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Open research questions in Gastroesophageal reflux and treatments

59 unresolved questions extracted from the limitations and future-work sections of 323 Gastroesophageal reflux and treatments papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Future large-scale randomized trials are recommended to further validate the outcomes. The study's findings can be used to refine guidelines for prokinetic use in GERD management.

    Comparative Study of Efficacy of Addition of Prokinetics to Proton Pump Inhibitors in Patients with Gastroesophageal Reflux Disease · 2026 · DOI

  • There is a need to evaluate the efficacy of combination therapy comprising PPIs with prokinetic agents in GERD patients. There is a lack of studies comparing the therapeutic efficacy of different prokinetic agents in combination with PPIs.

    Comparative Study of Efficacy of Addition of Prokinetics to Proton Pump Inhibitors in Patients with Gastroesophageal Reflux Disease · 2026 · DOI

  • Hiatal hernia is a prevalent condition with significant morbidity. Gastroesophageal reflux disease is a common complication of hiatal hernia. There is a need for structured approaches to aggregating expert opinion.

    Recommendations for the Management of Symptomatic Hiatal Hernia in Saudi Arabia, With Regional Input From the Middle East: A Structured Expert Consensus Survey · 2026 · DOI

  • The clinical-metabolic characteristics associated with endoscopy-confirmed RE in T2DM remain incompletely defined, particularly with regard to glycemic control, 25-hydroxyvitamin D [25(OH)D] status, and insulin-related indicators.

    Metabolic correlates of endoscopy-confirmed reflux esophagitis in hospital-based patients with type 2 diabetes mellitus · 2026 · DOI

  • Although gastric dysfunction is known to contribute to GERD, a comprehensive assessment of gastric motor function specifically in RE patients remains lacking.

    Reflux esophagitis patients exhibit reduced gastric tolerance, impaired slow-wave activity and esophageal dysmotility · 2026 · DOI

  • The combined predictive model of MNBI, PSPW index, and AET should be validated in larger, multicenter, prospective studies to confirm its ability to improve prediction of PPI response and support tailored patient management.

    A model combining nocturnal baseline impedance, post-reflux swallow-induced peristaltic wave, and acid exposure time enhances prediction of proton pump inhibitor response for extraesophageal symptoms in a Chinese population · 2026 · DOI

  • Most models lack CT-based body composition data. There is a need for more effective methods to identify reflux esophagitis.

    From body composition to reflux esophagitis: an interpretable machine learning model based on CT-derived features · 2026 · DOI

  • Future studies should consider adopting repeated or nested cross-validation approaches to more comprehensively quantify the impact of data partitioning on model stability. Therefore, the temporal sequence between variables could not be established, and causal relationships between the associated variables and RE could not be further determined.

    From body composition to reflux esophagitis: an interpretable machine learning model based on CT-derived features · 2026 · DOI

  • There is a need for translation and development of Chinese versions of GERD questionnaires for infants and young children. There is a need for the establishment of a multidimensional assessment system.

    [Research progress and clinical practice considerations on assessment tools for gastroesophageal reflux disease in infants and young children]. · 2026 · DOI

  • Clinical misdiagnosis and missed diagnosis of LPRD. Limited understanding of the pathogenic mechanisms of LPRD. Lack of a practical prediction model for LPRD.

    Current status and influencing factors of laryngopharyngeal reflux disease in outpatients with laryngeal diseases: key considerations for clinical practice · 2026 · DOI

  • There is a lack of research on the current status of LPRD comorbidity in outpatients with laryngeal diseases. There is a need for a practical prediction model for LPRD.

    Current status and influencing factors of laryngopharyngeal reflux disease in outpatients with laryngeal diseases: key considerations for clinical practice · 2026 · DOI

  • Lack of reliable non-invasive biomarkers for early detection and large-scale screening of RE.

    Identification of salivary lipid biomarkers for noninvasive diagnosis of reflux esophagitis via UHPLC-MS-based lipidomics · 2026 · DOI

  • There is a need to assess the dynamics of quality of life in patients after laparoscopic fundoplication for hiatal hernia. There is a lack of studies on the use of the GERD-HRQL questionnaire in assessing quality of life in patients with hiatal hernia.

    QUALITY OF LIFE IN PATIENTS AFTER LAPAROSCOPIC FUNDOPLICATION FOR HIATAL HERNIA BASED ON GERD-HRQL QUESTIONNAIRE DATA · 2026 · DOI

  • Future research should prioritize standardized phenotyping and durable outcome reporting. Prospective studies are needed to refine patient selection and determine the optimal timing of intervention. The application of emerging approaches, such as magnetic sphincter augmentation, should be further explored.

    The pathogenesis and surgical treatment progress of gastroesophageal reflux disease · 2026 · DOI

  • The concept of “asymptomatic elective repair” has not been fully explored in hiatal hernia patients. Standardized phenotyping and durable outcome reporting are needed to refine patient selection and determine the optimal timing of intervention.

    The pathogenesis and surgical treatment progress of gastroesophageal reflux disease · 2026 · DOI

  • High placebo response rates and frequent non-response. Lack of specificity in diagnostic tools. Risk of overtreatment.

    Acid Reflux and ENT manifestations: A review of Laryngopharyngeal Reflux · 2026 · DOI

  • There is uncertainty regarding the implications of chronic PPI therapy on the onset of IBD. The association between PPI use and IBD risk is not well understood.

    Association between proton pump inhibitor use and the risk of inflammatory bowel disease: A systematic review and meta-analysis · 2026 · DOI

  • The relationship between GERD and demographic and anthropometric parameters is not well understood. There is a need for larger studies using advanced diagnostic modalities to clarify the associations between GERD and these factors.

    Prevalence and Severity of Gastroesophageal Reflux Disease in Adults Using Gastroesophageal Reflux Scintigraphy · 2026 · DOI

  • However, the ideal gastric extension of the myotomy remains controversial, as it may influence both symptom relief and post-operative gastro-oesophageal reflux disease (GORD).

    Balancing relief and reflux: A prospective comparative study on gastric myotomy length and post-operative outcomes in laparoscopic Heller’s myotomy for achalasia · 2026 · DOI

  • The influence of digestive disorders, such as GERD, on sleep quality is less clear. Limited evidence is available on the association between GERD and sleep quality among medical students.

    Gastroesophageal reflux symptoms and sleep quality among medical students at a private university in Lima, Peru: A cross-sectional study · 2026 · DOI

  • In this context, systematic screening for GERD symptoms and sleep disturbances could facilitate early detection and timely management, considering that both are potentially modifiable factors and may reinforce each other. Furthermore, interventions aimed at modifying risk behaviors such as improving diet quality, regulating meal schedules (avoiding food intake close to bedtime), indicating pharmacological treatment when clinically justified, reducing energy drink consump- tion, and strengthening sleep hygiene together with a comprehensive approach to common mental health problems in this population could help reduce the burden and impact of both conditions [34].

    Gastroesophageal reflux symptoms and sleep quality among medical students at a private university in Lima, Peru: A cross-sectional study · 2026 · DOI

  • Current empiric-based, non-standardized GERD management practices are highly variable and untested for safety and efficacy. Prior trials have not adequately assessed the safety and efficacy of using acid suppression in this population.

    GERD management in neonatal ICU infants: study protocol for a randomized controlled trial comparing maturation, added rice starch formula and proton pump inhibitors · 2026 · DOI

  • The study aims to address the gap in understanding the role of laryngopharyngeal reflux in RLP. The current literature does not fully explain the variability in disease severity and recurrence. Additional cofactors, such as laryngopharyngeal reflux, may contribute to disease persistence and recurrence.

    Immunohistochemical detection of pepsin in recurrent laryngeal papillomatosis: findings consistent with laryngopharyngeal reflux exposure · 2026 · DOI

  • There are several reasons to interpret these results cautiously. This was a retrospective, archive-based study, and no control group was included; therefore, the findings cannot be used to infer causality or spec- ificity for recurrent laryngeal papillomatosis. In addi- tion, immunohistochemical detection of pepsin docu- ments tissue exposure but does not quantify reflux severity or frequency. Objective reflux assessment was not available (symptom scores, pH-impedance monitoring, or standardized salivary pepsin testing), and clinical outcome measures such as recurrence burden, lesion size, and surgical history were not re- corded in a manner that allowed correlation with im- munohistochemical results. Because reflux is com- mon in the general adult population, background exposure remains a relevant confounder; pepsin im- munoreactivity should therefore be interpreted as ev- idence of exposure rather than a disease-specific marker. Finally, immunohistochemistry has inherent technical limitations (pre-analytical variability, stain- ing thresholds, and potential antibody-related speci- ficity issues), and some selection bias is possible be- cause consecutive case inclusion could not be confirmed from the available records. In summary, pepsin immunoreactivity was com- mon in recurrent laryngeal papillomatosis, predomi- nantly in the epithelium and occasionally in stromal elements. The staining pattern is consistent with lar- yngopharyngeal reflux exposure, but prospective studies with controls, standardized reflux assess- ment, and clinical outcome data are needed to define clinical relevance. ConCLuSIonS 1. Pepsin immunoreactivity was identified in a substantial proportion of recurrent laryngeal papillomatosis cases, providing tissue-based evidence consistent with frequent laryn- gopharyngeal reflux exposure in this patient series.

    Immunohistochemical detection of pepsin in recurrent laryngeal papillomatosis: findings consistent with laryngopharyngeal reflux exposure · 2026 · DOI

  • The need to identify risk factors for the development of metabolic disorders in military personnel with erosive-ulcerative lesions of the esophagogastroduodenal zone. The lack of understanding of the effect of wartime factors on the development of metabolic disorders in military personnel.

    Influence of wartime factors on the development of metabolic disorders in military servicemen with erosive-ulcerative lesions of the esophagogastroduodenal zone · 2026 · DOI

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59 open questions have been extracted from the limitations and future-work passages of 323 Gastroesophageal reflux and treatments papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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