Contraction Reserve With Ineffective Esophageal Motility on Esophageal High-Resolution Manometry is Associated With Lower Acid Exposure Times Compared With Absent Contraction Reserve.

INTRODUCTION: Ineffective esophageal motility (IEM) is a minor motor disorder with potential reflux implications. Contraction reserve, manifested as augmentation of esophageal body contraction after multiple rapid swallows (MRS), may affect esophageal acid exposure time (AET) in IEM. METHODS: Esophageal high-resolution manometry (HRM) and ambulatory reflux monitoring studies were reviewed over 2 years to identify patients with normal HRM, IEM (≥50% ineffective swallows), and absent contractility (100% failed swallows). Single swallows and MRS were analyzed using HRM software tools (distal contractile integral, DCI) to determine contraction reserve (mean MRS DCI to mean single swallow DCI ratio >1). Univariate analysis and multivariable regression analyses were performed to determine motor predictors of abnormal AET in the context of contraction reserve. RESULTS: Of 191 eligible patients, 57.1% had normal HRM, 37.2% had IEM, and 5.8% had absent contractility. Contraction reserve had no affect on AET in normal HRM. Nonsevere IEM (5-7 ineffective swallows) demonstrated significantly lower proportions with abnormal AET in the presence of contraction reserve (30.4%) compared with severe IEM (8-10 ineffective swallows) (75.0%, P = 0.03). Abnormal AET proportions in nonsevere IEM with contraction reserve (32.7%) resembled normal HRM (33.0%, P = 0.96), whereas that in severe IEM with (46.2%) or without contraction reserve (50.0%) resembled absent contractility (54.5%, P ≥ 0.6). Multivariable analysis demonstrated contraction reserve to be an independent predictor of lower upright AET in nonsevere (odds ratio 0.44, 95% confidence interval 0.23-0.88) but not severe IEM. DISCUSSION: Contraction reserve affects esophageal reflux burden in nonsevere IEM. Segregating IEM into severe and nonsevere cohorts has clinical value.

Diagnosis of Eosinophilic Esophagitis at the Time of Esophageal Food Impaction.

BACKGROUND: Esophageal food impactions (EFI) often precede a diagnosis of eosinophilic esophagitis (EOE). Current guidelines suggest obtaining esophageal biopsies upon suspicion of EOE, treating with proton pump inhibitor (PPI), and repeating esophagogastroduodenoscopy (EGD). This study was conducted to determine provider practice patterns with these mentioned recommendations at the time of EFI. METHODS: In this retrospective study, key outcomes were the proportion of patients who had EOE mucosal biopsies, EOE diagnosis, PPI initiation, and recommendations and completions of repeat EGD. Differences in outcomes among age, sex, race, off-hours time of procedure, and trainee involvement were examined. EOE diagnosis predictors were explored with logistic regression. RESULTS: Twenty-nine percent of the patients had esophageal biopsies taken at the time of index EGD (iEGD). Sixteen patients were diagnosed with EOE at the time of index EFI, while fourteen patients were diagnosed on subsequent EGDs. Among those diagnosed with EOE at iEGD, 94% were placed on PPI. Of patients with confirmed EOE on index biopsy, 63% of patients were recommended repeat EGD, of which 50% completed it within 90 days. Older age was protective of EOE diagnosis while no GERD history and endoscopist suspicion of EOE predicted diagnosis of EOE. CONCLUSIONS: Endoscopists uncommonly take biopsies at the time of EFI, which may delay diagnosis and treatment of EOE.

Normal Ranges of Thiopurine Methyltransferase Activity Do Not Affect Thioguanine Nucleotide Concentrations With Azathioprine Therapy in Inflammatory Bowel Disease.

Background: Thiopurine methyltransferase (TPMT) activity influences azathioprine conversion into active metabolite 6-thioguanine nucleotide (6-TGN). Low TPMT activity correlates with high 6-TGN and risk for myelosuppression. Conversely, normal-to-high TPMT activity may be associated with low 6-TGN and drug resistance, the so-called hypermetabolizers. Our aim was to identify the effect of normal-to-high TPMT activity on 6-TGN concentrations in an inflammatory bowel disease population. Methods: A retrospective chart review of patients aged ≥18 with inflammatory bowel disease, on azathioprine, with documented TPMT activity and 6-TGN concentration was performed. Correlations were evaluated via the Spearman rho correlation coefficient. Linear regression was used to determine the effect of TPMT activity on 6-TGN accounting for confounders. Relationships between TPMT activity, drug dose, and 6-TGN levels were defined via average causal mediation effects. Results: One hundred patients were included. No correlation was observed between TPMT activity, azathioprine dosing, and metabolite concentrations. Overall, 39% of the cohort had a therapeutic 6-TGN level of >230 pmol/8 × 108 red blood cells (RBCs). No patient under 1 mg/kg achieved a therapeutic 6-TGN level, whereas 42% of patients taking 2.5 mg/kg did. The median 6-TGN concentration was higher for those in remission (254 pmol/8 × 108 RBCs, interquartile range: 174, 309) versus those not in remission (177 pmol/8 × 108 RBCs, interquartile range: 94.3, 287.8), though not significantly (P = 0.08). Smoking was the only clinical factor associated with 6-TGN level. On multivariate linear regression, only age, azathioprine dose, and obese body mass index were predictive of metabolite concentration. Conclusions: Variations within the normal range of TPMT activity do not affect 6-TGN concentration.