Symptoms Of Crohn's Disease Research Articles

Role of gut microbiota in Crohn's disease pathogenesis: Insights from fecal microbiota transplantation in mouse model.

Inflammatory bowel disease, particularly Crohn's disease (CD), has been associated with alterations in mesenteric adipose tissue (MAT) and the phenomenon termed "creeping fat". Histopathological evaluations showed that MAT and intestinal tissues were significantly altered in patients with CD, with these tissues characterized by inflammation and fibrosis. To evaluate the complex interplay among MAT, creeping fat, inflammation, and gut microbiota in CD. Intestinal tissue and MAT were collected from 12 patients with CD. Histological manifestations and protein expression levels were analyzed to determine lesion characteristics. Fecal samples were collected from five recently treated CD patients and five control subjects and transplanted into mice. The intestinal and mesenteric lesions in these mice, as well as their systemic inflammatory status, were assessed and compared in mice transplanted with fecal samples from CD patients and control subjects. Pathological examination of MAT showed significant differences between CD-affected and unaffected colons, including significant differences in gut microbiota structure. Fetal microbiota transplantation (FMT) from clinically healthy donors into mice with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD ameliorated CD symptoms, whereas FMT from CD patients into these mice exacerbated CD symptoms. Notably, FMT influenced intestinal permeability, barrier function, and levels of proinflammatory factors and adipokines. Furthermore, FMT from CD patients intensified fibrotic changes in the colon tissues of mice with TNBS-induced CD. Gut microbiota play a critical role in the histopathology of CD. Targeting MAT and creeping fat may therefore have potential in the treatment of patients with CD.

Content Validity and Psychometric Evaluation of the Crohn's Symptom Severity (CSS) Questionnaire in Patients with Moderately to Severely Active Crohn's Disease.

Individuals living with Crohn's disease (CD) experience burdensome symptoms. As such, it is important to measure CD symptom severity in clinical research. The goal of this study was to evaluate the content validity, psychometric performance, and score interpretability of a new patient-reported instrument, the Crohn's Symptom Severity (CSS) questionnaire, among adolescents and adults with moderately to severely active CD. Cognitive debriefing interviews (N = 30; n = 20 adults, n = 10 adolescents) were conducted to evaluate the content validity of the CSS. Additionally, the CSS scores were evaluated for reliability and validity using data from a phase3 randomized clinical trial of risankizumab (NCT03105128; N = 850). Meaningful within-patient change (MWPC) thresholds were estimated using anchor-based methods. All interview participants (n = 30/30, 100.00%) reported the CSS was easy to complete and most participants (n = 28/29, 96.55%) reported that the CSS was relevant to their experience of CD. Among the clinical trial subjects (N = 850) the following was found for the CSS: mostly acceptable item-total correlations (0.26-0.79); weak to moderate inter-item correlations (r = 0.07-0.57), good internal consistency (Cronbach's α = 0.76-0.87); intraclass correlation coefficients ranged from 0.48 to 0.70, not consistently exceeding the acceptable range for test-retest reliability (0.70); acceptable convergent validity and known-groups results; and demonstrated sensitivity to change. Analyses supported an MWPC estimate of 6-11 points. This study supports use of the CSS for measuring CD symptoms and sleep impact among adolescents and adults aged 16 and older with moderately to severely active CD in clinical research. NCT03105128 (registration date 4 April 2017).

Lifestyle Intervention Modulates the CD4+ T Cell Profile in the Blood of Crohn's Disease Patients.

Crohn's disease (CD) significantly affects patients' well-being and is influenced by stress and lifestyle factors, highlighting the importance of improving quality of life in CD management. An imbalance between pro- and anti-inflammatory CD4+ T cell responses is a key factor in CD, and stress has been shown to alter the function of CD4+ T cells. Therefore, this study aimed to evaluate the effect of a mind-body medicine stress management and lifestyle modification (MBM) program on the CD4+ T cell profile in CD patients. Circulating CD4+ T cells from CD patients were analyzed by flow cytometry following the MBM program. Patients were randomly assigned to either a guided intervention group (IG) or a self-guided waitlist control group (CG) over a 9-month trial and compared with healthy blood donors. Lifestyle intervention reduced regulatory T cell (Treg) frequencies in the blood of CD patients. Notably, we observed a significant correlation between the quality of life improvement and Treg frequencies in the IG but not in the CG. Furthermore, differential activation and expression of the gut-homing molecules G protein-coupled receptor 15 and CCR9 on circulating Tregs and CD4+ effector T cells were detected in both the IG and CG. The MBM program, whether guided or self-directed, has the potential to restore the CD4+ T cell profile of CD patients to levels comparable to healthy blood donors. Lifestyle interventions may benefit CD progression, symptoms, and immunological status, but further analysis is needed to substantiate these findings and to fully understand their clinical implications. (ClinicalTrials.gov: NCT05182645).

Randomized controlled trial of an Acceptance and Commitment Therapy and compassion-based group intervention for persons with inflammatory bowel disease: the LIFEwithIBD intervention.

This study tested the acceptability and efficacy of an Acceptance and Commitment Therapy and compassion-based intervention (LIFEwithIBD) in people with IBD through a two-arm RCT. Participants were recruited at the Gastroenterology Department of the Coimbra University Hospital between June and September 2019. Of the 355 patients screened, those who accepted to participate were randomly assigned to one of two conditions: experimental group (LIFEwithIBD; n = 25) or control group (waitlist; n = 29). Participants completed self-report measures at baseline (T0), post-intervention (T1), and 3-month (T2) and 12-month (T3) follow-ups. Intervention acceptability was assessed. Efficacy was examined using intent-to-treat ANCOVA at post-intervention after adjusting for baseline values of depressive, anxiety, and stress symptoms (primary outcomes). Linear mixed models for all longitudinal outcomes were also analysed. Inflammatory and disease biomarkers were determined at T0 and T3. Acceptability results revealed a high level of satisfaction and perceived usefulness regarding the intervention. Both groups experienced a significant decrease in stress symptoms and IBD symptom perception at T1. No significant differences were observed at follow-up for the primary outcomes. The experimental group reported significantly lower Crohn's disease Symptom severity at T2 than the control group. Post-hoc analyses designed to mitigate floor effects revealed substantial treatment effects for the experimental group regarding anxiety symptoms. No significant differences were observed in clinical biomarkers from T0 to T3. The LIFEwithIBD intervention shows promising, although preliminary, benefits for managing disease activity and reducing anxiety symptoms in IBD patients with high severity of psychological distress.Clinical trial registration: https://www.clinicaltrials.gov/ct2/show/NCT03840707, identifier NCT03840707.

COVID-19 impact in Crohn’s disease patients submitted to autologous hematopoietic stem cell transplantation

BACKGROUND Severe acute respiratory syndrome coronavirus 2 is the virus responsible for coronavirus disease 2019 (COVID-19), a disease that has been blamed for inducing or exacerbating symptoms in patients with autoimmune diseases. Crohn's disease (CD) is an inflammatory bowel disease that affects genetically susceptible patients who develop an abnormal mucosal immune response to the intestinal microbiota. Patients who underwent hematopoietic stem cell transplantation (HSCT) are considered at risk for COVID-19. AIM To describe for the first time the impact of COVID-19 in CD patients who had undergone autologous, non-myeloablative HSCT. METHODS In this descriptive study a series of 19 patients were diagnosed with positive COVID-19. For two patients there were reports of the occurrence of two infectious episodes. Parameters related to HSCT, such as time elapsed since the procedure, vaccination status, CD status before and after infection, and clinical manifestations resulting from COVID-19, were evaluated. RESULTS Among the patients with COVID-19, three, who underwent Auto HSCT less than six months ago, relapsed and one, in addition to the CD symptoms, started to present thyroid impairment with positive anti-TPO. Only one of the patients required hospitalization for five days to treat COVID-19 and remained in CD clinical remission. Nine patients reported late symptoms that may be related to COVID-19. There were no deaths, and a statistical evaluation of the series of COVID-19 patients compared to those who did not present any infectious episode did not identify significant differences regarding the analyzed parameters. CONCLUSION Despite the change in CD status in three patients and the presence of nine patients with late symptoms, we can conclude that there was no significant adverse impact concerning COVID-19 in the evaluated patients who underwent HSCT to treat CD.

Efficacy of vedolizumab during intravenous induction therapy in ulcerative colitis and Crohn's disease: post hoc analysis of patient-reported outcomes from the VISIBLE 1 and 2 studies.

Vedolizumab is an anti-α4β7 integrin antibody used to treat moderate to severe ulcerative colitis (UC) and Crohn's disease (CD). This post hoc analysis of patient-reported outcomes (PROs) from the VISIBLE 1 (NCT02611830) and 2 (NCT02611817) phase 3 studies evaluated onset of treatment effect on patient-reported symptoms during 6-week vedolizumab induction. Patient-reported stool frequency (SF) and rectal bleeding (RB) (UC Mayo score), and SF and abdominal pain (AP) in CD were collected via electronic diary from VISIBLE patients receiving one or more open-label intravenous (IV) vedolizumab induction doses (weeks 0 and 2). PRO data were analyzed using descriptive statistics. Data from 994 patients (UC 383, CD 611) showed mean ratings for all PROs declined consistently week-on-week from baseline through week 6, with early onset of improvement. By week 2, 22% of patients with UC reported RB improvement (≥1-point reduction in RB subscore, 7-day mean), rising to 45% by week 6. By week 6, 18% of patients with UC achieved SF improvement (SF subscore 0; 21% antitumor necrosis factor alpha [anti-TNFα] naive, 13% anti-TNFα experienced). SF improvement in patients with CD (reduction of ≥3 stools, 7-day mean) was achieved by 32% at week 6 (34% anti-TNFα naive, 30% anti-TNFα experienced). Fewer patients with CD reported severe/moderate AP at week 6 (5.1%/28.5%) than baseline (14.6%/61.5%). SF decline appeared greater and faster for anti-TNFα-naive vs. anti-TNFα-experienced patients (UC and CD). Results indicate early onset of patient-reported UC and CD symptom improvement during vedolizumab IV induction in VISIBLE 1 and 2.

The Crohn's Disease-Health Index: Development and Evaluation of a Novel Outcome Measure.

We sought to develop and validate the Crohn's Disease-Health Index (CD-HI), a disease-specific, patient-reported outcome measure that serially measures Crohn's disease (CD) symptomatic burden in adults with CD. As therapeutic interventions are tested among patients with CD, responsive outcome measures are needed to track disease progression and therapeutic gain during clinical trials. We conducted a national cross-sectional study of individuals with CD to identify the most prevalent and impactful symptoms of CD. The most relevant symptoms were included in the CD-HI. We used factor analysis, qualitative patient interviews, test-retest reliability evaluation, and known group validity testing to evaluate and optimize the CD-HI. The CD-HI contains 12 subscales that comprehensively measure CD burden using the patient's perspective. Fifteen adults with CD beta tested the CD-HI and found the instrument to be clear, easy to use, and relevant to them. Twenty-three adults with CD participated in an assessment of test-retest reliability, which indicated high reliability of individual questions, subscales, and the full instrument (intraclass correlation coefficient = 0.84 for the full instrument). The CD-HI and its subscales demonstrated a high internal consistency (Cronbach α = 0.98 for the full instrument). The CD-HI distinguished between groups of individuals with CD known to differ in disease severity. This research supports the use of the CD-HI as a valid, sensitive, reliable, and relevant patient-reported outcome to determine the multifactorial disease burden of those with CD, assess the relevance and merit of future CD therapies, and support drug labeling claims.

P302 Diagnostic Delayed is Associated with a Poor Prognosis in Patients with Crohn's Disease

Abstract Background The studies show that diagnostic delay, especially in Crohn’s disease (CD), is associated with a higher risk of complications and major surgery. We aimed to investigate timing of the diagnostic delay (DD) and its impact on the CD outcomes. Methods We retrospectively evaluated demographic and clinical features of CD patients between June 1993 and October 2023. Diagnostic delay was defined as the time interval from the onset of the first symptoms to the making of the CD diagnosis. The first CD related symptoms were evaluated by a review of the physician’s notes and medical record. Specific symptoms of CD included chronic or recurrent bloody or non-bloody diarrhea, and/or abdominal pain accompanied by noticeable weight loss, general weakness, and fever. Results 514 patients with CD were included in the study. The median age of disease onset was 34.14 years (16–84 years). Male sex was 299 (58.2%). DD was detected median 13 months (5-47) (14 months in male and 12 months in female). DD was 12 months for diseases with onsets before the age of 40 and 15 months for diseases with onsets after the age of 40. DD was 25 months in isolated ileal involvement, in terminal ileal involvement was 21.5 months, ileo-colonic involvement was 20 months, and colonic location was 10 months. Ileal involvement was found to have a longer duration for DD than colonic involvement. Compared to stenosing behavior (20 months) and penetrating behavior (17 months), DD was shorter in non-stenosing non-penetrating behavior (12 months). DD was longer in perianal disease (18 months) than in those without (12 months). Current smokers had a longer duration of the DD (20 months) compared to non-smokers (11.5 months) and ex-smokers (10 months). The duration of DD (18 months) was longer in CD patients with extraintestinal manifestations than in those without (12 months). Regarding the biological treatment, CD patients who experienced multiple biologics and resistance had longer DD (24 months) than those who experienced biologic monotherapy and responded (12 months). Compared to patients who had not had surgery (12 months), DD was longer in CD patients who had undergone surgery (15 months). Conclusion Our study showed that ileal involvement, stenosing-penetrating behavior, perianal disease, current smoking and existing extraintestinal manifestations were connected with DD. DD was also associated with multiple biologic needed and surgery. DD may have a role a significantly increased risk of bowel damage.

Allogeneic bone marrow transplantation for patients with treatment-refractory Crohn's Disease

Background & aimsDurable remissions of Crohn's Disease (CD) have followed myeloablative conditioning therapy and allogeneic marrow transplantation. For patients with treatment-refractory disease, we used reduced-intensity conditioning to minimize toxicity, marrow from donors with low Polygenic Risk Scores for CD as cell sources, and protracted immune suppression to lower the risk of graft-versus-host disease (GVHD). Our aim was to achieve durable CD remissions while minimizing transplant-related complications. MethodsDNA from patients and their HLA-matched unrelated donors was genotyped and Polygenic Risk Scores calculated. Donor marrow was infused following non-myeloablative conditioning. Patient symptoms and endoscopic findings were documented at intervals after transplant. ResultsWe screened 807 patients, 143 of whom met eligibility criteria; 2 patients received allografts. Patient 1 had multiple complications and died at day 332 from respiratory failure. Patient 2 had resolution of CD symptoms until day 178 when CD recurred, associated with persistent host chimerism in both peripheral blood and intestinal mucosa. Withdrawal of immune suppression was followed by dominant donor immune chimerism in peripheral blood and resolution of CD findings. Over time, mucosal T-cells became donor-dominant. At 5 years after allografting, Patient 2 remained off all medications but had mild symptoms related to a jejunal stricture that required stricturoplasty at 6 years. At 8 years, she remains stable off medications. ConclusionsThe kinetics of immunologic chimerism after allogeneic marrow transplantation for CD patients depends on the intensity of the conditioning regimen and the magnitude of immune suppression. One patient achieved durable improvement of her previously refractory CD only after establishing donor immunologic chimerism in intestinal mucosa. Her course provides proof-of-principal for allografting as a potential treatment for refractory CD, but an immunoablative conditioning regimen should be considered for future studies.(ClinicalTrials.gov, NCT01570348)

Creeping fat exhibits distinct Inflammation-specific adipogenic preadipocytes in Crohn's disease.

Creeping fat (CrF) is an extraintestinal manifestation observed in patients with Crohn's disease (CD). It is characterized by the accumulation of mesenteric adipose tissue (MAT) that wraps around the intestinal wall. Although the role of CrF in CD is still debated, multiple studies have highlighted a correlation between CrF and inflammation, as well as fibrostenosais of the intestine, which contributes to the worsening of CD symptoms. However, the mechanism underlying the potential role of CrF in the development of Crohn's fibrosis remains an enigma. This study aimed to analyze CrF comprehensively using single-cell RNA sequencing analysis. The data was compared with transcriptomic data from adipose tissue in other disease conditions, such as ulcerative colitis, lymphedema, and obesity. Our analysis classified two lineages of preadipocyte (PAC) clusters responsible for adipogenesis and fibrosis in CrF. Committed PACs in CrF showed increased cytokine expression in response to bacterial stimuli, potentially worsening inflammation in patients with CD. We also observed an increase in fibrotic activity in PAC clusters in CrF. Co-analyzing the data from patients with lymphedema, we found that pro-fibrotic PACs featured upregulated pentraxin-3 expression, suggesting a potential target for the treatment of fibrosis in CrF. Furthermore, PACs in CrF exhibited a distinct increase in cell-to-cell communication via cytokines related to inflammation and fibrosis, such as CCL, LIGHT, PDGF, MIF, and SEMA3. Interestingly, these interactions also increased in PACs of the lymphedema, whereas the increased MIF signal of PACs was found to be a distinct characteristic of CrF. In immune cell clusters in CrF, we observed high immune activity of pro-inflammatory macrophages, antigen-presenting macrophages, B cells, and IgG+ plasma cells. Finally, we have demonstrated elevated IgG+ plasma cell infiltration and increased pentraxin-3 protein levels in the fibrotic regions of CrF in CD patients when compared to MAT from both UC patients and healthy individuals. These findings provide new insights into the transcriptomic features related to the inflammation of cells in CrF and suggest potential targets for attenuating fibrosis in CD.

The Role of Chronic Fatigue in Patients with Crohn's Disease.

Crohn's disease (CD) is a chronic, relapsing disorder belonging to inflammatory bowel diseases (IBD). It is manifested by relapsing transmural inflammation found in any segment of the gastrointestinal tract. Chronic fatigue is a common and underrecognized symptom of CD for which the prevalence is much higher in the population of CD patients compared to the healthy population. It stems from an intricate web of interactions between various risk factors, and its pathophysiology is still not fully understood. The implementation of routine screening and a holistic, multidisciplinary approach involving psychological support may be crucial in the management of CD patients with chronic fatigue. There is currently no single intervention aimed at decreasing fatigue alone, and its treatment is especially difficult in patients with fatigue persisting despite clinical and endoscopic remission. Extensive research is still needed in order to be able to predict, prevent, identify, and ultimately treat fatigue associated with CD. The aim of this review is to summarize the knowledge on the etiology, diagnosis, and treatment of chronic fatigue in CD patients.

Network pharmacology and molecular docking reveal the mechanism of Qinghua Xiaoyong Formula in Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory illness of the digestive system with unknown etiology, and its incidence is increasing worldwide. However, there are currently no effective treatments or medications available for individuals with CD. Therefore, novel therapeutic strategies are urgently needed. The bioactive compounds and targets associated with compounds of Qinghua Xiaoyong Formula (QHXYF) were examined using The Traditional Chinese Medicine Systems Pharmacology database, and 5 disease target databases were also used to identify CD-related disease targets. A total of 166 overlapping targets were identified from QHXYF-related and CD-related disease targets and they were found to be enriched in oxidative stress-related pathways and the PI3K/AKT signaling pathway. Molecular docking was then used to predict how the bioactive compounds would bind to the hub targets. It was found that quercetin could be the core bioactive compound and had good binding affinity to the top 5 hub targets. Finally, animal experiments were performed to further validate the findings, and the results revealed that QHXYF or quercetin inhibited 2,4,6-trinitrobenzenesulfonic acid-induced inflammation and oxidative stress processes by inhibiting the PI3K/AKT pathway, thereby improving CD symptoms. These findings suggest that QHXYF and quercetin may be potential novel treatments for CD.

DietaAnti-Inflamatoria or DAIN: A Crohn's disease management strategy tailored for Puerto Ricans

Diet has been increasingly shown to be of therapeutic benefit for patients with inflammatory bowel diseases (IBD), especially Crohn's disease (CD). Yet dietary guidelines are nonexistent. Moreover, diets tailored to Puerto Ricans with IBD living on the island, have not been developed and tested. The rising prevalence of IBD in Puerto Rico warrants exploring the use of diet as part of the treatment strategies for these patients [1]. Here, we describe the study design of “Dieta Anti-Inflamatoria” or DAIN, a parallel two-arm randomized pilot trial aiming at testing the efficacy of IBD-Anti-inflammatory diet (IBD-AID) adapted for adults with CD living in Puerto Rico (clinical trial registration number: NCT05627128). We tailored the IBD-AID to the local cuisine preferences and food availability by creating and adapting recipes consistent with the IBD-AID principles [2,3]. In focus groups with a Community Research Advisory Panel and one-on-one consultations with implementation experts, we identified several aspects of the intervention to adapt before the implementation. The objectives of the stakeholder/expert-informed adaptation were to improve feasibility and compliance while developing the culturally tailored dietary intervention. DAIN was designed for adults living in Puerto Rico with CD and geared to be affordable, appropriate, and acceptable for patients with mild-to-moderate CD. The significance of this work is the validation of culturally appropriate nutritional guidelines to help manage CD symptoms. DAIN provides a blueprint for a comprehensive nutritional program that can be adapted to regional preferences and local food availability allowing wider implementation of diet as an adjunct treatment in diverse clinical settings.

P265 Evaluation of the quality-of-care parameters in patients with inflammatory bowel disease in Brazilian hospitals

Abstract Background There are few data on the quality-of-care for inflammatory bowel disease (IBD) in public, private or mixed hospitals, especially in Latin America. The aim of the study was to evaluated clinic and quality parameters and their association with need for ICU and death in Brazilian hospitals. Methods This was a multicentre study carried out in 26 hospitals. Four hundred eighty-eight admissions of patients with IBD were analysed between June 2021 and October 2022. Results The median stay length was 6 days (0–121). The median age was 38 years (16–87), and 265 (54.6%) were female. Three hundred and thirty-nine patients (69.5%) had Crohn’s disease (CD) and 149 (30.5%) ulcerative colitis (UC). The median time between symptoms onset and hospital admission was 72 months (1-504) in CD and 49 months (1-300) in UC. In the CD group, there was structural damage in 248 cases (73.2%). UC in pancolitis form was seen in 97 (66%). The Charlson Comorbidity Index (CCI) was scored at least at one point in 182 records (37.3%), and the median was 2 (1-17). Three hundred-seven admissions (62.9%) were urgent, and 208 cases (42.6%) remained in the emergency room (ER) for 2 days (1-22). Disease activity and structural damage accounted for 58.6% of admissions. One-hundred and eighty-three surgeries were performed (37.5%), and 35 (18.1%) postoperative complications were reported. The most prescribed drugs were biologicals (52.8%) before admission and corticosteroids during hospitalization (37.3%). Red days were verified in 45.3%. Intensive care unit (ICU) admission was required in 55 cases (11.3%). One hundred and nine (22.3%) bacterial infections were registered. There were 16 deaths (3.3%), and the main cause was sepsis (37.5%). Surgery, infection, duration of CD symptoms, and CCI were associated with the need for ICU (p= 0.000; 0.000; 0.043; 0.014, respectively). The CCI of 1 best predicted the need for ICU (AUROC 0.588; S 52.7%, E 64.7%). Infection, age, days in the ER, ICU, and CCI were associated with death (p= 0.004; 0.022; 0.006; 0.000; 0.000, respectively). The CCI of 1 is also the best predicted death (AUROC 0.782; S 81.3%, E 64.2%). The need to stay in ER and red days were lower in private and mixed hospitals (p= 0.000). Infection and death rates were similar (p= 0.323). Conclusion A sample with complications associated with IBD but with low CCI due to their younger age was characterized. The majority had CD, and more than 60% of admissions were urgent. The CCI accuracy in predicting ICU and death was obtained. A system deficiency was more evidenced in public hospitals in the rate of individuals who remained in ER. From the red days, greater problem-solving agility was found in private and mixed hospitals.

Moxibustion improves experimental colitis in rats with Crohn’s disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor

ObjectiveThis study was conducted to explore the mechanism of intestinal inflammation and barrier repair in Crohn’s disease (CD) regulated by moxibustion through bile acid (BA) enterohepatic circulation and intestinal farnesoid X receptor (FXR). MethodsSprague-Dawley rats were randomly divided into control group, CD model group, mild moxibustion group and herb-partitioned moxibustion group. CD model rats induced by 2,4,6-trinitrobenzene sulfonic acid were treated with mild moxibustion or herb-partitioned moxibustion at Tianshu (ST25) and Qihai (CV6). The changes in CD symptoms were rated according to the disease activity index score, the serum and colon tissues of rats were collected, and the pathological changes in colon tissues were observed via histopathology. Western blot, immunohistochemistry (IHC) and immunofluorescence were used to evaluate the improvement of moxibustion on intestinal inflammation and mucosal barrier in CD by the BA-FXR pathway. ResultsMild moxibustion and herb-partitioned moxibustion improved the symptoms of CD, inhibited inflammation and repaired mucosal damage to the colon in CD rats. Meanwhile, moxibustion could improve the abnormal expression of BA in the colon, liver and serum, downregulate the expression of interferon-γ and upregulate the expression of FXR mRNA, and inhibit Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) mRNA. The IHC results showed that moxibustion could upregulate the expression of FXR and mucin2 and inhibit TLR4 expression. Western blot showed that moxibustion inhibited the protein expression of TLR4 and MyD88 and upregulated the expression of FXR. Immunofluorescence image analysis showed that moxibustion increased the colocalization sites and intensity of FXR with TLR4 or nuclear factor-κB p65. In particular, herb-partitioned moxibustion has more advantages in improving BA and upregulating FXR and TLR4 in the colon. ConclusionMild moxibustion and herb-partitioned moxibustion can improve CD by regulating the enterohepatic circulation stability of BA, activating colonic FXR, regulating the TLR4/MyD88 pathway, inhibiting intestinal inflammation and repairing the intestinal mucosal barrier. Herb-partitioned moxibustion seems to have more advantages in regulating BA enterohepatic circulation and FXR activation.Please cite this article as: Shen JC, Qi Q, Han D, Lu Y, Huang R, Zhu Y, Zhang LS, Qin XD, Zhang F, Wu HG, Liu HR. Moxibustion improves experimental colitis in rats with Crohn’s disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor. J Integr Med. 2023; 21(2): 194–204.

Management of Pelvic Pain in Patients with Crohn's Disease-Current Overview.

Crohn's disease (CD) is a subtype of chronic inflammatory bowel diseases (IBD) with characteristic skip lesions and transmural inflammation that may affect the entire gastrointestinal tract from the mouth to the anus. Persistent pain is one of the main symptoms of CD. This pain has multifactorial pathogenesis, but most often arises from intestinal inflammation itself, as well as from gut distention or partial intestinal obstruction. Some current evidence also suggests sensitization of sensory pathways, as well as modulation of those signals by the central nervous system, which highlights the impact of biopsychosocial factors. To date, most studies have focused only on the pain located in the abdomen, while pelvic pain has rarely been explored, despite it being a common symptom. The aim of this study is to provide an abbreviated summary of the current state of knowledge on the origins and treatment of pelvic pain in CD.

Acupuncture for Crohn’s disease: protocol for a systematic review and meta-analysis of randomized clinical trials

Crohn's disease (CD) is a chronic recurrent gastrointestinal disorder with a high incidence of inflammation due to intestinal inflammation. Acupuncture is commonly used as an alternative therapy for patients with CD. The aim of this study was to design a systematic review and meta-analysis protocol, to provide guidance for the establishment of systematic evaluation and meta-analysis on the efficacy and safety of acupuncture on CD. We will search PubMed, the Cochrane Library, Embase, Web of Science, and 4 Chinese databases: China National Knowledge Infrastructure (CNKI), Wanfang database, VIP database, and Chinese Biomedical Database to obtain randomized controlled trials of CD treated with acupuncture from inception to November 5, 2022. Primary outcome include CD symptoms severity and clinical efficacy, secondary outcome indicators include laboratory indicators or inflammatory markers, severity of endoscopic lesions, quality of life, and safety outcomes. We will analyze the data using RevMan V.5.4 software. Two reviewers will assess the risk of bias and study quality by the Cochrane Collaboration Risk of Bias Tool and GRADE methods, respectively. This systematic review and meta-analysis protocol will analyze the efficacy, symptom improvement, quality of life, and safety of acupuncture therapy for CD. This protocol outlines the planned scope and methodology of a forthcoming systematic review and meta-analysis to provide guidelines for a rigorous assessment of the efficacy and safety of acupuncture for the treatment of CD.

Principles for Assessing Quality of Life in Patients With Crohn's Disease.

Crohn's disease (CD) is a lifelong inflammatory bowel disease that can severely impact quality of life. Many questionnaires exist to assess quality of life for patients with CD, but some of these questionnaires were developed without qualitative data from patients or include only limited symptoms. Patient-Reported Impact of Symptoms in CD provides an innovative and patient-centered framework for assessing quality of life in patients with CD, soliciting qualitative data from patient interviews, and using this to guide a cross-sectional study. Their findings should inform how clinicians guide conversations with their patients regarding quality of life.

Plain Language Summary of the VOLTAIRE-CD Study in People with Moderately to Severely Active Crohn’s Disease

This is a summary of the VOLTAIRE-CD study originally published in The Lancet Gastroenterology and Hepatology. BI 695501 is a medicine being developed to treat people with moderately to severely active Crohn's disease, a chronic inflammatory condition that usually affects the small bowel and colon. BI 695501 is a biosimilar, which means that it is designed to be highly similar to the original drug. The VOLTAIRE-CD study aimed to show whether BI 695501 is just as effective and safe as the original drug, adalimumab (Humira®) in treating Crohn's disease. Participants in the VOLTAIRE-CD study took either the original adalimumab product for 24weeks followed by BI 695501 for the next 22weeks, or just the biosimilar BI 695501 for the entire 46-week treatment period. Similar improvements in Crohn's disease symptoms and the number of participants with side effects were similar, regardless of whether they received the original drug or BI 695501. These results show that both drugs could be used in the treatment of people with Crohn's disease, with similar efficacy and safety.

Granulomatous tracheo-bronchitis from Crohn's disease.

Tracheo-bronchitis is an uncommon but important extra-intestinal manifestation of Crohn's disease. Our case demonstrates radiological and bronchoscopic evidence of tracheo-bronchitis secondary to Crohn's disease with pathology-proven granulomatous inflammation. This case highlights the importance of investigating airway involvement in patients with Crohn's disease and new respiratory symptoms.