A Prospective Open-Label Dose-Response Study to Correct Vitamin D Deficiency in Cirrhosis.

BACKGROUND: Patients with advanced liver disease often have vitamin D deficiency, but the daily dosages of vitamin D3 needed to raise their serum 25-hydrodroxyvitamin D [25(OH)D] concentrations are unknown. OBJECTIVE: We aimed to establish the dose-response relationship between vitamin D3 and 25(OH)D in patients with liver cirrhosis. DESIGN: An open-label study of orally-administered vitamin D3 (gelcaps) was conducted in patients with liver cirrhosis using a tiered-dosing regimen: 4,000 IU/d for baseline 25(OH)D ≤ 15 ng/mL and 2,000 IU/d for baseline 25(OH)D > 15 to ≤ 25 ng/mL (NCT01575717). Supplementation continued for 6 months, or until liver transplantation. Changes in 25(OH)D were measured after ≥ 3 months. Dose-response data on 48 patients (21 receiving 4000 IU/d and 27 receiving 2,000 IU/d) reporting ≥ 80% adherence were analyzed using generalized estimating equations (GEE). RESULTS: Among the 48 patients, 39 (81%) had 25(OH)D > 20 ng/mL while on supplements, and none experienced hypercalcemia. The magnitude of the increase in 25(OH)D was approximately twofold greater in patients receiving the higher dose. The mean incremental increase was 5.1 ng/ml ± 3.9 of 25(OH)D per 1000 IU/d of vitamin D3. Multivariable models demonstrated a significant positive relationship between baseline 25(OH)D and serum albumin (p < 0.01) and hemoglobin (p = 0.01), and a negative relationship with the MELD score (p < 0.01) and total bilirubin (p < 0.01). CONCLUSIONS: A two-tiered dosing regimen of daily oral vitamin D3 supplementation safely raised 25(OH)D concentrations in the majority of adults with liver cirrhosis who were adherent to supplement use.

Acid exposure time is sensitive for detecting gastroesophageal reflux disease and is associated with long-term survival after lung transplant.

Gastroesophageal reflux disease (GERD) is common in patients who have undergone lung transplantation and is associated with poorer outcomes, but guidelines are lacking to direct management strategies in this population. We assessed the diagnostic yield of impedance metrics compared to pH-metry alone for detecting GERD among lung transplant recipients and evaluated their association with clinical outcomes. We performed a retrospective cohort study of consecutive patients who underwent lung transplantation. Demographic data, acid exposure time (AET), number of reflux episodes, mean nocturnal baseline impedance (MNBI), post-reflux swallowing-induced peristaltic wave index (PSPWI), and clinical outcomes including mortality were collected. The relationship between GERD metrics and clinical outcomes was assessed using Wilcoxon signed-rank test and Fisher's exact test as appropriate. Of the 76 patients studied, 29 (38%) had GERD based on abnormal AET after lung transplantation. One (1.3%) patient had GERD based on elevated number of reflux episodes and abnormal distal MNBI detected GERD in 19 (26%) patients, resulting in 62% sensitivity and 94% specificity. Two (2.6%) patients had normal PSPWI. Patients with low distal MNBI had significantly decreased forced expiratory volume in 1 second (FEV1) at 3-year posttransplant compared to those without low distal MNBI (P = 0.03). Three-year survival was significantly worse among patients with elevated AET (66.7% vs. 89.1%, P = 0.03) but not with low distal MNBI (68.4% vs. 84.3%, P = 0.18). Abnormal AET is more sensitive for detecting GERD than other reflux metrics studied and is associated with survival, suggesting pH-metry alone may be sufficient to guide GERD management after lung transplant.

Esophageal Functional Lumen Imaging Probe (FLIP): How Can FLIP Enhance Your Clinical Practice?

Recent innovations in esophageal diagnostic testing have enhanced gastroenterology clinical practice by facilitating more nuanced and advanced evaluation of esophageal symptoms. Among these pivotal advances is the FDA-approved functional lumen imaging probe (FLIP), which utilizes impedance planimetry via volumetric distension of a catheter-mounted balloon at the time of sedated upper endoscopy, to acquire esophageal dimensions and pressures. In real time, FLIP can display cross-sectional areas (CSA) and distensibility indices (ratios of CSA to intra-balloon pressures) throughout the esophagus, most notably at the esophagogastric junction, as well as secondary peristaltic esophageal body contractile patterns. As the use of FLIP has progressively spread and permeated into the practice of clinical gastroenterology since its introduction, increasing data on and experiences with its applications have accumulated to guide its utility in clinical practice. In this current review developed for gastroenterologists and foregut surgeons across clinical practice, we provide an introduction to FLIP technology and metrics and discuss the clinical scenarios in which performance of or referral for FLIP may be helpful in the evaluation and management of patients with commonly encountered esophageal symptoms and disorders. Specifically, we discuss the potential applications and limitations of FLIP as a complementary diagnostic modality in patients with non-obstructive dysphagia, established or suspected achalasia spectrum disorders, eosinophilic esophagitis, gastroesophageal reflux disease and those undergoing esophageal surgery.

Esophageal contractile segment impedance from high-resolution impedance manometry correlates with mean nocturnal baseline impedance and acid exposure time from 24-hour pH-impedance monitoring.

Esophageal baseline impedance (BI) acquired during esophageal contraction (contractile segment impedance [CSI]) is proposed to improve BI accuracy in gastroesophageal reflux disease (GERD). We evaluated associations between CSI and conventional and novel GERD metrics. We analyzed high-resolution impedance manometry (HRIM) and ambulatory pH-impedance studies from 51 patients (58.6 ± 1.5 years; 26% F) with GERD symptoms studied off antisecretory therapy. Patients with achalasia or absent contractility were excluded. CSI (averaged across 10 swallows) and BI-HRIM (from the resting landmark phase) were acquired from the distal impedance sensors (distal sensor and 5 cm above the lower esophageal sphincter). Acid exposure time (AET) and mean nocturnal baseline impedance (MNBI) were calculated. Associations between CSI, BI-HRIM, MNBI, and AET were evaluated using correlation (Pearson) and receiver operating characteristic (ROC) analysis. Presenting symptoms included heartburn (67%), regurgitation (12%), cough (12%), and chest pain (10%). CSI-distal and CSI-5 each correlated with BI-HRIM, AET, and distal MNBI. Associations with AET were numerically stronger for CSI-distal (r = -0.46) and BI-HRIM-distal (r = -0.44) than CSI-5 (r = -0.33), BI-HRIM-5 (r = -0.28), or distal MNBI (r < -0.36). When compared to AET <4%, patients with AET >6% had significantly lower CSI-distal and BI-HRIM-distal values but not CSI-5, BI-HRIM-5, or MNBI. ROC areas under the curve for AET >6% were numerically higher for CSI-distal (0.81) than BI-HRIM-distal (0.77), distal MNBI (0.68-0.75), CSI-5 (0.68), or BI-HRIM-5 (0.68). CSI from HRIM studies inversely correlates with pathologic AET and has potential to augment the evaluation of GERD.

Correction to: Esophageal Function Tests are Not Associated with Barium Swallow Findings in Advanced Lung Disease.

The original version of this article unfortunately contained a mistake. The shared first authorship information was missing in the published article. It has been given below. The first authorship is shared between Dr. Shai Posner and Kurren Mehta.

Esophageal Function Tests are Not Associated with Barium Swallow Findings in Advanced Lung Disease.

Gastroesophageal reflux disease and esophageal dysmotility are common in patients with advanced lung disease (ALD) and are associated with worse outcomes. Assessing esophageal function in these patients is relevant for determining pulmonary transplant eligibility and prognosticating post-transplant outcomes. Barium Swallow (BaS) is a non-invasive testing modality often performed as a complement to formal esophageal function tests (EFTs), but its role and clinical utility in this context is unknown. Therefore, we aimed to determine the relationship between BaS and EFTs with high-resolution manometry (HRM) and 24-h ambulatory pH-metry in patients with ALD. We performed a retrospective study of 226 consecutive patients undergoing evaluation for lung transplantation at a single center. All patients underwent EFTs and BaS independent of clinical history or symptoms per institutional protocol. Appropriate statistical tests were performed to evaluate the relationship between EFTs and BaS. Mucosal, reflux and motility findings were categorized. Abnormal motility was reported in 133 (59%) patients by BaS and 99 (44%) by HRM, with a significant difference in the proportions of patients with abnormal studies (p < 0.01). There were 7 (26%) patients with abnormal barium tablet passage who had normal HRM. The sensitivity (35%) and specificity (77%) for detecting pathologic reflux with BaS was poor. Inducibility of reflux and barium column height were not associated with pH-metry results. No clinically significant luminal irregularities were identified. In conclusion, while BaS can non-invasively assess esophageal mucosa, its findings are not associated with EFTs in patients with ALD.

Esophageal contractility increases and gastroesophageal reflux does not worsen after lung transplantation.

Gastroesophageal reflux and esophageal dysmotility are common in patients with advanced lung disease and are associated with allograft dysfunction after lung transplantation. The effect of transplantation on reflux and esophageal motility is unclear. The aim of this study was to describe the changes in esophageal function occurring after lung transplantation. A retrospective cohort study was performed on lung transplant candidates evaluated at a tertiary care center between 2015 and 2016. A total of 76 patients who underwent lung transplantation had high-resolution manometry and ambulatory pH-metry before and after transplant. Demographic data, esophageal function testing results, and clinical outcomes such as pulmonary function testing were collected and analyzed using appropriate statistical tests and multivariable regression. Of the 76 patients, 59 (78%) received a bilateral transplant. There was a significant increase in esophageal contractility posttransplant, with an increase in median distal contractile integral from 1470 to 2549 mmHg cm s (P < 0.01). There were 19 patients with Jackhammer esophagus posttransplant, including 15 patients with normal motility pretransplant. Nine patients with ineffective or fragmented peristalsis pretransplant had normal manometry posttransplant. Abnormal pH-metry was observed in 35 (46%) patients pretransplant and 29 (38%) patients posttransplant (P = 0.33). Patients with gastroesophageal reflux disease posttransplant had less improvement in pulmonary function at one year, as measured by forced expiratory volume (P = 0.04). These results demonstrate that esophageal contractility increases significantly after lung transplantation, with an associated change in motility classification. In comparison, gastroesophageal reflux does not worsen, but is associated with worse pulmonary function, posttransplant.

Helicobacter pylori-associated peptic ulcer disease: A retrospective analysis of post-treatment testing practices.

BACKGROUND & AIMS: Guidelines recommend that patients with Helicobacter pylori (H. pylori)-associated peptic ulcer disease (PUD) receive H. pylori eradication therapy followed by post-treatment testing to prove eradication; however, post-treatment testing rates are suboptimal and barriers to testing are poorly understood. Our aim was to identify factors that predicted receipt of post-treatment testing. METHODS: We performed a retrospective cohort study of 152 patients with H. pylori-associated PUD diagnosed between 2007 and 2015 at a large tertiary medical center in the United States, who received standard eradication therapy and ambulatory follow-up within one year. The primary outcome of interest was receipt of post-treatment testing. Logistic regression models compared post-treatment testing rates in those diagnosed while outpatient vs inpatient, patients with vs without repeat endoscopy, and patients with vs without gastroenterology (GI) clinic follow-up. Propensity scores controlled for age, sex, race, ulcer location, and symptom persistence. RESULTS: Among 152 patients, 67 (44%) patients received post-treatment testing. There were significant differences in post-treatment testing rates in those diagnosed as outpatients vs inpatients (57% vs 33%; OR 3.87, P = 0.001) and in patients with vs without GI follow-up (62% vs 11%; OR 9.85, P < 0.0001). CONCLUSIONS: The rate of testing for eradication after treatment in patients with H. pylori- associated PUD was low. However, this was significantly improved in patients who have GI follow-up and whose diagnosis was made in the outpatient setting. Our study demonstrates a clear opportunity for quality improvement initiatives.