Therapeutic drug monitoring in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a problem that directly affects the quality of life of patients suffering from this condition. Monitoring the serum level of infliximab (IFX) (TDM) is an important tool for guiding therapeutic decisions in IBD patients. The purpose of this study was to determine the significance of quantitatively measuring the serum level of IFX (TDM) and antibody to IFX (ATI). Methods and materials: Prospective observational study involving 40 IBD patients on IFX therapy, including 14 Proactive (week 06 of the induction phase) and 26 Reactive (maintenance phase). Immediately prior to the infusion, blood samples were drawn and measured using a Bulhlmann rapid test instrument. Serum concentrations of IFX were categorized as supratherapeutic (>7.0 micrograms/ml), therapeutic (between 3.0 and 7.0 micrograms/ml), and subtherapeutic (3.0 micrograms/ml). When the serum concentration of IFX was 3 mcg/ml (subtherapeutic), the ATI was measured. 25 patients with CD and 15 patients with UC were evaluated. Only three of the twenty patients with subtherapeutic serum levels had a positive ATI, and both were reactive; two had CD and one had UC. There was a statistically significant difference between reactive and proactive patients with respect to levels of CRP (p = 0.042), with proactive DNS patients suffering greater alterations in CRP and albumin. (AU)

Prevalence of IgA anti-tissue transglutaminase antibody in a cohort of iranians patients with inflammatory bowel disease

Background and Aims: Some studies have reported the coexistence of inflammatory bowel disease (IBD) and celiac disease (CD). However, the prevalence of anti-tissue transglutaminase antibodies (IgA and IgG) and their screening value in patients with IBD is not yet clear. This study aimed to assess the prevalence of IgA anti-tTG and its potential correlation with disease status in patients with IBD. Materials and Methods: This cross-sectional study was conducted on 110 patients with confirmed IBD diagnosis at Ghaem Hospital, Mashhad, Iran. For each patient, all demographic and clinical data including age, extra intestinal manifestations, underlying diseases, types of diseases, and surgical history were collected. IgA anti-tissue transglutaminase titers were assessed by enzyme-linked immunosorbent assay. Results: None of the patients with IBD were positive for IgA anti-tTG antibodies, with a mean titer of 3.31 ± 1.3 AU/mL. Also, the mean titers were not associated with age, gender and various disease clinical features including the disease history, underlying disease, diagnosis type, extraintestinal manifestations, and surgery history. Conclusion: No significant prevalence pattern of IgA anti-tTG antibody was observed in patients with IBD. Accordingly, serological screening for CeD is not recommended in IBD patients, unless in a relevant clinical CeD suspicion. (AU)

Consenso colombiano de Falla Intestinal Crónica en Síndrome de Intestino Corto / Colombian Consensus on Chronic Intestinal Failure in Short Bowel Syndrome

Introducción. Los términos falla intestinal crónica, síndrome de intestino corto (SIC) y nutrición parenteral total son muy frecuentes en la práctica clínica cotidiana.El objetivo de esta guía fue establecer un marco de referencia de práctica clínica basado en el mejor de nivel de evidencia en pacientes con falla intestinal crónica secundaria a síndrome de intestino corto. Métodos. Se estableció un grupo de expertos interdisciplinarios en el manejo de la falla intestinal crónica quienes, previa revisión de la literatura escogida, se reunieron de manera virtual acogiendo el método Delphi para discutir una serie de preguntas seleccionadas, enfocadas en el contexto terapéutico de la falla intestinal crónica asociada al síndrome de intestino corto. Resultados. La recomendación del grupo de expertos colombianos es que se aconseje a los pacientes con SIC consumir dietas regulares de alimentos integrales que genere hiperfagia para compensar la malabsorción. Las necesidades proteicas y energéticas dependen de las características individuales de cada paciente; la adecuación del régimen debe ser evaluada a través de pruebas clínicas, antropométricas y parámetros bioquímicos. Se sugiere, especialmente a corto plazo después de la resección intestinal, el uso de análogos de somatostatina para pacientes con yeyunostomía de alto gasto en quienes el manejo de líquidos y electrolitos es problemático. En pacientes con SIC, que son candidatos a tratamiento con enterohormonas, Teduglutida es la primera opción. Conclusión. Existen recomendaciones en el manejo integral de la rehabilitación intestinal respaldadas ampliamente por este consenso y es importante el reconocimiento de alternativas terapéuticos enmarcadas en el principio de buenas prácticas clínicas.

Introduction. The terms chronic intestinal failure, short bowel syndrome (SBS), and total parenteral nutrition are very common in daily clinical practice. The objective of this guideline was to establish a reference framework for clinical practice based on the best level of evidence in patients with chronic intestinal failure secondary to short bowel syndrome. Methods. A group of interdisciplinary experts in the management of chronic intestinal failure was established who, after reviewing the selected literature, met virtually using the Delphi method to discuss a series of selected questions, focused on the therapeutic context of chronic intestinal failure associated with short bowel syndrome. Results. The recommendation of the Colombian expert group is that patients with SBS be advised to consume regular diets of whole foods that generate hyperphagia to compensate malabsorption. Protein and energy needs depend on the individual characteristics of each patient; the adequacy of the regimen must be evaluated through clinical, anthropometric tests and biochemical parameters. The use of somatostatin analogue is suggested, especially in the short term after bowel resection, for patients with high-output jejunostomy in whom fluid and electrolyte management is problematic. In SBS, who are candidates for enterohormonal therapy, Teduglutide is the first choice. Conclusion. There are recommendations on the comprehensive management of intestinal rehabilitation that are widely supported by this consensus and it is important to recognize therapeutic alternatives framed in the principle of good clinical practice.

Current treatment strategies for inflammatory bowel disease patients at the risk of developing cancer: a comprehensive review

Inflammatory bowel disease (IBD) is a chronic condition that affects the digestive tract and can lead to inflammation and damage to the intestinal lining. IBD patients with cancer encounter difficulties since cancer treatment weakens their immune systems. A multidisciplinary strategy that strikes a balance between the requirement to manage IBD symptoms and the potential effects of treatment on cancer is necessary for effective care of IBD in cancer patients. To reduce inflammation and avoid problems, IBD in cancer patients is often managed by closely monitoring IBD symptoms in conjunction with the necessary medication and surgical intervention. Anti-inflammatory medications, immunomodulators, and biologic therapies may be used for medical care, and surgical options may include resection of the diseased intestine or removal of the entire colon. The current study provides a paradigm for shared decision-making involving the patient, gastroenterologist, and oncologist while considering recent findings on the safety of IBD medicines, cancer, and recurrent cancer risk in individuals with IBD. We hope to summarize the pertinent research in this review and offer useful advice. (AU)

Acupuntura na qualidade de vida do paciente com retocolite ulcerativa inespecífica: relato de caso / Acupuntura en la calidad de vida de pacientes con colitis ulcerosa inespecífica: reporte de caso / Acupuncture on the quality of life of patients with nonspecific ulcerative colitis: case report

Objetivo: relatar a contribuição da acupuntura sistêmica na qualidade de vida de um paciente com retocolite ulcerativa inespecífica. Método:estudo descritivo, retrospectivo, na modalidade de relato de caso, desenvolvido em três etapas: coleta de dados pré-tratamento; aplicação dos protocolos de tratamento com acupuntura sistêmica; e coleta de dados pós-tratamento. Os acupontosescolhidosse relacionaram aos aspectos emocionais e fisiopatológicos, particularmenteos sintomas intestinais, aplicados em sessões semanais domiciliares. Para a avaliação da qualidade de vida, utilizou-se de instrumento adaptado e validado para a cultura brasileira, e específico para doenças inflamatórias intestinais. Resultados: observou-se melhora estatisticamente significativa nas dimensões "sintomas intestinais", "sintomas sistêmicos", "aspectos emocionais" e no escore total de qualidade de vida. Conclusão: a acupuntura contribuiu para a melhoria da qualidade de vida, especialmente na remissão dos sintomas intestinais e nos aspectos emocionais.

Objective: to report the contribution of systemic acupuncture to the quality of life of a patient with nonspecific ulcerative colitis.Method: descriptive, retrospective study, in the form of case report, developed in three stages: pre-treatment data collection; application of treatment protocols with systemic acupuncture; and post-treatment data collection. Acupoints were related to emotional and pathophysiological aspects, particularly intestinal symptoms, applied in weekly home sessions. To assess the quality of life, an instrument adapted and validated for the Brazilian culture was used, specifically for inflammatory bowel diseases. Results: there was a statistically significant improvement in the dimensions "intestinal symptoms", "systemic symptoms", "emotional aspects" and in the total quality of life score.Conclusion: acupuncture contributed to the improvement of quality of life, especially in the remission of intestinal symptoms and emotional aspects.

Objetivo: relatar la contribución de la acupuntura sistémica a la calidad de vida de un paciente con colitis ulcerosa inespecífica.Método: estudio descriptivo, retrospectivo, en forma de reporte de caso, desarrollado en tres etapas: recolección de datos pretratamiento; aplicación de protocolos de tratamiento con acupuntura sistémica; y recopilación de datos posteriores al tratamiento. Los puntos de acupuntura se relacionaron con aspectos emocionales y fisiopatológicos, particularmente síntomas intestinales, aplicados en sesiones domiciliarias semanales. Para evaluar la calidad de vida se utilizó un instrumento adaptado y validado para la cultura brasileña, específicamente para enfermedades inflamatorias intestinales.Resultados: hubo una mejora estadísticamente significativa en las dimensiones "síntomas intestinales", "síntomas sistémicos", "aspectos emocionales" y en el puntaje total de calidad de vida. Conclusión: la acupuntura contribuyó a la mejoría de la calidad de vida, especialmente en la remisión de los síntomas intestinales y aspectos emocionales.

Effects of Mimosa caesalpiniifolia pre-formulation on the intestinal barrier during sodium dextran sulfate-induced colitis in Wistar rats / Efectos de la preformulación de Mimosa caesalpiniifolia sobre la barrera intestinal durante la colitis inducida por sulfato de dextrano sódico en ratas Wistar

Introduction. Anti-inflammatories, immunosuppressants, and immunobiological are commonly used in the treatment of inflammatory bowel disease. However, some patients do not present an adequate response or lose effective response during the treatment. A recent study found a potential anti-inflammatory effect of the hydroalcoholic extract of Mimosa caesalpiniifolia on trinitrobenzene sulfonic acid-induced colitis in Wistar rats. Objective. To evaluate the effects of M. caesalpiniifolia pre-formulation on the intestinal barrier using dextran sulfate sodium-induced colitis model. Materials and methods. Leaf extracts were prepared in 70% ethanol and dried with a Buchi B19 Mini-spray dryer using 20% Aerosil® solution. Thirty-two male Wistar rats were randomized into four groups: basal control, untreated colitis, pre-formulation control (125 mg/kg/day), and colitis treated with pre-formulation (125 mg/kg/day). Clinical activity index was recorded daily and all rats were euthanized on the ninth day. Colon fragments were fixed and processed for histological and ultrastructural analyses. Stool samples were collected and processed for analysis of the short-chain fatty acid. Results. Treatment with the pre-formulation decreased the clinical activity (bloody diarrhea), inflammatory infiltrate, and the ulcers. Pre-formulation did not repair the epithelial barrier and there were no significant differences in the goblet cells index. There was a significant difference in butyrate levels in the rats treated with the pre-formulation. Conclusions. The pre-formulation minimized the clinical symptoms of colitis and intestinal inflammation, but did not minimize damage to the intestinal barrier.

Introducción. Los antiinflamatorios, inmunosupresores e inmunobiológicos se utilizan comúnmente para tratar la enfermedad intestinal inflamatoria. Sin embargo, algunos pacientes no presentan una respuesta adecuada o pierden respuesta efectiva durante el tratamiento. En un estudio reciente, se encontró un potencial efecto antiinflamatorio del extracto hidroalcohólico de Mimosa caesalpiniifolia en la colitis inducida por el ácido trinitrobenceno sulfónico utilizando ratas Wistar. Objetivo. Evaluar los efectos de la preformulación de M. caesalpiniifolia sobre la barrera intestinal durante la colitis inducida por sulfato de dextrano sódico. Materiales y métodos. Los extractos de hojas se prepararon con una solución que contenía 70 % de etanol y se secaron con un secador por aspersión Mini B19 de Buchi usando una solución con 20 % de Aerosil®. Treinta y dos ratas Wistar macho se aleatorizaron en cuatro grupos: control basal, colitis sin tratar, control con preformulación (125 mg/kg/ día) y colitis tratada con preformulación (125 mg/kg/día). El índice de actividad clínica se registró diariamente y todas las ratas se sacrificaron el noveno día. Los fragmentos de colon se fijaron y se procesaron para análisis histológicos y ultraestructurales. Se recolectaron muestras de heces y se procesaron para el análisis de ácidos grasos de cadena corta. Resultados. El tratamiento con la preformulación disminuyó la actividad clínica (diarrea sanguinolenta), el infiltrado inflamatorio y las úlceras. La preformulación no reparó la barrera epitelial y no hubo diferencias significativas en el índice de células caliciformes. Se obtuvo una diferencia significativa en los niveles de butirato en las ratas tratadas con la preformulación. Conclusiones: La preformulación minimizó los síntomas clínicos de colitis e inflamación intestinal pero no minimizó el daño a la barrera intestinal.

Transición en las enfermedades crónicas gastrointestinales. Del cuidado pediátrico al del adulto / Transition in chronic gastrointestinal diseases. From pediatric to adult care

Los avances tecnológicos y del conocimiento hicieron que un mayor número de pacientes con enfermedad crónica gastrointestinal pasen de ser atendidos por el pediatra al control por los médicos de adultos durante una de las etapas más vulnerables de la vida: la adolescencia. El Grupo de Trabajo de Transición del Comité de Gastroenterología de la Sociedad Argentina de Pediatría realizó una búsqueda de literatura exhaustiva y convocó a especialistas referentes del país, con el objeto de unificar los criterios basados en la evidencia y la experiencia. De esta manera, se proponen una serie de recomendaciones para todo el equipo de salud (pediatra, gastroenterólogo infantil, nutricionista, gastroenterólogo de adultos, psicólogo, enfermería), incluso para pacientes y familias, que faciliten el proceso de transición y optimicen el seguimiento, el control, la prevención de complicaciones y la calidad de vida de los pacientes con enfermedades crónicas gastrointestinales

Technological advances and the globalization of knowledge have led to a considerable increase in the number of patients with chronic gastrointestinal disease who transition from pediatric to adult care during one of the most vulnerable life stages: adolescence. The Transition Working Group of the Gastroenterology Committee of the Sociedad Argentina de Pediatría conducted an exhaustive literature search and summoned leading specialists in the most frequent chronic pathologies from all over the country to unify criteria based on evidence and experience. As a result, a series of recommendations are proposed for the whole health team (pediatrician, pediatric gastroenterologist, nutritionist, adult gastroenterologist, psychologist, and nurse) including patients and families, to facilitate the transition process, optimize follow-up, prevent complications, and improve the quality of life of patients with chronic gastrointestinal diseases.

Lacticaseibacillus casei decrease long-chain fatty acids and most substances in an experimental model of intestinal mucositis

Purpose: To evaluate the long-chain fatty acid and major compounds levels in the feces after prophylactic oral use of Lacticaseibacillus casei in an experimental model of intestinal mucositis. Methods: Fifteen Swiss mice were randomly divided into three groups (n=5/group): The negative or positive control groups (n = 5) received saline orally for 18 days and an the intraperitoneal (i.p.) of saline or 5 Fluorouracil (450 mg/kg) in 15th day, respectability. L. casei group received oral concentration of L. casei (1x109 CFU/mL) for 18 days, the i.p. injection of 5-fluorouracil (450 mg/kg) in 15th days. Tissue samples from colon and each small intestine segment were collected for histopathological analysis. Stool samples were collected. Fecal composition of long-chain fatty acids and sterols were analysed by gas chromatography-mass spectrometry on the 15th and the 18th day. Results: The mucosa layer of all small intestine segments of animals from L. casei showed well preserved epithelium and glands, without necrosis signs, but Goblet cells number decreased. Several long-chain fatty acids and sterols have been identified before and after in the groups. L. casei administration after 5-FU treatment reduced concentrations of linoleic acid (18:2) (p < 0.001) and oleic acid (18:1) (p < 0.001) in feces. Conclusions: L. casei prevented the mucosal damage associated with 5-FU-induced intestinal mucositis reduced long-chain fatty acid levels in the feces.

Impacto das funções executivas sobre a percepção de estresse na atividade das doenças inflamatórias intestinais / Impact of executive functions on stress perception in the activity of inflammatory bowel diseases

INTRODUÇÃO: As funções executivas (FE) constituem-se como importante mecanismo de controle cognitivo, responsável por direcionar e coordenar o comportamento de maneira adaptativa frente às novas exigências. Diante do diagnóstico da doença inflamatória intestinal (DII), ocorre sinalização excessiva de ameaças e sensibilidade à dor que afetam circuitos cerebrais relacionados às FE, o que culmina em maior vulnerabilidade ao estresse, e consequentemente à neuroinflamação. Diante de tais pressupostos, o posicionamento epistemológico deste estudo pauta-se na Psiconeuroimunologia. OBJETIVO: Investigar o impacto das FE sobre a percepção do estresse na atividade das doenças inflamatórias intestinais. METODOLOGIA: A pesquisa é de natureza quantitativa, de cunho descritivo e analítico, com corte transversal e correlacional. A amostra foi composta por 52 pacientes de um Ambulatório de Assistência Interdisciplinar às DII, integrado a uma universidade comunitária no sul do Brasil. Uma avaliação neuropsicológica realizada por meio de entrevista sociodemográfica e clínica, medidas de estresse, coping e FE possibilitou uma análise ecológica e sistêmica. O tratamento dos dados deu-se por meio da estatística descritiva e inferencial, correlacionando-se indicadores clínicos dos pacientes em fase remissiva e ativa da DII. RESULTADOS: A média de idade foi 43,6 anos, com predomínio de mulheres, cor branca, classe socioeconômica desfavorecida e atividade profissional autônoma. Evidenciou-se comprometimento leve nas FE, estabelecendo-se um perfil fenotípico com maiores prejuízos neurocognitivos na Doença de Crohn, em atividade, em uso de corticosteroides, com transtornos de humor e histórico de ideação suicida, maior idade e tempo de diagnóstico. Os prejuízos ocorreram tanto nos processos automáticos de velocidade de processamento, como nos processos controlados, atenção seletiva e alternada, memória de trabalho e flexibilidade cognitiva. A análise de regressão evidenciou que o comprometimento nas FE se constitui como preditor de estresse na DII, tendo como primeiro fator preditor o estresse financeiro; e o segundo, o estresse familiar. Na amostra total, o comprometimento nas FE explicou 18% da variância da percepção do impacto do estresse na saúde; já nos pacientes em atividade, explicou 24% da variância de estresse e 47% da variância do Coping Resolução de Problemas. Essa estratégia foi mais utilizada por pessoas com percepção de sucesso muito grande no alívio do estresse. Os níveis de estresse percebido foram moderados a elevados em mais de um quarto da amostra, sem diferenças significativas na emissão e atividade; e as estratégias de enfrentamento explicaram 62% da variância da percepção do impacto do suporte social recebido. CONCLUSÃO: Os resultados possibilitaram conhecer mecanismos associados às sobecargas inerentes ao processo adaptativo com a DII, sugerindo que os pacientes estão em risco elevado de disfunções executivas ao longo do tempo e suscetibilidade ao estresse. Por outro lado, o estresse interfere no desempenho das FE, retroalimentando esse circuito psiconeuroimunológico. Medidas interdisciplinares preventivas visando remissão duradoura, suporte social e aprendizagem de resolução de problemas poderão contribuir para a modulação dos estados cognitivos e emocionais. O estudo traz elementos relevantes para delineamento de alvos terapêuticos que guiem comportamentos autorregulatórios, prevenção da progressão de danos e incapacidades associadas aos comprometimentos como doenças neurodegenerativas, neuropsiquiátricas e risco de suicídio em pacientes com DII.

INTRODUCTION: Executive functions (EF) constitute an important mechanism of cognitive control, responsible for directing and coordinating behaviour in an adaptive manner, allowing for quick and flexible changes in response to new demands. In the context of inflammatory bowel disease (IBD) diagnosis, there is an excessive signalling of threats and sensitivity to pain that affect brain circuits involving the prefrontal cortex related to EF, resulting in increased vulnerability to stress and consequently to neuroinflammation. Based on these assumptions, the epistemological position of this study is grounded in Psychoneuroimmunology. OBJECTIVE: To investigate the impact of executive functions on stress perception in the activity of inflammatory bowel diseases. METHODOLOGY: This study is quantitative, descriptive, and analytical in nature, with a cross-sectional and correlational design. The sample consisted of 52 patients from an Interdisciplinary Outpatient Care Clinic for IBD, integrated into a community university in southern Brazil. A neuropsychological assessment, including sociodemographic and clinical interviews, stress measures, coping strategies, and executive functions, enabled an ecological and systemic analysis. Data analysis was conducted using descriptive and inferential statistics, correlating clinical indicators of patients in remission and active phases of IBD. RESULTS: The mean age was 43.6 years, with a predominance of women, white ethnicity, disadvantaged socioeconomic class and autonomous professional activity. Mild impairment in EF was evidenced, establishing a phenotypic profile with greater neurocognitive impairments in Crohn's Disease (CD), in activity, in use of corticosteroids, with mood disorders and history of suicidal ideation, older age and diagnosis time. Losses occurred both in automatic processes of processing speed and in controlled processes, selective and alternating attention, working memory and cognitive flexibility. The regression analysis showed that performance in EF is a predictor of stress in IBD, with financial stress as the first predictor; and the second, family stress. Performance in EF explained 18% of the variance in the perception of the impact of stress on health. In active patients, EF performance explained 24% of the stress variance and 47% of the Problem Solving variance. Moderate to high levels of perceived stress were evident in more than a quarter of the sample, with no significant differences in remission and activity. Coping strategies explained 62% of the variance in the perception of the impact of social support received. CONCLUSION: The results shed light on the mechanisms associated with the inherent burdens to the adaptive process with IBD, suggesting that patients are at high risk of executive dysfunction over time and susceptibility to stress. Conversely, stress also affects EF performance, thereby reinforcing this psychoneuroimmunological circuit. Preventive interdisciplinary measures aimed at last remission, social support and problem-solving learning may contribute to the modulation of cognitive and emotional states. The study provides relevant elements for the design of therapeutic targets that guide self-regulatory behaviors, prevention of the progression of damage and disabilities associated with impairments such as neurodegenerative and neuropsychiatric diseases and risk of suicide in patients with IBD.

Fibroblasts overpressing WNT2b cause impairment of intestinal mucosal barrier / 南方医科大学学报

OBJECTIVE@#To investigate the mechanism by which fibroblasts with high WNT2b expression causes intestinal mucosa barrier disruption and promote the progression of inflammatory bowel disease (IBD).@*METHODS@#Caco-2 cells were treated with 20% fibroblast conditioned medium or co-cultured with fibroblasts highly expressing WNT2b, with the cells without treatment with the conditioned medium and cells co-cultured with wild-type fibroblasts as the control groups. The changes in barrier permeability of Caco-2 cells were assessed by measuring transmembrane resistance and Lucifer Yellow permeability. In Caco-2 cells co-cultured with WNT2b-overexpressing or control intestinal fibroblasts, nuclear entry of β-catenin was detected with immunofluorescence assay, and the expressions of tight junction proteins ZO-1 and E-cadherin were detected with Western blotting. In a C57 mouse model of dextran sulfate sodium (DSS)-induced IBD-like enteritis, the therapeutic effect of intraperitoneal injection of salinomycin (5 mg/kg, an inhibitor of WNT/β-catenin signaling pathway) was evaluated by observing the changes in intestinal inflammation and detecting the expressions of tight junction proteins.@*RESULTS@#In the coculture system, WNT2b overexpression in the fibroblasts significantly promoted nuclear entry of β-catenin (P < 0.01) and decreased the expressions of tight junction proteins in Caco-2 cells; knockdown of FZD4 expression in Caco-2 cells obviously reversed this effect. In DSS-treated mice, salinomycin treatment significantly reduced intestinal inflammation and increased the expressions of tight junction proteins in the intestinal mucosa.@*CONCLUSION@#Intestinal fibroblasts overexpressing WNT2b causes impairment of intestinal mucosal barrier function and can be a potential target for treatment of IBD.

Clinical features of primary sclerosing cholangitis and inflammatory bowel disease / 中华内科杂志

Objective: To explore disease characteristics of primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) and compare the differences between PSC with and without IBD. Methods: Study design was cross sectional. Forty-two patients with PSC who were admitted from January 2000 to January 2021 were included. We analyzed their demographic characteristics, clinical manifestations, concomitant diseases, auxiliary examination, and treatment. Results: The 42 patients were 11-74(43±18) years of age at diagnosis. The concordance rate of PSC with IBD was 33.3%, and the age at PSC with IBD diagnosis was 12-63(42±17) years. PSC patients with IBD had higher incidences of diarrhea and lower incidences of jaundice and fatigue than in those without IBD (all P<0.05). Alanine aminotransferase, total bilirubin, direct bilirubin, total bile acid and carbohydrate antigen 19-9 levels were higher in PSC patients without IBD than in those with IBD (all P<0.05). The positive rates for antinuclear antibodies and fecal occult blood were higher in PSC patients with IBD than in those without IBD (all P<0.05). Patients with PSC complicated with ulcerative colitis mainly experienced extensive colonic involvement. The proportion of 5-aminosalicylic acid and glucocorticoid application in PSC patients with IBD was significantly increased compared with that of PSC patients without IBD (P=0.025). Conclusions: The concordance rate of PSC with IBD is lower at Peking Union Medical College Hospital than in Western countries. Colonoscopy screening may benefit PSC patients with diarrhea or fecal occult blood-positive for early detection and diagnosis of IBD.

Mechanism of intestinal injury induced by WNT2B high-expressed fibroblasts in Crohn's disease / 中华儿科杂志

Objective: To explore the mechanism of intestinal tissue damage induced by macrophages activated by WNT2B high-expressed fibroblasts. Methods: This study involved biological information analysis, pathological tissue research and cell experimental research. The biological information of the colon tissue from the children with inflammatory bowel disease in previous study was analyzed again with single-cell sequencing. The pathological tissues were collected by colonoscopy from 10 children with Crohn's disease treated in the Department of Gastroenterology of Guangzhou Women and Children's Medical Center from July 2022 to September 2022. According to the findings of colonoscopy, tissues with obvious inflammation or ulceration were classified as the inflammatory group, while tissues with slight inflammation and no ulceration were classified as the non-inflammatory group. HE staining was performed to observe the pathological changes of the colon tissues. Macrophage infiltration and CXCL12 expression were detected by immunofluorescence. In terms of cell experiments, fibroblasts transfected with WNT2B plasmid or empty plasmid were co-cultured with salinomycin treated or non-treated macrophages, respectively; the expression of proteins through Wnt classical pathway were detected by western blotting. Macrophages treated with SKL2001 were used as the experimental group, and those with phosphate buffer as the control group. The expression and secretion of CXCL12 in macrophages were detected by quantitative Real-time PCR and enzyme-linked immunosorbent assay (ELISA). T-test or rank sum test were used for the comparison between groups. Results: Single-cell sequencing analysis suggested that macrophages were the main cells in inflammatory bowel disease colon tissue, and there was interaction between WNT2B high-expressed fibroblasts and macrophages. HE staining of the 10 patients ((9.3±3.8) years old, 7 males and 3 females) showed that the pathological score of colon tissue in the inflammatory group was higher than that in the non-inflammatory group (4 (3, 4) vs. 2 (1, 2) points, Z=3.05, P=0.002). Tissue immunofluorescence indicated that the number of infiltrating macrophages in the inflammatory group was significantly higher than that in the non-inflammatory group under high power field of view (72.8±10.4 vs.8.4±3.5, t=25.10, P<0.001), as well as the number of cells expressing CXCL12 (14.0±3.5 vs. 4.7±1.9, t=14.68, P<0.001). In cell experiments, western blotting suggested an elevated level of glycogen synthase kinase-3β phosphorylation in macrophages co-cultured with fibroblast transfected with WNT2B plasmid, and salinmycin could reverse this change. Real-time PCR suggested that the transcription level of CXCL12 in the experimental group was higher than that in the control group (6.42±0.04 vs. 1.00±0.03, t=183.00, P<0.001), as well as the expression and secretion of CXCL12 by ELISA ((465±34) vs. (77±9) ng/L, t=13.21, P=0.006). Conclusion: WNT2B high-expressed fibroblasts can secrete WNT2B protein and activate the Wnt classical signaling pathway thus enhancing the expression and secretion of CXCL12 in macrophages, inducing the development of intestinal inflammation of Crohn's disease.

Excerpt from the 2022 American Association for the Study of Liver Diseases clinical practice guideline: management of primary sclerosing cholangitis and cholangiocarcinoma / 中华肝脏病杂志

What are the new contents of the guideline since 2010?A.Patients with primary and non-primary sclerosing cholangitis (PSC) are included in these guidelines for the diagnosis and management of cholangiocarcinoma.B.Define "related stricture" as any biliary or hepatic duct stricture accompanied by the signs or symptoms of obstructive cholestasis and/or bacterial cholangitis.C.Patients who have had an inconclusive report from MRI and cholangiopancreatography should be reexamined by high-quality MRI/cholangiopancreatography for diagnostic purposes. Endoscopic retrograde cholangiopancreatography should be avoided for the diagnosis of PSC.D. Patients with PSC and unknown inflammatory bowel disease (IBD) should undergo diagnostic colonoscopic histological sampling, with follow-up examination every five years until IBD is detected.E. PSC patients with IBD should begin colon cancer monitoring at 15 years of age.F. Individual incidence rates should be interpreted with caution when using the new clinical risk tool for PSC for risk stratification.G. All patients with PSC should be considered for clinical trials; however, if ursodeoxycholic acid (13-23 mg/kg/day) is well tolerated and after 12 months of treatment, alkaline phosphatase (γ- Glutamyltransferase in children) and/or symptoms are significantly improved, it can be considered to continue to be used.H. Endoscopic retrograde cholangiopancreatography with cholangiocytology brushing and fluorescence in situ hybridization analysis should be performed on all patients suspected of having hilar or distal cholangiocarcinoma.I.Patients with PSC and recurrent cholangitis are now included in the new unified network organ sharing policy for the end-stage liver disease model standard.J. Liver transplantation is recommended after neoadjuvant therapy for patients with unresectable hilar cholangiocarcinoma with diameter < 3 cm or combined with PSC and no intrahepatic (extrahepatic) metastases.

Nutritional status and its influencing factors in children with newly diagnosed inflammatory bowel disease / 中国当代儿科杂志

OBJECTIVES@#To investigate the nutritional status and its influencing factors in children with newly diagnosed inflammatory bowel disease (IBD).@*METHODS@#A retrospective analysis was conducted on the clinical data of children who were diagnosed with IBD for the first time in Hunan Children's Hospital from January 2015 to December 2021. Diagnostic delay was defined as the time from the symptom onset to IBD diagnosis being in the upper quartile (P76-P100) of all IBD children in the study. Multivariate logistic regression analysis was used to explore the risk factors for emaciation and growth retardation.@*RESULTS@#A total of 125 children with newly diagnosed IBD were included, with Crohn's disease being the main type (91.2%). The rates of emaciation and growth retardation were 42.4% (53 cases) and 7.2% (9 cases), respectively, and the rate of anemia was 77.6% (97 cases). Diagnostic delay was noted in 31 children (24.8%), with the time from the symptom onset to IBD diagnosis of 366 to 7 211 days. Multivariate logistic regression analysis showed that diagnostic delay was a risk factor for emaciation and growth retardation (OR=2.73 and OR=4.42, respectively; P<0.05) and that age was positively associated with emaciation (OR=1.30, P<0.05).@*CONCLUSIONS@#Children with newly diagnosed IBD have poor nutritional status, and the rates of anemia, emaciation, and growth retardation are high. Diagnostic delay is associated with malnutrition in children with IBD.

Inflammatory Bowel Disease and Pregnancy: Is It a Marker for Adverse Outcomes? / Doença inflamatória intestinal e gravidez: Será um marcador de desfechos adversos?

Abstract Objective To assess obstetric/puerperal/neonatal outcomes in an inflammatory bowel disease (IBD) population and to analyze disease characteristics that may be associated to adverse outcomes. Methods Retrospective descriptive analysis including 47 pregnant women with IBD (28 with Crohn's disease - CD and 19 with ulcerative colitis - UC) who delivered between March 2012 and July 2018 in a tertiary hospital. We reviewed clinical records to extract demographic information, previous medical history, disease subtype, activity, severity, treatment, and obstetric, puerperal, and neonatal outcome measures. Results Obstetric and neonatal complications (composite outcomes) occurred in 55.3% and 14.6% of the IBD population, respectively, and were more frequent in UC patients. Preterm birth (PTB), preeclampsia, anemia, low birth weight (LBW), and neonatal death were also more frequent in UC patients. The rate of postpartum hemorrhage (PPH) was 14.9%, and it was higher in CD patients. Women with active IBD had more obstetric/neonatal adverse outcomes (fetal growth restriction and LBW in particular) and cesarean sections. Patients with medicated IBD had less obstetric/neonatal complications (PTB and LBW in specific) and cesarean sections but more PPH. Conclusion Women with IBD may have an increased risk of obstetric/puerperal/neonatal adverse outcomes. Ulcerative colitis patients had more obstetric and neonatal complications, whereas PPH was more frequent if CD patients. Other disease characteristics were considered, which allowed a better understanding of their possible influence. Although more research is needed, this work reinforces the importance of adequate surveillance to allow prompt recognition and treatment of complications.

Resumo Objetivo Avaliar os desfechos obstétricos/puerperais/neonatais em uma população com doença inflamatória intestinal (DII) e analisar as características da doença, que podem estar associadas a desfechos adversos. Métodos Análise descritiva retrospectiva incluindo 47 gestantes com DII (28 com doença de Crohn - DC e 19 com retocolite ulcerativa - RCU) que deram à luz entre março de 2012 e julho de 2018 em um hospital terciário. Revisamos os registros clínicos para extrair informações demográficas, histórico médico prévio, subtipo da doença, atividade, gravidade, tratamento e medidas de resultados obstétricos, puerperais e neonatais. Resultados As complicações obstétricas e neonatais (desfechos compostos) ocorreram em 55,3% e 14,6% da população com DII, respectivamente; e foram mais frequentes em pacientes com RCU. Nascimento prematuro (PTB), pré-eclâmpsia, anemia, baixo peso ao nascer (BPN) e óbito neonatal também foram mais frequentes em pacientes com RCU. A taxa de hemorragia pós-parto (HPP) foi de 14,9% e foi maior em pacientes com DC. Mulheres com DII ativa tiveram mais desfechos obstétricos/neonatais adversos (restrição de crescimento fetal e BPN em particular) e cesarianas. Pacientes com DII medicada tiveram menos complicações obstétricas/neonatais (PTB e BPN em específico) e cesarianas, mas mais HPP. Conclusão Mulheres com DII podem ter um risco aumentado de desfechos adversos obstétricos/puerperais/neonatais. As pacientes com RCU apresentaram mais complicações obstétricas e neonatais, enquanto a HPP foi mais frequente em pacientes com DC. Outras características da doença foram consideradas, o que permitiu uma melhor compreensão de sua possível influência. Embora mais pesquisas sejam necessárias, este trabalho reforça a importância de uma vigilância adequada para permitir o reconhecimento e o tratamento imediatos das complicações.

Anemia en la enfermedad inflamatoria intestinal: un objetivo subestimado / Anemia in inflammatory bowel disease

Anemia is the most common extraintestinal manifestation of inflammatory bowel disease (IBD). Although there are several causes of anemia in IBD, the two most frequent etiologies are iron deficiency anemia and anemia of chronic disease. Despite the high prevalence of anemia in IBD and its significant impact on patient's quality of life, this complication is still underdiagnosed and undertreated by providers. Active screening for anemia, structured assessment, comprehensive management, and multidisciplinary collaboration are needed in IBD patients. The cornerstone of anemia management depends on the underlying etiology along with normalization of inflammatory activity. Although, oral iron is effective for the treatment of mild iron deficiency-related anemia, intravenous iron formulations have a good safety profile and can be used as first-line therapy in patients with active IBD, severe anemia and previous intolerance prior to oral iron. After proper treatment of anemia, careful monitoring is necessary to prevent its recurrence. Herein, we discuss the etiology, screening, diagnosis, therapy selection, and follow-up for anemia in IBD.

Colitis eosinofílica asociada a enfermedad inflamatoria intestinal / Eosinophilic colitis associated with inflammatory bowel disease

INTRODUCCIÓN: La colitis eosinofílica y la colitis de la enfermedad inflamatoria intestinal, son dos entidades que pueden compartir similares características clínicas, endoscópicas y terapéuticas pero diferentes criterios diagnósticos. OBJETIVOS: Describir el caso clínico de un niño preescolar con antecedente de alergia alimentaria, de hospitalizaciones y uso de antibióticos por varias ocasiones, que evoluciona con diarrea crónica intermitente. CASO CLÍNICO: Se trata de un paciente masculino, de 3 años 5 meses, con antecedente de alergia alimentaria con cuadro crónico de dolor abdominal, diarrea y retraso en el crecimiento. Se realiza abordaje de diarrea crónica. RESULTADOS: Con hallazgos clínicos de enfermedad inflamatoria intestinal y descripción histopatológica de colitis eosinofílica, se considera la asociación entre estas dos patologías sin dejar la posibilidad de que esta última se trate de una fase inicial de enfermedad inflamatoria intestinal. CONCLUSIONES: El tratamiento de pacientes con colitis eosinofílica complicada es similar a la enfermedad inflamatoria intestinal, se requiere seguimiento clínico, endoscópico e histopatológico de pacientes con colitis eosinofílica a largo plazo.

INTRODUCTION: Eosinophilic colitis and inflammatory bowel disease colitis are two entities that may share similar clinical, endoscopic and therapeutic features but different diagnostic criteria. OBJECTIVES: To describe the clinical case of a preschool child with a history of food allergy, hospitalizations and use of antibiotics for several occasions, who evolves with chronic intermittent diarrhea. CLINICAL CASE: This is a male patient, 3 years 5 months old, with a history of food allergy with chronic abdominal pain, diarrhea and growth retardation. Chronic diarrhea was approached. RESULTS: With clinical findings of inflammatory bowel disease and histopathological description of eosinophilic colitis, the association between these two pathologies is considered without leaving the possibility that the latter is an initial phase of inflammatory bowel disease. CONCLUSIONS: The treatment of patients with complicated eosinophilic colitis is similar to inflammatory bowel disease, clinical, endoscopic and histopathological follow-up of patients with eosinophilic colitis is required in the long term.

Can fecal calprotectin reflect your colonic status?

Background: Organic colonic manifestation may be difficult to be differentiated from functional one. Inflammatory bowel disease (IBD) is a common chronic inflammatory and destructive disease of the bowel wall. Chronic inflammation is associated with ulcerations, strictures, perforations, and it is a risk factor for dysplasia and cancer. To reduce these long-standing complications, IBD patients are in a continuous need for early diagnosis1. Markers, such as erythrocyte sedimentation rate (ESR), and c-reactive protein (CRP), fecal calprotectin (FC) have been widely used as noninvasive parameters for IBD monitoring. We aimed, in this current study, to evaluate the value of fecal calprotectin and other noninvasive biomarkers in predicting abnormal histologic findings in patients undergoing colonoscopy.in addition to determine the cutoff value which predict IBD2. Methods: The present prospective study included 160 patients with complaint of colicky abdominal pain with frequent diarrhea associated with mucous and infrequent bleeding per rectum for more than 6 months. They presented partial improvement with medication and recurrence once stopping the treatment These patients had been recently diagnosed with IBD at many primary healthcare centers covering the areas of the Kafrelsheikh and Zagazik governorate in the North of Egyptian Nile delta. After complete history, clinical examination, and laboratory investigation, they were referred to the IBD clinic at Kafrelsheikh University Hospital for assessment and ileocolonoscopy with biopsies. Results: There was a wide spectrum of age of the studied patients, with mean age 40.12±7.88 (minimum 18 and maximum 56 years). Regarding gender, males represented 87.5% of the studied patients. Forty percent of the patients with colonic manifestation were smokers, 57% preferred a spicy diet, and the majority had low educational level (77.5%). Forty percent had obvious blood in stool, 55% had occult blood, and raised ESR CRP occurred in 32.5% and 50%, respectively. Fecal calprotectin cutoff was>159, with sensitivity 92.8% and specificity 97.5%. Conclusions: Biomarkers (FC, ESR, CRP) can be used as noninvasive parameters for the early diagnosis and prediction of organic colonic disease. Fecal calprotectin in the IBD group revealed significant area under the curve (AUC) values and cutoff> 159, with sensitivity 92.8% and specificity 97.5%. (AU)