Immunoglobulin G-mediated food intolerance and metabolic syndrome influence the occurrence of reflux esophagitis in Helicobacter pylori-infected patients.

BACKGROUND: Reflux esophagitis has an increasing prevalence and complex and diverse symptoms. Identifying its risk factors is crucial to understanding the etiology, prevention, and management of the disease. The occurrence of reflux esophagitis may be associated with food reactions, Helicobacter pylori (H. pylori) infection, and metabolic syndromes. AIM: To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin (Ig) G-mediated food intolerance, H. pylori infection, and metabolic syndrome on reflux esophagitis. METHODS: Outpatients attending the Second Medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively enrolled. The patients' basic information, test results, gastroscopy results, H. pylori test results, and IgG-mediated food intolerance results were collected. Multivariate logistic regression analysis was used to analyze risk factors for reflux esophagitis. Statistical mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on H. pylori infection affecting reflux esophagitis. RESULTS: A total of 7954 outpatients were included; the prevalence of reflux esophagitis, IgG-mediated food intolerance, H. pylori infection, and metabolic syndrome were 20.84%, 61.77%, 35.91%, and 60.15%, respectively. Multivariate analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance (OR = 1.688, 95%CI: 1.497-1.903, P < 0.00001) and metabolic syndrome (OR = 1.165, 95%CI: 1.030-1.317, P = 0.01484), and the independent protective factor for reflux esophagitis was H. pylori infection (OR = 0.400, 95%CI: 0.351-0.456, P < 0.00001). IgG-mediated food intolerance had a partially positive mediating effect on H. pylori infection as it was associated with reduced occurrence of reflux esophagitis (P = 0.0200). Metabolic syndrome had a partially negative mediating effect on H. pylori infection and reduced the occurrence of reflux esophagitis (P = 0.0220). CONCLUSION: Patients with IgG-mediated food intolerance and metabolic syndrome were at higher risk of developing reflux esophagitis, while patients with H. pylori infection were at lower risk. IgG-mediated food intolerance reduced the risk of reflux esophagitis pathogenesis in patients with H. pylori infection; however, metabolic syndrome increased the risk of patients with H. pylori infection developing reflux esophagitis.

Xuanfu Daizhe Tang alleviates reflux esophagitis in rats by inhibiting the STAT1/TREM-1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Reflux esophagitis (RE) is a common chronic inflammatory disease of the esophageal mucosa with a high prevalence and recurrence rate, for which a satisfactory therapeutic strategy is still lacking. Chinese medicine has its characteristics and advantages in treating RE, and the clinical application of Xuanfu Daizhe Tang (XDT) in treating RE has achieved sound therapeutic effects. However, there needs to be more research on its mechanism of action. AIM OF THE STUDY: The present work aimed to investigate the mechanism of XDT action in RE through the Signal Transducer and Activator of Transcription 1 (STAT1)/Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) pathway. MATERIALS AND METHODS: The main active components of XDT were analyzed by ultra-performance liquid chromatography-mass spectrometer (UPLC-MS). The effect of XDT on RE was evaluated in a rat model of RE induced by "Cardioplasty + pyloric ligation + Roux-en-Y esophagojejunostomy". Each administration group was treated by gavage. The degree of damage to the esophageal mucosa was evaluated by visual observation, and the Potential of Hydrogen (PH) method and Hematoxylin-eosin staining (HE) staining were performed. Serum levels of Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6), Tumor Necrosis Factor alpha (TNF-α), and Inducible Nitric Oxide Synthase (iNOS) were measured by ELISA. Quantitative Real-time PCR (qPCR), Western Blot (WB), and Immunofluorescence (IF) methods were used to detect Claudin-4, Claudin-5, TREM-1, and p-STAT1 in esophageal tissues for studying the mechanism of action and signaling pathway of XDT. Immunohistochemistry (IHC) analysis was used to detect the expression of TREM-1 and CD68 in esophageal tissues. Flow Cytometry (FC) was used to detect the polarization of macrophages in the blood. After conducting preliminary experiments to verify our hypothesis, we performed molecular docking between the active component of XDT and STAT1 derived from rats and parallel experiments with STAT1 inhibitor. The selective increaser of STAT1 transcription (2-NP) group was used to validate the mechanism by which XDT acts. RESULTS: XDT alleviated esophageal injury and attenuated histopathological changes in RE rats. XDT also inhibited the inflammatory response and decreased serum IL-1ß, IL-6, TNF-α, and iNOS levels in RE rats. qPCR and WB results revealed that XDT inhibited the expression of Claudin-4, Claudin-5, TREM-1, and STAT1 in the esophageal mucosa of RE rats. IHC and FC results showed that XDT reduced TREM-1 levels in esophageal tissues and polarized macrophages toward M2. The molecular docking results showed that rat-derived STAT1 can strongly bind to Isochronogenic acid A in XDT. The parallel experimental results of STAT1 inhibitor showed that XDT has anti-inflammatory effects similar to STAT1 inhibitors. The 2-NP group confirmed that XDT exerts its therapeutic effect on reflux esophagitis through the STAT1/TREM-1 pathway, with STAT1 as the upstream protein. CONCLUSIONS: This study suggests that XDT may treat reflux esophagitis by modulating the STAT1/TREM-1 pathway.

Elevated Pro-inflammatory Cytokine Levels in Acute Reflux Esophagitis Are Reduced by 1,25 Dihydroxy Vitamin D3.

BACKGROUND/AIM: Gastric acid reflux into the esophagus can cause irritation and inflammation of the esophagus and progress to reflux esophagitis (RE). Vitamin D3 (VitD3) has anti-inflammatory effects and plays an important regulatory role in adaptive and innate immunity. We hypothesized that VitD3 may play a protective role in RE. MATERIALS AND METHODS: Seventy male Sprague-Dawley rats were used, and acute RE (n=35) or chronic RE (n=35) were surgically induced. The effects of different doses of VitD3 on morphological changes and alteration of pro-inflammatory cytokine levels were examined in the rat models. Western blot analysis was performed to determine protein expression levels of IL-1ß, IL-6, and IL-8 in esophageal tissues. Serum levels of VitD3 and calcium were determined using enzyme-linked immunosorbent assays. RESULTS: The protein expression of pro-inflammatory cytokines IL-1ß, IL-6, and IL-8 was found significantly increased in RE. VitD3 treatment significantly reduced the levels of these pro-inflammatory cytokines in both the low-dose and high-dose VitD3 groups compared to control groups in acute RE, but not chronic RE. Macrographic and histopathological examination revealed various degrees of esophageal impairment in rats following surgical induction of acute or chronic RE in rats. These impairments were not improved by VitD3. Morphological grading of esophageal mucosa showed no significant differences between acute and chronic RE. Elevated serum levels of calcium were observed after VitD3 treatment. CONCLUSION: IL-1ß, IL-6, and IL-8 levels were significantly elevated in RE. The abnormal increase in these important pro-inflammatory cytokines was suppressed by VitD3 in the rat models of acute RE. These novel findings suggest a potential protective role of VitD3 in early-stage RE.

[Clinical and gastroscopic features of children with cyclic vomiting syndrome: an analysis of 63 cases]. / 儿童周期性呕吐综合征63例临床与胃镜分析.

OBJECTIVES: To study the clinical and gastroscopic features of children with cyclic vomiting syndrome. METHODS: A retrospective analysis was performed on the medical data of 63 children with cyclic vomiting syndrome who were hospitalized and followed up in Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University from August 2019 to March 2022. RESULTS: Among the 63 children, there were 30 boys and 33 girls, with a mean age of 6.11 years, a mean course of disease of 2.57 years, and a mean vomiting period of 4.04 days. The most common accompanying symptom was listlessness or somnolence (55/63, 87%), followed by anorexia (45/63, 71%), abdominal pain or abdominal discomfort (40/63, 63%), constipation (19/63, 30%), salivation (12/63, 19%), nausea (11/63, 17%), headache (11/63, 17%), fever (6/63, 10%), and rash (1/63, 2%). All 63 children underwent gastroscopy, among whom 3 had no marked abnormalities, 22 (35%) had chronic superficial gastritis or chronic non-atrophic gastritis alone, and 38 (60%) had other abnormal changes aside from chronic gastritis (16 children with reflux esophagitis, 12 with bile reflux gastritis, 13 with duodenitis, 10 with erosive gastritis, and 5 with gastric or duodenal ulcer). Among the 63 children, 42 underwent pathological examinations of gastric mucosa, among whom 5 had no marked abnormalities, 34 had mild chronic gastritis, 2 had moderate chronic gastritis, and 1 had severe chronic gastritis. Among the 63 children, 15 received 24-hour dynamic esophageal pH monitoring during the interictal period, among whom 9 children were found to have pathological acid reflux. CONCLUSIONS: In addition to recurrent vomiting, most children with cyclic vomiting syndrome also have the symptoms such as somnolence or listlessness, anorexia, and abdominal pain. The main manifestation on gastroscopy is chronic gastritis, and most children may also have reflux esophagitis, bile reflux gastritis, and erosive gastritis. Mild chronic gastritis is the main pathological change of gastric mucosa.

Proteomic analysis reveals that ACSL4 activation during reflux esophagitis contributes to ferroptosis-mediated esophageal mucosal damage.

Ferroptosis has been shown to be involved in the pathological process of many diseases. However, the function and mechanism of ferroptosis in reflux esophagitis (RE), especially in the esophageal mucosal damage, remains unknown. The purpose of this study was to screen potential therapeutic target genes that mediate RE esophageal mucosal damage and regulate ferroptosis. RE rats were established by our previous protocol and proteomic analysis of esophageal mucosa was performed. In addition, the ferroptosis-related genes were retrieved from the FerrDb database and were cross analyzed with the differential proteins of proteomics to obtain potential therapeutic target genes Acyl-CoA synthetase long-chain family 4 (ACSL4), a key enzyme for ferroptosis. In the present study, we used the ACSL4 inhibitor rosiglitazone (ROSI) and the ferroptosis inhibitor ferrostatin-1 to intervene with RE rats, and evaluate the levels of protein, histological changes, lipid peroxidation levels, iron accumulation and morphological changes in esophageal tissue by HE staining, Western blot, related kit tests, and transmission electron microscope. The results showed that both ferrostatin-1 and ROSI treatment significantly reduced the levels of iron accumulation and lipid peroxidation, and protected against ferroptosis and esophageal tissue injury in RE rats. Through Immunohistochemical staining, 16SrDNA sequencing, Enzyme linked immunosorbent assay (ELISA), Western blot and other tests on the esophagus, gut, spleen and serum of RE rats, we further found that the changes of esophageal and intestinal microbiota and the increase of peripheral blood LPS were the key factors regulating ferroptosis in esophageal epithelial tissue. On the one hand, LPS could increase the expression of ACSL4 in esophageal tissue by up-regulating special protein 1 (Sp1). On the other hand, LPS could increase the secretion of serum ferritin in spleen and the accumulation of iron in esophageal tissue by activating Capase11/GSDMD pyroptosis pathway. Collectively, this study suggests that ACSL4 and ferroptosis are potential therapeutic targets for RE esophageal mucosal damage, and esophageal and gut microecology play a critical role in this process.

GASTROESOPHAGEAL SYMPTOMS AFTER LAPAROSCOPIC GASTRIC BYPASS: MISTAKES IN PERFORMING THE PROCEDURE?

AIM: Laparoscopic Roux-en-Y gastric bypass (LGB) is the recommended procedure for morbidly obese patients with gastroesophageal reflux disease (GERD). However, there have been reported gastroesophageal reflux symptoms or esophagitis after LGB. Few functional esophageal studies have been reported to date. To evaluate the anatomic and physiologic factors contributing to the appearance of these problems in patients who underwent LGB. METHODS: This prospective study included 38 patients with postoperative gastroesophageal reflux symptoms submitted to LGB. They were subjected to clinical, endoscopic, radiologic, manometric, and 24-h pH-monitoring evaluations. RESULTS: Eighteen (47.4%) of 38 patients presented with heartburn or regurgitation, 7 presented with pain, and 4 presented with dysphagia. Erosive esophagitis was observed in 11 (28.9%) patients, and Barrett's esophagus (5.7%) and jejunitis (10.5%) were also observed. Hiatal hernia was the most frequent finding observed in 15 (39.5%) patients, and most (10.5%) of these patients appeared with concomitant anastomotic strictures. A long blind jejunal loop was detected in one (2.6%) patient. Nearly 75% of the patients had hypotensive lower esophageal sphincter (9.61±4.05 mmHg), 17.4% had hypomotility of the esophageal body, and 64.7% had pathologic acid reflux (% time pH <4=6.98±5.5; DeMeester's score=32.4±21.15). CONCLUSION: Although rare, it is possible to observe gastroesophageal reflux and other important postoperative symptoms after LGB, which are associated with anatomic and physiologic abnormalities at the esophagogastric junction and proximal gastric pouch.

The path(ology) from reflux oesophagitis to Barrett oesophagus to oesophageal adenocarcinoma.

This review seeks to summarise the steps in the path from reflux oesophagitis to Barrett oesophagus to oesophageal adenocarcinoma. The epidemiology, clinical presentation, definitions, pathological features, diagnostic pitfalls, and emerging concepts are reviewed for each entity. The histological features of reflux oesophagitis can be variable and are not specific. Cases of reflux oesophagitis with numerous eosinophils are difficult to distinguish from eosinophilic oesophagitis and other oesophagitides with eosinophils (Crohn's disease, medication effect, and connective tissue disorders). In reflux oesophagitis, the findings are often most pronounced in the distal oesophagus, the eosinophils are randomly distributed throughout the epithelium, and eosinophilic abscesses and degranulated eosinophils are rare. For reflux oesophagitis with prominent lymphocytes, clinical history and ancillary clinical studies are paramount to distinguish reflux oesophagitis from other causes of lymphocytic oesophagitis pattern. For Barrett oesophagus, the definition remains a hotly debated topic for which the requirement for intestinal metaplasia to make the diagnosis is not applied unanimously across the globe. Assessing for dysplasia is a challenging aspect of the histological interpretation that guides clinical management. We describe the histological features that we find useful in making this evaluation. Oesophageal adenocarcinoma has been steadily increasing in incidence and has a poor prognosis. The extent of invasion can be overdiagnosed due to a duplicated muscularis mucosae. We also describe the technical factors that can lead to challenges in distinguishing the mucosal and deep margins of endoscopic resections. Lastly, we give an overview of targeted therapies with emerging importance and the ancillary tests that can identify the cases best suited for each therapy.

Obesity and its effects on the esophageal mucosal barrier.

Obesity is associated with gastroesophageal reflux disease (GERD) and its complications including reflux esophagitis, Barrett's esophagus, and esophageal adenocarcinoma. Traditionally, these associations have been attributed to the mechanical effect of abdominal fat in increasing intra-abdominal pressure, thereby promoting gastroesophageal reflux and causing disruption of antireflux mechanisms at the esophagogastric junction. However, recent studies suggest that visceral adipose tissue (VAT) produces numerous cytokines that can cause esophageal inflammation and impair esophageal mucosal barrier integrity through reflux-independent mechanisms that render the esophageal mucosa especially susceptible to GERD-induced injury. In this report, we review mechanisms of esophageal mucosal defense, the genesis and remodeling of visceral adipose tissue during obesity, and the potential role of substances produced by VAT, especially the VAT that encircles the esophagogastric junction, in the impairment of esophageal mucosal barrier integrity that leads to the development of GERD complications.

Correlation between gastroesophageal flap valve abnormality and novel parameters in patients with gastroesophageal reflux disease symptoms by the lyon consensus.

Gastroesophageal flap valve (GEFV) grading is a simple and reproducible parameter. There is limited information about the association between GEFV abnormality and novel parameters in patients with gastroesophageal reflux disease(GERD) symptoms by the Lyon Consensus. To investigate the value of GEFV grading in GERD, the clinical data of 320 patients with GERD symptoms who underwent endoscopy, 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring, and high-resolution manometry (HRM) were retrospectively analyzed. The percentage of acid exposure time (AET%)(4.2 [1.5-7.4] vs. 1.3 [0.3-4.2], P < 0.001) and the proportion of abnormal esophagogastric junction (EGJ) morphology (71 [87.7%] vs. 172 [72.0%], P = 0.011) were significantly higher, while the mean nocturnal baseline impedance (MNBI) (2068.3 [1658.4-2432.4] vs. 2228.5 [1794.8-2705.3]Ω, P = 0.012) and post-reflux swallow-induced peristaltic wave index (PSPWI) (19.7 [13.9-29.0] vs. 33.3 [25.0-44.0]%, P < 0.001) were significantly lower in the abnormal GEFV group compared with the normal GEFV group. AET% and EGJ morphology showed positive correlations with GEFV grade, while PSPWI and MNBI showed negative correlations. Patients with an abnormal GEFV had a significantly greater risk of conclusive evidence of GERD compared to those with a normal GEFV (OR 3.035, 95% CI 1.758-5.240, P < 0.001). Further, when identifying patients with conclusive evidence of GERD, abnormal GEFV had a specificity of 80.4% (95% CI 75.3-85.5%). GEFV grading might be regarded as supportive evidence for GERD diagnosis.

The Impact of Erosive Reflux Esophagitis on the Decline of Lung Function in the General Population.

BACKGROUND: The impact of reflux esophagitis on the decline of lung function has been rarely reported. This study was performed to evaluate the association between erosive reflux esophagitis and lung function changes. METHODS: We included patients with normal lung function who underwent esophagogastroduodenoscopy for health screening from a health screening center. Patients with persistent erosive reflux esophagitis on two discrete endoscopic examinations were designated as the erosive reflux esophagitis group. We also selected patients without erosive reflux esophagitis and matched them 1:4 with patients from the erosive reflux esophagitis group. We estimated annual forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) changes from baseline and compared these estimates by the linear mixed regression model. We also estimated the biannual incidence of chronic obstructive pulmonary disease (COPD). RESULTS: In total, 1,050 patients (210 patients with erosive reflux esophagitis, and 840 matched controls) were included. The median follow-up duration for spirometry was six years. In patients with erosive reflux esophagitis, mild reflux esophagitis (A grade) was most common (165 patients, 78.6%). The adjusted annual FEV1 change in patients with erosive reflux esophagitis was -51.8 mL/yr, while it decreased by 46.8 mL/yr in controls (P = 0.270). The adjusted annual FVC decline was similar between the two groups (-55.8 vs. -50.5 mL/yr, P = 0.215). The estimated COPD incidence during the follow-up period was not different between the erosive reflux esophagitis and control groups. CONCLUSION: In patients with normal lung function, the presence of erosive reflux esophagitis did not affect the annual declines in FEV1 or FVC.

Protective Effects of Inflammation of Curcumae Longae Rhizoma 30% EtOH Extract on Acute Reflux Esophagitis Rats.

Gastroesophageal reflux disease (GERD) is induced by the reflux of stomach contents or gastric acid, pepsin into the esophagus for prolonged periods of time due to defection of the lower esophageal sphincter. Reflux esophagitis is a disease found in less than 50% of GERD patients. This study is aimed at evaluating the protective effect of Curcumae longae Rhizoma 30% EtOH extract (CLR) in acute reflux esophagitis (ARE) rats. CLR measured antioxidant activity through in vitro experiments. Based on the results, we performed experiments in vivo. Before 90 min ARE induction, CLR was administered orally by concentration. ARE was derived by linking the metastatic junction between pylorus and forestomach and corpus in Sprague-Dawley rats. And rats were sacrificed 5 h after surgery. We analyzed the expression of antioxidant and inflammatory-related markers by western blot and observed the production of alanine aminotransferase (ALT), aspartate aminotransferase (AST), reactive oxygen species (ROS), peroxynitrite (ONOO-), and thiobarbituric acid reactive substance (TBARS). The administration of CLR reduced esophagus tissue damage in rats with acute reflux esophagitis and decreased the elevated ALT, AST, ROS, ONOO-, and TBARS. In addition, CLR effectively increased antioxidant-related factors and reduced inflammatory protein. Overall, these results suggest that CLR would be used as a therapeutic material in protection and treatment for ARE. Overall, CLR treatment informed that markedly ameliorated inactivation of NF-κB led to the inhibition of the expressions of proinflammatory proteins. These results suggest that CLR would be used as a therapeutic material in protection and treatment for ARE.

Low Levels of Gastrin 17 are Related with Endoscopic Findings of Esophagitis and Typical Symptoms of GERD.

BACKGROUND AND AIMS: In clinical practice, most patients with symptoms suggestive of gastroesophageal reflux disease (GERD) undergo esophago-gastro-duodenoscopy (EGD), despite its low sensitivity in detecting reflux stigmata. Gastrin 17 (G-17) has been proposed to be related with GERD, due to the negative feedback between acid secretion and this hormone. We assessed the clinical usefulness of fasting G-17 serum determination for a non-invasive diagnosis of GERD in patients with typical symptoms. METHODS: We consecutively enrolled patients complaining of typical GERD symptoms in two different settings: a single referral center and a primary care setting. Control groups consisted of dyspeptic patients. All subjects underwent assessment of serum levels of G-17 and EGD. RESULTS: At the academic hospital, 100 GERD patients (n=89 with erosive esophagitis and 11 with Barrett's esophagus) had statistically significant low levels of G-17 as compared with 184 dyspeptic patients (1.7±1.2 pg/L vs 8.9±5.7 pg/L p<0.0001). Similarly, in the primary care setting, 163 GERD patients had statistically significant low levels of G-17 as compared with 132 dyspeptic patients (0.5±0.2 pg/L vs. 4.0±2.6 pg/L, p<0.0001). Moreover, in the primary care setting, no statistically significant differences were found for G-17 levels between patients with erosive and non-erosive reflux pattern (0.4±0.2 vs 0.7±0.3; p=0.08). In primary care, the accuracy of G-17 less than 1 pg/L to diagnose non-invasively GERD was 94.3%. CONCLUSIONS: Low levels of G-17 were detected in patients with erosive esophagitis and Barrett's esophagus in a referral center and in patients with typical GERD symptoms in a sample of patients from a primary care setting.

Factors affecting the treatment outcomes of laparoscopic fundoplication for erosive reflux esophagitis: findings of esophageal pathological function tests.

PURPOSE: To identify the factors that affect laparoscopic fundoplication (LF) treatment efficacy in patients with erosive gastroesophageal reflux disease (e-GERD) esophagitis, based on the findings of multichannel intraluminal impedance pH (MII-pH) and high-resolution manometry (HRM). METHODS: The subjects were 102 patients with e-GERD diagnosed by endoscopy, who underwent LF as the initial surgery. To analyze the findings of MII-pH and HRM, the patients were divided into two groups: a cured group (CR), comprised of patients whose esophagitis was cured postoperatively; and a recurrence group (RE), comprised of patients who suffered recurrent esophagitis. RESULTS: There were 96 patients in the CR group and 6 in the RE group. MII-pH indicated that the acid reflux time, the longest reflux time, and the number of refluxes longer than 5 min, were significantly higher in the RE group than in the CR group (p = 0.0028, p = 0.0008, p = 0.012, respectively). The HRM indicated that only the distal contractile integral (DCI) was significantly lower in the RE group (p = 0.0109). CONCLUSION: The results of this study indicate that esophageal clearance may affect the treatment outcome of LF. Based on the findings of MII-pH, the longest reflux time and the number of refluxes longer than 5 min were important factors influencing the therapeutic effect, whereas based on the HRM, the DCI value was most important.

GERD for the nongastroenterologist: successful evaluation, management, and lifestyle-based symptom control.

Gastroesophageal reflux disease (GERD) is a complex disorder. Symptoms of heartburn can help find the disorder of GERD. pH testing is the mainstay of evaluation of symptoms, including 24-h and longer pH studies to detect pathologic acid exposure. The use of proton pump inhibitor (PPI) therapy for approved indications is helpful for both symptomatic relief and esophagitis healing in the majority of patients with abnormal acid exposure. PPI medications are safe in short- or long-term use. It is recommended not to maintain cirrhotic patients on PPI therapy without a meaningful indication. Dietary adjustment can provide benefit to some patients, but the data are mixed on how much benefit has been demonstrated from specific food avoidance. Reduction in weight improves reflux. Obesity has measurable effects on the esophageal acid exposure but fewer effects on the motility of the esophagus itself. Controlling weight and changing lifestyle can be helpful for improving GERD symptoms. For some patients in whom either the control of reflux with medications and lifestyle change is not sufficient or a hernia is contributing to symptom generation, surgical and endosurgical interventions can be considered to help manage reflux after a thorough workup with pH testing and manometry.

Extraesophageal syndrome of gastroesophageal reflux: relationships with lung disease and transplantation outcome.

Gastroesophageal reflux disease (GERD) is prevalent and may be associated with both esophageal and extraesophageal syndromes, which include various pulmonary conditions. GERD may lead to pulmonary complications through the "reflux" (aspiration) or "reflex" (refluxate-triggered, vagally mediated airway spasm) mechanisms. While GERD may cause or worsen pulmonary disorders, changes in respiratory mechanics due to lung disease may also increase reflux. Typical esophageal symptoms are frequently absent and objective assessment with reflux monitoring is often needed for diagnosis. Impedance monitoring should be considered in addition to traditional pH study due to the involvement of both acidic and weakly acidic/nonacidic reflux. Antireflux therapy may improve outcomes of some pulmonary complications of GERD, although careful selection of a candidate is paramount to successful outcomes. Further research is needed to identify the optimal testing strategy and patient phenotypes that would benefit from antireflux therapy to improve pulmonary outcomes.

Intestinal stem cells promote crypt fission during postnatal growth of the small intestine.

OBJECTIVE: Wnt-ß-catenin signalling is essential for intestinal stem cells. Our aim was to investigate the relationship between intestinal stem cells and crypt fission which peaks during infancy. DESIGN: Duodenal biopsies were obtained during endoscopy to assess the severity of reflux oesophagitis of 15 infants, children and teenagers, which would not affect the duodenum. Samples of small intestine were also obtained from rats 7-72 days of life. Crypt fission was assessed using microdissection of 100 whole crypts and recording the percentage of bifid crypts. Intestinal LGR5+ stem cells were identified by in situ hybridisation. Rats were treated with Dickkopf to block Wnt-ß-catenin signalling. RESULTS: Crypt fission peaked during infancy before declining after 3-4 years in humans and after 21 days of life in rats. Occasional mitotic figures were seen in bifid crypts during early fission. Stem cells were elevated for a greater period during infancy and childhood in humans. Clustering of Paneth cells was present around the stem cells at the crypt base. Dickkopf reduced the number of stem cells and crypt fission to 45% and 29%, respectively, of control values, showing dependence of both crypt fission and Lgr5+ stem cells on Wnt signalling. However, Dickkopf did not decrease mitotic count per crypt, indicating a difference in signalling between stem cells and their progeny in the transit amplifying zone. CONCLUSION: Crypt fission peaks during infancy and is dependent on intestinal stem cells. This is relatively hidden by 'a cloak of invisibility' due to the low proliferation of stem cells.

Improvement of Inflammation through Antioxidant Pathway of Gardeniae Fructus 50% EtOH Extract (GE) from Acute Reflux Esophagitis Rats.

Gardeniae Fructus 50% EtOH extract (GE) is a traditional herb that has been used to treat a variety of diseases. In this study, we investigate the antioxidant, anti-inflammatory, and antiapoptotic properties of GE on acute reflux-induced esophagitis (RE) model in rats. 2,2'-Azino-bis (3-ethylbenzothiazolin-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays were performed to determine the antioxidant activity of GE. GE was given orally at 50 and 100 mg/kg body weight 1h 30 min prior to RE induction. And its effect was assessed in comparison with RE control and normal groups. The administration of the extract of the GE showed remarkable protection of mucosal damage in esophageal tissue, and the histologic observation showed that the gastric lesion was improved. Increased reactive oxygen species (ROS) levels in the serum were diminished by GE treatment. The antioxidative biomarkers including nuclear factor-erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX) were significantly increased. GE administration significantly reduced the inflammatory protein expression through MAPK-related signaling pathways and the nuclear factor-kappa B (NF-κB) pathway. These results suggest that GE protects the esophagus mucosal membrane by attenuating oxidative stress and inflammatory response under reflux esophagitis condition through the antioxidant pathway. Therefore, it is suggested that GE may be a potential remedy for the treatment of reflux esophagitis.

A Novel Susceptibility Locus Near GRIK2 Associated With Erosive Esophagitis in a Korean Cohort.

INTRODUCTION: The male-predominant sex difference through the spectrum of erosive esophagitis to Barrett's esophagus is widely known. We conducted a genome-wide association study (GWAS) stratified by sex for identifying factors that can predict the endoscopically diagnosed erosive esophagitis. METHODS: Erosive esophagitis was diagnosed by endoscopy and assessed for severity. We identified genetic factors associated with erosive esophagitis that accounted for the sex differences in a cohort of 4,242 participants via a GWAS. After quality control and imputation, genetic associations with erosive esophagitis were investigated by multivariate linear regression in 3,620 subjects. Single-nucleotide polymorphisms (SNPs) with P < 5.0 × 10 were considered significant genome wide, and a genetic risk score was constructed for the prediction of erosive esophagitis risk. RESULTS: Six genome-wide significant SNPs near the GRIK2 gene on chromosome 6 were found to be associated with erosive esophagitis only in male subjects. These were predictive of severity through a genetic risk score (P < 0.05), and the findings were validated in a cohort of 622 subjects (P < 0.05). DISCUSSION: This is the first GWAS of erosive esophagitis, and we identified 6 genome-wide significant SNPs in male subjects. These SNPs could help explain the pathogenesis of erosive esophagitis and contribute to the understanding of sex differences. Further genetic investigation could allow for the prediction of high risk for erosive esophagitis and development of new treatment options.

[DIAGNOSTIC EFFICIENCY OF THE USE OF A MAGNIFYING CHROMOENDOSCOPY WHEN EXAMINING THE ORAL CAVITY IN PATIENTS WITH A GASTROENTEROLOGICAL PROFILE WITH EXTRAESOPHAGEAL MANIFESTATIONS OF REFLUX DISEASE].

The article is devoted to the study of the diagnostic effectiveness of using magnifying chromoendoscopy when examining the oral cavity in patients with a gastroenterological profile with extra-esophageal manifestations of reflux disease. Pathologies of the oral cavity are often one of the additional symptoms, according to the Montreal Consensus and classification of gastroesophageal reflux disease (GERD). Barrett's esophagus is a serious complication of GERD, in which a cylindrical epithelium with intestinal metaplasia is found in the epithelial lining of the mucous membrane of the esophagus, which is a marker of this disease often in combination with dysplasia instead of squamous stratified non-keratinized epithelium. The relevance is due to the fact that this disease is considered as a precancerous condition and is associated with an increased risk of developing adenocarcinoma of the lower third of the esophagus. In this regard, timely diagnosis of Barrett's esophagus and monitoring of these patients will improve the prognosis of the disease and reduce the frequency of deaths.

Efficacy of Vonoprazan for 48-Week Maintenance Therapy of Patients with Healed Reflux Esophagitis.

AIMS: We aimed to evaluate the efficacy of vonoprazan (VPZ) as maintenance therapy for healed reflux esophagitis (RE). METHODS: We enrolled 74 patients diagnosed with RE with frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) total score ≥8 after at least 8 weeks of treatment with standard proton pump inhibitors (PPIs). These patients were switched to VPZ 20 mg for 4 weeks. We also enrolled 71 patients with no endoscopic evidence of erosive esophagitis who received maintenance therapy with VPZ 10 mg for 48 weeks. The primary end point was the proportion of patients who maintained healed RE refractory to PPIs after 48 weeks of maintenance therapy with on demand 10 mg VPZ. Secondary assessment included the proportion of patients with symptomatic nonrelapse at 48 weeks. RESULTS: Fifty patients successfully completed 48-week maintenance therapy. Maintenance therapy with VPZ 10 mg prevented the relapse of esophageal mucosal breaks in 43 (86.0%) of 50 patients at 48 weeks. During the 48-week maintenance therapy, symptomatic nonrelapse rate for acid reflux-related symptom score of FSSG and acid reflux score of Gastrointestinal Symptom Rating Scale at 48 weeks were 70.0 and 72.0%, respectively. No serious adverse events were reported during the study. CONCLUSION: VPZ 10 mg is clinically effective for maintenance of healed RE for 48 weeks.