ABSTRACT
Gastroesophageal reflux disease (GERD), a prevalent clinical condition, is often attributed to aberrant esophageal motility, leading to gastric content reflux and associated symptoms or complications. The rising incidence of GERD presents an escalating healthcare challenge. Endoscopic and esophageal reflux monitoring can provide a basis for the diagnosis of patients with gastroesophageal reflux disease, but when the diagnostic basis is at an inconclusive value, some additional supportive evidence will be needed. Advanced technology is the key to improving patient diagnosis, accurate assessment, and the development of effective treatment strategies. High-resolution esophageal manometry (HREM) and endoscopic functional lumen imaging probe (EndoFLIP) represent the forefront of esophageal motility assessment. HREM, an evolution of traditional esophageal manometry, is considered the benchmark for identifying esophageal motility disorders. Its widespread application in esophageal dynamics research highlights its diagnostic significance. Concurrently, EndoFLIP's emerging clinical relevance is evident in diagnosing and guiding the treatment of coexisting esophageal motility issues. This review integrates contemporary research to delineate the contributions of HREM, EndoFLIP, and novel technologies in GERD. It examines their efficacy in facilitating an accurate diagnosis, differentiating similar gastrointestinal disorders, quantifying the extent of reflux, assessing the severity of the disease, forecasting patient responsiveness to proton pump inhibitor therapy, and guiding decisions for surgical interventions. The overarching aim is to deepen the understanding of GERD's underlying mechanisms and advance the formulation of holistic, efficacious treatment approaches.
ABSTRACT
Background: Inflammatory bowel disease (IBD) is a group of diseases characterized by chronic and recurrent inflammation of the gastrointestinal tract. The etiology of IBD remains multifaceted and poorly understood, resulting in limited treatment options that primarily target disease induction and remission maintenance. Thus, the exploration of novel therapeutic options for IBD among existing medications is advantageous. Mendelian randomization analysis (MR) serves as a valuable tool in investigating the relationship between drugs and diseases. In this study, MR analysis was employed to investigate the potential causal relationship between 23 approved drugs for the treatment of various diseases and IBD. Method: We performed a two-sample MR analysis using publicly available genome-wide association study (GWAS) statistics. The inverse variance weighting (IVW) method was used as the main analysis method, supplemented by the remaining four methods (weighted median, MR Egger regression, simple and weighted models), and Meta-analysis was performed to expand the sample size to obtain a more reliable composite causal effect. Finally, Cochran's Q statistic and the MR-Egger test for directed pleiotropy were applied to determine whether significant heterogeneity or directed pleiotropy existed. Results: In the main MR analysis (IVW), drugs with a negative causal association with the risk of IBD were immunosuppressant {OR (95% CI) = 0.7389 [0.6311-0.8651], p = 0.0046} and diabetes drugs {OR (95% CI) = 0.9266 [0.8876-0.9674], p = 0.0058}. A positive causal association with the risk of IBD was found for salicylic acid and derivatives {OR (95% CI) = 1.2737 [1.0778-1.5053], p = 0.0345}. Negative causal associations with UC risk were identified for immunosuppressants {OR (95% CI) = 0.6660 [0.5133-0.8640], p = 0.0169} and diabetes medications {OR (95% CI) = 0.9020 [0.8508-0.9551], p = 0.0046}; positive causal associations with UC risk were found for ß-receptor blockers {OR (95% CI) = 1.1893 [1.0823-1.3070], p = 0.0046}. A negative causal association with the risk of CD was found for immunosuppressants {OR (95% CI) = 0.6957 [0.5803-0.8341], p = 0.0023}. There was no statistically significant association between the remaining 19 drugs and IBD and subtypes. Conclusion: This MR study provides evidence suggesting that immunosuppressants have a mitigating effect on the risk of IBD and demonstrate consistent efficacy in subtypes of ulcerative colitis (UC) and Crohn's disease (CD). Additionally, diabetes medications show potential in reducing the risk of IBD, particularly in cases of UC, while ß-blockers may elevate the risk of UC. Conversely, salicylic acid and its derivatives may increase the risk of IBD, although this effect is not consistently observed in the subtypes of the disease. These findings offer new insights into the prevention and management of IBD.