Long-Term Safety Outcomes of Fecal Microbiota Transplantation: Real-World Data Over 8 Years From the Hong Kong FMT Registry.

BACKGROUND AND AIMS: Prospective long-term real-world safety data after fecal microbiota transplantation (FMT) remain limited. We reported long-term outcomes of FMT from a population-based FMT registry in Hong Kong. METHODS: We recruited patients undergoing FMT for recurrent Clostridioides difficile infection (CDI) and non-CDI indications from clinical trials, from June 2013 to April 2022 in Hong Kong. We captured data on demographics, FMT indications and procedures, clinical outcomes and short- to long-term safety. New medical diagnoses were obtained from electronic medical records and independently adjudicated by clinicians. Long-term safety in patients with recurrent CDI was compared with a control group treated with antibiotics. RESULTS: Overall, 123 subjects (median age 53 years, range 13-90 years; 52.0% male) underwent 510 FMTs and were prospectively followed up for a median of 30.3 (range, 1-57.9) months. The most common indication for FMT was type 2 diabetes mellitus. The most common short-term adverse events within 1 month of FMT included diarrhea and abdominal pain. At long-term follow-up beyond 12 months, 16 patients reported 21 new-onset medical conditions confirmed by electronic medical records. All were adjudicated to be unlikely to be related to FMT. There was no new case of inflammatory bowel disease, irritable bowel syndrome, allergy, diabetes mellitus, or psychiatric disorder. In a subgroup of patients with recurrent CDI, FMT was associated with a significantly higher cumulative survival probability compared with matched control subjects. CONCLUSIONS: This prospective real-world data from Asia's first FMT registry demonstrated that FMT has an excellent long-term safety profile. The risk of developing new medical conditions beyond 12 months after FMT is low.

Respiratory admissions before and during the COVID-19 pandemic with mediation analysis of air pollutants, mask-wearing and influenza rates.

BACKGROUND AND OBJECTIVE: Decline in hospitalizations for various respiratory diseases has been reported during the COVID-19 pandemic, but what led to such an observation is uncertain. METHODS: This was a territory-wide, retrospective cohort study involving all public hospital admissions in Hong Kong from 1 January 2017 to 31 December 2020. Hospital admissions for respiratory diseases, including asthma, COPD and non-COVID pneumonia, were assessed. COVID-related admissions were excluded from this study. The time of commencement of the pandemic was taken from the fourth week of January 2020. The associations between air pollutant levels, influenza and mask-wearing rates with hospital admissions were assessed by mediation analyses. RESULTS: There were altogether 19,485, 78,693 and 238,781 admissions for asthma, COPD and non-COVID pneumonia from January 2017 to December 2020. There was a marked reduction in hospital admissions of asthma, COPD and non-COVID pneumonia (37%, 36% and 12% decrease in average daily admissions, respectively) during the COVID-19 pandemic compared to before. Air pollutant levels and influenza rate were decreased while mask-wearing rate was increased. Collinearity of mask-wearing rates and pandemic year was observed. For COPD, NO2 , SO2 , PM10 and influenza rates (4%, 11%, 4% and 4% of the total effect, respectively), while for non-COVID pneumonia, PM10 and influenza rates (11% and 52%, respectively) had significant mediation effect on changes in hospital admissions before and during the COVID-19 pandemic. CONCLUSION: During the COVID-19 pandemic, a decrease in air pollutant levels and influenza rate had mediation effect on the reduction in hospitalizations of COPD and non-COVID pneumonia.

Telementoring for endoscopic submucosal dissection in vivo training.

The provision of endoscopic training was significantly disrupted during the coronavirus disease (COVID-19) pandemic. It is difficult to provide training on endoscopic submucosal dissection (ESD) due to the complexity of the procedure and the shortage of local trainers. We have designed and conducted a simulation training course with telementoring, incorporating the concept of rapid cycle deliberate practice (RCDP). After a short tutorial on basic setup and maneuvering, the participants undergo 2 h of training on a live anesthetized pig to acquire the necessary skills for ESD. Two overseas experts were involved virtually in real time as telementors. A video camera was set up at each station, and both external and endoscopic views were transmitted live between the animal laboratory and telementors via the Zoom application. The overseas experts actively engaged in the simulation by giving live feedback and instructions to participants using visual aids supported by the meeting application. The training model utilized the concept of RCDP, where repeated immediate feedback and discussion would be carried out to enhance the efficiency of learning. Eighteen trainees were invited to participate in the course, six of them instructed by overseas telementors. Four ESD procedures were performed by participants under telementoring and achieved 100% en bloc resection without perforation. The times required for each ESD were similar with telementoring than that of on-site mentors. The establishment of telementoring has enabled knowledge and skill transfer of complex endoscopic procedures of ESD. With the limitations of international travel, this could be an alternative model allowing remote training, particularly when local experts are not readily available.

Appendix removal affects the subsequent cancer risk in Asian adults: a territory-wide population-based cohort study.

Human appendix is critical for the maintenance of intestinal homeostasis. Appendicectomy has been the optimal treatment of acute appendicitis, yet the cancer incidence after appendix removal remains unclear. In this territory-wide retrospective cohort study, adult participants who underwent appendicectomy from 2000 to 2018 were retrieved from a population database (n=43,983), while matched reference participants were retrieved as controls (n=85,853). After appendicectomy, the overall cancer risk was significantly increased (subdistribution hazard ratio (SHR)=1.124) compared to the non-appendicectomy group. Appendicectomy-treated males had higher cancer risk than males without appendicectomy (SHR=1.197), while such difference was not observed in female participants. Significant increase in cancer risk was also observed in elder participants (age >60) with appendicectomy (SHR=1.390). Appendicectomy was positively correlated with the risk of digestive tract and respiratory cancers including colon (SHR=1.440), pancreas (SHR=1.930), and trachea, bronchus, and lung (SHR=1.394). In contrast, the risk of liver cancer was markedly decreased after appendicectomy (SHR=0.713). In conclusion, we reported the association of appendicectomy with subsequent cancer incidence. These findings highlight the potential complication after appendix removal and the necessity of post-operative management to monitor and prevent long-term adverse events.

Spatiotemporal genomic profiling of intestinal metaplasia reveals clonal dynamics of gastric cancer progression.

Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. Analyzing 1,256 gastric samples (1,152 IMs) across 692 subjects from a prospective 10-year study, we identify 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9). Single-cell and spatial profiles highlight changes in tissue ecology and IM lineage heterogeneity, including an intestinal stem-cell dominant cellular compartment linked to early malignancy. Expanded transcriptome profiling reveals expression-based molecular subtypes of IM associated with incomplete histology, antral/intestinal cell types, ARID1A mutations, inflammation, and microbial communities normally associated with the healthy oral tract. We demonstrate that combined clinical-genomic models outperform clinical-only models in predicting IMs likely to transform to GC. By highlighting strategies for accurately identifying IM patients at high GC risk and a role for microbial dysbiosis in IM progression, our results raise opportunities for GC precision prevention and interception.

TM9SF4 Is a Crucial Regulator of Inflammation and ER Stress in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is a major intestinal disease. Excessive inflammation and increased endoplasmic reticulum (ER) stress are the key events in the development of IBD. Search of a genome-wide association study database identified a remarkable correlation between a TM9SF4 single-nucleotide polymorphism and IBD. Here, we aimed to resolve its underlying mechanism. METHODS: The role of TM9SF4 was determined with experimental mouse models of IBD. ER stress cascades, barrier functions, and macrophage polarization in colonic tissues and cells were assessed in vivo and in vitro. The expression of TM9SF4 was compared between inflamed regions of ulcerative colitis patients and normal colon samples. RESULTS: In mouse models of IBD, genetic knockout of the TM9SF4 gene aggravated the disease symptoms. In colonic epithelial cells, short hairpin RNA-mediated knockdown of TM9SF4 expression promoted inflammation and increased ER stress. In macrophages, TM9SF4 knockdown promoted M1 macrophage polarization but suppressed M2 macrophage polarization. Genetic knockout/knockdown of TM9SF4 also disrupted epithelial barrier function. Mechanistically, TM9SF4 deficiency may act through Ca2+ store depletion and cytosolic acidification to induce an ER stress increase. Furthermore, the expression level of TM9SF4 was found to be much lower in the inflamed colon regions of human ulcerative colitis patients than in normal colon samples. CONCLUSIONS: Our study identified a novel IBD-associated protein, TM9SF4, the reduced expression of which can aggravate intestinal inflammation. Deficiency of TM9SF4 increases ER stress, promotes inflammation, and impairs the intestinal epithelial barrier to aggravate IBD.

Machine learning model to predict recurrent ulcer bleeding in patients with history of idiopathic gastroduodenal ulcer bleeding.

BACKGROUND: Patients with a history of Helicobacter pylori-negative idiopathic bleeding ulcers have an increased risk of recurring ulcer complications. AIM: To build a machine learning model to identify patients at high risk for recurrent ulcer bleeding. METHODS: Data from a retrospective cohort of 22 854 patients (training cohort) diagnosed with peptic ulcer disease in 2007-2016 were analysed to build a model (IPU-ML) to predict recurrent ulcer bleeding. We tested the IPU-ML in all patients with a diagnosis of gastrointestinal bleeding (n = 1265) in 2008-2015 from a different catchment population (independent validation cohort). Any co-morbid conditions which had occurred in >1% of study population were eligible as predictors. RESULTS: Recurrent ulcer bleeding developed in 4772 patients (19.5%) in the training cohort, during a median follow-up period of 2.7 years. IPU-ML model built on six parameters (age, baseline haemoglobin, and presence of gastric ulcer, gastrointestinal diseases, malignancies, and infections) identified patients with bleeding recurrence within 1 year with an area under the receiver operating characteristic curve (AUROC) of 0.648. When we set the IPU-ML cutoff value at 0.20, 27.5% of patients were classified as high risk for rebleeding with a sensitivity of 41.4%, specificity of 74.6%, and a negative predictive value of 91.1%. In the validation cohort, the IPU-ML identified patients with a recurrence ulcer bleeding within 1 year with an AUROC of 0.775, and 84.3% of overall accuracy. CONCLUSION: We developed a machine-learning model to identify those patients with a history of idiopathic gastroduodenal ulcer bleeding who are not at high risk for recurrent ulcer bleeding.