Expert Recommendations on the Diagnosis of Eosinophilic Esophagitis in the United Arab Emirates.

Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory esophageal disease presenting as dysphagia to solid food and non-obstructive food impaction. Knowledge gaps exist in its diagnosis and management. These expert recommendations focused on the diagnosis of EoE in the United Arab Emirates. An electronic search of PubMed and Embase databases was used to gather evidence from systematic reviews, randomized controlled trials, consensus papers, and expert opinions from the last five years on the diagnosis of EoE. The evidence was graded using the Oxford system. Literature search findings were shared with the expert panel. A 5-point scale (strongly agree, agree, neither agree nor disagree, disagree, and strongly disagree) was used, and a concordance rate of >75% among experts indicated agreement. Using a modified Delphi technique, 18 qualified experts provided 17 recommendations. Eleven statements achieved high agreement, four got moderate agreement, and two got low agreement. Challenges exist in diagnosing EoE, particularly in children. Esophageal biopsies were crucial in diagnosis, irrespective of visible mucosal changes. Further research on diagnostic tools like endoscopic mucosal impedance and biomarkers is needed. Diagnosis relies on esophageal biopsies and symptom-histology correlation; however, tools like EoE assessment questionnaires and endoscopic mucosal impedance could enhance the accuracy and efficiency of EoE diagnosis. The diagnosis of EoE is challenging since the symptoms seldom correlate with the histological findings. Currently, diagnosis is based on patient symptoms and endoscopic and histological findings. Further research into mucosal impedance tests and the role of biomarkers is needed to facilitate diagnosis.

Acute transcutaneous electrical stimulation (TES) augments esophageal contractility in patients with weak peristalsis.

BACKGROUND: Lung transplantation (LTx) remains controversial in patients with absent peristalsis (AP) given the increased risk for gastroesophageal reflux (GER), and chronic lung allograft dysfunction. Furthermore, specific treatments to facilitate LTx in those with AP have not been widely described. Transcutaneous Electrical Stimulation (TES) has been reported to improve foregut contractility in LTx patients and therefore we hypothesize that TES may augment the esophageal motility of patients with ineffective esophageal motility (IEM). METHODS: We included 49 patients, 14 with IEM, 5 with AP, and 30 with normal motility. All subjects underwent standard high-resolution manometry and intraluminal impedance (HRIM) with additional swallows as TES was delivered. RESULTS: TES induced a universal impedance change observable in real-time by a characteristic spike activity. TES significantly augmented the contractile vigor of the esophagus measured by the distal contractile integral (DCI) in patients with IEM [median DCI (IQR) 0 (238) mmHg-cm-s off TES vs. 333 (858) mmHg-cm-s on TES; p = .01] and normal peristalsis [median DCI (IQR) 1545 (1840) mmHg-cm-s off TES vs. 2109 (2082) mmHg-cm-s on TES; p = .01]. Interestingly, TES induced measurable contractile activity (DCI > 100 mmHg-cm-s) in three out of five patients with AP [median DCI (IQR) 0 (0) mmHg-cm-s off TES vs. 0 (182) mmHg-cm-s on TES; p < .001]. CONCLUSION: TES acutely augmented contractile vigor in patients with normal and weak/ AP. The use of TES may positively impact LTx candidacy, and outcomes for patients with IEM/AP. Nevertheless, further studies are needed to determine the long-term effects of TES in this patient population.

Influence of Butyrate on Impaired Gene Expression in Colon from Patients with High Blood Pressure.

Hypertension (HTN) is associated with gut dysbiosis and the depletion of butyrate-producing bacteria in animal models and people. Furthermore, fecal material transfer from donor hypertensive patients increases blood pressure in normotensive recipient animals and ameliorates HTN-associated pathophysiology. These observations have implications in the impaired interactions between the gut and gut microbiota in HTN. Although this concept is supported in animal models, little is known about human HTN. Therefore, our objective for this study was to compare gene expression with transcriptomics and its potential to influence microbiota in subjects with normal and high blood pressure (HBP). Colon samples from reference subjects with normal blood pressure (REF) and HBP were used for RNA-seq to analyze their transcriptomes. We observed the significant downregulation of gene sets governing immune responses (e.g., SGK1 and OASL), gut epithelial function (e.g., KRT20 and SLC9A3R1), gut microbiota (e.g., PPARG and CIDEC) and genes associated with cardiovascular and gut diseases (e.g., PLAUR and NLN) in HBP subjects; the expression of genes within these pathways correlated with blood pressure. Potential drug targets in the gut epithelium were identified using the Drug Gene International Database for possible use in HTN. They include peroxisome proliferator-activated receptor gamma (PPRG), active serum/glucocorticoid regulated kinase 1 (SGK1) and 3 beta-hydroxysteroid isomerase type II inhibitor (HSD3B). Finally, butyrate, a microbiota-derived short-chain fatty acid, restored the disrupted expression of certain functional genes in colonic organoids from HBP subjects. Patients with HBP exhibit a unique transcriptome that could underlie impaired gut-microbiota interactions. Targeting these interactions could provide a promising new therapeutic intervention for hypertension management.

Case Report: Chagas Disease in a Traveler Who Developed Esophageal Involvement Decades after Acute Infection.

Travelers to Chagas disease endemic regions of Latin America may be at risk for Trypanosoma cruzi infection. We report a 67-year-old woman who screened positive for T. cruzi infection while donating blood. The patient had a history of an unusual febrile illness and marked swelling of the face sustained at age 10 after camping in northern Mexico that led to a 3-week hospitalization without a diagnosis. More than 4 decades later, rapid diagnostic tests and commercial and confirmatory serology for Chagas disease were all positive for T. cruzi infection. On evaluation, the patient described a progressive chronic cough, gastroesophageal reflux, and dysphagia for > 10 years. There was no evidence of any cardiac complications. However, esophageal manometry demonstrated significant dysmotility, with 90% of swallows being ineffective with evidence of esophageal pressurization and retrograde peristalsis in several swallows, suggesting early autonomic disruption due to Chagas disease esophagopathy. In this report, we highlight the importance of travel-related Chagas disease among travelers to endemic regions and the need to further identify potential risks of transmission among this at-risk population.

Reprograming of transcriptional profile of colonic organoids from patients with high blood pressure by minocycline.

Minocycline, an anti-inflammatory antibiotic drug, rebalances impaired gut microbiota, attenuates neuroinflammation and lowers high blood pressure in animal models of hypertension and in hypertensive patients. Our objective in this study was to investigate if antihypertensive effects of minocycline involve the expression of gut epithelial genes relevant to blood pressure homeostasis using human colonic 3-dimensional organoid culture and high-throughput RNA sequencing. The data demonstrates that minocycline could restore impaired expression of functional genes linked to viral and bacterial immunity, inflammation, protein trafficking and autophagy in human hypertensive organoids.