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Gastric mucosal changes associated with long-term potassium-competitive acid blocker and proton pump inhibitor (PPI) therapy may raise concern. In contrast to that for PPIs, the evidence concerning the safety of long-term potassium-competitive acid blocker use is scant. Vonoprazan (VPZ) is a representative potassium-competitive acid blocker released in Japan in 2015. In order to shed some comparative light regarding the outcomes of gastric mucosal lesions associated with a long-term acid blockade, we have reviewed six representative gastric mucosal lesions: fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like gastric mucosal changes, gastric black spots, and stardust gastric mucosal changes. For these mucosal lesions, we have evaluated the association with the type of acid blockade, patient gender, Helicobacter pylori infection status, the degree of gastric atrophy, and serum gastrin levels. There is no concrete evidence to support a significant relationship between VPZ/PPI use and the development of neuroendocrine tumors. Current data also shows that the risk of gastric mucosal changes is similar for long-term VPZ and PPI use. Serum hypergastrinemia is not correlated with the development of some gastric mucosal lesions. Therefore, serum gastrin level is unhelpful for risk estimation and for decision-making relating to the cessation of these drugs in routine clinical practice. Given the confounding potential neoplastic risk relating to H. pylori infection, this should be eradicated before VPZ/PPI therapy is commenced. The evidence to date does not support the cessation of clinically appropriate VPZ/PPI therapy solely because of the presence of these associated gastric mucosal lesions.

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INTRODUCTION: Many preterm present somatic symptoms including aerodigestive and cardiorespiratory manifestations, in combination with irritability and/or distress, which are often attributed to gastroesophageal reflux (GER), albeit for unclear reasons. AREAS COVERED: We searched in PubMed, Google Scholar, and MEDLINE for guidelines, reviews, and randomized controlled trials up to March 2024. EXPERT OPINION: The diagnosis of GER-disease (GERD) in preterm is challenging because manifestations are atypical and diagnostic investigations difficult and not devoid of risk for adverse events. In case of vomiting or regurgitation, GER as a consequence of anatomical or metabolic conditions should be considered. Although many preterm infants are treated with proton pump inhibitors, this is seldom needed. Low-quality evidence for alginates is available, but needs further evaluation. There is a need for an effective and safe prokinetic favoring esophageal clearance, increasing lower esophageal sphincter pressure and stimulating gastric emptying. Non-drug treatment such as feeding adaptations (volume, duration, and composition) and positional changes are insufficiently applied. Thickened formula is not indicated in preterm babies. In case none of the above recommendations did result in sufficient improvement, and if documentation of acid GER is not possible, a 2-4 week trial of a proton pump inhibitor is acceptable.

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BACKGROUND AND AIMS: Transoral incisionless fundoplication (TIF) is an established safe endoscopic technique for the management of GERD but with variable efficacy. In the last decade, the TIF technology and technique have been optimized and more widely accepted but data on outcomes outside clinical trials are limited. We tracked patient-reported and clinical outcomes of GERD patients after TIF 2.0. METHODS: Patients with BMI < 35, hiatal hernia < 2cm, and confirmed GERD with typical and/or atypical symptoms from 9 academic and community medical centers were enrolled in a prospective registry and underwent after TIF 2.0 performed by gastroenterologists and surgeons. The primary outcomes were safety and clinical success (response in >2 of 4 endpoints). Secondary endpoints were symptom improvement, acid exposure time (AET), esophagitis healing, proton pump inhibitor (PPI) use, and satisfaction. Outcomes were assessed at last follow-up within 12 months. RESULTS: 85 patients underwent TIF 2.0, 81 were included in the outcomes analysis. Clinical success was achieved in 94%, GERD-HRQL scores improved in 89%, and elevated RSI score normalized in 85% of patients with elevated baseline. Patient satisfaction improved from 8% to 79% (p <0.0001). At baseline, 81% were taking at least daily PPI, while 80% were on no or occasional PPI after TIF 2.0 (p<0.0001). Esophageal AET was normal in 72%, greater with an optimized TIF 2.0 valve >300 degree circumference, >3cm length (94% vs 57%, p=0.007). There were no TIF 2.0-related serious adverse events. CONCLUSION: TIF 2.0 is a safe and effective endoscopic outpatient treatment option for select patients with GERD.

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PURPOSE: A fixed-dose combination (FDC) of proton pump inhibitors (PPIs) and antacid salts enables rapid acid suppression through the neutralizing effect of the antacid salt and the rapid absorption of PPIs. This study aimed to compare the pharmacokinetics (PKs) and pharmacodynamics (PDs) of a recently formulated FDC of esomeprazole and magnesium hydroxide to the enteric-coated esomeprazole in healthy subjects. METHODS: A randomized, open-label, multiple-dose, two-treatment, two-way crossover design was conducted in healthy subjects. Forty-nine subjects were randomized to one of the two treatment sequences and received either the test drug (esomeprazole/magnesium hydroxide 40/350 mg) or reference drug (enteric-coated esomeprazole 40 mg) for 7 days in the first period and the alternative in the second period with a 14-day washout period. Blood samples were collected for up to 24 hours for PK assessment, and 24-hour gastric pH monitoring was conducted for PD assessment both before and after a single administration, as well as at a steady state after seven consecutive days of administration. The PK and PD parameters were compared between the two drugs. FINDINGS: After multiple administrations, the median value of time to reach maximum concentration was faster in the test drug than in the reference drug, with a difference of 1.68 hours. The overall systemic exposure of the test drug was similar to that of the reference drug, and the PK parameter fell within the equivalence criteria. The test drug demonstrated a shorter time to reach gastric pH ≥ 4 compared to the reference drug (P = 0.0463). A decrease from baseline in integrated gastric acidity over 24 hours, which represents the degree of inhibition of gastric acid secretion, was equivalent between the two drugs. IMPLICATIONS: The fixed-dose combination of esomeprazole and magnesium hydroxide showed rapid absorption and quicker gastric acid suppression than enteric-coated esomeprazole with comparable PK and PD properties. CLINICALTRIALS: gov identifier: NCT04324905 (https://classic. CLINICALTRIALS: gov/ct2/show/NCT04324905).

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OBJECTIVE: The association between gastroesophageal reflux disease (GERD) and laryngeal disorders remains debatable, although it has been the focus of extensive clinical and laboratory research. We conducted this study to obtain evidence on the association. STUDY DESIGN: Population-based cohort study. SETTING: Taiwan National Health Insurance Research Database (NHIRD). METHODS: Using data from Taiwan's NHIRD (January 2000 to December 2018), we performed a population-based analysis to estimate the risk of laryngeal disorders in patients with GERD and those without GERD. RESULTS: The GERD and non-GERD cohorts comprised 176,319 and 705,276 patients, respectively. The cohorts were matched at a ratio of 1:4 based on sex, age, urbanization level, and income level. The risk of laryngeal disorders was higher in the GERD cohort than in the non-GERD cohort (adjusted hazard ratio: 1.64; 95% confidence interval: 1.61-1.67). CONCLUSION: This study is the first to use population data for identifying the association between GERD and laryngeal disorders for real-world findings. Our population-based analysis indicates that patients with GERD have an elevated risk of laryngeal disorders.

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BACKGROUND: Gastroesophageal Reflux Disease (GERD) is caused by the reflux of gastric contents into the esophagus and has a 13% global prevalence that is increasing. GERD symptoms negatively impact physical, social, and emotional quality of life. The Frequency Scale for the Symptoms of GERD (FSSG) and the Gastrointestinal Symptom Rating Scale (GSRS) determine the efficacy of treatment but may not correlate with endoscopically estimated esophageal mucosal injury severity. We aimed to probe the correlation between FSSG, GSRS, and esophageal injury severity to evaluate whether these scores can predict GERD severity. METHODS: A total of 2962 patients who underwent physical examinations, including upper gastrointestinal endoscopy, at the Kyoto Kuramaguchi Medical Center, Japan, were enrolled in this study. Upper gastrointestinal endoscopy was used to diagnose fundic mucosal atrophy, reflux esophagitis based on the Los Angeles (LA) classification, gastroesophageal flap value function (GEFV) based on Hill's classification, and Barrett's esophagus. Endoscopic diagnoses were examined for correlations with FSSG and GSRS scores. RESULTS: In reflux esophagitis, FSSG and GSRS scores correlated with LA-B and LA-C endoscopic diagnosis but not with LA-M and LA-A endoscopic findings. Multiple regression analysis results were similar. FSSG scores reflected advanced fundic gland mucosal atrophy, while GSRS scores associated with high grade of GEFV. CONCLUSIONS: This is the first report to examine the correlation between FSSG and GSRS scores and endoscopic findings in a relatively large patient population. Our findings suggest that these scores can diagnose the severity of reflux esophagitis.

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DESCRIPTION: The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) is to summarize the available evidence and offer expert Best Practice Advice on the integration of potassium-competitive acid blockers (P-CABs) in the clinical management of foregut disorders, specifically including gastroesophageal reflux disease, Helicobacter pylori infection, and peptic ulcer disease. METHODS: This expert review was commissioned and approved by the AGA Institute Governing Board and CPU Committee to provide timely guidance on a topic of high clinical importance to the AGA membership. This CPU expert review underwent internal peer review by the CPU Committee and external peer review through the standard procedures of Gastroenterology. These Best Practice Advice statements were developed based on review of the published literature and expert consensus opinion. Because formal systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings of the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Based on nonclinical factors (including cost, greater obstacles to obtaining medication, and fewer long-term safety data), clinicians should generally not use P-CABs as initial therapy for acid-related conditions in which clinical superiority has not been shown. BEST PRACTICE ADVICE 2: Based on current costs in the United States, even modest clinical superiority of P-CABs over double-dose proton pump inhibitors (PPIs) may not make P-CABs cost-effective as first-line therapy. BEST PRACTICE ADVICE 3: Clinicians should generally not use P-CABs as first-line therapy for patients with uninvestigated heartburn symptoms or nonerosive reflux disease. Clinicians may use P-CABs in selected patients with documented acid-related reflux who fail therapy with twice-daily PPIs. BEST PRACTICE ADVICE 4: Although there is currently insufficient evidence for clinicians to use P-CABs as first-line on-demand therapy for patients with heartburn symptoms who have previously responded to antisecretory therapy, their rapid onset of acid inhibition raises the possibility of their utility in this population. BEST PRACTICE ADVICE 5: Clinicians should generally not use P-CABs as first-line therapy in patients with milder erosive esophagitis (EE) (Los Angeles classification of erosive esophagitis grade A/B EE). Clinicians may use P-CABs in selected patients with documented acid-related reflux who fail therapy with twice-daily PPIs. BEST PRACTICE ADVICE 6: Clinicians may use P-CABs as a therapeutic option for the healing and maintenance of healing in patients with more severe EE (Los Angeles classification of erosive esophagitis grade C/D EE). However, given the markedly higher costs of the P-CAB presently available in the United States and the lack of randomized comparisons with double-dose PPIs, it is not clear that the benefits in endoscopic outcomes over standard-dose PPIs justify the routine use of P-CABs as first-line therapy. BEST PRACTICE ADVICE 7: Clinicians should use P-CABs in place of PPIs in eradication regimens for most patients with H pylori infection. BEST PRACTICE ADVICE 8: Clinicians should generally not use P-CABs as first-line therapy in the treatment or prophylaxis of peptic ulcer disease. BEST PRACTICE ADVICE 9: Although there is currently insufficient evidence for clinicians to use P-CABs as first-line therapy in patients with bleeding gastroduodenal ulcers and high-risk stigmata, their rapid and potent acid inhibition raises the possibility of their utility in this population.

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Background: The relationship between laparoscopic sleeve gastrectomy (LSG) and gastroesophageal reflux disease (GERD) is intricate. Hiatal hernia repair or gastropexy can have an impact on postoperative GERD. Aim: To assess the effect of the repair of an accidentally discovered HH and/or gastropexy on the development of de novo postoperative GERD symptoms after LSG. Methods: This retrospective study included all obese patients who underwent LSG at our hospital from January 2018 to June 2022. The data retrieved from patients' files comprised demographic and clinical data, including BMI, GERD symptoms, and comorbidities. Hiatal hernias, surgical technique, gastropexy, duration, and intraoperative complications were recorded. Postoperative data included early and late postoperative complications, weight loss, de novo GERD, and medication use. Results: The study included 253 patients, 89 males (35.2%) and 164 females (64.8%), with a mean age of 33.3±10.04 years. De novo GERD was detected in 94 individuals (37.15%). HH was accidentally found and repaired in 29 patients (11.5%). Only 10.3% of LSG and HH repair patients had de novo GERD symptoms, compared to 40.6% of non-HH patients. 149 patients (58.9%) had gastropexy with LSG. Postoperative de novo GERD symptoms were comparable for LSG with gastropexy (40.5%) and LSG alone (40.9%). Conclusion: After one year, concurrent hiatal hernia repair and LSG seem to be safe and beneficial in lowering postoperative de novo GERD symptoms. The inclusion of gastropexy with LSG had no significant impact on postoperative de novo GERD. Both HH repair and gastropexy lengthened the operation but did not increase its complications.

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This systematic review elucidates the complex interplay between gastroesophageal reflux disease (GERD) and diabetes mellitus, integrating findings from various studies to highlight pathophysiological connections and effective clinical management strategies. Our examination reveals that mechanisms such as delayed gastric emptying and autonomic neuropathy significantly contribute to the exacerbation of GERD symptoms in diabetic patients, influencing clinical outcomes and treatment efficacy. The review underscores the necessity of multidisciplinary approaches in treating these comorbid conditions and advocates for therapeutic strategies that simultaneously address GERD and diabetes, such as the use of prokinetic agents and tailored surgical interventions like laparoscopic Roux-en-Y gastric bypass. This synthesis advances our understanding and proposes a foundation for future research and clinical practice, aiming to improve the quality of life and treatment outcomes for affected patients. This work contributes significantly to gastroenterology and endocrinology, providing a comprehensive resource for clinicians and researchers alike.

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Correcting a gut sphincter malfunction is a difficult problem. Because each sphincter has two opposite functions, that of closure and opening, repairing one there is a risk of damaging the other. Indeed, widening a narrow sphincter, such as lower esophageal sphincter (LES) and anal sphincter, may cause gastroesophageal reflux and fecal incontinence, respectively, whereas narrowing a wide sphincter, may cause a difficult transit. All the corrective treatments for difficult or retrograde transit concerning LES and anal sphincter with their unwanted consequences have been analyzed and discussed. To overcome the drawbacks of sphincter surgical repairs, researchers have devised devices capable of closing and opening the gut lumen, named artificial sphincters (ASs). Their function is based on various mechanisms, e.g., hydraulic, magnetic, mechanical etc, operating through many complicated components, such as plastic cuffs, balloons, micropumps, micromotors, connecting tubes and wires, electromechanical clamps, rechargeable batteries, magnetic devices, elastic bands, etc. Unfortunately, these structures may facilitate the onset of infections and induce a local fibrotic reaction, which may cause device malfunctioning, whereas the compression of the gut wall to occlude the lumen may give rise to ischemia with erosions and other lesions. Some ASs are already being used in clinical practice, despite their considerable limits, while others are still at the research stage. In view of the adverse events of the ASs mentioned above, we considered applying bioengineering methods to analyze and resolve biomechanical and biological interaction problems with the aim to conceive and build efficient and safe biomimetic ASs.

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OBJECTIVES: Patients with systemic sclerosis present with severe gastroesophageal reflux disease, often refractory to proton-pump inhibitors (PPI) treatment. The aim of the present study was to identify factors associated with PPI-refractory esophagitis. METHODS: We performed a cross-sectional study in a single-center cohort of patients diagnosed with systemic sclerosis. We included patients who underwent an esophagogastroduodenoscopy while on PPI treatment. Patients with PPI-refractory erosive esophagitis were compared with those with endoscopically normal esophageal mucosa. RESULTS: A total of 69 patients were included, from these, 23 patients (33%) had PPI-refractory esophagitis (Grade A, n = 11; Grade B, n = 7; Grade C, n = 2; Grade D, n = 3) and 46 (67%) had an endoscopically normal esophageal mucosa. On univariate analysis, patients with PPI-refractory esophagitis were more frequently diffuse SSc subset (43% vs 17%; p= 0.041). Evaluating gastrointestinal motility tests, neither absent esophageal contractility (39% vs 25%, p= 0.292) nor hypotensive lower esophageal sphincter (47% vs 44%, p= 0.980) were significantly associated with PPI-refractory esophagitis. Gastrointestinal dysmotility, defined as abnormal gastric emptying and/or small bowel dilated loops, was significantly associated with PPI-refractory esophagitis (66 vs 8%, p = <0.001). On a multivariate regression model to evaluate the association between motility test results adjusted for the diffuse subset, gastrointestinal dysmotility (ß = 0.751, p= 0.010) was independently associated with PPI-refractory esophagitis, while absent esophageal contractility (ß = 0.044, p= 0.886) or a hypotensive LES were not (ß=-0.131, p= 0.663). CONCLUSIONS: Our findings suggest that gastric and small intestinal motor dysfunction may be an important contributor to the development of PPI-refractory esophagitis in patients with systemic sclerosis.

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BACKGROUND: Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder. Recent studies indicate that GERD may exert systemic effects, potentially elevating the risk of severe infections, including sepsis. Nevertheless, the causal relationship between GERD and sepsis, as well as sepsis-related 28-day mortality, remains uncertain. AIM: The aim of this study is to investigate the causal relationship between GERD and the risk of sepsis, including 28-day mortality of sepsis. METHODS: This study utilized a two-sample Mendelian Randomization (MR) approach to analyze data from publicly available genome-wide association studies (GWAS) databases ( https://gwas.mrcieu.ac.uk/ ). The analysis comprised 129,080 cases and 473,524 controls for GERD; 11,643 patients and 474,841 controls for sepsis; and 1,896 patients and 484,588 controls for 28-day mortality from sepsis. The objective was to evaluate the causal impact of GERD on the risk of sepsis and 28-day sepsis mortality. Genetic variation data pertinent to GERD were obtained from the most recent genome-wide association studies (GWAS). The primary analysis employed the Inverse Variance Weighted (IVW) method. Sensitivity and pleiotropy analyses were performed to validate the robustness of the findings. RESULTS: MR analysis revealed a notable link between genetically predicted GERD and increased sepsis risk (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.24-1.52; p = 2.79 × 10-9). Moreover, GERD correlated with elevated 28-day mortality of sepsis (OR 1.44, 95% CI 1.11-1.85; p = 5.34 × 10-3). These results remained consistent throughout various sensitivity analyses, indicating their resilience against potential pleiotropy and other biases. CONCLUSION: This study indicates that genetic predisposition to GERD may be linked to an elevated risk of sepsis and its associated 28-day mortality. However, the study does not establish a direct causal relationship for GERD itself, nor does it assess the impact of GERD treatment. Further research is needed to explore the underlying mechanisms and potential therapeutic interventions involved.

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BACKGROUND AND PURPOSE: The definitive diagnosis of gastroesophageal reflux disease (GERD) often requires invasive investigations like upper gastrointestinal endoscopy or reflux monitoring. We aimed to explore the relationship between salivary pepsin and GERD and its value as a non-invasive diagnostic tool. METHODS: Databases (PubMed, Web of Science, Cochran Library, and EMBASE) were searched from their inception to January 22, 2024 to explore the correlation of salivary pepsin with GERD. The meta-analysis data retrieved were summarized, including the salivary pepsin concentration, sensitivity of diagnosis (SEN), specificity of diagnosis (SPE), negative likelihood ratio, positive likelihood ratio, diagnostic odds ratio, and receiver operating characteristic (ROC) curve. RESULTS: The meta-analysis comparing salivary pepsin concentration in two groups (proven GERD and non-GERD) with 18 studies revealed that the proven GERD group had higher salivary pepsin concentration than the non-GERD group (SMD = 1.74 [95% CI 1.14-2.34]). The meta-analysis of salivary pepsin diagnostic value for proven GERD incorporated 23 studies. The results showed pooled SEN (0.73 [95% CI 0.66-0.80]), SPE (0.72 [95% CI 0.65-0.78]), positive likelihood ratio (2.61 [95% CI 2.02-3.39]), negative likelihood ratio (0.37 [95% CI 0.28-0.50]), diagnostic odds ratio (7.03 [95% CI 4.24-11.66]) and area under the SROC curve (0.79 [95% CI 0.75-0.82]). CONCLUSION: GERD patients presented a higher salivary pepsin concentration. Salivary pepsin is both sensitive and specific in identifying GERD, making it a promising non-invasive marker for diagnosis.

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BACKGROUND: Gastroesophageal reflux disease (GERD) refers to a clinical condition characterized by gastric content reflux into the esophagus, causing symptoms like acid regurgitation and heartburn. While patient education is essential for GERD treatment, traditional educational models often struggle to effectively improve treatment outcomes. METHODS: Between January 2021 and April 2022, we enrolled 257 patients and assessed their GERD knowledge. The patients were randomly assigned to either the WeChat group (60 participants) for health education via WeChat platform or the control group (60 participants) for conventional education only. GERD-Q scores were collected at 1, 3, and 6 months post-intervention, with compliance and satisfaction assessed at the study's conclusion. RESULTS: The overall awareness rate of GERD among patients was approximately 22.3 %. The WeChat group showed better compliance than the control group in terms of adhering to a proper diet, taking medication on time, and engaging in moderate exercise (P < 0.05 for all). Furthermore, the WeChat group demonstrated significantly higher treatment effectiveness and satisfaction than the control group (P < 0.05 for all). CONCLUSION: Patients have a relatively low level of knowledge regarding GERD. WeChat has the potential to facilitate lifestyle changes and improve compliance, treatment effectiveness, and treatment satisfaction among patients with gastroesophageal reflux disease.

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Introduction: Esophageal atresia (EA) is a congenital defect that causes esophageal discontinuity, often with an associated tracheo-esophageal fistula (TEF) in 70%-90% of cases. When the distance between esophageal ends precludes primary anastomosis, it results in long gap esophageal atresia (LGEA), complicating the surgical management. This study retrospectively reviewed LGEA cases from the past decade, treated with the goal of preserving the native esophagus, comparing surgical techniques and outcomes with current literature. Materials and methods: The data of patients treated for LGEA between 2013 and 2024 were collected from medical charts, focusing on patients treated with the preservation of their native esophagus. Results: Ten patients were enrolled for this study. All of them had a gap between the esophageal ends equal to or greater than three vertebral bodies. Four patients (40%) underwent a delayed primary anastomosis (DPA) procedure, while the remaining six (60%) underwent a traction staged repair. All patients were treated with open surgery. The follow-up period extended from 3 months to 10 years. Conclusion: Preserving the native esophagus in patients with LGEA is a challenging but feasible goal, with delayed primary anastomosis and traction techniques playing key roles. We advocate for the preservation of the native esophagus as the preferred approach for ensuring a high quality of life for patients, as it helps to avoid severe long-term complications associated with esophageal substitution.

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OBJECTIVE: To study the safety and efficacy of laparoscopic fundoplication and hiatal hernia repair for gastroesophageal reflux disease following hiatal hernia. MATERIAL AND METHODS: We retrospectively analyzed 56 patients with gastroesophageal reflux disease and hiatal hernia .They underwent laparoscopic fundoplication and hiatal hernia repair between January 2020 and January 2023. RESULTS: All surgeries were successful without conversion to open surgery. Surgery time was 56-180 min (mean 68.4±3.6), blood loss 30-200 ml (mean 40.3±5.6). No mortality and severe complications occurred. All patients were followed-up for 6-24 months. The GERD-Q and De Meester scores were significantly lower after 6 months compared to baseline values (p <0.05), and resting pressure was lower. Tone of lower esophageal sphincter was significantly higher compared to preoperative level (p <0.05). In 1-2 years after surgery, symptoms completely disappeared in 48 patients and significantly improved in 6 patients. Two patients had no improvement. Contrast-enhanced examination found no recurrent hiatal hernia and digestive tract obstruction. CONCLUSION. L: Aparoscopic fundoplication and hiatal hernia repair is safe and effective for gastroesophageal reflux disease with hiatal hernia.

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BACKGROUND: Transoral incisionless fundoplication (TIF) is safe and effective in select patients with hiatal hernias ≤ 2 cm with refractory gastroesophageal reflux disease (GERD). For patients with hiatal hernias > 2 cm, concomitant hiatal hernia (HH) repair with TIF (cTIF) is offered as an alternative to conventional anti-reflux surgery (ARS). Yet, data on this approach is limited. Through a comprehensive systematic review, we aim to evaluate the efficacy and safety of cTIF for managing refractory GERD in patients with hernias > 2 cm. STUDY DESIGN: We conducted a systematic review of studies evaluating cTIF outcomes from PubMed, EMBASE, SCOPUS, and Cochrane databases up to February 14, 2024. Primary outcomes included complete cessation of proton pump inhibitors (PPIs). Secondary outcomes included objective GERD assessment, adverse events, and treatment-related side effects. Pooled analysis was employed wherever feasible. RESULTS: Seven observational studies (306 patients) met the inclusion criteria. Five were retrospective cohort studies and two were prospective observational studies. The median rate of discontinuation of PPIs was 73.8% (range 56.4-94.4%). Significant improvements were observed in disease-specific, validated GERD questionnaires. The median rate for complications was 4.4% (range 0-7.9%), and the 30-day readmission rate had a median of 3.3% (range 0-5.3%). The incidence of dysphagia was 11 out of 164 patients, with a median of 5.3% (range 0-8.3%), while the incidence of gas bloating was 15 out of 127 patients, with a median of 6.9% (range 0-13.8%). CONCLUSION: Current data on cTIF suggests a promising alternative to ARS with comparable short-term efficacy and safety profile for managing refractory GERD with a low side effect profile. However, longer-term data and comparative efficacy studies are needed.

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Normal and optimal functioning of the gastrointestinal tract is paramount to ensure optimal nutrition through digestion, absorption and motility function. Disruptions in these functions can lead to adverse physiological symptoms, reduced quality of life and increased nutritional risk. When disruption or dysfunction of neuromuscular function occurs, motility disorders can be classified depending on whether coordination or strength/velocity of peristalsis are predominantly impacted. However, due to their nonspecific presenting symptoms and overlap with sensory disruption, they are frequently misdiagnosed as disorders of the gut-brain interaction. Motility disorders are a prevalent issue in the pediatric population, with management varying from medical therapy to psychological therapy, dietary manipulation, surgical intervention or a multimodal approach. This narrative review aims to discuss the dietary management of common pediatric motility disorders including gastroesophageal reflux, esophageal atresia, achalasia, gastroparesis, constipation, and the less common but most severe motility disorder, pediatric intestinal pseudo-obstruction.

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BACKGROUND: The role of gastroesophageal reflux in progressive lung damage is increasingly recognized. We have proposed, based on our work with lung transplant recipients, a novel immune mechanism of pulmonary injury after aspiration of gastric contents, during which higher levels of normally sequestered lung self-antigens (SAgs) collagen V (Col-V) and K-alpha-1 tubulin (Kα1T) in circulating small extracellular vesicles (EVs) induce the production of self-antibodies (SAbs) anti-Col-V and anti-Kα1T. Thus, we aimed to determine whether levels of SAbs or SAgs increased in an animal model of aspiration-induced lung damage in a nontransplant setting. METHODS: We created a murine model of repetitive lung aspiration using C57BL/6J mice. Mice were aspirated weekly with 1 mL/kg of hydrochloric acid (n = 9), human gastric contents (n = 9), or combined (1:1) fluid (n = 9) once, three, or six times (n = 3 in each subgroup; control group, n = 9). Blood samples were periodically obtained, and all animals were sacrificed at day 90 for pathological assessment. SAbs were measured using an enzyme-linked immunosorbent assay; SAgs and NF-κB contained in small EVs were assessed by western blot. RESULTS: Aspirated mice weighed significantly less than controls throughout the study and had histological evidence of pulmonary injury at day 90. Overall, aspirated mice developed higher concentrations of anti-Col-V at day 28 (53.9 ± 28.7 vs. 29.9 ± 4.5 ng/mL, p < 0.01), day 35 (42.6 ± 19.8 vs. 28.6 ± 7.2 ng/mL, p = 0.038), and day 90 (59.7 ± 27.7 vs. 34.1 ± 3.2 ng/mL, p = 0.014) than the control group. Circulating small EVs isolated from aspirated mice on day 90 contained higher levels of Col-V (0.7 ± 0.56 vs. 0.18 ± 0.6 m.o.d., p = 0.009) and NF-κB (0.42 ± 0.27 vs. 0.27 ± 0.09 m.o.d., p = 0.095) than those from controls. CONCLUSIONS: This experimental study supports the theory that gastroesophageal reflux leads to the development of lung damage and an increase of humoral markers that may serve as noninvasive biomarkers to detect asymptomatic lung injury among patients with gastroesophageal reflux disease.

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BACKGROUND: Gastroesophageal reflux disease (GERD) and cholecystitis share overlapping symptoms, including belching, acid reflux, and heartburn. Despite this, the causal relationship between these two conditions remains unclear. This study aimed to investigate the causal link between GERD and cholecystitis using a Mendelian randomization (MR) approach. METHODS: A two-sample MR analysis was conducted using the inverse variance weighted (IVW), weighted median, weighted mode, and MR-Egger method to assess the causal effects of GERD on the cholecystitis risk. Genome-wide association studies (GWASs) on GERD (N cases = 129080; N controls = 473524) and cholecystitis (N cases = 1930; N controls =359264) were obtained from the IEU Open GWAS project. Various techniques were employed to assess pleiotropy and heterogeneity. RESULTS: Seventy-seven single nucleotide polymorphisms from GERD GWASs were selected as instrumental variables (IVs). The primary IVW method revealed a significant association between GERD and an increased risk of cholecystitis (odds ratio = 1.004; 95% confidence interval = 1.003-1.005, p = 2.68 × 10- 9). The absence of heterogeneity and pleiotropy in the data supports the reliability of the results. CONCLUSIONS: GERD was positively associated with the risk of cholecystitis. This study provides insights into potential avenues for the development of prevention strategies and treatment options for cholecystitis in patients with GERD. These findings contribute to our understanding of the complex interplay between GERD and cholecystitis.

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