Search Results (22)

Background/Objectives: Chimeric antigen receptor T-cell (CAR-T) therapy has been approved for the management of relapsed and refractory hematologic malignancies, transforming the oncologic landscape and producing durable remissions in patient populations with limited alternatives. The systemic adverse events of CAR-T are well characterized; however, the orofacial adverse events have not been well described. The objective of this study is to leverage a large, de-identified, real-world dataset to (1) estimate the prevalence of orofacial adverse events following CAR-T, (2) compare event rates with the general population, and (3) directly contrast the orofacial toxicity burden of CAR-T with that observed after hemopoietic stem cell transplant (HSCT). Methods: We performed a retrospective cohort study using de-identified electronic health record data from TriNetX. CAR-T and HSCT cohorts were identified via RxNorm and procedure codes; a non-exposed control cohort was included. Patients with prior orofacial conditions or confounding therapies were excluded. New adverse orofacial events within one year were identified by International Classification of Diseases, 10th Revision (ICD-10) codes. Cohorts were 1:1 propensity-matched by age and sex; associations were estimated as odds ratios with two-sided 95% CIs. Results: In 1142 CAR-T recipients (mean age of 62), gastroesophageal reflux disease (GERD) was most frequent (5.18%). Oral mucosal events included stomatitis in 1.52%, mucositis in 1.31%, and lichenoid reactions in 1.03%. Dysphagia occurred in 1.8% and oral candidiasis in 1.6%. Several severe oral conditions were absent. Compared with the general population (CART vs. general population): mucositis—[12/995 vs. 0/1112] (OR 28.3)—and stomatitis—[16/987 vs. 0/1119] (OR 38)—risks were significantly increased, while CAR-T patients had significant lower risks of mucosal complications than HSCT recipients in this analysis (CART vs. HSCT): mucositis—[1.21% vs. 3.72%] (OR 0.316) and stomatitis—[1.42% vs. 3.91%] (OR 0.354). Conclusions: CAR-T therapy carries a distinct and generally lower orofacial toxicity burden than HSCT, but targeted dental assessment and prospective surveillance remain important to optimize supportive care for cellular therapy recipients. Full article

For over three decades, Proton Pump Inhibitors (PPIs) have served as the established primary therapy for acid-suppressive therapy; however, their clinical utility is frequently compromised by their slow onset of action, meal-time dependency, and metabolic variability driven by CYP2C19 polymorphisms. Potassium-competitive acid blockers (P-CABs) represent a definitive pharmacological shift, offering rapid, reversible, and genotype-independent inhibition of the H⁺/K⁺-ATPase. This review outlines the emergence of South Korea as a global epicenter for P-CAB innovation, predicated upon a strategic partnership between a high domestic burden of Helicobacter pylori infection and a rising incidence of refractory gastroesophageal reflux disease (GERD). We analyze the clinical and structural developments of indigenous Korean agents, specifically tegoprazan and fexuprazan, the latter of which features an optimized 9-h elimination half-life engineered to mitigate nocturnal acid breakthrough. A critical evaluation of recent clinical evidence is provided, including the most recent 2024 prospective Phase III data, which demonstrate that 14-day P-CAB-based triple therapy achieves significantly improved eradication rates in high-clarithromycin-resistance environments. Furthermore, we explore the emerging 2025 trend toward personalized, on-demand maintenance therapy and address critical long-term safety considerations, including the duration-dependent risk of metachronous gastric cancer identified in recent multicenter longitudinal studies. Ultimately, the South Korean clinical framework is providing the foundational evidence for a global transition toward P-CAB-centered treatment algorithms, redefining the standards of care in modern gastroenterology. Full article

Background/Objectives: The association between gastroesophageal reflux disease (GERD) and chronic rhinosinusitis (CRS) has been debated, with conflicting evidence regarding its magnitude and clinical significance. This systematic review and meta-analysis aimed to evaluate the epidemiological association between GERD and CRS, assess the potential pathophysiological mechanisms, and determine the impact of diagnostic methodology on the observed relationship. Methods: A literature search was conducted across PubMed, Embase, the Cochrane Library, and Web of Science for observational studies published up to January 2026. Studies reporting the prevalence or odds of GERD in adult patients with CRS compared with controls were included. Methodological quality was assessed using ROBINS-E, JBI, and Hoy et al. Data were pooled using random-effects models with Hartung–Knapp–Sidik–Jonkman adjustment. Heterogeneity was explored using subgroup and meta-regression analyses. The certainty of the evidence was graded using the GRADE approach. Results: Twenty-two studies, involving 45,618 participants, met the inclusion criteria. Patients with CRS had significantly higher odds of having GERD than controls (OR 5.39; 95% CI: 2.06–14.11; p < 0.001). This association was corroborated by longitudinal data (aOR, 1.77; 95% CI: 1.44–2.17; p < 0.0001) and genetic evidence from Mendelian randomization. Subgroup analysis revealed that the magnitude of association was significantly stronger in studies utilizing objective diagnostic tools, such as pepsin assays (OR 15.20) and pH monitoring (OR 6.94), compared to subjective questionnaires (OR 1.43). This association was significant for CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Meta-regression analysis indicated a stronger association in younger populations (p = 0.034). Moderate-certainty evidence supports a positive epidemiological association between GERD and CRS, although substantial between-study heterogeneity (I² = 69–89%) and wide 95% prediction intervals limit the precision and generalizability of the pooled estimates. Conclusions: An association between GERD and CRS is observed in studies using objective markers of extraesophageal reflux, whereas the association is attenuated and not statistically significant when reflux is assessed by subjective questionnaires. Objective reflux assessment may be considered in selected patients with medically and surgically refractory CRS, but routine reflux testing in unselected CRS patients is not yet supported by the available evidence. Full article

Recurrent wheezing represents a significant cause of respiratory morbidity in preschool children. While viral infections in the context of immune dysregulation are primary drivers, gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) are increasingly recognized as critical triggers. The link between GERD and respiratory symptoms has historically been controversial; however, recent advances necessitate a re-evaluation of this relationship. This review critically analyzes the pathophysiological nexus between reflux and airway hyperresponsiveness, emphasizing the dual mechanism of microaspiration and vagal reflex, while integrating the concept of reverse causality (where respiratory effort actively exacerbates reflux). We highlight that the “respiratory reflux” phenotype in preschoolers is often characterized by non-acid and proximal episodes, which standard pH-metry fails to detect. Consequently, we discuss the diagnostic shift towards multichannel intraluminal impedance-pH (MII-pH) monitoring and the incorporation of novel metrics defined by the Lyon Consensus 2.0 (MNBI, PSPW index), alongside specific biomarkers such as pepsin. Finally, we propose a phenotype-driven management algorithm, differentiating between acid-suppressive therapy and alginate-based interventions, to mitigate disease burden and improve clinical outcomes in refractory cases. Full article

Purpose: Zollinger–Ellison syndrome (ZES) is the most frequent, functional, malignant pancreatic neuroendocrine tumor syndrome (pNET), which is due to ectopic secretion of gastrin by a pNET/NET (i.e., gastrinomas) resulting in severe, refractory acid-peptic disease (ulcer, GERD). ZES has several unique management features, which lead to a number of unresolved controversies. Areas covered: Whereas both medical and surgical controversies exist, they have not been examined in detail for some time. This review contains an analysis of a number of the main current, medical controversies that are unresolved in ZES patients, including insights into the basis of these controversies and possible insights into their resolution from recent studies in patients with gastrinomas or from recent studies in other pNET syndromes or other neuroendocrine tumors (NETs). These include the following: controversies in the long-term control of acid secretion and acid antisecretory drug side-effects; controversies related to the difficulty in making the diagnosis of ZES; nonsurgical MEN1/ZES controversies related to the management of gastric carcinoids (Type II); nonsurgical MEN1/ZES controversies related to whether genotype–phenotype correlations exist in MEN1 patients including MEN1/ZES patients; nonsurgical MEN1/ZES controversies related to the roles of imaging/tumor localization in MEN1 patients for gastrinomas/pNETs in their initial/follow-up management; controversies related to the role of non-surgical tumor ablation for treatment of ZES/gastrinomas; and controversies related to medical treatment selection for advanced, metastatic disease in patients with ZES/gastrinomas/other malignant pNETs. Conclusions: In this paper, the basis for the development of each of these unique ZES-related controversies is discussed and insights into progress that could lead to their resolution are reviewed. Full article

Background: Refractory epilepsy refers to a type of epilepsy in which anti-epileptic medications do not yield results, necessitating alternative medical interventions. The ketogenic diet (KD) is utilized as a non-pharmacologic treatment for refractory epilepsy. This study aims to assess details regarding caregivers’ awareness and practices, challenges faced, and other details regarding the KD as a treatment option for children with refractory epilepsy. Methods: A cross-sectional study included 15 caregivers of children with refractory epilepsy who adhere to the KD. Data were collected using an online, self-administered questionnaire including socio-demographic characteristics and descriptive aspects of KD on 15 caregivers. Results: Caregivers’ awareness scores varied, over half of the caregivers (53.3%) demonstrated low awareness levels, scoring below the midpoint on the awareness scale, while both caregivers’ adherence (t value = 31.5; p < 0.001) and patients’ adherence levels (t value = 26.1; p < 0.001) significantly exceeded the minimum expected thresholds, indicating effective implementation of the diet protocols. Challenges faced by caregivers were categorized as follow: logistical challenges (e.g., issues related to KD availability, cost, and weighing (15.6%)), behavioral challenges (e.g., avoiding prohibited foods (18.8%), feelings of hunger, the social environment, and never eating without caregivers), and medical challenges (e.g., frequent blood glucose monitoring (25%)). The most common side effects of the KD were gastrointestinal symptoms, including constipation (33.3%) and gastroesophageal reflux disease (GERD). Physical symptoms such as dyslipidemia were also reported by 13.3% of participants. In terms of neurological and behavioral improvements, the three most reduced symptoms following KD adoption were hyperactive attention deficit (25%), tremors (20%), and insomnia (20%). Conclusions: This study reveals a significant gap between high adherence and low awareness of the KD among caregivers of children with refractory epilepsy. While adherence is crucial for the success of KD, this discrepancy highlights the need for comprehensive caregiver education that not only focuses on practical implementation but also on the underlying rationale of the diet. This study underscores the importance of multidisciplinary support, by including dietitians, to bridge the knowledge gap. These findings suggest that dietary education programs should aim to improve caregivers’ understanding, ultimately enhancing adherence and long-term outcomes. Future research should explore the psychosocial factors influencing adherence and the role of trust in healthcare professionals in shaping caregiver behaviors. The findings also call for further exploration into the impact of caregiver education on child health outcomes in the long term. The varied knowledge among caregivers indicates a need for further educational interventions or increased visits from dietitians. Strategies need to be framed to overcome the challenges faced and improve adherence. Full article

Background: A low-FODMAP diet is considered as a potential supportive treatment approach in some gastrointestinal disorders. The aim of this study was to systematically review the literature for randomized controlled trials assessing the efficacy of the low-FODMAP diet on the severity of gastrointestinal symptoms and quality of life in patients with gastrointestinal disorders. Methods: This review was conducted in accordance with CASP tool and PRISMA guidelines. A comprehensive search of the PubMed, Scopus, and Web of Science databases resulted in the identification of fourteen randomized controlled trials. Results: Ten studies examined the effect of the low-FODMAP diet in patients with irritable bowel syndrome (IBS), three with inflammatory bowel disease (IBD), and one with symptomatic proton pump inhibitor (PPI) refractory gastroesophageal reflux disease (GERD). All interventions compared the low-FODMAP diet with another diet and lasted from 3 to 12 weeks. Most studies on IBS showed significant improvements in abdominal pain, bloating, and quality of life compared to control diets. In IBD, improvements were mainly observed in functional gastrointestinal symptoms, while no clear benefit was demonstrated in GERD. Heterogeneity in study designs, intervention durations, comparator diets, and outcome measures limited the ability to conduct a meta-analysis. Conclusions: Although a low-FODMAP diet may reduce symptoms in selected individuals, it is not universally necessary. Importantly, the diet’s restrictive nature and potential long-term effects—such as nutritional deficiencies and alterations in gut microbiota—highlight the need for clinical supervision by dietitians with expertise in gastrointestinal disorders. Furthermore, in some cases, symptom improvement may be achievable through less restrictive changes, such as improving food hygiene and reducing intake of processed or high-sugar foods. Further high-quality randomized controlled trials with standardized endpoints and longer follow-up are needed to clarify the efficacy and safety of the low-FODMAP diet across various gastrointestinal conditions. Full article

Gastroesophageal reflux disease (GERD) is a prevalent chronic gastrointestinal disorder that affects a substantial proportion of the global population. It is characterized by the extensive backward flow of stomach contents into the esophagus, leading to troublesome symptoms and potential complications. Proton pump inhibitors (PPIs) have long been the cornerstone of pharmacological treatment for GERD, effectively suppressing gastric acid secretion. However, a substantial subset of patients, referred to as PPI-refractory GERD, experience inadequate symptom control despite optimal PPI therapy. GERD significantly impacts patients’ quality of life, affecting domains, such as vitality, pain, and physical functioning. Consequently, there is an urgent need for alternative therapeutic strategies and novel pharmacologic agents to provide more effective, long-term relief. Emerging treatment options include potassium-competitive acid blockers (PCABs) like vonoprazan, which offer more potent and sustained inhibition of gastric acid secretion compared to traditional PPIs. Additionally, prokinetic agents such as itopride have gained attention due to their potential to improve GERD symptoms by enhancing gastrointestinal motility and accelerating gastric emptying. This article reviews the mechanisms of action, clinical efficacy, and potential of these novel therapeutic approaches in improving patient outcomes in GERD management. With the growing prevalence of PPI resistance and side effects, a personalized, multifaceted approach to treatment is becoming increasingly necessary to optimize care for patients with GERD. Full article

Objectives: Gastroesophageal reflux disease (GERD) is commonly encountered in adults and children. A subset of patients with GERD are refractory to acid suppressants, implicating other factors in the refluxate. Duodenogastric reflux (DGR) produces similar symptoms through reflux of non-acidic duodenal content and the cytotoxic effect of bile in the esophageal mucosa. Various methods have been utilized to detect DGR using a Bilitec device or Hepatobiliary scintigraphy, amongst the most common, each with their own limitations. We aimed to use combined multichannel intraluminal impedance and pH (MII-pH) monitoring with an additional gastric pH sensor to collect information about acidic and non-acidic gastroesophageal refluxes and to assess whether continuous gastric pH measurement in children provides indirect evidence of DGR for better understanding of the symptoms. Methods: From 2022 through 2023, clinically symptomatic pediatric patients scheduled for esophagogastroduodenoscopy (EGD) and MII-pH at Arnold Palmer Hospital for Children in the United States were included (n = 26). Exclusions included patients taking acid suppressants prior to the start of this study. The data were analyzed for subjects completing at least 18 h of the study protocol. Results: Subjects with a normal pH impedance (n = 5) showed a median non-meal gastric pH of 1.8. Subjects with an abnormal pH impedance (n = 21) showed a median non-meal gastric pH of 2.2. Of the 26 subjects enrolled, the duration of non-meal gastric pH 4.0–7.0 was positively correlated with non-acidic gastroesophageal refluxes. Although all acidic reflux events occurred at gastric pH < 4.0, there was no correlation between the duration of non-meal gastric pH < 4.0 and impedance changes or reflux index. Conclusions: The results showed daily variability in the non-meal gastric pH of pediatric patients and a statistically significant correlation between its duration at pH 4.0 to 7.0 and non-acidic refluxes suggestive of the implication of DGR. Further research is required to assess this association with gastroesophageal reflux and dyspeptic symptoms to investigate the diagnostic tools and therapeutic interventions, including the role of prokinetics and surface protective agents for DGR. Full article

Background: Gastroesophageal reflux disease (GERD) is a prevalent and severe condition in neurologically impaired (NI) children, often requiring surgical intervention. This study evaluates the outcomes of two surgical techniques, fundoplication and total esophagogastric dissociation (EGD), in managing GERD in this vulnerable population. Methods: We conducted a retrospective analysis of 56 NI children who underwent surgery for GERD at our institution from 2012 to 2023. Outcomes assessed included post-operative weight gain, pneumonia rates, hospitalization duration, and complications. Results: Of the cohort, 39 patients underwent fundoplication and 17 underwent EGD. Both groups experienced significant weight gain post-operatively, with comparable rates between procedures. Fundoplication was associated with shorter hospitalization (16 ± 10 days vs. 35 ± 16 days, p < 0.001) and earlier resumption of enteral feeding (5.5 ± 2 days vs. 10.2 ± 3 days). EGD significantly reduced pneumonia rates (70.59% to 17.65%, p = 0.006) compared to fundoplication (58.97% to 41.03%, p = 0.174). Early complication rates were higher in the EGD group (41% vs. 23%), but long-term GERD-related hospitalizations were fewer (0.8 ± 1/year vs. 3 ± 2/year, p = 0.003). Conclusions: Fundoplication offers shorter recovery times and lower early complication rates, making it suitable for many patients. However, EGD may be preferable for those with severe, refractory GERD, given its superior long-term outcomes, particularly in reducing pneumonia and hospitalizations. Prospective studies are needed to confirm these findings and refine surgical indications in NI children. Full article

Chronic cough is a distressing and prevalent symptom in interstitial lung disease (ILD), significantly impairing quality of life (QoL) and contributing to disease progression, particularly in idiopathic pulmonary fibrosis (IPF). It is associated with physical discomfort, psychological distress, and social isolation and is often refractory to conventional therapies. The pathophysiology of cough in ILD is complex and multifactorial, involving neural hypersensitivity, structural lung changes, inflammatory processes, and comorbid conditions such as gastroesophageal reflux disease (GERD). Evaluating cough in ILD relies on subjective and objective tools to measure its severity, frequency, and impact on daily life, although standardization of these measures remains challenging. Management strategies span pharmacological interventions, including neuromodulators such as opiates, antifibrotic agents, pharmacologic and surgical GERD treatments, and non-pharmacological approaches like behavioral therapies, cough suppression techniques, and pulmonary rehabilitation and physiotherapy. Emerging treatments, such as P2X3 receptor antagonists and airway hydration therapies, offer promising avenues but require further investigation through robust clinical trials. This review aims to demonstrate the importance of addressing cough in ILD as a significant symptom and present objective and subjective methods of quantifying coughs, while providing insights into effective and emerging therapeutic options. By highlighting these potential therapies, we hope to guide healthcare practitioners in considering them through a thorough evaluation of benefits and risks on a case-by-case basis, with relevance both in the U.S. and internationally. Full article

Background/objectives: An increase in the incidence of eosinophilic esophagitis (EoE) in children has been reported worldwide in the last decade. We conducted a study in a tertiary pediatric gastroenterology unit aimed at analyzing the clinical manifestations, biochemical markers, and endoscopic features of children with EoE in comparison to patients with non-eosinophilic esophagitis. Methods: This is a prospective analysis involving children with symptoms related to esophageal dysfunction, who had esophagogastroduodenoscopies with esophageal biopsies between January 2021 and April 2024 at “Dr. Victor Gomoiu” Clinical Children’s Hospital, in Bucharest, Romania. For the analysis, patients were considered in either Group 1, classified as EoE, or in Group 2, classified as reflux esophagitis. Results: Among the total of 72 patients diagnosed with esophagitis, 17 patients (Group 1—study group) were classified as EoE and 55 were classified as reflux esophagitis (Group 2—control group). The sex ratio analysis showed a male predominance in the study group (71% vs. 32%, p = 0.002). The main symptoms were regurgitation, eructation, and nausea. Dysphagia was present in two (11.76%) patients from Group 1. Eosinophilia was more prevalent in the EoE group than in the individuals with gastroesophageal reflux disease (GERD) (10 (58.85%) vs. 10 (18.18%, p = 0.001)), as well as the total IgE (11 (64.70%) vs. 6 (10.9%, p = 0.001)). Conclusions: Pediatric gastroenterologists need to be aware of EoE atypical presentation and perform adequate biopsies, mainly in children with refractory GERD-like symptoms, dysphagia, and food bolus impaction. Further analyses in terms of prognosis and treatment response should be addressed in longitudinal studies. Full article

Anti-reflux surgery (ARS) is an efficient treatment option for gastroesophageal reflux disease (GERD). Despite growing evidence of the efficacy and safety of ARS, medications including proton pump inhibitors (PPIs) remain the most commonly administered treatments for GERD. Meanwhile, ARS can be an effective treatment option for patients who need medications continuously or for those who are refractory to PPI treatment, if proper candidates are selected. However, in practice, ARS is often regarded as a last resort for patients who are unresponsive to PPIs. Accumulating ARS-related studies indicate that surgery is equivalent to or better than medical treatment for controlling typical and atypical GERD symptoms. Furthermore, because of overall reduced medication expenses, ARS may be more cost-effective than PPI. Patients are selected for ARS based on endoscopic findings, esophageal acid exposure time, and PPI responsiveness. Although there is limited evidence, ARS may be expanded to include patients with normal acid exposure, such as those with reflux hypersensitivity. Additionally, other factors such as age, body mass index, and comorbidities are known to affect ARS outcomes; and such factors should be considered. Nissen fundoplication or partial fundoplication including Dor fundoplication and Toupet fundoplication can be chosen, depending on whether the patient prioritizes symptom improvement or minimizing postoperative symptoms such as dysphagia. Furthermore, efforts to reduce and manage postoperative complications and create awareness of the long-term efficacy and safety of the ARS are recommended, as well as adequate training programs for new surgeons. Full article

High-resolution manometry (HRM) facilitates the detailed evaluation of esophageal motility. In December 2020, Chicago classification (CC) version 4.0 introduced modifications to improve consistency and accuracy. We conducted this study to compare the differences in the interpretations of HRM examinations between CC 3.0 and 4.0. Consecutive HRM records at a Taiwan tertiary medical center, including wet swallows and MRS performed in both supine and sitting positions from October 2019 to May 2021, were retrospectively reviewed and analyzed using both CC versions 3.0 and 4.0. A total of 105 patients were enrolled, and 102 patients completed the exam, while three could not tolerate HRM sitting up. Refractory gastroesophageal reflux disease (GERD) symptoms (n = 65, 63.7%) and dysphagia (n = 37, 36.3%) were the main indications. A total of 18 patients (17.6%) were reclassified to new diagnoses using CC 4.0. Of the 11 patients initially diagnosed with absent contractility, 3 (27.3%) were reclassified as having Type 1 achalasia. Of the 18 patients initially diagnosed with IEM, 6 (33.3%) were reclassified as normal. The incidence of diagnosis changes was similar in both the dysphagia and refractory GERD symptoms groups (21.6% versus 15.3%, p = 0.43). The use of CC 4.0 led to changes in the diagnoses of esophageal motility disease, irrespective of examination indications. Early adoption improves the accuracy of diagnoses and affects patient management. Full article

Background: Gastroesophageal reflux disease (GERD) affects a significant proportion of individuals, with life stress being a contributing factor. This study aimed to investigate the correlation between psychosomatic evaluations, heart rate variability (HRV), and GERD in a cohort of individuals. Additionally, the study aimed to analyze the sequencing changes following proton pump inhibitor (PPI) treatment and identify predictive factors associated with refractory GERD. Methods: A prospective cohort of 105 individuals with reflux esophagitis and a control group of 50 participants without acid reflux symptoms were enrolled. Psychosomatic evaluations, including GERDQ, GERDQLQ, RSI, BAI, BDI, and SSS-8, were assessed at baseline and during treatment. HRV parameters were also evaluated. Multivariate analysis was used to identify predictive factors for refractory GERD. PPIs were administered regularly for the initial 2 months and then used on-demand. Refractory GERD was defined as less than 50% improvement in symptom relief or GERDQLQ score ≥ 20 after 8 weeks of PPI treatment. Results: The GERD group had higher scores in all psychosomatic evaluations compared to the control group (all p-values < 0.001). There were no significant changes in any parameters of HRV before and after treatment in the GERD group. Strong and consistent correlations were observed between GERD symptoms and psychological scores (BAI, BDI, and SSS-8) across all time points (W0, W4, and W8). Sequential reductions in GERD symptom scores and psychosomatic evaluations were observed during the initial eight weeks of treatment. Higher GERDQ (≥10) and SSS-8 (≥12) scores were predictive of refractory GERD (p = 0.004 and p = 0.009, respectively). Conclusions: This study emphasizes the importance of considering physiological and psychological factors in the management of GERD. Psychosomatic evaluations provide valuable insights for assessing and treating GERD patients. Integrating stress management and comprehensive assessments into personalized treatment strategies is crucial. Full article