SECOND BRAZILIAN CONSENSUS ON THE MANAGEMENT OF ULCERATIVE COLITIS IN ADULTS: A CONSENSUS OF THE BRAZILIAN ORGANIZATION FOR CROHN'S DISEASE AND COLITIS (GEDIIB).

BACKGROUND: Inflammatory bowel diseases are immune-mediated disorders that include Crohn's disease (CD) and ulcerative colitis (UC). UC is a progressive disease that affects the colorectal mucosa causing debilitating symptoms leading to high morbidity and work disability. As a consequence of chronic colonic inflammation, UC is also associated with an increased risk of colorectal cancer. OBJECTIVE: This consensus aims to provide guidance on the most effective medical management of adult patients with UC. METHODS: A consensus statement was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's Disease and Colitis [GEDIIB]). A systematic review including the most recent evidence was conducted to support the recommendations and statements. All recommendations/statements were endorsed using a modified Delphi Panel by the stakeholders/experts in inflammatory bowel disease with at least 80% or greater consensus. RESULTS AND CONCLUSION: The medical recommendations (pharmacological and non-pharmacological) were mapped according to the stage of treatment and severity of the disease onto three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus targeted general practitioners, gastroenterologists and surgeons who manage patients with UC, and supports decision-making processes by health insurance companies, regulatory agencies, health institutional leaders, and administrators.

SECOND BRAZILIAN CONSENSUS ON THE MANAGEMENT OF CROHN'S DISEASE IN ADULTS: A CONSENSUS OF THE BRAZILIAN ORGANIZATION FOR CROHN'S DISEASE AND COLITIS (GEDIIB).

BACKGROUND: Inflammatory bowel disease (IBD) is an immune-mediated disorder that includes Crohn's disease (CD) and ulcerative colitis. CD is characterized by a transmural intestinal involvement from the mouth to the anus with recurrent and remitting symptoms that can lead to progressive bowel damage and disability over time. OBJECTIVE: To guide the safest and effective medical treatments of adults with CD. METHODS: This consensus was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's disease and Colitis (GEDIIB)). A systematic review of the most recent evidence was conducted to support the recommendations/statements. All included recommendations and statements were endorsed in a modified Delphi panel by the stakeholders and experts in IBD with an agreement of at least 80% or greater consensus rate. RESULTS AND CONCLUSION: The medical recommendations (pharmacological and non-pharmacological interventions) were mapped according to the stage of treatment and severity of the disease in three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus is targeted towards general practitioners, gastroenterologists, and surgeons interested in treating and managing adults with CD and supports the decision-making of health insurance companies, regulatory agencies, and health institutional leaders or administrators.

Uma revisão sobre instrumentos de avaliação do Burnout na segurança pública / A review of Burnout assessment instruments in public safety / Una revisión de los instrumentos de evaluación del desgaste en la seguridad pública

Objetivou-se mapear os instrumentos utilizados na avaliação da síndrome de Burnout em profissionais da segurança pública, indicando os aspectos psicométricos, amostras e variáveis associadas. Foram selecionados 19 estudos nas bases de dados pesquisadas (PsycINFO, PubMED e Google Scholar). Os resultados indicaram a utilização dos instrumentos MBI-GS, MBI-HSS, BM-S, CBI e CESQT, mas apenas um dos instrumentos apresentou evidência de validade nesse contexto. Constatou-se a associação do Burnout com variáveis pessoais, organizacionais e específicas. A comparação dos estudos e dos índices de Burnout foi limitada devido à falta de padronização. A ausência de evidências de validade e de padronização dos resultados acarreta problemas como a falta de suporte empírico das pontuações e dificuldade na comparação dos estudos. Os dados revelam limitações na avaliação dos níveis de Burnout utilizadas no contexto de segurança pública, uma vez que as medidas não apresentam evidências de validade para esse contexto, indicando a necessidade de pesquisas na área. (AU)

Aimed to map the instruments used in evaluating Burnout syndrome in public security professionals, indicating the psychometric aspects, samples, and associated variables. Nineteen studies were selected from the searched databases (PsycINFO, PubMED and Google Scholar). Results indicated that the instruments MBI-GS, MBI-HSS, BM-S, CBI and CESQT, but only one of the instruments showed evidence of validity in this context. Burnout was associated with personal, organizational, and specific variables. Comparison of studies and Burnout indices was limited due to the lack of standardization. The absence of evidence of validity and standardization of results leads to problems such as the lack of empirical support for the scores and difficulty in comparing studies. The data reveal limitations in the assessment of burnout levels used in the context of public safety, as the measures do not present validity evidence for this context, pointing to the need for research in the area. (AU)

El objetivo fue mapear los instrumentos utilizados en la evaluación del síndrome de Burnout en profesionales de la seguridad pública, indicando los aspectos psicométricos, muestras y variables asociadas. Se seleccionaron diecinueve estudios de las bases de datos buscadas (PsycINFO, PubMED y Google Scholar). Los resultados indicaron el uso de los instrumentos MBI-GS, MBI-HSS, BM-S, CBI y CESQT, pero solo uno de los instrumentos mostró evidencia de validez en este contexto. El Burnout se encuentra asociado con variables personales, organizacionales y específicas. La comparación de estudios e índices fue limitada debido a la falta de estandarización. La ausencia de evidencia de validez y estandarización de resultados conduce a problemas como la falta de soporte empírico para las puntuaciones y la dificultad para comparar estudios. Los datos revelan limitaciones en la evaluación de los niveles de burnout utilizados en el contexto de la seguridad pública, ya que las medidas no presentan evidencia de validez para este contexto, lo que apunta a la necesidad de realizar investigaciones en el área. (AU)

Proximal humeral locking plate: a viable alternative for fixation of distal femoral fractures in children / Placa de fixação de úmero proximal: uma alternativa para fixação de fraturas do fêmur distal em criança

ABSTRACT Distal femoral metaphyseal fractures are rare in children, and the proximity of the fracture to the growth plate makes their approach challenging. Objective Evaluate outcomes and complications of treatment of distal femoral metaphyseal fractures in children with proximal humeral locking plates. Method Retrospective study between 2018 and 2021, including seven patients. The analysis included general characteristics, trauma mechanism, classification, clinical and radiographic outcomes, and complications. Results The mean follow-up was 20 months, the average age was nine years, five patients were boys, and six fractured on the right side. Five fractures were caused by car accidents, one by falling from their own height and one by playing soccer. Five fractures were classified as 33-M/3.2 and two as 33-M/3.1. Three fractures were open, Gustilo IIIA. All seven patients recovered mobility and resumed their pre-trauma activities. All seven healed, and one fracture was reduced to 5 degrees valgus, without any other complications. Six patients had the implant removed and did not present refracture. Conclusion Treatment of distal femoral metaphyseal fractures with proximal humeral locking plates is a viable option that offers good results and fewer complications, saving the epiphyseal cartilage. Level of Evidence II; Controlled study without randomization.

RESUMO As fraturas metafisárias distais do fêmur são raras em crianças, a proximidade da fratura com a placa de crescimento torna a sua abordagem desafiadora. Objetivo Avaliar resultados e complicações do tratamento das fraturas da metáfise distal do fêmur em crianças com placas de úmero proximal. Método Estudo retrospectivo entre 2018 e 2021 incluindo sete pacientes. A análise incluiu características gerais, mecanismo do trauma, classificação, resultados clínicos, radiográficos e complicações. Resultados A média do acompanhamento foi de 20 meses, a idade média foi de nove anos, cinco pacientes eram meninos e seis fraturas do lado direito. Cinco fraturas por acidentes automobilísticos, uma por queda da própria altura e uma jogando futebol. Cinco fraturas classificadas como 33-M/3,2 e duas como 33-M/3,1. Três fraturas foram expostas, Gustilo IIIA. Todos os sete pacientes recuperaram a mobilidade e retomaram às atividades anteriores ao trauma. Todas as sete fraturas consolidaram, uma fratura foi reduzida com valgo de 5 graus, e não houveram outras complicações. Seis pacientes tiveram o implante removido e não apresentaram refratura. Conclusão O tratamento das fraturas da metáfise distal do fêmur com placas de úmero proximal é uma opção viável que oferece bons resultados com poucas complicações, poupando a cartilagem epifisária. Nível de Evidência II; Estudo controlado sem randomização.

Implementation of a patient blood management program based on a low-income country-adapted clinical decision support system

ABSTRACT Introduction: Patient blood management (PBM) programs are associated with better patient outcomes, a reduced number of transfusions and cost-savings The Clinical Decision Support (CDS) systems are valuable tools in this process, but their availability is limited in developing countries This study assesses the feasibility and effectiveness of an adapted CDS system for low-income countries. Methods: This was a prospective study of the PBM program implementation, in a 200-bed tertiary hospital, between February 2019 and May 2020. Outcome measures were red blood cell (RBC), fresh frozen plasma (FFP) and platelet unit transfusions, the transfusion of a single unit of red blood cells and an RBC adequacy index (RAI). Results: Comparing the post-PBM program era with the pre-PBM system era, there was a decrease in red blood cell transfusions (p = 0.05), with an increase in single unit red blood cell transfusions (p = 0.005) and RAI (p < 0.001). Conclusions: The PBM programs, including electronic transfusion guidelines with pre-transfusion medical auditing, was associated with improved transfusion practices and reduced product acquisition-related costs.

Risk factors for acute kidney injury after liver transplantation in intensive care unit: a retrospective cohort study

ABSTRACT BACKGROUND: Acute kidney injury (AKI) is a frequent complication during the postoperative period following liver transplantation. Occurrence of AKI in intensive care unit (ICU) patients is associated with increased mortality and higher costs. OBJECTIVE: To evaluate occurrences of moderate or severe AKI among patients admitted to the ICU after liver transplantation and investigate characteristics associated with this complication. DESIGN AND SETTING: Single-center retrospective cohort study in a public hospital, Belo Horizonte, Brazil. METHODS: Forty-nine patients admitted to the ICU between January 2015 and April 2017 were included. AKI was defined from a modified Kidney Disease Improving Global Outcomes (KDIGO) score (i.e. based exclusively on serum creatinine levels). RESULTS: Eighteen patients (36.7%) developed AKI KDIGO 2 or 3; mostly KDIGO 3 (16 out of the 18 patients). Lactate level within the first six hours after ICU admission (odds ratio, OR: 1.3; 95% confidence interval, CI: 1.021-1.717; P = 0.034) and blood transfusion requirement within the first week following transplantation (OR: 8.4; 95% CI: 1.687-41.824; P = 0.009) were independently associated with development of AKI. Patients with AKI KDIGO 2 or 3 underwent more renal replacement therapy (72.2% versus 3.2%; P < 0.01), had longer hospital stay (20 days versus 15 days; P = 0.001), higher in-hospital mortality (44.4% versus 6.5%; P < 0.01) and higher mortality rate after one year (44.4% versus 9.7%; P = 0.01). CONCLUSION: Need for blood transfusion during ICU stay and hyperlactatemia within the first six postoperative hours after liver transplantation are independently associated with moderate or severe AKI. Developing AKI is apparently associated with poor outcomes.

Cancer risk-reducing surgery: Brazilian society of surgical oncology guideline part 1 (gynecology and breast).

BACKGROUND: Risk-reducing operations are an important part of the management of hereditary predisposition to cancer. In selected cases, they can considerably reduce the morbidity and mortality associated with cancer in this population. OBJECTIVES: The Brazilian Society of Surgical Oncology (BSSO) developed this guideline to establish national benchmarks for cancer risk-reducing operations. METHODS: The guideline was prepared from May to December 2021 by a multidisciplinary team of experts to discuss the surgical management of cancer predisposition syndromes. Fourteen questions were defined and assigned to expert groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments, classified the level of evidence, and voted on the recommendations. RESULTS: For all questions including risk-reduction bilateral salpingo-oophorectomy, hysterectomy, and mastectomy, major agreement was achieved by the participants, always using accessible alternatives. CONCLUSION: This and its accompanying article represent the first guideline in cancer risk reduction surgery developed by the BSSO, and it should serve as an important reference for the management of families with cancer predisposition.

COLONOSCOPY FINDINGS IN LIVER TRANSPLANTATION CANDIDATES.

BACKGROUND: Mandatory colonoscopy in liver transplantation (LT) candidates is recommended but still controversial. OBJECTIVE: To investigate the frequency of colonoscopy lesions in order to support colorectal cancer (CRC) screening in a real-world pre-LT cohort. METHODS: Retrospective study conducted at a single-center included 632 subjects who underwent pre-transplantation colonoscopy. RESULTS: Median age was 56.9 years (yr.) old (82.3% were ≥50 yr.). Primary sclerosing cholangitis (PSC) occurred in 4.6%. Colonoscopy was abnormal in 438 (69.3%) by detection of polyps (37.7%), vascular changes (29.9%), diverticulosis (18.4%), inflammatory bowel disease features (5.2%) and CRC (0.6%). Histology was available in 66.8% of polyps: hyperplastic (47.8%), low-grade dysplasia (56.6%) and high-grade dysplasia (3.8%). High-risk adenomas occurred in 8.2% of the 594 subjects evaluated. Individuals ≥50 yr. were more likely to present abnormal colonoscopy and polyps. High-grade dysplasia and CRC were only found in individuals ≥50 yr. Patients with high-risk adenomas were more likely to be ≥50 yr.: there was no association between high-risk adenomas detection and liver disease etiology or PSC diagnosis. CONCLUSION: Most LT candidates presented abnormal colonoscopy examination, especially by polyps presence. All cases of high-grade dysplasia and CRC occurred in patients ≥50 yr., regardless of disease etiology.

Achados da colonoscopia em candidatos a transplante hepático / Colonoscopy findings in liver transplantation candidates

ABSTRACT Background Mandatory colonoscopy in liver transplantation (LT) candidates is recommended but still controversial. Objective To investigate the frequency of colonoscopy lesions in order to support colorectal cancer (CRC) screening in a real-world pre-LT cohort. Methods Retrospective study conducted at a single-center included 632 subjects who underwent pre-transplantation colonoscopy. Results Median age was 56.9 years (yr.) old (82.3% were ≥50 yr.). Primary sclerosing cholangitis (PSC) occurred in 4.6%. Colonoscopy was abnormal in 438 (69.3%) by detection of polyps (37.7%), vascular changes (29.9%), diverticulosis (18.4%), inflammatory bowel disease features (5.2%) and CRC (0.6%). Histology was available in 66.8% of polyps: hyperplastic (47.8%), low-grade dysplasia (56.6%) and high-grade dysplasia (3.8%). High-risk adenomas occurred in 8.2% of the 594 subjects evaluated. Individuals ≥50 yr. were more likely to present abnormal colonoscopy and polyps. High-grade dysplasia and CRC were only found in individuals ≥50 yr. Patients with high-risk adenomas were more likely to be ≥50 yr.: there was no association between high-risk adenomas detection and liver disease etiology or PSC diagnosis. Conclusion Most LT candidates presented abnormal colonoscopy examination, especially by polyps presence. All cases of high-grade dysplasia and CRC occurred in patients ≥50 yr., regardless of disease etiology.

RESUMO Contexto Colonoscopia mandatória em candidatos a transplante hepático (TH) é recomendada, mas ainda é controversa. Objetivo Investigar a frequência de lesões detectadas pela colonoscopia para endossar o screening de câncer colorretal (CCR) em uma coorte pré-TH de mundo real. Métodos Estudo retrospectivo conduzido em um centro único que incluiu 632 indivíduos submetidos a colonoscopia pré-TH. Resultados Idade mediana foi 56.9 anos (82,3% eram ≥50 anos). Colangite esclerosante primária (CEP) estava presente em 4.6%. Colonoscopia foi anormal em 438 (69,3%) por: detecção de pólipos (37,7%), alterações vasculares (29,9%), diverticulose (18,4%), características de doença inflamatória intestinal (5,2%) e CCR (0,6%). Histologia estava disponível em 66,8% dos pólipos: hiperplásicos (47,8%), displasia de baixo grau (56,6%) e displasia de alto grau (3,8%). Adenomas de alto risco ocorreram em 8,2% dos 594 indivíduos avaliados. Indivíduos ≥50 anos eram mais prováveis de apresentar colonoscopia anormal e pólipos. Displasia de alto grau e CCR foram encontrados somente em indivíduos ≥50 anos. Pacientes com adenoma de alto risco eram mais prováveis de ter ≥50 anos: não houve associação entre a detecção de adenomas de alto risco e a etiologia da hepatopatia ou o diagnóstico de CEP. Conclusão A maioria dos candidatos a TH apresentaram achados anormais na colonoscopia, principalmente pela presença de pólipos. Todos os casos de displasia de alto grau e CCR ocorreram em pacientes ≥50 anos, independente da etiologia da hepatopatia.

Segundo Consenso Brasileiro de Manejo da Doença de Crohn em adultos: um consenso da Organização Brasileira de Doença de Crohn e Colite (GEDIIB) / Second brazilian consensus on the management of crohn's disease in adults: a consensus of the brazilian organization for crohn's disease and colitis (gediib)

ABSTRACT Background: Inflammatory bowel disease (IBD) is an immune-mediated disorder that includes Crohn's disease (CD) and ulcerative colitis. CD is characterized by a transmural intestinal involvement from the mouth to the anus with recurrent and remitting symptoms that can lead to progressive bowel damage and disability over time. Objective: To guide the safest and effective medical treatments of adults with CD. Methods: This consensus was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's disease and Colitis (GEDIIB)). A systematic review of the most recent evidence was conducted to support the recommendations/statements. All included recommendations and statements were endorsed in a modified Delphi panel by the stakeholders and experts in IBD with an agreement of at least 80% or greater consensus rate. Results and conclusion: The medical recommendations (pharmacological and non-pharmacological interventions) were mapped according to the stage of treatment and severity of the disease in three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus is targeted towards general practitioners, gastroenterologists, and surgeons interested in treating and managing adults with CD and supports the decision-making of health insurance companies, regulatory agencies, and health institutional leaders or administrators.

RESUMO Contexto: A doença inflamatória intestinal (DII) é uma doença imunomediada que inclui a doença de Crohn (DC) e a retocolite ulcerativa. A DC é caracterizada por um envolvimento intestinal transmural da boca ao ânus com sintomas recorrentes e remitentes que podem levar a danos intestinais progressivos e incapacidade ao longo do tempo. Objetivo: Orientar os tratamentos médicos mais seguros e eficazes de adultos com DC. Métodos: Este consenso foi desenvolvido por autores que representam gastroenterologistas e cirurgiões brasileiros especialistas em doenças colorretais (GEDIIB, Organização Brasileira de Doença de Crohn e Colite). Uma revisão sistemática das evidências mais recentes foi realizada para apoiar as recomendações/declarações. Todas as recomendações e declarações incluídas foram endossadas em um painel Delphi modificado pelas partes interessadas e especialistas em DII com uma concordância de pelo menos 80% ou mais. Resultados e conclusão: As recomendações médicas (intervenções farmacológicas e não farmacológicas) foram mapeadas de acordo com o estágio de tratamento e gravidade da doença em três domínios: manejo e tratamento (intervenções medicamentosas e cirúrgicas), critérios para avaliar a eficácia do tratamento médico, e acompanhamento/monitoramento do paciente após o tratamento inicial. O consenso é direcionado a clínicos gerais, gastroenterologistas e cirurgiões interessados em tratar e gerenciar adultos com DC e apoia a tomada de decisões de companhias de seguro de saúde, agências reguladoras e líderes ou administradores de instituições de saúde.

Segundo Consenso Brasileiro no manejo da retocolite ulcerativa em adultos: um consenso da Organização Brasileira para Doença de Crohn e Colite (GEDIIB) / Second brazilian consensus on the management of ulcerative colitis in adults: a consensus of the brazilian organization for crohn's disease and colitis (gediib)

ABSTRACT Background: Inflammatory bowel diseases are immune-mediated disorders that include Crohn's disease (CD) and ulcerative colitis (UC). UC is a progressive disease that affects the colorectal mucosa causing debilitating symptoms leading to high morbidity and work disability. As a consequence of chronic colonic inflammation, UC is also associated with an increased risk of colorectal cancer. Objective: This consensus aims to provide guidance on the most effective medical management of adult patients with UC. Methods: A consensus statement was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's Disease and Colitis [GEDIIB]). A systematic review including the most recent evidence was conducted to support the recommendations and statements. All recommendations/statements were endorsed using a modified Delphi Panel by the stakeholders/experts in inflammatory bowel disease with at least 80% or greater consensus. Results and conclusion: The medical recommendations (pharmacological and non-pharmacological) were mapped according to the stage of treatment and severity of the disease onto three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus targeted general practitioners, gastroenterologists and surgeons who manage patients with UC, and supports decision-making processes by health insurance companies, regulatory agencies, health institutional leaders, and administrators.

RESUMO Contexto: As doenças inflamatórias intestinais são doenças imunomediadas que incluem a doença de Crohn (DC) e a retocolite ulcerativa (RCU). A RCU é uma doença progressiva que acomete a mucosa colorretal causando sintomas debilitantes levando a alta morbidade e incapacidade laboral. Como consequência da inflamação crônica do cólon, a RCU também está associada a um risco aumentado de câncer colorretal. Objetivo: Este consenso visa fornecer orientações sobre o manejo médico mais eficaz de pacientes adultos com RCU. Métodos: As recomendações do consenso foram desenvolvidas por gastroenterologistas e cirurgiões colorretais referências no Brasil (membros da Organização Brasileira para Doença de Crohn e Colite [GEDIIB]). Uma revisão sistemática, incluindo as evidências mais recentes, foi conduzida para apoiar as recomendações. Todas as recomendações foram endossadas pelas partes interessadas/especialistas em doença inflamatória intestinal usando um Painel Delphi modificado. O nível de concordância para alcançar consenso foi de 80% ou mais. Resultados e conclus ão: As recomendações médicas (farmacológicas e não farmacológicas) foram mapeadas de acordo com o estágio de tratamento e gravidade da doença em três domínios: manejo e tratamento (intervenções medicamentosas e cirúrgicas), critérios para avaliar a eficácia do tratamento médico, e acompanhamento/monitoramento do paciente após o tratamento inicial. O consenso foi direcionado a clínicos gerais, gastroenterologistas e cirurgiões que tratam pacientes com RCU e apoia os processos de tomada de decisão por companhias de seguro de saúde, agências reguladoras, líderes institucionais de saúde e administradores.

Real-world disease activity and sociodemographic, clinical and treatment characteristics of moderate-to-severe inflammatory bowel disease in Brazil.

BACKGROUND: Understanding the treatment landscape of inflammatory bowel diseases (IBD) is essential for improving disease management and patient outcomes. Brazil is the largest Latin American country, and it presents socioeconomic and health care differences across its geographical regions. This country has the highest increase in IBD incidence and prevalence in Latin America, but information about the clinical and treatment characteristics of IBD is scarce. AIM: To describe the sociodemographic, clinical, and treatment characteristics of IBD outpatients in Brazil overall and in the Southeast, South and Northeast/Midwest regions. METHODS: Multicenter, cross-sectional study with a 3-year retrospective chart review component. Patients with moderate-to-severe Crohn's disease (CD) or ulcerative colitis (UC) were consecutively enrolled between October 2016 and February 2017. Active CD at enrollment was defined as a Harvey Bradshaw Index ≥ 8 or a CD Activity Index ≥ 220 or a calprotectin level > 200 µg/g or an active result based on colonoscopy suggestive of inadequate control during the previous year; active UC was defined as a partial Mayo score ≥ 5. Descriptive statistics were used to analyze all variables. RESULTS: In a total of 407 included patients, CD was more frequent than UC, both overall (264 CD/143 UC patients) and by region (CD:UC ratios of 2.1 in the Southeast, 1.6 in the South and 1.2 in the Northeast/Midwest). The majority of patients were female (54.2% of CD; 56.6% of UC), and the mean ages were 45.9 ± 13.8 years (CD) and 42.9 ± 13.0 years (UC). The median disease duration was 10.0 (range: 0.5-45) years for both IBD types. At enrollment, 44.7% [95% confidence interval (CI): 38.7-50.7] of CD patients and 25.2% (95%CI: 18.1-32.3) of UC patients presented with active disease. More than 95% of IBD patients were receiving treatment at enrollment; CD patients were commonly treated with biologics (71.6%) and immunosuppressors (67.4%), and UC patients were commonly treated with mesalazine [5-Aminosalicylic acid (5-ASA)] derivates (69.9%) and immunosuppressors (44.1%). More than 50% of the CD patients had ileocolonic disease, and 41.7% presented with stricturing disease. One-quarter of CD patients had undergone CD-related surgery in the past 3 years, and this proportion was lower in the Northeast/Midwest region (2.9%). CONCLUSION: In Brazil, there are regional variations in IBD management. CD outweighs UC in both frequency and disease activity. However, one-quarter of UC patients have active disease, and most are receiving 5-ASA treatment.

Combined evaluation of fecal calprotectin and C-reactive protein as a therapeutic target in the management of patients with Crohn's disease.

OBJECTIVES: Proper management of the inflammatory process in Crohn's disease (CD) results in lower rates of complications. The objective of this study was to investigate the performance of isolated and combined use of fecal calprotectin (FC) and serum levels of C-reactive protein (CRP) as markers of inflammatory activity in CD and the possibility of their use as a therapeutic target. PATIENTS AND METHODS: Patients with CD and indication for colonoscopy were prospectively enrolled in the study and allocated according to the presence or absence of endoscopic inflammatory activity. The correlation between FC and CRP levels and the Simplified Endoscopic Score of Crohn's Disease (SES-CD) was performed, and the accuracy of these markers was evaluated for the diagnosis of inflammatory activity, when used alone or in series. RESULTS: Eighty colonoscopies were performed in patients with CD. The FC cut-off value of 155µg/g showed high sensitivity (96%) and accuracy (78%) for the diagnosis of endoscopic activity. For CRP, the value of 6.7mg/L demonstrated sensitivity of 75% and specificity of 67%. The sequential usage of these markers (FC+CRP) showed greater specificity (82%) when compared to the use of these markers alone. Depending on the probability of inflammatory activity, different scenarios were used to evaluate the performance of these markers and an algorithm is proposed. DISCUSSION: Combined analysis of FC and CRP, when performed consecutively, allows decisions to be made with a high degree of certainty and even eliminates the need for colonoscopy in many situations.

Expressive and receptive vocabulary in preschool children and socioeconomic factors / Vocabulário expressivo e receptivo em crianças da pré-escola e fatores socioeconômicos

ABSTRACT Purpose: to assess the expressive and receptive vocabulary of preschool children and trace the relationship with different socioeconomic factors. Methods: 108 children, aged between 4 and 6 years, were evaluated, 84 from a public preschool and 24 from a private preschool, using the following instruments: CMMS - Columbia Mental Maturity Scale; ABFW; Peabody Image Vocabulary Test (PPVT); CONFIAS - Phonological Awareness: Sequential Assessment Instrument; Rapid Automatic Naming Test (NAR); Questionnaires for the definition of economic classification, general health and family habits. For statistical analyses, the non-parametric Kruskal-Wallis test, Bonferroni post hoc corrections to check significant differences and Spearman correlation were used. Results: the results found showed a statistically significant relationship between factors such as salary range, mother's and father's education and performance on tests of receptive and expressive vocabulary and mental maturity. Conclusion: evidence showed the relationship of socioeconomic factors with language development in preschoolers.

RESUMO Objetivo: avaliar o vocabulário expressivo e receptivo de crianças pré-escolares e traçar a relação com diferentes fatores socioeconômicos. Métodos: foram avaliadas 108 crianças, com idades entre 4 e 6 anos, sendo 84 de uma pré-escola pública e 24 de pré-escola particular, com os seguintes instrumentos: CMMS - Escala de Maturidade Mental Colúmbia; ABFW; Teste de Vocabulário por Imagens Peabody (TVIP); CONFIAS - Consciência Fonológica: Instrumento de Avaliação Sequencial; Teste de Nomeação Automática Rápida (NAR); Questionários para a definição de classificação econômica, saúde geral e hábitos familiares. Para as análises estatísticas foram utilizados: o teste não-paramétrico de Kruskal-Wallis, as correções Bonferroni post hoc para verificar diferenças significantes e a correlação de Sperman. Resultados: os resultados demonstraram relação estatisticamente significante entre fatores como faixa salarial, escolaridade da mãe e do pai e desempenho nos testes de vocabulário receptivo, expressivo e maturidade mental. Conclusão: evidências mostram a relação dos fatores socioeconômicos com o desenvolvimento da linguagem em pré-escolares.

Taxas de descontinuação do tratamento após a troca de um biológico originador por um biossimilar em pacientes com doenças inflamatórias intestinais: revisão sistemática e metanálise / Discontinuation rates following a switch from a reference to a biosimilar biologic in patients with inflammatory bowel disease: a systematic review and meta-analysis

ABSTRACT BACKGROUND: Biologics have revolutionized the treatment of inflammatory bowel disease (IBD). However, these drugs had a significant influence on treatment-related costs, which resulted in the development of biosimilars. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the drug discontinuation rate in the IBD population who switched from originator to biosimilars in real-world switching studies and address potential nocebo effects as reasons for drug discontinuation. METHODS: Medline (via PubMed), EMBASE, Cochrane Library, and abstract databases of selected congresses were screened for reports of monoclonal antibody (mAb) switching with a minimum post-switch follow-up of >6 months or three infusions. All available information on discontinuation rates was assessed. RESULTS: A total of 30 observational studies were included, involving 3,594 patients with IBD. Twenty-six studies reported a switch from infliximab to CT-P13, two studies involved a switch to SB2, and switching information was not available in two studies. The discontinuation rates were 8%, 14%, and 21% at 6, 12, and 24 months, respectively. The main reasons for drug discontinuation and their respective risks were: disease worsening (2%), remission (4%), loss of adherence (4%), adverse events (5%), and loss of response (7%). The quality of the evidence ranged from low to very low depending on the outcome analyzed. Subjective symptoms leading to drug discontinuation were infrequently reported, and the nocebo effect was clearly assessed in just one of the included papers. CONCLUSION: Discontinuation rates following a switch to a biosimilar in patients with IBD increase over time. However, it was not possible to confirm the nocebo effect as a reason for discontinuation. Therefore, long-term studies evaluating the use of biosimilars to monitor adverse events and potential nocebo effects in post-marketing surveillance are still needed.

RESUMO CONTEXTO: Os biológicos revolucionaram o tratamento da doença inflamatória intestinal (DII). Ademais, esses medicamentos influenciaram os custos relacionados ao tratamento. Tal aumento significativo nos gastos com o tratamento motivou desenvolvimento dos biossimilares. OBJETIVO: Esta revisão sistemática e metanálise objetivou avaliar a taxa de descontinuação de medicamentos na população com DII que foi submetida à troca do biológico originador para um biossimilar, em estudos observacionais que abordaram possíveis razões para a descontinuação do tratamento. MÉTODOS: Tendo como base de dados Medline (via PubMed), EMBASE, Cochrane Library e resumos de congressos médicos, foram rastreados artigos com relatos de troca de um biológico originador por um biossimilar, com acompanhamento pós-troca de no mínimo 6 meses ou três infusões. Todas as informações disponíveis sobre as taxas de descontinuação foram avaliadas. RESULTADOS: Foram incluídos no total 30 estudos observacionais, envolvendo 3.594 pacientes com DII. Vinte e seis estudos relataram uma mudança do infliximabe para CT-P13, dois estudos envolveram uma mudança para o SB2, e as informações sobre a troca não estavam disponíveis em dois estudos. As taxas de descontinuação foram de 8%, 14% e 21% aos 6, 12 e 24 meses, respectivamente. Os principais motivos para a descontinuação do medicamento e seus respectivos riscos foram: agravamento da doença (2%), remissão (4%), perda de adesão (4%), eventos adversos (5%) e perda de resposta (7%). A qualidade da evidência variou de baixa a muito baixa, dependendo do resultado analisado. Os sintomas subjetivos que levaram à descontinuação do medicamento foram relatados com pouca frequência, e o efeito nocebo foi claramente avaliado em apenas um dos artigos incluídos. CONCLUSÃO: As taxas de descontinuação após a mudança para um biossimilar em pacientes com DII aumentam com o tempo. No entanto, não foi possível confirmar o efeito nocebo como motivo da descontinuação. Portanto, ainda são necessários estudos em longo prazo avaliando o uso de biossimilares para monitorar eventos adversos e potenciais efeitos nocebo na vigilância pós-comercialização.

Faecal calprotectin is the biomarker that best distinguishes remission from different degrees of endoscopic activity in Crohn's disease.

BACKGROUND: Effective control of the inflammatory process in Crohn's disease (CD) is reflected in intestinal mucosal healing. The performances of faecal calprotectin (fcal), clinical and serologic parameters in the inflammatory activity evaluation and their correlation to the simple endoscopic score (SES-CD) are the goals of this study. METHODS: Patients with CD referred for ileocolonoscopy were prospectively included and distributed according to the degree of endoscopic inflammatory activity into remission, mild activity, and moderate to severe activity groups. The different degrees of endoscopic activity were correlated with the following indexes: Crohn's disease activity index (CDAI), fCal, serum C-reactive protein (CRP), and haemogram. The control group comprised individuals without known intestinal disease who were referred for colorectal cancer screening. RESULTS: Eighty colonoscopies were performed in patients with CD and 21 in the control group. The control group had a lower median fCal (59.7 mcg/g) than patients with CD (683 mcg/g, p < 0.001). A moderate Spearman correlation occurred between SES-CD and CRP (r = 0.525), fCal (r = 0.450), and CDAI (r = 0.407), while a weak correlation was found with the platelet count (r = 0.257). Only fCal distinguished patients in remission from those with mild activity (236.6 mcg/g × 654.9 mcg/g, p = 0.014) or moderate to severe activity (236.6 mcg/g × 1128 mcg/g, p < 0.001). An fCal cut-off of 155 mcg/g was sensitive (96%) and accurate (78%) for the diagnosis of endoscopic activity. CONCLUSIONS: fCal provides greater diagnostic accuracy than the other activity markers for endoscopic activity of patients with CD, moderate correlation to SES-CD, and a capacity to discriminate patients in remission from those with mild or moderate to severe activity.

Effect of Oral Nutrition Supplements and TGF-ß2 on Nutrition and Inflammatory Patterns in Patients With Active Crohn's Disease.

BACKGROUND: Crohn's disease (CD) is often associated with nutrition disorders. Many nutrition therapeutic alternatives have been studied. Nevertheless, the actual role of nutrition therapy is still controversial. The objective of this study was to assess the effects of nutrition supplementation with and without transforming growth factor-beta 2 (TGF-ß2) on inflammatory, endoscopic, histopathologic, and nutrition parameters in active CD. MATERIALS AND METHODS: Thirty-eight patients were allocated into 3 groups: group 1 (patients who received only nutrition orientation), group 2 (nutrition orientation and a normoproteic, normocaloric nutrition supplement), and group 3 (nutrition orientation and the nutritional supplement with TGF-ß2). Clinical and nutrition evaluation, C-reactive protein (CRP) levels, and assessment of endoscopic and histologic parameters in the intestinal mucosa were performed before and after nutrition intervention. RESULTS: The mean follow-up period was 3 months. In the beginning of the study, groups were homogeneous regarding age, gender, CD behavior and localization, and medication in use. In the end of the study, the Clinical Disease Activity Index score was reduced in groups 2 and 3; in group 3, a reduction in CRP levels and an improvement in histologic findings were observed. Among patients who received nutritional supplement, some anthropometric patterns were improved. CONCLUSION: The results of the study indicate that nutritional supplementation improved nutrition and inflammatory patterns in patients with active CD. However, only patients receiving TGF-ß2-enriched formula showed improvement in histologic parameters and significant reduction in CRP levels.

Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cells.

Genome lesions trigger biological responses that help cells manage damaged DNA, improving cell survival. Pol eta is a translesion synthesis (TLS) polymerase that bypasses lesions that block replicative polymerases, avoiding continued stalling of replication forks, which could lead to cell death. p53 also plays an important role in preventing cell death after ultraviolet (UV) light exposure. Intriguingly, we show that p53 does so by favoring translesion DNA synthesis by pol eta. In fact, the p53-dependent induction of pol eta in normal and DNA repair-deficient XP-C human cells after UV exposure has a protective effect on cell survival after challenging UV exposures, which was absent in p53- and Pol H-silenced cells. Viability increase was associated with improved elongation of nascent DNA, indicating the protective effect was due to more efficient lesion bypass by pol eta. This protection was observed in cells proficient or deficient in nucleotide excision repair, suggesting that, from a cell survival perspective, proper bypass of DNA damage can be as relevant as removal. These results indicate p53 controls the induction of pol eta in DNA damaged human cells, resulting in improved TLS and enhancing cell tolerance to DNA damage, which parallels SOS responses in bacteria.

O-glycan sialylation alters galectin-3 subcellular localization and decreases chemotherapy sensitivity in gastric cancer.

ST6GalNAc-I, the sialyltransferase responsible for sialyl-Tn (sTn) synthesis, has been previously reported to be positively associated with cancer aggressiveness. Here we describe a novel sTn-dependent mechanism for chemotherapeutic resistance. We show that sTn protects cancer cells against chemotherapeutic-induced cell death by decreasing the interaction of cell surface glycan receptors with galectin-3 and increasing its intracellular accumulation. Moreover, exogenously added galectin-3 potentiated the chemotherapeutics-induced cytotoxicity in sTn non-expressing cells, while sTn overexpressing cells were protected. We also found that the expression of sTn was associated with a reduction in galectin-3-binding sites in human gastric samples tumors. ST6GalNAc-I knockdown restored galectin-3-binding sites on the cell surface and chemotherapeutics sensibility. Our results clearly demonstrate that an interruption of O-glycans extension caused by ST6GalNAc-I enzymatic activity leads to tumor cells resistance to chemotherapeutic drugs, highlighting the need for the development of novel strategies to target galectin-3 and/or ST6GalNAc-I.

Association between the p27 rs2066827 variant and tumor multiplicity in patients harboring MEN1 germline mutations.

OBJECTIVE: To date, no evidence of robust genotype-phenotype correlation or disease modifiers for multiple endocrine neoplasia type 1 (MEN1) syndrome has been described, leaving the highly variable clinical presentation of patients unaccounted for. DESIGN: As the CDKN1B (p27) gene causes MEN4 syndrome and it is transcriptionally regulated by the product of the MEN1 gene (menin), we sought to analyze whether p27 influences the phenotype of MEN1-mutated patients. The cohort consisted of 100 patients carrying germline MEN1 gene mutations and 855 population-matched control individuals. METHODS: Genotyping of the coding p27 c.326T>G (V109G) variant was performed by sequencing and restriction site digestion, and the genotypes were associated with clinical parameters by calculating odds ratios (ORs) and their 95% CIs using logistic regression. RESULTS: There were significant differences in p27 V109G allele frequencies between controls and MEN1-mutated patients (OR=2.55, P=0.019, CI=1.013-5.76). Among patients who are ≥30 years old carrying truncating MEN1 mutations, the T allele was strongly associated with susceptibility to tumors in multiple glands (three to four glands affected vs one to two glands affected; OR=18.33; P=0.002, CI=2.88-16.41). This finding remained significant after the Bonferroni's multiple testing correction, indicating a robust association. No correlations were observed with the development of MEN1-related tumors such as hyperparathyroidism, pituitary adenomas, and enteropancreatic and adrenocortical tumors. CONCLUSIONS: Our study suggests that the p27 tumor suppressor gene acts as a disease modifier for the MEN1 syndrome associated with MEN1 germline mutations. If confirmed in independent patient cohorts, this finding could facilitate the management of this clinically complex disease.