The association of three vaccination doses with reduced gastrointestinal symptoms after severe acute respiratory syndrome coronavirus 2 infections in patients with inflammatory bowel disease.

Background: The protective efficacy of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination against the new-onset gastrointestinal (GI) symptoms following COVID-19 infection is critical among patients with inflammatory bowel disease (IBD); however, the optimal protective vaccine dose remains unknown. Therefore, this study aimed to clarify whether there is a correlation between SARS-CoV-2 vaccinations and GI symptoms following Omicron infection in patients with IBD. Methods: We conducted a multicenter cross-sectional study of IBD patients among three tertiary hospitals in eastern China. Professional physicians collected all data using online questionnaires. The patients were stratified into four groups: patients who were unvaccinated and patients who received one, two, or three vaccination doses. The primary outcome was the presence of any new-onset GI symptoms after SARS-CoV-2 infection before a negative SARS-CoV-2 nucleic acid test or a negative self-testing for antigens. Results: In total, 536 patients with IBD (175 unvaccinated, 31 vaccinated, 166 vaccinated with two doses, and 164 vaccinated with three doses) reported having COVID-19 infection. Compared with the unvaccinated, the three vaccination doses group was associated with reduced GI symptoms after infection (adjusted odds ratio = 0.56, 95% confidence interval 0.34-0.90, P < 0.05). Reduced diarrhea (adjusted odds ratio = 0.54, 95% confidence interval 0.31-0.92, P < 0.05) and nausea or vomiting (adjusted odds ratio = 0.45, 95% confidence interval 0.21-0.92, P < 0.05) were observed in the three vaccination doses group compared with the unvaccinated group. Conclusions: In conclusion, in the 536 patients with IBD who reported COVID-19 infection, we found that the three vaccination doses, but not the one or two doses group, were associated with reduced GI symptoms after infection compared with the unvaccinated group.

AMBRA1 promotes intestinal inflammation by antagonizing PP4R1/PP4c mediated IKK dephosphorylation in an autophagy-independent manner.

IκB kinase (IKK) complex is central regulators of the NF-κB pathway, and dysregulation of IKK phosphorylation leads to hyperactivation of proinflammatory response in various chronic inflammatory diseases, including inflammatory bowel disease (IBD). However, the dynamic modulation of IKK phosphorylation and dephosphorylation in intestinal inflammation remains uncharacterized. Here, we found that autophagy/beclin-1 regulator 1 (AMBRA1) was highly expressed in inflamed colons in a colitis mouse model and in clinical IBD samples. Importantly, AMBRA1 deletion significantly decreased proinflammatory cytokine expression and enhanced the therapeutic effect of infliximab on intestinal inflammation. Mechanistically, the N-term F1 domain of AMBRA1 was required for AMBRA1 to competitively interact with protein phosphatase 4 regulatory subunit 1 (PP4R1) and catalytic protein phosphatase 4 (PP4c) to suppress their interactions with IKK, promote the dissociation of the PP4R1/PP4c complex, and antagonize the dephosphorylation activity of this complex towards the IKK complex. In response to TNF-α stimulation, IKKα phosphorylates AMBRA1 at S1043 to stabilize AMBRA1 expression by impairing its binding to Cullin4A (CUL4A) to decrease its CUL4A-mediated K48-linked ubiquitination. Overall, our study identifies an autophagy-independent function of AMBRA1 as a positive modulator of IKK phosphorylation to promote intestinal inflammation, thus providing a new targeted therapeutic strategy for patients with refractory IBD.

Risk of Tuberculosis and Hepatitis B Reactivation in Patients With Crohn's Disease on Ustekinumab: A Nationwide Real-World Study.

BACKGROUND: Ustekinumab (UST) was approved in China for moderate-to-severe Crohn's disease (CD) in 2020. The prevalence rates of tuberculosis and hepatitis B virus (HBV) infection are high in China, and no guideline clearly states that tuberculosis chemoprophylaxis or prophylactic anti-HBV therapy should be prescribed before UST administration. This study aimed to assess the risk of tuberculosis and HBV reactivation in CD patients with latent tuberculosis infection (LTBI) and previous HBV infection receiving UST. METHODS: A multicenter retrospective cohort study was carried out at 68 hospitals in China to assess 721 adult CD cases administered UST between May 1, 2020, and December 31, 2021. CD and concurrent LTBI or HBV carrier were included. Hepatitis B serology, T-SPOT.TB, and tuberculin skin tests were performed at baseline. The primary outcome was tuberculosis or HBV reactivation. RESULTS: Patients with CD-concomitant LTBI or who were HBV carriers receiving UST therapy were retrospectively enrolled from 15 hospitals in China. A total of 53 CD with LTBI patients and 17 CD with HBV carrier patients receiving UST were included. Treatment and follow-up durations were 50 ± 20 weeks and 50 ± 15 weeks in the LTBI and HBV carrier groups, respectively. A total of 25 CD patients with LTBI underwent chemoprophylaxis and 28 did not. A total of 11 HBV carriers had antiviral prophylaxis and 6 did not. No patient experienced tuberculosis or HBV reactivation or liver dysfunction during follow-up. CONCLUSIONS: UST was safe for treatment of CD because no patient developed tuberculosis, persistent hepatitis, or acute liver failure during therapy, whether with a prophylactic regimen or not, based on our sample size and limited follow-up time.

LAMB3 Promotes Intestinal Inflammation Through SERPINA3 and Is Directly Transcriptionally Regulated by P65 in Inflammatory Bowel Disease.

BACKGROUND: Various extracellular matrix (ECM) reshaping events are involved in inflammatory bowel disease (IBD). LAMB3 is a vital subunit of laminin-332, an important ECM component. Data on the biological function of LAMB3 in intestinal inflammation are lacking. Our aim is to discuss the effect of LAMB3 in IBD. METHODS: LAMB3 expression was assessed in cultured intestinal epithelial cells, inflamed mucosal tissues of patients and mouse colitis models. RNA sequencing, quantitative real-time polymerase chain reaction and Western blotting were used to detect the LAMB3 expression distribution and potential downstream target genes. Dual-luciferase assays and chromatin immunoprecipitation-quantitative polymerase chain reaction were used to determine whether P65 could transcriptionally activate LAMB3 under tumor necrosis factor α stimulation. RESULTS: LAMB3 expression was increased in inflammatory states in intestinal epithelial cells and colonoids and was associated with adverse clinical outcomes in Crohn's disease. Knockdown of LAMB3 inhibited the expression of proinflammatory cytokines. Mechanistically, LAMB3 expression was directly transcriptionally activated by P65 and was inhibited by nuclear factor kappa B inhibitors under tumor necrosis factor α stimulation. Furthermore, RNA sequencing and replenishment experiments revealed that LAMB3 upregulated SERPINA3 to promote intestinal inflammation via the integrin α3ß1/FAK pathway. CONCLUSION: We propose that LAMB3 could serve as a potential therapeutic target of IBD and a predictor of intestinal stenosis of Crohn's disease. Our findings demonstrate the important role of ECM in the progression of IBD and offer an experimental basis for the treatment and prognosis of IBD.

HLF promotes ovarian cancer progression and chemoresistance via regulating Hippo signaling pathway.

Hepatic leukemia factor (HLF) is aberrantly expressed in human malignancies. However, the role of HLF in the regulation of ovarian cancer (OC) remains unknown. Herein, we reported that HLF expression was upregulated in OC tissues and ovarian cancer stem cells (CSCs). Functional studies have revealed that HLF regulates OC cell stemness, proliferation, and metastasis. Mechanistically, HLF transcriptionally activated Yes-associated protein 1 (YAP1) expression and subsequently modulated the Hippo signaling pathway. Moreover, we found that miR-520e directly targeted HLF 3'-UTR in OC cells. miR-520e expression was negatively correlated with HLF and YAP1 expression in OC tissues. The combined immunohistochemical (IHC) panels exhibited a better prognostic value for OC patients than any of these components alone. Importantly, the HLF/YAP1 axis determines the response of OC cells to carboplatin treatment and HLF depletion or the YAP1 inhibitor verteporfin abrogated carboplatin resistance. Analysis of patient-derived xenografts (PDXs) further suggested that HLF might predict carboplatin benefits in OC patients. In conclusion, these findings suggest a crucial role of the miR-520e/HLF/YAP1 axis in OC progression and chemoresistance, suggesting potential therapeutic targets for OC.

Rapidly degrading and mussel-inspired multifunctional carboxymethyl chitosan/montmorillonite hydrogel for wound hemostasis.

The conventional method of using montmorillonite hemostatic materials affects the hemostatic effect due to easy dislodgement on the wound surface. In this paper, a multifunctional bio-hemostatic hydrogel (CODM) was prepared based on hydrogen bonding and Schiff base bonding using modified alginate, polyvinylpyrrolidone (PVP), and carboxymethyl chitosan. The amino group-modified montmorillonite was uniformly dispersed in the hydrogel by its amido bond formation with the carboxyl groups of carboxymethyl chitosan and oxidized alginate. The catechol group, -CHO, and PVP can form hydrogen bonds with the tissue surface to afford the firm tissue adhesion to afford the wound hemostatic. The addition of montmorillonite-NH2 further improves the hemostatic ability, making it better than commercial hemostatic materials. Moreover, the photothermal conversion ability (derived from the polydopamine) was synergized with the phenolic hydroxyl group, quinone group, and the protonated amino group to effectively kill the bacteria in vitro and in vivo. Based on its in vitro and in vivo biosafety and satisfactory degradation ratio anti-inflammatory, antibacterial, and hemostatic properties, the CODM hydrogel holds promising potential for emergency hemostasis and intelligent wound management.

Comparison of The Toronto IBD Global Endoscopic Reporting (TIGER) score, Mayo endoscopic score (MES), and ulcerative colitis endoscopic index of severity (UCEIS) in predicting the need for ileal pouch-anal anastomosis in patients with ulcerative colitis.

BACKGROUND: Total proctocolectomy (TPC) with ileal pouch-anal anastomosis (IPAA) has been accepted as a radical surgery for refractory ulcerative colitis (UC). We aimed to assess the predictive value of several novel and widely used endoscopic core systems, The Toronto IBD Global Endoscopic Reporting (TIGER) score, Mayo endoscopic score (MES), and ulcerative colitis endoscopic index of severity (UCEIS) in guiding the need for IPAA. METHODS: Data on patients with UC from June 1986 and June 2022 at our institute were collected. The endoscopic evaluation was recorded according to the first colonoscopy after hospitalization. Primary outcome was the need for IPAA during admission and follow-up. RESULTS: A total of 313 patients with a median follow-up time and a median TIGER score of 12.0 years (interquartile range (IQR): 6.0-17.0) and 212.0 (IQR: 7.0-327.0) were enrolled. IPAA was conducted in 110 (35.1%) patients, which significantly improved the long-term quality of life. TIGER score had the biggest area under the receiver-operating characteristic curve of 0.810 with a sensitivity of 75.0% and specificity of 87.1% at the cut-off value of 315 (p < 0.001). TIGER score ≥ 315 was an independent risk factor with the highest odds ratio for the need for IPAA and associated with the shortest IPAA-free survival time compared with UCEIS and MES. CONCLUSION: TIGER score was superior to UCEIS and MES in predicting the need for IPAA. For colorectal surgeons, three or more segments with moderate-to-severe endoscopic activity should be considered as a threshold value for decision-making for IPAA.

The endoscopic prediction model of simple endoscopic score for Crohn's disease (SES-CD) as an effective predictor of intestinal obstruction in Crohn's disease: A multicenter long-term follow-up study.

Background: The simple endoscopic score for Crohn's disease (SES-CD) is a widely used index to evaluate clinical and endoscopic activity. However, the association and predictive value of SES-CD for intestinal obstruction in Crohn's disease (CD) remains unclear. We aimed to establish the best cut-off indicators of SES-CD for early clinical intervention and subsequent prevention of intestinal obstruction in CD. Methods: Data on patients with CD evaluated at our institute from January 2016 to January 2022 were retrospectively collected. The SES-CD and Crohn's Disease Activity Index scores used in the analysis indicated the results of the first clinical and colonoscopy evaluations after hospitalization. The primary outcome was the occurrence of intestinal obstruction during admission and follow-up. Results: A total of 248 patients with a median follow-up time of 2 years [interquartile range: 1.0-4.0] were enrolled, of which 28.2% developed intestinal obstruction. An SES-CD score of 8 was the most significant threshold evaluation, and SES-CD ≥8 had the largest area under the receiver operating characteristic curve (0.705), with a sensitivity of 52.9% and specificity of 88.2% in predicting intestinal obstruction. Furthermore, SES-CD ≥8 had the greatest risk factor for intestinal obstruction (odds ratio: 7.731; 95% confidence interval: 3.901-15.322; p < 0.001) and significantly decreased the overall intestinal obstruction-free survival (p < 0.001). Conclusion: The SES-CD endoscopic prediction model could be an effective predictor of intestinal obstruction in patients with CD. More frequent follow-up and colonoscopic surveillance should be considered in patients with SES-CD score ≥8 to prevent the development of intestinal obstruction.

Butyrate-producing Eubacterium rectale suppresses lymphomagenesis by alleviating the TNF-induced TLR4/MyD88/NF-κB axis.

Microbiota-induced tumorigenesis is well established in solid tumors of the gastrointestinal tract but rarely explored in hematologic malignancies. To determine the role of gut microbiota in lymphoma progression, we performed metagenomic sequencing on human primary gastrointestinal B cell lymphomas. We identified a distinct microbiota profile of intestinal lymphoma, with significantly decreased symbiotic microbes, particularly the genus Eubacterium and notably butyrate-producing Eubacterium rectale. Transfer of E. rectale-deficit microbiota of intestinal lymphoma patients to mice caused inflammation and tumor necrosis factor (TNF) production. Conversely, E. rectale treatment reduced TNF levels and the incidence of lymphoma in sensitized Eµ-Myc mice. Moreover, lipopolysaccharide from the resident microbiota of lymphoma patients and mice synergizes with TNF signaling and reinforces the NF-κB pathway via the MyD88-dependent TLR4 signaling, amalgamating in enhanced intestinal B cell survival and proliferation. These findings reveal a mechanism of inflammation-associated lymphomagenesis and a potential clinical rationale for therapeutic targeting of gut microbiota.

The Mayo Endoscopic Score Is a Novel Predictive Indicator for Malignant Transformation in Ulcerative Colitis: A Long-Term Follow-Up Multicenter Study.

Background: Data on the relative risk of malignant transformation in ulcerative colitis (UC) are insufficient. We investigated the potential value of the Mayo endoscopic score (MES) for predicting malignant transformation in patients with UC. Methods: Data of patients with UC evaluated at our institute from June 1986 to December 2019 were retrospectively analyzed. The MES used in the study indicated the results of the first colonoscopy after hospitalization. We defined MES of 0-1 as low and MES of 2-3 as high. Univariable and multivariate logistic regression models were used for statistical analysis. Results: Among the 280 eligible patients with UC with a median follow-up time of 14 (interquartile range, 10.0-18.0) years, those with a high MES were more likely to develop malignant transformation. High MES positively correlated with the degree of malignancy and was an independent risk factor for UC-associated dysplasia and colorectal cancer (CRC, odds ratio [OR], 9.223; 95% confidence interval [CI], 1.160-73.323; p = 0.036). Disease duration >5 years (OR, 2.05; 95% CI, 1.177-3.572; p = 0.011), immunomodulator use (OR, 4.314; 95% CI, 1.725-10.785; p = 0.002), biologics nonuse (OR, 3.901; 95%CI, 2.213-6.876; p < 0.001), and Hb <90 g/L (OR, 2.691; 95% CI, 1.251-5.785; p = 0.011) were contributing factors for high MES. Conclusion: High MES could be a novel predictor of malignant transformation in UC. Clinicians should optimize the use of biologics and immunomodulators early and should actively correct anemia to improve the MES and then reduce the incidence of UC-associated dysplasia and CRC.

Association between Dietary Inflammatory Index and Sarcopenia in Crohn's Disease Patients.

BACKGROUND: Chronic inflammation is a pathophysiological cause of sarcopenia in Crohn's disease (CD) patients. However, the potential impact of diet-related inflammation on sarcopenia has not yet been adequately investigated. We examined the associations between Dietary Inflammatory Index (DII) and sarcopenia in CD patients. METHODS: A total of 140 CD patients from Ruijin Hospital in Shanghai were included in this cross-sectional study. DII scores were calculated from the dietary data collected using a validated food frequency questionnaire (FFQ). Sarcopenia was determined according to the Asian Working Group for Sarcopenia. Multivariable logistic regression analyses were performed to determine the association between DII and sarcopenia. RESULTS: The mean DII score was 0.81 ± 2.13, ranging from -3.24 to 4.89. The overall prevalence of sarcopenia was 26.4%. The higher DII score significantly increased the risk of sarcopenia in CD patients (ORQuartile4vs1: 9.59, 95% CI: 1.69, 54.42, ptrend = 0.031) in the multivariable model after adjusting for more potential confounders. Moreover, CD patients with a lower DII had a significantly higher appendicular skeletal muscle mass index (ASMI, ORQuartile4vs1: 5.48, 95% CI: 1.51, 19.87, ptrend = 0.018) after adjusting for age, gender, BMI, smoking status and drinking status model. Yet, there were no significant differences between DII and ASMI after adjusting for more potential confounders. Additionally, no significant association was observed between DII and handgrip strength in the multivariable-adjusted models. CONCLUSIONS: Pro-inflammatory diet was associated with increased risk of sarcopenia in CD patients. CD patients should have a proper intake of energy and protein. These patients could also benefit from supplementation with enteral nutrition due to its anti-inflammatory potential.

Treatment Decision-making in Chinese Inflammatory Bowel Disease Patients.

BACKGROUND: Inflammatory bowel disease (IBD) is rising in China, and the tendency for lifelong recurrence decreases patients' quality of life. However, no studies on treatment decision-making in Chinese patients with IBD exist. Thus, this study aimed to determine the actual and ideal decision-making, as well as factors affecting decision-making in Chinese IBD patients. METHODS: A multicenter online questionnaire was distributed among patients diagnosed with IBD. To assess factors that influence treatment decision-making, univariate and multivariate logistic regression analyses were performed. RESULTS: From March 20, 2018, to May 20, 2018, a total of 866 patients completed the questionnaires, including 222 patients with ulcerative colitis, 588 patients with Crohn's disease, and 56 patients with unclassified IBD. There was a significant difference between ideal and actual decision-making in Chinese IBD patients (P < .005). The factors affecting ideal decision-making included income, education, illness severity, religiosity, the importance of the treatment decision, the employment situation, and occupation area. The factors affecting actual decision-making included age, illness severity, religiosity, the employment situation, economic anxiety, concern about the side effects, and the importance of the treatment decision. CONCLUSIONS: There is a significant difference between ideal and actual decision-making in IBD patients in China. That is, the economy, religiosity, illness severity, and concern about the side effects of treatment are the most important factors affecting treatment decisions in Chinese IBD patients.

Cut-off value of ulcerative colitis endoscopic index of severity (UCEIS) score for predicting the need for pouch construction in ulcerative colitis: results of a multicenter study with long-term follow-up.

BACKGROUND: Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) was the first choice for the surgical treatment of the ulcerative colitis (UC) patients. The data on the predictive value of the ulcerative colitis endoscopic index of severity (UCEIS) for the need for IPAA in UC patients is scarce. We aimed to establish the UCEIS cut-off value to further analyse whether the UCEIS cut-off was suitable for predicting the need for IPAA in UC patients. METHODS: The clinical data of UC patients from June 1986 to March 2020 at our institute were retrospectively assessed. The UCEIS scores recorded at the time of the first colonoscopy after hospitalization were used in the study. Receiver operating characteristic curve analysis was performed to determine the UCEIS cut-off value for predicting the need for IPAA. RESULTS: A total of 283 UC patients were included in the study, with a median UCEIS of 4. During a median follow-up of 13 years, 80 patients (28.3%) received surgery invention, among whom 75 (93.8%) underwent IPAA surgery and 5 (6.2%) received subtotal colectomy with permanent ostomy. A UCEIS cut-off of 6 had the most significant area under the curve of 0.769 for predicting the need for IPAA (P < 0.001), with a sensitivity of 72.0% and specificity of 81.8%. UCEIS ≥6 was an independent predictive factor for the need for IPAA (P < 0.001) and malignant transformation (P = 0.010). Patients with UCEIS ≥6 had a significantly shorter IPAA-free survival time than those with UCEIS <6 (P < 0.001). CONCLUSIONS: UCEIS ≥6 may be a threshold value for decision-making for IPAA and should be recommended for UC patients for reducing the incidence of malignant transformation.

Body Mass Index and Disease Activity Are Associated With Moderate to Severe Disability in Crohn's Disease: A Cross-Sectional Study in Shanghai.

Background: The inflammatory bowel disease disability index (IBD-DI) was used to access body functional consequences and disease burden. However, Chinese population data are considerably limited. Objective: We aimed to screen for disability in patients with Crohn's disease (CD) and to assess potential associations with clinical parameters as well as indices related to sarcopenia. Methods: This cross-sectional study includes 146 CD patients from Ruijin Hospital in Shanghai, China. All patients were screened for disability and sarcopenia on the basis of the IBD-DI scale, and the criteria for Asian Working Group for Sarcopenia, respectively. Clinical and demographic variables were collected. Results: Approximately 52.05% of the subjects suffered from moderate or severe disabilities. The prevalence of sarcopenia (48.68 vs. 31.43%, P = 0.043), Patient-Generated Subjective Global Assessment score or PG-SGA≥4 (39.47 vs. 17.14%, P = 0.003), and high-level C- reactive protein (27.63 vs. 11.43%, P = 0.021) were higher in patients with moderate to severe disability than in those without to minimal disability. By multivariate regression modeling, the following were identified as independent factors related to moderate to severe disability: disease activity (OR:10.47, 95% CI: 2.09-52.42) and body mass index (BMI) (OR:4.11, 95% CI: 1.80-9.38). Conclusions: Disability is common in CD patients. Our study showed that moderate to severe disability is not directly associated with muscle mass or muscle quantity but is mostly correlated with disease activity as well as BMI. Thus, close monitoring and follow-up should be conducted on patients who are at high risk of disability, and effective measures should be taken, which may be the best way to prevent disability.

miR-369 inhibits Liver Cancer progression by targeting ZEB1 pathway and predicts the prognosis of HCC patients.

Increasing evidences show that microRNAs (miRNAs) are involved in the regulation of tumorigenesis, progression, recurrence and drug resistance of hepatocellular carcinoma (HCC). miR-369 works as a tumor suppressor in both lung cancer and thyroid cancer. However, the potential biological function of miR-369 in HCC is unknown. Herein, we for first found that miR-369 expression was downregulated in HCC tissues and predicted the poor prognosis of HCC patients. Forced miR-369 expression inhibited the proliferation and metastasis of HCC cells in vitro and in vivo. Mechanically, bioinformatics and luciferase reporter analysis identified Zinc finger E-box binding homeobox 1 (ZEB1) as a direct target of miR-369 in HCC cells. miR-369 overexpressing downregulated the ZEB1 mRNA and protein expression in HCC cells. miR-369 expression was negatively associated with ZEB1 expression in human HCC tissues. More importantly, the ZEB1 siRNA diminished the discrepancy of growth and metastasis capacity between miR-369 overexpression HCC cells and control cells.

miR-124 regulates liver cancer stem cells expansion and sorafenib resistance.

Liver cancer stem cells (CSCs) contribute to tumorigenesis, progression, recurrence and drug resistance of hepatocellular carcinoma (HCC). However, the underlying mechanism for liver CSCs expansion remains unclear. Herein, we report that miR-124 is downregulated in liver CSCs and associated with the poor prognosis of HCC. Functional studies revealed that a forced expression of miR-124 inhibits liver CSCs self-renew and tumorigenesis. Conversely, miR-124 knockdown promotes liver CSCs self-renew and tumorigenesis. Mechanistically, miR-124 directly target Caveolin-1 (CAV1) via its mRNA 3'UTR in liver CSCs. Furthermore, miR-124 expression determines the responses of hepatoma cells to sorafenib treatment. The analysis of patient cohort and patient-derived xenografts (PDXs) further demonstrated that miR-124 may predict sorafenib benefits in HCC patients. In conclusion, our findings revealed the crucial role of the miR-124 in liver CSCs expansion and sorafenib response, rendering miR-124 an optimal target for the prevention and intervention in HCC.

Risk Factors of Colorectal Stricture Associated with Developing High-Grade Dysplasia or Cancer in Ulcerative Colitis: A Multicenter Long-term Follow-up Study.

Background/Aims: The risk factors of colorectal stricture associated with ulcerative colitis (UC) carcinogenesis in the long-term disease duration remain unclear. Methods: This study included all UC patients registered from a prospectively maintained database between June 1986 to July 2018. The demographic data, clinical features, and outcomes in patients with dysplasia and stricture were assessed using univariable analysis and multivariate logistic regression models. Results: A total of 246 eligible patients were included in the analysis. The median follow-up time was 13.0 years (interquartile range [IQR], 9.0 to 16.0). There were 35 cases (14.2%) of colorectal stricture. Patients with stricture had worse clinical outcomes. Stricture formation (odds ratio [OR], 9.350; 95% confidence interval [CI], 2.842 to 30.762), inflammatory polyps (OR, 5.464; 95% CI, 1.692 to 17.638), disease duration of more than 10 years (OR, 3.223; 95% CI, 1.040 to 9.985), and age >40 years at diagnosis (OR, 8.499; 95% CI, 1.903 to 37.956) were significantly associated with high-grade dysplasia or colorectal cancer. In addition, disease duration of more than 5 years (OR, 3.211; 95% CI, 1.168 to 8.881), moderated anemia (OR, 3.373; 95% CI, 1.472 to 7.731), and primary sclerosing cholangitis (OR, 5,842; 95% CI, 1.395 to 24.468) were contributing factors for the development of colorectal stricture. Conclusions: Colorectal stricture had the highest risk for malignant transformation. Earlier initiation of colonoscopic surveillance in UC patients with risk factors for stricture should be considered to prevent stricture formation and further malignant transformation.

Clinical outcomes and risk factors of secondary extraintestinal manifestation in ulcerative colitis: results of a multicenter and long-term follow-up retrospective study.

BACKGROUND: Extraintestinal manifestations (EIM) are common in ulcerative colitis (UC). In Shanghai, China, data on the incidence rate and risk factors of EIM in UC patients remain scarce. METHODS: The study population consisted of UC patients who were identified from a prospectively maintained, institutional review board-approved database at our institutes from June 1986 to December 2018. The demographic and clinical characteristics of the study participants were analyzed. The study included secondary EIM in UC patients and follow-up, while primary EIM was excluded. The diagnosis of EIM was based on clinical, radiological, endoscopic, and immunologic examination and histological findings. RESULTS: In total, 271 eligible patients were included in the current study, with a median follow-up time of 13.0 years (interquartile range, 9.0-17.0), and including 31 cases (11.4%) that developed EIM. EIM was associated with clinical outcomes in UC patients and the following factors were identified as contributing factors for the development of EIM: a disease duration of >5 years (odds ratio (OR), 3.721; 95% confidence interval (CI) [1.209-11.456]), age at diagnosis >40 years (OR, 2.924, 95% CI [1.165-7.340]), refractory clinical symptoms (OR, 4.119; 95% CI [1.758-9.650]), and moderate or severe anemia (OR, 2.592; 95% CI [1.047-6.413]). CONCLUSION: In this study, approximately 11.4% UC patients go on to develop at least one EIM. Clinicians should prioritize early control of the disease and treatment of anemia in UC in order to prevent the development of EIM and improve disease prognosis.