Higher Intra-Abdominal Visceral Adipose Tissue Mass Is Associated With Lower Rates of Clinical and Endoscopic Remission in Patients With Inflammatory Bowel Diseases Initiating Biologic Therapy: Results of the Constellation Study.

BACKGROUND & AIMS: We sought to assess the association between intra-abdominal visceral adipose tissue (IA-VAT) and response to 3 different biologic drugs in patients with inflammatory bowel disease (IBD) and to investigate its effects on inflammatory cytokine expression, pharmacokinetics, and intestinal microbiota. METHODS: We prospectively enrolled subjects with active IBD initiating infliximab, vedolizumab, or ustekinumab and a healthy control group. Baseline body composition (including IA-VAT as percent of total body mass [IA-VAT%]) was measured using GE iDXA scan. Primary outcome was corticosteroid- free deep remission at weeks 14-16, defined as Harvey Bradshaw Index <5 for Crohn's disease and partial Mayo score <2 for ulcerative colitis, with a normal C-reactive protein and fecal calprotectin. Secondary outcomes were corticosteroid-free deep remission and endoscopic remission (Endoscopic Mayo Score ≤1 in ulcerative colitis or Simple Endoscopic Score for Crohn's disease ≤2) at weeks 30-46. RESULTS: A total of 141 patients with IBD and 51 healthy controls were included. No differences in body composition parameters were seen between the IBD and healthy control cohorts. Patients with higher IA-VAT% were less likely to achieve corticosteroid-free deep remission (P < .001) or endoscopic remission (P = .02) vs those with lower IA-VAT%. Furthermore, nonresponders with high IA-VAT% had significantly higher serum interleukin-6 and tumor necrosis factor at baseline compared with responders and patients with low IA-VAT%. Drug pharmacokinetic properties and microbiota diversity were similar when comparing high and low IA-VAT% groups. CONCLUSIONS: Higher IA-VAT% was independently associated with worse outcomes. This association could be driven at least partially by discrete differences in inflammatory cytokine expression.

Ultraviolet A light effectively reduces bacteria and viruses including coronavirus.

Antimicrobial-resistant and novel pathogens continue to emerge, outpacing efforts to contain and treat them. Therefore, there is a crucial need for safe and effective therapies. Ultraviolet-A (UVA) phototherapy is FDA-approved for several dermatological diseases but not for internal applications. We investigated UVA effects on human cells in vitro, mouse colonic tissue in vivo, and UVA efficacy against bacteria, yeast, coxsackievirus group B and coronavirus-229E. Several pathogens and virally transfected human cells were exposed to a series of specific UVA exposure regimens. HeLa, alveolar and primary human tracheal epithelial cell viability was assessed after UVA exposure, and 8-Oxo-2'-deoxyguanosine was measured as an oxidative DNA damage marker. Furthermore, wild-type mice were exposed to intracolonic UVA as an in vivo model to assess safety of internal UVA exposure. Controlled UVA exposure yielded significant reductions in Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Enterococcus faecalis, Clostridioides difficile, Streptococcus pyogenes, Staphylococcus epidermidis, Proteus mirabilis and Candida albicans. UVA-treated coxsackievirus-transfected HeLa cells exhibited significantly increased cell survival compared to controls. UVA-treated coronavirus-229E-transfected tracheal cells exhibited significant coronavirus spike protein reduction, increased mitochondrial antiviral-signaling protein and decreased coronavirus-229E-induced cell death. Specific controlled UVA exposure had no significant effect on growth or 8-Oxo-2'-deoxyguanosine levels in three types of human cells. Single or repeated in vivo intraluminal UVA exposure produced no discernible endoscopic, histologic or dysplastic changes in mice. These findings suggest that, under specific conditions, UVA reduces various pathogens including coronavirus-229E, and may provide a safe and effective treatment for infectious diseases of internal viscera. Clinical studies are warranted to further elucidate the safety and efficacy of UVA in humans.

A qualitative inquiry into patients' perspectives on individualized priorities for treatment outcomes in inflammatory bowel diseases.

PURPOSE: Patients with inflammatory bowel diseases (IBD) experience a variety of symptoms and limitations due to their condition. While many outcome measures are available to assess IBD symptom level and disease activity, individual patients' preferences are usually not accounted for. Individualized outcome measures allow individual patients to select and weigh outcomes based on their relative importance, and have been developed in other medical disciplines. In this study, we explored IBD patients' perspectives on different strategies to prioritize IBD-specific health outcomes. METHODS: Existing individualized measures were modified for relevance to IBD patients. We performed six focus groups, in which patients were asked to rate and weigh these measures in a series of exercises and to discuss the pros and cons of five different prioritization methods (Likert scale, ranking, selecting outcomes, distribute points, and using a rotating disk) using a semi-structured approach. A thematic analysis revealed key themes in the data. RESULTS: Patients' thoughts could be grouped into four key themes with 2-4 subthemes each: (1) prioritizing outcomes; (2) differences between methods; (3) outcomes to include; and (4) practical use. Overall, it was challenging for many patients to prioritize outcomes. Among the different prioritization methods, the rotating disk was perceived as the most intuitive. Patients anticipated that this visualization would also help them communicate with their physician. CONCLUSION: In a series of focus groups, a visual rotating disk was found to be an intuitive and holistic way to elicit the relative importance of different outcomes for individual IBD patients.

Therapy for Crohn's Disease: a Review of Recent Developments.

PURPOSE OF REVIEW: To review recent advances in the treatment of Crohn's disease. RECENT FINDINGS: Several key advances are highlighted, including the increasing role of treatment algorithms and where new therapies can be used most effectively, the appropriate use of therapeutic drug monitoring, optimal management of post-surgical patients, and the role of multi-disciplinary clinics. The last several years have seen a number of exciting developments in the field of Crohn's therapy. This review covers research advances including updated treatment algorithms focusing on identifying patient risk as well as the role of drug monitoring in managing the disease. We also review the optimal management of post-surgical patients as well as new biologics and biosimilars. Finally, we describe innovations in care delivery including multi-disciplinary clinics and emerging evidence from developing therapeutics.

Future biologic targets for IBD: potentials and pitfalls.

The treatment of patients with IBD has evolved towards biologic therapy, which seeks to target specific immune and biochemical abnormalities at the molecular and cellular level. Multiple genes have been associated with susceptibility to IBD, and many of these can be linked to alterations in immune pathways. These immune pathways provide avenues for understanding the pathogenesis of IBD and suggest future drug targets, such as the IL-12-IL-23 pathway. In addition, failed therapeutic drug trials can provide valuable information about pitfalls in study design, drug delivery and disease activity assessment. Future biologic drug development will benefit from the early identification of subsets of patients who are most likely to respond to therapy by use of biological markers of genetic susceptibility or immunologic susceptibility.

A new method for endoscopic closure of gastrocolonic fistula: novel application of a cardiac septal defect closure device (with video).

BACKGROUND: Gastrocolonic fistula after percutaneous endoscopic gastrostomy PEG tube placement is an uncommon but serious complication. These fistulous tracts are often fibrotic and frequently require surgical intervention. OBJECTIVE: To describe a novel endoscopic treatment for gastrocolonic fistula. DESIGN: Case report. SETTING: Inpatient hospital setting. PATIENT: An 82-year-old woman was seen 1 year after PEG placement with feculent vomiting; imaging studies showed a gastrocolonic fistula. Cardiopulmonary comorbidities posed an unacceptable surgical risk. Endoscopic attempts at fistula closure with hemoclip placement and biodegradable plug were unsuccessful. Total parenteral nutrition resulted in multiple metabolic and infectious complications. INTERVENTION: Gastrocolonic fistula closure was performed twice by using cardiac septal defect closure devices. The first closure was achieved by using the Amplatzer double-disk nitinol wire mesh atrial septal defect closure device, which was deployed under endoscopic and fluoroscopic guidance across the fistula tract. The proximal disk was then injected with cyanoacrylate glue to create a watertight seal. The second closure, performed 4 months later after collapse of the initial device, was performed by using the CardioSEAL septal repair implant. This was secured in place with hemoclips and similarly injected with cyanoacrylate glue to create a watertight seal. MAIN OUTCOME MEASUREMENTS: Fistula closure, as determined by contrast gastrogram through a PEG tube and gastrograffin enema. RESULTS: Successful fistula closure was achieved for 4 months after initial device placement. After the second device was placed, the patient remained clinically well until her demise 18 months later from unrelated causes. LIMITATIONS: These procedures were performed on only one subject. CONCLUSIONS: Successful endoscopic closure of gastrocolonic fistula can be achieved, even with long-standing, fibrotic fistulous tracts by using a novel endoscopic approach.