Association Between Vedolizumab Treatment and Arthritis/Arthralgia in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Vedolizumab is a humanized gut selective drug that targets α4ß7 integrin and has been used successfully in the treatment of inflammatory bowel disease (IBD). Pivotal studies have already demonstrated the drug's safety, but some real-life cohorts have shown an increase in arthralgia and arthritis in patients using vedolizumab. These findings raised the question of whether these joint symptoms are extraintestinal manifestations of IBD (since the drug acts only in the gut) or if they are associated with the use of vedolizumab. This systematic review and meta-analysis aimed to assess the incidence of arthralgia/arthritis in patients receiving vedolizumab and to investigate whether these events are indeed drug related. METHODS: Pubmed, Cochrane, and Scopus were searched for randomized clinical trials reporting the incidence of joint manifestations in patients with Crohn's disease (CD) or ulcerative colitis (UC) who were treated with vedolizumab. The considered outcomes were arthritis and arthralgia. We used RevMan to calculate the pooled incidence of the reported outcomes and their corresponding 95% confidence intervals (95% CI). RESULTS: The search strategy yielded 4,206 articles. After removal of duplicates and screening of results, 6 randomized studies met the inclusion criteria. A total of 3,134 patients with moderately to severe IBD were included. Of those, 2,119 were randomized to receive vedolizumab and 1,015 to placebo. In the intervention group, 210 patients developed arthritis or arthralgia of any kind while 84 patients developed those symptoms in the placebo group (RR=1.09; 95%CI: 0.86-1.38; p=0.49, I2=0%), showing no significant association. Results also showed no significant association between exposure and the studied outcome after comparing CD (RR=1.02; 95%CI: 0.76-1.37, p=0.89, I2=0%) and UC (RR=1.24; 95%CI: 0.81-1.89, p=0.32, I2=43%) separately. CONCLUSIONS: The meta-analysis showed no association of these symptoms to the treatment with vedolizumab. Therefore, the new onset of worsening arthritis and arthralgia may be associated with the course of the disease itself, with the body's response to the drugs or with the exclusion of corticosteroids or anti-TNF from concomitant treatment with vedolizumab. Further studies with larger sample sizes are required, especially randomized clinical trials comparing anti-TNF, corticosteroid and immunomodulators to evaluate the incidence of joint manifestations in patients with IBD and even other rheumatological manifestations that may be associated as well.

Correlation between the Quantity and Type of Dietary Fiber with the Activity in Mexican Patients with Ulcerative Colitis (UC).

Background/Objective: Ingestion of dietary fiber can influence in the remission of patients with ulcerative colitis (UC). There are no current recommendations for fiber intake in UC; therefore, we evaluate the association between dietary fiber and the activity of the disease. Methods: Ours is a cross-sectional study in patients with a confirmed diagnosis of UC to whom a 24 h recall was applied; this allowed for the estimation and classification of type of dietary fiber. The patients were divided into two groups: (1) remission and (2) active UC. We analyzed the quantity and type of fiber with the grades of disease activity through Spearman correlation and logistic regression. Results: A total of 152 patients were included; it was found that those with clinically active UC consumed less total fiber (p = 0.016) and insoluble fiber (p = 0.018). Meanwhile, in endoscopic grade, the difference was for insoluble fiber (p = 0.038). Insoluble fiber had an inversely significant correlation with fecal calprotectin levels (r = -0.204; p = 0.018). Logistic regression showed that less than 11 g of insoluble fiber was a risk factor for clinical activity (OR = 2.37; 95% CI 1.107-5.019; p = 0.026). Conclusions: Consumption below the current recommendation of total and insoluble dietary fiber is associated with clinical activity of UC.

Can serum M30 levels be utilized as an activation marker in patients with ulcerative colitis?

OBJECTIVE: Ascertainment of disease activation is an important component of therapeutic decisions in ulcerative colitis patients and may present certain clinical challenges. The objective of this study was to determine serum levels of the M30 fragment of cytokeratin 18 and its utility as an activation marker in patients with ulcerative colitis, who are known to have increased apoptosis. METHODS: A total of 60 ulcerative colitis (30 active and 30 remission) patients aged over 18 years and 29 healthy individuals as controls were included in the study. M30, C-reactive protein, and mean platelet volume were evaluated in all participants and compared between ulcerative colitis patients and controls, as well as between those with active disease or remission. RESULTS: Although ulcerative colitis patients with active disease had higher M30 levels than those in remission, the difference was not statistically significant (p=0.085). The mean M30 levels tended to increase with increasing extent of involvement, although the differences were not significant (p=0.065). The comparison of C-reactive protein and mean platelet volume according to the site of involvement, however, showed significant differences (p=0.02 and 0.004, respectively). M30 did not show significant correlations with C-reactive protein, mean platelet volume, and Mayo Score (p=0.0834, 0.768, and 0.401, respectively). CONCLUSIONS: Our results suggest that, in contrast to C-reactive protein and mean platelet volume, M30 levels do not have a significant role as an activation marker in ulcerative colitis patients. Thus, we believe that M30 may not represent an appropriate marker to be used for this purpose.

Improvement effect of compound Ento-PB on oxazolone-induced ulcerative colitis in rats.

PURPOSE: To investigate the impact of the Chinese medicine compound Ento-PB on oxazolone (OXZ)-induced ulcerative colitis (UC) in rats. METHODS: UC rats induced by OXZ were treated with Ento-PB. The damage to the colon was assessed using several measures, including the disease activity index (DAI), colon length, colon weight/length ratio, colonic mucosal damage index, and histological score. The levels of interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-13 (IL-13), epidermal growth factor (EGF), inducible nitric oxide synthase, and total nitric oxide synthase (tNOS) in rat serum, as well as the levels of tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) in rat colon tissue, were determined using enzyme-linked immunosorbent assay and conventional kits. RESULTS: After being treated with Ento-PB, the DAI score and macroscopic lesion score of OXZ-induced UC rats were significantly reduced. Ento-PB prevented the shortening of rat colons, reduced the ratio of colon weight to length, and improved colon tissue lesions. Meanwhile, Ento-PB could significantly inhibit the activities of proinflammatory cytokines TNF-α, IL-13, and MPO, as well as tNOS and iNOS, while upregulating the expression of anti-inflammatory cytokines IL-4 and IL-10. Moreover, a significant increase in the expression level of EGF was observed in UC rats treated with Ento-PB, indicating that Ento-PB could enhance the repair of damaged intestinal epithelial tissue. CONCLUSIONS: Ento-PB demonstrates significant anti-UC activities in OXZ-induced UC rats by regulating the expression levels of inflammatory factors and promoting the repair of colon tissue. This study provides scientific evidence to support the further development of Ento-PB.

Involvement of IL17A and IL17RA variants in interleukin-17A levels and disease activity in ulcerative colitis.

Ulcerative colitis (UC) is characterized by chronic inflammation of the large intestine with involvement of Th17 cells and interleukin (IL)-17A. The role of IL17A and IL17A receptor (IL17RA) variants in pathophysiology of UC still remains inconclusive. The aim was to evaluate the association between IL17A and IL17RA variants with susceptibility, IL-17A plasma levels, and endoscopic activity in UC. The study included 104 patients with UC and 213 controls. Patients were divided according to endoscopic activity (remission/mild and moderate/severe). The IL17A rs3819024 A>G and rs3819025 G>A, and IL17RA rs2241043 C>T, rs2241049 A>G, and rs6518661 G>A variants were genotyped using real time polymerase chain reaction. IL-17A plasma levels were determined using immunofluorimetric assay. Neither IL17A nor IL17RA variants were associated with UC susceptibility. The IL17A rs3819024 AG genotype was associated to high levels of IL-17 only in patients. Patients with the G allele of IL17RA rs2241049 showed 2.944 more chance of developing moderate/severe disease. The haplotype analysis showed that IL17RA rs2241049 and rs6518661 was not associated with UC susceptibility and haplotypes constituted with G allele of these variants were not associated with disease severity (p = 0.09). In conclusion, the IL17A rs3819024 AG genotype was associated with elevated IL-17A plasma levels in patients with UC but not in controls and the IL17RA rs2241049 AG+GG genotypes were associated to severity of UC. These results suggest a possible hidden interaction between the IL17A rs3819024 variant and other genetic, environmental, and epigenetic factors in the IL-17A expression that is present only in patients with UC.

Risks and benefits of anti-TNF therapy for ulcerative colitis in a patient with autoimmune hepatitis-related cirrhosis: Case report.

RATIONALE: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by continuous inflammation of the colonic mucosa. Autoimmune hepatitis (AIH) is a chronic liver disease characterized by hypergammaglobulinemia, circulating autoantibodies, interface hepatitis, and favorable response to immunosuppression. An association between IBD and AIH is uncommon, and experts have suggested that in patients with overlapping IBD and AIH, the anti-tumor necrosis factor agents can be used. Therefore, this study reports a rare case of a patient with liver cirrhosis due to AIH and UC refractory to conventional treatment and discusses the risks and benefits of using anti-tumor necrosis factor in both conditions. PATIENT CONCERNS: A 28-year-old female presented with symptoms of diarrhea, abdominal pain, asthenia, and inappetence, accompanied by abdominal collateral circulation, anemia, alteration of liver enzymes, and elevation of C-reactive protein levels. DIAGNOSES: The patient underwent a liver biopsy, which was consistent with liver cirrhosis due to AIH. Colonoscopy showed an inflammatory process throughout the colon, compatible with moderately active UC. INTERVENTIONS: The patient received mesalazine, azathioprine, and corticotherapy, with no control of the inflammatory process. Faced with refractoriness to drug treatment and side effects of corticosteroids with an increased risk of severe infection due to cirrhosis, we opted to use infliximab for the treatment of UC. The patient presented with a clinical response and infliximab therapy was maintained. OUTCOMES: Eight months after starting infliximab therapy, the patient developed pneumonia with complications from disseminated intravascular coagulation and died. LESSONS SUBSECTIONS: AIH is a rare cause of elevated transaminase levels in patients with UC. The best treatment to control the 2 conditions should be evaluated with vigilance for the side effects of medications, mainly infections, especially in patients with cirrhosis.

Cross-cultural adaptation and validation of Work Productivity and Activity Impairment questionnaires for caregivers of patients with pediatric inflammatory bowel disease in Spain. A multicenter study. / Adaptación transcultural y validación de cuestionarios WPAI (Work Productivity and Activity Impairment) para cuidadores de pacientes con enfermedad inflamatoria intestinal pediátrica en España. Estudio multicéntrico.

Introduction. The WPAI-UC/CD-Caregiver questionnaires assess the impact of ulcerative colitis (UC) or Crohn's disease (CD) on parents'/caregivers' work life and daily activities. Our objective was to adapt and validate these questionnaires in the Spanish population. Methods. A translation and back-translation were done. The document was assessed by an expert committee and a pilot group of families of patients with pediatric inflammatory bowel disease (p-IBD). For validation, the parents/caregivers of patients with p-IBD (10-18 years old) were recruited. The expert committee and the pilot group conducted a subjective assessment of the format and time necessary to complete the questionnaires. Cronbach's alpha coefficient was estimated and a factor analysis with varimax rotation was done. Kaiser- Meyer-Olkin (KMO) coefficients and Bartlett's sphericity test were estimated to test the adequacy of the factor analysis. Results. A total of 370 patients (median age: 14.1 years) and 263 parents/caregivers of patients with UC or unclassified IBD and 261 parents/caregivers of patients with CD were included. The KMO coefficients (0.6947 and 0.7179) and Bartlett's sphericity test (p < 0.001) confirmed the adequacy of the factor analysis. The 6 items targeted the same domain. The factor model accounted for 99.99% and 94.68% of variance, and Cronbach's alpha coefficients (0.6581 and 0.6968) showed an adequate consistency. The format and the median time of 2 minutes to complete the questionnaires were considered optimal. Conclusions. The versions of the WPAI-Caregiver questionnaires validated in the Spanish population may be used in families whose children have IBD.

Introducción. Los cuestionarios WPAI-UC/CD-Caregiver evalúan la repercusión laboral y en actividades cotidianas de los padres/cuidadores de pacientes con colitis ulcerosa (CU) o enfermedad de Crohn (EC). El objetivo fue adaptar y validar estos cuestionarios en la población española. Métodos. Se realizó la traducción y la retrotraducción. El documento fue evaluado por un comité de expertos y por un grupo piloto de familias de pacientes con enfermedad inflamatoria intestinal pediátrica (EII-p). Para la validación, se reclutaron padres/cuidadores de pacientes con EII-p (10-18 años). El comité de expertos y el grupo piloto evaluaron subjetivamente el formato y el tiempo necesario para completar los cuestionarios. Se calculó el coeficiente alfa de Cronbach y se realizó el análisis factorial con rotación Varimax. Se calcularon los coeficientes de Kaiser-Meyer-Olkin (KMO) y la prueba de esfericidad de Bartlett para comprobar la adecuación del análisis factorial. Resultados. Se incluyeron 370 pacientes (mediana 14,1 años), y 263 padres/cuidadores de pacientes con colitis ulcerosa o EII no clasificada y 261 padres/cuidadores de pacientes con enfermedad de Crohn. Los coeficientes KMO (0,6947 y 0,7179) y la prueba de esfericidad de Barttlet (p <0,001) confirmaron la adecuación del análisis factorial. Los 6 ítems se dirigieron a la misma dimensión. El modelo factorial explicó el 99,99 % y el 94,68 % de la varianza, y los alfa de Cronbach (0,6581 y 0,6968) indicaron buena consistencia. El formato y la mediana de 2 minutos para completarlos se consideraron óptimos. Conclusiones. Las versiones validadas en la población española de los cuestionarios WPAI-Caregiver pueden considerarse para su uso en familias con hijos con EII.

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.

Dietary Profile of Patients with Inflammatory Bowel Disease in Clinical Remission-A Preliminary Study.

Imbalanced dietary intake is associated with the development of inflammatory bowel diseases (IBDs) and is often observed during the active phases of Crohn's disease (CD) and ulcerative colitis (UC). Cumulative data also suggest the potential for dietary manipulation in avoiding IBD relapse. However, there is a paucity of dietary data from patients in clinical remission to guide such an approach. Our study aimed to characterize the dietary pattern and adequacy of patients with IBD in clinical remission. Data on dietary intake (three alternate 24 h food records) were collected from 40 patients with IBD (20 CD and 20 UC) and 45 gender-matched healthy controls (HC). Statistical comparisons between patients and controls employed Student's t-test, Mann-Whitney U, chi-squared, and Fisher's exact tests. The adequacy of dietary intake of IBD patients was further studied by assessing the nutrient inadequacy prevalence, estimated using the Dietary Reference Intakes (DRI) framework and the Estimated Average Requirement (EAR) parameter. We observed significant dietary imbalances among patients with IBD compared to the HC group, marked by disparities in both macronutrient and micronutrient intakes. Inadequacies with frequencies >80% were observed for the ingestion of total fiber and 13 micronutrients in IBD patients. Our preliminary findings suggest that imbalanced dietary intake is also characteristic among individuals with IBD during clinical remission, corroborating the need for dietary interventions in this population.

ASSESSMENT OF QUALITY OF LIFE IN ELDERLY PATIENTS WITH INFLAMMATORY BOWEL DISEASE WITH MILD ACTIVITY AND IN CLINICAL REMISSION.

BACKGROUND: Inflammatory bowel disease (IBD), represented by Crohn's disease (CD) and ulcerative colitis (UC), is a chronic condition that affects all age groups, predominantly in young individuals. Currently, an increase in the prevalence of IBD has been documented, in parallel with the increase in the elderly population. The scarce number of studies that better characterize the impact of IBD on Quality of Life (QoL) in the elderly motivated the present study. OBJECTIVE: To evaluate the impact of IBD on the QoL of elderly people treated at a Tertiary IBD Center. METHODS: Prospective cross-sectional study that included elderly patients (age ≥60 years) with quiescent or mildly active IBD treated at the HU-UFJF IBD Center between March 2019 and December 2022. Elderly companions without severe comorbidities who attended the consultation with the patients were included as a control group. Sociodemographic and IBD-related characteristics were recorded. QoL was assessed using previously validated questionnaires (WHOQOL-BREF and IBDQ). Patients with IBD with moderate to severe activity, history of recent or imminent hospitalization, serious or opportunistic infections in the last 6 months, previous neoplasia, dementia, and difficulty understanding/fulfilling the questionnaires were excluded. RESULTS: A total of 123 patients were included (74 with IBD and 49 in the control group), with a mean age of 67±6.2 years, 52.7% with CD, and 47.3% with UC. Mild disease activity was observed in 31.1%. Both groups (IBD patients and control) were comparable based on age, sex, BMI, and the Charlson Comorbidity Index. Patients with IBD and controls had similar QoL scores in the different domains assessed by the WHOQOL-BREF. On the other hand, when evaluating the general facet of QoL, IBD patients had significantly lower scores in General QoL (3.71±0.87 versus 4.02±0.62, respectively; P=0.021) and General Health (3.32±1.05 versus 3.69±0.94, respectively; P=0.035). The presence of mildly active IBD negatively impacted the general health score (2.91±0.99 versus 3.47±1.04, respectively; P=0.035) and the physical domain of the WHOQOL-BREF (12.27±2.63 versus 13.86±2.61, respectively; P=0.019) when compared to patients in remission. Conversely, no impact on QoL was observed with the Application of the IBDQ questionnaire regarding the type of the disease (161±38.5 versus 163.1±42.6 for CD and UC, respectively; P=0.84) or the presence of activity (152.5±38.8 versus 166.4±40.5, respectively; P=0.17). CONCLUSION: No statistically significant differences were found between elderly patients with mildly active or quiescent IBD and elderly patients without IBD when observing global QoL scores. However, IBD negatively impacted the general facet of QoL, just as mild activity was associated with lower scores in general health and the physical domain assessed by the WHOQOL-BREF. Patients with IBD treated with biological therapy had better Qol than those on conventional therapy. Future studies are needed to choose the most appropriate tool for assessing QoL in this population.

Exploring the anti-inflammatory effects of postbiotic proteins from Lactobacillus delbrueckii CIDCA 133 on inflammatory bowel disease model.

Lactobacillus delbrueckii CIDCA 133 is a promising health-promoting bacterium shown to alleviate intestinal inflammation. However, the specific bacterial components responsible for these effects remain largely unknown. Here, we demonstrated that consuming extractable proteins from the CIDCA 133 strain effectively relieved acute ulcerative colitis in mice. This postbiotic protein fraction reduced the disease activity index and prevented colon shortening in mice. Furthermore, histological analysis revealed colitis prevention with reduced inflammatory cell infiltration into the colon mucosa. Postbiotic consumption also induced an immunomodulatory profile in colitic mice, as evidenced by both mRNA transcript levels (Tlr2, Nfkb1, Nlpr3, Tnf, and Il6) and cytokines concentration (IL1ß, TGFß, and IL10). Additionally, it enhanced the levels of secretory IgA, upregulated the transcript levels of tight junction proteins (Hp and F11r), and improved paracellular intestinal permeability. More interestingly, the consumption of postbiotic proteins modulated the gut microbiota (Bacteroides, Arkkemansia, Dorea, and Oscillospira). Pearson correlation analysis indicated that IL10 and IL1ß levels were positively associated with Bacteroides and Arkkemansia_Lactobacillus abundance. Our study reveals that CIDCA 133-derived proteins possess anti-inflammatory properties in colonic inflammation.

Silencing ANGPT2 alleviates ulcerative colitis by regulating autophagy-mediated NLRP3 inflammasome inactivation via the mTOR signaling pathway.

Ulcerative colitis (UC) is a difficult intestinal disease characterized by inflammation, and its mechanism is complex and diverse. Angiopoietin-like protein 2 (ANGPT2) plays an important regulatory role in inflammatory diseases. However, the role of ANGPT2 in UC has not been reported so far. After exploring the expression level of ANGPT2 in serum of UC patients, the reaction mechanism of ANGPT2 was investigated in dextran sodium sulfate (DSS)-induced UC mice. After ANGPT2 expression was suppressed, the clinical symptoms and pathological changes of UC mice were detected. Colonic infiltration, oxidative stress, and colonic mucosal barrier in UC mice were evaluated utilizing immunohistochemistry, immunofluorescence, and related kits. Finally, western blot was applied for the estimation of mTOR signaling pathway and NLRP3 inflammasome-related proteins. ANGPT2 silencing improved clinical symptoms and pathological changes, alleviated colonic inflammatory infiltration and oxidative stress, and maintained the colonic mucosal barrier in DSS-induced UC mice. The regulatory effect of ANGPT2 on UC disease might occur by regulating the mTOR signaling pathway and thus affecting autophagy-mediated NLRP3 inflammasome inactivation. ANGPT2 silencing alleviated UC by regulating autophagy-mediated NLRP3 inflammasome inactivation via the mTOR signaling pathway.

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

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 multi-gene 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.

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.

MicroRNAs in inflammatory bowel disease: What do we know and what can we expect?

MicroRNAs (miRNAs), small non-coding RNAs composed of 18-24 nucleotides, are potent regulators of gene expression, contributing to the regulation of more than 30% of protein-coding genes. Considering that miRNAs are regulators of inflammatory pathways and the differentiation of intestinal epithelial cells, there is an interest in exploring their importance in inflammatory bowel disease (IBD). IBD is a chronic and multifactorial disease of the gastrointestinal tract; the main forms are Crohn's disease and ulcerative colitis. Several studies have investigated the dysregulated expression of miRNAs in IBD, demonstrating their important roles as regulators and potential biomarkers of this disease. This editorial presents what is known and what is expected regarding miRNAs in IBD. Although the important regulatory roles of miRNAs in IBD are clearly established, biomarkers for IBD that can be applied in clinical practice are lacking, emphasizing the importance of further studies. Discoveries regarding the influence of miRNAs on the inflammatory process and the exploration of their role in gene regulation are expected to provide a basis for the use of miRNAs not only as potent biomarkers in IBD but also as therapeutic targets for the control of inflammatory processes in personalized medicine.

Controversies in IPAA for Ulcerative Colitis: A Systematic Review of Different Anastomotic Techniques.

BACKGROUND: Available techniques for IPAA in ulcerative colitis include handsewn, double-stapled, and single-stapled anastomoses. There are controversies, indications, and different outcomes regarding these techniques. OBJECTIVE: To describe technical details, indications, and outcomes of 3 specific types of anastomoses in restorative proctocolectomy. DATA SOURCE: Systematic literature review for articles in the PubMed database according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. STUDY SELECTION: Studies describing outcomes of the 3 different types of anastomoses, during pouch surgery, in patients undergoing restorative proctocolectomy for ulcerative colitis. INTERVENTION: IPAA technique. MAIN OUTCOME MEASURES: Postoperative outcomes (anastomotic leaks, overall complication rates, and pouch function). RESULTS: Twenty-one studies were initially included: 6 studies exclusively on single-stapled IPAA, 2 exclusively on double-stapled IPAA, 6 studies comparing single-stapled to double-stapled techniques, 6 comparing double-stapled to handsewn IPAA, and 1 comprising single-stapled to handsewn IPAA. Thirty-seven studies were added according to authors' discretion as complementary evidence. Between 1990 and 2015, most studies were related to double-stapled IPAA, either only analyzing the results of this technique or comparing it with the handsewn technique. Studies published after 2015 were mostly related to transanal approaches to proctectomy for IPAA, in which a single-stapled anastomosis was introduced instead of the double-stapled anastomosis, with some studies comparing both techniques. LIMITATIONS: A low number of studies with handsewn IPAA technique and a large number of studies added at authors' discretion were the limitations of this strudy. CONCLUSIONS: Handsewn IPAA should be considered if a mucosectomy is performed for dysplasia or cancer in the low rectum or, possibly, for re-do surgery. Double-stapled IPAA has been more widely adopted for its simplicity and for the advantage of preserving the anal transition zone, having lower complications, and having adequate pouch function. The single-stapled IPAA offers a more natural design, is feasible, and is associated with reasonable outcomes compared to double-stapled anastomosis. See video from symposium.

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.

The histamine H4 receptor antagonist 1-[(5-chloro-2,3-dihydro-1-benzofuran-2-yl)methyl]-4-methyl-piperazine(LINS01007) prevents the development of DSS-induced colitis in mice.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with growing incidence worldwide. Our group reported the compound 5-choro-1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazine (LINS01007) as H4R antagonist (pKi 6.2) and therefore the effects and pharmacological efficacy on a DSS-induced mice model of UC were assessed in this work. Experimental acute colitis was induced in male BALB/c mice (n = 5-10) by administering 3 % DSS in the drinking water for six days. The test compound LINS01007 was administered daily i.p. (5 mg/kg) and compared to control group without treatment. Body weight, water and food consumption, and the presence of fecal blood were monitored during 7-day treatment period. The levels of inflammatory markers (PGE2, COX-2, IL-6, NF-κB and STAT3) were also analyzed. Animals subjected to the acute colitis protocol showed a reduction in water and food intake from the fourth day (p < 0.05) and these events were prevented by LINS01007. Histological signs of edema, hyperplasia and disorganized intestinal crypts, as well as neutrophilic infiltrations, were found in control mice while these findings were significantly reduced in animals treated with LINS01007. Significant reductions in the levels of PGE2, COX-2, IL-6, NF-κB and STAT3 were observed in the serum and tissue of treated animals. The results demonstrated the significant effects of LINS01007 against DSS-induced colitis, highlighting the potential of H4R antagonism as promising treatment for this condition.

Are we ready to use new endoscopic scores for ulcerative colitis?

For ulcerative colitis (UC), the variability in inflammatory activity along the colon poses a challenge in management. The focus on achieving endoscopic healing in UC is evident, where the UC Endoscopic Index of Severity and Mayo Endoscopic Subscore are commonly used for evaluation. However, these indices primarily consider the most severely affected region. Liu et al recent study validates the Toronto Inflammatory Bowel Disease Global Endoscopic Reporting (TIGER) score offering a comprehensive assessment of inflammatory activity across diverse segments of the colon and rectum and a reliable index correlating strongly with UC Endoscopic Index of Severity and moderately with Mayo Endoscopic Subscore (MES). Despite recommendation, certain aspects warrant further investigation. Fecal calprotectin, an intermediate target, correlates with TIGER and should be explored. Determining TIGER scores defining endoscopic remission and response, evaluating agreement with histological activity, and assessing inter-endoscopist agreement for TIGER require scrutiny. Exploring the correlation between TIGER and intestinal ultrasound, akin to MES, adds value.

BODY FAT COMPOSITION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES: A COMPARATIVE STUDY BETWEEN SKINFOLDS AND ULTRASONOGRAPHY.

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. BACKGROUND: • Inflammatory bowel diseases are associated with changes in nutritional status. BACKGROUND: • Skinfolds measurements and ultrasound are valid methods for assessing body composition and body fat. BACKGROUND: • These methods despite comparable are not identical and are useful in clinical nutritional practices in IBD.