Hydroalcoholic extract of Araucaria sp. brown propolis alleviates ulcerative colitis induced by TNBS in rats by reducing inflammatory cell infiltration and oxidative damage.

OBJECTIVE: To investigate the effects of Araucaria sp. brown propolis (ABP) against trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. METHODS: Animals received vehicle (1% DMSO, 1 ml/kg) or hydroalcoholic extract of ABP (hydroalcoholic extract of Araucaria sp. brown propolis (HEABP), 30, 100, and 300 mg/kg) orally, or dexamethasone (25 mg/kg, s.c.) for 5 days. On day 4, the animals received intracolonic TNBS (150 mg/kg), on day 6 they were euthanized. The weight of the animals, the macroscopic and microscopic colonic damage, reduced glutathione (GSH) and malondialdehyde (MDA) levels, and the activity of glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) were measured in colon homogenate. The action of HEABP and two isolated compounds in neutrophil migration was recorded. KEY FINDINGS: HEABP (100 and 300 mg/kg), but not dexamethasone, decreased colonic lesion, and increased colonic mucin staining. In parallel, HEABP decreased MDA and restored GSH levels and the activity of SOD, CAT, and GST in the colon. A dose-dependent inhibition of MPO activity was observed (LogIC50 = 1.9). Moreover, HEBPA and the junicedric and abietic acids inhibited the neutrophil chemotaxis in vitro and HEBPA reduced neutrophil migration in vivo. CONCLUSION: HEABP may be promising in the therapies for inflammatory bowel diseases, reducing oxidative and inflammatory damage, especially mediated by neutrophils.

Fecal calprotectin and endoscopic scores: The cornerstones in clinical practice for evaluating mucosal healing in inflammatory bowel disease.

Managing inflammatory bowel disease (IBD) is becoming increasingly complex and personalized, considering the advent of new advanced therapies with distinct mechanisms of action. Achieving mucosal healing (MH) is a pivotal therapeutic goal in IBD management and can prevent IBD progression and reduce flares, hospitalization, surgery, intestinal damage, and colorectal cancer. Employing proactive disease and therapy assessment is essential to achieve better control of intestinal inflammation, even if subclinical, to alter the natural course of IBD. Periodic monitoring of fecal calprotectin (FC) levels and interval endoscopic evaluations are cornerstones for evaluating response/remission to advanced therapies targeting IBD, assessing MH, and detecting subclinical recurrence. Here, we comment on the article by Ishida et al Moreover, this editorial aimed to review the role of FC and endoscopic scores in predicting MH in patients with IBD. Furthermore, we intend to present some evidence on the role of these markers in future targets, such as histological and transmural healing. Additional prospective multicenter studies with a stricter MH criterion, standardized endoscopic and histopathological analyses, and virtual chromoscopy, potentially including artificial intelligence and other biomarkers, are desired.

Transición en enfermedades inflamatorias intestinales: de la pediatría a la adultez / Transition in inflammatory bowel diseases: from childhood to adulthood

El 25% de los pacientes con Enfermedades Inflamatorias Intestinales (EII) se diagnostican antes de los 20 años. En la mayor parte de los centros del país se lleva a cabo la "transferencia" del paciente desde un centro de atención pediátrico a uno de adultos. La "transición" es un criterio de calidad con beneficios en el control de la EII reduciendo el número de recaídas, de hospitalizaciones y de cirugías. Por tal motivo hemos desarrollado un Programa Interdisciplinario de Transición entre dos hospitales de referencia nacional e internacional en EII. Materiales y métodos: Entre 1/2021 y 12/ 2022 se incorporaron 24 pacientes que ingresaron en 3 fases: Fase 1 Pacientes entre 14 y 16 años asistidos en el Hospital Garrahan (HG) con un abordaje interdisciplinario. Fase 2. A partir de los 17 años se realizaron 2 (dos) encuentros en el HG en conjunto con gastroenterólogos de adultos evaluando adherencia y autonomía y la Fase 3 llevada a cabo en el Hospital B. Udaondo (HBU) sólo con el equipo de adultos luego de 6 meses de realizada la transferencia evaluando adherencia al tratamiento, consultas a emergencias, internación y/o cirugías Resultados: Al inicio del Programa el 66% de los pacientes presentaban una actividad moderada a severa vs el 8% al finalizar la fase 3. Luego de la transferencia el 12,5% necesito ingreso a guardia e internación y un 8% tratamiento quirúrgico. El 83% de los pacientes continúan en seguimiento luego de 6 meses de haber sido transferidos (AU)

Twenty-five percent of patients with inflammatory bowel diseases (IBD) are diagnosed before the age of 20 years. In most centers in the country, the "transfer" of the patient from a pediatric to an adult care center is done. However, "transition" is a quality criterion with benefits in the control of IBD by reducing the number of relapses, hospitalizations, and surgeries. For this reason, we developed an Interdisciplinary Transition Program between two national and international reference hospitals in IBD. Materials and Methods: Between January 2021 and December 2022, we incorporated 24 patients into a three-phase program. Phase 1 involved patients between 14 and 16 years of age seen at Garrahan Hospital (HG) with an interdisciplinary approach. Phase 2 began from 17 years of age, with two meetings held at HG involving adult gastroenterologists to evaluate adherence and autonomy. Phase 3 was conducted at Hospital B. Udaondo (HBU) only with the adult team, six months after the transfer, evaluating adherence to treatment, emergency consultations, hospitalizations, and/or surgeries. Results: At the beginning of the program, 66% of the patients presented with moderate to severe disease activity, compared to 8% at the end of Phase 3. After the transfer, 12.5% of the patients required emergency department visits and hospitalization, and 8% required surgical treatment. Eighty-three percent of the patients continue in the program and are still being followed up six months after the transfer (AU)

Identification of master regulator genes controlling pathogenic CD4+ T cell fate in inflammatory bowel disease through transcriptional network analysis.

Inflammatory bowel diseases (IBD) are a group of chronic inflammatory conditions of the gastrointestinal tract associated with multiple pathogenic factors, including dysregulation of the immune response. Effector CD4+ T cells and regulatory CD4+ T cells (Treg) are central players in maintaining the balance between tolerance and inflammation. Interestingly, genetic modifications in these cells have been implicated in regulating the commitment of specific phenotypes and immune functions. However, the transcriptional program controlling the pathogenic behavior of T helper cells in IBD progression is still unknown. In this study, we aimed to find master transcription regulators controlling the pathogenic behavior of effector CD4+ T cells upon gut inflammation. To achieve this goal, we used an animal model of IBD induced by the transfer of naïve CD4+ T cells into recombination-activating gene 1 (Rag1) deficient mice, which are devoid of lymphocytes. As a control, a group of Rag1-/- mice received the transfer of the whole CD4+ T cells population, which includes both effector T cells and Treg. When gut inflammation progressed, we isolated CD4+ T cells from the colonic lamina propria and spleen tissue, and performed bulk RNA-seq. We identified differentially up- and down-regulated genes by comparing samples from both experimental groups. We found 532 differentially expressed genes (DEGs) in the colon and 30 DEGs in the spleen, mostly related to Th1 response, leukocyte migration, and response to cytokines in lamina propria T-cells. We integrated these data into Gene Regulatory Networks to identify Master Regulators, identifying four up-regulated master gene regulators (Lef1, Dnmt1, Mybl2, and Jup) and only one down-regulated master regulator (Foxo3). The altered expression of master regulators observed in the transcriptomic analysis was confirmed by qRT-PCR analysis and found an up-regulation of Lef1 and Mybl2, but without differences on Dnmt1, Jup, and Foxo3. These two master regulators have been involved in T cells function and cell cycle progression, respectively. We identified two master regulator genes associated with the pathogenic behavior of effector CD4+ T cells in an animal model of IBD. These findings provide two new potential molecular targets for treating IBD.

W-GA nanodots restore intestinal barrier functions by regulating flora disturbance and relieving excessive oxidative stress to alleviate colitis.

Inflammatory bowel disease (IBD) may arise due to disruption of mucosal barriers as a result of dysregulation of the intestinal flora and excessive oxidative stress. The creation of nanomaterials with only microbiota-regulating effects often leads to inadequate therapeutic outcomes caused by the disruption of a healthy microbial balance and the emergence of tissue harm caused by excessive oxidative stress. This report describes the multifunctional activity of ultrasmall W-GA nanodots, which can precisely regulate the intestinal microbiome by inhibiting the abnormal expansion of Enterobacteriaceae during colitis and alleviating the damage caused by oxidative stress to the reconstructive microflora, ultimately restoring intestinal barrier function. W-GA nanodots have been synthesized through a simple coordination reaction and can be dispersed in various solvents in vitro, demonstrating favorable safety profiles in cells, significant clearance of reactive oxygen and nitrogen species (RONS), and increased cell survival in models of oxidative stress induced by hydrogen peroxide (H2O2). Through oral or intravenous administration, the W-GA nanodots were shown to be highly safe when tested in vivo, and they effectively reduced colon damage in mice with DSS-induced colitis by restoring the integrity of the intestinal barrier. W-GA nanodots have enabled the integration of microflora reprogramming and RONS clearance, creating a potent therapeutic strategy for treating gut inflammation. Consequently, the development of W-GA nanodots represents a promising strategy for enhancing the formation and preservation of the intestinal barrier to treat IBD by suppressing the growth of Enterobacteriaceae, a type of facultative anaerobic bacterium, and facilitating the effective removal of RONS. Ultimately, this leads to the restoration of the intestinal barrier's functionality. STATEMENT OF SIGNIFICANCE: An increasing number of nanoparticles are under development for treating inflammatory bowel disease. Although they can alleviate inflammation symptoms by regulating reactive oxygen and nitrogen species (RONS) and microbiota, their understanding of the mechanism behind microbiota regulation is limited. This study synthesized W-GA nanodots using a straightforward one-pot synthesis method. Simple synthesis holds significant promise for clinical applications, as it encompasses multiple nanoenzyme functions and also exhibits Enterobacteriaceae inhibitory properties.Thus, it contributes to ameliorating the current medical landscape of inflammatory bowel disease.

Patients with Inflammatory Bowel Disease who regularly consume fruits and vegetables present lower prevalence of disease activation: A cross-sectional study.

BACKGROUND: Exclusion diets are common practices among individuals with Inflammatory Bowel Disease (IBD). Reports that certain foods trigger or worsen symptoms are recurrent but lack evidence. The aim of the study was to identify which foods were most frequently avoided by patients with Crohn's Disease (CD) and Ulcerative Colitis (UC) and whether the consumption of any food group was associated with disease activity. METHODS: Cross-sectional study with adult patients seen at an outpatient clinic in a tertiary public hospital. Dietary intake and eating habits were accessed through questionnaires administered via telephone interview. Disease activity and symptoms were assessed using the Harvey-Bradshaw Index (IHB) for CD and the Lichtiger Index (LI) for UC. Poisson regression with a robust variance estimator was used to estimate prevalence ratios. Analyzes were performed using SPSS - Statistical Package for the Social Sciences. RESULTS: The study included 145 patients. Of these, 69.7% avoided certain foods, with citrus fruits and raw vegetables among the most avoided (16.8% and 13.8%, respectively). Regular consumption of fruits (PR = 0.56; CI 95% 0.32-0.97; p = 0.042) and vegetables (PR = 0.56; CI 95% 0.32-0.98; p = 0.045) was associated with a 44% lower prevalence of the active phase of the disease, compared to those who do not consume these foods, adjusted for age, sex and type of disease. Other food items did not present significant associations in the adjusted model. CONCLUSIONS: Fruit and vegetable intake appears to have a protective role in the recurrence of IBD. Excluding foods is a common practice, even among patients in remission, and this should be combated as it can lead to nutritional losses. It is important to reinforce with patients the benefits of a varied and less restrictive diet.

Is religiosity/spirituality in patients with Crohn's disease important to their quality of life?

The authors aim to study Religiosity/Spirituality (R/S) and Quality of Life (QoL) in patients with Crohn's disease and their correlation with the disease phenotypes. METHODS: Prospective cross-sectional cohort study with 151 consecutive patients enrolled from March 2021 to October 2021 at the Colorectal IBD Outpatient of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP). Sociodemographic, Religiosity/Spirituality (Duke University Religion Index - Durel) questionnaires and QoL (Inflammatory Bowel Disease Questionnaire - Short IBDQ-S) were applied. When necessary, qualitative variables were evaluated using the chi-square or Fisher's exact test. The Mann-Whitney and Kruskall-Wallis tests were used to analyze quantitative variables and compare more than two groups, both non-parametric statistical techniques. RESULTS: The most frequent location was Ileocolonic followed by Ileal and colonic (41.1 %, 27.2 %, and 25.2 %); only 6.6 % of subjects had a perianal presentation. Inflammatory, stenosing, and penetrating behaviors showed 36.4 %, 19.1 %, and 44.4 % respectively. The majority of the population is Catholic, Evangelical, or Spiritualist (92.4 %). QoL score showed no significant difference in the phenotypes. The scores for DUREL domains were 61.4 % for organizational religiosity, 75 % for non-organizational religiosity, 98.6 %, 93.6 % and 89.3 % for intrinsic spirituality, with high results in all disease phenotypes. CONCLUSIONS: The studied population presented homogeneous sociodemographic results and high religious and spiritual activity. R/S in a positive context were not associated with better QoL or phenotype. R/S is present in the patients' lives and could be seen as an important tool for adherence to treatment and the professional relationship between doctor and patient. The homogeneity of the sample difficult for an appropriate evaluation, which leads us to suggest new studies with more heterogeneous groups.

Interaction between diet and genetics in patients with inflammatory bowel disease.

In this editorial, we comment on the article by Marangoni et al, published in the recent issue of the World Journal of Gastroenterology 2023; 29: 5618-5629, about "Diet as an epigenetic factor in inflammatory bowel disease". The authors emphasized the role of diet, especially the interaction with genetics, in promoting the inflammatory process in inflammatory bowel disease (IBD) patients, focusing on DNA methylation, histone modifications, and the influence of microRNAs. In this editorial, we explore the interaction between genetics, gut microbiota, and diet, in an only way. Furthermore, we provided dietary recommendations for patients with IBD. The Western diet, characterized by a low fiber content and deficiency the micronutrients, impacts short-chain fatty acids production and may be related to the pathogenesis of IBD. On the other hand, the consumption of the Mediterranean diet and dietary fibers are associated with reduced risk of IBD flares, particularly in Crohn's disease (CD) patients. According to the dietary guidance from the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD), the regular consumption of fruits and vegetables while reducing the consumption of saturated, trans, dairy fat, additives, processed foods rich in maltodextrins, and artificial sweeteners containing sucralose or saccharine is recommended to CD patients. For patients with ulcerative colitis, the IOIBD recommends the increased intake of natural sources of omega-3 fatty acids and follows the same restrictive recommendations aimed at CD patients, with the possible inclusion of red meats. In conclusion, IBD is a complex and heterogeneous disease, and future studies are needed to elucidate the influence of epigenetics on diet and microbiota in IBD patients.

Intervención nutricional orientada al control del proceso inflamatorio en pacientes con espondilitis enteropática

Introducción: La espondilitis enteropática es una enfermedad inflamatoria, sistémica y crónica que se caracteriza por afectar el aparato digestivo y el sistema osteomioarticular; el proceso inflamatorio genera manifestaciones clínicas que afectan la capacidad funcional y la percepción de calidad de vida de los pacientes. Objetivo: Evaluar los resultados de una intervención nutricional orientada al control del proceso inflamatorio en pacientes con espondilitis enteropática. Métodos: Se realizó una investigación observacional y descriptiva longitudinal que incluyó como universo a 19 pacientes con diagnóstico confirmado de espondilitis enteropática atendidos en el Hospital Andino de Chimborazo en el periodo comprendido entre julio 2022 y julio 2023. La muestra quedó conformada por 17 pacientes. Se aplicó una intervención nutricional durante 10 meses que incluyó como elemento central la suplementación con alimentos ricos en probióticos según esquema definido por especialista en nutrición clínica. Resultados: Promedio de edad de 43,51 años, predominio del sexo femenino (64,70 %) y del tiempo de evolución de la enfermedad entre 5 y 10 años (58,82 %). Todos los marcadores de inflamación medidos durante el estudio mejoraron durante el seguimiento realizado a los pacientes; a los 9 meses se identificó aumento del porcentaje de pacientes con proteína C reactiva negativa y fibrinógeno y velocidad de sedimentación globular normal. Conclusiones: La intervención nutricional aplicada contribuye a mejorar los valores séricos de los marcadores de inflamación en los pacientes con diagnóstico de espondilitis enteropática.

Introduction: Enteropathic spondylitis is an inflammatory, systemic and chronic disease that is characterized by affecting the digestive system and the osteomyoarticular system; The inflammatory process generates clinical manifestations that affect the functional capacity and perception of quality of life of patients. Objective: To evaluate the results of a nutritional intervention aimed at controlling the inflammatory process in patients with enteropathic spondylitis. Methods: A longitudinal observational and descriptive investigation was carried out that included as a universe 19 patients with a confirmed diagnosis of enteropathic spondylitis treated at the Andino Hospital of Chimborazo in the period between July 2022 and July 2023. The sample was made up of 17 patients. A nutritional intervention was applied for 10 months that included as a central element supplementation with foods rich in probiotics according to a scheme defined by a clinical nutrition specialist. Results: Average age of 43.51 years, predominance of the female sex (64.70%) and duration of the disease between 5 and 10 years (58.82%). All inflammation markers measured during the study improved during the patients' follow-up; At 9 months, an increase in the percentage of patients with negative C-reactive protein and fibrinogen and normal erythrocyte sedimentation rate was identified. Conclusions: The applied nutritional intervention contributed to improving serum values ​​of inflammation markers in patients diagnosed with enteropathic spondylitis.

Repercussion of inflammatory bowel disease on lung homeostasis: The role of photobiomodulation.

Inflammatory bowel diseases (IBD) are chronic and multifactorial diseases characterized by dysfunction of the intestinal mucosa and impaired immune response. Data show an important relationship between intestine and respiratory tract. The treatments of IBD are limited. Photobiomodulation (PBM) is an effective anti-inflammatory therapy. Our objective was to evaluate the repercussion of IBD as well as its treatment with PBM on pulmonary homeostasis. Male Wistar rats were submitted to IBD induction by acetic acid and treated or not with PBM. Rats were irradiated with red LED on both right and left sides of the ventral surface and beside the external anal region during 3 consecutive days (wavelenght 660 nm, power 100 mw, total energy 15 J and time of irradiation 150 s per point). Our results showed that IBD altered pulmonary homeostasis, since we observed an increase in the histopathological score, in myeloperoxidase activity (MPO), in mast cell degranulation, and in the release and gene expression of cytokines. We also showed that PBM treatment reduced biomarkers of IBD and reverted all augmented parameters in the lung, restoring its homeostasis. Thus, we confirm experimentally the important gut-lung axis and the role of PBM as a promising therapy.

Fenotipificación y genotipificación en pacientes con enfermedad inflamatoria intestinal en un centro de referencia de Colombia / Phenotyping and genotyping in patients with inflammatory bowel disease in a reference center in Colombia

RESUMEN Introducción: Se ha tratado de identificar los factores genéticos relacionados con susceptibilidad para enfermedad inflamatoria intestinal (EII), y los hallazgos actuales se inclinan por un modelo de patología complejo, sin un patrón hereditario claro. Objetivo: Realizar caracterización fenotípica y genotípica de pacientes con EII en población colombiana y describir su posible asociación con predisposición. Materiales y métodos: Serie de casos, 16 pacientes con EII por criterios clínicos y anatomopatológicos, inicio de síntomas gastrointestinales después de los 18 años. Todos tuvieron asesoramiento genético pre-test y se realizaron árboles genealógicos de mínimo tres generaciones. También, genotipificación, por medio de un panel de genes múltiples que incluía genes relacionados con EII y algunos trastornos autoinmunitarios. Finalmente, se realizó análisis genómico de variantes. Resultados: 9 mujeres y 7 hombres, con edad media de diagnóstico de EII 35 años, y 32 años para aparición de síntomas gastrointestinales. 11/16(68,75%) requirieron terapia biológica. 10/16 (62,5%) presentaron refractariedad a terapia estándar. 3/16 (18,75%) tenían antecedentes familiares positivos de EII. 100% casos presentaron al menos un single nucleotide polymorphism relacionado con riesgo de EII en más de un gen. Los genes más relacionados con colitis ulcerosa (CU), fueron CD48, CD6, y TYK2 para CU, y CD6 e ITGAM para la enfermedad de Crohn. El gen más frecuente fue CD6. Se observó en 3/16 (18,75%) presencia de hasta 5 genes, 4 en 3/16 (18,75%), y tres en 5/16 (31,25%). Conclusión: En EII hay presencia de variantes genéticas con predisposición asociada, pero sin patogenicidad confirmada, y cuya sumatoria parece contribuir en su fisiopatología.

ABSTRACT Introduction: Attempts have been made to identify the genetic factors related to susceptibility to inflammatory bowel disease (IBD), and the current conclusions are in favor of a complex pathology model, without a clear hereditary pattern. Objective: To perform phenotypic and genotypic characterization of patients with IBD in Colombian population and to describe its possible association with predisposition. Materials and methods: case series, 16 patients with IBD according to clinical and pathological criteria, onset of gastrointestinal symptoms after 18 years of age. All had pre-test genetic counseling and family trees of at least three generations were made. Also, genotyping, using a multigene panel that included genes related to IBD and some autoimmune disorders. Finally, a genomic analysis of variants was performed. Results: 9 women and 7 men, with mean age of diagnosis of IBD of 35 years, and gastrointestinal symptoms appearance of 32 years. 11/16 (68.75%) required biological therapy. 10/16 (62.5%) were refractory to standard therapy. 3/16 (18.75%) had positive family history of IBD. 100% cases presented at least one single nucleotide polymorphism related to IBD risk in more than one gene. The genes most related to ulcerative colitis (UC) were CD48, CD6, and TYK2 for UC, and CD6 and ITGAM for Crohn's disease. The most frequent gene was CD6. It was found presence of up to 5 genes in 3/16 (18.75%), 4 in 3/16 (18.75%), and three in 5/16 (31.25%). Conclusion: In IBD there is the presence of genetic variants with associated predisposition, but without confirmed pathogenicity, and whose sum seems to contribute to its pathophysiology.

Cannabidiol - Help and hype in targeting mucosal diseases.

Cannabidiol (CBD) is one of the most commonly utilised phytocannabinoids due to its non-psychoactive and multiple potential therapeutic properties and its non-selective pharmacology. Recent studies have demonstrated efficacy of CBD in some types of drug resistant epilepsies in combination with other therapies; comparative efficacy to other agents or placebo has been hoped for anxiety, chronic pain, and inflammatory disorders based on animal data. Although CBD products are generally treated as a restricted substance, these are being eased, partially in response to significant growth in CBD product usage and increased production but more due to emerging evidence about its safety and pharmacological properties. Currently, only one CBD product (Epidiolex®) has been approved by the Australian Therapeutic Goods Administration and US Food and Drug Administration. CBD has demonstrated promise in alleviating gut and lung diseases in vitro; however, its physicochemical properties pose a significant barrier to achieving pharmacological effects in in vivo and clinical trials. Improving CBD formulations and delivery methods using technologies including self-emulsifying emulsion, nano and micro particles could overcome these shortfalls and improve its efficacy. This review focuses on the therapeutic potential of CBD in gastrointestinal and lung diseases from the available in vitro, in vivo, and clinical research. We report on identified research gaps and obstacles in the development of CBD-based therapeutics, including novel delivery methods.

Composição da gordura corporal em pacientes com doenças inflamatórias intestinais: um estudo comparativo entre dobras cutâneas e ultrassonografia / Body fat composition in patients with inflammatory bowel diseases: a comparative study between skinfolds and ultrasonography

ABSTRACT Background: Inflammatory bowel diseases (IBD) are associated with important changes in nutritional status. Objective: The aim of the study was to compare body fat composition between two anthropometric methods: skinfolds and ultrasonography, in patients with IBD. Methods: Single-center cross-sectional study with IBD patients in remission or active disease. For the agreement analysis between the body fat assessment methods, the Bland Altman method was used. Results: A total of 101 patients with IBD were included, 75 with Crohn's disease and 26 with ulcerative colitis. Approximately 56% of the patients with Crohn's disease and 65.4% of those with ulcerative colitis had a body fat composition above normal levels, with no significant difference between the diseases (P=0.63). The Bland-Altman concordance analysis showed that the methods for assessing the percentage of fat by the adipometer and ultrasound were not in full agreement (P=0.001), despite both presented good correlation (CC 0.961; P=0.000). Conclusion: The analysis of body fat percentage in patients with IBD was different between the skinfolds and ultrasound. Both methods can be used to assess the of body fat percentage of patients with IBD. However, monitoring of body fat sequentially and longitudinally should always be performed using the same method throughout the disease course. Prospective longitudinal studies are warranted to precisely define the role of these two methods of measuring body composition in patients with IBD.

RESUMO Contexto: As doenças inflamatórias intestinais (DII) estão associadas a alterações importantes no estado nutricional. Objetivo: O objetivo do estudo foi comparar a composição da gordura corporal entre dois métodos antropométricos: dobras cutâneas e ultrassonografia, em pacientes com DII. Métodos: Estudo transversal de centro único com pacientes com DII em remissão ou doença ativa. Para a análise de concordância entre os métodos de avaliação da gordura corporal foi utilizado o método de Bland-Altman. Resultados: Foram incluídos 101 pacientes com DII, 75 com doença de Crohn e 26 com colite ulcerativa. Aproximadamente 56% dos pacientes com doença de Crohn e 65,4% daqueles com colite ulcerativa apresentaram composição de gordura corporal acima dos níveis normais, sem diferença significativa entre as doenças (P=0,63). A análise de concordância de Bland-Altman mostrou que os métodos de avaliação do percentual de gordura pelo adipômetro e ultrassonografia não foram totalmente concordantes (P=0,001), apesar de ambos apresentarem boa correlação (CC 0,961; P=0,000). Conclusão: A análise do percentual de gordura corporal em pacientes com DII foi diferente entre as dobras cutâneas e a ultrassonografia. Ambos os métodos podem ser usados para avaliar o percentual de gordura corporal de pacientes com DII. Entretanto, o monitoramento da gordura corporal de forma sequencial e longitudinal deve ser sempre realizado utilizando o mesmo método durante todo o curso da doença. Estudos longitudinais prospectivos são necessários para definir com precisão o papel desses dois métodos de medição da composição corporal em pacientes com DII.

Adesão e persistência ao tratamento com infliximabe: análise de uma coorte de um programa de suporte ao paciente no Brasil / Adherence and persistence to treatment with infliximab: analysis of a patient support program cohort in brazil

ABSTRACT Background: Monoclonal antibodies have proven efficacy in the management of several conditions and infliximab (IFX) is one of the most important drugs of the class. Some recent data have shown low rates of both persistence and adherence to several available biologics. Objective: The objective of this study was to describe adherence and persistence rate to IFX treatment and also persistence in the patient support program (PSP), among patients diagnosed with inflammatory bowel diseases (IBD) or rheumatic diseases (RD) enrolled in the program of a large pharmaceutical company in Brazil. Methods: Retrospective observational analysis using the PSP database. IBD or RD patients using IFX enrolled on the PSP database between September 2015 and August 2019 were retrospectively evaluated to identify the persistence rate and adherence and followed up until March 1, 2020. Patients were excluded if treatment start date was prior to program entry; first infusion prior to September 1st, 2015 or after August 31st, 2019; the patients did not started treatment; and patients with "OTHERS" in "Indication" field. Persistence was assessed considering both persistence in the program ("PSP persistence") and persistence on IFX in the PSP ("IFX persistence in the PSP"). PSP persistence was defined as the proportion of patients remaining in the program at 6, 12, 24, 36 and 48 months after initiating IFX. To determine IFX persistence in the PSP, censoring was defined at the time the patient left the program, died, or was lost to follow-up. Adherence to treatment was measured by medication possession ratio ((MPR) - All days supply / elapsed days from first prescription to last day of medication possession)). Descriptive statistics were initially used. Kaplan-Meier curve, the median time estimated by the survival function, Cox regression model, and restricted mean survival time (RMST) were used to evaluate the treatment persistence time at 24 months and the logistic regression model was performed aiming to identify variables associated with adherence (MPR ≥80%). Results: A total of 10,233 patients were analyzed, 5,826 (56.9%) with the diagnosis of RD and 4,407 (43.1%) of IBD. At the end of the follow-up (median 9.1 months from PSP entry to the last infusion), persistence in the PSP was 65.6%, 48.2%, 31.0%, 20.7% and 13.1% at 6, 12, 24, 36 and 48 months, respectively. Considering persistence on IFX in the PSP, estimates were 93.7%, 87.8%, 77.0%, 62.4% and 53.0% at 6, 12, 24, 36 and 48 months, respectively. Variables associated with the risk of non-persistence were gender, country region and diagnosis of rheumatoid arthritis and ankylosing spondylitis. Median MPR was 94.2%, while the percentage of patients with MPR ≥80% was 91.0%. Variables associated with MPR≥80% were country region and diagnosis of Crohn's disease. Conclusion: Many patients leave the program without discontinuing IFX, since the 12-month persistence were very different between program and medication estimates, while high adherence rates were observed among patients enrolled in the PSP. Data highlights the benefits of a PSP.

RESUMO Contexto: Os anticorpos monoclonais têm eficácia comprovada no manejo de diversas condições e o infliximabe (IFX) é um dos medicamentos mais importantes da classe. Alguns dados recentes demonstram baixas taxas de persistência e adesão a vários dos biológicos disponíveis. Objetivo: O objetivo deste estudo foi descrever a adesão e persistência ao tratamento com IFX e a persistência no programa de suporte ao paciente (PSP), entre pacientes diagnosticados com doenças inflamatórias intestinais (DII) ou doenças reumáticas (DR) inscritos no PSP de uma grande indústria farmacêutica no Brasil. Métodos: Análise observacional retrospectiva utilizando o banco de dados do PSP. Pacientes com DII ou DR usando IFX inscritos no banco de dados do PSP entre setembro de 2015 e agosto de 2019 foram avaliados retrospectivamente para identificar a taxa de persistência e adesão e acompanhados até 1º de março de 2020. Os pacientes foram excluídos se a data de início do tratamento fosse anterior à entrada no programa; primeira infusão antes de 1º de setembro de 2015 ou após 31 de agosto de 2019; o paciente não iniciou o tratamento; e pacientes com "OUTROS" no campo "indicação". A persistência foi avaliada considerando tanto a persistência no programa ("persistência PSP") quanto a persistência em uso de infliximabe no PSP ("persistência IFX no PSP"). A persistência no PSP foi definida como a proporção de pacientes que permaneceram no programa aos 6, 12, 24, 36 e 48 meses após o início do IFX. Para determinar a persistência do IFX no PSP, a censura foi definida quando o paciente deixou o programa, morreu ou perdeu o acompanhamento. A adesão ao tratamento foi medida pela razão de posse do medicamento (MPR)): todos os dias de fornecimento / decorridos da primeira prescrição ao último dia de posse do medicamento). A estatística descritiva foi inicialmente utilizada. A curva de Kaplan-Meier, o tempo mediano estimado pela função de sobrevida, o modelo de regressão de Cox e o tempo de sobrevida médio restrito (RMST) foram utilizados para avaliar o tempo de persistência do tratamento em 24 meses e o modelo de regressão logística foi realizado para identificar variáveis associadas à adesão (MPR ≥80%). Resultados: Foram analisados 10.233 pacientes, 5.826 (56,9%) com diagnóstico de DR e 4.407 (43,1%) de DII. Ao final do seguimento (mediana de 9,1 meses desde a entrada no PSP até a última infusão), a persistência no PSP foi de 65,6%, 48,2%, 31,0%, 20,7% e 13,1% aos 6, 12, 24, 36 e 48 meses, respectivamente. Considerando a persistência no IFX no PSP, as estimativas foram de 93,7%, 87,8%, 77,0%, 62,4% e 53,0% aos 6, 12, 24, 36 e 48 meses, respectivamente. As variáveis associadas ao risco de não persistência foram sexo, região do país e diagnóstico de artrite reumatoide e espondilite anquilosante. A mediana do MPR foi de 94,2%, enquanto o percentual de pacientes com MPR ≥80% foram de 91,0%. As variáveis associadas a MPR ≥80% foram região do país e diagnóstico de doença de Crohn. Conclusão: Muitos pacientes abandonam o programa sem interromper o IFX, pois a persistência em 12 meses foi muito diferente entre as estimativas do programa e da medicação, enquanto altas taxas de adesão foram observadas entre os pacientes inscritos no PSP. Os dados destacam os benefícios de um PSP.

Is religiosity/spirituality in patients with Crohn's disease important to their quality of life?

Abstract The authors aim to study Religiosity/Spirituality (R/S) and Quality of Life (QoL) in patients with Crohn's disease and their correlation with the disease phenotypes. Methods Prospective cross-sectional cohort study with 151 consecutive patients enrolled from March 2021 to October 2021 at the Colorectal IBD Outpatient of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP). Sociodemographic, Religiosity/Spirituality (Duke University Religion Index - Durel) questionnaires and QoL (Inflammatory Bowel Disease Questionnaire - Short IBDQ-S) were applied. When necessary, qualitative variables were evaluated using the chi-square or Fisher's exact test. The Mann-Whitney and Kruskall-Wallis tests were used to analyze quantitative variables and compare more than two groups, both non-parametric statistical techniques. Results The most frequent location was Ileocolonic followed by Ileal and colonic (41.1 %, 27.2 %, and 25.2 %); only 6.6 % of subjects had a perianal presentation. Inflammatory, stenosing, and penetrating behaviors showed 36.4 %, 19.1 %, and 44.4 % respectively. The majority of the population is Catholic, Evangelical, or Spiritualist (92.4 %). QoL score showed no significant difference in the phenotypes. The scores for DUREL domains were 61.4 % for organizational religiosity, 75 % for non-organizational religiosity, 98.6 %, 93.6 % and 89.3 % for intrinsic spirituality, with high results in all disease phenotypes. Conclusions The studied population presented homogeneous sociodemographic results and high religious and spiritual activity. R/S in a positive context were not associated with better QoL or phenotype. R/S is present in the patients' lives and could be seen as an important tool for adherence to treatment and the professional relationship between doctor and patient. The homogeneity of the sample difficult for an appropriate evaluation, which leads us to suggest new studies with more heterogeneous groups.

Metabolic dysfunction-associated steatotic liver disease prevalence and risk factors in inflammatory bowel disease in tertiary center

SUMMARY OBJECTIVE: The aim of this study was to evaluate the prevalence and risk factors related to metabolic dysfunction-associated steatotic liver disease in inflammatory bowel disease patients. METHODS: This is a cross-sectional study conducted on adults with inflammatory bowel disease from 2019 to 2021. Metabolic dysfunction-associated steatotic liver disease encompasses patients with steatosis and at least one cardiometabolic risk factor. Patients with alcohol consumption ≥20 g/day, chronic liver diseases, or methotrexate use were excluded. RESULTS: Almost 140 patients were included: 67.1% were female, with a mean age of 49.7±13.7 years, and 63.6% had Crohn's disease. The mean duration of inflammatory bowel disease was 9.7±7.9 years. Metabolic dysfunction-associated steatotic liver disease was observed in 44.3% and advanced liver fibrosis was excluded in 63.5% by Fibrosis-4. Patients with metabolic dysfunction-associated steatotic liver disease were older (p = 0.003) and had a higher number of metabolic syndrome components (2.9±1.1 versus 1.6±1.0; p<0.001), greater abdominal circumference (p<0.001), and body mass index (p<0.001). The only factor related to inflammatory bowel disease associated with metabolic dysfunction-associated steatotic liver disease was disease duration (11.6±9.5 versus 8.3±6.2; p = 0.017). A higher number of metabolic syndrome components and obesity increase by 2.2 times and an altered waist circumference by 2.6 times the occurrence of metabolic dysfunction-associated steatotic liver disease. CONCLUSION: A high prevalence of metabolic dysfunction-associated steatotic liver disease was observed in patients with inflammatory bowel disease, with the main risk factors being associated with metabolic syndrome predicting it, but not with inflammatory bowel disease features and/or its treatment.

Brechas de acceso en el manejo y tratamiento en Enfermedad Inflamatoria Intestinal / Access gaps in the management and treatment of Inflammatory Bowel Disease

Social determinants of health can mean difficulties in access to diagnosis, management and adequate treatment of IBD. Income, educational level, age, sex, and rurality, among other factors, can influence the health outcomes of specific populations, such as IBD patients. It is essential to be aware of these gaps and advocate for public policies that address socioeconomic disparities and promote a healthy environment for all people. This includes providing equitable access to quality healthcare and supporting patients in managing their disease.

Los determinantes sociales de la salud pueden significar dificultades en el acceso a diagnóstico, manejo y trata- miento adecuado de la EII. El ingreso, el nivel educacional, la edad, el sexo y la ruralidad, entre otros factores pueden influir en los resultados en salud de poblaciones determinadas, como los pacientes con EII. Es fundamental, conocer estas brechas y abogar por políticas públicas que aborden las disparidades socioeconómicas y promuevan un entorno saludable para todos. Esto incluye brindar acceso equitativo a la atención médica de calidad y apoyar a los pacientes en la gestión de su enfermedad.

Personalised therapy in inflammatory bowel disease. / Terapia personalizada en la enfermedad inflamatoria intestinal.

Inflammatory bowel diseases (IBD), with ulcerative colitis and Crohn's disease being their most common presentations, comprise a spectrum of diverse disease phenotypes, exhibiting variable behaviors ranging from an indolent course to aggressive phenotypes that impact quality of life of these patients. The last two decades have been marked by the development of new medications (biological therapy and novel small molecules) with diverse mechanisms of action, which have revolutionized the management of IBD, thereby enhancing the quality of life for these patients. This landscape of multiple therapeutic options underscores the need to define which medication will benefit each patient the most and at what speed it should be started. The objective of this review is to present personalized approaches for patients with IBD, thus contributing to therapeutic management.

A spurious elevation of serum creatinine level in a patient with Crohn's disease without histologic kidney damage: a case report and review of the literature / Elevação espúria do nível de creatinina sérica em ­paciente com doença de Crohn sem lesão renal histológica: relato de caso e revisão da literatura

ABSTRACT Patients with inflammatory bowel disease (IBD) are prone to develop kidney injury. Renal involvement in IBD patients is usually diagnosed by the measurement of serum creatinine and the estimation of the glomerular filtration rate. We describe a patient with IBD who presented with large fluctuations in his serum creatinine level (~3.0-fold) without significant histologic abnormalities and with a normal cystatin C level. This appears to be related to a high-protein diet and intermittent fasting. Even though the impact of a high-protein diet on mild elevations of the serum creatinine level has been described, large fluctuations in serum creatinine from diet alone, as seen in this case, have never been reported, raising the question about the potential contribution of inflamed bowel on gut absorption or metabolism of creatinine. This case highlights the importance of a detailed history, including the dietary habits, when encountering a patient with increased serum creatinine level, and careful interpretation of serum creatinine in a patient with a creatinine high-protein diet or underlying IBD.

RESUMO Pacientes com doença inflamatória intestinal (DII) são propensos a desenvolver lesão renal. O envolvimento renal em pacientes com DII é geralmente diagnosticado pela medição da creatinina sérica e pela estimativa da taxa de filtração glomerular. Descrevemos um paciente com DII que apresentou grandes flutuações em seu nível de creatinina sérica (~3,0 vezes) sem anormalidades histológicas significativas e com nível normal de cistatina C. Isso parece estar relacionado a uma dieta rica em proteínas e jejum intermitente. Ainda que o impacto de uma dieta rica em proteínas em elevações leves do nível de creatinina sérica tenha sido descrito, nunca foram relatadas grandes flutuações na creatinina sérica apenas devido à dieta, como observado neste caso, o que levanta a questão sobre a possível contribuição do intestino inflamado na absorção intestinal ou no metabolismo da creatinina. Esse caso destaca a importância de um histórico detalhado, incluindo os hábitos alimentares, ao se deparar com um paciente com nível de creatinina sérica aumentado, e a interpretação cuidadosa da creatinina sérica em um paciente com dieta rica em proteínas ou DII subjacente.

The Role of Pharmacogenetics in the Therapeutic Response to Thiopurines in the Treatment of Inflammatory Bowel Disease: A Systematic Review.

This study focuses on the use of thiopurines for treating inflammatory bowel diseases (IBD). These drugs undergo enzymatic changes within the body, resulting in active and inactive metabolites that influence their therapeutic effects. The research examines the role of genetic polymorphisms in the enzyme thiopurine S-methyltransferase (TPMT) in predicting the therapeutic response and adverse effects of thiopurine treatment. The TPMT genotype variations impact the individual responses to thiopurines. Patients with reduced TPMT activity are more susceptible to adverse reactions (AEs), such leukopenia, hepatotoxicity, pancreatitis, and nausea, which are common adverse effects of thiopurine therapy. The therapeutic monitoring of the metabolites 6-thioguanine nucleotides (6-TGN) and 6-methyl mercaptopurine (6-MMP) is proposed to optimize treatment and minimize AEs. Patients with higher 6-TGN levels tend to have better clinical responses, while elevated 6-MMP levels are linked to hepatotoxicity. Genotyping for TPMT before or during treatment initiation is suggested to tailor dosing strategies and enhance treatment efficacy while reducing the risk of myelosuppression. In conclusion, this study highlights the importance of considering genetic variations and metabolite levels in optimizing thiopurine therapy for IBD patients, focusing on balance therapeutic efficacy with the prevention of adverse effects and contributing to personalized treatment and better patient outcomes.