Research Spotlight

Smilowitz, N. R., R. Dubner, A. S. Hellkamp, R. J. Widmer and H. R. Reynolds (2021). “Variability of discharge medical therapy for secondary prevention among patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) in the United States.” PLoS One 16(8): e0255462.

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BACKGROUND: Optimal medical therapy after myocardial infarction with nonobstructive coronary arteries (MINOCA; <50% stenosis) is uncertain. We evaluated variability in discharge prescription of angiotensin-converting enzyme inhibitors / angiotensin receptor blockers (ACEI/ARB) and beta-blockers (BB) to MINOCA patients between hospitals to assess physician equipoise about secondary prevention. METHODS: Patients with MINOCA between 2007-2014 were identified in the NCDR Chest Pain-MI Registry. Those with prior revascularization or missing demographic, angiographic, or medication data were excluded. Analysis was limited to high-volume hospitals with ≥20 MINOCA total discharges. Discharge prescriptions for ACEI/ARB and BB after MINOCA were analyzed for each hospital. Clinical data on left ventricular ejection fraction (LVEF), glomerular filtration rate (GFR), and diabetes mellitus status were extracted to identify other indications for ACEI/ARB or BB. RESULTS: Clinical data were available for 17,849 MINOCA patients, of whom 8,752 (49%) had LVEF <40%, GFR ≤60 mL/min, and/or diabetes. 5,913 patients without one of these indications for ACEI/ARB or BB were discharged from 156 high-volume hospitals. At discharge, ACEI/ARB was prescribed to between 16.0% and 88.8% of MINOCA patients (median 45.6%, IQR 38.0%-56.5%) and BB to between 28.0% and 97.5% (median 74.1%, IQR 64.7%-80.0%). CONCLUSION: There is marked variability between hospitals in the proportions of patients receiving ACEI/ARB and BB after hospitalization for MINOCA, suggesting clinical equipoise about the routine use of these agents. Randomized clinical trials are necessary to establish the benefit of ACEI/ARB and BB to improve outcomes after MINOCA.

Goligher, E. C., C. A. Bradbury, B. J. McVerry, P. R. Lawler, J. S. Berger, M. N. Gong, M. Carrier, H. R. Reynolds, A. Kumar, A. F. Turgeon, L. Z. Kornblith, S. R. Kahn, J. C. Marshall, K. S. Kim, B. L. Houston, L. P. G. Derde, M. Cushman, T. Tritschler, D. C. Angus, L. C. Godoy, Z. McQuilten, B. A. Kirwan, M. E. Farkouh, M. M. Brooks, R. J. Lewis, L. R. Berry, E. Lorenzi, A. C. Gordon, T. Ahuja, F. Al-Beidh, D. Annane, Y. M. Arabi, D. Aryal, L. Baumann Kreuziger, A. Beane, Z. Bhimani, S. Bihari, H. H. Billett, L. Bond, M. Bonten, F. Brunkhorst, M. Buxton, A. Buzgau, L. A. Castellucci, S. Chekuri, J. T. Chen, A. C. Cheng, T. Chkhikvadze, B. Coiffard, A. Contreras, T. W. Costantini, S. de Brouwer, M. A. Detry, A. Duggal, V. Džavík, M. B. Effron, H. F. Eng, J. Escobedo, L. J. Estcourt, B. M. Everett, D. A. Fergusson, M. Fitzgerald, R. A. Fowler, J. D. Froess, Z. Fu, J. P. Galanaud, B. T. Galen, S. Gandotra, T. D. Girard, A. L. Goodman, H. Goossens, C. Green, Y. Y. Greenstein, P. L. Gross, R. Haniffa, S. M. Hegde, C. M. Hendrickson, A. M. Higgins, A. A. Hindenburg, A. A. Hope, J. M. Horowitz, C. M. Horvat, D. T. Huang, K. Hudock, B. J. Hunt, M. Husain, R. C. Hyzy, J. R. Jacobson, D. Jayakumar, N. M. Keller, A. Khan, Y. Kim, A. Kindzelski, A. J. King, M. M. Knudson, A. E. Kornblith, M. E. Kutcher, M. A. Laffan, F. Lamontagne, G. Le Gal, C. M. Leeper, E. S. Leifer, G. Lim, F. Gallego Lima, K. Linstrum, E. Litton, J. Lopez-Sendon, S. A. Lother, N. Marten, A. Saud Marinez, M. Martinez, E. Mateos Garcia, S. Mavromichalis, D. F. McAuley, E. G. McDonald, A. McGlothlin, S. P. McGuinness, S. Middeldorp, S. K. Montgomery, P. R. Mouncey, S. Murthy, G. B. Nair, R. Nair, A. D. Nichol, J. C. Nicolau, B. Nunez-Garcia, J. J. Park, P. K. Park, R. L. Parke, J. C. Parker, S. Parnia, J. D. Paul, M. Pompilio, J. G. Quigley, R. S. Rosenson, N. S. Rost, K. Rowan, F. O. Santos, M. Santos, M. O. Santos, L. Satterwhite, C. T. Saunders, J. Schreiber, R. E. G. Schutgens, C. W. Seymour, D. M. Siegal, D. G. Silva, Jr., A. B. Singhal, A. S. Slutsky, D. Solvason, S. J. Stanworth, A. M. Turner, W. van Bentum-Puijk, F. L. van de Veerdonk, S. van Diepen, G. Vazquez-Grande, L. Wahid, V. Wareham, R. J. Widmer, J. G. Wilson, E. Yuriditsky, Y. Zhong, S. M. Berry, C. J. McArthur, M. D. Neal, J. S. Hochman, S. A. Webb and R. Zarychanski (2021). “Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19.” N Engl J Med 385(9): 777-789.

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BACKGROUND: Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. METHODS: In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. RESULTS: The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis. CONCLUSIONS: In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis. (REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707, NCT04505774, NCT04359277, and NCT04372589.).

Raffals, L. E., S. Saha, M. Bewtra, C. Norris, A. Dobes, C. Heller, S. O’Charoen, T. Fehlmann, S. Sweeney, A. Weaver, S. Bishu, R. Cross, T. Dassopoulos, M. Fischer, A. Yarur, D. Hudesman, D. Parakkal, R. Duerr, F. Caldera, J. Korzenik, J. Pekow, K. Wells, M. Bohm, L. Perera, M. Kaur, M. Ciorba, S. Snapper, E. A. Scoville, S. Dalal, U. Wong and J. D. Lewis (2021). “The Development and Initial Findings of A Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD).” Inflamm Bowel Dis Aug 26;izab071. [Epub ahead of print].

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BACKGROUND: Clinical and molecular subcategories of inflammatory bowel disease (IBD) are needed to discover mechanisms of disease and predictors of response and disease relapse. We aimed to develop a study of a prospective adult research cohort with IBD (SPARC IBD) including longitudinal clinical and patient-reported data and biosamples. METHODS: We established a cohort of adults with IBD from a geographically diverse sample of patients across the United States with standardized data and biosample collection methods and sample processing techniques. At enrollment and at time of lower endoscopy, patient-reported outcomes (PRO), clinical data, and endoscopy scoring indices are captured. Patient-reported outcomes are collected quarterly. The quality of clinical data entry after the first year of the study was assessed. RESULTS: Through January 2020, 3029 patients were enrolled in SPARC, of whom 66.1% have Crohn’s disease (CD), 32.2% have ulcerative colitis (UC), and 1.7% have IBD-unclassified. Among patients enrolled, 990 underwent colonoscopy. Remission rates were 63.9% in the CD group and 80.6% in the UC group. In the quality study of the cohort, there was 96% agreement on year of diagnosis and 97% agreement on IBD subtype. There was 91% overall agreement describing UC extent as left-sided vs extensive or pancolitis. The overall agreement for CD behavior was 83%. CONCLUSION: The SPARC IBD is an ongoing large prospective cohort with longitudinal standardized collection of clinical data, biosamples, and PROs representing a unique resource aimed to drive discovery of clinical and molecular markers that will meet the needs of precision medicine in IBD.

Beyer, A., V. Lam, B. Fagel, S. Dong, C. Hebert, C. Wallace, N. Theyyunni, R. Tucker, M. Cover, R. Kessler, J. A. Cranford, R. Huang, A. A. Majkrzak, N. R. Seleno and C. M. Fung (2021). “Undifferentiated Dyspnea with Point-of-Care Ultrasound, Primary Emergency Physician Compared with a Dedicated Emergency Department Ultrasound Team.” J Emerg Med Aug 1;S0736-4679(21)00188-8. [Epub ahead of print].

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BACKGROUND: Emergency physicians (EPs) perform critical actions while operating with diagnostic uncertainty. Point-of-care ultrasound (POCUS) is useful in evaluation of dyspneic patients. In prior studies, POCUS is often performed by ultrasound (US) teams without patient care responsibilities. OBJECTIVES: This study evaluates the effectiveness of POCUS in narrowing diagnostic uncertainty in dyspneic patients when performed by treating EPs vs. separate US teams. METHODS: This multicenter, prospective noninferiority cohort study investigated the effect of a POCUS performing team in patient encounters for dyspnea. Before-and-after surveys assessing medical decision-making were administered to attending physicians. Primary outcome was change in most likely diagnosis after POCUS. This was assessed for noninferiority between encounters where the primary or US team performed POCUS. Secondary outcomes included change in differential diagnosis, confidence in diagnosis, interventions considered, and image quality. RESULTS: There were 156 patient encounters analyzed. In the primary team group, most likely diagnosis changed in 40% (95% confidence interval 28-52%) of encounters vs. 32% (95% confidence interval 22-41%) in the US team group. This was noninferior using an a priori specified margin of 20% (p < .0001). Post-POCUS differential decreased by a mean 1.8 diagnoses and was equivalent within a margin of 0.5 diagnoses between performing teams (p = 0.034). Other outcomes were similar between groups. CONCLUSION: POCUS performed by primary teams was noninferior to POCUS performed by US teams for changing the most likely diagnosis, and equivalent when considering mean reduction in number of diagnoses. POCUS performed by treating EPs reduces cognitive burden in dyspneic patients.

Kitano, M., S. Keswani, L. Erdahl, B. Bankhead-Kendall, A. Wall, K. Bilimoria and E. Kim (2021). “How to Optimize Your Research During a Pandemic – A Summary of Discussions From the Association for Academic Surgery Town Hall and Lessons Learned From 2020.” J Surg Res Aug 11;268:244-252. [Epub ahead of print].

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The year 2020 was an unprecedented year for all of us, including for the academic surgery research community. Both stay-at-home and social distancing restrictions posed challenges to our personal and professional lives. The Association for Academic Surgery held its inaugural webinar-based panel discussion titled Association for Academic Surgery Town Hall with its topic on how to optimize research during a pandemic. This article summarizes the highlights from that discussion and lessons learned from the academic surgery research community in 2020.