PREVALENCE OF SERRATED POLYPS AND THEIR ASSOCIATION WITH SYNCHRONOUS COLORECTAL ADVANCED ADENOMAS.

•This study revealed a similar prevalence of clinically significant serrated polyps and advanced adenomas among patients who underwent colonoscopy. •Multivariate analysis demonstrated an association between clinically significant serrated polyps and synchronous advanced adenomas, though the strength of this association was stronger for proximal advanced adenomas. •Large serrated polyps and sessile serrated adenomas were associated with proximal advanced adenomas. Background - Serrated lesions are the precursors of up to one-third of colorectal cancer (CRC) cases and share molecular and epidemiological features with interval CRC. Previous studies have reported wide variation in serrated polyp prevalence and diverse magnitude of its relationship with synchronous advanced adenomas.Objective - Describe the prevalence of serrated polyps and evaluate their association with synchronous advanced adenomas. Methods - The study is a retrospective analysis of 1208 colonoscopies performed in patients aged 45 to 75, predominantly for CRC screening. Data on the prevalence of serrated polyps subsets and advanced adenomas were collected, and multivariate analysis were performed to identify the association between serrated polyps and synchronous advanced adenomas. Results - The prevalence of clinically significant serrated polyps (CSSP), large serrated polyps (LSP), and sessile serrated adenomas (SSA) were 11.3%, 6%, and 3.7%. CSSP were associated with synchronous advanced adenomas (OR 2.121, 95%CI 1.321-3.406), regardless of proximal (OR 2.966, 95%CI 1.701-5.170) or distal (OR 1.945, 95%CI 1.081-3.499) location, while LSP (OR 2.872, 95%CI 1.425-5.787) and SSA (OR 5.032, 95%CI 2.395-10.576) were associated with proximal advanced adenomas. Conclusion - The prevalence of CSSP and advanced adenomas were alike. CSSP is a risk factor for advanced adenomas, and the strength of this association is stronger for proximal advanced adenomas. LSP and SSA are associated with proximal advanced adenomas.

Prevalência de pólipos serrilhados e sua associação com adenomas avançados colorretais síncronos / Prevalence of serrated polyps and their association with synchronous colorectal advanced adenomas

ABSTRACT Background: Serrated lesions are the precursors of up to one-third of colorectal cancer (CRC) cases and share molecular and epidemiological features with interval CRC. Previous studies have reported wide variation in serrated polyp prevalence and diverse magnitude of its relationship with synchronous advanced adenomas. Objective: Describe the prevalence of serrated polyps and evaluate their association with synchronous advanced adenomas. Methods: The study is a retrospective analysis of 1208 colonoscopies performed in patients aged 45 to 75, predominantly for CRC screening. Data on the prevalence of serrated polyps subsets and advanced adenomas were collected, and multivariate analysis were performed to identify the association between serrated polyps and synchronous advanced adenomas. Results: The prevalence of clinically significant serrated polyps (CSSP), large serrated polyps (LSP), and sessile serrated adenomas (SSA) were 11.3%, 6%, and 3.7%. CSSP were associated with synchronous advanced adenomas (OR 2.121, 95%CI 1.321-3.406), regardless of proximal (OR 2.966, 95%CI 1.701-5.170) or distal (OR 1.945, 95%CI 1.081-3.499) location, while LSP (OR 2.872, 95%CI 1.425-5.787) and SSA (OR 5.032, 95%CI 2.395-10.576) were associated with proximal advanced adenomas. Conclusion: The prevalence of CSSP and advanced adenomas were alike. CSSP is a risk factor for advanced adenomas, and the strength of this association is stronger for proximal advanced adenomas. LSP and SSA are associated with proximal advanced adenomas.

RESUMO Contexto: Lesões serrilhadas são precursoras de até um terço dos casos de câncer colorretal (CCR) e compartilham características moleculares e epidemiológicas com o CCR de intervalo. Estudos prévios relataram ampla variação na prevalência de pólipos serrilhados e na magnitude da sua relação com adenomas avançados sincrônicos. Objetivo: Descrever a prevalência de pólipos serrilhados colorretais e avaliar sua associação com adenomas avançados sincrônicos. Métodos: O estudo é uma análise retrospectiva de 1208 colonoscopias realizadas em pacientes com idades entre 45 e 75 anos, predominantemente para rastreamento de CCR. Dados sobre a prevalência de subtipos de pólipos serrilhados e de adenomas avançados foram coletados, e análises multivariadas foram realizadas para identificar a associação entre pólipos serrilhados e adenomas avançados sincrônicos. Resultados: A prevalência de pólipos serrilhados clinicamente significativos (PSCS), pólipos serrilhados grandes (PSG) e adenomas sésseis serrilhados (ASS) foi de 11,3%, 6% e 3,7%, respectivamente. PSCS foram associados a adenomas avançados sincrônicos (OR 2,121, IC95% 1,321-3,406), independentemente da localização proximal (OR 2,966, IC95% 1,701-5,170) ou distal (OR 1,945, IC95% 1,081-3,499), enquanto PSG (OR 2,872, IC 95%1,425-5,787) e ASS (OR 5,032, IC95% 2,395-10,576) foram associados a adenomas avançados proximais. Conclusão: A prevalência de PSCS e de adenomas avançados foi semelhante. PSCS é um fator de risco para adenomas avançados, e a força dessa associação é maior para adenomas avançados proximais. PSG e ASS estão associados a adenomas avançados proximais.

EVALUATION OF UNDERWATER ENDOSCOPIC MUCOSAL RESECTION FOR COLORECTAL POLYPS IN AN OUTPATIENT CLINIC IN BRAZIL.

BACKGROUND: Since 2012, a new technique for resection of large polyps has been described, the underwater endoscopic mucosal resection (UEMR). Some advantages that emerge from it is the needless of injection in submucosal layer and a greater chance of complete capture of the polyp. OBJECTIVE: There are few studies of UEMR in Brazil. The aim of this study is to evaluate the safety and efficacy of this technique in one Brazilian center. METHODS: This case series was conducted from February to December of 2020. Colorectal polyps greater than 9 mm without features of deep submucosal invasion were resected using UEMR. RESULTS: Twenty-four large polyps were resected with the UEMR approach from 24 patients. The mean size of the polys was 19 mm, ranging from 12 to 35 mm. All lesions were successful resected and 66% (16/24) were resected en bloc. In histologic analyses, most of them were adenomas (70.8%) and only one had deep submucosal invasion. There were no cases of acute complications, such perforation or acute bleeding. CONCLUSION: The UEMR is a safe and feasible procedure. With the emerging data on the procedure, it seems to be a wonderful tool in preventing colorectal cancer and its applicability and scope should be encourage to surpass reference centers.

Avaliação de ressecção de mucosa endoscópica sob imersão d'água de pólipos colorretais em um centro ambulatorial no Brasil / Evaluation of underwater endoscopic mucosal resection for colorectal polyps in an outpatient clinic in brazil

ABSTRACT BACKGROUND: Since 2012, a new technique for resection of large polyps has been described, the underwater endoscopic mucosal resection (UEMR). Some advantages that emerge from it is the needless of injection in submucosal layer and a greater chance of complete capture of the polyp. OBJECTIVE: There are few studies of UEMR in Brazil. The aim of this study is to evaluate the safety and efficacy of this technique in one Brazilian center. METHODS: This case series was conducted from February to December of 2020. Colorectal polyps greater than 9 mm without features of deep submucosal invasion were resected using UEMR. RESULTS: Twenty-four large polyps were resected with the UEMR approach from 24 patients. The mean size of the polys was 19 mm, ranging from 12 to 35 mm. All lesions were successful resected and 66% (16/24) were resected en bloc. In histologic analyses, most of them were adenomas (70.8%) and only one had deep submucosal invasion. There were no cases of acute complications, such perforation or acute bleeding. CONCLUSION: The UEMR is a safe and feasible procedure. With the emerging data on the procedure, it seems to be a wonderful tool in preventing colorectal cancer and its applicability and scope should be encourage to surpass reference centers.

RESUMO CONTEXTO: Desde 2012, uma nova técnica para ressecção de pólipos grandes tem sido descrita, a ressecção da mucosa endoscópica sob imersão d'água (REMS). Algumas vantagens que surgem desta técnica são evitar a injeção na camada submucosa e a maior chance de captura completa do pólipo. Objetivo - Há poucos estudos com REMS no Brasil. Nosso objetivo é avaliar a segurança e a eficácia da técnica em um centro brasileiro. MÉTODOS: Esta série de casos foi conduzida de fevereiro a dezembro de 2020. Pólipos colorretais maiores que 9 mm sem sinais endoscópicos de invasão de submucosa foram ressecados utilizando RMES. RESULTADOS: Vinte e quatro pólipos foram ressecados com RMES em 24 pacientes diferentes. O tamanho médio dos pólipos era de 19 mm, variando de 12 a 35 mm. Todas as lesões foram ressecadas e 66% (16/24) foram ressecadas em monobloco. Na análise histológica, a maioria era adenoma (70.8%) e apenas uma havia invasão profunda da submucosa. CONCLUSÃO: O uso de REMS é um procedimento seguro e factível. Com o aumento de dados relativos ao procedimento, esta parece ser uma excelente ferramenta na prevenção do câncer colorretal e sua aplicabilidade deve ser encorajada para fora dos centros de referência.

Interferon-lambda 3 and 4 Polymorphisms Increase Sustained Virological Responses and Regulate Innate Immunity in Antiviral Therapy With Pegylated Interferon-Alpha.

Sustained virologic response (SVR) in chronic hepatitis C (CHC) treatment denotes that the host genetics controls the immune response and unequivocally contribute to viral clearance or disease severity. In this context, single nucleotide polymorphisms (SNPs) in the locus of interferon lambda 3 and 4 genes (IFNL3/4) have been important genetic markers of responsiveness to CHC as prognostic markers for the pegylated-Interferon-alpha/ribavirin (Peg-IFN-α/RBV). Here, we analyzed 12 SNPs at the IFNL3/4 region in 740 treatment-naïve patients with CHC infected with hepatitis C virus (HCV) genotypes 1, 2, or 3 treated with Peg-IFN-α/RBV. Individually, rs12979860-CC, rs8109886-CC, or rs8099917-TT were predictive markers of SVR, while rs12979860-CC demonstrated the stronger effect. Besides, the genotypic combination of these three predictors' genotypes, CC/CC/TT, increased the rate of SVR. Serum levels of cytokines and gene expression analysis on the genes IFNL3, IFNL4, IFNA1, and some of the IFN-stimulated genes (ISGs) were measured in a subgroup of 24 treated patients and 24 healthy volunteers. An antagonist effect was highlighted between the expression of IFNL3/4 and IFNA1 mRNA among patients. Besides, a prominent production of the pro-inflammatory chemokines CCL4 and CXCL10 was observed at a 12-week treatment follow-up. Lower serum levels of these chemokines were detected in patients with an rs12979860-CC genotype associated with the better treatment outcome. Also, lower expression levels of the IFI6, IFI16, IRF9 genes were observed among rs12979860-CC individuals. In conclusion, a combination of the genotypes at the IFNL3/4 locus can act as a better marker for the prognosis for virological responses in an admixed Brazilian population presenting the modulating effect over innate immunity and inflammation that are controlling the outcome of the viral infection, but also other infectious diseases. This study is registered on the ClinicalTrials.gov platform (accession number NCT01889849 and NCT01623336).

Patient safety in an endoscopy unit: an observational retrospective analysis of reported incidents.

INTRODUCTION: Patient safety is a serious public health with serious implications on morbidity, mortality, and quality of life of patients, in addition to negatively affecting the public image of healthcare institutions and professionals. It requires further investigation, especially in specialties lacking published data, such as endoscopy. OBJECTIVE: To analyze patient safety incidents reported in a gastrointestinal endoscopy unit of a tertiary hospital in southern Brazil. METHODS: This retrospective, cross-sectional study quantitatively described patient safety incidents related to endoscopic procedures. The sample consisted of reports of incidents that occurred from 2015 to 2017. The data were descriptively analysed, and the study was approved by the relevant research ethics committee. RESULTS: Overall, 42,863 endoscopic procedures were performed and 167 reports were submitted in the period, accounting for a prevalence of incidents of 0.38%. Most incidents did not result in unnecessary harm to patients (76.6%). The most prevalent incidents were those related to patient identification, followed by those related to pathology exams, exam reports, gastrointestinal perforations, skin lesions, falls and medication errors. The rate of adverse events (harm to patient) in patients undergoing any endoscopic procedure was 0.06%. CONCLUSIONS: The incidence of unnecessary harm (adverse event) associated with any endoscopic procedure was relatively low in this study. However, the identification of reported incidents is crucial for evaluating and improving the quality of care provided to patients.

ASSOCIATION OF DUODENAL EOSINOPHILIC INFILTRATE WITH HELICOBACTER PYLORI INFECTION, BUT NOT WITH FUNCTIONAL DYSPEPSIA.

BACKGROUND: The role of Helicobacter pylori infection on eosinophilic infiltration in duodenal mucosa is poorly studied. An increase in the number of eosinophils in duodenum has been associated with functional dyspepsia. OBJECTIVE: To evaluate the influence of H. pylori infection on duodenal eosinophil count and the role of eosinophilic infiltrate of duodenum in functional dyspepsia. METHODS: Positive and negative H. pylori individuals were included. Both functional dyspeptic patients according to Rome III criteria (cases) and individuals without gastrointestinal symptoms (controls) were enrolled. They were submitted to upper endoscopy and H. pylori infection was verified by gastric histopathology and urease test. Eosinophils in the duodenal mucosa were counted in five high-power fields, randomly selected on slides of endoscopic biopsies. RESULTS: Thirty-nine H. pylori positive (mean age 40.5 and 69.2% women) and 24 negative patients (mean age 37.3 and 75% women) were included. The influence of the infection was observed in the duodenal eosinophil count, which was higher in infected individuals: median 13.2 vs 8.1 in non-infected individuals (P=0.005). When we analyzed patients according to symptoms, cases - mean age 39.6; 71.4% women - and controls - mean age 38.7; 71.4% women - had similar duodenal eosinophil count: median 11.9 and 12.6 respectively (P=0.19). CONCLUSIONS: We did not demonstrate association of duodenal eosinophil count with functional dyspepsia but found association with H. pylori infection.

Associação de infiltrado eosinofílico duodenal com infecção por Helicobacter pylori, mas não com dispepsia funcional / Association of duodenal eosinophilic infiltrate with helicobacter pylori infection, but not with functional dyspepsia

ABSTRACT BACKGROUND: The role of Helicobacter pylori infection on eosinophilic infiltration in duodenal mucosa is poorly studied. An increase in the number of eosinophils in duodenum has been associated with functional dyspepsia. OBJECTIVE: To evaluate the influence of H. pylori infection on duodenal eosinophil count and the role of eosinophilic infiltrate of duodenum in functional dyspepsia. METHODS: Positive and negative H. pylori individuals were included. Both functional dyspeptic patients according to Rome III criteria (cases) and individuals without gastrointestinal symptoms (controls) were enrolled. They were submitted to upper endoscopy and H. pylori infection was verified by gastric histopathology and urease test. Eosinophils in the duodenal mucosa were counted in five high-power fields, randomly selected on slides of endoscopic biopsies. RESULTS: Thirty-nine H. pylori positive (mean age 40.5 and 69.2% women) and 24 negative patients (mean age 37.3 and 75% women) were included. The influence of the infection was observed in the duodenal eosinophil count, which was higher in infected individuals: median 13.2 vs 8.1 in non-infected individuals (P=0.005). When we analyzed patients according to symptoms, cases - mean age 39.6; 71.4% women - and controls - mean age 38.7; 71.4% women - had similar duodenal eosinophil count: median 11.9 and 12.6 respectively (P=0.19). CONCLUSIONS: We did not demonstrate association of duodenal eosinophil count with functional dyspepsia but found association with H. pylori infection.

RESUMO CONTEXTO: O papel de infecção por Helicobacter pylori no infiltrado eosinofílico duodenal ainda é pouco compreendido. Um aumento no número de eosinófilos duodenais tem sido associado a dispepsia funcional. OBJETIVO: Avaliar a influência do H. pylori na contagem de eosinófilos duodenais e o papel do infiltrado eosinofílico duodenal na dispepsia funcional. MÉTODOS: Indivíduos H. pylori positivo e negativo foram incluídos. Ambos os grupos, compreendendo dispépticos funcionais pelos critérios de Roma III (casos) e indivíduos sem sintomas gastrointestinais (controles), foram submetidos à endoscopia digestiva alta para pesquisa de H. pylori, efetuada por histopatologia e teste de urease. Eosinófilos na mucosa duodenal foram contabilizados em cinco campos de maior aumento, selecionados randomicamente nas lâminas de biópsia endoscópicas. RESULTADOS: Trinta e nove indivíduos H. pylori positivo (média de idade 40,5 e 69,2% mulheres) e 24 H. pylori negativos (média de idade 37,3 e 75% mulheres) foram incluídos. A influência da infecção por H. pylori foi observada na contagem de eosinófilos, que foi maior nos positivos: mediana 13,2 vs 8,1 (P=0,005). Quando analisados pacientes de acordo com sintomas, os casos (média de idade 39,6 e 71,4% mulheres) e controles (média de idade 38,7 e 71,4% mulheres), apresentaram semelhante contagem de eosinófilos duodenais: mediana 11,9 e 12,6, respectivamente (P=0,19). CONCLUSÃO: Não demonstramos associação da contagem de eosinófilos duodenais com dispepsia duodenal, mas encontramos associação com infecção por H. pylori.

Analysis of the Influence of Interleukin-1ß Gene Polymorphism on Gastric Inflammatory Response and Precancerous Lesions Development in Patients with Functional Dyspepsia.

The present study aimed to evaluate the influence of the IL1B -31C/T polymorphism on gastric inflammatory response and precancerous lesions development - atrophic gastritis (AG) and intestinal metaplasia (IM) - in patients positive for Helicobacter pylori infection with functional dyspepsia (FD). The diagnosis of FD followed the Rome III criteria, and the H. pylori infection was evaluated by urease test and histological examination of gastric biopsies (corpus, antrum, and incisura). The severity of chronic inflammation and inflammatory activity, as well as the presence of precancerous lesions were evaluated accordingly to the updated Sydney System. Genotyping of the IL1B -31C/T polymorphism (rs1143627) was performed by polymerase chain reaction-restriction fragment length polymorphism. A total of 303 patients positive for H. pylori infection with FD were analyzed (81.8% women; mean age of 46.3 ± 12.3 years). No differences were observed in overall genotype frequencies among outcomes evaluated. However, in the dominant -31C allele model (CC+CT vs. TT), the frequency of the TT genotype was significantly higher among patients with moderate/severe chronic inflammation of the antrum than the frequency of the CC+CT genotypes (80.8% vs. 65.2%; OR = 2.25; 95% CI = 1.23-4.24; P = .005). The presence of AG and IM in the gastric mucosa of patients was of 19.5% and 19.1%, respectively. No significant association was observed concerning the frequencies of the genotypes of IL1B -31C/T polymorphism with development of precancerous lesions. In conclusion, our data suggest that genetic variants of the IL1B -31C/T polymorphism play a role in chronic inflammation of the gastric mucosa in H. pylori-infected FD patients.

Potential roles of Helicobacter pylori treatment, body mass index and waist circumference in the causation of erosive esophagitis: a randomized clinical trial (HEROES-GERD).

BACKGROUND: In recent decades, the prevalence of gastroesophageal reflux disease (GERD) and obesity has been increasing while Helicobacter pylori infection has been decreasing. OBJECTIVE: To evaluate if H. pylori treatment, excess body weight and other anthropometric measurements are associated with incident erosive esophagitis, as a secondary objective of a trial which tested the efficacy of treatment of H. pylori on the symptoms of functional dyspepsia. SUBJECTS/METHODS: Upper gastrointestinal endoscopy and anthropometric assessments were performed, at baseline and after 12 months, in H. pylori positive patients with functional dyspepsia who had no baseline reflux symptoms or esophagitis. Patients were randomly assigned to receive omeprazole, amoxicillin, and clarithromycin (antibiotic group; n = 201) or omeprazole plus placebo (control group; n = 203). The primary outcome was the incidence of esophagitis 12 months after randomization, according to treatment groups, and the association of BMI and other anthropometric measurements. RESULTS: Four hundred and four patients were included (mean age, 46.1 years; 78.7% women). The 12-month follow-up endoscopic esophagitis rates for the antibiotic and control groups were 10.9% (22/201) and 9.4% (19/203), respectively (p = 0.60). The number needed to harm was 67. Baseline anthropometric measurements were performed in 94% (380/404) of patients. The 12-month follow-up esophagitis rates for overweight and normal body weight patients were 13.6% (29/213) and 6.0% (10/167), respectively (p = 0.015); rates for patients with and without increased baseline waist circumference were 15.4% (24/156) and 6.7% (15/224), respectively (p = 0.006). Following logistic regression, only the combination of increased baseline body mass index and waist, but not H. pylori treatment, was independently associated with new-onset esophagitis (OR 2.88; 95% CI: 1.28-6.45). CONCLUSIONS: Excess body weight and concomitant increased waist circumference, but not H. pylori treatment, predicts new-onset esophagitis.

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

ABSTRACT Aim To analyze the influence of the -31 C/T polymorphism of the interleukin-1β 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.

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-1ß 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.

The association between adult-type hypolactasia and symptoms of functional dyspepsia

Abstract Functional dyspepsia and lactose intolerance (adult-type hypolactasia, ATH) are common conditions that may coexist or even be confounded. Their clinical presentation can be similar, however, lactose intolerance does not form part of the diagnostic investigation of functional dyspepsia. Studies on the association between functional dyspepsia and ATH are scarce. This study aimed to evaluate whether ATH is associated with symptoms of functional dyspepsia. Patients fulfilling the Rome III diagnostic criteria for functional dyspepsia underwent genetic testing for ATH. Dyspeptic symptoms were evaluated and scored according to a validated questionnaire. The diagnostic criteria for ATH was a CC genotype for the -13910C/T polymorphism, located upstream of the lactase gene. The mean scores for dyspeptic symptoms were compared between patients with ATH and those with lactase persistence. A total of 197 functional dyspeptic patients were included in the study. Mean age was 47.7 years and 82.7% patients were women. Eighty-eight patients (44.7%) had a diagnosis of ATH. Abdominal bloating scores were higher in ATH patients compared to the lactase persistent patients (P=0.014). The remaining dyspeptic symptom scores were not significantly different between the two groups. The study results demonstrate an association between ATH and bloating in patients with functional dyspepsia.

The association between adult-type hypolactasia and symptoms of functional dyspepsia.

Functional dyspepsia and lactose intolerance (adult-type hypolactasia, ATH) are common conditions that may coexist or even be confounded. Their clinical presentation can be similar, however, lactose intolerance does not form part of the diagnostic investigation of functional dyspepsia. Studies on the association between functional dyspepsia and ATH are scarce. This study aimed to evaluate whether ATH is associated with symptoms of functional dyspepsia. Patients fulfilling the Rome III diagnostic criteria for functional dyspepsia underwent genetic testing for ATH. Dyspeptic symptoms were evaluated and scored according to a validated questionnaire. The diagnostic criteria for ATH was a CC genotype for the -13910C/T polymorphism, located upstream of the lactase gene. The mean scores for dyspeptic symptoms were compared between patients with ATH and those with lactase persistence. A total of 197 functional dyspeptic patients were included in the study. Mean age was 47.7 years and 82.7% patients were women. Eighty-eight patients (44.7%) had a diagnosis of ATH. Abdominal bloating scores were higher in ATH patients compared to the lactase persistent patients (P=0.014). The remaining dyspeptic symptom scores were not significantly different between the two groups. The study results demonstrate an association between ATH and bloating in patients with functional dyspepsia.

Pharmacokinetics comparison of two pegylated interferon alfa formulations in healthy volunteers.

BACKGROUND: Several countries have used pegylation technology to improve the pharmacokinetic properties of essential drugs. Recently, a novel interferon alfa-2b protein conjugated to four-branched 12 kDa polyethylene glycol molecules was developed jointly between Cuba and Brazil. The aim of this study was to compare the pharmacokinetic properties of BIP48 (pegylated interferon alfa-2b from Bio-Manguinhos/Fiocruz, Brazil) to those of PEGASYS® (commercially available pegylated interferon alfa-2a from Roche Pharmaceutical). METHODS: This phase I, single-centre, randomized, double-blind crossover trial enrolled 31 healthy male volunteers aged 19 to 35 who were allocated to two stages, either side of a 5-week wash-out period, with each arm lasting 14 consecutive days after subcutaneous administration of 180 µg of one formulation or the other (study or comparator). The main outcome variable was serum pegylated interferon concentrations in 15 samples collected during the course of the study and tested using an enzyme immunoassay. RESULTS: There were no differences between formulations in terms of magnitude or absorption parameters. Analysis of time parameters revealed that BIP48 remained in the body significantly longer than PEGASYS® (Tmax: 73 vs. 54 h [p = 0.0010]; MRT: 133 vs. 115 h [p = 0.0324]; ke: 0.011 vs. 0.013 h(-1) [p = 0.0153]; t1/2: 192 vs. 108 h [p = 0.0218]). CONCLUSION: BIP48 showed the expected pharmacokinetic profile for a pegylated product with a branched molecular structure. Compared to PEGASYS®, the magnitude absorption was similar, but time parameters were consistent with slower elimination. Further studies should be conducted to evaluate the clinical implications of these findings. A phase II-III repeated-dose clinical trial is ongoing to study these findings in patients with chronic hepatitis C virus infection. TRIAL REGISTRATION: This study is registered on the ClinicalTrials.gov platform (accession number NCT01889849 ). This trial was retrospectively registered in June 2013.

LACK OF ASSOCIATION BETWEEN HELICOBACTER PYLORI'S VIRULENCE AND INCREASED SERUM C-REACTIVE PROTEIN LEVELS IN FUNCTIONAL DYSPEPTIC PATIENTS.

BACKGROUND: Recently, a great variety of studies aimed to investigate and even suggest Helicobacter pylori as an important key factor in gastrointestinal and non-gastrointestinal events development. The well-established relationship between bacterial virulence and increased risk for peptic ulcer or gastric carcinoma is not so clear when comparing inflammation markers alterations, such C-reactive protein, with the pathogen. OBJECTIVE: The objective of this study was to evaluate the presence of H. pylori, bacterial virulence and C-reactive protein serum levels in individuals diagnosed with functional dyspepsia. METHODS: Were prospectively included in this study 489 dyspeptic individuals. They fulfill Rome III clinical criteria for the diagnosis of functional dyspepsia with no organic disease at endoscopy. The bacterial infection was established by histology and urease rapid test. The levels of serum C-reactive protein were obtained by immunonefelometry and CagA status of H. pylori positive individuals was determined through an imunoenzimatic assay. RESULTS: Prevalence rate of H. pylori was 66.3% and virulence factor CagA was detected in nearly 43% of positive samples. In addition, it has been noticed an association between Ilex paraguariensis (yerba maté) consumption and pathogen's prevalence. An important effect of bacterial infection on inflammation was only observed in gastric epithelium. CONCLUSION: No systemic response to the pathogen, measured through C-reactive protein levels, was observed, regardless of CagA status. Otherwise, the intake of yerba maté should be considered as a cultural factor possibly related to H. pylori's transmission.

Lack of association between helicobacter pylori's virulence and increased serum c-reactive protein levels in functional dyspeptic patients

ABSTRACT Background Recently, a great variety of studies aimed to investigate and even suggestHelicobacter pylori as an important key factor in gastrointestinal and non-gastrointestinal events development. The well-established relationship between bacterial virulence and increased risk for peptic ulcer or gastric carcinoma is not so clear when comparing inflammation markers alterations, such C-reactive protein, with the pathogen. Objective The objective of this study was to evaluate the presence of H. pylori, bacterial virulence and C-reactive protein serum levels in individuals diagnosed with functional dyspepsia. Methods Were prospectively included in this study 489 dyspeptic individuals. They fulfill Rome III clinical criteria for the diagnosis of functional dyspepsia with no organic disease at endoscopy. The bacterial infection was established by histology and urease rapid test. The levels of serum C-reactive protein were obtained by immunonefelometry and CagA status ofH. pylori positive individuals was determined through an imunoenzimatic assay. Results Prevalence rate of H. pylori was 66.3% and virulence factor CagA was detected in nearly 43% of positive samples. In addition, it has been noticed an association between Ilex paraguariensis(yerba maté) consumption and pathogen's prevalence. An important effect of bacterial infection on inflammation was only observed in gastric epithelium. Conclusion No systemic response to the pathogen, measured through C-reactive protein levels, was observed, regardless of CagA status. Otherwise, the intake of yerba maté should be considered as a cultural factor possibly related toH. pylori's transmission.

RESUMO Contexto Recentemente, uma grande variedade de estudos tem investigado e até mesmo sugerido a presença de Helicobacter pylori como um importante fator no desenvolvimento de eventos restritos ou não ao trato gastrointestinal. A relação já bem estabelecida entre virulência bacteriana e risco aumentado para úlcera péptica ou adenocarcinoma gástrico não parece estar tão elucidada quando se comparam alterações de marcadores inflamatórios, como a proteína C-reativa, com a presença do patógeno. Objetivo O objetivo deste estudo foi avaliar a presença da infecção por H. pylori, a virulência bacteriana e os níveis séricos de proteína C-reativa em indivíduos diagnosticados com dispepsia funcional. Métodos Foram incluídos neste estudo, prospectivamente, 489 indivíduos dispépticos. Os pacientes deveriam preencher os critérios clínicos de Roma III para o diagnóstico de dispepsia funcional sem apresentar doença orgânica evidenciada a partir da endoscopia. A infecção bacteriana foi estabelecida por histologia e pelo teste rápido da urease. Os níveis de proteína C-reativa foram quantificados através de imunonefelometria e o status para a presença da CagA dos indivíduos infectados por H. pylorifoi determinado por ensaio imunoenzimático. Resultados A taxa de prevalência de H. pylori foi de 66.3% e o fator de virulência CagA foi detectado em aproximandamente 43% das amostras positivas. Adicionalmente, denotou-se uma associação entre o consumo deIlex paraguariensis (chimarrão) e a prevalência do patógeno. Um importante efeito da infecção bacteriana na inflamação apenas foi observado localmente, no epitélio gástrico. Conclusão Não foi evidenciada resposta sistêmica ao patógeno aferido através dos níveis de proteína C-reativa, independentemente do status para CagA. Por outro lado, o consumo de chimarrão pode ser sugerido como um fator cultural possivelmente relacionado à transmissão de H. pylori.

Effectiveness of alpha interferon (+ ribavirin) in the treatment of chronic viral hepatitis C genotypes 2 and 3 in a Brazilian sample.

CONTEXT: Pharmacovigilance studies aim to detect, assess, understand and prevent risks of adverse effects of medications or any other possible drug related problem. Alpha interferon is being produced by Bio-Manguinhos/Fiocruz, Rio de Janeiro, RJ, Brazil and used in the treatment of chronic hepatitis C at Brazilian National Health System. OBJECTIVE: To study the safety profile and effectiveness of alpha interferon in a sample of Brazilian patients with chronic hepatitis C genotypes 2 and 3, in Porto Alegre, RS, Brazil. METHOD: We followed a cohort of chronic hepatitis C genotypes 2 and 3 patients treated with alpha interferon plus ribavirin in a specialized outpatient clinic in southern Brazil. Adverse events were collected and classified according to severity in monthly structured interviews. To measure effectiveness, hepatitis C viral load was evaluated before, at the end and 24 weeks after the treatment. RESULTS: We followed 141 patients during the study period, of which 52.5% were female with mean age of 52 years. The most frequent adverse events were fatigue (84%), headache (79%) and myalgia (75%). There were 13 treatment interruptions due to adverse events, 9 of those considered serious adverse events. Virological response at end of treatment was 54.6% and after 24 weeks 39.7%, considering all patients who started treatment. CONCLUSION: The product produced by Bio-Manguinhos has similar efficacy and adverse event and sustained virological response profiles comparable to those found in the literature. This is the first study of pharmacovigilance performed with the Brazilian product. These data will be useful for planning and management of this disease in Brazil.

Effectiveness of alpha interferon (+ ribavirin) in the treatment of chronic viral hepatitis C genotypes 2 and 3 in a brazilian sample / Efetividade da alfainterferona (+ribavirina) no tratamento da hepatite viral crônica C genótipos 2 e 3 em amostra brasileira

CONTEXT: Pharmacovigilance studies aim to detect, assess, understand and prevent risks of adverse effects of medications or any other possible drug related problem. Alpha interferon is being produced by Bio-Manguinhos/Fiocruz, Rio de Janeiro, RJ, Brazil and used in the treatment of chronic hepatitis C at Brazilian National Health System. OBJECTIVE: To study the safety profile and effectiveness of alpha interferon in a sample of Brazilian patients with chronic hepatitis C genotypes 2 and 3, in Porto Alegre, RS, Brazil. METHOD: We followed a cohort of chronic hepatitis C genotypes 2 and 3 patients treated with alpha interferon plus ribavirin in a specialized outpatient clinic in southern Brazil. Adverse events were collected and classified according to severity in monthly structured interviews. To measure effectiveness, hepatitis C viral load was evaluated before, at the end and 24 weeks after the treatment. RESULTS: We followed 141 patients during the study period, of which 52.5% were female with mean age of 52 years. The most frequent adverse events were fatigue (84%), headache (79%) and myalgia (75%). There were 13 treatment interruptions due to adverse events, 9 of those considered serious adverse events. Virological response at end of treatment was 54.6% and after 24 weeks 39.7%, considering all patients who started treatment. CONCLUSION: The product produced by Bio-Manguinhos has similar efficacy and adverse event and sustained virological response profiles comparable to those found in the literature. This is the first study of pharmacovigilance performed with the Brazilian product. These data will be useful for planning and management of this disease in Brazil.

CONTEXTO: Estudos de farmacovigilância têm por objeto a detecção, avaliação, compreensão e prevenção dos riscos dos efeitos adversos dos medicamentos ou qualquer outro possível problema relacionado com medicamento. A alfainterferona (IFN) está sendo produzida por Bio-Manguinhos/Fiocruz e utilizada no tratamento da hepatite C crônica no âmbito do Sistema Único de Saúde (SUS). OBJETIVO: Conhecer o perfil de segurança e efetividade deste IFN em uma amostra de pacientes brasileiros com hepatite crônica pelo vírus C genótipos 2 e 3, em Porto Alegre, RS, Brasil. MÉTODO: Trata-se de uma coorte de pacientes com hepatite crônica pelo vírus C genótipos 2 e 3 tratados com IFN e ribavirina e acompanhados em um serviço ambulatorial especializado no sul do Brasil. Os eventos adversos foram coletados e classificados de acordo com a gravidade em entrevistas mensais estruturadas. Para medida de eficácia foi avaliada a carga viral do HCV antes, ao final e 24 semanas após o término do tratamento. RESULTADOS: Foram acompanhados 141 pacientes no período do estudo, sendo 52,5% do sexo feminino com média de idade de 52 anos. Os eventos adversos mais frequentes foram fadiga (84%), cefaleia (79%) e mialgia (75%). Ocorreram 13 interrupções de tratamento por eventos adversos, sendo nove destes considerados eventos adversos graves. A resposta virológica ao final do tratamento foi de 54,6% e 24 semanas após de 39,7%, considerando todos os pacientes que iniciaram o tratamento. CONCLUSÃO: O produto produzido por Bio-Manguinhos possui eficácia e um perfil de eventos adversos e de resposta virológica sustentada comparáveis aos encontrados na literatura. Este é o primeiro estudo de farmacovigilância realizado com o produto brasileiro. Estes dados serão úteis para planejamento e gestão do tratamento desta doença no Brasil.

Helicobacter pylori eradication in functional dyspepsia: HEROES trial.

BACKGROUND: Eradication of Helicobacter pylori in patients with functional dyspepsia continues to be a matter of debate. We studied eradication effects on symptoms and quality of life of primary care patients. METHODS: Helicobacter pylori -positive adult patients with functional dyspepsia meeting the Rome III International Consensus criteria were randomly assigned to receive omeprazole, amoxicillin trihydrate, and clarithromycin, or omeprazole plus placebo for 10 days. Endoscopy and H pylori tests were performed at screening and at 12 months. Outcome measures were at least 50% symptomatic improvement at 12 months using a validated disease-specific questionnaire (primary end point), patient global assessment of symptoms, and quality of life. RESULTS: We randomly assigned 404 patients (78.7% were women; mean age, 46.1 years); 201 were assigned to be treated with antibiotics (antibiotics group) and 203 to a control group. A total of 389 patients (96.3%) completed the study. The proportion of patients who achieved the primary outcome was 49.0% (94 of 192) in the antibiotics group and 36.5% (72 of 197) in the control group (P = .01; number needed to treat, 8). In the patient global assessment of symptoms, 78.1% in the antibiotics group (157 of 201) answered that they were better symptomatically, and 67.5% in the control group (137 of 203) said that they were better (P = .02). The antibiotics group had a significantly larger increase in their mean (SD) Medical Outcomes Study 36-Item Short Form Health Survey physical component summary scores than the control group did (4.15 [8.5] vs 2.2 [8.1]; P = .02). CONCLUSION: Helicobacter pylori eradication provided significant benefits to primary care patients with functional dyspepsia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00404534.