Comparative Long-Term Drug Survival of Vedolizumab, Adalimumab, and Infliximab in Biologic-Naïve Patients with Ulcerative Colitis.

BACKGROUND: The comparative long-term survival of first-line biologics for UC and reasons for drug discontinuation are poorly understood. We sought to compare the long-term drug survival related to non-response (NR) and adverse effects (AEs) for vedolizumab, adalimumab, and infliximab among biologic-naïve patients with UC. METHODS: This was a retrospective cohort study of adult biologic-naïve patients with moderate-to-severe UC initiating vedolizumab, adalimumab, or infliximab 6/1/14-12/31/20 at a large academic medical center. The primary outcome was time to biologic discontinuation for primary or secondary NR (including colectomy). The secondary outcome was time to biologic discontinuation due to AEs. Inverse probability of treatment-weighted (IPTW) Cox regression was used to perform three pair-wise comparisons of drug survival. RESULTS: The cohort included 805 patients with UC who initiated vedolizumab (n = 195), adalimumab (n = 278), or infliximab (n = 332). The adjusted hazard of biologic discontinuation for NR was significantly lower for vedolizumab vs adalimumab (HR 0.51, 95% CI 0.34-0.75), similar for vedolizumab vs infliximab (HR 1.32, 95% CI 0.79-2.18), and greater for adalimumab vs infliximab (HR 2.07, 95% CI 1.51-2.86). The adjusted hazard of discontinuation for AEs was significantly lower for vedolizumab vs adalimumab (HR 0.25, 95% CI 0.09-0.64), lower for vedolizumab vs infliximab (HR 0.21, 95% CI 0.10-0.46), and similar for adalimumab vs infliximab (HR 0.85, 95% CI 0.53-1.35). CONCLUSIONS: There was greater survival of vedolizumab compared to adalimumab for clinical response and greater survival of vedolizumab compared to both adalimumab and infliximab for AEs. These long-term data support the use of vedolizumab as a first-line biologic over adalimumab for biologic-naïve patients with UC.

Effectiveness and Safety of Colonic and Capsule Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) emerged as rescue treatment for multiply recurrent Clostridioides difficile infections (rCDIs) nonresponsive to standard therapy. However, estimation of FMT efficacy varies among different protocols and formulations, while placebo-controlled clinical trials have excluded most rCDI patients because of medical comorbidities. This study aimed to determine the safety and effectiveness of capsule FMT (cap-FMT) and colonoscopy FMT (colo-FMT) for rCDI using standardized products in a large, multicenter, prospective, real-world cohort. METHODS: Clinical outcomes and adverse events after FMT performed for rCDI at 6 sites were captured in a prospective registry. FMT was performed using 1 of 2 standardized formulations of microbiota manufactured by the University of Minnesota Microbiota Therapeutics Program, freeze-dried/encapsulated or frozen-thawed/liquid. The FMT administration route was determined by the treating physician. The rCDI cure rate was assessed at 1 and 2 months. Safety data were collected within the first 72 hours and at 1 and 2 months. Logistic regression was used to investigate factors associated with FMT failure. RESULTS: A total of 301 FMTs were performed in 269 unique patients. Two-thirds were cap-FMT. CDI cure rates were 86% (95% CI, 82%-90%) at 1 month and 81% (95% CI, 75%-86%) at 2 months. There was no difference in the 1-month or 2-month cure rate between cap-FMT and colo-FMT. Cap-FMT recipients were older and less likely to be immunosuppressed or have inflammatory bowel disease. Patient factors of older age and hemodialysis were associated with FMT failure by 2 months on multivariate logistic regression. In addition, post-FMT antibiotic use was associated with FMT failure at 2 months. One serious adverse event was related to colonoscopy (aspiration pneumonia), otherwise no new safety signals were identified. CONCLUSIONS: Cap-FMT using freeze-dried capsules has a similar safety and effectiveness profile compared with colo-FMT, without the procedural risks of colonoscopy. Although highly effective overall, patient selection is a key factor to optimizing FMT success.

Assessing the clinical value of faecal bile acid profiling to predict recurrence in primary Clostridioides difficile infection.

BACKGROUND: Factors influencing recurrence risk in primary Clostridioides difficile infection (CDI) are poorly understood, and tools predicting recurrence are lacking. Perturbations in bile acids (BAs) contribute to CDI pathogenesis and may be relevant to primary disease prognosis. AIMS: To define stool BA dynamics in patients with primary CDI and to explore signatures predicting recurrence METHODS: Weekly stool samples were collected from patients with primary CDI from the last day of anti-CDI therapy until recurrence or, otherwise, through 8 weeks post-completion. Ultra-high performance liquid chromatography-mass spectrometry was used to profile BAs. Stool bile salt hydrolase (BSH) activity was measured to determine primary BA bacterial deconjugation capacity. Multivariate and univariate models were used to define differential BA trajectories in patients with recurrence versus those without, and to assess faecal BAs as predictive markers for recurrence. RESULTS: Twenty (36%) of 56 patients (median age: 57, 64% male) had recurrence; 80% of recurrences occurred within the first 9 days post-antibiotic treatment. Principal component analysis of stool BA profiles demonstrated clustering by recurrence status and post-treatment timepoint. Longitudinal faecal BA trajectories showed recovery of secondary BAs and their derivatives only in patients without recurrence. BSH activity increased over time only among non-relapsing patients (ß = 0.056; likelihood ratio test p = 0.018). A joint longitudinal-survival model identified five stool BAs with area under the receiver operating characteristic curve >0.73 for predicting recurrence within 9 days post-CDI treatment. CONCLUSIONS: Gut BA metabolism dynamics differ in primary CDI patients between those developing recurrence and those who do not. Individual BAs show promise as potential novel biomarkers to predict CDI recurrence.

Tofacitinib for the Treatment of Pouch-Related Disorders: A Case Series.

In this case series, 6 patients with chronic pouchitis (n = 3), cuffitis (n = 2), or Crohn's-like disease of the pouch (n = 1) were treated with tofacitinib. One patient achieved clinical response; however, all patients ultimately discontinued therapy due to nonresponse or adverse events.

Gut metabolites predict Clostridioides difficile recurrence.

BACKGROUND: Clostridioides difficile infection (CDI) is the most common hospital acquired infection in the USA, with recurrence rates > 15%. Although primary CDI has been extensively linked to gut microbial dysbiosis, less is known about the factors that promote or mitigate recurrence. Moreover, previous studies have not shown that microbial abundances in the gut measured by 16S rRNA amplicon sequencing alone can accurately predict CDI recurrence. RESULTS: We conducted a prospective, longitudinal study of 53 non-immunocompromised participants with primary CDI. Stool sample collection began pre-CDI antibiotic treatment at the time of diagnosis, and continued up to 8 weeks post-antibiotic treatment, with weekly or twice weekly collections. Samples were analyzed using (1) 16S rRNA amplicon sequencing, (2) liquid chromatography/mass-spectrometry metabolomics measuring 1387 annotated metabolites, and (3) short-chain fatty acid profiling. The amplicon sequencing data showed significantly delayed recovery of microbial diversity in recurrent participants, and depletion of key anaerobic taxa at multiple time-points, including Clostridium cluster XIVa and IV taxa. The metabolomic data also showed delayed recovery in recurrent participants, and moreover mapped to pathways suggesting distinct functional abnormalities in the microbiome or host, such as decreased microbial deconjugation activity, lowered levels of endocannabinoids, and elevated markers of host cell damage. Further, using predictive statistical/machine learning models, we demonstrated that the metabolomic data, but not the other data sources, can accurately predict future recurrence at 1 week (AUC 0.77 [0.71, 0.86; 95% interval]) and 2 weeks (AUC 0.77 [0.69, 0.85; 95% interval]) post-treatment for primary CDI. CONCLUSIONS: The prospective, longitudinal, and multi-omic nature of our CDI recurrence study allowed us to uncover previously unrecognized dynamics in the microbiome and host presaging recurrence, and, in particular, to elucidate changes in the understudied gut metabolome. Moreover, we demonstrated that a small set of metabolites can accurately predict future recurrence. Our findings have implications for development of diagnostic tests and treatments that could ultimately short-circuit the cycle of CDI recurrence, by providing candidate metabolic biomarkers for diagnostics development, as well as offering insights into the complex microbial and metabolic alterations that are protective or permissive for recurrence. Video Abstract.

COVID-19 Vaccination Intent and Perceptions Among Patients With Inflammatory Bowel Diseases.

Patients with inflammatory bowel disease (IBD) develop coronavirus disease 2019 (COVID-19) at similar rates as the general population, and there was initial concern regarding potential for severe illness.1-4 Vaccinations were authorized for emergency use in the United States in December 2020 and aim to halt the spread of COVID-19. However, there are concerns that people will be hesitant to receive the vaccine for a variety of reasons including insufficient data in certain populations including those with IBD. We surveyed patients with IBD to identify potential concerns regarding COVID-19 vaccination.

Nanoscale and Macroscale Effects of Mineral Deposition During Water Evaporation on Nanoporous Surfaces.

Recent studies have indicated that droplet evaporation heat transfer can be substantially enhanced by fabricating a thin nanoporous superhydrophilic layer on a metal substrate. Such surfaces have immense potential to improve spray cooling processes, however, little durability testing of the surface has been performed. In spray cooling applications, as water evaporates any impurities in the water will be deposited onto the surface. Primarily, this investigation serves to demonstrate how minerals in hard water deposit on the surface and interact with the ZnO nanopillars of the superhydrophilic surface. Quantifying the effects of mineral scale on droplet spreading and vaporization heat transfer on the surface is important in determining implementation requirements to advance the surface into industry applications. Micrographs of the surface demonstrate minerals deposit nonuniformly and quickly fill the nanostructure. Despite a reduction in the extent of droplet spreading due to the mineral deposition, scaled surfaces still demonstrated improved thermal performance compared to an uncoated, smooth copper surface. Scale tended to build up on previously deposited scale, leaving largely uncoated areas where droplets chose to preferentially spread and resulting in a continued low contact angle. Maintaining these uncoated areas and reducing the contaminants present in the water will extend the life and performance of the nanostructured surface.