Lazarescu A, Chan WW, Gyawali P, Lee YY, Xiao Y, Wu P. Updates on diagnostic modalities for esophageal dysphagia. Annals of the New York Academy of Sciences. 2020;1481(1):108-116. doi:10.1111/nyas.14453

Esophageal dysphagia is a common symptom in adults. Fluoroscopic contrast studies, endoscopy, and esophageal manometry have been used in the diagnosis of esophageal dysphagia for many years. The diagnostic yield has been improved with new test protocols that highlight abnormal bolus transit in the esophagus and outflow obstruction, as well as new high-definition and high-resolution technical advances in equipment. Functional luminal impedance planimetry and the addition of impedance to high-resolution esophageal manometry have also allowed the assessment of new parameters to better understand esophageal structure and function. In this concise review, we describe the role and utility of various diagnostic modalities in the assessment of patients with esophageal dysphagia.

Li M, Chan WW, Zucker SD. Association Between Atazanavir-Induced Hyperbilirubinemia and Cardiovascular Disease in Patients Infected with HIV. Journal of the American Heart Association. 2020;9(19):e016310. doi:10.1161/JAHA.120.016310

BACKGROUND: Serum bilirubin is inversely associated with cardiovascular risk. Atazanavir, an HIV protease inhibitor that competitively inhibits bilirubin conjugation, provides a unique opportunity to examine whether selectively increasing bilirubin is cardioprotective. We sought to determine whether patients receiving atazanavir manifest a reduced risk of cardiovascular disease compared with those receiving darunavir, an HIV protease inhibitor that does not increase serum bilirubin.

METHODS AND RESULTS: This was a retrospective cohort study of 1020 patients with HIV. The main outcome was time to myocardial infarction or ischemic stroke. Mean follow-up was 6.6±3.4 years, with 516 receiving atazanavir and 504 darunavir. Atazanavir patients exhibited significantly higher serum total bilirubin (1.7 versus 0.4 mg/dL; P<0.001) and longer mean time to ischemic event (10.2 versus 9.4 years; P<0.001). On Cox regression, atazanavir treatment (hazard ratio [HR], 0.38; 95% CI, 0.21-0.71; P=0.002) and serum bilirubin (HR, 0.60; 95% CI, 0.41-0.89; P=0.011) were independently associated with a lower risk of an ischemic event. Notably, when atazanavir and bilirubin were included together in the Cox regression model, atazanavir lost significance (HR, 0.55; 95% CI, 0.24-1.29; P=0.169) consistent with bilirubin being an intermediate variable on the causal pathway between atazanavir and its effect on cardiovascular disease. Patients on atazanavir also had a significantly lower risk of developing new cardiovascular disease (HR, 0.53; 95% CI, 0.33-0.86; P=0.010) and longer mean time to death (12.2 versus 10.8 years; P<0.001).

CONCLUSIONS: Patients with HIV on atazanavir manifest a decreased risk of cardiovascular disease when compared with those on darunavir, an effect that appears to be mediated by serum bilirubin.

Lo WK, Moniodis A, Goldberg HJ, Feldman N, Chan WW. Increased Acid Exposure on Pretransplant Impedance-pH Testing Is Associated With Chronic Rejection After Lung Transplantation. Journal of clinical gastroenterology. 2020;54(6):517-521. doi:10.1097/MCG.0000000000001331

GOAL: The goal of this study was to assess the relationship between pretransplant measures of reflux and longer-term outcomes of chronic allograft rejection in lung transplant recipients.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a primary measure of morbidity and mortality following lung transplantation, and a manifestation of chronic lung allograft dysfunction (CLAD). Acid reflux has been associated with early allograft injury through a proposed mechanism of aspiration and activation of the inflammatory cascade, but its association with chronic rejection is unclear.

STUDY: This was a retrospective cohort study of lung transplant recipients undergoing impedance-pH testing off proton pump inhibitor from 2007 to 2016. Patients with pretransplant antireflux surgery were excluded. Time-to-event analysis using the Cox proportional hazards model was applied to assess the relationship between pretransplant reflux measures and the development of BOS, defined histologically and clinically. A secondary analysis was completed using CLAD as the outcome variable.

RESULTS: Fifty-one subjects (59% men, mean age: 56, mean follow-up: 2.2 y) met inclusion criteria for the study. The BOS endpoint was reached in 13 subjects (28%). In time-to-event analyses, BOS was associated with increased acid exposure, defined as >4.2% of time with pH<4 [hazard ratio (HR): 4.18; 95% confidence interval (CI): 1.31-13.4; P=0.01], and elevated DeMeester score >14.7 (HR: 3.08; 95% CI: 1.02-9.26; P=0.04), with confirmation from Kaplan-Meier analyses. The secondary analysis demonstrated a similar association between increased acid exposure and CLAD (HR: 3.28; 95% CI: 1.09-9.88; P=0.03), which persisted on multivariate models.

CONCLUSION: Increased acid exposure on pretransplant reflux testing was associated with the development of BOS and CLAD, both measures of chronic allograft rejection, after lung transplantation, and may provide clinically relevant information to improve lung allograft survival through aggressive reflux management.

Hathorn KE, Chan WW, Aihara H, Thompson CC. Determining the Safety and Effectiveness of Electrocautery Enhanced Scissors for Peroral Endoscopic Myotomy (with Video). Clinical endoscopy. 2020;53(4):443-451. doi:10.5946/ce.2019.214

BACKGROUND/AIMS: Peroral endoscopic myotomy (POEM) has recently come to the forefront in the management of achalasia. We aimed to analyze the efficacy and safety of the use of electrocautery enhanced scissors (EES) for POEM.

METHODS: This retrospective cohort study prospectively collected the data of all adult patients (aged ≥18 years) with normal foregut anatomy who underwent POEM using EES. The patients' baseline characteristics and procedure details (time, tunnel length, myotomy length, depth, and location) were recorded. The primary outcome was clinical success (3-month post-procedure Eckardt score of ≤3). The secondary outcomes were technical success and adverse events. A paired Student's t-test was performed.

RESULTS: Fifteen patients were included in this study. The technical success rate of myotomy using EES was 100%. Fellows participated in the myotomy in all cases. The clinical success rate was 93.3% (14/15). The mean pre-Eckardt score was 5.4±2.5, while the mean post-Eckardt score was 1.3±1.3, which indicated a significant improvement (p≤0.0001). The most common treatment-related adverse events were post-procedure pain (4, 26.7%) and symptomatic reflux disease (4, 26.7%).

CONCLUSION: In the largest series to date on the use of EES in POEM, we demonstrated that this technique has both technical and clinical efficacy as well as an excellent safety profile.

McNabb-Baltar J, Jin DX, Grover AS, et al. Lipase Elevation in Patients With COVID-19. The American journal of gastroenterology. 2020;115(8):1286-1288. doi:10.14309/ajg.0000000000000732

INTRODUCTION: Although coronavirus disease (COVID-19) has been associated with gastrointestinal manifestations, its effect on the pancreas remains unclear. We aimed to assess the frequency and characteristics of hyperlipasemia in patients with COVID-19.

METHODS: A retrospective cohort study of hospitalized patients across 6 US centers with COVID-19.

RESULTS: Of 71 patients, 9 (12.1%) developed hyperlipasemia, with 2 (2.8%) greater than 3 times upper limit of normal. No patient developed acute pancreatitis. Hyperlipasemia was not associated with poor outcomes or symptoms.

DISCUSSION: Although a mild elevation in serum lipase was observed in some patients with COVID-19, clinical acute pancreatitis was not seen.

BACKGROUND: The 2019 novel coronavirus disease (COVID-19) has created unprecedented medical challenges. There remains a need for validated risk prediction models to assess short-term mortality risk among hospitalized patients with COVID-19. The objective of this study was to develop and validate a 7-day and 14-day mortality risk prediction model for patients hospitalized with COVID-19.

METHODS: We performed a multicenter retrospective cohort study with a separate multicenter cohort for external validation using two hospitals in New York, NY, and 9 hospitals in Massachusetts, respectively. A total of 664 patients in NY and 265 patients with COVID-19 in Massachusetts, hospitalized from March to April 2020.

RESULTS: We developed a risk model consisting of patient age, hypoxia severity, mean arterial pressure and presence of kidney dysfunction at hospital presentation. Multivariable regression model was based on risk factors selected from univariable and Chi-squared automatic interaction detection analyses. Validation was by receiver operating characteristic curve (discrimination) and Hosmer-Lemeshow goodness of fit (GOF) test (calibration). In internal cross-validation, prediction of 7-day mortality had an AUC of 0.86 (95%CI 0.74-0.98; GOF p = 0.744); while 14-day had an AUC of 0.83 (95%CI 0.69-0.97; GOF p = 0.588). External validation was achieved using 265 patients from an outside cohort and confirmed 7- and 14-day mortality prediction performance with an AUC of 0.85 (95%CI 0.78-0.92; GOF p = 0.340) and 0.83 (95%CI 0.76-0.89; GOF p = 0.471) respectively, along with excellent calibration. Retrospective data collection, short follow-up time, and development in COVID-19 epicenter may limit model generalizability.

CONCLUSIONS: The COVID-AID risk tool is a well-calibrated model that demonstrates accuracy in the prediction of both 7-day and 14-day mortality risk among patients hospitalized with COVID-19. This prediction score could assist with resource utilization, patient and caregiver education, and provide a risk stratification instrument for future research trials.

Hashemi N, Viveiros K, Redd WD, et al. Impact of chronic liver disease on outcomes of hospitalized patients with COVID-19: A multicentre United States experience. Liver international : official journal of the International Association for the Study of the Liver. 2020;40(10):2515-2521. doi:10.1111/liv.14583

Liver injury has been described with COVID-19, and early reports suggested 2%-11% of patients had chronic liver disease (CLD). In this multicentre retrospective study, we evaluated hospitalized adults with laboratory-confirmed COVID-19 and the impact of CLD on relevant clinical outcomes. Of 363 patients included, 19% had CLD, including 15.2% with NAFLD. Patients with CLD had longer length of stay. After controlling for age, gender, obesity, cardiac diseases, hypertension, hyperlipidaemia, diabetes and pulmonary disorders, CLD and NAFLD were independently associated with ICU admission ([aOR 1.77, 95% CI 1.03-3.04] and [aOR 2.30, 95% CI 1.27-4.17]) and mechanical ventilation ([aOR 2.08, 95% CI 1.20-3.60] and [aOR 2.15, 95% CI 1.18-3.91]). Presence of cirrhosis was an independent predictor of mortality (aOR 12.5, 95% CI 2.16-72.5). Overall, nearly one-fifth of hospitalized COVID-19 patients had CLD, which was associated with more critical illness. Future studies are needed to identify interventions to improve clinical outcomes.


Runge TM, Jirapinyo P, Chan WW, Thompson CC. Dysphagia predicts greater weight regain after Roux-en-Y gastric bypass: a longitudinal case-matched study. Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2019;15(12):2045-2051. doi:10.1016/j.soard.2019.06.041

BACKGROUND: Weight regain (WR) after gastric bypass is thought to be multifactorial in etiology with behavioral, neurohormonal, and anatomic features playing a role. A significant proportion of patients complain of dysphagia after Roux-en-Y gastric bypass (RYGB) and may have difficulty tolerating solid foods. Our observations suggest that this subgroup of patients compensate for esophageal symptoms by increasing their intake of calorie-dense liquid and soft foods, which can precipitate WR.

OBJECTIVES: We hypothesize that dysphagia predisposes to greater WR than seen in individuals without swallowing symptoms.

SETTING: Single tertiary care referral center.

METHODS: This was a matched-cohort study analysis of prospectively collected data on RYGB patients. All individuals who underwent high-resolution manometry after RYGB were enrolled. Controls were identified via a retrospective analysis of a prospective institutional database. Patients who developed dysphagia were matched with controls, from a subset of 450 eligible controls. Each patient with dysphagia was matched with 4 control patients based on age, body mass index, and time since surgery. WR was defined as an increase of ≥15% from nadir. Χ2 and t test (or Wilcoxon rank sum, if applicable) were used for bivariable analysis. Multiple logistic and linear regression were used for multivariable calculations.

RESULTS: Forty-nine patients with dysphagia were included. After matching, there were 196 RYGB controls that did not have swallowing or esophageal symptoms. Controls had similar baseline demographic characteristics and initial weight loss compared with dysphagia cases. WR was common in both groups; however, total WR in those with dysphagia was greater than controls (15.7 versus 11.4 kg, respectively; P = .02). In addition, percent WR in those with dysphagia exceeded that seen in controls (mean 37% versus 25%, P = .003), and more individuals regained 15% of nadir weight (55% of dysphagia cases versus 38% of controls, P = .03) when adjusting for baseline body mass index, age at surgery, and race. Dietary histories suggested that, among those with dysphagia, patients with partial or complete conversion to soft or liquid calories had greater WR than those who adhered to the solid food diet.

CONCLUSIONS: Dysphagia is a risk factor for WR post-RYGB. This is likely due to increased intake of soft or liquid foods that are tolerable in these patients but lead to a positive energy balance and accelerated WR. More than half of patients with dysphagia after RYGB regain significant weight. Screening for and aggressively managing dysphagia in patients before or after RYGB may be warranted to prevent significant WR.

Jirapinyo P, Makuvire TT, Dong WY, Chan WW, Thompson CC. Impact of Oral-Cecal Transit Time on the Interpretation of Lactulose Breath Tests After RYGB: a Personalized Approach to the Diagnosis of SIBO. Obesity surgery. 2019;29(3):771-775. doi:10.1007/s11695-018-3575-3

BACKGROUND: Traditionally, small intestinal bacterial overgrowth (SIBO) is diagnosed when there is an early peak in breath hydrogen or methane. Given unclear intestinal transit time in Roux-en-Y gastric bypass (RYGB) patients, it is unknown if the traditional approach at diagnosing SIBO is adequate in this patient population.

AIM: To assess oral-cecal transit time (OCTT) and its impact on the interpretation of breath tests in the diagnosis of SIBO in patients with RYGB.

METHODS: This study was a retrospective review of prospectively collected data on RYGB patients who underwent testing for SIBO using lactulose breath test (LBT) with or without small bowel follow-through (SBFT) to assess OCTT. Outcomes of SIBO test based on LBT alone versus LBT with OCTT were compared using a chi-squared test.

RESULTS: Sixty-two of the 151 RYGB patients who underwent LBT underwent an additional SBFT to assess OCTT. Median OCTT was 60 min. Of these, 59.7% had OCTT shorter than 90 min. Based on LBT alone, 36/62 patients (58.1%) were classified as positive SIBO. When LBT results were combined with OCTT, 26/36 patients (72.2%) had hydrogen or methane rise within OCTT, suggesting 27.8% false positive rate. Patients with true positive SIBO based on LBT and OCTT had a higher response rate to antibiotics compared to those with false positive SIBO (78.3% vs. 33.3%, p = 0.03).

CONCLUSION: A personalized approach of combining LBT with SBFT to assess OCTT may improve the accuracy of SIBO testing and enhance clinical outcomes in patients with RYGB.