Research Spotlight

Posted January 15th 2021

Multicenter study on the diagnostic performance of multiframe volumetric laser endomicroscopy targets for Barrett’s esophagus neoplasia with histopathology correlation.

Vani J.A. Konda M.D.

Vani J.A. Konda M.D.

Struyvenberg, M.R., de Groof, A.J., Kahn, A., Weusten, B., Fleischer, D.E., Ganguly, E.K., Konda, V.J.A., Lightdale, C.J., Pleskow, D.K., Sethi, A., Smith, M.S., Trindade, A.J., Wallace, M.B., Wolfsen, H.C., Tearney, G.J., Meijer, S.L., Leggett, C.L., Bergman, J. and Curvers, W.L. (2020). “Multicenter study on the diagnostic performance of multiframe volumetric laser endomicroscopy targets for Barrett’s esophagus neoplasia with histopathology correlation.” Dis Esophagus 33(12).

Full text of this article.

Volumetric laser endomicroscopy (VLE) has been shown to improve detection of early neoplasia in Barrett’s esophagus (BE). However, diagnostic performance using histopathology-correlated VLE regions of interest (ROIs) has not been adequately studied. We evaluated the diagnostic accuracy of VLE assessors for identification of early BE neoplasia in histopathology-correlated VLE ROIs. In total, 191 ROIs (120 nondysplastic and 71 neoplastic) from 50 BE patients were evaluated in a random order using a web-based module. All ROIs contained histopathology correlations enabled by VLE laser marking. Assessors were blinded to endoscopic BE images and histology. ROIs were first scored as nondysplastic or neoplastic. Level of confidence was assigned to the predicted diagnosis. Outcome measures were: (i) diagnostic performance of VLE assessors for identification of BE neoplasia in all VLE ROIs, defined as accuracy, sensitivity, and specificity; (ii) diagnostic performance of VLE assessors for only high level of confidence predictions; and (iii) interobserver agreement. Accuracy, sensitivity, and specificity for BE neoplasia identification were 79% (confidence interval [CI], 75-83), 75% (CI, 71-79), and 81% (CI, 76-86), respectively. When neoplasia was identified with a high level of confidence, accuracy, sensitivity, and specificity were 88%, 83%, and 90%, respectively. The overall strength of interobserver agreement was fair (k = 0.29). VLE assessors can identify BE neoplasia with reasonable diagnostic accuracy in histopathology-correlated VLE ROIs, and accuracy is enhanced when BE neoplasia is identified with high level of confidence. Future work should focus on renewed VLE image reviewing criteria and real-time automatic assessment of VLE scans.


Posted January 15th 2021

Advances in Biomarkers for Risk Stratification in Barrett’s Esophagus.

Rhonda Souza M.D.

Rhonda Souza M.D.

Souza, R.F. and Spechler, S.J. (2021). “Advances in Biomarkers for Risk Stratification in Barrett’s Esophagus.” Gastrointest Endosc Clin N Am 31(1): 105-115.

Full text of this article.

Dysplasia currently is the primary biomarker used to risk stratify patients with Barrett’s esophagus, but dysplasia has a number of considerable limitations in this regard. Thus, investigators over the years have explored innumerable alternative molecular biomarkers for risk stratification in Barrett’s esophagus. This report focuses only on those biomarkers that appear most promising based on the availability of multiple published studies corroborating good results, and on the commercial availability of the test. These promising biomarkers include p53 immunostaining, TissueCypher, BarreGEN, and wide-area transepithelial sampling with computer-assisted 3-dimensional analysis (WATS(3D)).


Posted January 15th 2021

Reducing Antibiotic Use in Ambulatory Care Through Influenza Vaccination.

Manjusha Gaglani M.D.

Manjusha Gaglani M.D.

Smith, E.R., Fry, A.M., Hicks, L.A., Fleming-Dutra, K.E., Flannery, B., Ferdinands, J., Rolfes, M.A., Martin, E.T., Monto, A.S., Zimmerman, R.K., Nowalk, M.P., Jackson, M.L., McLean, H.Q., Olson, S.C., Gaglani, M. and Patel, M.M. (2020). “Reducing Antibiotic Use in Ambulatory Care Through Influenza Vaccination.” Clin Infect Dis 71(11): e726-e734.

Full text of this article.

BACKGROUND: Improving appropriate antibiotic use is crucial for combating antibiotic resistance and unnecessary adverse drug reactions. Acute respiratory illness (ARI) commonly causes outpatient visits and accounts for ~41% of antibiotics used in the United States. We examined the influence of influenza vaccination on reducing antibiotic prescriptions among outpatients with ARI. METHODS: We enrolled outpatients aged ≥6 months with ARI from 50-60 US clinics during 5 winters (2013-2018) and tested for influenza with RT-PCR; results were unavailable for clinical decision making and clinical influenza testing was infrequent. We collected antibiotic prescriptions and diagnosis codes for ARI syndromes. We calculated vaccine effectiveness (VE) by comparing vaccination odds among influenza-positive cases with test-negative controls. We estimated ARI visits and antibiotic prescriptions averted by influenza vaccination using estimates of VE, coverage, and prevalence of antibiotic prescriptions and influenza. RESULTS: Among 37 487 ARI outpatients, 9659 (26%) were influenza positive. Overall, 36% of ARI and 26% of influenza-positive patients were prescribed antibiotics. The top 3 prevalent ARI syndromes included: viral upper respiratory tract infection (47%), pharyngitis (18%), and allergy or asthma (11%). Among patients testing positive for influenza, 77% did not receive an ICD-CM diagnostic code for influenza. Overall, VE against influenza-associated ARI was 35% (95% CI, 32-39%). Vaccination prevented 5.6% of all ARI syndromes, ranging from 2.8% (sinusitis) to 11% (clinical influenza). Influenza vaccination averted 1 in 25 (3.8%; 95% CI, 3.6-4.1%) antibiotic prescriptions among ARI outpatients during influenza seasons. CONCLUSIONS: Vaccination and accurate influenza diagnosis may curb unnecessary antibiotic use and reduce the global threat of antibiotic resistance.


Posted January 15th 2021

Impact of COPD on Outcomes After MitraClip for Secondary Mitral Regurgitation: The COAPT Trial.

Michael J. Mack M.D.

Michael J. Mack M.D.

Saxon, J.T., Cohen, D.J., Chhatriwalla, A.K., Kotinkaduwa, L.N., Kar, S., Lim, D.S., Abraham, W.T., Lindenfeld, J., Mack, M.J., Arnold, S.V. and Stone, G.W. (2020). “Impact of COPD on Outcomes After MitraClip for Secondary Mitral Regurgitation: The COAPT Trial.” JACC Cardiovasc Interv 13(23): 2795-2803.

Full text of this article.

OBJECTIVES: The aim of this study was to examine the relationship between chronic obstructive pulmonary disease (COPD) and outcomes after transcatheter mitral valve repair (TMVr) for severe secondary mitral regurgitation. BACKGROUND: TMVr with the MitraClip improves clinical and health-status outcomes in patients with heart failure and severe (3+ to 4+) secondary mitral regurgitation. Whether these benefits are modified by COPD is unknown. METHODS: COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) was an open-label, multicenter, randomized trial of TMVr plus guideline-directed medical therapy (GDMT) versus GDMT alone. Patients on corticosteroids or continuous oxygen were excluded. Multivariable models were used to examine the associations of COPD with mortality, heart failure hospitalization (HFH), and health status and to test whether COPD modified the benefit of TMVr compared with GDMT. RESULTS: Among 614 patients, 143 (23.2%) had COPD. Among patients treated with TMVr, unadjusted analyses demonstrated increased 2-year mortality in those with COPD (hazard ratio [HR]: 2.08; 95% confidence interval [CI]: 1.33 to 3.26), but this association was attenuated after risk adjustment (adjusted HR: 1.48; 95% CI: 0.87 to 2.52). Although TMVr led to reduced 2-year mortality among patients without COPD (adjusted HR: 0.47; 95% CI: 0.33 to 0.67), for patients with COPD, 2-year all-cause mortality was similar after TMVr versus GDMT alone (adjusted HR: 0.94; 95% CI: 0.54 to 1.65; p(int) = 0.04), findings that reflect offsetting effects on cardiovascular and noncardiovascular mortality. In contrast, TMVr reduced HFH (adjusted HR: 0.48 [95% CI: 0.28 to 0.83] vs. 0.46 [95% CI: 0.34 to 0.63]; p(int) = 0.89) and improved both generic and disease-specific health status to a similar extent compared with GDMT alone in patients with and without COPD (p(int) >0.30 for all scales). CONCLUSIONS: In the COAPT trial, COPD was associated with attenuation of the survival benefit of TMVr versus GDMT compared with patients without COPD. However, the benefits of TMVr on both HFH and health status were similar regardless of COPD. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] [COAPT]; NCT01626079).


Posted January 15th 2021

Early Feasibility Studies for Cardiovascular Devices in the United States: JACC State-of-the-Art Review.

Michael J. Mack M.D.

Michael J. Mack M.D.

Holmes, D.R., Jr., Farb, A.A., Chip Hance, R., Leon, M.B., Goldberg, P., Zuckerman, B.D., Kaplan, A.V., Rincon-Gonzalez, L., Hunt, J., Walkowiak, J. and Mack, M.J. (2020). “Early Feasibility Studies for Cardiovascular Devices in the United States: JACC State-of-the-Art Review.” J Am Coll Cardiol 76(23): 2786-2794.

Full text of this article.

The development of technology to treat unmet clinical patient needs in the United States has been an important focus for the U.S. Food and Drug Administration and the 2016 Congressional 21st Century Cures Act. In response, a program of early feasibility studies (EFS) has been developed. One of the important issues has been the outmigration of the development and testing of medical devices from the United States. The EFS committee has developed and implemented processes to address issues to develop strategies for early treatment of these patient groups. Initial implementation of the U.S. Food and Drug Administration EFS program has been successful, but residual significant problems have hindered the opportunity to take full advantage of the program. These include delays in gaining Institutional Review Board approval, timeliness of budget and contractual negotiations, and lack of access to and enrollment of study subjects. This paper reviews improvements that have been made to the U.S. EFS ecosystem and outlines potential approaches to address remaining impediments to program success.