Eosinófilos duodenais : potencial associação com a infecção pelo Helicobacter pylori e com os sintomas da dispepsia funcional

Introdução e objetivos: Eosinofilia duodenal está associada com parasitoses intestinais e com alergias alimentares, e tem sido sugerida como possível fator etiológico da dispepsia funcional, pela capacidade de causar alterações na motilidade e na sensibilidade do aparelho digestivo. Sua relação com o Helicobacter pylori é pouco conhecida, tendo sido avaliada apenas como achado secundário em alguns estudos, com resultados controversos. Esse estudo tem como objetivos avaliar o papel da infecção gástrica pelo H. pylori no número de eosinófilos duodenais e avaliar a relação dos eosinófilos duodenais com os sintomas da dispepsia funcional. Métodos: foram avaliados 100 pacientes dispépticos funcionais, de acordo com os critérios de Roma III, dos quais 50 foram H. pylori positivos e 50 negativos. Os pacientes foram submetidos à endoscopia digestiva alta com biópsias gástricas e duodenais. A positividade do H. pylori foi avaliada pelo teste de urease e pelo exame histológico (Hematoxilina-eosina e Giemsa). As biópsias duodenais foram avaliadas com hematoxilina-eosina e a número de eosinófilos duodenais foi quantificada pela média de eosinófilos por 5 campos de grande aumento (CGA) aleatórios e não sobrepostos. Eosinofilia duodenal foi definida pela presença de >22 eosinófilos/CGA. As medianas das médias aritméticas dos eosinófilos duodenais por cinco CGA foram comparadas entre os pacientes H. pylori positivos e negativos. Também foi avaliada a relação do número de eosinófilos duodenais com a intensidade e tipo de sintomas dispépticos, determinados por questionário validado (PADYQ). Os eosinófilos duodenais foram avaliados para variáveis demográficas e endoscópicas. Resultados: Pacientes do sexo feminino representaram 88% da amostra e a idade média foi de 41,7 anos As características basais dos pacientes H. pylori positivos e H. pylori negativos foram semelhantes. Apenas um paciente, no grupo H. pylori positivo, apresentou eosinofilia duodenal. As medianas dos eosinófilos duodenais/CGA foram 4,6 [P25-75: 2,8-7,2] nos pacientes H. pylori negativos e 4,7 [P25-75: 3,4-8,4] nos H. pylori positivos (p= 0,403). O número de eosinófilos 8 duodenais foi significativamente maior em pacientes com sintomas mais intensos: pacientes com escore do PADYQ >22 (>50% da pontuação máxima) apresentaram mediana de eosinófilos duodenais/CGA de 5,4 [P25-75: 3,4–7,6] e pacientes com escore ≤22 de 3,4 [P25-75: 2,2–6,0] (p= 0,018). Os pacientes foram divididos em tercis, de acordo com a intensidade dos sintomas: grupo 1 com 31 pacientes (sintomas leves); grupo 2 com 30 pacientes (sintomas moderados); e grupo 3 com 31 pacientes (sintomas acentuados). A mediana dos eosinófilos duodenais/CGA no grupo 1 foi de 3,4 [P25-75: 2,2 -6,0]; no grupo 2 de 4,7 [P25-75: 3,2-6,4]; e o grupo 3 de 5,8 [P25-75: 3,6-8,2] (P=0,033). Houve diferença estatisticamente significativa no número de eosinófilos duodenais entre fumantes e não fumantes (p= 0,030) e entre pacientes com índice de massa corporal (IMC) 22 eosinophils/HPF. The median of the arithmetic means of the duodenal eosinophils counts per high power field were compared between H. pylori positive and H. pylori negative subjects. The relationship between the number of duodenal eosinophils and the intensity and type of dyspeptic symptoms was determined by validated questionnaire (PADYQ). Duodenal eosinophils counts were also evaluated by demographic variables and endoscopic findings. Results: 88% of the subjects were female and the mean age was 41.7 years. Baseline characteristics were similar between H. pylori positive and H. pylori negative subjects. Only one patient, in the H. pylori positive group, had duodenal eosinophilia. The median duodenal eosinophils/HPF were 4.6 [Percentiles 25-75(P25-75): 2.8-7.2] in H. pylori negative and 4.7 [P25-75: 3.4-8.4] in H. pylori positive subjects (p= 0.403). The duodenal eosinophil count was greater in subjects with higher symptoms severity: patients with PADYQ score more than 22 (>50% of the maximum score) had median duodenal eosinophil/HPF of 5.4 [P25-75: 3,4–7,6] and subjects with PADYQ score ≤22 of 3.4 [P25-75: 2.2–6.0] (p= 0.018). The patients were divided into terciles, according to symptoms severity: group 1 with 31 subjects (mild symptoms); group 2 with 30 subjects (moderate symptoms); and group 3 with 31 subjects (severe symptoms). 10 The median duodenal eosinophils/HPF was 3.4 [P25-75: 2.2-6.0] in group 1; 4.7 [P25-75: 3.2-6.4] in group 2; and 5.8 [P25-75: 3.6-8.2] in group 3 (p=0.033). There was a higher duodenal eosinophils count in smokers (current or former) (p=0.030), and subjects with BMI ≥ 25 kg/m2 (p=0.035). In the multivariate analysis by linear regression, the duodenal eosinophil count were influenced by smoking (p = 0.026) and dyspeptic symptoms severity (p= 0.039). Conclusion: This study did not show an association between H. pylori infection and the number of duodenal eosinophils, in this population of functional dyspeptic patients. However, a directly proportional and statistically significant relationship between the number of duodenal eosinophils and the intensity of dyspeptic symptoms has been demonstrated

Helicobacter pylori eradication : influence of interleukin-1beta –31 C/T polymorphism

Aim: To analyze the influence of the –31 C/T polymorphism of the interleukin-1 gene on Helicobacter pylori eradication therapy success in patients with functional dyspepsia. Methods: Functional dyspepsia was diagnosed according to the Rome III criteria. All patients underwent upper gastrointestinal endoscopy, and gastric biopsies were obtained at screening and 12 months after randomization (last follow-up visit). Urease test and histological examination were performed to define the H. pylori status. Patients received twice-daily amoxicillin, clarithromycin and omeprazole for 10 days. Genotyping of the interleukin-1beta –31 C/T polymorphism (rs1143627)was performed using polymerase chain reaction-restriction fragment length polymorphism. Results: One hundred forty-nine patients received treatment with triple therapy for H. pylori eradication. Only one patient was lost to follow-up, and adherence to study medication was 94.6%. A total of 148 patients (mean age 46.08±12.24 years; 81.8% women) were evaluated for the influence of the interleukin-1beta –31 C/T polymorphism on the outcome of H. pylori eradication therapy. After treatment, bacteria were eradicated in 87% of patients (129/148). Genotype frequencies of the polymorphism were as follows: CC, 38/148 (25.7%); CT, 71/148 (47.9%); and TT, 39/148 (26.4%). Successful eradication rate was 78.9%, 94.4% and 82.1% for the CC, CT and TT genotypes, respectively. The CT genotype was significantly associated with successful H. pylori eradication (p = 0.039). Conclusion: This study suggests that the CT genotype of the interleukin-1beta –31 C/T polymorphism plays a role in the successful eradication of H. pylori among patients with functional dyspepsia

Efficacy and safety of glecaprevir/pibrentasvir in treatment-naïve adults with chronic hepatitis C virus genotypes 1–6 in Brazil

Introduction and objectives: Glecaprevir/pibrentasvir is a highly effective and well tolerated treatment for hepatitis C infection. Brazilian patients were not included in the original development studies for glecaprevir/pibrentasvir. This study aimed to assess safety and efficacy of glecaprevir/pibrentasvir in treatment-naïve Brazilian adults without cirrhosis or with compensated cirrhosis. Patients and methods: EXPEDITION-3 was a Phase 3, open-label, multicenter study in treatment-naïve Brazilian adults with hepatitis C infection genotype 1–6. Patients without cirrhosis (F2 or F3) or with compensated cirrhosis (F4) received 8 or 12 weeks of glecaprevir/pibrentasvir, respectively. The primary efficacy endpoint was the rate of sustained virologic response at post-treatment Week 12. Secondary endpoints were on-treatment virologic failure and relapse rates. Baseline polymorphisms were assessed in NS3 and NS5A. Adverse events and laboratory abnormalities were monitored. Results: 100 patients were enrolled, 75 received 8 weeks of treatment and 25 received 12 weeks; all patients completed treatment. Overall sustained virologic response at post-treatment Week 12 rate was high (98.0%; 98/100; 95% confidence interval: 93.0–99.4) and remained high regardless of baseline viral or host factors, including demographics, hepatitis C virus RNA levels, polymorphisms in NS3 and/or NS5A, genotype, and relevant comorbidities. 55% of patients reported ≥1 adverse event, the most common beingheadache (18.0%). Four patients reported serious adverse events; none were considered drug related orled to study drug discontinuation. No hepatic decompensations were observed.Conclusions: Glecaprevir/pibrentasvir was effective and well tolerated in treatment-naïve Brazilianpatients with hepatitis C infection without cirrhosis and with compensated cirrhosis

Panta Rhei benchmark dataset: socio-hydrological data of paired events of floods and droughts

As the adverse impacts of hydrological extremes increase in many regions of the world, a better understanding of the drivers of changes in risk and impacts is essential for effective flood and drought risk management and climate adaptation. However, there is currently a lack of comprehensive, empirical data about the processes, interactions and feedbacks in complex human-water systems leading to flood and drought impacts. Here we present a benchmark dataset containing socio-hydrological data of paired events, i.e., two floods or two droughts that occurred in the same area. The 45 paired events occurred in 42 different study areas and cover a wide range of socio-economic and hydro-climatic conditions. The dataset is unique in covering both floods and droughts, in the number of cases assessed, and in the quantity of socio-hydrological data. The benchmark dataset comprises: 1) detailed review style reports about the events and key processes between the two events of a pair; 2) the key data table containing variables that assess the indicators which characterise management shortcomings, hazard, exposure, vulnerability and impacts of all events; 3) a table of the indicators-of-change that indicate the differences between the first and second event of a pair. The advantages of the dataset are that it enables comparative analyses across all the paired events based on the indicators-of-change and allows for detailed context- and location-specific assessments based on the extensive data and reports of the individual study areas. The dataset can be used by the scientific community for exploratory data analyses e.g. focused on causal links between risk management, changes in hazard, exposure and vulnerability and flood or drought impacts. The data can also be used for the development, calibration and validation of socio-hydrological models. The dataset is available to the public through the GFZ Data Services (Kreibich et al. 2023, link for review: https://dataservices.gfz-potsdam.de/panmetaworks/review/923c14519deb04f83815ce108b48dd2581d57b90ce069bec9c948361028b8c85/).</p

Twenty-three unsolved problems in hydrology (UPH) – a community perspective

This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through on-line media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focussed on process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems

Influence of CYP2C19 on Helicobacter pylori eradication in Brazilian patients with functional dyspepsia

The aim of this study was to examine the effect of polymorphisms in the cytochrome P450 (CYP) 2C19 gene (CYP2C19) on the Helicobacter pylori eradication rate in Brazilian patients with functional dyspepsia. Adults diagnosed with functional dyspepsia based on the ROME III criteria and infected with H. pylori were recruited to this study. The patients were subjected to gastrointestinal endoscopy and the H. pylori status was defined when both urease test and histopathology results were negative or positive. The patients were treated with proton pump inhibitor-based triple therapy (omeprazole, amoxicillin, and clarithromycin). CYP2C19*2 and CYP2C19*3 were genotyped by polymerase chain reaction-restriction fragment length polymorphism. One hundred and forty-eight patients (81.8% women) with a mean (± SD) age of 46.1 (12.2) years were included in this study. Based on the CYP2C19 genotypes, the patients were classified as homozygous extensive metabolizer (HomEM; 67.6%), heterozygous extensive metabolizer (HetEM; 26.3%), or poor metabolizer (PM; 6.1%). The H. pylori eradication rates in patients with HomEM, HetEM, and PM were 85.0, 89.7, and 100.0% (P = 0.376), respectively. The included study population comprised a high frequency of patients carrying the HomEM genotype. Although the genotypes of CYP2C19 variants were not statistically significant, the results of this study suggest a possible effect of the PM genotype on the efficacy of H. pylori eradication