Evaluation of the Effects of Gastro Protect as an Alternative Medicine on Gastritis and Other Gastrointestinal Symptoms.

INTRODUCTION: The use of herbal medicine as a part of the Complementary and Alternative Medicine is increasing worldwide. Herbal remedies are used to better different conditions including gastritis. MATERIAL AND METHODS: We conducted a prospective randomized control clinical trial on a total sample of 72 patients with gastritis in order to examine the effects of the commercial herbal product Gastro Protect. After 6 weeks of conventional therapy the patients were divided into two groups with 36 patients each. As a continuation of the treatment, Group 1 received conventional therapy + Gastro Protect and Group 2 received conventional therapy + Placebo. We analyzed 14 selected gastrointestinal symptoms, five related to digestive problems, and nine related to stool and bowel problems. For assessing the selected symptoms we used seven point gastrointestinal symptom rating scale (GSRS). RESULTS: The Gastro Protect group had a significantly lower GSRS score (better condition) compared to the Placebo group related to all five selected symptoms of digestive problems as: abdominal pain (p=0.0250), hunger pain (p=0.0276), nausea (p=0.0019), heartburn (p=0.00001), and acid reflux (p=0.0017). The Gastro Protect group, also had a significantly lower GSRS score (better condition) compared to the Placebo group related to three out of nine selected bowel symptoms: rumbling (p=0.0022), abdominal distension (p=0.0029), and gas or flatus (p=0.0039). CONCLUSION: Gastro protect was effective in treating gastritis and other gastrointestinal symptoms. It was safe for usage and showed almost no side effects. In our study, Gastro Protect reduced the examined gastric symptoms and related examined intestinal symptoms.

Effectiveness analysis of herbal medicine for gastroesophageal reflux disease: A retrospective study.

This study aimed to identify the clinical features of gastroesophageal reflux disease (GERD) in primary clinics and the effectiveness and safety of herbal medicine (HM). Thirty-five patients with gastroesophageal-reflux symptom who visited the 16 Korean medicine (KM) primary clinics from June 2022 to October 2022 were included in the study. We retrospectively analyzed the charts of 35 patients and collected clinical characteristics, HM, and outcome variables such as the numerical rating scale, gastroesophageal reflux disease questionnaire, frequency scale for symptoms of gastroesophageal reflux disease, Euro-Quality Of Life-5 Dimension, and adverse events. Of the 35 patients, 12 (34.3%) were men, and the average age of all patients was 47.0 ±â€…14.3 years. HM was prescribed for all 35 patients; Pinelliae Tuber (n = 31, 88.57%), Zingiberis Rhizoma Recens (n = 30, 85.71%), and Poria Sclerotium (n = 28, 80%) were the most prescribed herbs. All scores including numerical rating scale, frequency scale for symptoms of gastroesophageal reflux disease, gastroesophageal reflux disease questionnaire, and Euro-Quality Of Life-5 Dimension after 30 and 60 days from baselines showed significant improvement, and there were only a few adverse events. This study supports the effectiveness and safety of HM in reducing GERD symptoms in primary Korean medicine clinics. The most frequently used herbs may play significant roles in GERD symptom management.

[Vitamin D intoxication and "milk alkali syndrome"]. / 5 minutes pour apprendre. Intoxication à la vitamine D et « milk alkali syndrome ¼.

A 80-year-old patient treated with calcium bicarbonate for a reflux developed a milk alkali syndrome after a high doses of vitamin D for a conservatively treated heel fracture. The article highlights the milk alkali syndrome as a potential complication of excessive vitamin D supplementation, emphasizing that routine vitamin D testing and supplementation should be limited to specific situations.

Efficacy of an oral suspension containing xyloglucan and pea proteins on a murine model of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is the most common foregut disease, affecting about 20% of the adult population. Esophageal epithelial barrier plays a fundamental role in the pathophysiology of GERD; however, pharmacological therapies mainly aim to reduce the acidity of the gastroesophageal environment rather than to protect esophageal tissue integrity. This study aims to evaluate the efficacy of an oral solution containing xyloglucan and pea proteins (XP) in reestablishing gastroesophageal tissue integrity and biochemical markers. To induce GERD, C57BL/6 mice were alternatively overfed and fasted for 56 days and then treated with XP, sodium alginate, omeprazole, or omeprazole+XP twice daily for 7 days. Gastric pain and inflammatory markers were evaluated after 3 and 7 days of treatment. After sacrifice, the esophagi and stomachs were surgically removed for macroscopic and histological examination. Gastric pain was significantly reduced at days 3 and 7 by XP, omeprazole, and omeprazole+XP, while alginates were ineffective at day 3. XP was able to diminish gastric macroscopic damage and demonstrated the same efficacy as omeprazole in reducing esophageal damage. XP significantly reduced histological damage, with an efficacy comparable to that of omeprazole, but superior to alginates. Inflammatory markers were significantly reduced by XP, with superior efficacy compared with alginates at day 7. Interestingly, XP was also able to significantly increase gastric pH. This study demonstrated that XP restored gastric homeostasis, improved esophageal integrity, and decreased inflammation and pain with a similar efficacy to omeprazole and greater than alginates.

A rapid-floating natural polysaccharide gel-raft with double-effect for the treatment of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal condition characterized by regurgitating stomach contents into the esophagus, causing mucosal damage or erosion. Clinical physical protection treatment mainly relies on the use of floating rafts. Bletilla striata (BS) is widely regarded as the first-choice drug for treating digestive tract injuries in Chinese Medicine. The rapid-floating gel-raft (B-R) was prepared via a one-step swelling method using natural BS polysaccharide and glyceryl monooleate. Panax notoginseng saponins (PNS) were loaded to further prepare P/B-R according to clinical experience. Possessing hydrophobic dense, stratified porous structure and stable rheological properties, an outperforming floating performance of P/B-R was proven compared with Gaviscon® (alginate-antacid formulation) in vitro. In vivo imaging results showed that P/B-R can retain and adhere to the gastric mucosa of rats for up to 90 min, protecting and repairing the mucosa. Besides physical protection in situ, the systemic effects of antioxidant and anti-inflammatory actions for treating GERD were achieved through the intestinal release of PNS. Acid-labile PNS was protected by P/B-R against gastric acid, attaining the desired release and permeability. A significantly effective mucosa injury protective effect of P/B-R was found in ethanol-induced gastric damage model on rats. Moreover, P/B-R exhibits excellent biosafety at the cellular level.

Characterization of novel alginate-Aloe Vera raft systems for treatment of gastroesophageal reflux disease.

Raft-forming systems are designed to relieve reflux symptoms by forming a physical barrier on top of the stomach. The present study aimed to evaluate the physico-chemical properties of alginate-aloe vera raft-forming systems for the first time. To achieve this goal, aloe vera was used in the proportion of 1 and 1.5 % in raft suspensions containing 5 % alginate as the main component of gel structure. Rafts were characterized by their volume, floating behavior, thickness, swelling properties, strength, resilience, reflux resistance, and acid neutralization capacity (ANC). Results showed the effectiveness of aloe vera in forming rafts that were voluminous, buoyant with greater total floating time (TFT), and stronger than formulations with no aloe vera. Furthermore, data showed that the presence of aloe vera could improve resilience time, swelling proportions, resistance to reflux under simulant conditions of movement in the stomach, and ANC values of rafts. Rafts were further characterized by oscillatory strain sweep test, differential scanning calorimetry, and Fourier transform infrared spectroscopy. Evaluation of the mechanical properties of rafts displayed a viscoelastic behavior of gels corresponding to the internal cross-linked structure of rafts. This study demonstrated that designing of alginate-aloe vera rafts can be suitable for the treatment of gastro-esophageal reflux disorders.

Gastroesophageal Reflux Disease: Pathophysiology and New Treatment Trends.

Gastroesophageal reflux disease (GERD) is caused by the reflux of gastric contents into the esophagus due to a decline in esophageal clearance and anti-reflux barrier mechanisms. Mucosal injury is caused by a combination of gastric juice directly damaging the esophageal mucosa and the immune and inflammatory mechanism in which inflammatory cytokines released from the esophageal mucosal epithelium cause neutrophil migration, triggering inflammation. Gastric secretion inhibitors are the first-line treatment for GERD, but they can be combined with prokinetic agents and Chinese herbal remedies. However, pharmacotherapy cannot improve anatomical problems or prevent physical causes of GERD, such as reflux of non-acidic contents. Therefore, surgery can be warranted, depending on the pathology. Intraluminal endoscopic therapy, which is both less invasive and more effective than surgery, was recently developed and applied in Europe and the United States. In Japan, intraluminal endoscopic therapies, such as anti-reflux mucosectomy, anti-reflux mucosal ablation, and endoscopic submucosal dissection, for GERD have been independently developed.

Clinical efficacy of Yukgunja-tang combined with a proton pump inhibitor for refractory gastroesophageal reflux disease: study protocol for randomized, double-blind, double-dummy clinical trial.

BACKGROUND: Yukgunja-tang (YGJ) is an herbal prescription used to treat the symptoms of gastroesophageal reflux disease (GERD). Although many preclinical and clinical studies on YGJ have been conducted on GERD, there is a lack of evidence from blinded studies to exclude placebo effects. Therefore, this protocol proposes a clinical trial that is single-centered, randomized, double-blinded, double-dummy to objectively evaluate the efficacy and safety of co-administered YGJ and rabeprazole (RPZ) in patients with GERD previously treated with proton pump inhibitors (PPIs) and still experiencing symptoms. METHODS: A total of 86 participants with refractory GERD (rGERD) will be randomized in a 1:1 ratio to the treatment [YGJ and RPZ (10 mg/d)] and control groups [double-dose RPZ (20 mg/d)] for 4 weeks of treatment (weeks 0-4) followed by 4 weeks of follow-up (weeks 4-8). The Frequency Scale for the Symptoms of GERD will be analyzed for the primary endpoint. Reflux Disease Questionnaire, Reflux Symptom Score, GERD-Health Related Quality of Life, Overall Treatment Evaluation, Spleen Qi Deficiency Questionnaire, Damum Questionnaire, and dyspepsia Visual Analogue Scale will be used to evaluate treatment effects on GERD related symptoms and quality of life and to compare treatment effects by subgroups. Safety tests will be analyzed by investigating adverse events. DISCUSSION: This clinical trial will be the first rigorous double-blind, double-dummy, placebo-controlled study to precisely evaluate the efficacy and safety of the combination of YGJ and PPIs in the treatment of rGERD. The results of this study will provide a reliable clinical basis for selecting botanical drug treatments for patients with rGERD. TRIAL REGISTRATION: Clinical Research Information Service (registration number: KCT0008600, July 13, 2023, https://cris.nih.go.kr ).

Prescribing Patterns of Proton Pump Inhibitors in Germany: A Retrospective Study Including 472 146 Patients.

The aims of this study were to analyze proton pump inhibitor (PPI) users in Germany, defining and classifying them in terms of treatment appropriateness, and to analyze the PPI prescription practices of healthcare providers. The updated DGVS (Deutsche Gesellschaft für Gastroenterologie, Verdauungs-und Stoffwechselkrankheiten) gastroesophageal reflux disease (GERD) treatment guideline (published March 2023) for mild heartburn symptoms recommends carrying out a probatory treatment of mild symptoms via other medication such as antacids, alginates, and H2 blockers before escalating to PPI treatments, if the patient profile allows. This retrospective cross-sectional study was based on data from the IQVIA™ Disease Analyzer database (DA) and included adult patients (18 years or older) in 1006 general and 39 gastroenterological practices in Germany who received at least 1 PPI prescription or alginate between September 2019 and September 2021 (hereinafter referred to as the index period). Analyses included indications associated with PPI prescription, co-diagnoses, co-therapies of PPI patients, duration of PPI therapy, dosages of PPI prescriptions, and proportions of practices prescribing PPIs and alginates. A total of 472 146 patients taking PPIs and 9101 patients taking alginates were available for analysis. Very few patients (4.5%) of the total cohort were treated in complete adherence to treatment guidelines. Conditions such as gastritis and duodenitis (47.2%) and reflux diseases (38.4%) were more frequently associated with PPI prescriptions. The average PPI treatment period lasted 141 days, and 36.6% of patients were treated for >6 months. High doses were prescribed relatively often (ie, 42.8% of esomeprazole prescriptions were 40 mg, 59.1% of lansoprazole prescriptions 30 mg, 28.6% of omeprazole prescriptions 40 mg). With each practice prescribing PPIs to at least 10% of their patients; 72% of general practitioners (GPs) and 8% of GENTS (Gastroenterologists) prescribed alginates. This study highlights that discrepancies exist between clinical guidelines and real-life prescribing practices of PPIs in Germany. Particular attention should be given to the incidence of patients being prescribed high-dose or long-duration PPI with mild indications. These findings are particularly apt considering the publication (March 2023) of new guidelines on the "management of gastroesophageal reflux disease and eosinophilic esophagitis," by the DGVS.

The clinical effect of benesco™ on reflux symptoms: A double-blind randomized placebo-controlled trial.

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal diseases in the western world. Lifestyle modifications and proton pump inhibitors (PPIs) form the basis of the management of GERD. A subset of patients seeks for (natural) alternative therapies besides PPIs. benesco™ is an over-the-counter nutrition based on quercetin which has a presumed positive effect on esophageal barrier function. Therefore we aim to assess the effect of benesco™ on reflux symptoms. METHODS: We performed a double-blind randomized placebo-controlled trial in participants with reflux symptoms. Participants were assigned randomly (1:1) to receive 6 weeks of benesco™ (three times daily one lozenge containing 200 mg of quercetin) or placebo. The primary outcome was treatment success (≥50% reduction in Reflux Disease Questionnaire Score). Secondary outcomes included GERD-related quality of life, reflux-free days and nights, and participant-reported treatment success. KEY RESULTS: One hundred participants were randomized. Treatment success was seen in 18 (39%) of 46 participants in the intervention group versus 21 (47%) of 45 in the placebo group (p = 0.468). In the intervention group 10 (1-21) reflux-free days were reported compared to 10 (2-25) in the placebo group (p = 0.673). In addition, 38 (34-41) versus 39 (35-42) reflux-free nights were reported (p = 0.409). CONCLUSIONS & INFERENCES: In our trial benesco™ showed no significant benefit over placebo at group level.

A single-center retrospective study on epidemiological and Traditional Chinese Medicine syndrome characteristics of 21010 patients with reflux/heartburn symptoms.

OBJECTIVE: To provide a basis for the clinical identification of true and false reflux, integrated traditional Chinese and Western medicine, and psychosomatic treatment, we conducted a retrospective study of the etiology and epidemiological and Traditional Chinese Medicine (TCM) syndrome characteristics of patients with reflux/heartburn symptoms. METHODS: The 210 10 patients with reflux/heartburn treated at Tianjin Nankai Hospital from January 1, 2016, to December 31, 2019, were divided into four groups according to their pathogenesis. Sex, age, course of disease, incidence rate, gastroscopy, 24-h pH-impedance, esophageal manometry, Hamilton Anxiety Scale (HAMA) / Hamilton Depression Scale (HAMD) score, 8-week proton pump inhibitor (PPI) treatment effect, and TCM syndrome characteristics were statistically analyzed. RESULTS: A total of 21010 patients (8864 men and 12146 women), with reflux/heartburn symptoms were screened, including 6284 (29.9%) patients with reflux esophagitis (RE), 10427 (49.6%) patients with non-erosive reflux esophagitis (NERD), 2430 (11.6%) patients with reflux hypersensitivity (RH), and 1870 (8.9%) patients with functional heartburn (FH). The incidence of the disease was higher in women than in men (0.0001). The ranking of the incidence of anxiety and depression in these four groups was FH>RH>NERD>RE ( 0.0001). There were more women than men in the groups with anxiety and more men than women in the groups with depression ( 0.0001), and there was no significant difference in the distribution of anxiety and depression between men and women ( 0.5689). There were significant differences in TCM syndrome characteristics between NERD, RE, and functional esophageal diseases ( 0.01). The highest proportion of functional esophageal disease TCM symptoms was stagnation and phlegm obstruction syndrome (36.16%), and there was no significant difference between RH and FH. The effective rates of PPI treatment at 8 weeks in patients in the RE, NERD, RH, and FH groups were 89%, 72%, 54%, and 0%, respectively. RE was classified into grades A, B, C, and D according to the Los Angeles grading system. The ranking of the incidence of these four grades was A>B>C>D ( 0.0001). The effective rates of PPI treatment at 8 weeks were 91%, 81%, 69%, and 63% in patients with grade A, B, C, and D RE, respectively ( 0.0001). The highest proportion of TCM syndrome types of NERD and RE was the stagnated heat syndrome in the liver and stomach syndrome, 38.99% and 33.90%, respectively. CONCLUSION: Reflux/heartburn symptoms are relatively common in middle-aged women, and NERD is the most common etiology, followed by RE, RH, and FH. The most common TCM syndrome characteristics in NERD and RE were stagnated heat syndrome in the liver and stomach syndrome, and stagnation and phlegm obstruction syndrome in functional esophageal diseases. Most patients with reflux/heartburn symptoms also experienced anxiety and depression.

Longer-term outcomes of gastroesophageal reflux disease treated with magnetic sphincter augmentation.

Surgical intervention for gastroesophageal reflux disease (GERD) has historically been limited to fundoplication. Magnetic sphincter augmentation (MSA) is a less invasive alternative that was introduced 15 years ago, and it may have a superior side-effect profile. To date, however, there has been just a single published study reporting outcomes in a UK population. This study reports quality-of-life (QOL) outcomes and antacid use in patients undergoing MSA, with a particular focus on postoperative symptoms and those with severe reflux. A single-center cohort study was carried out to assess the QOL outcomes and report long-term safety outcomes in patients undergoing MSA. GERD-health-related quality of life (GERD-HRQL) and Reflux Symptom Index (RSI) scores were collected preoperatively, and immediately postoperatively, at 1-, 2-, 3-, and 5-year follow-up time points. All patients underwent preoperative esophagogastroduodenoscopy, impedance, and manometry. Two hundred and two patients underwent laparoscopic MSA over 9 years. The median preoperative GERD-HRQL score was 31, and the median RSI score was 17. There was a reduction in all scores from preoperative values to each time point, which was sustained at 5-year follow-up; 13% of patients had a preoperative DeMeester score of >50, and their median preoperative GERD-HRQL and RSI scores were 32 and 15.5, respectively. These were reduced to 0 at the most recent follow-up. There was a significant reduction in antacid use at all postoperative time points. Postoperative dilatation was necessary in 7.4% of patients, and the device was removed in 1.4%. Erosion occurred in no patients. MSA is safe and effective at reducing symptom burden and improving QOL scores in patients with both esophageal and laryngopharyngeal symptoms, including those with severe reflux.

The role of magnetic sphincter augmentation in the gastroesophageal reflux disease treatment pathway: the gastroenterology perspective.

Magnetic sphincter augmentation (MSA) is a surgical intervention for well-characterized gastroesophageal reflux disease (GERD), where the esophagogastric junction barrier is augmented using a bracelet of magnetized titanium beads. MSA could be an attractive option for patients with documented GERD who wish to avoid long-term pharmacologic therapy or whose symptoms are not adequately managed with lifestyle modifications and pharmacologic therapy. The 'ideal' MSA patient is one with prominent regurgitation, without dysphagia or esophageal motor dysfunction, with objective evidence of GERD on upper endoscopy and/or ambulatory reflux monitoring. Appropriate candidates with significant hiatus hernia may pursue MSA with concomitant hiatus hernia repair. The increasing adoption of MSA in the GERD treatment pathway reflects research that shows benefits in long-term outcomes and healthcare costs compared with other established therapies in appropriate clinical settings.

Ex vivo evaluation of adhesive strength and barrier effect of a novel treatment for esophagitis.

AIM: To investigate the mucoadhesive strength and barrier effect of Esophacare® (Atika Pharma SL, Las Palmas de Gran Canaria) in an ex vivo model of gastro-oesophageal reflux. METHODS: An ex vivo evaluation through the Falling Liquide Film Technique with porcine esophagi was performed, compared to a positive control (Ziverel®; Norgine, Amsterdam), after different washing periods with saline, acidified saline (pH 1.2) and acidified saline with pepsin (2000U/mL). RESULTS: The adhesive mean strength on the oesophageal mucosa of Esophacare was 94.7 (6.0)%, compared to 27.6 (19.1)% of the positive control (p<0.05). These results were homogeneous across the different washes and throughout the tissue. The area covered by 1mL of Esophacare, and its respective persistence after washing was also assessed, yielding a mean global persistence of 74.29 (19.7)% vs. 18.9 (12.3)% for the control (p<0.05). In addition, after 30min exposure to acidified saline with pepsin, Esophacare shows a protective effect on the oesophageal mucosa, detectable histologically: preserved integrity and structure of the apical layers was observed, as well as reduced permeability to the washing solution. CONCLUSIONS: Esophacare shows an adhesive strength close to 100%, irrespective of the washing solution applied or the oesophageal region studied. Histologically, it reduces the abrasive effects of the acidic solution on the oesophageal epithelium, reducing permeability to the washing solution. The results in this ex vivo model of gastro-oesophageal reflux disease (GERD) support its therapeutic potential.

Mechanisms of Chinese Medicine in Gastroesophageal Reflux Disease Treatment: Data Mining and Systematic Pharmacology Study.

OBJECTIVE: To identify specific Chinese medicines (CMs) that may benefit patients with gastroesophageal reflux disease (GERD), and explore the action mechanism. METHODS: Domestic and foreign literature on the treatment of GERD with CMs was searched and selected from China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and PubMed from October 1, 2011 to October 1, 2021. Data from all eligible articles were extracted to establish the database of CMs for GERD. Apriori algorithm of data mining techniques was used to analyze the rules of herbs selection and core Chinese medicine formulas were identified. A system pharmacology approach was used to explore the action mechanism of these medicines. RESULTS: A total of 278 prescriptions for GERD were analyzed, including 192 CMs. Results of Apriori algorithm indicated that Evodiae Fructus and Coptidis Rhizoma were the highest confidence combination. A total of 32 active ingredients and 66 targets were screened for the treatment of GERD. Enrichment analysis showed that the mechanisms of action mainly involved pathways in cancer, fluid shear stress and atherosclerosis, advanced glycation end product (AGE), the receptor for AGE signaling pathway in diabetic complications, bladder cancer, and rheumatoid arthritis. CONCLUSION: Evodiae Fructus and Coptidis Rhizoma are the core drugs in the treatment of GERD and the potential mechanism of action of these medicines includes potential target and pathways.

Changes in bone turnover markers in adolescents with gastroesophageal reflux disease treated with lansoprazole.

Background: Proton pump inhibitors (PPIs) have been suggested to lead to bone resorption, while the effects of PPIs on the bone mineral metabolism in children has received only limited attention in literature to date. The present study investigates whether lansoprazole alters bone turnover markers in adolescents with gastroesophageal reflux disease (GERD). Patients and methods: Included in the study were adolescents aged 16-18 with GERD and a healthy volunteers group. The GERD patient group was treated with lansoprazole 30 mg once daily for eight weeks. The serum calcium, phosphorus, magnesium, alkaline phosphatase (ALP), parathormone (PTH), 25 (OH) vitamin D, osteocalcin and urinary calcium, creatinine, deoxypyridinoline (DPD), collagen type-1 crosslinked C-telopeptide (CTX) and collagen type-1 crosslinked N-telopeptide (NTX) of both groups were studied before and after the end of the treatment. Results: A comparison of the 30 patients with GERD and the 30 volunteers revealed no significant difference in the serum calcium, phosphorus, magnesium, ALP, urinary calcium/creatinine ratio, 25 (OH) vitamin D and PTH levels measured before and after the lansoprazole treatment, while the osteocalcin, DPD, CTX and NTX values were found to be higher after treatment when compared to those at pre- treatment. Conclusions: The results of this study reveal that eight weeks of treatment with 30 mg lansoprazole daily increased the bone turnover markers of CTX, NTX, DPD and osteocalcin in adolescents aged 16-18.

What is the efficacy of dietary, nutraceutical, and probiotic interventions for the management of gastroesophageal reflux disease symptoms? A systematic literature review and meta-analysis.

BACKGROUND: Treatments for Gastroesophageal Reflux Disease (GERD) symptoms include pharmaceutical, surgical, dietary, and lifestyle behaviors; however, dietary interventions lack evidence synthesis. RESEARCH QUESTION: What is the effect of dietary, probiotic, and nutraceutical interventions on GERD symptoms, with or without pharmaceutical therapy, in adults with a history of GERD or functional dyspepsia compared to no intervention, placebo, or usual care? METHOD: A systematic review and meta-analysis was performed according to PRISMA. The search strategy was implemented in MEDLINE, CINAHL, CENTRAL, and Embase on the 28th October 2020 and updated to 27th July 2021. Intervention studies were eligible if they evaluated the effect of a dietary, nutraceutical, or probiotic intervention on GERD symptoms in adults with a history of GERD or functional dyspepsia. The internal validity of studies was assessed using the Academy Quality Criteria Checklist; Review Manager software was used to perform meta-analysis; and certainty in the body of evidence was assessed using GRADE. RESULTS: 6,608 study records were retrieved from the search, with 21 studies (n = 24 highly heterogenous intervention groups) included (n = 10 restrictive dietary interventions; n = 3 non-restrictive dietary interventions; n = 8 nutraceutical interventions; and n = 3 probiotic interventions). GERD symptoms were clinically and statistically improved by a test-based elimination diet (n = 1 study), low nickel diet (n = 1 study), probiotic yoghurt (n = 1 study), psyllium husk (n = 1 study), prickly pear and olive leaf extract supplement (n = 1 study), and melatonin, amino acid and b-group vitamin supplement (n = 1 study) according to qualitative synthesis. Ginger-containing supplements could be meta-analyzed, and improved incidence of GERD symptom alleviation (n = 2 studies, OR: 7.50 [95%CI: 3.62-15.54], GRADE: high). No clinically and/or statistically significant effects were found for the remaining n = 16 highly heterogenous interventions. CONCLUSION: Evidence to guide the dietary management of GERD symptoms is limited in scope, quality, and feasibility. Based on the limited evidence available, dietary GERD management should be long-term, individualized, and consider both dietary restrictions and/or additions. PROSPERO ID: CRD42021224082.

Traditional Chinese medicine based on Tongjiang methodology combined with proton pump inhibitor (PPI) step-down in treating non-erosive reflux disease: a study protocol for a multicentered, randomized controlled clinical trial.

BACKGROUND: Non-erosive reflux disease (NERD) is characterized by typical gastroesophageal reflux symptoms, such as heartburn and regurgitation but an absence of esophageal mucosal damage during upper gastrointestinal endoscopy. Although proton pump inhibitors (PPIs) are the first line therapy, almost 50% of patients with NERD fail to respond to this treatment. Traditional Chinese medicine (TCM) can better relieve the symptoms of NERD. Therefore, a randomized controlled trial (RCT) was designed to investigate the efficiency of TCM granules based on Tongjiang (TJ) methodology combined with PPI step-down therapy for NERD patients who did not respond to PPIs alone. METHOD: This multicentered, double-blinded, RCT with two parallel groups will recruit 174 participants who will be randomized into the TCM granules combined with PPI step-down group (n = 87) and the TCM granules placebo combined with PPI step-down group (n = 87). Both groups of participants will receive 6 weeks of treatment and 4 weeks of follow-up, and all participants will be assessed for related symptoms, mental health status, and quality of life at each visit. The primary outcome measurements include visual analog scale (VAS) for heartburn and regurgitation and the major symptoms scale. The secondary outcome measurements include PPI withdrawal rate, symptom recurrence rate, minor symptoms scale, SF-36, PRO, SAS, SDS, GERD-HRQL, and TCM syndromes scales. DISCUSSION: Previous research has shown that TCM is capable to alleviate NERD symptoms. This trial will help to provide a better understanding of the synergistic efficiency of the combination of TCM and PPIs, to explore whether the dosage of PPIs can be reduced after the supplement of TCM granules and to provide a feasible plan to reduce dependencies or withdraw NERD patients from PPIs. The outcome of this trial is expected to reduce the symptom recurrence rates, lessen patients' physical and psychological burdens, and achieve good social benefits. TRIAL REGISTRATION: Clinicaltrials.gov NCT04340297. Registered on April 9, 2020.

Network Pharmacology Analysis of Hewei Jiangni Granule for Gastroesophageal Reflux Disease and Experimental Verification of Its Anti-Neurogenic Inflammation Mechanism.

Purpose: Proton pump inhibitors, as the first-line drugs for treating gastroesophageal reflux disease (GERD), are unable to completely relieve patients' symptoms and patients are prone to recurrence after prolonged drug withdrawal. Thus, it is crucial to find herbal medicines as a complementary and alternative treatment. Hewei Jiangni granule (HWJNG) is a classical Chinese medicinal formula with clinical therapeutic effects on GERD, but its pharmacological mechanism of action remains unclear. This study aimed to explore and then verify the pharmacological mechanisms of HWJNG in GERD therapy. Methods: A network pharmacology approach was applied to explore and then verify the pharmacological mechanisms of HWJNG in GERD therapy. The active ingredients of HWJNG, as well as therapeutic targets of GERD were acquired from specialized databases. The "herb-ingredient-gene-target" network for HWJNG in GERD treatment was built. The protein-protein interaction (PPI) network was constructed to screen the core coincident targets. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. The core targets and signaling pathways associated with the anti-neurogenic inflammatory effect were partially verified via experiments in vivo at molecular level. Results: In total, 179 chemical ingredients in HWJNG and 298 intersection targets between GERD and HWJNG were selected from databases. A large proportion of core targets and top signaling pathways were involved in neurogenic inflammation. HWJNG significantly alleviated pathological injuries of esophagus and reversed dilated intracellular spaces. Additionally, HWJNG markedly inhibited the excessive release of inflammatory cytokines such as interleukin (IL)-1ß, IL-6, tumor necrosis factor receptor (TNF-a), as well as regulated stimulation sensors including transient receptor potential vanilloid type 1 (TRPV1) and its related neuroinflammatory mediators in GERD mice. Conclusion: HWJNG is a promising therapeutic strategy for GERD treatment via regulation of multiple targets and pathways, its effects in alleviating neurogenic inflammation are especially acknowledged.

Knowledge gaps in the management of refractory reflux-like symptoms: Healthcare provider survey.

BACKGROUND: Refractory reflux-like symptoms have a substantial impact on patients and healthcare providers. The aim of the survey was to qualitatively assess the needs and attitudes of practicing clinicians around the management of refractory reflux symptoms and refractory gastroesophageal reflux disease (rGERD). METHODS: An International Working Group for the Classification of Oesophagitis (IWGCO) steering committee invited clinicians to complete an online survey including 17 questions. KEY RESULTS: Of the 113 clinicians who completed the survey, 70% were GIs, 20% were primary care physicians, and 10% were other specialties. Functional heartburn was considered the most common reason for an incomplete response to proton pump inhibitor (PPI) therapy (82%), followed by stress/anxiety (69%). More GIs identified esophageal hypersensitivity as a cause, while more non-GIs identified esophageal dysmotility and non-reflux-related esophageal conditions. As the first step, most clinicians would order investigations (70-88%). Overall, 72% would add supplemental therapy for patients with partial response, but only 58% for those with non-response. Antacid/alginate was the most common choice overall, while non-GIs were more likely to add a prokinetic than were GIs (47.8 vs. 24.1%). Approximately 40% of clinicians would switch PPIs in patients with partial response, but only 29% would do so in non-responders. Preferences for long-term therapy were highly variable. The most common initial investigation was upper endoscopy. Choice of esophageal manometry and pH monitoring was more variable, with no clear preference for whether pH monitoring should be conducted on, or off, PPI therapy. CONCLUSIONS AND INFERENCES: The survey identified a number of challenges for clinicians, especially non-GI physicians, treating patients with refractory reflux-like symptoms or rGERD on a daily basis.