Artificial intelligence (AI) is increasingly used to improve adenoma detection during colonoscopy. This meta-analysis aimed to provide an updated evaluation of computer-aided detection (CADe) systems and their impact on key colonoscopy quality indicators. We searched the Embase, PubMed and MEDLINE databases from inception until February 15, 2024, for randomised control trials (RCTs) comparing the performance CADe systems with routine unassisted colonoscopy in the detection of colorectal adenomas. 28 RCTs were selected for inclusion involving 23861 participants. Random-effects meta-analysis demonstrated a 20% increase in ADR (RR 1.20, 95% CI 1.14-1.27, p<0.01) and 55% decrease in AMR (RR 0.45, 95% CI 0.37-0.54, p<0.01) with AI-assisted colonoscopy. Subgroup analyses involving only expert endoscopists demonstrated a similar effect size (RR 1.19, 95% CI 1.11-1.27, p<0.001), with similar findings seen in analysis of differing CADe systems and healthcare settings. CADe use also significantly increased adenomas per colonoscopy (weighted mean difference 0.21, 95% CI 0.14-0.29, p<0.01), primarily due to increased diminutive lesion detection, with no significant difference seen in detection of advanced adenoma. Sessile serrated lesion detection (RR 1.10, 95% CI 0.93-1.30, p=0.27) and miss rates (RR 0.44, 95% CI 0.16-1.19, p=0.11) were similar. There was an average 0.15 minute prolongation of withdrawal time with AI-assisted colonoscopy (weighted mean difference 0.15, 95% CI 0.04-0.25, p = 0.01) and a 39% increase in the rate of non-neoplastic resection (RR 1.39, 95% CI 1.23-1.57, p<0.001). AI-assisted colonoscopy significantly improved adenoma, but not sessile serrated lesion, detection irrespective of endoscopist experience, system type or healthcare setting.

Age-related macular degeneration (AMD) is the leading cause of blindness in the industrialized world. AMD is associated with dysfunction and atrophy of the retinal pigment epithelium (RPE), which provides critical support for photoreceptor survival and function. RPE transplantation is a promising avenue towards a potentially curative treatment for early stage AMD patients, with encouraging reports from animal trials supporting recent progression toward clinical treatments. Mature RPE cells have been reported to be superior, but a detailed investigation of the specific changes in the expression pattern of key RPE genes during maturation is lacking. To understand the effect of maturity on RPE, we investigated transcript levels of 19 key RPE genes using ARPE-19 cell line and human embryonic stem cell-derived RPE cultures. Mature RPE cultures upregulated PEDF, IGF-1, CNTF and BDNF—genes that code for trophic factors known to enhance the survival and function of photoreceptors. Moreover, the mRNA levels of these genes are maximized after 42 days of maturation in culture and lost upon dissociation to single cells. Our findings will help to inform future animal and human RPE transplantation efforts.

Background: The management of inflammatory bowel disease [IBD] patients with concurrent liver transplantation is challenging, and data regarding the safety and efficacy of Janus kinase [JAK] inhibitors with anti-rejection medications are required. We report the experience of all liver transplant recipients receiving tofacitinib and/or upadacitinib for IBD across three states in Australia. Methods: All liver transplant recipients from the Australian states of Victoria, New South Wales, and Tasmania, who required tofacitinib or upadacitinib for the treatment of IBD, were identified using prospectively maintained liver transplant databases. Patients were followed up until medication cessation or last follow-up. Clinical safety and efficacy data were collected. Results: Eight patients [median age 30 years] were included, seven of whom received first-line JAK inhibition with tofacitinib. All patients had failed one or more biologic therapies prior to commencing JAK inhibition, including six patients who had failed two or more agents. JAK inhibition was continued for a median of 17 months, with 143 patient-months of combined follow-up. The anti-rejection medication tacrolimus was prescribed in all patients. Overall, seven [88%] patients achieved clinical remission, including all three patients who were switched from tofacitinib to upadacitinib. One patient required colectomy after 1 month of treatment. There were no other cases of serious infection, venous thromboembolism, or major adverse cardiovascular events during follow-up. Conclusions: As the largest case series to date, these data indicate that combining JAK inhibition with transplant anti-rejection medication may be a safe and clinically effective method of treating IBD in patients with prior biologic failure.

Anchorage-independent survival after intravasation of cancer cells from the primary tumor site represents a critical step in metastasis. Here, we reveal new insights into how MUC13-mediated anoikis resistance, coupled with survival of colorectal tumor cells, leads to distant metastasis. We found that MUC13 targets a potent transcriptional coactivator, YAP1, and drives its nuclear translocation via forming a novel survival complex, which in turn augments the levels of pro-survival and metastasis-associated genes. High expression of MUC13 is correlated well with extensive macrometastasis of colon cancer cells with elevated nuclear YAP1 in physiologically relevant whole animal model systems. Interestingly, a positive correlation of MUC13 and YAP1 expression was observed in human colorectal cancer tissues. In brief, the results presented here broaden the significance of MCU13 in cancer metastasis via targeting YAP1 for the first time and provide new avenues for developing novel strategies for targeting cancer metastasis.

Diversion of the faecal stream is associated with diversion colitis (DC). Preliminary studies indicate that microbiome dysbiosis contributes to its development and potentially treatment. This review aims to characterise these changes in the context of faecal diversion and identify their clinical impact. A systematic search was conducted using MEDLINE, EMBASE and CENTRAL databases using a predefined search strategy identifying studies investigating changes in microbiome following diversion. Findings reported according to PRISMA guidelines. Of 743 results, 6 met inclusion criteria. Five reported significantly decreased microbiome diversity in the diverted colon. At phylum level, decreases in Bacillota with a concomitant increase in Pseudomonadota were observed, consistent with dysbiosis. At genus level, studies reported decreases in beneficial lactic acid bacteria which produce short-chain fatty acid (SCFA), which inversely correlated with disease severity. Significant losses in commensals were also noted. These changes were seen to be partially reversible with restoration of bowel continuity. Changes within the microbiome were reflected by histopathological findings suggestive of intestinal dysfunction. Faecal diversion is associated with dysbiosis in the diverted colon which may have clinical implications. This is reflected in loss of microbiome diversity, increases in potentially pathogenic-associated phyla and reduction in SCFA-producing and commensal bacteria.

Dysregulated ribosome biogenesis and p53 mutations are known to play oncogenic roles in various cancers, including pancreatic cancer. In this study, we demonstrated the therapeutic potential of BMH-21, a pharmacologic inhibitor of RNA polymerase I, against pancreatic cancer by uncovering a novel molecular mechanism involving RPA194-mediated ubiquitination of mutant p53 without affecting the ubiquitination of wild-type p53. Our key findings are that (i) BMH-21 selectively induces apoptosis and cell growth inhibition of pancreatic cancer cells with no effect on normal human pancreatic ductal epithelial cells; (ii) BMH-21 degrades RPA194; (iii) BMH-21 inhibits recruitment of both RPA194 and RPA135 on rDNA to suppress pre-rRNA synthesis; (iv) RPA194 physically interacts with p53 and BMH-21–induced degradation of RPA194 selectively exposes truncated and mutated p53 for ubiquitination with no effect on ubiquitination of wild-type p53 in pancreatic cancer cells; and (v) BMH-21 treatment significantly reduces the growth of orthotopic xenograft pancreatic tumors in athymic nude mice with no observed toxicity. Altogether, these findings suggest that BMH-21 is a promising, nontoxic therapeutic agent for patients with pancreatic cancer with aberrant ribosome biogenesis and mutant p53, offering a potential new avenue for targeted treatment.