Engineering tumor-colonizing E. coli Nissle 1917 for detection and treatment of colorectal neoplasia.

Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment. Here, first, we demonstrate selective colonization of colorectal adenomas after oral delivery of probiotic E. coli Nissle 1917 (EcN) to a genetically-engineered murine model of CRC predisposition and orthotopic models of CRC. We next undertake an interventional, double-blind, dual-centre, prospective clinical trial, in which CRC patients take either placebo or EcN for two weeks prior to resection of neoplastic and adjacent normal colorectal tissue (ACTRN12619000210178). We detect enrichment of EcN in tumor samples over normal tissue from probiotic-treated patients (primary outcome of the trial). Next, we develop early CRC intervention strategies. To detect lesions, we engineer EcN to produce a small molecule, salicylate. Oral delivery of this strain results in increased levels of salicylate in the urine of adenoma-bearing mice, in comparison to healthy controls. To assess therapeutic potential, we engineer EcN to locally release a cytokine, GM-CSF, and blocking nanobodies against PD-L1 and CTLA-4 at the neoplastic site, and demonstrate that oral delivery of this strain reduces adenoma burden by ~50%. Together, these results support the use of EcN as an orally-deliverable platform to detect disease and treat CRC through the production of screening and therapeutic molecules.

Cost-effectiveness of taurolidine-citrate in a cohort of patients with intestinal failure receiving home parenteral nutrition.

BACKGROUND: Catheter-related bloodstream infections (CRBSIs) in patients receiving home parenteral nutrition (HPN) for chronic intestinal failure (CIF) are associated with significant morbidity and financial costs. Taurolidine is associated with a reduction in bloodstream infections, with limited information on the cost-effectiveness as the primary prevention. This study aimed to determine the cost-effectiveness of using taurolidine-citrate for the primary prevention of CRBSIs within a quaternary hospital. METHODS: All patients with CIF receiving HPN were identified between January 2015 and November 2022. Data were retrospectively collected regarding patient demographics, HPN use, CRBSI diagnosis, and use of taurolidine-citrate. The direct costs associated with CRBSI-associated admissions and taurolidine-citrate use were obtained from the coding department using a bottom-up approach. An incremental cost-effective analysis was performed, with a time horizon of 4 years, to compare the costs associated with primary and secondary prevention against the outcome of cost per infection avoided. RESULTS: Forty-four patients received HPN within this period. The CRBSI rates were 3.25 infections per 1000 catheter days before the use of taurolidine-citrate and 0.35 infections per 1000 catheter days after taurolidine-citrate use. The incremental cost-effectiveness ratio indicates primary prevention is the weakly dominant intervention, with the base case value of $27.04 per CRBSI avoided. This held with one-way sensitivity analysis. CONCLUSION: Taurolidine-citrate in the primary prevention of CRBSIs in patients with CIF receiving HPN is associated with reduced hospital costs and infection rates.

The Impact of Obesity on Inflammatory Bowel Disease.

Obesity is prevalent in the inflammatory bowel disease (IBD) population, particularly in newly developed countries where both IBD and obesity in the general population are on the rise. The role of obesity in the pathogenesis of IBD was entertained but results from available studies are conflicting. It does, however, appear to negatively influence disease course whilst impacting on our medical and surgical therapies. The pro-inflammatory profile of the visceral adipose tissue might play a role in the pathogenesis and course of Crohn's Disease (CD). Interestingly, isolating the mesentery from the surgical anastomosis using a KONO-S technique significantly decreases anastomotic recurrence rate. Anti-obesity therapy is not widely used in IBD but was suggested as an adjunctive therapy in those patients. In this review, we aimed to highlight the epidemiology of obesity in IBD and to describe its influence on disease course and outcomes.

Colorectal cancer detection and treatment with engineered probiotics.

Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment strategies. Here, we demonstrate the phenomenon of selective, long-term colonization of colorectal adenomas after oral delivery of probiotic E. coli Nissle 1917 (EcN) to a genetically-engineered murine model of CRC predisposition. We show that, after oral administration, adenomas can be monitored over time by recovering EcN from stool. We also demonstrate specific colonization of EcN to solitary neoplastic lesions in an orthotopic murine model of CRC. We then exploit this neoplasia-homing property of EcN to develop early CRC intervention strategies. To detect lesions, we engineer EcN to produce a small molecule, salicylate, and demonstrate that oral delivery of this strain results in significantly increased levels of salicylate in the urine of adenoma-bearing mice, in comparison to healthy controls. We also assess EcN engineered to locally release immunotherapeutics at the neoplastic site. Oral delivery to mice bearing adenomas, reduced adenoma burden by ∻50%, with notable differences in the spatial distribution of T cell populations within diseased and healthy intestinal tissue, suggesting local induction of robust anti-tumor immunity. Together, these results support the use of EcN as an orally-delivered platform to detect disease and treat CRC through its production of screening and therapeutic molecules.

Assessing effectiveness and patient perceptions of a novel electronic medical record for the management of inflammatory bowel disease.

BACKGROUND AND AIM: There is an increasing prevalence of chronic disease worldwide, resulting in multiple management challenges. Inflammatory bowel disease (IBD) is an exemplar chronic disease requiring coordinated longitudinal care. We propose that Crohn's Colitis Care (CCCare), a novel IBD-specific, structured electronic medical record is effective at improving data capture and is acceptable to patients. METHODS: A comparison was made between IBD-data completeness in usual records and CCCare. CCCare's acceptability to patients was assessed in two independent IBD patient cohorts and included:• Overall ratings of acceptability.• Factors associated with pre-exposure acceptability ratings.• Whether exposure and security concerns influenced acceptability ratings.• Direct patient feedback through CCCare's patient portal. RESULTS: In all cases reviewed, there was data gain using structured CCCare fields compared with IBD documentation in usual medical records. The overall acceptability in the combined cohort (n = 310) was very high. More than three-quarters of patients rated acceptability as >7 of 10. Self-reported information technology (IT) literacy positively associated with acceptability. Exposure had a small positive affect on acceptability, whereas security concerns had little impact on acceptability. Patient portal feedback revealed that most patients are very likely to recommend CCCare to others (8.56 ± 2.2 [out of 10]). CONCLUSION: CCCare is effective in supporting more complete IBD-specific data capture compared with usual medical records. It is highly acceptable to patients, especially those with reasonable IT literacy. Patient concerns about privacy and security of electronic medical records (EMRs) did not significantly affect acceptability.

Infliximab-related weight gain in inflammatory bowel disease: associations and financial impacts.

Association between tumour necrosis alpha inhibitors and weight gain has been reported. We examined weight change in our cohort of inflammatory bowel disease patients treated with infliximab (IFX) for over 12 months, its associations and financial implications. Two-thirds of patients gained weight during the course of therapy. The mean change in weight after 12 months of IFX therapy was 3.3 (±6.5) kg.