Impact of Cuminaldehyde and Indomethacin Co-Administration on Inflammatory Responses in MIA-Induced Osteoarthritis in Rats.

Osteoarthritis (OA) remains a chronic incurable condition, presenting substantial challenges in treatment. This study explores a novel strategy by investigating the concurrent use of cuminaldehyde, a natural compound, with indomethacin in animal models of MIA-induced OA. Our results demonstrate that the co-administration of cuminaldehyde and indomethacin does indeed produce a superior effect when compared to these compounds individually, significantly enhancing therapeutic outcomes. This effect is evidenced by a marked reduction in pro-inflammatory cytokines IL-6 and IFN-γ, alongside a significant increase in the anti-inflammatory cytokine IL-10, compared to treatments with each compound alone. Radiographic analyses further confirm the preservation of joint integrity and a reduction in osteoarthritic damage, highlighting the association's efficacy in cartilage-reducing damage. These findings suggests that the association of cuminaldehyde and indomethacin not only slows OA progression but also offers enhanced cartilage-reducing damage and fosters the production of protective cytokines. This study underscores the potential benefits of integrating natural products with pharmaceuticals in OA management and stresses the importance of further research to fully understand the mechanisms underlying the observed potentiated effects.

BRAZILIAN CLINICAL GUIDELINE FOR THE THERAPEUTIC MANAGEMENT OF GASTROESOPHAGEAL REFLUX DISEASE (BRAZILIAN FEDERATION OF GASTROENTEROLOGY, FBG).

BACKGROUND: Gastroesophageal Reflux Disease (GERD) is a prevalent condition in Brazil, affecting 12% to 20% of the urban population, with significant implications for patient quality of life and potential for complications. OBJECTIVE: This paper focuses on the recent update of the Brazilian guidelines for GERD, a necessary revision due to advancements in knowledge and practice since the last publication over a decade ago. The update pays particular attention to the role and safety of proton pump inhibitors (PPIs), acknowledging the growing concerns about their long-term use, adverse events, and overprescription. METHODS: The methodology of the guideline update involved an extensive literature review in multiple languages (English, French, Italian, Spanish, and Portuguese), drawing from major databases such as Medline, Embase, and SciELO-Lilacs. RESULTS: This comprehensive approach resulted in a carefully curated selection of studies, systematic reviews, and meta-analyses, specifically focusing on PPIs and other therapeutic strategies for GERD. The updated guidelines are presented in a user-friendly question-and-answer format, adhering to the PICO system (Population, Intervention, Comparison, Outcomes) for clarity and ease of interpretation. The recommendations are supported by robust scientific evidence and expert opinions, enhancing their practical applicability in clinical settings. To ensure the reliability and clarity of the recommendations, the GRADE system (Grading of Recommendations Assessment, Development, and Evaluation) was employed. This system categorizes the strength of recommendations as strong, weak, or conditional and classifies evidence quality as high, moderate, low, or very low. These classifications provide insight into the confidence level of each recommendation and the likelihood of future research impacting these guidelines. CONCLUSION: The primary aim of these updated guidelines is to offer practical, evidence-based advice for the management of GERD in Brazil, ensuring that healthcare professionals are equipped with the latest knowledge and tools to deliver optimal patient care. BACKGROUND: •Gastrointestinal specialists rely heavily on guidelines to manage digestive pathologies effectively. The Brazilian clinical guideline for therapeutic management of gastroesophageal reflux disease (GERD) is an invaluable tool for these specialists. BACKGROUND: •It critically analyzes practical aspects of therapy through 12 questions covering a wide range of topics, from behavioral measures to surgical and endoscopic indications. BACKGROUND: •The recommendations in this guideline are justified using the GRADE system (Grading of Recommendations Assessment, Development, and Evaluation), and experienced experts provide comments and suggestions at the end of each question.

Latin American consensus on diagnosis of gastroesophageal reflux disease.

BACKGROUND: Diagnosing gastroesophageal reflux disease (GERD) can be challenging given varying symptom presentations, and complex multifactorial pathophysiology. The gold standard for GERD diagnosis is esophageal acid exposure time (AET) measured by pH-metry. A variety of additional diagnostic tools are available. The goal of this consensus was to assess the individual merits of GERD diagnostic tools based on current evidence, and provide consensus recommendations following discussion and voting by experts. METHODS: This consensus was developed by 15 experts from nine countries, based on a systematic search of the literature, using GRADE (grading of recommendations, assessment, development and evaluation) methodology to assess the quality and strength of the evidence, and provide recommendations regarding the diagnostic utility of different GERD diagnosis tools, using AET as the reference standard. KEY RESULTS: A proton pump inhibitor (PPI) trial is appropriate for patients with heartburn and no alarm symptoms, but nor for patients with regurgitation, chest pain, or extraesophageal presentations. Severe erosive esophagitis and abnormal reflux monitoring off PPI are clearly indicative of GERD. Esophagram, esophageal biopsies, laryngoscopy, and pharyngeal pH monitoring are not recommended to diagnose GERD. Patients with PPI-refractory symptoms and normal endoscopy require reflux monitoring by pH or pH-impedance to confirm or exclude GERD, and identify treatment failure mechanisms. GERD confounders need to be considered in some patients, pH-impedance can identify supragrastric belching, impedance-manometry can diagnose rumination. CONCLUSIONS: Erosive esophagitis on endoscopy and abnormal pH or pH-impedance monitoring are the most appropriate methods to establish a diagnosis of GERD. Other tools may add useful complementary information.

Potassium-competitive acid blockers, a new therapeutic class, and their role in acid-related diseases: a narrative review.

Introduction: A new therapeutic class, potassium-competitive acid blockers (P-CABs), has emerged in Brazil to promote a superior antisecretory effect addressing the unmet needs related to acid-related disease management. Vonoprazan fumarate showed a good safety profile and was approved by the Brazilian regulatory agency - ANVISA. Aim: This narrative review was conducted to review the general concepts regarding P-CABs, focussing on vonoprazan fumarate. Material and methods: A literature search was conducted through April-May 2021 using official databases with a combination of MeSH controlled vocabulary and text words. The authors selected articles that described pivotal and novel insights about P-CABs and vonoprazan fumarate. Results: Vonoprazan is a drug of the P-CABs class newly approved for the management of acid-related diseases in Brazil. P-CABs achieve rapid, potent, and prolonged acid suppression (including night-time) and promise to address some unmet clinical needs in GERD. Furthermore, considering the difficulties encountered in attaining effective symptomatic control - particularly at night - using currently available PPIs, this new drug class is promising. Conclusions: This review brings important information about vonoprazan, a new therapeutic option in Brazil, which may be considered as a valuable tool for managing acid-related diseases.

Cuminaldehyde Effects in a MIA-Induced Experimental Model Osteoarthritis in Rat Knees.

Osteoarthritis (OA) is a chronic degenerative disease that has a significant global impact. It is associated with aging and characterized by widespread joint destruction. Cuminaldehyde is a biologically active component of essential oils that has shown promise in the treatment of nociceptive and inflammatory diseases. This study investigated the effects of cuminaldehyde on an experimental model of osteoarthritis induced in rat knees. Cuminaldehyde was found to be as effective as indomethacin in reducing pain in all evaluated tests, including forced walking, functional disability of weight distribution on the legs, and spontaneous pain in animals with osteoarthritis. The knees of animals treated with cuminaldehyde had significantly higher radiographic and histopathological scores than those of animals that did not receive the treatment. Cuminaldehyde also modulated the production of pro-inflammatory cytokines. In vitro assays showed that cuminaldehyde preferentially inhibits COX-2 enzyme activity. In silico studies demonstrated that cuminaldehyde has satisfactory energy affinity parameters with opioid receptors and COX-2. These findings suggest that cuminaldehyde's anti-inflammatory activity is multifactorial, acting through multiple pathways. Its nociceptive activity occurs via central and peripheral mechanisms. Cuminaldehyde modulates the immune response of the inflammatory process and may be considered a leading compound for the development of new anti-inflammatory and analgesic drugs.

Vonoprazan in the management of gastric/peptic ulcers: a systematic review of safety data.

Introduction: Although potassium-competitive acid blockers (P-CABs) prompted safety concerns when first developed, they ultimately proved to have a favourable safety profile. Aim: To assess the safety of vonoprazan in the management of gastroesophageal reflux disease (GERD), peptic ulcers, or gastroduodenal mucosal lesions induced by chronic use of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs). Material and methods: From March to June 2021, a literature search was conducted using Medline via PubMed, Cochrane library, Lilacs, SciELO, and Centre for Reviews and Dissemination (CRD) electronic databases. After applying the eligibility criteria, 10 studies were included in this review. Of these 10 articles, vonoprazan was used as initial therapy in 6 and as maintenance therapy in 4. Adverse event rates were similar for vonoprazan and proton-pump inhibitors (PPIs). Conclusions: Our findings suggest that vonoprazan is a safe option for the management of erosive oesophagitis, gastric/peptic ulcers, or peptic ulcers induced by chronic use of aspirin or NSAIDs.

Vonoprazan in the management of erosive oesophagitis and peptic ulcer-induced medication: a systematic review.

Introduction: Vonoprazan has been found to promote a better antisecretory effect addressing acid-related diseases' unmet needs. Aim: To assess if vonoprazan effectively treats patients diagnosed with gastroesophageal reflux disease esophagitis or with peptic ulcers induced by chronic use of aspirin or non-steroidal anti-inflammatory drugs. Material and methods: A literature search was conducted (April/2021) using Medline via PubMed, Cochrane library, Lilacs, Scielo, and Centre for Reviews and Dissemination electronic databases. Results: We retrieved 55 titles. Of these, 13 met the eligibility criteria and were included in this review. Of these 13 articles, 4 were prospective cohort studies, 1 was a follow-up analysis of a preceding prospective study, 1 was a retrospective cohort study, and 6 were randomized clinical trials. Conclusions: Our findings suggest that vonoprazan was effective and non-inferior to proton pump inhibitors in healing and maintaining healed reflux oesophagitis, leading to faster symptom relief. Vonoprazan may also be considered for preventing aspirin- or non-steroidal anti-inflammatory drug-related peptic ulcer recurrence.

SAFETY OF LONG-TERM PROTON PUMP INHIBITORS: FACTS AND MYTHS.

BACKGROUND: Proton pump inhibitors (PPIs) are one of the most prescribed drugs in the world. Frequent use and long-term maintenance of these drugs drew the attention of researchers for sporadic adverse effects reports. OBJECTIVE: The purpose of this narrative review is to discuss appropriate data and causality related to these adverse events and PPIs. METHODS: A narrative review was conducted by systematizing information about safety and adverse events on PPIs from 2015 to 2020. A structured search on Pubmed was performed to identify systematic reviews and meta-analysis investigating the following situations: a) gastric cancer; b) micronutrients deficiency; c) acid rebound; d) infections; e) fractures; f) dementia; g) kidney disease; and h) sudden death and cardiovascular changes. RESULTS: Recent studies have potentially associated PPIs with some adverse events as osteoporosis-related fractures. There are also reports of intestinal infections, including Clostridium difficile, besides poor vitamins absorption and minerals such as vitamin B12, magnesium, and iron. Furthermore, there are some dementia, pneumonia, kidney disease, myocardial infarction, and stroke reports. For kidney diseases, studies consistently suggest that the use of PPI may be associated with an increased risk of adverse kidney events, especially in the elderly, with long-term PPI use and pre-existing kidney disease. Another additional question is whether chronic PPI use would also lead to the onset of gastric cancer. The abrupt discontinuation of PPIs is also related to increased gastric acid production above pre-PPI treatment levels; this phenomenon is called acid rebound. CONCLUSION: The key to mitigate adverse effects is the rational use of PPIs at the lowest effective dose and in the shortest possible duration. Although these adverse effects have a potential clinical impact, their causal association is still subject to validation.

Segurança dos inibidores de bomba de prótons utilizados a longo prazo: fatos e fantasias / Safety of long-term proton pump inhibitors: facts and myths

ABSTRACT Background: Proton pump inhibitors (PPIs) are one of the most prescribed drugs in the world. Frequent use and long-term maintenance of these drugs drew the attention of researchers for sporadic adverse effects reports. Objective: The purpose of this narrative review is to discuss appropriate data and causality related to these adverse events and PPIs. Methods: A narrative review was conducted by systematizing information about safety and adverse events on PPIs from 2015 to 2020. A structured search on Pubmed was performed to identify systematic reviews and meta-analysis investigating the following situations: a) gastric cancer; b) micronutrients deficiency; c) acid rebound; d) infections; e) fractures; f) dementia; g) kidney disease; and h) sudden death and cardiovascular changes. Results: Recent studies have potentially associated PPIs with some adverse events as osteoporosis-related fractures. There are also reports of intestinal infections, including Clostridium difficile, besides poor vitamins absorption and minerals such as vitamin B12, magnesium, and iron. Furthermore, there are some dementia, pneumonia, kidney disease, myocardial infarction, and stroke reports. For kidney diseases, studies consistently suggest that the use of PPI may be associated with an increased risk of adverse kidney events, especially in the elderly, with long-term PPI use and pre-existing kidney disease. Another additional question is whether chronic PPI use would also lead to the onset of gastric cancer. The abrupt discontinuation of PPIs is also related to increased gastric acid production above pre-PPI treatment levels; this phenomenon is called acid rebound. Conclusion: The key to mitigate adverse effects is the rational use of PPIs at the lowest effective dose and in the shortest possible duration. Although these adverse effects have a potential clinical impact, their causal association is still subject to validation.

RESUMO: Contexto: Os inibidores da bomba de prótons (IBPs) são um dos medicamentos mais prescritos no mundo. O uso frequente e a manutenção a longo prazo dessas drogas chamaram a atenção dos pesquisadores devido aos relatos esporádicos de efeitos adversos. Objetivo: Esta revisão narrativa tem o objetivo de discutir os dados e a causalidade relacionada a esses eventos adversos e o uso de IBPs. Métodos: Uma revisão narrativa foi conduzida através da sistematização das informações sobre segurança e eventos adversos de IBPs de 2015 a 2020. Uma busca estruturada na base de dados PubMed foi realizada visando identificar revisões sistemáticas e meta-análises investigando as situações a seguir: a) câncer gástrico; b) deficiência de microelementos; c) acidez de rebote; d) infecções; e) fraturas; f) demência; g) doença renal; e h) morte súbita e alterações cardiovasculares. Resultados: Estudos recentes têm potencialmente associado IBPs a alguns eventos adversos, como fraturas relacionadas à osteoporose. Também há relatos de infecções intestinais, incluindo Clostridium difficile, além de má absorção de vitaminas e minerais como vitamina B12, magnésio e ferro. Além disso, há alguns relatos de demência, pneumonia, doença renal, infarto do miocárdio e acidente vascular cerebral. Na doença renal, os estudos sugerem consistentemente que o uso de IBPs pode estar associado a um risco aumentado de eventos renais adversos, especialmente em idosos, com o uso de IBPs a longo prazo e doença renal preexistente. Outra questão adicional é se o uso crônico de IBPs também levaria ao aparecimento de câncer gástrico. A descontinuação abrupta de IBPs também está relacionada ao aumento da produção de ácido gástrico acima dos níveis de tratamento pré-IBPs; este fenômeno é conhecido como rebote ácido. Conclusão: A chave para mitigar esses efeitos adversos é o uso racional de IBPs na menor dose efetiva e com a menor duração possível. Embora esses efeitos adversos tenham um impacto clínico potencial, sua associação causal ainda está pendente de uma validação.

GASTROESOPHAGEAL REFLUX DISEASE: A PRACTICAL APPROACH.

Gastroesophageal reflux disease (GERD) presents typical manifestations such as heartburn and/or regurgitation as well as atypical manifestations such as throat symptoms, laryngitis, hoarseness, chronic cough, asthma, and sleep alterations. There are two phenotypes of the disease: erosive GERD, when erosions are identified by upper digestive endoscopy, and non-erosive GERD, when the esophageal mucosa presents a normal endoscopic aspect. Relevant clinical findings are usually absent in the physical examination, but it should be highlighted that obesity is an important aggravating factor of reflux. The treatment is established based on clinical findings and, according to the clinical situation, on complementary exams such as upper digestive endoscopy. In dubious cases where a precise diagnosis is required, the indicated test is esophageal pHmetry or impedance-pHmetry. Clinical treatment is divided into behavioral/dietary measures and pharmacological measures. Most patients benefit from clinical treatment, but surgical treatment may be indicated in the presence of a larger hiatal hernia and complications of the disease.

Doença do refluxo gastroesofágico: uma abordagem prática / Gastroesophageal reflux disease: a practical approach

ABSTRACT Gastroesophageal reflux disease (GERD) presents typical manifestations such as heartburn and/or regurgitation as well as atypical manifestations such as throat symptoms, laryngitis, hoarseness, chronic cough, asthma, and sleep alterations. There are two phenotypes of the disease: erosive GERD, when erosions are identified by upper digestive endoscopy, and non-erosive GERD, when the esophageal mucosa presents a normal endoscopic aspect. Relevant clinical findings are usually absent in the physical examination, but it should be highlighted that obesity is an important aggravating factor of reflux. The treatment is established based on clinical findings and, according to the clinical situation, on complementary exams such as upper digestive endoscopy. In dubious cases where a precise diagnosis is required, the indicated test is esophageal pHmetry or impedance-pHmetry. Clinical treatment is divided into behavioral/dietary measures and pharmacological measures. Most patients benefit from clinical treatment, but surgical treatment may be indicated in the presence of a larger hiatal hernia and complications of the disease.

RESUMO A doença do refluxo gastroesofágico (DRGE) apresenta manifestações típicas, pirose e/ou regurgitação, assim como, manifestações atípicas, pigarro, laringite, rouquidão, tosse crônica, asma, alterações do sono. Existem dois fenótipos da doença: a DRGE erosiva, quando são identificadas erosões pela endoscopia digestiva alta (EDA) e a DRGE não-erosiva, com mucosa esofágica de aspecto endoscópico normal. Ao exame físico não costumam ser encontrados achados relevantes, mas a obesidade deve ser destacada como importante fator agravante do refluxo. O tratamento é estabelecido com base nos achados clínicos e, conforme a situação clínica, em exames complementares como a EDA. Nos casos duvidosos onde o diagnóstico preciso se impõe, o exame indicado é a pHmetria esofágica ou a impedância-pHmetria. O tratamento clínico é dividido em medidas comportamentais/dietéticas e medidas farmacológicas. A maioria dos pacientes se beneficia com o tratamento clínico, mas o tratamento cirúrgico pode estar indicado como na presença de hérnia hiatal de maior dimensão e nas complicações da doença.

IMPACT OF HEARTBURN AND REGURGITATION ON INDIVIDUALS' WELL-BEING IN THE GENERAL POPULATION: A BRAZILIAN NATIONAL SURVEY.

BACKGROUND: Heartburn and acid regurgitation are typical symptoms usually associated with gastroesophageal reflux disease (GERD). GERD is one of the gastrointestinal diagnosis with higher prevalence worldwide, significantly impairing patients' quality of life. OBJECTIVE: The objective of this study was to analyze the impact of GERD-related symptoms in the Brazilian urban population. METHODS: National telephone survey with community-dwelling Brazilian individuals. Self-reported prevalence and frequency of symptoms (heartburn / regurgitation) were assessed. Individuals rated the impact of symptoms in their general well-being using a numeric scale from 1 to 10 (1 = no impact; 10 = very intense, preventing the person to eat and perform daily routine activities). Descriptive and bivariate statistical analyses were performed. RESULTS: The final sample was comprised of 1,773 subjects, 935 (52.7%) females, an average of 40 years old. The prevalence of heartburn and regurgitation in the past 6 months was 26.2% (n=466) and 11.0% (n=196), respectively. Women presented higher prevalence (heartburn n=266, 28.5% and regurgitation n=119, 12.7%) than men (n=200, 23.1% and n=78, 8.9%, respectively) (P<0.05). Heartburn in the past week was reported by 175 individuals (9.8%), while regurgitation episodes by 67 (3.8%). Absence of impact of the symptom in the overall well-being was observed for 82 subjects (17.6%) with heartburn and 18 individuals (9.2%) with regurgitation. Very intense impact was reported by 46 subjects (9.8%) with heartburn and 41 (20.9%) with regurgitation. Women's well-being was more affected than men's (mean score 5.45 vs 4.71, P<0.05). CONCLUSION: Heartburn and regurgitation were frequent symptoms, women with higher prevalence. These symptoms led to a substantial impact on individuals' well-being, women being more affected.

Impacto da pirose e regurgitação no bem-estar de indivíduos da população geral: um inquérito nacional brasileiro / Impact of heartburn and regurgitation on individuals' well-being in the general population: a brazilian national survey

ABSTRACT BACKGROUND: Heartburn and acid regurgitation are typical symptoms usually associated with gastroesophageal reflux disease (GERD). GERD is one of the gastrointestinal diagnosis with higher prevalence worldwide, significantly impairing patients' quality of life. OBJECTIVE: The objective of this study was to analyze the impact of GERD-related symptoms in the Brazilian urban population. METHODS: National telephone survey with community-dwelling Brazilian individuals. Self-reported prevalence and frequency of symptoms (heartburn / regurgitation) were assessed. Individuals rated the impact of symptoms in their general well-being using a numeric scale from 1 to 10 (1 = no impact; 10 = very intense, preventing the person to eat and perform daily routine activities). Descriptive and bivariate statistical analyses were performed. RESULTS: The final sample was comprised of 1,773 subjects, 935 (52.7%) females, an average of 40 years old. The prevalence of heartburn and regurgitation in the past 6 months was 26.2% (n=466) and 11.0% (n=196), respectively. Women presented higher prevalence (heartburn n=266, 28.5% and regurgitation n=119, 12.7%) than men (n=200, 23.1% and n=78, 8.9%, respectively) (P<0.05). Heartburn in the past week was reported by 175 individuals (9.8%), while regurgitation episodes by 67 (3.8%). Absence of impact of the symptom in the overall well-being was observed for 82 subjects (17.6%) with heartburn and 18 individuals (9.2%) with regurgitation. Very intense impact was reported by 46 subjects (9.8%) with heartburn and 41 (20.9%) with regurgitation. Women's well-being was more affected than men's (mean score 5.45 vs 4.71, P<0.05). CONCLUSION: Heartburn and regurgitation were frequent symptoms, women with higher prevalence. These symptoms led to a substantial impact on individuals' well-being, women being more affected.

RESUMO CONTEXTO: Pirose e regurgitação ácida são sintomas típicos usualmente relacionados à doença do refluxo gastroesofágico (DRGE). A DRGE é um dos diagnósticos gastrointestinais com maior prevalência mundial, afetando significativamente a qualidade de vida dos pacientes. OBJETIVO: Analisar o impacto de sintomas relacionados à DRGE em uma amostra da população brasileira urbana. MÉTODOS: Inquérito nacional via telefone com indivíduos brasileiros em contexto comunitário. O inquérito foi conduzido entre 6 de agosto e 12 de setembro de 2018. A prevalência autorrelatada e a frequência dos sintomas foram avaliadas. Os respondentes classificaram o impacto dos sintomas no seu bem-estar geral utilizando uma escala numérica de 1 a 10 (1 = ausência de impacto; 10 = impacto muito grave, impedindo a pessoa de comer ou realizar atividades da vida diária). Análises estatísticas descritivas e bivariadas foram conduzidas. RESULTADOS: A amostra final foi constituída por 1.773 indivíduos, 935 (52,7%) mulheres, com idade média de 40 anos. A prevalência de pirose e regurgitação nos últimos 6 meses foi de 26,2% (n=466) e 11,0% (n=196), respectivamente. Sexo feminino (pirose n=266, 28,5% e regurgitação n=119, 12,7%) apresentou prevalência mais alta do que o masculino (n=200, 23,1% e n=78, 8,9%, respectivamente) (P<0,05). Pirose na última semana foi relatada por 175 indivíduos (9,8%), enquanto episódios de regurgitação por 67 (3,8%). Ausência de impacto dos sintomas no bem-estar geral dos indivíduos foi observada para 82 respondentes (17,6%) com pirose e 18 (9,2%) daqueles com regurgitação. Impacto muito grave foi reportado por 46 (9,8%) indivíduos com pirose e 41 (20,9%) com regurgitação. Sexo feminino foi mais afetado pelos sintomas do que o masculino. CONCLUSÃO: Pirose e regurgitação foram bastante frequentes sendo o sexo feminino mais afetado. Tais sintomas levaram a impacto no bem-estar dos indivíduos, com maior prejuízo para mulheres.

BRAZILIAN PHYSICIANS' PRACTICES ON THE MANAGEMENT OF SYMPTOMS SUGGESTING GASTROESOPHAGEAL REFLUX DISEASE: A MULTIDISCIPLINARY SURVEY.

BACKGROUND: Clinical guidelines are available to steer decisions regarding diagnosis, management and treatment of gastrointestinal disorders. Despite this, variations in physician's practices regarding gastroesophageal reflux disease (GERD) symptoms are well described in the literature. OBJECTIVE: To describe practices of physicians from different specialties on the management of patients with typical symptoms of GERD (heartburn and regurgitation) in a Brazilian sample. METHODS: National online survey enrolling a sample of general practitioners, gastroenterologists, cardiologists and otolaryngologists. The survey was conducted from August 6th to September 12th, 2018. Subjects answered a structured questionnaire addressing variables regarding physicians' profile (age, sex, specialty, practice setting, years in practice, type of medical expense reimbursement), their patients characteristics and prescribing behaviors. RESULTS: The final weighted sample was comprised of 400 physicians, 64% male, with an average of 15 years of experience. Physicians' estimates of gastroesophageal symptoms prevalence among their pool of patients was 37.6% for the total sample, reaching 70.3% among gastroenterologists. The medical specialty with lower average percentage of patients presenting gastroesophageal symptoms was otolaryngology (24.5%). Physicians reported that they request ancillary tests for 64.5% of patients with GERD typical symptoms. The most common diagnostic test was endoscopy (69.4%), followed by video nasolaryngoscopy (16.6%). The percentage of patient to whom endoscopy is performed was significantly higher among gastroenterologists and general practitioners as compared to otolaryngologists and cardiologists, while video nasolaryngoscopy is markedly more frequent among otolaryngologists. In terms of therapeutic options, the most frequently reported strategy was lifestyle modifications followed by proton pump inhibitors. CONCLUSION: Overall patients' profile and patterns of GERD diagnosis and management seem different between gastroenterologists, general practitioners, otolaryngologists, and cardiologists. Clinical guidelines should address this variability and include other medical specialties besides gastroenterologists in their scope.

Práticas de médicos brasileiros no manejo de sintomas sugestivos de doença do refluxo gastroesofágico: uma avaliação multidisciplinar / Brazilian physicians' practices on the management of symptoms suggesting gastroesophageal reflux disease: a multidisciplinary survey

ABSTRACT BACKGROUND: Clinical guidelines are available to steer decisions regarding diagnosis, management and treatment of gastrointestinal disorders. Despite this, variations in physician's practices regarding gastroesophageal reflux disease (GERD) symptoms are well described in the literature. OBJECTIVE: To describe practices of physicians from different specialties on the management of patients with typical symptoms of GERD (heartburn and regurgitation) in a Brazilian sample. METHODS: National online survey enrolling a sample of general practitioners, gastroenterologists, cardiologists and otolaryngologists. The survey was conducted from August 6th to September 12th, 2018. Subjects answered a structured questionnaire addressing variables regarding physicians' profile (age, sex, specialty, practice setting, years in practice, type of medical expense reimbursement), their patients characteristics and prescribing behaviors. RESULTS: The final weighted sample was comprised of 400 physicians, 64% male, with an average of 15 years of experience. Physicians' estimates of gastroesophageal symptoms prevalence among their pool of patients was 37.6% for the total sample, reaching 70.3% among gastroenterologists. The medical specialty with lower average percentage of patients presenting gastroesophageal symptoms was otolaryngology (24.5%). Physicians reported that they request ancillary tests for 64.5% of patients with GERD typical symptoms. The most common diagnostic test was endoscopy (69.4%), followed by video nasolaryngoscopy (16.6%). The percentage of patient to whom endoscopy is performed was significantly higher among gastroenterologists and general practitioners as compared to otolaryngologists and cardiologists, while video nasolaryngoscopy is markedly more frequent among otolaryngologists. In terms of therapeutic options, the most frequently reported strategy was lifestyle modifications followed by proton pump inhibitors. CONCLUSION: Overall patients' profile and patterns of GERD diagnosis and management seem different between gastroenterologists, general practitioners, otolaryngologists, and cardiologists. Clinical guidelines should address this variability and include other medical specialties besides gastroenterologists in their scope.

RESUMO CONTEXTO: Diretrizes clínicas estão disponíveis para orientar decisões sobre diagnóstico, manejo e tratamento de desordens gastrointestinais. Apesar disso, variações nas práticas relacionadas aos sintomas de doença do refluxo gastroesofágico (DRGE) são observadas na literatura. OBJETIVO: Descrever os conhecimentos e práticas relacionados ao manejo de pacientes com sintomas típicos de DRGE (pirose e regurgitação) em uma amostra brasileira de médicos de especialistas e não especialistas. MÉTODOS: Inquérito nacional online investigando a conduta frente ao diagnóstico de DRGE em uma amostra de médicos generalistas, gastroenterologistas, cardiologistas e otorrinolaringologistas. O inquérito foi conduzido entre 6 de agosto e 12 de setembro de 2018. Os sujeitos responderam a um questionário estruturado avaliando variáveis relacionadas ao perfil dos médicos (idade, sexo, especialidade, contexto de prática, anos de experiência, tipo de reembolso de despesas médicas), características dos pacientes e comportamentos de prescrição. RESULTADOS: A amostra final ponderada foi composta por 400 médicos, 64% homens, com um tempo médio de experiência de 15 anos. A estimativa dos médicos a respeito da prevalência de sintomas gastroesofágicos entre seus pacientes foi de 37,6% para a amostra total, alcançando 70,3% entre gastroenterologistas. A especialidade médica com menor percentual de pacientes apresentando sintomas gastroesofágicos foi otorrinola­ringologia (24,5%). Os médicos requisitaram exames complementares em 64,5% dos pacientes com sintomas típicos de DRGE. O exame diagnóstico mais frequente foi endoscopia (69,4%), seguida de nasolaringoscopia (16,6%). O percentual de pacientes nos quais uma endoscopia é realizada é significativamente maior entre gastroenterologistas e médicos generalistas, quando comparado a otorrinolaringologistas e cardiologistas, enquanto nasolaringoscopia é marcadamente mais frequente entre otorrinolaringologistas. Em termos de opções terapêuticas, a estratégia mais frequentemente reportada foi modificações no estilo de vida, seguida de inibidores da bomba de prótons. CONCLUSÃO: De modo geral, o perfil de pacientes e os padrões de diagnóstico e manejo de DRGE parecem diferir entre gastroenterologistas, médicos generalistas, otorrinolaringologistas e cardiologistas. Diretrizes clínicas devem abordar esta variabilidade e incluir outras especialidades médicas além de gastroenterologistas em seu escopo.

Valores normais da manometria de alta resolução de esôfago: estudo multicêntrico brasileiro / Normal values of esophageal high-resolution manometry: a brazilian multicenter study

ABSTRACT BACKGROUND: The high-resolution manometry has been a significant advance in esophageal diagnostics. There are different types of catheter and systems devices to capture esophageal pressures that generate variable data related to Chicago Classification (CC) and consequently influence normal values results. There are not normative data for the 24-channel water-perfused high-resolution manometry system most used in Brazil with healthy volunteers in supine posture. OBJECTIVE: To determine manometric esophageal normative values for a 24-channel water-perfused high-resolution manometry catheter in supine posture using healthy volunteers according to CC 3.0 parameters. METHODS: A total of 92 volunteers with no gastrointestinal symptoms or medications affecting GI motility underwent esophageal high-resolution manometry by standard protocol. Age, gender and manometry parameters analyzed using Alacer software were collected. The median, range, and 5th and 95th percentiles (where applicable) were obtained for all high-resolution manometry metrics. Normal value percentiles were defined as 95th integrated relaxation pressure, 5th-100th distal contractile integral, and 5th distal latency. RESULTS: The mean age was 40.5±13.2 years. Our normative metrics were integrated relaxation pressure <16 mmHg and distal contractile integral (708-4111 mmHg.cm.s) distal latency was <6 s and peristaltic break size (>4 cm). For EGJ-CI the range 5th-95th was 21.7-86.9 mmHg.cm.s. CONCLUSION: This is the first report of normative data for the 24-channel water-perfused system in supine posture. It revealed higher integrated relaxation pressure and distal latency duration which suggest the need to change CC 3.0 cutoffs for this system. It is observed that there is a tendency that DCI >7000 mmHg.cm.s may represent the lower limit of hypercontractility, and when <700 mmHg.cm.s (<5% percentile) interpreted as ineffective esophageal motility or failcontraction. Also compared to Chicago 3.0, higher integrated relaxation pressure and duration of distal latency were found. We emphasize that these data must be confirmed by future studies.

RESUMO CONTEXTO: A manometria de alta resolução tem sido um avanço significativo nos diagnósticos esofágicos. Existem diferentes tipos de cateteres e sistemas dispositivos para capturar pressões esofágicas que geram dados variáveis relacionados à Classificação de Chicago (CC) e, consequentemente, podem influenciar os resultados de valores da normalidade. Não há dados normativos com voluntários saudáveis na postura supina, para o sistema manométrico sob perfusão em água de 24 canais, o mais utilizado no Brasil. OBJETIVO: Determinar os valores normativos manométricos do esôfago para um cateter sob perfusão de alta resolução de 24 canais na postura supina utilizando-se voluntários saudáveis assintomáticos de acordo com os parâmetros CC. MÉTODOS: Um total de 92 voluntários sem sintomas gastrointestinais ou medicamentos que afetassem a motilidade gastrointestinal foram submetidos à manometria de alta resolução do esôfago por protocolo padrão (Sistema Alacer Multiplex). Foram coletados parâmetros de idade, sexo e os da manometria analisados pelo software Alacer versão 6.2. A mediana, os limites, e 5% e 95% percentis (quando aplicável) foram obtidos para todas as métricas de alta resolução. Os valores normais foram definidos como percentis de 95% da integral da pressão de relaxamento (IRP), 5%-100% da integral contrátil distal (DCI), e 5% latência distal. RESULTADOS: A média de idade foi de 40,5±13,2 anos. As métricas normativas foram definidas como IRP <16 mmHg) e DCI (708-4111 mmHg.cm.s). Para a latência distal foi de 5,8-9,9 s (faixa: 5,3-10,7s). O comprimento total de quebra na contração esofágica foi de 4,0 cm (faixa: 0,1-6,8 cm). Para a EGJ-CI a faixa 5%-95% percentis foi de 21,7-86,9 mmHg.cm.s. CONCLUSÃO: Este é o primeiro relatório de dados normativos para o sistema de 24 canais perfundido por água na postura supina. A partir dos dados encontrados observa-se a possibilidade de alterar os cortes CC 3.0 para este sistema. Observa-se que há uma tendência que DCI >7000 mmHg.cm.s possa representar o limite inferior da hipercontratilidade e quando <700 mmHg.cm.s (<5% percentil) interpretada como motilidade esofágica ineficaz ou contração falha. Também em comparação com Chicago 3.0, foi encontrada maior pressão de relaxamento integrado e duração da latência distal. Ressaltamos que esses dados devem ser confirmados por estudos futuros.

NORMAL VALUES OF ESOPHAGEAL HIGH-RESOLUTION MANOMETRY: A BRAZILIAN MULTICENTER STUDY.

BACKGROUND: The high-resolution manometry has been a significant advance in esophageal diagnostics. There are different types of catheter and systems devices to capture esophageal pressures that generate variable data related to Chicago Classification (CC) and consequently influence normal values results. There are not normative data for the 24-channel water-perfused high-resolution manometry system most used in Brazil with healthy volunteers in supine posture. OBJECTIVE: To determine manometric esophageal normative values for a 24-channel water-perfused high-resolution manometry catheter in supine posture using healthy volunteers according to CC 3.0 parameters. METHODS: A total of 92 volunteers with no gastrointestinal symptoms or medications affecting GI motility underwent esophageal high-resolution manometry by standard protocol. Age, gender and manometry parameters analyzed using Alacer software were collected. The median, range, and 5th and 95th percentiles (where applicable) were obtained for all high-resolution manometry metrics. Normal value percentiles were defined as 95th integrated relaxation pressure, 5th-100th distal contractile integral, and 5th distal latency. RESULTS: The mean age was 40.5±13.2 years. Our normative metrics were integrated relaxation pressure <16 mmHg and distal contractile integral (708-4111 mmHg.cm.s) distal latency was <6 s and peristaltic break size (>4 cm). For EGJ-CI the range 5th-95th was 21.7-86.9 mmHg.cm.s. CONCLUSION: This is the first report of normative data for the 24-channel water-perfused system in supine posture. It revealed higher integrated relaxation pressure and distal latency duration which suggest the need to change CC 3.0 cutoffs for this system. It is observed that there is a tendency that DCI >7000 mmHg.cm.s may represent the lower limit of hypercontractility, and when <700 mmHg.cm.s (<5% percentile) interpreted as ineffective esophageal motility or failcontraction. Also compared to Chicago 3.0, higher integrated relaxation pressure and duration of distal latency were found. We emphasize that these data must be confirmed by future studies.

IVTH BRAZILIAN CONSENSUS CONFERENCE ON HELICOBACTER PYLORI INFECTION.

Significant progress has been obtained since the III Brazilian Consensus Conference on H. pylori infection held in 2012, in Bento Gonçalves, Brazil, and justify a fourth meeting to establish updated guidelines on the current management of H. pylori infection. Therefore, the Núcleo Brasileiro para Estudo do Helicobacter pylori e Microbiota (NBEHPM), association linked to Brazilian Federation of Gastroenterology (FBG) held its fourth meeting again in Bento Gonçalves, RS, Brazil, on August 25-27, 2017. Twenty-six delegates, including gastroenterologists, endoscopists, and pathologists from the five regions of Brazil as well as one international guest from the United States, participated in the meeting. The participants were invited based on their knowledge and contribution to the study of H. pylori infection. The meeting sought to review different aspects of treatment for infection; establish a correlation between infection, dyspepsia, intestinal microbiota changes, and other disorders with a special emphasis on gastric cancer; and reassess the epidemiological and diagnostic aspects of H. pylori infection. Participants were allocated into four groups as follows: 1) Epidemiology and Diagnosis, 2) Dyspepsia, intestinal microbiota and other afections, 3) Gastric Cancer, and, 4) Treatment. Before the consensus meeting, participants received a topic to be discussed and prepared a document containing a recent literature review and statements that should be discussed and eventually modified during the face-to-face meeting. All statements were evaluated in two rounds of voting. Initially, each participant discussed the document and statements with his group for possible modifications and voting. Subsequently, during a second voting in a plenary session in the presence of all participants, the statements were voted upon and eventually modified. The participants could vote using five alternatives: 1) strongly agree; 2) partially agree; 3) undecided; 4) disagree; and 5) strongly disagree. The adopted consensus index was that 80% of the participants responded that they strongly or partially agreed with each statement. The recommendations reported are intended to provide the most current and relevant evidences to management of H. pylori infection in adult population in Brazil.

Refractory Heartburn: A Challenging Problem in Clinical Practice.

Gastroesophageal reflux disease (GERD) is a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications. Heartburn and regurgitation are the typical symptoms of GERD. The treatment of GERD encompasses lifestyle modifications, pharmacological, endoscopic, and surgical therapy. The majority of the patients respond to 4-8 weeks of proton-pump inhibitors therapy, but 20-42% will demonstrate partial or complete lack of response to treatment. While these patients have been considered as having refractory heartburn, a subset of them does not have GERD or have not been adequately treated. The main causes of refractory heartburn include: poor compliance; inadequate proton-pump inhibitors dosage; incorrect diagnosis; comorbidities; genotypic differences; residual gastroesophageal reflux; eosinophilic esophagitis and others. Treatment is commonly directed toward the underlying cause of patients' refractory heartburn.