Search

Biological agents known as anti-tumor necrosis factor (TNF) drugs are frequently utilized in the treatment of inflammatory bowel disease (IBD). In this study, we analyzed the shared processes of pyroptosis in Ulcerative colitis (UC) and Crohn's disease (CD), as well as explored the correlation between the burden of pyroptosis and the results of anti-TNF treatment based on bioinformatics analyses. We identified CAPS1, CASP5, GSDMD, AIM2, and NLRP3 as the hub genes, with AIM2 being the most effective indicator for predicting the response to anti-TNF therapy. We also noticed that non-responders received anti-TNF therapy exhibited elevated AIM2 protein expression. Subsequently, we conducted a cluster analysis based on AIM2-inflammasome-related genes and discovered that patients with a higher burden of AIM2 inflammasome displayed stronger immune function and a poor response to anti-TNF therapy. Overall, our study elucidates the pathway of pyroptosis in IBD and reveals AIM2 expression level as a potential biomarker for predicting the effectiveness of anti-TNF therapy., (© 2023. Springer Nature Limited.)

There is great heterogeneity among inflammatory bowel disease (IBD) patients in terms of pathogenesis, clinical manifestation, response to treatment, and prognosis, which requires the individualized and precision management of patients. Many studies have focused on prediction biomarkers and models for assessing IBD disease type, activity, severity, and prognosis. During the era of biologics, how to predict the response and side effects of patients to different treatments and how to quickly recognize the loss of response have also become important topics. Multiomics is a promising area for investigating the complex network of IBD pathogenesis. Integrating numerous amounts of data requires the use of artificial intelligence., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To explore the diagnostic value of different serological markers and the correlation with disease phenotype in inflammatory bowel disease (IBD). Methods: The clinical data of 445 IBD patients in Peking Union Medical College Hospital from June 2010 to December 2020 were retrospectively collected, including 223 cases of ulcerative colitis (UC) [111 males, 112 females, with a median age of 46(20,79) years] and 222 cases of Crohn's disease (CD) [147 males, 75 females, with a median age of 39 (19, 72) years]. The positive rates of serum anti-neutrophil cytoplasmic antibodies (ANCA), anti-Saccharomyces cerevisiae antibodies (ASCA), goblet cell autoantibodies (GAB) and pancreatic autoantibodies (PAB) in the two groups were analyzed. The sensitivity, specificity, positive predictive value and negative predictive value of UC and CD were calculated. Logistic regression was performed to analyze the relationship between different combinations of antibodies and disease phenotype. Results: The positive rates of ASCA and PAB in CD patients were 34.7% (77/222) and 38.3% (85/222), respectively, which were higher than those in UC patients [10.3% (23/223) and 4.5% (10/223), P <0.001]. The positive rate of ANCA in UC patients was 50.2% (112/223), which was higher than that in CD patients [5.4% (12/222), P <0.001]. The positive rates of serum GAB in CD and UC patients were 21.6% (48/222) and 28.3% (63/223), respectively, with no significant difference ( P =0.760). In patients with CD, the sensitivity of mono-marker ASCA (+), dual-marker ASCA (+) ANCA (-), quadruple-marker ASCA (+) ANCA (-) PAB (+) GAB (-) in diagnosing CD was 34.7%, 32.9%, 20.7%, the specificity was 89.7%, 95.5%, 100.0%, the positive predictive value was 77.0%, 90.1%, 100.0%, and the negative predictive value was 58.0%, 58.7%, 55.9%, respectively. In patients with UC, the sensitivity of mono-marker ANCA (+), dual-marker ANCA (+) ASCA (-), quadruple-marker ANCA (+) ASCA (-) PAB (-) GAB (+) in diagnosing UC was 50.2%, 40.4%, 24.2%, the specificity was 94.6%, 95.5%, 100.0%, the positive predictive value was 90.3%, 90.0%, 100.0%, and the negative predictive value was 65.4%, 61.4%, 56.8%, respectively. Mono-marker ASCA (+) ( OR =3.39, 95% CI : 1.59-7.21), dual-marker ASCA (+) ANCA (-) ( OR =2.87, 95% CI : 1.34-6.14), triple-marker ASCA (+) ANCA (-) GAB (-) ( OR =3.09, 95% CI : 1.31-7.31) and quadruple-marker ASCA (+) ANCA (-) PAB (+) GAB (-) ( OR =3.15, 95% CI : 1.56-8.03) were associated with stenosis and/or penetrating type CD. The mono-marker ANCA (+) ( OR =2.69, 95% CI : 1.42-5.12) and dual-marker ANCA (+) ASCA (-) ( OR =2.11, 95% CI : 1.03-4.16) were associated with extensive colonic lesions in UC. Conclusion: Based on ASCA or ANCA, the combination with PAB or GAB, is conducive to IBD diagnosis, and is associated with stenosis and/or penetrating type of CD and extensive type of UC.

Objective: To evaluate the short-term efficacy and safety of vedolizumab in patients with inflammatory bowel disease (IBD). Methods: Patients with moderate and severe active IBD at the first use of vedolizumab from May 1 to October 31, 2021 were retrospectively enrolled. Then the clinical characteristics, and the efficacy and safety of vedolizumab were evaluated. Meanwhile, the clinical response rate, biological response rate and endoscopic response rate were calculated. Multivariate analysis was used to evaluate the independent influencing factors of short-term clinical efficacy and safety. Results: A total of 78 patients (44 males and 34 females) with IBD were enrolled, with a mean age of (40.5±11.9) years. The clinical remission rate, clinical response rate, biological remission rate, biological response rate and endoscopic remission rate was 60.3% (47/78), 85.9% (67/78), 70.5% (55/78), 43.6% (34/78) and 47.0% (31/66) respectively after 14 weeks of treatment. Body mass index (BMI) ≥ 18.5 kg/m 2 ( HR =5.04, 95% CI : 1.50-16.91, P =0.009) and biological remission at 6 weeks of treatment ( HR =15.22, 95% CI : 3.16-73.38, P =0.001) were predictors of endoscopic remission at 14 weeks of treatment. Adverse reactions occurred in 57 patients, with an incidence of 73.1%. The main manifestations were liver and kidney damage (37.2%) and infection (26.9%). Conclusions: More than half of patients with moderate and severe active IBD can achieve clinical remission after 14 weeks of vedolizumab treatment. Baseline BMI level and biological remission at 6 weeks of treatment are predictors of mucosal healing at 14 weeks. The incidence of adverse reactions is not low, although serious adverse reactions are rare in short-term treatment.

Background/aims: Opportunistic infection in inflammatory bowel disease (IBD) has become a serious problem. However, its status of doctors' opinions and test equipment in hospitals are unclear. The aim of the study was to investigate these issues to improve the prognosis of IBD patients., Methods: This retrospective, multicenter study was conducted by 83 investigators who were members of the Asian Organization for Crohn's and Colitis. Data on opportunistic infection were collected from hospital databases between January 2017 and December 2017. The survey consisted of 11 items., Results: Most physicians appreciated the diagnostic value of tissue cytomegalovirus (CMV) DNA, accounting for 86.1% of members in China, 37.5% in Japan, 52.9% in South Korea, and 66.7% in Southeast Asia. Only 83.1% of hospitals had the ability to test for CMV immunohistochemistry in Asia. Hepatitis B surface antigen (HBsAg) screening was recommended by all members. However, only 66.7% in China, 70.6% in South Korea, and 66.7% in Southeast Asia agreed to routinely vaccinate IBD patients when HBsAg tested negative. Most members preferred metronidazole (74.7%) as the first choice for patients with Clostridium difficile infection. However, the proportion of stool C. difficile toxin test was lower in China than in other areas (75.0% in China vs 95.8% in Japan and 100% in South Korea and Southeast Asia, p<0.05)., Conclusions: Opportunistic infection from CMV, hepatitis B virus, and C. difficile should be of high concern for IBD patients. More efforts are needed, such as understanding consensus in clinical practice and improving testing facilities in hospitals.

Background: This systematic review and meta-analysis aims to evaluate efficacy and safety of endoscopic treatment for the non-polypoid dysplasia in patients with long-standing IBD., Methods: Medline, Embase, Cochrane, and clinicaltrials.gov registry were comprehensively searched. Pooled estimates of curative, R0, en-bloc resection rates, CRC, metachronous dysplasia, and local recurrence rates were calculated. Subgroup analysis according to areas, lesion size, endoscopic resection techniques, and grades of dysplasia were conducted. Data synthesis was completed in R using the package "meta"., Results: Of the 973 studies initially identified, 7 met the inclusion/exclusion criteria. These were all single-arm cohorts and included a total of 202 patients with IBD and non-polypoid dysplasia. The combined R0 and en-bloc resection rate were 0.70 (95% CI 0.55-0.81) and 0.86 (95% CI 0.65-0.95), respectively, with a recurrence rate of 0.08 (95% CI 0.05-0.13). CRC and metachronous dysplasia incidences were pooled as 32.53 (95% CI 12.21-86.67) and 90.24 (95% CI 44.91-181.33) per 1000 patient years., Conclusions: Non-polypoid dysplasia associated with IBD can be resected endoscopically, especially by ESD. However, these patients have higher CRC and metachronous dysplasia incidence rates than patients with polypoid dysplasia, indicating a closer endoscopic surveillance.

Objective: To determine the clinical features and genetic characters of patients with chronic enteropathy associated SLCO2A1 gene (CEAS). Methods: Five CEAS patients diagnosed at Peking Union Medical College Hospital from January 2012 to December 2019 were enrolled in this study. The clinical manifestations, laboratory test, radiological and endoscopic findings, gene detections, treatments and prognosis of these patients were reviewed and analyzed. Results: Five male patients presented gastrointestinal symptoms after puberty, including abdominal pain, diarrhea, intermittent melena or hematochezia, incomplete bowel obstruction, anemia, hypoalbuminemia and hypokalemia. The whole gastrointestinal tract except esophagus could be involved, especially the stomach and ileum. Intestinal lesions were characterized by multiple shallow ulcers with stenosis in the layers of mucosa and submucosa. Five patients were all accompanied with primary hypertrophic osteoarthropathy (PHO), and 1 with myelofibrosis and thoracic duct dysplasia. All patients were homozygous or compound heterozygous mutations of SLCO2A1 gene. Conventional treatment of inflammatory bowel disease and COX-2 inhibitors were ineffective. Conclusions: CEAS is an autosomal recessive genetic disease which widely involves the gastrointestinal tract, and can be associated with skin and bone involvement. There is no effective treatment for CEAS at present. CEAS is a different entity from other inflammatory gastrointestinal diseases.

Objective To investigate the correlation between serum total 25-hydroxyvitamin D[T-25(OH)D]level and fecal microbiota in patients with inflammatory bowel disease(IBD). Methods Twenty-three patients with IBD completed the tests for serum T-25(OH)D,and the fecal microbiota was studied using V4 hypervariable region of 16S ribosomal RNA(rRNA)gene sequencing.According to serum T-25(OH)D level,the patients were divided into three groups including vitamin D normal group( n =5),vitamin D insufficiency group( n =5),and vitamin D deficiency group( n =13). Results There was no significant difference between these three groups in Alpha diversity or Beta diversity.Ternary pot at phylum level revealed that the abundance of Proteobacteria was the highest in the vitamin D deficiency group and Actinomycete was the highest in the vitamin D sufficiency group.Spearman correlation analysis showed that at the phylum level serum T-25(OH)D level was negatively correlated with the abundance of Proteobacteria ( r =-0.445, P =0.033)and positively correlated with the abundance of Actinomycetes ( r =0.447, P =0.033);at family level it was positively correlated with the abundance of Lachnospiraceae ( r =0.414, P =0.049), Bifidobacteriaceae ( r =0.468, P =0.024), Erysipelotrichacea ( r =0.584, P =0.003),and Eggerthellaceae ( r =0.507, P =0.014)and negatively correlated with the abundance of Aerococcaceae ( r =-0.514, P =0.012);and at genus level it was positively correlated with the abundance of Blautia ( r =0.459, P =0.028), Bifidobacterium ( r =0.468, P =0.024),unidentified Erysipelotrichacea ( r =0.485, P =0.019), Faecalitalea ( r =0.544, P =0.007), Anaerostipes ( r =0.475, P =0.022), Romboutsia ( r =0.510, P =0.013), Flavonifractor ( r =0.455, P =0.029),and Erysipelatoclostridium ( r =0.617, P =0.002). Conclusions The fecal microbiota composition varies in IBD patients with different serum T-25(OH)D levels.The abundance of Proteobacteria increases and the abundance of Actinomyces decreases in IBD patients with vitamin D deficiency compared with IBD patients with normal vitamin D level.Serum T-25(OH)D level is negatively correlated with the abundance of some harmful bacteria(e.g. Proteobacteria )but is positively correlated with the abundance of some probiotics such as Lachnospiraceae , Bifidobacteriaceae ,and Anaerostipes .

Purpose: Inflammatory bowel disease (IBD) is an important risk factor for colon cancer. Novel serum immunoinflammation-related protein complexes (IIRPCs) have shown associations with early cancer detection. Herein, we investigated the potential of serum IIRPCs for discriminating between IBD and colorectal cancer (CRC) patients., Methods: Serum protein complexes of 65 healthy controls, 57 CRC, 69 (ulcerative colitis) UC, and 67 (Crohn's disease) CD patients were isolated by native-PAGE. The gray values of serum IIRPCs bands in the gel were quantified using Quantity One software. The receiver-operating characteristic (ROC) curves were constructed to assess the discriminating ability by calculating the area under the ROC curve., Results: The serum IIRPCs levels in IBD and CRC patients were significantly elevated compared to healthy controls. ROC analysis indicated certain diagnostic ability of serum IIRPCs in differentiating IBD from CRC. Specifically, "a3" complex discriminated UC from CRC, with an AUC value of 0.722, sensitivity of 69.4% and specificity of 63.8%. Similarly, "b4" complex discriminated UC from CRC, with an AUC value of 0.709, sensitivity of 70.4%, and specificity of 60.0%. In addition, the "a3" complex also discriminated CD from CRC, with an AUC value of 0.785, sensitivity of 73.1%, and specificity of 74.1%, while the "b4" complex showed a tendency to discriminate CD from CRC, with an AUC value of 0.663, sensitivity of 67.9% and specificity of 50.0%. Thus, an equation based on multiple IIRPCs was built to further improve the discriminating power., Conclusions: Serum IIRPCs can be used to discriminate IBD from CRC and may also be associated with early screening of colitis-associated cancer.

Background: Colorectal cancer (CRC) has become one of the major life-threatening complications in patients with inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). This study aimed to explore the clinical-pathologic similarities and differences in the IBD-associated CRC (IBD-CRC) between patients in China and Canada., Methods: Data of 78 patients with IBD-CRC retrospectively retrieved from two representative medical institutions in Beijing (China) and Calgary (Canada) over the same past 13 years, including 25 (22 UC-associated and three CD-associated) from Beijing group and 53 (32 UC-associated and 21 CD-associated) from Calgary group, were compared with regards to their clinical and pathologic characteristics., Results: Several known features of IBD-CRC were seen in both groups, including long duration and large extent of colitis, active inflammation background, multifocal lesions, and advanced tumor-node-metastasis stage. Beijing group showed a significantly higher percentage of UC (88.0% vs. 60.4%, P = 0.018), younger age at diagnosis of CRC (48.6 ± 12.8 years vs. 61.6 ± 14.7 years, P < 0.001), lower ratio of mucinous adenocarcinoma (7.1% vs. 42.4%, P = 0.001) compared with Calgary group. None of the Beijing group had concurrent primary sclerosing cholangitis, while 5.7% of Calgary group did. Surveillance colonoscopy favored the detection rate of precancerous lesions (41.4% vs.17.0%, P = 0.002)., Conclusions: As compared with patients from the Calgary group, the IBD-CRC patients in Beijing group were younger, less CD-associated and had less mucinous features, otherwise they were similar in many common features.

Objective To investigate the clinical features of patients with inflammatory bowel disease (IBD) complicated with Pneumocystis Jiroveci Pneumonia (PJP). Methods We retrospectively analyzed the clinical data of 5 patients who were hospitalized in Peking Union Medical College Hospital from January 2012 to July 2017 for treatment of IBD complicated with PJP. Demographic characteristics,clinical manifestations,treatments,and outcomes were descriptively analyzed. Results Of these five patients,four had ulcerative colitis (UC) and one had Crohn's disease (CD). All patients were males,with an average age of (61.8±1.9) years. All patients were in active disease status and had symptoms including cough and suffocation. Three patients had hypoxemia,among whom two developed type 1 respiratory failure. Three patients were treated with immunosuppressive medications (corticosteroids and/or immunosuppressant drugs) before the diagnosis of PJP. Lymphocyte counts in three patients were less than 0.6×10 9 /L. CD4+T cells in two patients were less than 200×10 6 /L. Four patients had elevated serum cytomegalovirus DNA. The level of β-D-glucan was elevated in four patients. Chest CT showed bilateral diffuse ground glass opacification. PJP-DNA was positive in sputum or bronchoalveolar lavage fluid in all patients. Two patients with type 1 respiratory failure required invasive mechanical ventilation. All patients received trimethoprim-sulfamethoxazole and methylprednisolone treatment. Four patients recovered completely and one died. Conclusion Elderly (aged>55 years) IBD patients who are receiving immune-suppressive therapy or with decreased peripheral blood lymphocyte count are at higher risk of PJP.

Objective: To assess the necessity and efficacy of vitamin D (VitD) supplementation in Chinese ulcerative colitis (UC) and Crohn's disease (CD) patients with vitamin D insufficiency/deficiency., Methods: UC and CD patients were randomly assigned into one of the three arms for 12 months: arm A (VitD 3 150 000 IU once per 3 months plus elemental calcium 200 mg thrice daily), arm B (elemental calcium 200 mg thrice daily) and arm C (vehicle control group), in addition to conventional treatment. Improvement in 25-hydroxyvitamin D [25(OH)D] level was the primary outcome of the study. Secondary outcomes were changes in bone mineral density (BMD) and disease activity., Results: Sixty-five UC and 59 CD patients completed the study. The difference in the pre-and post-treatment 25(OH)D [Δ25(OH)D] of arm A was significantly higher than in arm B or C (UC: 17.47 ± 13.01 ng/mL vs 5.30 ± 6.28 ng/mL or 2.02 ± 6.19 ng/mL, P < 0.001; CD: 12.47 ± 9.15 ng/mL vs 4.73 ± 6.97 ng/mL or 1.36 ± 4.75 ng/mL, P < 0.01). There was no significant difference between pre- and post-treatment BMD and disease activity in arm A compared to those in arms B and C (P > 0.05). Although the Mayo score and Crohn's disease activity index decreased by conventional treatment, serum 25(OH)D did not improve in arm C without vitamin D supplementation (P > 0.05)., Conclusion: VitD supplementation is necessary to treat hypovitaminosis D in UC and CD patients, even with background amelioration of disease activity., (© 2018 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that is highly associated with inflammatory bowel disease (IBD). Certain PG patients with no systemic disorders have been diagnosed with idiopathic PG. This study sought to clarify the difference between PG with IBD and idiopathic PG based on clinical features, laboratory tests, and medications., Methods: Twelve patients with PG and IBD and 24 patients with idiopathic PG, who were hospitalized in Peking Union Medical College Hospital from 2000 to 2017, were retrospectively categorized into the IBD group and control group, respectively. Data of clinical features, laboratory tests, and medications were collected and compared between the two groups., Results: Both groups were similar with respect to their clinical features. However, the IBD group had an increased occurrence of arthralgia or arthritis (58.3% vs. 12.5%, P = 0.007), anemia (83.3% and 29.2%, P = 0.004), and an increased percentage of antineutrophilic cytoplasmic antibody (ANCA)-positive patients (85.7% and 0.0%, P < 0.001), compared to the control group., Conclusion: PG patients with IBD had increased occurrence rates of arthralgia or arthritis, anemia, and ANCA-positive status compared to idiopathic PG patients.

Objective: We aimed to investigate the serum 25-hydroxyvitamin D3 (25[OH]D3 ) levels and bone metabolism in adult Chinese patients with inflammatory bowel disease (IBD) and to evaluate the correlation between vitamin D levels and the disease activity as well as the potential risk factors., Methods: Age- and gender-matched cohort of IBD patients (124 with ulcerative colitis [UC] and 107 with Crohn's disease [CD]) and 122 healthy controls were enrolled in this study. Serum levels of 25(OH)D3 and bone mineral density (BMD) were measured, and the correlation between the two parameters and the severity of the disease as well as the clinical risk factors were analyzed., Results: Serum 25(OH)D3 levels were lower in UC (10.32 ± 4.46 ng/mL, P < 0.001) and CD patients (11.57 ± 5.02 ng/mL, P = 0.029) than that in healthy controls (12.87 ± 4.40 ng/mL). 25(OH)D3 levels were negatively correlated with the disease severity of both UC (r = -0.371, P < 0.001) and CD (r = -0.285, P = 0.030). The incidences of osteopenia and osteoporosis were high in the IBD patients (37.9% and 3.2% in UC and 30.8% and 4.7% in CD, respectively). Cumulative quantity of glucocorticoids use was significantly associated with osteopenia and osteoporosis in both UC (odds ratio [OR] 1.219, 95% confidence interval [CI] 1.054-1.410, P = 0.008) and CD patients (OR 1.288, 95% CI 1.033-1.606, P = 0.025)., Conclusions: Vitamin D deficiency is likely to occur in Chinese patients with IBD and is closely associated with the severity of the disease. Glucocorticoids accumulation is a risk factor for osteopenia and osteoporosis., (© 2013 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

The efficacy of conventional drug therapy for inflammatory bowel disease (IBD) is not satisfactory. As monoclonal antibody has been widely used and increasingly understood, biological agent therapy has been proved as ideal strategy in attaining mucosal healing, preventing complications, improving quality of life, and reducing hospitalization and surgical intervention. Furthermore, different randomized clinical trials assessed the efficacy in reducing the need for repeat surgery because of recurrence. Besides, biological agent therapy dose not increase most of postoperative side effects such as infection. However, adverse events of biological agents including serious infection, infusion reactions, delay type allergic reaction and myelosuppression should be paid attention to.