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Abstract Objective: This study aimed to evaluate the diagnostic utility, disease activity, and phenotypic association of serum anti-Saccharomyces cerevisiae antibody (ASCA), perinuclear anti-neutrophil cytoplasmic antibody (pANCA), PR3-ANCA, and MPO-ANCA in pediatric patients with inflammatory bowel disease (IBD). Methods: Pediatric patients diagnosed with IBD were recruited and classified as Crohn's disease (CD), ulcerative colitis (UC), and IBD-unclassified (IBD-U) through full investigation. The Paris classification was used to evaluate disease phenotypes of pediatric CD and UC. Results: In all, 229 pediatric patients with IBD (CD 147, UC 53, IBD-U 29) were included. The ASCA IgG seropositivity significantly differed among the three groups (CD 75.4%, UC 17.5%, and IBD-U 60.0%; p < 0.001). PR3-ANCA positive rates were the highest in UC (24.0%), followed by IBD-U (17.6%), and none in CD (p = 0.002); pANCA-positive rates were higher in IBD-U (33.6%), followed by UC (28.0%) than in CD (1.4%) (p < 0.001). Regarding disease phenotype, perianal disease revealed higher serum ASCA IgG titers (median 36.7 U/mL in P1 vs. 25.2 U/mL in P0, p = 0.019). Serum ASCA IgG and IgA cutoff values to distinguish CD were 32.7 (U/mL) and 11.9 (U/mL), respectively, with a specificity of 80.0%. Conclusion: Serological biomarkers of ASCA IgG and IgA were effective for differentiating CD in pediatric IBD patients, and serum pANCA and PR3-ANCA, but not MPO-ANCA, were effective in distinguishing UC and IBD-U. Furthermore, measuring serological titers of ASCA IgG and IgA may help differentiate CD and evaluate the disease activity and phenotype of pediatric IBD in practice.
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ABSTRACT Malnutrition/sarcopenia is frequent in patients with inflammatory bowel diseases (IBD), and results in muscle catabolism, impacting treatment response, postoperative complications, and quality of life. Objective: This study aims to assess whether the phase angle (PhA) is a parameter for predicting reduced muscle mass in patients with IBD. Methods: Adult patients with IBD were included in this cross-sectional study. For the estimation of muscle mass and the calculation of the PhA, we used bioelectrical impedance analysis (BIA). Crohn's disease (CD) and ulcerative colitis (UC) activity scores were defined using the Harvey-Bradshaw index and partial Mayo score, respectively. The area under the ROC curve was calculated to identify the PhA cut-off point for reduced muscle mass. Results: The sample consisted of 145 patients, with 39 (26.9%) with IBD in the active phase. There was a correlation of the PhA with skeletal muscle mass (SMM) (rs 0.35, P<0.001) and with the skeletal muscle mass index (SMI) (rs 0.427, P<0.001), and the associations remained in the most active form (moderate or severe) of IBD. The ROC curve analysis indicated that the cut-offs points of the PhA ≤5.042 for female and PhA ≤6.079 for male can be used to predict muscle mass reduction. Conclusion: The PhA can be considered a predictor of muscle mass reduction in IBD patients, and we can use it for screening and monitoring the evolution of malnutrition.
RESUMO A desnutrição/sarcopenia é frequente em pacientes com doenças inflamatórias intestinais (DII), resultando em catabolismo muscular, com impacto nas respostas aos tratamentos, complicações cirúrgicas e na qualidade de vida. Objetivo: Este estudo tem como objetivo, avaliar se o ângulo de fase (AF) é um parâmetro para a predição de redução de massa muscular em pacientes com DII. Métodos: Pacientes adultos com DII foram incluídos neste estudo transversal. A estimativa da massa muscular e o cálculo do AF foram realizados a partir do exame de bioimpedância elétrica (BIA). As atividades da doença de Crohn e retocolite ulcerativa foram definidas pelo índice Harvey-Bradshaw e escore parcial de Mayo, respectivamente. A área de curva ROC foi calculada para identificar o ponto de corte do AF para a massa muscular reduzida. Resultados: A amostra foi composta por 145 pacientes, sendo 39 (26.9%) com DII em fase ativa. Houve correlação do AF com massa muscular esquelética (MME) (rs 0.35, P<0.001) e com o índice de massa muscular esquelética (IMME) (rs 0.427, P<0.001), mantendo-se as associações na forma mais ativa (moderada ou grave) da DII. A análise da curva ROC indicou que os pontos de corte de AF ≤5.042 para mulheres e ≤6.079 para homens podem ser usados para prever a redução da massa muscular. Conclusão: O AF pode ser considerado um preditor de redução de massa muscular nos pacientes com DII e ser utilizado para triagem e acompanhamento da evolução da desnutrição.
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ABSTRACT Inflammatory bowel disease (IBD) can be accompanied by several neurological disorders. Since 2004, we started a Brazilian cohort to assess neuropsychiatric complications in IBD patients. Changes in therapeutic strategy and differences in the prevalence and relevance of neuropsychiatric disorders have been reported in the literature. We conducted a short patient-reported survey about the medical management of IBD (with a special focus on neuropsychiatric management) and its complications. During the enrollment period (9/1/2021 to 8/31/2022), 279 patients with IBD answered the survey (128 patients with ulcerative colitis and 151 with Crohn's disease). This is the first medical management survey aimed to verify the level of perception of IBD patients about their neuropsychiatric conditions. We found a high prevalence of neurologic (59%), psychiatric (32%), and neuropsychiatric co-morbidities (69%). There is a marked discrepancy between the findings of neurological disorders reported in our studies over the first 10 years of the cohort in comparison with the current perception/knowledge among the patients registered in the present management survey. Patients tend to have a better understanding of central rather than peripheral nerve conditions.
RESUMO A doença inflamatória intestinal (DII) pode ser acompanhada por vários distúrbios neurológicos. Desde 2004, iniciamos uma coorte brasileira para avaliar complicações neuropsiquiátricas em pacientes com DII. Mudanças na estratégia terapêutica e diferenças na prevalência e relevância dos transtornos neuropsiquiátricos têm sido relatadas na literatura. Realizamos uma breve pesquisa relatada pelos pacientes sobre o manejo médico da DII (com foco especial no manejo neuropsiquiátrico) e suas complicações. Durante o período de 01/09/2021 a 31/08/2022, 279 pacientes com DII responderam à pesquisa (128 pacientes com retocolite ulcerativa e 151 com doença de Crohn). Esta é a primeira pesquisa de gestão médica que visa verificar o nível de percepção dos pacientes com DII acerca de suas condições neuropsiquiátricas. Encontramos uma alta prevalência de comorbidades neurológicas (59%), psiquiátricas (32%) e neuropsiquiátricas (69%). Há uma discrepância marcante entre os achados de distúrbios neurológicos relatados em nossos estudos durante os primeiros 10 anos da coorte em comparação com a percepção/conhecimento atual entre os pacientes da presente pesquisa de manejo. Os pacientes tendem a ter uma melhor compreensão das condições que afetam o sistema nervoso central do que as que afetam o sistema nervoso periférico.
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ABSTRACT Background: Inflammatory bowel diseases (IBD) have rising incidence and prevalence rates globally. In IBD, there are scarce studies comparing differences between patients according to socioeconomic status. Our aim was to comparatively evaluate hospitalizations, use of biologics and rates of surgery in patients with IBD between public and private healthcare systems. Methods: Single-center retrospective cohort study in patients with IBD from a tertiary referral unit from Latin America, between 2015 and 2021. CD and UC patients were classified into two subgroups: public and private systems. Demographic characteristics, hospitalizations, need for surgery and biologics were compared. Results: A total of 500 patients were included, 322 with CD and 178 with UC. CD-related hospitalizations were frequently observed in both healthcare systems (76.28% in private and 67.46% in public). More than half of the patients had been submitted to one or more CD-related abdominal surgery, with no significant difference between the subgroups. Although there was no difference in the rates of use of biological therapy in CD subgroups, infliximab was more used in the public setting (57.69% vs 43.97%). There was no difference in UC-related hospitalizations between the subgroups (public 30.69% and private 37.66%) as well as the rates of colectomy (public: 16.83%, private: 19.48%). Biologics were prescribed almost twice as often in private as compared to public (45.45 vs 22.77%). Conclusion: There were no differences in the rates of hospitalization and abdominal surgery between the systems. In patients with UC, there was greater use of biological therapy in the private healthcare setting.
RESUMO Contexto: As doenças inflamatórias intestinais (DII) têm taxas crescentes de incidência e prevalência em todo o mundo. Na DII, são escassos os estudos comparando as diferenças entre os pacientes de acordo com o nível socioeconômico. Objetivo: Nosso objetivo foi avaliar comparativamente as hospitalizações, o uso de biológicos e as taxas de cirurgia em pacientes com DII entre os sistemas público e privado de saúde. Métodos: Estudo de coorte retrospectivo unicêntrico em pacientes com DII de uma unidade terciária de referência da América Latina, entre 2015 e 2021. Os pacientes com DC (doença de Crohn) e retocolite ulcerativa foram classificados em dois subgrupos: sistema público e privado. Características demográficas, hospitalizações, necessidade de cirurgia e biológicos foram comparadas. Resultados: Foram inclusos 500 pacientes, sendo 322 com DC e 178 com retocolite ulcerativa. Internações por DC foram frequentes em ambos os sistemas de saúde (76,28% na rede privada e 67,46% na rede pública). Mais da metade dos pacientes havia sido submetida a uma ou mais cirurgias abdominais relacionadas à DC, sem diferença significativa entre os subgrupos. Embora não tenha havido diferença nas taxas de uso de terapia biológica nos subgrupos de DC, o infliximabe foi mais utilizado no ambiente público (57,69% vs 43,97%). Não houve diferença nas internações relacionadas a retocolite ulcerativa entre os subgrupos (público 30,69% e privado 37,66%) e nas taxas de colectomia (público: 16,83%, privado: 19,48%). Os biológicos foram prescritos quase duas vezes mais no privado do que no público (45,45 vs 22,77%). Conclusão: Não houve diferença nas taxas de internação hospitalar e de cirurgia abdominal entre os sistemas. Nos pacientes com retocolite ulcerativa, houve maior utilização da terapia biológica no setor privado de saúde.
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ABSTRACT Backgrounds: Fortunately, much has been studied about COVID-19 in patients with inflammatory bowel diseases (IBD). Evidence suggests that these patients do not appear to be at increased risk of severe COVID-19. However, there are still some uncertainties regarding the clinical manifestations of COVID-19 in patients with immune-mediated diseases. Objective: This study aimed to describe the main symptoms of COVID-19 and their frequency in IBD patients and evaluate the impact of the IBD therapeutic drugs on clinical presentation of COVID-19 and to determine factors associated with COVID-19 in this population. Methods: Adult patients with IBD from three tertiary-care public, teaching hospitals in Ceará, Northeastern Brazil, were evaluated during one scheduled appointment from March to December 2020. Patients with possible or confirmed COVID-19 were compared with patients without COVID-19. Furthermore, incidences of each symptom were evaluated based on the use of IBD therapeutic drugs. Results: A total of 515 patients with IBD were included in the study: 234 with CD, and 281 with UC. Of these, 174 patients (34%) had possible/confirmed COVID-19 of whom 156 (90%) were symptomatic. Main symptoms were fever (65%) and headache (65%); gastrointestinal symptoms occurred in one third of patients and were higher than COVID-19 in general population. The factors associated with having COVID-19 were female gender (OR 1.71, 95%CI: 1.17-2.50); contact at home (OR 5.07, 95%CI: 3.31-7.78) and outside the home (OR 3.14, 95%CI: 2.10-4.71) with a case of COVID-19; work outside of the home (OR 1.87, 95%CI: 1.26-2.78); family history of COVID-19 (OR 2.29, 95%CI 1.58-3.33) use of salicylate (OR 1.71, 95%CI: 1.17-4.28); and asthma (OR 7.10, 95%CI: 1.46-34.57). Conclusion: IBD patients at high risk of COVID-19 infection may need to avoid salicylate therapy but further studies are necessary to confirm this association.
RESUMO Contexto: Felizmente, muito se tem estudado sobre a COVID-19 em pacientes com doenças inflamatórias intestinais (DII). As evidências sugerem que esses pacientes não parecem ter risco aumentado de COVID-19 grave. Mas ainda se tem algumas incertezas com relação às manifestações clínicas da COVID-19 em portadores de doenças imunomediadas. Objetivo: Este estudo teve como objetivo descrever os principais sintomas da COVID-19 e sua frequência em pacientes com DII e avaliar o impacto dos medicamentos utilizados no tratamento das DII na apresentação clínica da COVID-19. Métodos: Pacientes adultos com DII de três hospitais públicos terciários de ensino do Ceará, Nordeste do Brasil, foram avaliados em consulta ambulatorial no período de março a dezembro de 2020. Pacientes com COVID-19 possível ou confirmada foram comparados com pacientes sem COVID-19. Além disso, as incidências de cada sintoma foram avaliadas com base no uso de medicamentos utilizados para tratamento da DII. Resultados: Foram incluídos no estudo 515 pacientes com DII: 234 com DC e 281 com RCU. Destes, 174 pacientes (34%) tinham COVID-19 possível/confirmado, dos quais 156 (90%) eram sintomáticos. Os principais sintomas foram febre (65%) e dor de cabeça (65%); sintomas gastrointestinais ocorreram em um terço dos pacientes, sendo mais frequentes do que na população geral com COVID-19. Os fatores associados a ter COVID-19 foram sexo feminino (OR 1,71, IC95%: 1,17-2,50); ter contato com caso de COVID-19, tanto intradomiciliar (OR 5,07; IC95%: 3,31-7,78) como fora do domicílio (OR 3,14; IC95%: 2,10-4,71); trabalhar fora de casa (OR 1,87; IC95%: 1,26-2,78); história familiar de COVID-19 (OR 2,29, IC95% 1,58-3,33), uso de salicilato (OR 1,71, IC95%: 1,17-4,28) e asma (OR 7,10; IC95%: 1,46-34,57). Conclusão: Pacientes com DII com alto risco de infecção por COVID-19 podem precisar evitar a terapia com salicilatos, mas mais estudos são necessários para confirmar esta associação.
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ABSTRACT Inflammatory bowel diseases (IBD) currently impose an immense social and economic burden on society in terms of both direct and indirect healthcare costs. Their incurable and progressive nature results in an unavoidable lifetime expense. The introduction of infliximab more than two decades ago had revolutionized IBD treatment. Nowadays, while biologic drugs comprise various vital therapeutic options for patients, they can be associated to significant costs to healthcare systems. The most crucial benefit of biosimilars is that they bring more significant cost reduction and increase access to advanced therapies. They also allow the treatment of newly diagnosed patients and dose optimization for those who need it. There is an inverse relationship between price and demand for treatment with biologics. For a more significant reduction in cost to be possible, greater use of biosimilars is necessary. For this to occur, it is imperative not only to use biosimilars in naïve patients but also to switch to biosimilars in those patients who have started therapy with reference biologics. At present, randomized and observational studies have demonstrated effectiveness and safety results in recommending a single switch between a reference product and a biosimilar, and vice versa. The purpose of this manuscript is to review the literature and discuss whether scientific evidence is enough to support multiple switches of biologics and biosimilars in IBD patients.
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ABSTRACT Background: Inflammatory bowel disease (IBD), represented by Crohn's disease (CD) and ulcerative colitis (UC), is a chronic condition that affects all age groups, predominantly in young individuals. Currently, an increase in the prevalence of IBD has been documented, in parallel with the increase in the elderly population. The scarce number of studies that better characterize the impact of IBD on Quality of Life (QoL) in the elderly motivated the present study. Objective: To evaluate the impact of IBD on the QoL of elderly people treated at a Tertiary IBD Center. Methods: Prospective cross-sectional study that included elderly patients (age ≥60 years) with quiescent or mildly active IBD treated at the HU-UFJF IBD Center between March 2019 and December 2022. Elderly companions without severe comorbidities who attended the consultation with the patients were included as a control group. Sociodemographic and IBD-related characteristics were recorded. QoL was assessed using previously validated questionnaires (WHOQOL-BREF and IBDQ). Patients with IBD with moderate to severe activity, history of recent or imminent hospitalization, serious or opportunistic infections in the last 6 months, previous neoplasia, dementia, and difficulty understanding/fulfilling the questionnaires were excluded. Results: A total of 123 patients were included (74 with IBD and 49 in the control group), with a mean age of 67±6.2 years, 52.7% with CD, and 47.3% with UC. Mild disease activity was observed in 31.1%. Both groups (IBD patients and control) were comparable based on age, sex, BMI, and the Charlson Comorbidity Index. Patients with IBD and controls had similar QoL scores in the different domains assessed by the WHOQOL-BREF. On the other hand, when evaluating the general facet of QoL, IBD patients had significantly lower scores in General QoL (3.71±0.87 versus 4.02±0.62, respectively; P=0.021) and General Health (3.32±1.05 versus 3.69±0.94, respectively; P=0.035). The presence of mildly active IBD negatively impacted the general health score (2.91±0.99 versus 3.47±1.04, respectively; P=0.035) and the physical domain of the WHOQOL-BREF (12.27±2.63 versus 13.86±2.61, respectively; P=0.019) when compared to patients in remission. Conversely, no impact on QoL was observed with the Application of the IBDQ questionnaire regarding the type of the disease (161±38.5 versus 163.1±42.6 for CD and UC, respectively; P=0.84) or the presence of activity (152.5±38.8 versus 166.4±40.5, respectively; P=0.17). Conclusion: No statistically significant differences were found between elderly patients with mildly active or quiescent IBD and elderly patients without IBD when observing global QoL scores. However, IBD negatively impacted the general facet of QoL, just as mild activity was associated with lower scores in general health and the physical domain assessed by the WHOQOL-BREF. Patients with IBD treated with biological therapy had better Qol than those on conventional therapy. Future studies are needed to choose the most appropriate tool for assessing QoL in this population.
RESUMO Contexto: Doença inflamatória intestinal (DII), representada pela doença de Crohn (DC) e retocolite ulcerativa (RCU), é uma condição crônica e progressiva que afeta todas as faixas etárias, embora predomine em indivíduos jovens. Atualmente, tem sido documentado um aumento na prevalência de DII, de forma paralela ao aumento da população idosa. O escasso número de estudos que melhor caracterizem o impacto da DII na qualidade de vida (QV) em idosos motivou o presente estudo. Objetivo: Avaliar o impacto da DII na QV de idosos atendidos em um centro terciário de DII. Métodos: Estudo prospectivo transversal que incluiu pacientes idosos (idade ≥60 anos) com DII, atendidos pelo Centro de DII do HU-UFJF, entre março de 2019 a dezembro de 2022, e que apresentavam remissão clínica ou atividade leve de doença. Acompanhantes idosos sem comorbidades graves que compareceram à consulta com os pacientes foram incluídos como grupo controle. Foram registradas características sociodemográficas e relativas a DII. A QV foi avaliada por meio de questionários previamente validados (WHOQOL-BREF e IBDQ). Pacientes com DII com atividade moderada a grave, história de hospitalização recente ou iminente, infecções graves ou oportunistas nos últimos 6 meses, neoplasia prévia, demência, dificuldade de compreensão/ preenchimento dos questionários foram excluídos. Resultados: Foram incluídos 123 pacientes (74 com DII e 49 no grupo controle), com idade média de 67±6,2 anos, sendo 52,7% com DC e 47,3% com RCU. Atividade leve da doença foi observada em 31,1%. Ambos os grupos (pacientes com DII e controle) foram comparáveis com base na idade, sexo, IMC e Índice de Comorbidade de Charlson. Pacientes com DII e controle apresentaram escores de QV similares nos diferentes domínios avaliados pelo WHOQOL-BREF. Por outro lado, quando avaliada a faceta geral de QV, pacientes com DII apresentaram escores significativamente menores na QV geral (3,71±0,87 versus 4,02±0,62, respectivamente; P=0,021) e na saúde geral (3,32±1,05 versus 3,69±0,94, respectivamente; P=0,035). A presença de atividade leve impactou negativamente nos escores de saúde geral e de domínio físico do WHOQOL-BREF quando comparados com pacientes em remissão (2,91±0,99 versus 3.47±1,04, respectivamente; P=0,035 e 12,27±2.63 versus 13,86±2,61, respectivamente; P=0,019). Não foi observado impacto na QV com a aplicação do questionário IBDQ no que se refere ao tipo de DII (161±38.5 versus 163.1±42,6 para DC e RCU, respectivamente; P=0.84) ou a presença de atividade (152.5±38.8 versus 166.4±40.5, respectivamente; P=0.17). Conclusão: Não foram encontradas diferenças estatisticamente significativas entre pacientes idosos com DII em atividade leve ou quiescente e pacientes idosos sem DII quando observados os escores globais de QV. Porém, a DII impactou negativamente a faceta geral de QV, assim como a presença de atividade leve esteve associada a menores escores na saúde geral e no domínio físico avaliado pelo WHOQOL-BREF. Pacientes com DII tratados com terapia biológica apresentaram melhor QV do que aqueles em terapia convencional. Estudos futuros são necessários para escolha de ferramenta mais adequada para avaliação de QV nessa população.
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Objective: To describe the pro file of surgeons who treat patients with inflammatory bowel disease as well as the characteristics of inflammatory bowel disease care, unmet demands, and difficulties. Methods: The research participants answered a Google Forms questionnaire. Results: Of the 99 surgeons who participated in the survey, 84.5% were coloproctologists, 40% were from the southeastern region of Brazil, and 77.7% were male and had been working for more than 19 years. Regarding the healthcare sector, 63.6% of surgeons worked in both public and private clinics, and most clinically cared for up to 50 patients with inflammatory bowel disease and operated on up to 5 cases per year. Conclusion: This is the first national study that aimed to identify the profile of surgeons working with inflammatory bowel disease in Brazil. The vast majority are experienced male coloproctologists, located in the southern and southeastern regions, who perform clinical and surgical treatment of these pathologies, with major surgeries being performed in large centers by a small number of surgeons. (AU)
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Inflammatory Bowel Diseases , Surgeons/statistics & numerical data , Colitis, Ulcerative/surgery , Crohn Disease/surgery , Surveys and QuestionnairesABSTRACT
Abstract Aim: Using Mendelian Randomization (MR) analysis to investigate the potential causal association between Inflammatory Bowel Disease (IBD) and the occurrence of parenteral malignancies, in order to provide some reference for the parenteral malignancy prevention in patients with IBD. Methods: This was a two-sample MR study based on independent genetic variants strongly linked to IBD selected from the Genome-Wide Association Study (GWAS) meta-analysis carried out by the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). Parenteral malignancy cases and controls were obtained from the FinnGen consortium and the UK Biobank (UKB) release data. Inverse Variance Weighted (IVW), weighted median, MR-Egger, and strength test (F) were utilized to explore the causal association of IBD with parenteral malignancies. In addition, Cochran's Q statistic was performed to quantify the heterogeneity of Instrumental Variables (IVs). Results: The estimates of IVW showed that patients with IBD had higher odds of diffuse large B-cell lymphoma (OR = 1.2450, 95% CI: 1.0311‒1.5034). UC had potential causal associations with non-melanoma skin cancer (all p < 0.05), melanoma (OR = 1.0280, 95% CI: 0.9860‒1.0718), and skin cancer (OR = 1.0004, 95% CI: 1.0001‒1.0006). Also, having CD was associated with higher odds of non-melanoma skin cancer (all p < 0.05) and skin cancer (OR = 1.0287, 95% CI: 1.0022‒1.0559). In addition, results of pleiotropy and heterogeneity tests indicated these results are relatively robust. Conclusions: IBD has potential causal associations with diffuse large B-cell lymphoma and skin cancers, which may provide some information on the prevention of parenteral malignancies in patients with IBD. Moreover, further studies are needed to explore the specific mechanisms of the effect of IBD on skin cancers.
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La enfermedad inflamatoria intestinal es un problema de salud que actualmente genera alta morbilidad en el paciente pediátrico. Existen múltiples métodos diagnósticos que permiten su evaluación, entre los cuales y de creciente uso, está la ecografía digestiva. El objetivo de la presente investigación fue mostrar una panorámica actualizada de la utilidad e idoneidad de esta técnica en el seguimiento de la enfermedad inflamatoria intestinal en pacientes pediátricos. Se hizo una recopilación y revisión de la literatura nacional e internacional de mayor novedad y profundidad en el tratamiento del tema, en un período de 4 meses (febrero de 2022 a mayo de 2022). La estrategia de búsqueda adoptada fue el uso de las palabras clave o descriptores en español e inglés como: enfermedad inflamatoria intestinal, pediatría, enfermedad de Crohn, colitis ulcerosa, ultrasonido, ecografía digestiva. En total se utilizaron 50 artículos, de diferentes bases de datos como:Scielo, PubMed/Medline, Ebesco, Clinical Key y Springer. Se escogieron 30 citas para realizar la revisión, donde se analizó la importancia de la técnica en la descripción de las características ecográficas intestinales en pacientes pediátricos, confirmándose el papel que tiene en la identificación e intervención temprana de la enfermedad inflamatoria intestinal.
Inflammatory bowel disease is a health problem that currently causes high morbidity in pediatric patients. There are several diagnostic methods that allow its evaluation, among which gastrointestinal ultrasound is increasingly used. The aim of this research was to provide an updated review of the usefulness and suitability of this technique in the follow-up of inflammatory bowel disease in pediatric patients. A compilation and review of the national and international literature of greater novelty and depth in the treatment of the subject was made over a period of 4 months (February 2022 to May 2022). The search strategy adopted was the use of keywords or descriptors in Spanish and English such as: inflammatory bowel disease; pediatrics; Crohn's disease; ulcerative colitis; ultrasound; digestive ultrasound. A total of 50 articles were used from different databases such as: Scielo, PubMed/Medline, Ebesco, Clinical Key and Springer. Thirty citations were selected for review, analyzing the importance of the technique in the description of intestinal ultrasound characteristics in pediatric patients, confirming its role in the identification and early intervention of inflammatory bowel disease.
A doença inflamatória intestinal é um problema de saúde que atualmente causa elevada morbilidade no doente pediátrico. Existem vários métodos de diagnóstico que permitem a sua avaliação, entre os quais a ecografia gastrointestinal é cada vez mais utilizada. O objetivo deste trabalho foi fazer uma revisão actualizada da utilidade e adequação desta técnica no seguimento da doença inflamatória intestinal em idade pediátrica. Foi feita uma compilação e revisão da literatura nacional e internacional de maior novidade e profundidade no tratamento do tema, durante um período de 4 meses (fevereiro de 2022 a maio de 2022). A estratégia de busca adotada foi o uso de palavras-chave ou descritores em espanhol e inglês, tais como: doença inflamatória intestinal; pediatria; doença de Crohn; colite ulcerativa; ultrassom; ultrassom digestivo. Foram utilizados 50 artigos de diferentes bases de dados, como: Scielo, PubMed/Medline, Ebesco, Clinical Key e Springer. Foram selecionadas 30 citações para revisão, analisando a importância da técnica na descrição das características ultra-sonográficas intestinais em pacientes pediátricos, confirmando seu papel na identificação e intervenção precoce da doença inflamatória intestinal.
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Inflammatory bowel disease （IBD）， mainly including ulcerative colitis （UC） and Crohn's disease （CD）， is a common chronic inflammatory disease of the gastrointestinal tract， with its incidence increasing year by year. Due to its long treatment duration， difficulty in treatment， prolonged remission， and high costs， it has attracted global attention. Exploring safe， effective， and sustainable treatment regimens has become an urgent global issue. The pathogenesis of IBD is complex， involving intestinal mucosal injury，disturbances in the internal environment， and inflammatory responses. In recent years， research has found that ferroptosis is also one of the important pathogenic factors of IBD. Ferroptosis， as a new form of non-apoptotic cell death， is characterized by iron dependence， lipid peroxidation， and imbalance in the redox system. Studies have shown that inhibiting ferroptosis in intestinal epithelial cells can protect the intestinal mucosa. Targeted intervention in ferroptosis may be a new direction for the treatment of IBD. IBD is mainly treated with drugs， including corticosteroids， aminosalicylates， biologics， and immunomodulators， but drug resistance and adverse reactions are common. Traditional Chinese medicine （TCM） has unique advantages such as low cost， low drug resistance， and fewer side effects， and has accumulated rich experience in the treatment of IBD. Scholars have confirmed that TCM can inhibit ferroptosis， and recent studies have shown that TCM can not only inhibit iron-dependent lipid peroxidation in intestinal cells but also enhance the antioxidant and anti-inflammatory abilities of intestinal mucosa， thus playing a role in the treatment of IBD. Increasing evidence suggests that TCM may treat IBD by interfering with ferroptosis. This article explores the relevance of TCM intervention in ferroptosis and the treatment of IBD， discusses the possible mechanisms of ferroptosis in IBD， and aims to provide a basis for the diagnosis and treatment of IBD.
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@#Abstract: Inflammatory bowel disease (IBD), whose pathogenesis remains elusive, is a group of autoimmune diseases characterized by chronic, progressive, and lifelong inflammation of the digestive tract. The pathogenesis of IBD remains elusive. Although a number of drugs have been developed to treat IBD, their effects are merely anti-inflammatory. In addition, current treatments for IBD are easily susceptible to resistance in clinical practice. Mesenchymal stem cells (MSCs) have been reported to have the ability to migrate to the site of inflammation, with potent immunoregulatory effects, and to rebalance the immune microenvironment and restore the integrity of the epithelial barrier with significant value of application, particularly for patients who are refractory to classic medicines. In this paper, we reviewed the clinical applications, mechanisms and engineerable properties of MSC products and their exosomes to provide some reference for the use of MSCs and their exosomes in the treatment of IBD.
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Objective·To investigate the effect of ceria nanoparticles-polyethylene glycol(CeNP-PEG)on scavenging reactive oxygen species(ROS)and alleviating disease activity in dextran sulphate sodium(DSS)-induced colitis mice.Methods·CeNP was synthesized with the hydrates of cerium acetate,oleamine,and xylene,which was modified with polyethylene glycol-stearyl phosphatidylethanolamine(mPEG-DPSE)to obtain CeNP-PEG.Then CeNP-PEG was purified.The particle size and zeta potential of CeNP-PEG were measured by using transmission electron microscopy(TEM)and dynamic light scattering(DLS).Mouse macrophages(Raw264.7)were cultured in vitro and induced to a pro-inflammatory phenotype(M1 phenotype).M1 macrophages were treated with 0.5 μg/mL and 1.0 μg/mL CeNP-PEG,respectively,and then Western blotting was used to detect the expression changes of the proteins related with nuclear factor-κB(NF-κB)signaling pathway.DSS-induced colitis mice models were constructed,and CeNP-PEG(1.0 mg/mL)was intravenously administrated for 3 times via tail vein during the modeling period.Meanwhile,the body weight,fecal characteristics,and frequency of rectal bleeding in mice were monitored in the normal control group(Normal group),the model group(DSS group),and the CeNP-PEG treatment group.The disease activity index(DAI)was calculated to evaluate the intestinal inflammation.The level of ROS in mouse intestinal tissues was detected by dihydroethidine(DHE)staining and the mRNA expression levels of inflammatory cytokines interferon-γ(Ifn-γ),interleukin-6(Il-6),Il-1β and tumor necrosis factor-α(Tnf-α)were detected by real-time quantitative PCR(RT-qPCR).Results·The hydrated particle size of synthesized CeNP-PEG was(6.96±0.27)nm,and the average zeta potential was(-6.02±1.31)mV.Western blotting results showed that the expression of p-P65 increased in the pro-inflammatory macrophages compared with the control group.The expression of NF-κB inhibitor-α(IκB-α)decreased,and their expressions tended to recover after the intervention of different concentrations of CeNP-PEG.In the DSS-induced colitis models,mice in the CeNP-PEG treatment group lost less weight than those in the DSS group(P= 0.000)and had lower DAI scores(P=0.000).The RT-qPCR results of intestinal tissues showed that the mRNA levels of Ifn-γ,Il-1β,Il-6 and Tnf-α in the DSS group were significantly up-regulated compared with those in the Normal group(P=0.000),and all of them significantly decreased in the CeNP-PEG treatment group.The results of DHE staining showed that the fluorescence intensity of intestinal tissues in the DSS group was significantly enhanced than that in the Normal group,and the fluorescence intensity decreased in the CeNP-PEG treatment group.Conclusion·CeNP-PEG can inhibit the expression of intestinal inflammatory factors and the activation of NF-κB-related inflammatory pathway of pro-inflammatory macrophages,eliminate intestinal ROS,improve the intestinal inflammatory microenvironment,and alleviate the disease activity of DSS-induced colitis in mice.
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Very early onset inflammatory bowel disease (VEO-IBD) in children refers to an IBD with the onset age of less than 6 years old, clinically characterized by recurrent colitis, perianal lesions, and nutrient absorption disorders.Different from adults, single gene mutation plays an important role in the pathogenesis of VEO-IBD.To date, about 70 single gene defects have been identified involving the pathogenesis of VEO-IBD, including epithelial barrier, neutrophil and phagocyte function, immune cell selection and activation, immunosuppressive mechanism, or apoptosis.Interleukin-10 (IL-10) is an anti-inflammatory cytokine that regulates innate and adaptive immunity, influences the expression of pro-inflammatory molecules and the function of multiple immune cells, and plays a vital role in the development and progression of IBD.Patients with defects in the IL-10 signaling pathway (IL-10 or IL-10 receptor deficiency) may develop life-threatening colitis as early as childhood.This article reviews the progress in the pathogenesis and treatment of VEO-IBD caused by IL-10 signaling pathway defects.
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Objective:To explore the clinical characteristics and outcomes of type 2 autoimmune pancreatitis (AIP) and compare with type 1 AIP.Methods:Clinical data of the patients diagnosed with type 2 AIP by the International Consensus on diagnostic criteria of AIP at Peking Union Medical College Hospital from January 2001 to December 2022 were retrospectively analyzed, and type 1 AIP patients diagnosed in Peking Union Medical College Hospital from January 1985 to December 2016 were collected as controls. The clinical symptoms, treatments and follow-ups were analyzed.Results:A total of 25 patients with type 2 AIP were included, of which 16 cases (64.0%) were pathologically confirmed cases (13 cases by endoscopic ultrasound puncture, 2 cases by surgery, and 1 case by interventional puncture), and 9 cases (36.0%) were suspected. The average age of onset was 40 years old. Most patients ( n=23, 92.0%) had abdominal pain along with emaciation to a various degree. Among them, 3 cases primarily presented as acute pancreatitis. Two cases were diagnosed after surgery for pancreatic masses. Eighteen cases were complicated with inflammatory bowel disease, including 16 cases with ulcerative colitis, one case with Crohn's disease, and one case with indeterminate colitis. All patients had typical imaging manifestations, including 13 cases (52.0%) with diffuse pancreatic enlargement, 12 cases (48.0%) with focal or multifocal pancreatic lesions, and 5 cases (20.0%) with simultaneous focal pancreatic masses and diffuse enlargement. All patients had normal serum IgG4 levels, anti-neutropil cytoplasmic antibodies (ANCA) positivity rate was 35.3% (6/17), and anti-nuclear antibody (ANA) positivity rate was 29.2% (7/24). Two surgical patients recovered well after surgery, and the other patients all achieved clinical and imaging relief after hormone therapy, and no recurrence was seen during follow-up. Compared with type 1 AIP, type 2 AIP had younger onset age, main manifestation as abdominal pain without jaundice, rare involvement with extra-pancreatic organs, the lesions mainly located in the intestine and normal IgG4 level with statistically significant differences. The recurrence rate of type 2 AIP was lower than that of type 1 AIP (0 vs 16%). Conclusions:Type 2 AIP has different clinical characteristics from type 1 AIP. Due to the lack of specific serum markers, the diagnosis is more difficult. It responds well to glucocorticoids and has a low recurrence rate.
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Objective:To explore the protective effect of 18α glycyrrhetinic acid (18α-GA) on acute ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in mice, providing theoretical and experimental basis for the clinical application of 18α-GA.Methods:Forty male C57BL/6J mice were randomly divided into 5 groups: DSS model group, positive drug control group, high, medium, and low dose groups of 18α-GA, with 8 mice in each group. The 5 groups of mice were continuously fed with 3% DSS solution for 7 days to establish an acute UC animal model. At the same time, each group was intraperitoneally injected with 100 mg/kg physiological saline, 100 mg/kg sulfasalazine, 40 mg/kg 18α-GA, 20 mg/kg 18α-GA, and 10 mg/kg 18α-GA daily. The weight of mice was measured and recorded daily, and the Disease Activity Index (DAI) of mice was evaluated. On the 8th day, the mice were euthanized and their colon length was measured; After slicing, the colon mucosa was observed and pathological scoring was performed; Western blot was used to detect the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome pathway related proteins in colon tissue; Enzyme linked immunosorbent assay (ELISA) was used to determine the content of interleukin(IL)-1β in colon tissue.Results:Compared with the DSS model group, the weight loss amplitude of the 18α-GA high and medium dose groups was significantly smaller on the 7th day (all P<0.05); Colon length was longer (all P<0.05), the pathological score of colon mucosa was significantly lower (all P<0.05); The expression of GSDMD, cleaved caspase1, and IL-1β in colon tissue was significantly lower (all P<0.05); The 18α-GA high-dose group had lower DAI scores ( P<0.05); The expression of NLRP3 was lower in colon tissue ( P<0.05). Conclusions:18α-GA can improve DSS induced acute ulcerative colitis in mice by inhibiting the activation of NLRP3 inflammasome pathway.
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@#Objective: To investigate the effect of isoimperatorin on histopathological and biochemical changes in acetic acid-induced colitis rats. Methods: Colitis was induced by intracolonic administration of acetic acid solution (4% v/v) in rats. Rats were divided into six groups including the sham group, the negative control group, the dexamethasone-treated group, and the groups treated with isoimperatorin (0.1, 1, and 10 mg/kg/d by gavage). The treatments were administered for three days and then colonic status was assessed by macroscopic, histopathological, and biochemical analyses. Results: Isoimperatorin significantly alleviated colonic damage in a dose-dependent manner and improved histological changes in rats with acetic acid-induced colitis. It also significantly reduced myeloperoxidase, TNF-α, IL-1β, and malodialdehyde levels. Conclusions: Isoimperatorin alleviates acetic acid-induced colitis in rats and may be a potential therapeutic agent for the treatment of colitis.
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OBJECTIVE To provide reference for safe drug use in the clinic by mining the adverse drug event （ADE） signals of 4 kinds of biological agents for the treatment of inflammatory bowel disease （IBD）. METHODS ADE data of infliximab， adalimumab， ustekinumab and vedolizumab were collected from the FDA adverse event reporting system between the first quarter in 2004 and the fourth quarter in 2022， and were mined by using reporting odds ratio （ROR） method and proportional reporting ratio （PRR） method. The system organ class （SOC） was used for the classification and statistics of drug ADE terminology. RESULTS & CONCLUSIONS A total of 65 173， 247 894， 37 596 and 6 134 ADE reports were retrieved for the above 4 biologic agents， involving 1 664， 1 731， 588， 303 ADE signals and 27， 27， 24， 26 SOC， respectively. The largest number of ADE reported of infliximab were various musculoskeletal and connective tissue diseases， and the signal intensity of disseminated tuberculosis was stronger. The largest number of ADE reported of adalimumab were systemic disease and various reactions at the administration site， and the signal intensity of papular at the injection site was stronger. The largest number of ADE reported of ustekinumab were various injuries， poisoning and operation complications， and the signal intensity of latent tuberculosis was slightly stronger. The largest number of ADE reported of vedolizumab were systemic diseases and various reactions at the administration site， and the signal intensity of shorter treatment response time was stronger. When clinically administering the four drugs， it is crucial to pay close attention to common ADEs and other ADE not mentioned in the drug label. For infliximab， clinicians should exercise caution due to the potential risk of synovitis and basal cell carcinoma； when prescribing adalimumab， caution should be exercised due to ADEs related to synovitis and hernia； for ustekinumab， the ADE associated with hepatobiliary diseases should be vigilant； for vedolizumab， clinicians should be vigilant for blood in the stool， increasing frequency of defecation. Except for ustekinumab， the other 3 biological agents also require attention for ADE associated with pregnancy.
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OBJECTIVE To investigate the effects of formononetin （FMN） on the apoptosis of intestinal epithelial cells in inflammatory bowel disease （IBD） rats and its possible mechanism. METHODS IBD rat model was constructed by using trinitrobenzene sulfonic acid （TNBS） induction. Forty-eight rats with successful modeling were divided into model group （normal saline）， low-dose and high-dose FMN groups （20 and 40 mg/kg FMN）， and high-dose FMN+YAP inhibitor Verteporfin （VTPF） group （40 mg/kg FMN+10 mg/kg VTPF）， with 12 rats in each group. Another 12 rats were set as the normal group （normal saline）. They were given drug/normal saline， once a day， for 7 consecutive days. After the last administration， the disease activity index （DAI） of rats was calculated， and the colon length of rats in each group was measured. The pathological changes in the colon tissue of rats were observed. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-10 in serum were detected， and the apoptosis of intestinal epithelial cells was detected. The expressions of Yes associated protein （YAP）， cleaved cysteine-containing aspartate proteolytic enzyme 3 （cleaved-caspase-3）， B-cell lymphoma-2 （Bcl-2） and Bcl-2 associated X protein （Bax） were detected in colon tissue of rats. RESULTS Compared with the normal group， DAI score， the levels of TNF-α and IL- 6， the apoptotic rate of intestinal epithelial cells， and the expressions of cleaved-caspase-3 and Bax protein in the model group were increased greatly （P＜0.05）； the length of the colon was greatly decreased （P＜0.05）， and the serum level of IL-10 and the protein expressions of YAP and Bcl-2 were greatly reduced （P＜0.05）. The cell morphology of colon tissue was abnormal， with disordered arrangement and inflammatory cell infiltration. Compared with IBD group， the above indexes of rats were improved significantly in low-dose and high-dose FMN groups （P＜0.05）， in dose-dependent manner （P＜0.05）. VTPF significantly alleviated the effects of FMN on the above indexes of IBD rats （P＜0.05）. CONCLUSIONS FMN may promote the expression of YAP by inhibiting the Hippo/YAP signaling pathway， thereby inhibiting apoptosis of intestinal epithelial cells in IBD rats.
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The diagnosis and treatment of digestive system complications of kidney transplant recipients is related to the long-term survival and quality of life of patients, which needs great attention. In order to further standardize its diagnosis and treatment, Branch of Organ Transplantation of Chinese Medical Association initiated the formulation of “Clinical Diagnosis and Treatment Guidelines for Digestive System Complications in Kidney Transplant Recipients in China”, and organized experts in organ transplantation and related disciplines to summarize the new progress in diagnosis and treatment of digestive system complications of kidney transplant recipients at home and abroad in recent years based on existing clinical research, systematic evaluation, case study, expert consensus and existing guidelines, and reached a consensus after many discussions. This paper focuses on 11 clinical problems, forming 16 recommendations, and grading the evidence quality and recommendation strength of each clinical problem by the evidence grading and recommendation strength standard of Oxford University Evidence-based Medicine Center in 2009, in order to provide reference for the diagnosis and treatment of digestive system complications of kidney transplant recipients, comprehensively improve the management ability of digestive system complications of clinicians in an all-round way and benefit transplant recipients.