Recent advances in devices and technologies that might prove revolutionary for colonoscopy procedures.

INTRODUCTION: Colorectal cancer (CRC) is the third most common malignancy and second leading cause of cancer-related mortality in the world. Adenoma detection rate (ADR), a quality indicator for colonoscopy, has gained prominence as it is inversely related to CRC incidence and mortality. As such, recent efforts have focused on developing novel colonoscopy devices and technologies to improve ADR. AREAS COVERED: The main objective of this paper is to provide an overview of advancements in the fields of colonoscopy mechanical attachments, artificial intelligence-assisted colonoscopy, and colonoscopy optical enhancements with respect to ADR. We accomplished this by performing a comprehensive search of multiple electronic databases from inception to September 2023. This review is intended to be an introduction to colonoscopy devices and technologies. EXPERT OPINION: Numerous mechanical attachments and optical enhancements have been developed that have the potential to improve ADR and AI has gone from being an inaccessible concept to a feasible means for improving ADR. While these advances are exciting and portend a change in what will be considered standard colonoscopy, they continue to require refinement. Future studies should focus on combining modalities to further improve ADR and exploring the use of these technologies in other facets of colonoscopy.

The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results From the SUCCESS Consortium.

INTRODUCTION: We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS: This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. RESULTS: A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients. DISCUSSION: UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

Prevalence and factors associated with vitamin C deficiency in inflammatory bowel disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are prone to several nutritional deficiencies. However, data are lacking on vitamin C deficiency in Crohn's disease (CD) and ulcerative colitis (UC) patients, as well as the impact of clinical, biomarker and endoscopic disease severity on the development of vitamin C deficiency. AIM: To determine proportions and factors associated with vitamin C deficiency in CD and UC patients. METHODS: In this retrospective study, we obtained clinical, laboratory and endoscopic data from CD and UC patients presenting to the IBD clinic at a single tertiary care center from 2014 to 2019. All patients had an available plasma vitamin C level. Of 353 subjects who met initial search criteria using a cohort discovery tool, 301 ultimately met criteria for inclusion in the study. The primary aim described vitamin C deficiency (≤ 11.4 µmol/L) rates in IBD. Secondary analyses compared proportions with deficiency between active and inactive IBD. Multivariate logistic regression analysis evaluated factors associated with deficiency. RESULTS: Of 301 IBD patients, 21.6% had deficiency, including 24.4% of CD patients and 16.0% of UC patients. Patients with elevated C-reactive protein (CRP) (39.1% vs 16.9%, P < 0.001) and fecal calprotectin (50.0% vs 20.0%, P = 0.009) had significantly higher proportions of deficiency compared to those without. Penetrating disease (P = 0.03), obesity (P = 0.02) and current biologic use (P = 0.006) were also associated with deficiency on univariate analysis. On multivariate analysis, the objective inflammatory marker utilized for analysis (elevated CRP) was the only factor associated with deficiency (odds ratio = 3.1, 95% confidence interval: 1.5-6.6, P = 0.003). There was no difference in the presence of clinical symptoms of scurvy in those with vitamin C deficiency and those without. CONCLUSION: Vitamin C deficiency was common in IBD. Patients with elevated inflammatory markers and penetrating disease had higher rates of vitamin C deficiency.

Crohn's Disease of the Elderly: Unique Biology and Therapeutic Efficacy and Safety.

The incidence and prevalence of inflammatory bowel disease (IBD) is increasing in the elderly population. Compared with patients with onset during younger years, patients with elderly-onset IBD have a distinct clinical presentation, disease phenotype, and natural history. Genetics contribute less to pathogenesis of disease, whereas aging-related biological changes, such as immunosenescence and dysbiosis, are associated with elderly-onset IBD. Frailty is an increasingly recognized predictor of adverse outcomes. As an increasingly wider array of biologic and small molecule therapeutic options becomes available, data regarding efficacy and safety of these agents in patients are paramount given the unique characteristics of this population.

A Quality Improvement Initiative Is Associated With Reduced Time to Administer Biologics and Small Molecules and Emergency Room Visits in Inflammatory Bowel Disease.

BACKGROUND: Delays in biologic or small molecule medication administration are associated with increased adverse events, hospitalization, and surgery in inflammatory bowel disease (IBD). We evaluated the impact of a quality improvement (QI) intervention on the time to administration of biologics or small molecules (TABS) in IBD. METHODS: Data were retrospectively extracted for IBD patients prescribed biologics or small molecules from a convenience sample of providers participating in an accredited QI educational intervention (baseline cohort). Subsequent to the intervention, data were prospectively collected from patients prescribed these medications (postintervention cohort). Dates related to steps between a treatment decision to medication administration were collected. The primary outcome compared TABS in baseline and postintervention cohorts. RESULTS: Eighteen physicians provided survey and patient data for 200 patients in each cohort (n=400). The median time to medication administration (TABS) decreased from baseline to postintervention cohorts (30 vs. 26 d, P=0.04). Emergency room visits before medication administration also decreased (25.5% vs. 12.5%, P=0.001). Similar numerical TABS reductions were observed in subgroups limited to physicians providing patients to both cohorts and for individual medications prescribed. Primary contributors to delays included filling prescriptions subsequent to insurance approval and dispensation subsequent to this. CONCLUSIONS: A QI intervention successfully reduced medication administration times (TABS) by accelerating provider-dependent steps. This intervention was associated with reduced emergency room visits. We propose TABS as a quality metric to assess the effective delivery of therapies in IBD. Further evaluation of QI interventions, patient education on prescription drug insurance, and quality metrics are warranted.

Dual Biologic or Small Molecule Therapy for Treatment of Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: We conducted a systematic review and meta-analysis to summarize emerging data on the safety and effectiveness of dual biologic therapy in combination or with tofacitinib in patients with refractory inflammatory bowel disease (IBD). METHODS: Through a systematic search of multiple electronic databases through November 9, 2020, we identified cohort studies or case series (>10 patients) reporting the safety and effectiveness of simultaneous use of biologic agents in combination or with tofacitinib in patients with IBD. Rates of adverse events, clinical remission, and endoscopic remission were synthesized using pooled data, and we identified factors associated with successful dual therapy. RESULTS: We identified 30 studies reporting 288 trials of dual biologic or small molecule therapy in 279 patients (76% Crohn's disease; median duration of treatment 24 weeks (IQR25-IQR75 1332)). The main indications for dual therapy included medically refractory IBD (81%) and concurrent extra-intestinal manifestations or rheumatologic disease (12%). The most common combinations of dual therapy included tumor necrosis factor-α antagonists & anti-integrins (48%), ustekinumab & anti-integrins (19%); 61% of patients had previously failed at least one of the two therapies used in combination. Over a median follow-up of 32 weeks (IQR25-IQR75 24-52), pooled rates of adverse and serious adverse events were 31% (95% CI, 13%-54%) and 6.5% (95% CI, 2.1%-13.1%); pooled rates of clinical and endoscopic remission were 59% (95% CI, 42%-74%), and 34% (95% CI, 23%-46%), respectively. 12% (95% CI, 4%-24%) of patients required surgery. Rates of success were higher in patients on dual therapy due to EIM. Heterogeneity was not significant for endoscopic response (P = .88, I2 = 0%), endoscopic remission (P = .44, I2 = 0%), and malignancy (P = .87, I2 = 0%). However, significant heterogeneity existed for other outcomes. CONCLUSIONS: Dual biologic or small molecule therapy may be a possible option in highly selected, refractory IBD patients at specialized centers. Higher quality combination of therapies with a significant improvement in the quality of data is required prior to more widespread use.

Vitamin C Deficiency: An Under-Recognized Condition in Crohn's Disease.

Although many nutritional deficiencies are associated with Crohn's disease (CD), vitamin C deficiency is less frequently diagnosed and reported despite its prevalence. Vitamin C deficiency may be more difficult to diagnose in patients with CD because symptoms from active CD may overlap with scurvy. Identification of the deficiency is vital, however, because treatment can lead to swift, marked resolution of symptoms. We present a patient with long-standing CD who presented with gum bleeding and was found to have scurvy.

Disability in inflammatory bowel disease patients is associated with race, ethnicity and socio-economic factors.

BACKGROUND: Race, ethnicity and socio-economic status impact clinical outcomes in inflammatory bowel disease (IBD) patients. However, their impact on disability has not been studied. AIM: To determine the association between race, ethnicity and socio-economic factors with disability in IBD, using the validated IBD disability index (IBD-DI). METHODS: Ambulatory IBD patients were enrolled at five academic centres participating in the New York Crohn's and Colitis Organization. We assessed the IBD-DI, and collected clinical and socio-economic data. Factors associated with moderate-to-severe disability (IBD-DI score > 35) on univariable analysis were tested in multivariable models with adjusted odds ratios (aOR) and 95% confidence intervals (CI) reported. RESULTS: In this study, 323 patients (57.3% CD, 51.4% female) were enrolled; 17.7% were Hispanic, 17% were non-Hispanic black, 56.0% were non-Hispanic Caucasian and 9.3% belonged to non-Hispanic non-black minority races. However, 39.0% of patients were publicly insured and 38.4% of patients had low annual household income (<$50 000). 100 (31.0%) patients reported moderate-to-severe disability. On multivariable analysis, Hispanic ethnicity (aOR 2.7, 95% CI 1.3-5.6), non-Hispanic non-black minority race (aOR 3.5, 95% CI 1.3-8.9), public payer (aOR 2.1, 95% CI 1.1-4.0) and low annual household income (aOR 3.0, 95% CI 1.7-5.4) were associated with moderate-to-severe disability controlling for disease characteristics. CONCLUSIONS: IBD patients who are minorities, have public insurance, or low household income, are 2-3 times more likely to report moderate-to-severe disability independent of disease characteristics in the United States. Future studies are needed to study their complex relationship and to mitigate disability.

Maternal iron status during pregnancy compared with neonatal iron status better predicts placental iron transporter expression in humans.

The placenta richly expresses nonheme and heme Fe transport proteins. To address the impact of maternal and neonatal Fe status and hepcidin on the regulation of these proteins, mRNA expression and protein abundance of nonheme and heme Fe transport proteins were evaluated in placental tissue from 154 adolescents. Regression analyses found maternal Fe status was significantly associated with multiple placental nonheme and heme transporters, whereas neonatal Fe status was related to only 3 heme transporters. Across statistical analyses, maternal Fe status was consistently associated with the placental nonheme Fe importer transferrin receptor 1 (TfR1). Protein abundance of TfR1 was related to midgestation maternal serum ferritin (SF) (ß = -0.32; P = 0.005) and serum TfR (ß = 0.25; P = 0.024). Protein abundance of the heme importer, proton-coupled folate transporter, was related to neonatal SF (ß = 0.30; P = 0.016) and serum TfR (ß = -0.46; P < 0.0001). Neonatal SF was also related to mRNA expression of the heme exporter feline leukemia virus subgroup C receptor 1 (ß = -0.30; P = 0.004). In summary, maternal Fe insufficiency during pregnancy predicts increased expression of the placental nonheme Fe transporter TfR1. Associations between placental heme Fe transporters and neonatal Fe status require further study.-Best, C. M., Pressman, E. K., Cao, C., Cooper, E., Guillet, R., Yost, O. L., Galati, J., Kent, T. R., O'Brien, K. O. Maternal iron status during pregnancy compared with neonatal iron status better predicts placental iron transporter expression in humans.