Research Spotlight

Cravedi, P., Schold, J.D., Safa, K., Kates, O.S., Elfadawy, N., Mannon, R.B., Shah, M.B., Hammond, S.P., Avery, R., Guerrero Miranda, C., Riella, L.V., Jowsey-Gregoire, S., Akalin, E., Camirand, G., Alegre, M.L. and Azzi, J. (2020). “The COVID-19 pandemic: A community approach.” Clin Transplant 34(11): e14059.

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An unprecedented global pandemic caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has quickly overwhelmed the health care systems worldwide. While there is an absence of consensus among the community in how to manage solid organ transplant recipients and donors, a platform provided by the American Society of Transplantation online community “Outstanding Questions in Transplantation,” hosted a collaborative multicenter, multinational discussions to share knowledge in a rapidly evolving global situation. Here, we present a summary of the discussion in addition to the latest published literature.

Froehlich-Grobe, K., Betts, A.C., Driver, S.J., Carlton, D.N., Lopez, A.M., Lee, J. and Kramer, M.K. (2020). “Group Lifestyle Balance Adapted for Individuals With Impaired Mobility: Outcomes for 6-Month RCT and Combined Groups at 12 Months.” Am J Prev Med 59(6): 805-817.

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INTRODUCTION: This study examines the feasibility and effectiveness of an intensive lifestyle intervention adapted for people with impaired mobility. STUDY DESIGN: This was a randomized, wait-list controlled trial. The experimental group immediately received the 12-month weight loss program; the wait-list control group received it after a 6-month delay. Between-group comparisons were conducted for the 6-month RCT study design. Repeated measures were conducted for both groups combined after receiving the 12-month intervention. Data were collected August 2015-February 2017 and analyzed in 2017. SETTING/PARTICIPANTS: A community-based sample received 23, group-based sessions via a mix of telephone and in-person sessions in a hospital-based setting. Participants with impaired mobility (n=66) were middle-aged (49.80 [SD=11.37] years), mostly White (66.7%), female (66.7%), and most commonly had spinal cord injury (47.0%). INTERVENTION: The 12-month intervention delivered 23 group-based sessions that promoted weight loss through reducing caloric intake and increasing physical activity. MAIN OUTCOME MEASURES: Primary outcomes were effectiveness measured as change in weight and time spent in moderate physical activity. Feasibility was assessed in 12-month combined group analyses, measured as retention, attendance, and dietary self-monitoring. RESULTS: The 6-month RCT results showed that the immediate and delayed groups differed significantly (p<0.05) in weight (-1.66 [SD=4.42] kg loss vs 0.05 [SD=4.15] kg gain) and moderate physical activity (52.93 [SD=90.74] minutes/week increase vs -14.22 [SD=96.02] minutes/week decrease), accounting for baseline weight, time with disability, and age of onset. The 12-month results with groups combined demonstrated 74.2% retention and 77.7% core session attendance. Self-monitoring was higher in the delayed group (77.3%), who used a smartphone app, than the immediate group (47.3%), who mostly used paper trackers. Participants achieved significant 12-month weight loss of 3.31 (SD=10.13) kg (d=0.33) in mixed modeling analyses with groups combined yet did not significantly increase moderate physical activity. CONCLUSIONS: Group Lifestyle Balance Adapted for Individuals with Impaired Mobility is a feasible, effective approach to teach healthy lifestyle skills to individuals with mobility impairment, yielding modest weight loss and enhanced self-efficacy.

Webb, J., Hensey, M., Fam, N., Rodés-Cabau, J., Daniels, D., Smith, R., Szeto, W., Boone, R., Ye, J., Moss, R., Peterson, M., Ong, G., Paradis, J.M., Dagenais, F., Wintzer-Wehekind, J., Shafi, B., Nair, D., Szerlip, M., Grayburn, P., Silvestry, F., Koulogiannis, K., Hermiller, J., Guyton, R. and Herrmann, H. (2020). “Transcatheter Mitral Valve Replacement With the Transseptal EVOQUE System.” JACC Cardiovasc Interv 13(20): 2418-2426.

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OBJECTIVES: The aim of this study was to examine the initial experience with a novel transseptal transcatheter mitral valve replacement (TMVR) system. BACKGROUND: Transseptal TMVR may offer a less invasive option than surgery for mitral regurgitation (MR) with greater efficacy and fewer anatomic limitations than transcatheter repair. METHODS: Patients were treated with the EVOQUE TMVR system from September 2018 to October 2019. Key inclusion criteria were moderate or greater MR, New York Heart Association functional class ≥II, and high or prohibitive surgical risk. The primary outcome was technical success, defined by Mitral Valve Academic Research Consortium criteria. RESULTS: Fourteen patients were treated, all with at least moderate to severe MR. The median age was 84 years, and the median Society of Thoracic Surgeons score was 4.6%. MR was degenerative in 4 (28.6%), functional in 3 (21.4%), and mixed in 7 (50%). Technical success was achieved in 13 patients (92.9%), and 1 patient was converted to surgery. At 30 days there was 1 noncardiovascular mortality (7.1%), 2 strokes (14.3%), no myocardial infarctions, and no rehospitalizations. Two patients (14.3%) underwent paravalvular leak closure. One patient (7.1%) underwent alcohol septal ablation for left ventricular outflow tract obstruction. Including the 2 patients with paravalvular leak closure, MR was mild or less in all implanted patients at 30 days, with no MR in 10 (83.3%). Mean mitral gradient was 5.8 mm Hg (median). New York Heart Association functional class improved to ≤II in 9 patients (81.8%). CONCLUSIONS: This first-in-human experience has demonstrated the feasibility of the transseptal EVOQUE TMVR system. Further clinical studies are required to establish safety and clinical outcomes.

Chen, P., Nirula, A., Heller, B., Gottlieb, R.L., Boscia, J., Morris, J., Huhn, G., Cardona, J., Mocherla, B., Stosor, V., Shawa, I., Adams, A.C., Van Naarden, J., Custer, K.L., Shen, L., Durante, M., Oakley, G., Schade, A.E., Sabo, J., Patel, D.R., Klekotka, P. and Skovronsky, D.M. (2020). “SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19.” N Engl J Med Oct 28;NEJMoa2029849. [Epub ahead of print].

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BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (Covid-19), which is most frequently mild yet can be severe and life-threatening. Virus-neutralizing monoclonal antibodies are predicted to reduce viral load, ameliorate symptoms, and prevent hospitalization. METHODS: In this ongoing phase 2 trial involving outpatients with recently diagnosed mild or moderate Covid-19, we randomly assigned 452 patients to receive a single intravenous infusion of neutralizing antibody LY-CoV555 in one of three doses (700 mg, 2800 mg, or 7000 mg) or placebo and evaluated the quantitative virologic end points and clinical outcomes. The primary outcome was the change from baseline in the viral load at day 11. The results of a preplanned interim analysis as of September 5, 2020, are reported here. RESULTS: At the time of the interim analysis, the observed mean decrease from baseline in the log viral load for the entire population was -3.81, for an elimination of more than 99.97% of viral RNA. For patients who received the 2800-mg dose of LY-CoV555, the difference from placebo in the decrease from baseline was -0.53 (95% confidence interval [CI], -0.98 to -0.08; P = 0.02), for a viral load that was lower by a factor of 3.4. Smaller differences from placebo in the change from baseline were observed among the patients who received the 700-mg dose (-0.20; 95% CI, -0.66 to 0.25; P = 0.38) or the 7000-mg dose (0.09; 95% CI, -0.37 to 0.55; P = 0.70). On days 2 to 6, the patients who received LY-CoV555 had a slightly lower severity of symptoms than those who received placebo. The percentage of patients who had a Covid-19-related hospitalization or visit to an emergency department was 1.6% in the LY-CoV555 group and 6.3% in the placebo group. CONCLUSIONS: In this interim analysis of a phase 2 trial, one of three doses of neutralizing antibody LY-CoV555 appeared to accelerate the natural decline in viral load over time, whereas the other doses had not by day 11.

Martin, E.T., Cheng, C., Petrie, J.G., Alyanak, E., Gaglani, M., Middleton, D.B., Ghamande, S., Silveira, F.P., Murthy, K., Zimmerman, R.K., Monto, A.S., Trabue, C., Talbot, H.K. and Ferdinands, J.M. (2020). “Low influenza vaccine effectiveness against A(H3N2) associated hospitalizations in the 2016-2017 and 2017-2018 seasons of the Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN).” J Infect Dis Nov 3;jiaa685. [Epub ahead of print].

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INTRODUCTION: The 2016-2017 and 2017-2018 influenza seasons were notable for high number of hospitalizations for influenza A(H3N2) despite vaccine and circulating strain match. METHODS: We evaluated vaccine effectiveness (VE) against hospitalization in the test-negative HAIVEN study. Nasal-throat swabs were tested by RT-PCR for influenza and VE was determined based on odds of vaccination by generalized estimating equations. Vaccine-specific antibody was measured in a subset of enrollees. RESULTS: A total of 6,129 adults were enrolled from ten hospitals. Adjusted VE against A(H3N2) was 22.8% (95% C.I. 8.3%, 35.0%), pooled across both years and 49.4% (95% C.I. 34.3%, 61.1%) against B/Yamagata. In 2017-2018, the A(H3N2) VE point estimate for the cell-based vaccine was 43.0% (95% C.I. -36.3%, 76.1%; 56 vaccine recipients) compared to 24.0% (95% C.I. 3.9%, 39.9%) for egg based vaccines. Among 643 with serology data, hemagglutinin antibodies against the egg-based A(H3N2) vaccine strain were increased in influenza-negative individuals. CONCLUSIONS: Low VE for the A/Hong Kong/4801/2014 vaccine virus in both A(H3N2) seasons emphasizes concerns for continued changes in H3N2 antigenic epitopes, including changes that may impact glycosylation and ultimately reduce VE.