sample. The cagA-positive samples showed distinct patterns in the 3’ variable region of cagA and 18 of the 30 (60%) strains contained 1 EPIYA-C motif, whereas 12 (40%) strains contained two EPIYA-C motifs. We confirmed that the studied population was colonised early by the most virulent H. pylori strains, as demonstrated by the high frequency of the vacA i1 allele and the high number of EPIYA-C motifs. Therefore, asymptomatic children from an urban community in Fortaleza in northeastern Brazil are frequently colonised with the most virulent H. pylori strains.

Helicobacter pylori causes chronic gastric inflammation and significantly increases the risk of duodenal and gastric ulcer disease and distal gastric carcinoma. In this study, we evaluated the Helicobacter pylori vacA and cagA genotypes in patients from a Brazilian region where there is a high prevalence of gastric cancer. Polymerase chain reaction (PCR) was used to investigate vacA mosaicism and cagA status in the gastric mucosa of 134 H. pylori-positive patients, including 76 with gastritis: 28 with peptic ulcer disease and 30 with gastric cancer. The s1m1 variant was the predominant vacA genotype observed, whereas the s1 allele was more frequently observed in patients with more severe diseases associated with H. pylori infection [p = 0.03, odds ratio (OR) = 5.72, 95% confidence interval (CI) = 1.15-38.60]. Furthermore, all of the s1 alleles were s1b. Mixed vacA m1/m2 strains were found more frequently in patients with gastric cancer and a cagA-positive status was significantly associated with gastric cancer (p = 0.016, OR = 10.36, 95% CI = 1.35-217.31). Patients with gastric cancer (21/21, 100%, p = 0.006) or peptic ulcers (20/21, 95%, p = 0.02) were more frequently colonised by more virulent H. pylori strains compared to gastritis patients (41/61, 67.2%). In conclusion, in the northeastern of Brazil, which is one of the regions with the highest prevalence of gastric cancer in the country, infection with the most virulent H. pylori strains, carrying the cagA gene and s1m1 vacA alleles, predominates and is correlated with more severe H. pylori-associated diseases.

CONTEXTO E OBJETIVO: Peritonite bacteriana espontânea (PBE) é uma freqüente e grave complicação em pacientes cirróticos com ascite. Vem sendo proposto o uso de fitas reagente para esterase leucocitária, utilizadas para diagnóstico de infecção urinária, como instrumento para diagnosticar PBE. O objetivo deste estudo é avaliar a sensibilidade e a especificidade da fita reagente Combur Test® UX no diagnóstico de PBE em pacientes cirróticos com ascite. TIPO DE ESTUDO E LOCAL: Estudo prospectivo, realizado no Hospital Universitário Walter Cantídio, Fortaleza, Ceará, Brasil. MÉTODOS: Quarenta e dois pacientes consecutivos, não selecionados (32 homens, com média de idade de 51,7 ± anos) foram incluídos e um total de 100 paracenteses foram realizadas. O líquido ascítico foi avaliado pela fita reagente (Combur Test® UX), citologia, contagem de neutrófilos, linfócitos, testes bioquímicos e cultura. As fitas reagentes foram consideradas positivas se havia mudança na cor para roxo na escala colorimétrica fornecida pelo fabricante. RESULTADOS: Foram diagnosticados nove pacientes com PBE pela citologia (> 250 neutrófilos/mm³), estando a fita Combur Test® UX positiva em todos os nove pacientes. Em uma amostra o teste da fita foi positivo, embora a contagem de neutrófilos fosse < 250 células/mm³. Nas outras 86 amostras ambos os testes foram negativos. Tendo-se como ponto de corte 250 PMN/mm³ no líquido ascítico, a sensibilidade, a especificidade, o valor preditivo positivo e o valor preditivo negativo foram respectivamente 100%, 98,9%, 92,3% e 100%. CONCLUSÕES: Combur Test® UX (fita reagente para urinanálise) é um método sensível e específico para o diagnóstico de PBE em pacientes cirróticos com ascite.

CONTEXT AND OBJECTIVE: Spontaneous bacterial peritonitis (SBP) is a frequent and severe complication of cirrhotic patients with ascites. It has been proposed that the reagent strip for leukocyte esterase designed for the testing of urine (Combur test® UX) could be a useful tool for diagnosing SPB. The aim of this study was to assess the sensitivity and specificity of urine test strips for diagnosing SBP in cirrhotic patients with ascites. DESIGN AND SETTING: Prospective study, at a university hospital in northeastern Brazil. METHODS: Forty-two unselected consecutive cirrhotic patients (32 males; mean age: 51.7 ± years) were included, and a total of 100 paracenteses were performed. All ascitic fluid samples were analyzed using the reagent strip and cytology, neutrophils, lymphocyte count, appropriate biochemical tests and culturing. The strips were considered positive if the color became purple on a colorimetric scale. RESULTS: Nine patients were diagnosed with SBP using cytology (> 250 neutrophils/mm³), and the strips were positive for all these nine patients with SBP. In one sample, the strip was positive but the neutrophil count was less than 250 cells/mm³. For 86 samples, both the strips and cytology were negative. At the threshold of 250 neutrophils/mm³ in ascitic fluid, the sensitivity, specificity, positive predictive value and negative predictive value for the strips were respectively 100%, 98.9%, 92.3% and 100%. CONCLUSION: The Combur test® UX urine screening test is a very sensitive and specific method for diagnosing SBP in cirrhotic patients with ascites.

RACIONAL: Ainda não está estabelecida a melhor terapêutica anti-H. pylori. OBJETIVO: Avaliar a erradicação de H.pylori usando tetraciclina e furazolidona versus amoxicilina e azitromicina em terapia tríplice com lansoprazol no nordeste do Brasil. PACIENTES E MÉTODOS: Cento e quatro pacientes infectados por H. pylori, diagnosticado através do teste rápido da urease e histologia, foram selecionados aleatoriamente para receber: lansoprazol (30 mg q.d.), tetraciclina (500 mg q.i.d.), furazolidona (200 mg t.i.d.) por 7 dias (LTF; n = 52); ou lansoprazol (30 mg b.i.d.) e amoxicilina (1 g b.i.d.) por 1 semana, mais azitromicina (500 mg q.d.) nos primeiros 3 dias (LAAz; n = 52). A erradicação de H.pylori foi avaliada 3 meses após término da terapia através do teste da urease, histologia e teste respiratório usando uréia marcada com 14Carbono. RESULTADOS: A erradicação do H. pylori foi atingida em 46 de 52 (88.4%, 95% CI: 77.5%-95.1%) pacientes no grupo LTF e em 14 de 52 (26.9%, 95% CI: 16.2%-40,1%) pacientes no grupo LAAz. Na análise per-protocolo, a taxa de erradicação foi de 91.8% (95% CI: 81.4%-97.3%) e 28.5% (95% CI: 17.2%-42.3%), respectivamente no grupo de LTF e LAAz. CONCLUSÃO: O esquema com LAAz ofereceu taxas de erradicação inaceitáveis. Por outro lado, o esquema com LTF representa alternativa adequada para erradicação de H.pylori.

BACKGROUND: Optimal anti-Helicobacter pylori treatment has not yet been established. AIM: To evaluate H. pylori eradication using tetracycline and furazolidone versus amoxicillin and azithromycin in lansoprazole based triple therapy in northeastern of Brazil. PATIENTS AND METHODS: One hundred and four patients with H. pylori infection, as determined by rapid urease testing and histology, were randomly assigned to receive either: lansoprazole (30 mg q.d.), tetracycline (500 mg q.i.d.), and furazolidone (200 mg t.i.d.) for 7 days (LTF; n = 52); or lansoprazole (30 mg b.i.d.) and amoxicillin (1 g b.i.d.) for 1 week, plus azithromycin (500 mg q.d.) for the first 3 days (LAAz; n = 52). H. pylori eradication was assessed 3 months following completion of therapy by means of rapid urease testing, histology and a 14C-urea breath test. RESULTS: H. pylori eradication was achieved in 46 of 52 (88.4%, 95% CI: 77.5%-95.1%) patients in LTF group and in 14 of 52 (26.9%, 95% CI: 16.2%-40,1%) patients in LAAz group. On a per-protocol analysis, eradication rates were 91.8% (95% CI: 81.4%-97.3%) and 28.5% (95% CI: 17.2%-42.3%), respectively in LTF and LAAz groups. CONCLUSION: The LAAz regimen yielded unacceptably low eradication rates. On the other hand, the LTF scheme represents a suitable alternative for H. pylori eradication.