MAP3K2-regulated intestinal stromal cells define a distinct stem cell niche.

Intestinal stromal cells are known to modulate the propagation and differentiation of intestinal stem cells1,2. However, the precise cellular and molecular mechanisms by which this diverse stromal cell population maintains tissue homeostasis and repair are poorly understood. Here we describe a subset of intestinal stromal cells, named MAP3K2-regulated intestinal stromal cells (MRISCs), and show that they are the primary cellular source of the WNT agonist R-spondin 1 following intestinal injury in mice. MRISCs, which are epigenetically and transcriptomically distinct from subsets of intestinal stromal cells that have previously been reported3-6, are strategically localized at the bases of colon crypts, and function to maintain LGR5+ intestinal stem cells and protect against acute intestinal damage through enhanced R-spondin 1 production. Mechanistically, this MAP3K2 specific function is mediated by a previously unknown reactive oxygen species (ROS)-MAP3K2-ERK5-KLF2 axis to enhance production of R-spondin 1. Our results identify MRISCs as a key component of an intestinal stem cell niche that specifically depends on MAP3K2 to augment WNT signalling for the regeneration of damaged intestine.

Simultaneous profiling of host expression and microbial abundance by spatial metatranscriptome sequencing.

We developed an analysis pipeline that can extract microbial sequences from spatial transcriptomic (ST) data and assign taxonomic labels, generating a spatial microbial abundance matrix in addition to the default host expression matrix, enabling simultaneous analysis of host expression and microbial distribution. We called the pipeline spatial metatranscriptome (SMT) and applied it on both human and murine intestinal sections and validated the spatial microbial abundance information with alternative assays. Biological insights were gained from these novel data that showed host-microbe interaction at various spatial scales. Finally, we tested experimental modification that can increase microbial capture while preserving host spatial expression quality and, by use of positive controls, quantitatively showed the capture efficiency and recall of our methods. This proof-of-concept work shows the feasibility of SMT analysis and paves the way for further experimental optimization and application.

Methionine-choline deficient diet deteriorates DSS-induced murine colitis through disturbance of gut microbes and infiltration of macrophages.

Ulcerative colitis (UC) is associated with changed dietary habits and mainly linked with the gut microbiota dysbiosis, necroptosis of epithelial cells, and mucosal ulcerations. Liver dysfunction and abnormal level of liver metabolism indices were identified in UC patients, suggesting a close interaction between gut and liver disorders. Methionine-choline deficient diet (MCD) has been shown to induce persistent alterations of gut microbiota and metabolome during hepatitis. In this study we further explored the disease phenotypes in UC patients and investigated whether MCD functioned as a trigger for UC susceptibility. After assessing 88 serum specimens from UC patients, we found significant liver dysfunction and dyslipidemia including abnormal ALT, AST, TG, TC, LDL-c and HDL-c. Liver dysfunction and dyslipidemia were confirmed in DSS-induced colitis mice. We fed mice with MCD for 14 days to cause mild liver damage, and then treated with DSS for 7 days. We found that MCD intake significantly exacerbated the pathogenesis of mucosal inflammation in DSS-induced acute, progressive, and chronic colitis, referring to promotion of mucosal ulcers, colon shortening, diarrhea, inflammatory immune cell infiltration, cytokines release, and abnormal activation of inflammatory macrophages in colon and liver specimens. Intraperitoneal injection of clodronate liposomes to globally delete macrophages dramatically compromised the pathogenesis of MCD-triggering colitis. In addition, MCD intake markedly changed the production pattern of short-chain fatty acids (SCFAs) in murine stools, colons, and livers. We demonstrated that MCD-induced colitis pathogenesis largely depended on the gut microbes and the disease phenotypes could be transmissible through fecal microbiota transplantation (FMT). In conclusion, this study supports the concept that intake of MCD predisposes to experimental colitis and enhances its pathogenesis via modulating gut microbes and macrophages in mice.

Upregulation of acid sensing ion channels is associated with esophageal hypersensitivity in GERD.

Proton pump inhibitors (PPIs) are the mainstay of therapy for gastroesophageal reflux disease (GERD) but up to 60% of patients have inadequate response to therapy. Acid sensing ion channels (ASICs) play important roles in nociception. This study aimed to investigate whether the increased expression of ASICs results in neuronal hyperexcitability in GERD. Esophageal biopsies were taken from GERD patients and healthy subjects to compare expression of ASIC1 and 3. Next, gene and protein expression of ASIC1 and 3 from esophageal mucosa and dorsal root ganglia (DRG) neurons were measured by qPCR, Western-blot and immunofluorescence in rodent models of reflux esophagitis (RE), non-erosive reflux disease (NERD), and sham operated groups. Excitability of DRG neurons in the GERD and sham groups were also tested by whole-cell patch-clamp recordings. We demonstrated that ASIC1 and 3 expression were significantly increased in patients with RE compared with healthy controls. This correlated positively with symptom severity of heartburn and regurgitation (p < .001). Next, ASIC1 and 3 gene and protein expression in rodent models of RE and NERD were similarly increased in esophageal mucosa as well as T3-T5 DRG neurons compared with sham operation. DRG neurons from RE animals showed hyperexcitability compared with sham group. However, intrathecal injection of ASIC specific inhibitors, PcTx1 and APTEx-2, as well as silencing ASIC1 and 3 genes with specific siRNAs prevented visceral hypersensitivity. Overall, upregulation of ASIC1 and 3 may lead to visceral hypersensitivity in RE and NERD and may be a potential therapeutic target for PPI non-responsive patients.

Therapeutic strategies following endoscopic submucosal dissection for T1a-MM/T1b-SM1 esophageal squamous cell carcinoma: comparisons of long-term outcomes with propensity score-matched analysis.

BACKGROUND: For esophageal squamous cell carcinoma (ESCC) invading the muscularis mucosa (T1a-MM) or upper submucosa (T1b-SM1, up to 200 µm), the curative effectiveness of endoscopic submucosal dissection (ESD) and additional therapeutic strategies remain controversial. The present study aims to investigate the effectiveness of ESD followed by different therapeutic strategies in treating such patients. METHODS: A total of 242 patients with T1a-MM/T1b-SM1 ESCCs were involved. Data on therapeutic outcomes and long-term survivals were collected for analysis. Propensity score-matched analysis was performed to compensate for selection bias between patients with no additional therapy (NAT group) and those with additional therapy (AT group). RESULTS: R0 resection rate was 83.1% and curative resection rate was 78.5%. After a mean follow-up period of 57.8 ± 27.3 months, the cumulative recurrence rate was 7.9%. The 5-year overall survival (OS) and cause-specific survival (CSS) rate was 91.1% and 94.0%. In a matched cohort of 24 pairs, the 5-year OS and CSS rates showed no significant difference between NAT group (82.0% and 87.1%) and AT group (86.0% and 89.9%) (P > 0.05). In the subgroup of patients with noncurative ESD (n = 52), the 5-year OS and CSS rates were significantly higher in surgery group (90.2% and 95.2%) than that in NAT group (50.1% and 59.5%) and chemoradiotherapy group (51.4% and 60.0%) (P < 0.05). CONCLUSIONS: ESD with no additional therapy could achieve favorable long-term outcomes in treating T1a-MM/T1b-SM1 ESCCs. For patients with noncurative ESD, surgery ranks a prime recommendation over CRT.

A combined radiomic model distinguishing GISTs from leiomyomas and schwannomas in the stomach based on endoscopic ultrasonography images.

BACKGROUND: Endoscopic ultrasonography (EUS) is recommended as the best tool for evaluating gastric subepithelial lesions (SELs); nonetheless, it has difficulty distinguishing gastrointestinal stromal tumors (GISTs) from leiomyomas and schwannomas. GISTs have malignant potential, whereas leiomyomas and schwannomas are considered benign. PURPOSE: This study aimed to establish a combined radiomic model based on EUS images for distinguishing GISTs from leiomyomas and schwannomas in the stomach. METHODS: EUS images of pathologically confirmed GISTs, leiomyomas, and schwannomas were collected from five centers. Gastric SELs were divided into training and testing datasets based on random split-sample method (7:3). Radiomic features were extracted from the tumor and muscularis propria regions. Principal component analysis, least absolute shrinkage, and selection operator were used for feature selection. Support vector machine was used to construct radiomic models. Two radiomic models were built: the conventional radiomic model included tumor features alone, whereas the combined radiomic model incorporated features from the tumor and muscularis propria regions. RESULTS: A total of 3933 EUS images from 485 cases were included. For the differential diagnosis of GISTs from leiomyomas and schwannomas, the accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve were 74.5%, 72.2%, 78.7%, and 0.754, respectively, for the EUS experts; 76.8%, 74.4%, 81.0%, and 0.830, respectively, for the conventional radiomic model; and 90.9%, 91.0%, 90.6%, and 0.953, respectively, for the combined radiomic model. For gastric SELs <20 mm, the accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of the combined radiomic model were 91.4%, 91.6%, 91.1%, and 0.960, respectively. CONCLUSIONS: We developed and validated a combined radiomic model to distinguish gastric GISTs from leiomyomas and schwannomas. The combined radiomic model showed better diagnostic performance than the conventional radiomic model and could assist EUS experts in non-invasively diagnosing gastric SELs, particularly gastric SELs <20 mm.

Kyoto international consensus report on anatomy, pathophysiology and clinical significance of the gastro-oesophageal junction.

OBJECTIVE: An international meeting was organised to develop consensus on (1) the landmarks to define the gastro-oesophageal junction (GOJ), (2) the occurrence and pathophysiological significance of the cardiac gland, (3) the definition of the gastro-oesophageal junctional zone (GOJZ) and (4) the causes of inflammation, metaplasia and neoplasia occurring in the GOJZ. DESIGN: Clinical questions relevant to the afore-mentioned major issues were drafted for which expert panels formulated relevant statements and textural explanations.A Delphi method using an anonymous system was employed to develop the consensus, the level of which was predefined as ≥80% of agreement. Two rounds of voting and amendments were completed before the meeting at which clinical questions and consensus were finalised. RESULTS: Twenty eight clinical questions and statements were finalised after extensive amendments. Critical consensus was achieved: (1) definition for the GOJ, (2) definition of the GOJZ spanning 1 cm proximal and distal to the GOJ as defined by the end of palisade vessels was accepted based on the anatomical distribution of cardiac type gland, (3) chemical and bacterial (Helicobacter pylori) factors as the primary causes of inflammation, metaplasia and neoplasia occurring in the GOJZ, (4) a new definition of Barrett's oesophagus (BO). CONCLUSIONS: This international consensus on the new definitions of BO, GOJ and the GOJZ will be instrumental in future studies aiming to resolve many issues on this important anatomic area and hopefully will lead to better classification and management of the diseases surrounding the GOJ.

Clinical practice guidelines for esophageal ambulatory reflux monitoring in Chinese adults.

Esophageal ambulatory reflux monitoring is the current gold standard for the diagnosis of gastroesophageal reflux disease (GERD). In order to facilitate standardized procedure and improve diagnostic accuracy, clinical guidelines for ambulatory esophageal reflux monitoring were developed based on thorough literature search and working group conference by experts in gastrointestinal motility. Indications, contraindications, methodology, and reporting of ambulatory esophageal reflux monitoring were discussed in these clinical guidelines.

Nicotine promotes tumor progression and epithelial-mesenchymal transition by regulating the miR-155-5p/NDFIP1 axis in pancreatic ductal adenocarcinoma.

BACKGROUND: Nicotine, the major component of cigarette smoke, has been reported to promote pancreatic ductal adenocarcinoma (PDAC) growth and invasion. Deregulation of microRNA (miRNA) expression is found in many cancers, including PDAC. The effects of nicotine on miRNAs change in PDAC progression remain unknown. METHODS: The effects of cigarette smoking/nicotine exposure on PDAC cell lines and tissues were evaluated. Quantitative real-time PCR and in situ hybridization assays were used to determine miR-155-5p expression in human PDAC tissue and cell lines upon cigarette smoking/nicotine exposure. Bioinformatics, loss-of-function experiments, luciferase reporter assay were performed to validate Nedd4 family interacting protein 1 (NDFIP1) as a direct target of miR-155-5p. The potentials of systemic miR-155-5p inhibitor-based therapy in overcoming nicotine exposure were evaluated in tumor xenograft model. RESULTS: Nicotine promoted PDAC cells proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in a dose-response manner. MiR-155-5p was found to be highly expressed in PDAC cell lines and tissues upon cigarette smoking/nicotine exposure. Functional studies showed that miR-155-5p knockdown could override the enhancement of oncogenic activity due to nicotine exposure in vitro and in vivo by directly interacting with the 3' untranslated regions (UTRs) of NDFIP1. CONCLUSIONS: These data demonstrate that nicotine-regulated miR-155-5p/NDFIP1 promotes tumor progression and EMT of PDAC.

Altered diversity and composition of gut microbiota in Chinese patients with chronic pancreatitis.

BACKGROUND/OBJECTIVES: Gut microbiota alterations in chronic pancreatitis (CP) are seldomly described systematically. It is unknown whether pancreatic exocrine insufficiency (PEI) and different etiologies in patients with CP are associated with gut microbiota dysbiosis. METHODS: The fecal microbiota of 69 healthy controls (HCs) and 71 patients with CP were compared to investigate gut microbiome alterations in CP and the relationship among gut microbiome dysbiosis, PEI and different etiologies. Fecal microbiomes were analyzed through 16S ribosomal RNA gene profiling, based on next-generation sequencing. Pancreatic exocrine function was evaluated by determining fecal elastase 1 activity. RESULTS: Patients with CP showed gut microbiota dysbiosis with decreased diversity and richness, and taxa-composition changes. On the phylum level, the gut microbiome of the CP group showed lower Firmicutes and Actinobacteria abundances than the HC group and higher Proteobacteria abundances. The abundances of Escherichia-Shigella and other genera were high in gut microbiomes in the CP group, whereas that of Faecalibacterium was low. Kyoto Encyclopedia of Genes and Genomes pathways (lipopolysaccharide biosynthesis and bacterial invasion of epithelial cells) were predicted to be enriched in the CP group. Among the top 5 phyla and 8 genera (in terms of abundance), only Fusobacteria and Eubacterium rectale group showed significant differences between CP patients, with or without PEI. Correlation analysis showed that Bifidobacterium and Lachnoclostridium correlated positively with fecal elastase 1 (r = 0.2616 and 0.2486, respectively, P < 0.05). CONCLUSIONS: The current findings indicate that patients with CP have gut microbiota dysbiosis that is partly affected by pancreatic exocrine function.

Comparison of smear cytology and liquid-based cytology in EUS-guided FNA of pancreatic lesions: experience from a large tertiary center.

BACKGROUND AND AIMS: Studies comparing the diagnostic efficacy of liquid-based cytology (LBC) and smear cytology (SC) of pancreatic tissue sampling obtained via EUS-guided FNA (EUS-FNA) are still insufficient, mainly because results were controversial. We compared the diagnostic efficiency of LBC and SC of EUS-FNA of pancreatic lesions in one of the largest tertiary hospitals in China. METHODS: A retrospective database search (January 2015 to January 2019) was performed for patients who underwent EUS-FNA with both LBC and SC. Demographic, cytologic, and endosonographic data were collected from 819 patients; 514 cases met the inclusion criteria. Diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were compared. Rapid on-site evaluation was not available in all cases. RESULTS: Three hundred eighty-five cases (74.90%) had confirmed malignancy, and 40 cases (7.78%) confirmed benign neoplasm. Adequate tissue sampling rates showed no significant difference between the 2 groups. The sensitivity, accuracy, and negative predictive value (NPV) of LBC were higher than those of SC with statistical significance (71.4% vs 55.1%, 76.1% vs 61.6%, and 40.6% vs 27.7%, respectively). The sensitivity, accuracy, and NPV of combined SC and LBC were higher than those of LBC alone with statistical significance (83.9% vs 71.4%, 86.5% vs 76.1%, and 56.8% vs 40.6%, respectively). Multivariate analysis revealed that pancreatic neck/body/tail lesions (P = .003), solid lesions (P < .001), 22-gauge needle size (P < .001), and number of needle passage >3 (P = .041) were associated with higher diagnostic sensitivity in all participants using LBC, whereas number of needle passage >3 (P = .017) was associated with higher diagnostic sensitivity using SC. CONCLUSIONS: LBC was more accurate and sensitive than SC in EUS-FNA of pancreatic lesions with higher NPV when rapid on-site evaluation is unavailable. Pancreatic neck/body/tail lesions, solid lesions, 22-gauge needle, and more than 3 passes were associated with higher sensitivity when using LBC. Performing more than 3 passes is associated with higher sensitivity when using SC.

Predictive factors for extraction of common bile duct stones during endoscopic retrograde cholangiopancreatography in Billroth II anatomy patients.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) for extraction of common bile duct (CBD) stones in Billroth II anatomy patients is still a technical challenge and factors affecting stone extraction have not yet been clarified. This study aimed to analyze our experience and evaluate potential factors affecting CBD stone extraction. METHODS: A retrospective analysis of CBD stones patients with a history of Billroth II gastrectomy, who underwent therapeutic ERCP for stone extraction at our center from August 1999 to December 2017, was conducted. The outcomes of ERCP and potential factors affecting stone extraction were examined. RESULTS: A total of 227 patients were enrolled, and 176 patients (77.5%) achieved technical success. The success rate of duodenal ampullary access and selective biliary cannulation was 84.1% (191/227) and 92.1% (176/191), respectively. The mean CBD diameter was 15 mm (range 6-35 mm), and the largest stone size was 13 mm (range 4-36 mm). CBD stones were ultimately removed in 137 patients (77.8%), and 105 patients (59.7%) for the first session. Mechanical lithotripsy was used in 17 patients (9.7%). The overall ERCP-related complication rate was 6.3% (11/176), including bleeding in 3 patients (1.7%) and mild pancreatitis in 6 patients (3.4%). The multivariate analysis indicated that CBD stone number ≥ 2 (OR 2.171; 95% CI 1.095-4.306; p = 0.027), and the largest CBD stone size ≥ 12 mm (OR 3.646; 95% CI 1.833-7.251; p < 0.001) were patient-related risk factors for failed stone removal; while the use of endoscopic papillary (large) balloon dilation (EPBD/EPLBD) (OR 0.291; 95% CI 0.147-0.576; p < 0.001) was a procedure-related protective factor for successful stone extraction. CONCLUSIONS: ERCP is safe and effective for extraction of CBD stones in Billroth II anatomy patients. The number and the largest size of CBD stones, and the use of EPBD/EPLBD are predictive factors for CBD stone extraction.

Impact of the supine position versus left horizontal position on colonoscopy insertion: a 2-center, randomized controlled trial.

BACKGROUND AND AIMS: Colonoscopy insertion is painful for some patients and is one of the main barriers to screening colonoscopy. Few studies have assessed the impact of the supine position (SP) on colonoscopy insertion, especially for unsedated patients. The aim of this randomized controlled trial was to clarify this issue. METHODS: Unsedated patients were randomized to SP or left horizontal position (LHP) as the starting position of colonoscopy insertion. The primary outcome measure was cecal intubation time (CIT), and the secondary outcome measures were descending colon intubation time (DIT), pain score of patients, difficulty score according to the endoscopist, and patients' acceptance of unsedated colonoscopy. RESULTS: A total of 347 patients were randomized to the SP group (175) or the LHP group (172). The CIT in the SP group was significantly shorter than that in the LHP group (275.0 seconds [interquartile range (IQR), 234.0-328.5 seconds] versus 316.0 seconds [IQR, 261.0-370.0 seconds], P < .001). The DIT was also shorter in the SP group (64.5 seconds [IQR, 52.0-86.3 seconds] versus 74.0 seconds [IQR, 62.0-92.0 seconds], P = .001). Compared with the LHP, the SP had a lower pain score (3.3 versus 3.9, P = .002), a lower difficulty score (3.1 versus 3.7, P < .001), a lower frequency of position change (7.1% versus 38.0%, P < .001), and less need for abdominal compression (39.1% versus 45.5%, P = .02). SP was the only modifiable and independent factor identified to reduce CIT and pain score and improve patients' acceptance of unsedated colonoscopy. CONCLUSIONS: As an economical and convenient method, SP can reduce CIT, ease pain, and improve patients' acceptance of unsedated colonoscopy. (Clinical trial registration number: NCT03289442.).

Current diagnosis and management of Crohn's disease in China: results from a multicenter prospective disease registry.

BACKGROUND: This study aimed to understand the disease characteristics and treatment outcomes of Crohn's disease (CD) in a real-world setting in China. METHODS: In this prospective, non-interventional, multicenter disease registry, adults (≥18 years) with existing and newly diagnosed CD were recruited from 14 medical centers across China from January 2015 to January 2017. The study consisted of the enrollment and follow-up periods, of 12 months each. Demographic, clinical characteristics, diagnostic duration and management of CD at enrollment were evaluated. Logistic regression analysis and stepwise multivariate logistic regression analysis used to assess the relationship between the risk factors and CD. RESULTS: Of 504 enrolled patients, 499 (99.0%) were eligible for analysis. The mean (SD) age at study enrollment was 32.3 (11.43) years and the majority (69.7%) of participants were male. In the past 15 years, a sustained decrease of the period of time in the diagnosis of CD was observed, at about 39.4 (24.11) months in 2010, which decreased to 3.1 (2.13) months in 2015. The most common presenting symptoms of CD included abdominal pain (78.0%), diarrhea (58.1%), weight loss (52.9%) and fever (30.1%). Oral ulcer (19.4%) and arthritis (9.8%) were the most common extra-intestinal manifestations. Non-stricturing non-penetrating (B1) (49.9%) behavior and ileocolonic involvement (L3) (56.2%) location were more frequent. Perianal disease was observed in 29.1% of the patients. Around 23.8% (119/499) patients had CD-related surgery other than perianal disease surgery. Older age at enrollment, longer disease course, complicated disease behavior and absence of perianal disease were all surgery risk factors (p < 0.05). The most common medications was immunomodulators (e.g., azathioprine) (41.5%), anti-TNFα agents (32.9%) and aminosalicylates (20.6%). The mean (SD) Crohn's Disease Active Index (CDAI) score was 159.1 (91.45) and almost half of the patients (49.1%, 81/165) were in remission. CONCLUSIONS: This study demonstrated the CD-disease characteristics, risk factors of CD-related surgery and perianal disease, and treatment strategies in a real-world setting in China and may help in developing programs to diagnose and manage patients with CD.

Is ERCP-BD or EUS-BD the preferred decompression modality for malignant distal biliary obstruction? A meta-analysis of randomized controlled trials.

BACKGROUND: endoscopic retrograde cholangiopancreatography (ERCP)-guided biliary drainage (ERCP-BD) with transpapillary stent placement is the standard palliative treatment for malignant distal biliary obstruction. Endoscopic ultrasound-guided biliary drainage (EUS-BD) has been evaluated for efficacy and safety as an alternative for failed ERCP. PURPOSE: we aimed to determine whether ERCP-BD or EUS-BD is the preferred treatment modality for decompressing malignant distal biliary obstruction. METHODS: we systematically searched for relevant published, prospective, and randomized trials comparing ERCP-BD with EUS-BD in decompressing malignant distal biliary obstruction in databases (i.e., PubMed and Cochrane). Technical success, treatment success, and procedure duration were primary outcome measurements; overall adverse events, post-ERCP pancreatitis (PEP), and stent reintervention rate were the secondary outcomes. RESULTS: three trials with 220 patients met the inclusion criteria. Technical success, treatment success, procedure duration, and overall adverse event rate were similar between ERCP-BD and EUS-BD. However, ERCP-BD had a significantly higher PEP rate than EUS-BD (9.2% vs. 0%), the difference being significant (risk ratio [RR] = 8.5; 95% confidence interval (CI): 1.03-69.91, p = 0.05). Similarly, ERCP-BD had a higher stent reintervention rate than EUS-BD (28.4% vs. 4.5%), although the difference was not significant (RR = 1.91; 95% CI: 0.94-3.88, p = 0.07). CONCLUSION: technical success, treatment success, procedure duration, and overall adverse event rate were comparable between ERCP-BD and EUS-BD in decompressing malignant distal biliary obstruction. Nevertheless, EUS-BD had a significantly lower rate of PEP and a lower tendency toward stent reintervention than ERCP-BD. Therefore, EUS-BD might be a suitable alternative to ERCP-BD when performed by experts.

Empirical treatment of outpatients with gastroesophageal reflux disease with proton pump inhibitors: A survey of Chinese patients (the ENLIGHT Study).

BACKGROUND AND AIM: Empirical proton pump inhibitor (PPI) treatment is recommended as a diagnostic indicator for gastroesophageal reflux disease (GERD) and as a therapy for symptomatic control, with responses generally seen within 4 weeks. However, there are no real-world data assessing the effectiveness of short-term empirical treatment with PPIs in patients with GERD in China. METHODS: The ENLIGHT study was a multicenter, prospective, observational study conducted in China. The primary outcome was the overall response rate after 4 weeks' empirical treatment with PPIs. Adult patients aged between 18 and 65 years of age, with a gastroesophageal reflux disease questionnaire score of ≥ 8, prescribed empirical PPI treatment by their physicians and with no planned endoscopy were eligible to participate. Statistical analyses were primarily descriptive. RESULTS: Overall, 987 patients were eligible to participate and were included in the full analysis set (FAS); 707 patients were included in the per protocol set. In the FAS, esomeprazole was received by 57.1% of patients and was the most commonly used PPI. After 4-week treatment, 71.1% (95% confidence interval [CI], 67.9% to 74.2%) of patients were considered responders to PPI. The response rate at the end of 2-week PPI treatment reached 57.0% (95% CI, 52.5% to 61.7%). The median time to response was 13 days (95% CI, 12 to 15). Response rates at 2 and 4 weeks of the per protocol set were similar to those of the FAS. CONCLUSIONS: Short-term empirical PPI treatment can provide an effective relief of GERD symptoms in most Chinese patients in real-world practice.

East Asian perspective on the interaction between proton pump inhibitors and clopidogrel.

Both proton pump inhibitors (PPIs) and clopidogrel are widely prescribed in the Asia-Pacific population. PPIs are the mainstay therapeutic agents for prophylaxis against aspirin gastropathy and for acid-related disorders including gastroesophageal reflux disease. They are also co-prescribed with oral anticoagulant agents and with dual-antiplatelet therapy for the treatment and prevention of gastrointestinal bleeding. Clopidogrel belongs to the drug class of thienopyridines and is currently the most widely prescribed oral anticoagulant agent either alone or in combination with aspirin. Platelet inhibition by clopidogrel is prone to significant inter-individual variability and is believed to be affected by several factors such as genetics and drug-drug interactions. Since it was first reported in 2009, the potential for drug-drug interactions between PPIs and clopidogrel has remained headline news, and its significance in clinical practice is the subject of an ongoing debate. For East Asian patients in particular, the clinical relevance of the interaction between PPIs and clopidogrel remains unclear because of conflicting data, as well as underrepresentation of East Asian subjects in landmark trials. Increased CYP2C19 genetic polymorphisms in individuals from Asia-Pacific countries only fuel the confusion. Recent studies in East Asian cohorts suggests that the potential of PPIs to attenuate the efficacy of clopidogrel could be minimized by the use of newer PPIs with weaker affinity for the CYP2C19 isoenzyme, namely, pantoprazole, dexlansoprazole, and rabeprazole. This review aims to help clinicians choose the most appropriate PPI for co-prescription with clopidogrel in patients from Asia-Pacific countries.

Prevalence of esophageal eosinophilia and eosinophilic esophagitis in adults: a population-based endoscopic study in Shanghai, China.

BACKGROUND AND AIM: Population-based endoscopic studies of esophageal eosinophilia and eosinophilic esophagitis are limited in the world. This study was aiming to describe features of esophageal eosinophilia and eosinophilic esophagitis in a representative sample of the adult in Shanghai, China. METHODS: As part of a large epidemiological study, 3,600 individuals (aged 18-80 years) were randomly selected in Shanghai, China. They were asked to undergo endoscopy and have at least four esophageal biopsies taken from 0.5 cm above the Z-line and any abnormal areas. Any eosinophil infiltration of the epithelium was defined as esophageal eosinophilia. Eosinophilic esophagitis was defined as ≥15 eosinophils/high-power field in esophageal biopsies. RESULTS: A total of 1,030 individuals accepted to have endoscopy and 1,021 individuals with biopsy results were suitable for analysis. Esophageal eosinophilia was present in 67 subjects (6.6 %). Eosinophilic esophagitis was present in four cases (0.4 %). No significant association was found between the presence of esophageal eosinophilia and reflux esophagitis, Barrett's esophagus, symptom-defined gastroesophageal reflux disease or H. pylori infection. Most individuals with esophageal eosinophilia (80.6 %) did not have any of the upper gastrointestinal symptoms. CONCLUSIONS: Esophageal eosinophilia was present in nearly 6.6 % of the general adult population of China; 0.4 % had eosinophilic esophagitis. Most of individuals with esophageal eosinophilia were asymptomatic.

Efficacy and safety of cinitapride in the treatment of mild to moderate postprandial distress syndrome-predominant functional dyspepsia.

GOALS AND BACKGROUND: Functional dyspepsia (FD) is a complex disease with a variety of dyspeptic symptoms. Little is known about the clinical efficacy of cinitapride, a 5-HT4 agonist and D2 antagonist, in treating FD. STUDY: This randomized, double-blind, double-dummy, positive-controlled study compared the efficacy and safety of cinitapride (1 mg) and domperidone (10 mg) tid for 4 weeks in 383 consecutive patients with mild to moderate, postprandial distress syndrome-predominant dyspeptic symptoms according to Rome III criteria. The primary endpoint was the noninferiority of cinitapride compared with domperidone in relief of symptoms. The overall patient evaluation of treatment and open gastric emptying effects of both drugs were treated as the secondary endpoints. RESULTS: The rates of symptom relief by cinitapride and domperidone after 4 weeks did not differ significantly on intension-to-treat analysis (85.8% vs. 81.8%, P=0.332). Cinitapride significantly reduced the overall severity of postprandial fullness, early satiation, and bloating (4.3±3.9 vs. 17.8±6.6, P<0.001); and it was superior to the effects of domperidone (5.4±4.9 vs. 18.4±6.9, P<0.001; P=0.021 between groups). Cinitapride also decreased the mean half-gastric emptying time from 131.1±119.4 to 86.5±18.7 minutes (P=0.0002). There was a positive relationship between symptoms and gastric emptying time (r=0.332, P=0.041). Cinitapride-related adverse events were observed in 9.1% of patients, including 1 patient with extrapyramidal symptoms. No patient experienced QT interval prolongation. CONCLUSIONS: This phase III trial has confirmed a noninferior efficacy of cinitapride over domperidone for patients with mild to moderate, postprandial distress syndrome-predominant FD. Cinitapride usage is well tolerated, but its cardiovascular events need further evaluation.