Diagnostic accuracy of magnetically guided capsule endoscopy with a detachable string for detecting oesophagogastric varices in adults with cirrhosis: prospective multicentre study.

OBJECTIVE: To evaluate the diagnostic accuracy and safety of using magnetically guided capsule endoscopy with a detachable string (ds-MCE) for detecting and grading oesophagogastric varices in adults with cirrhosis. DESIGN: Prospective multicentre diagnostic accuracy study. SETTING: 14 medical centres in China. PARTICIPANTS: 607 adults (>18 years) with cirrhosis recruited between 7 January 2021 and 25 August 2022. Participants underwent ds-MCE (index test), followed by oesophagogastroduodenoscopy (OGD, reference test) within 48 hours. The participants were divided into development and validation cohorts in a ratio of 2:1. MAIN OUTCOME MEASURES: The primary outcomes were the sensitivity and specificity of ds-MCE in detecting oesophagogastric varices compared with OGD. Secondary outcomes included the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices and the diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices. RESULTS: ds-MCE and OGD examinations were completed in 582 (95.9%) of the 607 participants. Using OGD as the reference standard, ds-MCE had a sensitivity of 97.5% (95% confidence interval 95.5% to 98.7%) and specificity of 97.8% (94.4% to 99.1%) for detecting oesophagogastric varices (both P<0.001 compared with a prespecified 85% threshold). When using the optimal 18% threshold for luminal circumference of the oesophagus derived from the development cohort (n=393), the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices in the validation cohort (n=189) were 95.8% (89.7% to 98.4%) and 94.7% (88.2% to 97.7%), respectively. The diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices was 96.3% (92.6% to 98.2%), 96.9% (95.2% to 98.0%), and 96.7% (95.0% to 97.9%), respectively. Two serious adverse events occurred with OGD but none with ds-MCE. CONCLUSION: The findings of this study suggest that ds-MCE is a highly accurate and safe diagnostic tool for detecting and grading oesophagogastric varices and is a promising alternative to OGD for screening and surveillance of oesophagogastric varices in patients with cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03748563.

Gut microbial DL-endopeptidase alleviates Crohn's disease via the NOD2 pathway.

The pattern-recognition receptor NOD2 senses bacterial muropeptides to regulate host immunity and maintain homeostasis. Loss-of-function mutations in NOD2 are associated with Crohn's disease (CD), but how the variations in microbial factors influence NOD2 signaling and host pathology is elusive. We demonstrate that the Firmicutes peptidoglycan remodeling enzyme, DL-endopeptidase, increased the NOD2 ligand level in the gut and impacted colitis outcomes. Metagenomic analyses of global cohorts (n = 857) revealed that DL-endopeptidase gene abundance decreased globally in CD patients and negatively correlated with colitis. Fecal microbiota from CD patients with low DL-endopeptidase activity predisposed mice to colitis. Administering DL-endopeptidase, but not an active site mutant, alleviated colitis via the NOD2 pathway. Therapeutically restoring NOD2 ligands with a DL-endopeptidase-producing Lactobacillus salivarius strain or mifamurtide, a clinical analog of muramyl dipeptide, exerted potent anti-colitis effects. Our study suggests that the depletion of DL-endopeptidase contributes to CD pathogenesis through NOD2 signaling, providing a therapeutically modifiable target.

The intestinal microbiota influences the microenvironment of metastatic colon cancer by targeting miRNAs.

This study aimed to investigate the molecular mechanisms through which the intestinal microbiota and microRNAs (miRNAs) participate in colon cancer metastasis. Intestinal flora data, and the GSE29621 (messenger RNA/long non-coding RNA [mRNA/lncRNA]) and GSE29622 (miRNA) datasets, were downloaded from The Cancer Gene Atlas and Gene Expression Omnibus databases, respectively. Immune-related cells in M1 vs. M0 samples were analyzed using the Wilcoxon test. Furthermore, an lncRNA-miRNA-mRNA (competing endogenous RNA [ceRNA]) network was constructed, and survival analysis of RNAs in the network was performed. A total of 16 miRNA-genus co-expression pairs containing eight microbial genera and 15 miRNAs were screened; notably, Porphyromonas and Bifidobacterium spp. were found to be associated with most miRNAs, and has-miR-3943 was targeted by most microbial genera. Furthermore, five immune cell types, including activated natural killer cells, M1 macrophages, resting mast cells, activated mast cells and neutrophils, were differentially accumulated between the M1 and M0 groups. Enrichment analysis suggested that mRNAs related to colon cancer metastasis were mainly involved in pathways related to bacterial and immune responses. Survival analysis revealed that TMEM176A and PALM3 in the ceRNA network were significantly associated with the prognosis of patients with colon cancer. In conclusion, this study revealed a potential mechanism by which the intestinal microbiota influences the colon cancer microenvironment by targeting miRNAs.

Detachable string magnetically controlled capsule endoscopy for detecting high-risk varices in compensated advanced chronic liver disease (CHESS1801): A prospective multicenter study.

BACKGROUND: Gastroesophageal varices is a serious complication of compensated advanced chronic liver disease (cACLD). Primary prophylaxis to reduce the risk of variceal hemorrhage is recommended if high-risk varices (HRV) are detected. We performed this study to compare the accuracy, patients' satisfaction and safety of detection of HRV by detachable string magnetically controlled capsule endoscopy (DS-MCCE) with esophagogastroduodenoscopy (EGD) as the reference. METHODS: We prospectively recruited participants with cACLD from 12 university hospitals (11 in China and one in the United Kingdom) between November 2018 and December 2019 (ClinicalTrials.gov, NCT03749954). All participants underwent DS-MCCE, followed by EGD within a week in a blinded fashion. Following endoscopy, and on the same day, participants were asked to fill in a satisfaction questionnaire regarding their experience. FINDINGS: A total of 105 eligible participants were enrolled. With EGD as the reference standard, the concordance index, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of DS-MCCE in diagnosis of HRV were 0•90 (95% confidence interval [CI]: 0•83-0•95), 92% (95% CI: 78-98%), 88% (95% CI: 78-95%), 80% (95% CI: 70-92%), 95% (95% CI: 90-100%), 7•91 (95% CI: 4•10-15•30), and 0•09 (95% CI: 0•03-0•30), respectively. The kappa score of 0•78 (95% CI: 0•65-0•90) suggested substantial agreement between DS-MCCE and EGD. Moreover, in participants undergoing EGD without sedation, the satisfaction of DS-MCCE was significantly better than that of EGD (p < 0•0001, d = 1•15 [95%CI: 0•88-1•42]). All participants confirmed the excretion of the capsule, and no adverse events occurred. INTERPRETATION: DS-MCCE is an accurate alternative to EGD for detecting HRV in cACLD, which is safe and associated with better satisfaction. FUNDING: A full list of funding can be found in the Funding Support section.

CRISPR-based detection of Helicobacter pylori in stool samples.

BACKGROUND: Noninvasive detection of Helicobacter pylori plays an important role in clinical practice. However, few noninvasive methods have been applied in epidemiological studies due to the requirement for expensive equipment and complicated processes. The aim of this study was to establish a reliable, fast, and inexpensive noninvasive method based on CRISPR-Cas12a technology for the detection of Helicobacter pylori in stool specimens. METHOD: A novel detection method based on CRISPR-Cas12a technology was established and validated with 41 stool specimens collected from Zhujiang Hospital and compared with reliable Helicobacter pylori detection assays, such as the rapid urease test and urea breath test. RESULT: A CRISPR-Cas12a system-based method was established, and its sensitivity and specificity were evaluated. Utilizing a lateral flow biosensor, the limit of detection was 5 copies/µl, and our method could successfully distinguish Helicobacter pylori from other pathogens, suggesting no cross-reactivity with other pathogens. Furthermore, lateral flow biosensor strips were utilized to test stool specimens, which could display the detection results in an accessible way. CONCLUSION: Our CRISPR-Cas12a system-based method successfully detected Helicobacter pylori in stool specimens. It is a rapid, simple, and inexpensive method for the detection and screening of Helicobacter pylori, which makes it a very promising supplemental test. However, its sensitivity and specificity compared with those of the gold standard test still need to be examined.

Clinical Efficiency and Safety of Magnetic-Controlled Capsule Endoscopy for Gastric Diseases in Aging Patients: Our Preliminary Experience.

BACKGROUND: The elderly assess higher incidence of gastric diseases and may meet challenges and contraindications when flexible esophagogastroduodenoscopy intubating. Magnetic-controlled capsule endoscopy (MCE) is declared as a promising alternative, but its applications in elderly population do not attach enough importance. AIMS: To explore MCE's efficiency and safety in the elderly. METHODS: A single-center retrospective study has been conducted. Data from the elderly group (>65 year-old) who underwent MCE examination, including indications, MCE outcomes, gastric conditions, evaluations from MCE manipulators and endoscopists, subjective discomforts, adverse events, etc., had been collected, then analyzed, and compared with the ones from the middle-aged group (>40, ≤ 65 year-old). RESULTS: During April 2015 and September 2018, 98 elderly patients and 72 middle-aged patients underwent MCE examination. In the elderly, the indications included poor physical condition (28.6%), severe angiocardiopathy (39.8%), EGD rejection (13.3%), severe respiratory disorder (8.2%), craniocerebral injury (8.2%), and allergy to anesthetics (2.0%). Rate of complete gastric observation and positive finding were 98.0% and 72.4% (vs. middle-aged group, 94.4%, 56.9%, P = 0.220, 0.035), and gastric conditions showed relatively inferior. Gastric preparation and MCE procedure were generally tolerated, but three elderly patients (3.1%) experienced capsule blockage in stomach. CONCLUSIONS: Our preliminary data support that MCE offers considerable benefit and is general safe for the elderly. We hope such data promote greater awareness of innovative attempts for the specific elderly, and expect multi-center, large-scale trials with randomized controlled design bring optimized strategies for better gastric visibility, efficacy and lower potential risk.

Drop coating deposition Raman spectroscopy of blood plasma for the detection of colorectal cancer.

We have recently applied the technique of drop coating deposition Raman (DCDR) spectroscopy for colorectal cancer (CRC) detection using blood plasma. The aim of this study was to develop a more convenient and stable method based on blood plasma for noninvasive CRC detection. Significant differences are observed in DCDR spectra between healthy (n = 105) and cancer (n = 75) plasma from 15 CRC patients and 21 volunteers, particularly in the spectra that are related to proteins, nucleic acids, and ß-carotene. The multivariate analysis principal components analysis and the linear discriminate analysis, together with leave-one-out, cross validation were used on DCDR spectra and yielded a sensitivity of 100% (75/75) and specificity of 98.1% (103/105) for detection of CRC. This study demonstrates that DCDR spectroscopy of blood plasma associated with multivariate statistical algorithms has the potential for the noninvasive detection of CRC.

[Near-infrared Raman spectroscopy for diagnosis of gastric cancer].

OBJECTIVE: To establish a method for early diagnosis of gastric cancer using near-infrared Raman spectroscopy. METHODS: A rapid near-infrared Raman system was used to examine the tissue specimens of pathologically confirmed gastric cancer (33 cases), gastric precancerous lesions (27 cases), and normal gastric mucosa (45 cases). All the specimens were obtained from 105 patients undergoing gastrectomy or endoscopic biopsy of suspected gastric lesions. RESULTS: High-quality Raman spectra ranging from 700 to 1800 cm(-1) were acquired from the gastric tissues within 5 s. The distribution pattern of Raman spectra in gastric cancer differed significantly from those of gastric precancerous lesions and normal gastric mucosa, particularly in the spectral ranges of 853 cm(-1), 936 cm(-1), 1003 cm(-1), 1032 cm(-1), 1174 cm(-1), 1208 cm(-1), 1323 cm(-1), 1335 cm(-1), 1450 cm(-1), and 1655 cm(-1), which contained signals related to proteins, nucleic acids and lipids. The diagnostic decision algorithm based on the Raman peak intensity ratios of I1003/ I1337, I1003/I1445, I1003/I1655, and I1156/I1655 yielded remarkable differences in gastric cancer from gastric precancerous lesions and normal gastric mucosa, and the ratios were significantly higher in normal gastric tissues (P<0.05). The discrimination based on near-infrared Raman spectroscopy using PCA-LDA algorithms associated with leave- one-out and cross-validation method showed diagnostic sensitivities of 81.5%, 85.3%, and 100%, and specificities of 86.4%, 100%, and 97.4% for normal gastric mucosa, precancerous lesions and gastric cancer, respectively. CONCLUSIONS: near-infrared Raman spectroscopy in conjunction with intensity ratio algorithms shows the potential for noninvasive diagnosis and detection of gastric malignancy at the molecular level.

Discrimination of premalignant lesions and cancer tissues from normal gastric tissues using Raman spectroscopy.

The feasibility of early detection of gastric cancer using near-infrared (NIR) Raman spectroscopy (RS) by distinguishing premalignant lesions (adenomatous polyp, n=27) and cancer tissues (adenocarcinoma, n=33) from normal gastric tissues (n=45) is evaluated. Significant differences in Raman spectra are observed among the normal, adenomatous polyp, and adenocarcinoma gastric tissues at 936, 1003, 1032, 1174, 1208, 1323, 1335, 1450, and 1655 cm(-1). Diverse statistical methods are employed to develop effective diagnostic algorithms for classifying the Raman spectra of different types of ex vivo gastric tissues, including principal component analysis (PCA), linear discriminant analysis (LDA), and naive Bayesian classifier (NBC) techniques. Compared with PCA-LDA algorithms, PCA-NBC techniques together with leave-one-out, cross-validation method provide better discriminative results of normal, adenomatous polyp, and adenocarcinoma gastric tissues, resulting in superior sensitivities of 96.3%, 96.9%, and 96.9%, and specificities of 93%, 100%, and 95.2%, respectively. Therefore, NIR RS associated with multivariate statistical algorithms has the potential for early diagnosis of gastric premalignant lesions and cancer tissues in molecular level.