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Dedicated studies evaluating the impact of COVID-19 on outcomes of pancreatobiliary IgG4 related disease (IgG4-RD) patients are scarce. Whether COVID-19 infection or vaccination would trigger IgG4-RD exacerbation remains unknown.Pancreatobiliary IgG4-RD patients ≥ 18 years old with active follow-up since January 2020 from nine referral centers in Asia, Europe, and North America were included in this multicenter retrospective study. Outcome measures include incidence and severity of COVID-19 infection, IgG4-RD disease activity and treatment status, interruption of indicated IgG4-RD treatment. Prospective data on COVID-19 vaccination status and new COVID-19 infection during the Omicron outbreak were also retrieved in the Hong Kong cohort.Of the 124 pancreatobiliary IgG4-RD patients, 25.0% had active IgG4-RD, 71.0% were on immunosuppressive therapies and 80.6% had ≥ 1 risk factor for severe COVID. In 2020 (pre-vaccination period), two patients (1.6%) had COVID-19 infection (one requiring ICU admission), and 7.2% of patients had interruptions in indicated immunosuppressive treatment for IgG4-RD. Despite a high vaccination rate (85.0%), COVID-19 infection rate has increased to 20.0% during Omicron outbreak in the Hong Kong cohort. A trend towards higher COVID-19 infection rate was noted in the non-fully vaccinated/unvaccinated group (17.6% vs 33.3%, P = 0.376). No IgG4-RD exacerbation following COVID-19 vaccination or infection was observed.While a low COVID-19 infection rate with no mortality was observed in pancreatobiliary IgG4-RD patients in the pre-vaccination period of COVID-19, infection rate has increased during the Omicron outbreak despite a high vaccination rate. No IgG4-RD exacerbation after COVID-19 infection or vaccination was observed.

The Asia-Pacific region has the largest number of cases of colorectal cancer (CRC) and one of the highest levels of mortality due to this condition in the world. Since the publishing of two consensus recommendations in 2008 and 2015, significant advancements have been made in our knowledge of epidemiology, pathology and the natural history of the adenoma-carcinoma progression. Based on the most updated epidemiological and clinical studies in this region, considering literature from international studies, and adopting the modified Delphi process, the Asia-Pacific Working Group on Colorectal Cancer Screening has updated and revised their recommendations on (1) screening methods and preferred strategies; (2) age for starting and terminating screening for CRC; (3) screening for individuals with a family history of CRC or advanced adenoma; (4) surveillance for those with adenomas; (5) screening and surveillance for sessile serrated lesions and (6) quality assurance of screening programmes. Thirteen countries/regions in the Asia-Pacific region were represented in this exercise. International advisors from North America and Europe were invited to participate.

Obesity is a major risk factor for cancers including hepatocellular carcinoma (HCC) that develops from a background of non-alcoholic fatty liver disease (NAFLD). Hypercholesterolemia is a common comorbidity of obesity. Although cholesterol biosynthesis mainly occurs in the liver, its role in HCC development of obese people remains obscure. Using high-fat high-carbohydrate diet-associated orthotopic and spontaneous NAFLD-HCC mouse models, we found that hepatic cholesterol accumulation in obesity selectively suppressed natural killer T (NKT) cell-mediated antitumor immunosurveillance. Transcriptome analysis of human liver revealed aberrant cholesterol metabolism and NKT cell dysfunction in NAFLD patients. Notably, cholesterol-lowering rosuvastatin restored NKT expansion and cytotoxicity to prevent obesogenic diet-promoted HCC development. Moreover, suppression of hepatic cholesterol biosynthesis by a mammalian target of rapamycin (mTOR) inhibitor vistusertib preceded tumor regression, which was abolished by NKT inactivation but not CD8(+) T cell depletion. Mechanistically, sterol regulatory element-binding protein 2 (SREBP2)-driven excessive cholesterol production from hepatocytes induced lipid peroxide accumulation and deficient cytotoxicity in NKT cells, which were supported by findings in people with obesity, NAFLD and NAFLD-HCC. This study highlights mTORC1/SREBP2/cholesterol-mediated NKT dysfunction in the tumor-promoting NAFLD liver microenvironment, providing intervention strategies that invigorating NKT cells to control HCC in the obesity epidemic.

Occlusion of the T-tube (tympanostomy tube) is a common postoperative sequela related to bacterial biofilms. Confronting biofilm-related infections of T-tubes, maneuverable and effective treatments are still challenging presently. Here, we propose an endoscopy-assisted treatment procedure based on the wobbling Fe 2 O 3 helical micromachine (HMM) with peroxidase-mimicking activity. Different from the ideal corkscrew motion, the Fe 2 O 3 HMM applies a wobbling motion in the tube, inducing stronger mechanical force and fluid convections, which not only damages the biofilm occlusion into debris quickly but also enhances the catalytic generation and diffusion of reactive oxygen species (ROS) for killing bacteria cells. Moreover, the treatment procedure, which integrated the delivery, actuation, and retrieval of Fe 2 O 3 HMM, was validated in the T-tube implanted in a human cadaver ex vivo. It enables the visual operation with ease and is gentle to the tympanic membrane and ossicles, which is promising in the clinical application.

Background and Aim: Environmental factors play a key role in development of Crohn's disease (CD), thought to be mediated by changes in the gut microbiota. We aimed to delineate the potential contribution of antibiotic exposure to subsequent development of CD, across diverse geographical populations. Methods: This case–control study in Australia and three cities in China (Hong Kong, Guangzhou, and Kunming) included four groups: patients with CD, at-risk individuals including non-affected first-degree relatives (FDRs) and household members of CD patients (HM), and unrelated healthy controls (HCs). Environmental risk factors, including childhood antibiotic use and 13 other categories, were assessed using a self-developed questionnaire. Logistic regression and conditional logistic regression were used to determine environmental factors associated with CD development. Results: From 2017 to 2019, a total of 254 patients with CD (mean age: 37.98 ± 13.76 years; 58.3% male), 73 FDR (mean age: 49.35 ± 13.28 years; 46.6% male), 122 HMs (including FDR) (mean age: 45.50 ± 13.25 years; 47.5% male), and 78 HC (mean age: 45.57 ± 11.24; 47.4% male) were included. Comparing CD patients with their FDR and HMs, antibiotic use before 18 years old was a risk factor for CD development (adjusted odds ratio [OR] 3.46, 95% confidence interval [CI] 1.38–8.69; P = 0.008). There were no significant differences in other childhood environmental risk factors between CD and their FDR or HMs. Subgroup analysis showed that antibiotic use

Emerging data supports the existence of a microbial 'gut-lung' axis that remains unexplored in bronchiectasis.Prospective and concurrent sampling of gut (stool) and lung (sputum) was performed in a cohort of n=57 individuals with bronchiectasis and subjected to bacteriome (16S rRNA) and mycobiome (18S ITS) sequencing (total 228 microbiomes). Shotgun metagenomics was performed in a subset (n=15; 30 microbiomes). Data from gut and lung compartments were 'integrated' by weighted Similarity Network Fusion (wSNF), clustered and subjected to co-occurrence analysis to evaluate 'gut-lung' networks. Murine experiments were undertaken to validate specific Pseudomonas-driven 'gut-lung' interactions.Microbial communities in stable bronchiectasis demonstrate significant 'gut-lung' interaction. Multi-biome integration followed by unsupervised clustering reveals two patient clusters, differing by 'gut-lung' interactions and with contrasting clinical phenotypes. A 'high gut-lung interaction' cluster characterized by lung Pseudomonas, gut Bacteroides and gut Saccharomyces associates with increased exacerbations, greater radiological and overall bronchiectasis severity while the 'low gut-lung interaction' cluster demonstrates an overrepresentation of lung commensals including Prevotella, Fusobacterium and Porphyromonas with gut Candida. The lung Pseudomonas-gut Bacteroides relationship, observed in the 'high gut-lung interaction' bronchiectasis cluster, was validated in a murine model of lung Pseudomonas aeruginosa (PAO1) infection. This interaction was abrogated following antibiotic (imipenem) pre-treatment in mice confirming the relevance and therapeutic potential of targeting the gut microbiome to influence the 'gut-lung' axis. Metagenomics in a subset of individuals with bronchiectasis corroborated our findings from targeted analyses.A dysregulated 'gut-lung' axis, driven by lung Pseudomonas, associates with poorer clinical outcomes in bronchiectasis. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Adequate bowel preparation is an important colonoscopy quality indicator. Reinforced education is effective in improving bowel preparation quality of colonoscopy with mixed indications. However, it remains unclear whether such improvement can be consistently observed in pre- and post-irrigation during colonoscopy in screening population.We aimed to study the effectiveness of nurse-led reinforced education delivered via mobile messenger (WhatsApp Messenger) on pre- and post-irrigation bowel preparation adequacy in colonoscopies for positive fecal immunochemical test in a population-based colorectal cancer screening program.Randomized controlled trial.A hospital-based endoscopy centre in Hong Kong, China.Patients undergoing colonoscopy for positive fecal immunochemical test in a population-based colorectal cancer screening program.The recruited patients were randomized to receive either WhatsApp Reinforced Education (WRE) or No Reinforced Education (NRE) (1:1). Patients in WRE group received one-off reinforced education of bowel preparation in text and video formats via WhatsApp Messenger four days prior to colonoscopy sent by investigator while NRE group received standard-of-care only. Primary outcome was the bowel preparation adequacy rate as evaluated by Aronchick Scale. Secondary outcomes included bowel preparation adequacy rate as evaluated by Boston Bowel Preparation Scale, adenoma detection rate and risk factors of bowel preparation inadequacy. Continuous variables were described as means with standard deviation (SD) and analyzed with Student's t-test. The Pearson Chi Square Test or Fisher Exact Test was used to assess categorical variables when appropriate. Risk factors were determined by logistic regression.From July 2017 to April 2019, 685 eligible patients were randomized to WRE (n = 343) and NRE (n = 342) groups. Patients in WRE group had higher bowel preparation adequacy rate as evaluated by Aronchik Scale (83.4% vs 75.4%, p = 0.010) and Boston Bowel Preparation Scale (94.2% vs 88.9%, p = 0.013). Adenoma detection rate was higher in WRE group but without statistical significance (71.4% vs 67.5%, p = 0.27). In logistic regression, WhatsApp Reinforced Education reduced the inadequate bowel preparation risk (Adjusted odds ratio: 0.564; 95% confidence interval: 0.371-0.856, p = 0.007). Male gender (Adjusted odds ratio [AOR]: 1.638; 95% confidence interval [CI]: 1.054-2.546, p = 0.028) and diabetes (AOR: 2.062; 95% CI: 1.215-3.497, p = 0.007) were risk factors of bowel preparation inadequacy.Nurse-led mobile messenger-initiated reinforced education improves both pre- and post-irrigation bowel preparation quality of screening colonoscopy following positive fecal immunochemical test. It is readily incorporable in clinical practice because of its low setup cost.Registered on 4 July 2017 on https://clinicaltrials.gov/ (NCT03209739).

ImportanceDespite the potential of machine learning to improve multiple aspects of patient care, barriers to clinical adoption remain. Randomized clinical trials (RCTs) are often a prerequisite to large-scale clinical adoption of an intervention, and important questions remain regarding how machine learning interventions are being incorporated into clinical trials in health care.ObjectiveTo systematically examine the design, reporting standards, risk of bias, and inclusivity of RCTs for medical machine learning interventions.Evidence ReviewIn this systematic review, the Cochrane Library, Google Scholar, Ovid Embase, Ovid MEDLINE, PubMed, Scopus, and Web of Science Core Collection online databases were searched and citation chasing was done to find relevant articles published from the inception of each database to October 15, 2021. Search terms for machine learning, clinical decision-making, and RCTs were used. Exclusion criteria included implementation of a non-RCT design, absence of original data, and evaluation of nonclinical interventions. Data were extracted from published articles. Trial characteristics, including primary intervention, demographics, adherence to the CONSORT-AI reporting guideline, and Cochrane risk of bias were analyzed.FindingsLiterature search yielded 19 737 articles, of which 41 RCTs involved a median of 294 participants (range, 17-2488 participants). A total of 16 RCTS (39%) were published in 2021, 21 (51%) were conducted at single sites, and 15 (37%) involved endoscopy. No trials adhered to all CONSORT-AI standards. Common reasons for nonadherence were not assessing poor-quality or unavailable input data (38 trials [93%]), not analyzing performance errors (38 [93%]), and not including a statement regarding code or algorithm availability (37 [90%]). Overall risk of bias was high in 7 trials (17%). Of 11 trials (27%) that reported race and ethnicity data, the median proportion of participants from underrepresented minority groups was 21% (range, 0%-51%).Conclusions and RelevanceThis systematic review found that despite the large number of medical machine learning–based algorithms in development, few RCTs for these technologies have been conducted. Among published RCTs, there was high variability in adherence to reporting standards and risk of bias and a lack of participants from underrepresented minority groups. These findings merit attention and should be considered in future RCT design and reporting.

The evolution of drug-resistant pathogenic bacteria remains one of the most urgent threats to public health worldwide. Even worse, the bacterial cells commonly form biofilms through aggregation and adhesion, preventing antibiotic penetration and resisting environmental stress. Moreover, biofilms tend to grow in some hard-to-reach regions, bringing difficulty for antibiotic delivery at the infected site. The drug-resistant pathogenic bacteria and intractable biofilm give rise to chronic and recurrent infections, exacerbating the challenge in combating bacterial infections. Micro/nanorobots (MNRs) are capable of active cargo delivery, targeted treatment with high precision, and motion-assisted mechanical force, which enable transport and enhance penetration of antibacterial agents into the targeted site, thus showing great promise in emerging as an attractive alternative to conventional antibacterial therapies. This review summarizes the recent advances in micro-/nanorobots for antibacterial applications, with emphasis on those novel strategies for drug-resistance bacterium and stubborn biofilm infections. Insights on the future development of MNRs with good functionality and biosafety offer promising approaches to address infections in the clinic setting.

Objective Helicobacter pylori is associated with gastric inflammation, precancerous gastric atrophy (GA) and intestinal metaplasia (IM). We aimed to identify microbes that are associated with progressive inflammation, GA and IM 1 year after H. pylori eradication. Design A total of 587 H. pylori–positive patients were randomised to receive H. pylori eradication therapy (295 patients) or placebo (292 patients). Bacterial taxonomy was analysed on 404 gastric biopsy samples comprising 102 pairs before and after 1 year H. pylori eradication and 100 pairs before and after 1 year placebo by 16S rRNA sequencing. Results Analysis of microbial sequences confirmed the eradication of H. pylori in treated group after 1 year. Principal component analysis revealed distinct microbial clusters reflected by increase in bacterial diversity (p

Objective There is a need for early detection of colorectal cancer (CRC) at precancerous-stage adenoma. Here, we identified novel faecal bacterial markers for diagnosing adenoma. Design This study included 1012 subjects (274 CRC, 353 adenoma and 385 controls) from two independent Asian groups. Candidate markers were identified by metagenomics and validated by targeted quantitative PCR. Results Metagenomic analysis identified ‘m3’ from a Lachnoclostridium sp., Fusobacterium nucleatum (Fn) and Clostridium hathewayi (Ch) to be significantly enriched in adenoma. Faecal m3 and Fn were significantly increased from normal to adenoma to CRC (p

Emerging evidence implicates a role of the gut microbiota in colorectal cancer (CRC). Peptostreptococcus anaerobius (P. anaerobius) is an anaerobic bacterium selectively enriched in the faecal and mucosal microbiota from patients with CRC, but its causative role and molecular mechanism in promoting tumorigenesis remain unestablished. We demonstrate that P. anaerobius adheres to the CRC mucosa and accelerates CRC development in Apc

We report fluorescent magnetic spore–based microrobots for remote sensing of C. diff toxins in clinical stool supernatants., A rapid, direct, and low-cost method for detecting bacterial toxins associated with common gastrointestinal diseases remains a great challenge despite numerous studies and clinical assays. Motion-based detection through tracking the emerging micro- and nanorobots has shown great potential in chemo- and biosensing due to accelerated “chemistry on the move”. Here, we described the use of fluorescent magnetic spore–based microrobots (FMSMs) as a highly efficient mobile sensing platform for the detection of toxins secreted by Clostridium difficile (C. diff) that were present in patients’ stool. These microrobots were synthesized rapidly and inexpensively by the direct deposition of magnetic nanoparticles and the subsequent encapsulation of sensing probes on the porous natural spores. Because of the cooperation effect of natural spore, magnetic Fe3O4 nanoparticles, and functionalized carbon nanodots, selective fluorescence detection of the prepared FMSMs is demonstrated in C. diff bacterial supernatant and even in actual clinical stool samples from infectious patients within tens of minutes, suggesting rapid response and good selectivity and sensitivity of FMSMs toward C. diff toxins.

Proximal migration of colonic lesion has been observed; however, risk factors of lesions in the proximal colon remain uncertain. This study aimed to investigate risk factors of lesions in the proximal colon.Consecutive subjects with complete colonoscopy were included. The primary outcome was risk factors associated with advanced neoplasm (AN) and serrated lesion in the proximal colon. Age, gender, first-degree relative (FDR) with colorectal cancer (CRC), smoking, alcohol consumption, body mass index, hypertension, diabetes, ischemic heart disease, and the use of aspirin, non-steroidal anti-inflammatory drug, and anticoagulants were fitted into a regression model, with reference to subjects without colonic finding. Results were measured by odds ratio (OR) with 95% confidence interval (CI).Among 6218 subjects (mean age 56.65 ± 6.15 years; 46.8% male), 352 (5.7%) had AN; 809 (13.0%) had serrated lesions, and 3648 (58.7%) had no colonic finding. There were 148 (2.4%) and 235 (3.8%) subjects having AN and serrated lesion in the proximal colon. Age ≥ 50 (OR: 13.30; 95% CI: 1.85-95.76), male gender (OR: 1.82; 95% CI: 1.26-2.62), FDR with CRC (OR: 2.12; 95% CI: 1.43-3.15), and hypertension (OR: 1.86; 95% CI: 1.30-2.68) were associated with AN in the proximal colon. Age ≥ 50 (OR: 5.72; 95% CI: 2.10-15.53), male gender (OR: 1.54; 95% CI: 1.15-2.05), and smoking (OR: 1.85; 95% CI: 1.23-2.79) increased risk of serrated lesions in the proximal colon.Age ≥ 50 and male gender were associated with both proximally located AN and serrated lesion; FDR with CRC and hypertension increased the risk of proximal AN, while ever smoking increased the risk of proximal serrated lesion. FDR with CRC was not associated with serrated lesion.

We validated a modified risk algorithm based on the Asia-Pacific Colorectal Screening (APCS) score that included body mass index (BMI) for prediction of advanced neoplasia.Among 5744 Chinese asymptomatic screening participants undergoing a colonoscopy in Hong Kong from 2008 to 2012, a random sample of 3829 participants acted as the derivation cohort. The odds ratios for significant risk factors identified by binary logistic regression analysis were used to build a scoring system ranging from 0 to 6, divided into "average risk" (AR): 0; "moderate risk" (MR): 1-2; and "high risk" (HR): 3-6. The other 1915 subjects formed a validation cohort, and the performance of the score was assessed.The prevalence of advanced neoplasia in the derivation and validation cohorts was 5.4% and 6.0%, respectively (P = 0.395). Old age, male gender, family history of colorectal cancer, smoking, and BMI were significant predictors in multivariate regression analysis. A BMI cut-off at 23 kg/mIncorporating BMI into the predictors of APCS score was found to improve risk prediction of advanced neoplasia and reduce colonoscopy resources.

Objective There is a need for an improved biomarker for colorectal cancer (CRC) and advanced adenoma. We evaluated faecal microbial markers for clinical use in detecting CRC and advanced adenoma. Design We measured relative abundance of Fusobacterium nucleatum (Fn), Peptostreptococcus anaerobius (Pa) and Parvimonas micra (Pm) by quantitative PCR in 309 subjects, including 104 patients with CRC, 103 patients with advanced adenoma and 102 controls. We evaluated the diagnostic performance of these biomarkers with respect to faecal immunochemical test (FIT), and validated the results in an independent cohort of 181 subjects. Results The abundance was higher for all three individual markers in patients with CRC than controls (p

Colorectal cancer (CRC) incidence is rising among50-year olds. The objective of this study was to determine screening colonoscopy outcomes among 40- to 49-year olds, which are currently limited.Asymptomatic 40- to 49-year olds underwent one time CRC screening colonoscopy at The Chinese University of Hong Kong between 2007 and 2011. Screening outcomes, including prevalence, distribution, and predictive factors for overall and specifically proximal colorectal neoplasia were determined.Among 1133 ethnic Chinese, colorectal neoplasia prevalence was 20.5%. In men, distal adenomas were associated with proximal colorectal neoplasia. Men, advancing age, a first degree relative (FDR) with CRC, and diabetes mellitus were independently associated with colorectal neoplasia. A colorectal neoplasia was three times more likely to be found in a 45- to 49-year-old man with FDR of CRC compared with a 40- to 44-year-old woman without a FDR of CRC. The numbers needed to screen one colorectal neoplasia, and one advanced neoplasm in the highest risk group of 45- to 49-year-old men with FDR with CRC were 2.8 (95% CI: 2.2-4.4) and 18.5 (95% CI: 8.9-39.2), respectively.Colorectal neoplasia prevalence in this 40- to 49-year-old Chinese cohort was higher than previous studies. Men, advancing age, FDR with CRC, and diabetes mellitus, can be used to risk stratify for neoplasia development. Men 45-49 years old with FDR with CRC represented the highest risk subgroup, with the lowest number needed to screen.