The Multiple Waves of COVID-19 in Patients With Inflammatory Bowel Disease: A Temporal Trend Analysis

Background Cases of coronavirus disease 2019 (COVID-19) have emerged in discrete waves. We explored temporal trends in the reporting of COVID-19 in inflammatory bowel disease (IBD) patients. Methods The Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) is an international registry of IBD patients diagnosed with COVID-19. The average percent changes (APCs) were calculated in weekly reported cases of COVID-19 during the periods of March 22 to September 12, September 13 to December 12, 2020, and December 13 to July 31, 2021. Results Across 73 countries, 6404 cases of COVID-19 were reported in IBD patients. COVID-19 reporting decreased globally by 4.2% per week (95% CI, −5.3% to −3.0%) from March 22 to September 12, 2020, then climbed by 10.2% per week (95% CI, 8.1%-12.3%) from September 13 to December 12, 2020, and then declined by 6.3% per week (95% CI, −7.8% to −4.7%). In the fall of 2020, weekly reporting climbed in North America (APC, 11.3%; 95% CI, 8.8-13.8) and Europe (APC, 17.7%; 95% CI, 12.1%-23.5%), whereas reporting was stable in Asia (APC, −8.1%; 95% CI, −15.6-0.1). From December 13, 2020, to July 31, 2021, reporting of COVID-19 in those with IBD declined in North America (APC, −8.5%; 95% CI, −10.2 to −6.7) and Europe (APC, −5.4%; 95% CI, −7.2 to −3.6) and was stable in Latin America (APC, −1.5%; 95% CI, −3.5% to 0.6%). Conclusions Temporal trends in reporting of COVID-19 in those with IBD are consistent with the epidemiological patterns COVID-19 globally.

Tofacitinib Inhibits Leukocyte Trafficking Across the Intestinal Endothelial Barrier in a Specific Cohort of Ulcerative Colitis Patients

Lay Summary The JAK/STAT inhibitor tofacitinib, recently approved for the treatment of ulcerative colitis, is found to modulate the intestinal endothelial barrier functions in directing the leukocyte adhesion and transmigration in ulcerative colitis patients displaying high levels of endothelial STAT3/STAT6 phosphorylation.

Predicting Risk of Surgery in Patients With Small Bowel Crohn’s Disease Strictures Using Computed Tomography and Magnetic Resonance Enterography

Background We aimed to determine if patient symptoms and computed tomography enterography (CTE) and magnetic resonance enterography (MRE) imaging findings can be used to predict near-term risk of surgery in patients with small bowel Crohn’s disease (CD). Methods CD patients with small bowel strictures undergoing serial CTE or MRE were retrospectively identified. Strictures were defined by luminal narrowing, bowel wall thickening, and unequivocal proximal small bowel dilation. Harvey-Bradshaw index (HBI) was recorded. Stricture observations and measurements were performed on baseline CTE or MRE and compared to with prior and subsequent scans. Patients were divided into those who underwent surgery within 2 years and those who did not. LASSO (least absolute shrinkage and selection operator) regression models were trained and validated using 5-fold cross-validation. Results Eighty-five patients (43.7 ± 15.3 years of age at baseline scan, majority male [57.6%]) had 137 small bowel strictures. Surgery was performed in 26 patients within 2 years from baseline CTE or MRE. In univariate analysis of patients with prior exams, development of stricture on the baseline exam was associated with near-term surgery (P = .006). A mathematical model using baseline features predicting surgery within 2 years included an HBI of 5 to 7 (odds ratio [OR], 1.7 × 105; P = .057), an HBI of 8 to 16 (OR, 3.1 × 105; P = .054), anastomotic stricture (OR, 0.002; P = .091), bowel wall thickness (OR, 4.7; P = .064), penetrating behavior (OR, 3.1 × 103; P = .096), and newly developed stricture (OR: 7.2 × 107; P = .062). This model demonstrated sensitivity of 67% and specificity of 73% (area under the curve, 0.62). Conclusions CTE or MRE imaging findings in combination with HBI can potentially predict which patients will require surgery within 2 years.

High Degree of Practice Variability in Colonic Dysplasia Surveillance for Patients With Inflammatory Bowel Disease

Lay Summary Dysplasia surveillance practice varies widely among high-volume inflammatory bowel disease providers. We surveyed high-volume inflammatory bowel disease providers about practice patterns to detect dysplasia. Regular use of dye-based chromoendoscopy was reported by 20%, virtual chromoendoscopy by 27%, and random biopsies by 58%.

Caveolin-1 Alleviates Crohn’s Disease–induced Intestinal Fibrosis by Inhibiting Fibroblasts Autophagy Through Modulating Sequestosome 1

Background Intestinal fibrosis is a common complication of Crohn’s disease (CD) and is characterized by the excessive accumulation of extracellular matrix produced by activated myofibroblasts. Caveolin-1 (CAV1) inhibits fibrosis. However, limited data show that CAV1 affects intestinal fibrosis. Methods Human CD tissue samples were gained from patients with CD who underwent surgical resection of the intestine and were defined as stenotic or nonstenotic areas. A dextran sodium sulfate–induced mouse model of intestinal fibrosis was established. For in vitro experiments, we purchased CCD-18Co intestinal fibrosis cells and isolated and cultured human primary colonic fibroblasts. These fibroblasts were activated by transforming growth factor β administration for 48 hours. In the functional experiments, a specific small interfering RNA or overexpression plasmid was transfected into fibroblasts. The messenger RNA levels of fibrosis markers, such as α-smooth muscle actin, fibronectin, connective tissue growth factor, and collagen I1α, were determined using quantitative polymerase chain reaction. Western blot analysis was applied to detect the expression of CAV1, SQSTM1/p62 (sequestosome 1), and other fibrosis markers. Results In human CD samples and the dextran sodium sulfate–induced mouse model of intestinal fibrosis, we observed a downregulation of CAV1 in fibrosis-activated areas. Mechanistically, CAV1 knockdown in both human primary colonic fibroblasts and CCD-18Co cells promoted fibroblast activation, while CAV1 overexpression inhibited fibroblast activation in vitro. We found that SQSTM1/p62 positively correlated with CAV1 expression levels in patients with CD and that it was indirectly modulated by CAV1 expression. Rescue experiments showed that CAV1 decreased primary human intestinal fibroblast activation by inhibiting fibroblast autophagy through the modulation of SQSTM1/p62. Conclusions Our data demonstrate that CAV1 deficiency induces fibroblast activation by indirectly regulating SQSTM1/p62 to promote fibroblast autophagy. CAV1 or SQSTM1/p62 may be potential therapeutic targets for intestinal fibrosis.

Inflammatory Bowel Disease Risk Variants Are Associated with an Increased Risk of Skin Cancer

Background Inflammatory bowel disease is associated with an increased risk of skin cancer. The aims of this study were to determine whether IBD susceptibility variants are also associated with skin cancer susceptibility and if such risk is augmented by use of immune-suppressive therapy. Methods The discovery cohort included participants in the UK Biobank. The validation cohort included participants in the Michigan Genomics Initiative. The primary outcome of interest was skin cancer, subgrouped into nonmelanoma skin cancers (NMSC) and melanoma skin cancers (MSC). Multivariable logistic regression with matched controls (3 controls:1 case) was performed to identify genomic predictors of skin malignancy in the discovery cohort. Variants with P < .05 were tested for replication in the validation cohort. Validated Single nucleotide polymorphisms were then evaluated for effect modification by immune-suppressive medications. Results The discovery cohort included 10,247 cases of NMSC and 1883 cases of MSC. The validation cohort included 7334 cases of NMSC and 3304 cases of MSC. Twenty-nine variants were associated with risk of NMSC in the discovery cohort, of which 5 replicated in the validation cohort (increased risk, rs7773324-A [DUSP22; IRF4], rs2476601-G [PTPN22], rs1847472-C [BACH2], rs72810983-A [CPEB4]; decreased risk, rs6088765-G [PROCR; MMP24]). Twelve variants were associated with risk of MSC in the discovery cohort, of which 4 were replicated in the validation cohort (increased risk, rs61839660-T [IL2RA]; decreased risk, rs17391694-C [GIPC2; MGC27382], rs6088765-G [PROCR; MMP24], and rs1728785-C [ZFP90]). No effect modification was observed. Conclusions The results of this study highlight shared genetic susceptibility across IBD and skin cancer, with increased risk of NMSC in those who carry risk variants in IRF4, PTPN22, CPEB4, and BACH2 and increased risk of MSC in those who carry a risk variant in IL2RA.

Histologic Evaluation Using the Robarts Histopathology Index in Patients With Ulcerative Colitis in Deep Remission and the Association of Histologic Remission With Risk of Relapse

Background This study prospectively evaluated the risk of relapse according to the status of histologic activity in patients with ulcerative colitis (UC) who achieved deep remission. Methods Patients with UC in clinical remission (partial Mayo score ≤1) and endoscopic remission (ulcerative colitis endoscopic index of severity ≤1) were enrolled. Rectal biopsies were performed in patients, and histologic remission was defined as a Robarts histopathology index of ≤3. Receiver-operating characteristic curve analysis was conducted to determine fecal calprotectin cutoff values for histologic remission. The cumulative risk of relapse was evaluated using the Cox proportional hazards model. Results Among the 187 patients enrolled, 82 (43.9%) achieved histologic remission. The best cutoff value of fecal calprotectin for predicting histologic remission was 80 mg/kg (area under the curve of 0.646, sensitivity of 74%, and specificity of 61%). Among 142 patients who were followed up for >3 months, 56 (39.4%) showed clinical relapse during a median of 42 weeks. The risk of relapse was lower in patients with histologic remission than in those with histologic activity (P = .026). In multivariable analysis, histologic remission (hazard ratio [HR], 0.551; 95% confidence interval [CI], 0.316-0.958; P = .035), elevated C-reactive protein levels (HR, 3.652; 95% CI, 1.400-9.526; P = .008), and history of steroid use (HR, 2.398; 95% CI, 1.196-4.808; P = .014) were significantly associated with clinical relapse. Conclusions In patients with UC who achieved clinical and endoscopic remission, histologic remission was independently associated with a lower risk of clinical relapse.

Current status of cytomegalovirus colitis among patients with inflammatory bowel disease in China: A questionnaire-based multi-center study

Background Cytomegalovirus (CMV) causes infection in patients with inflammatory bowel disease (IBD). This study investigated the prevalence of CMV colitis, the current status of laboratory testing equipment, and physicians’ opinions regarding CMV and IBD in China. Methods This retrospective multi-center study was conducted by Chinese members of the Asian Organization for Crohn’s and Colitis and included 36 hospitals/institutes divided according to municipality, provincial capital city, and prefectural-level city. A survey questionnaire was administered, and chi-square and Fisher’s exact tests were performed. Results A total of 4 823 inpatients with ulcerative colitis (UC) and 4.622 inpatients with Crohn’s disease (CD) were included. The percentages of patients with moderate UC in the provincial capital city and municipality were significantly higher than that in the prefectural-level city (38.3% vs. 29.1% and 40.1% vs. 29.1%, respectively). The percentage of patients with mild CD was significantly lower in the provincial capital city than in the prefectural-level city and municipality (30.4% vs. 40.3%; 30.4% vs. 39.3%, respectively). There were 3.1% patients with UC and 0.8% patients with CD who had CMV colitis. The prevalence of CMV colitis was lower in patients with CD than in patients with UC (0.8% vs. 3.1%). Of the 150 patients with UC and concurrent CMV colitis, 17.3% patients underwent surgery, 2.0% died, and 23.3% experienced complications. Punched-out ulcerations were the major characteristic features for detecting CMV colitis. Approximately 77.8% of hospitals possessed testing facilities capable of conducting CMV immunohistochemistry. Conclusions CMV colitis is an important issue during the disease progression of IBD. However, improvement in knowledge and facilities is required to enhance the prognosis of patients.