Research Spotlight

Johannesson, L., K. Wallis, E. C. Koon, G. J. McKenna, T. Anthony, S. G. Leffingwell, G. B. Klintmalm, R. T. Gunby, Jr. and G. Testa (2017). “Living uterus donation and transplantation: experience of interest and screening in a single center in the United States.” Am J Obstet Gynecol.

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BACKGROUND: Little is known about attitudes toward uterus donation and transplantation in society and the interest of the women the treatment is aimed to assist. OBJECTIVE: This study examined the interest of recipients and living donors in our uterus transplantation program; it describes the screening protocol we developed and the results of the screening and reports demographic data and characteristics of screened candidates. STUDY DESIGN: Initial screening and evaluation included physical examinations by a gynecologist and a transplant surgeon; psychological evaluation; imaging (x-ray, computed tomography, ultrasound); blood tests; immunological testing; viral, bacterial, and fungal testing; drug screen; hormonal testing; Papanicolau smear; urinalysis; and electrocardiogram. For selected recipients, the process also included in vitro fertilization. RESULTS: A total of 351 women contacted our department with interest in participating in uterus transplantation; 272 were potential recipients and 79 were potential donors. Among these women, 179 potential recipients and 62 potential donors continued the evaluation after the initial telephone screening. The mean age of the donor candidates was 40 years; all had completed their own family, and 80% were nondirected. Most recipient candidates (92%) had an anatomical lack of the uterus, and of these, 36% had a congenital malformation. The women with a congenital uterine absence were in general younger than the women in the group whose uterus had been removed (mean of 28 and 33 years, respectively). In every step of the initial screening and evaluation process, there were donor and recipient candidates that chose not to continue the process. The reasons for self-withdrawal after expressing interest were not returning phone calls or e-mails (17 donors and 76 recipients); after initial phone screening, no longer interested (1 donor and 9 recipients); in step 1, health history questionnaire not returned after 1 reminder (10 donors and 9 recipients); step 2, not right in their current life situation (2 donors and 2 recipients), and in step 3, chose another way to achieve motherhood (1 recipient). Most donor and recipient candidates (52% and 78%, respectively) could be screened out (because of self-withdrawal or transplant team’s decision) during the noninvasive and cost-efficient initial screening. CONCLUSION: Our initial experience shows a great interest in participating in a trial of uterus transplantation by both potential recipients and donors. It is the first study to show interest in nondirected donation. A sufficient but thoughtful screening process of living donors and recipients is essential and should aim both to assure donor/recipient safety and to provide good quality grafts.

Jackson, M. L., C. H. Phillips, J. Benoit, L. A. Jackson, M. Gaglani, K. Murthy, H. Q. McLean, E. A. Belongia, R. Malosh, R. Zimmerman and B. Flannery (2017). “Burden of medically attended influenza infection and cases averted by vaccination – United States, 2013/14 through 2015/16 influenza seasons.” Vaccine.

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BACKGROUND: In addition to preventing hospitalizations and deaths due to influenza, influenza vaccination programs can reduce the burden of outpatient visits for influenza. We estimated the incidence of medically-attended influenza at three geographically diverse sites in the United States, and the cases averted by vaccination, for the 2013/14 through 2015/16 influenza seasons. METHODS: We defined surveillance populations at three sites from the United States Influenza Vaccine Effectiveness Network. Among these populations, we identified outpatient visits laboratory-confirmed influenza via active surveillance, and identified all outpatient visits for acute respiratory illness from healthcare databases. We extrapolated the total number of outpatient visits for influenza from the proportion of surveillance visits with a positive influenza test. We combined estimates of incidence, vaccine coverage, and vaccine effectiveness to estimate outpatient visits averted by vaccination. RESULTS: Across the three sites and seasons, incidence of medically attended influenza ranged from 14 to 54 per 1000 population. Incidence was highest in children aged 6months to 9years (33 to 70 per 1000) and lowest in adults aged 18-49years (21 to 27 per 1000). Cases averted ranged from 9 per 1000 vaccinees (Washington, 2014/15) to 28 per 1000 (Wisconsin, 2013/14). DISCUSSION: Seasonal influenza epidemics cause a considerable burden of outpatient medical visits. The United States influenza vaccination program has caused meaningful reductions in outpatient visits for influenza, even in years when the vaccine is not well-matched to the dominant circulating influenza strain.

Hollander, P., J. Liu, J. Hill, J. Johnson, Z. W. Jiang, G. Golm, S. Huyck, S. G. Terra, J. P. Mancuso, S. S. Engel and B. Lauring (2017). “Ertugliflozin Compared with Glimepiride in Patients with Type 2 Diabetes Mellitus Inadequately Controlled on Metformin: The VERTIS SU Randomized Study.” Diabetes Ther.

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INTRODUCTION: This study assessed the safety and efficacy of ertugliflozin (an oral sodium-glucose cotransporter 2 inhibitor) vs. glimepiride in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin. METHODS: This phase III, double-blind, non-inferiority study (NCT01999218) randomized patients with HbA1c >/= 7.0% and /= 1500 mg/day 1:1:1 to ertugliflozin 15 or 5 mg once-daily (QD), or glimepiride (titrated from 1 mg QD). The primary hypothesis was that ertugliflozin 15 mg was non-inferior to glimepiride on HbA1c (non-inferiority criterion: upper bound of the 95% confidence interval [CI] about the treatment difference < 0.3%). RESULTS: Mean baseline HbA1c of randomized patients (N = 1326) was 7.8%. Mean and median doses of glimepiride were 3.0 mg/day throughout the study. At week 52, the least squares mean change (95% CI) from baseline in HbA1c was - 0.6% (- 0.7, - 0.5), - 0.6% (- 0.6, - 0.5), and - 0.7% (- 0.8, - 0.7) in the ertugliflozin 15 mg, ertugliflozin 5 mg, and glimepiride groups, respectively. The between-group difference for ertugliflozin 15 mg and glimepiride of 0.1% (- 0.0, 0.2) met the pre-specified non-inferiority criterion. Relative to glimepiride, greater body weight and systolic blood pressure (SBP) reductions were observed with ertugliflozin. The overall incidence of adverse events (AEs) was similar across groups. The incidence of symptomatic hypoglycemia and genital mycotic infection (GMI) were, respectively, lower and higher with ertugliflozin relative to glimepiride. The incidences of urinary tract infection and hypovolemia AEs were not meaningfully different among the groups. CONCLUSIONS: Ertugliflozin 15 mg was non-inferior to glimepiride in reducing HbA1c when added to metformin in patients with T2DM. Ertugliflozin had an acceptable safety profile and resulted in less hypoglycemia and more GMIs than glimepiride.

Hall, S. A., N. Uriel, S. A. Carey, M. Edens, G. Gong, M. Esposito, R. O’Kelly, S. Annamalai, N. Aghili, S. Adatya and N. K. Kapur (2018). “Use of a percutaneous temporary circulatory support device as a bridge to decision during acute decompensation of advanced heart failure.” J Heart Lung Transplant 37(1): 100-106.

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BACKGROUND: Prognosis is poor for patients with decompensated advanced heart failure (HF) refractory to medical therapy. Evaluating candidacy for durable mechanical circulatory support (MCS), cardiac transplantation, or palliative care is complex, and time is often needed to stabilize the patient hemodynamically. The Impella 5.0 (Abiomed, Danvers, MA) is a minimally invasive axial-flow catheter capable of providing full temporary hemodynamic support. We report a multicenter series on the use of this device for bridge to decision (BTD) in decompensated advanced HF patients. METHODS: In a retrospective evaluation at 3 centers of patients with advanced HF who acutely decompensated and received the Impella 5.0 for BTD, we analyzed demographics, procedural characteristics, in-hospital and intermediate-term outcomes, and in-hospital complications. RESULTS: There were 58 patients who met inclusion criteria from 2010 to 2015. All were inotrope dependent. The mean ejection fraction was 13%, and median age was 59 years (interquartile range, 48-64 years). Mean duration of support was 7 days (range, 0-22 days). Thirty-nine patients survived to next therapy (67%), with most receiving durable MCS (n = 20) or heart transplantation (n = 15). In-hospital complications included bleeding (n = 9) and hemolysis (n = 4). Of patients who survived to the next therapy, 1-year survival was 65% for those who received durable MCS, 87% for those who received a transplant, and 75% for those who were stabilized and weaned. CONCLUSIONS: The Impella 5.0 may provide a BTD strategy for patients with advanced HF and acute hemodynamic instability. Prospective studies are needed to evaluate the safety and effectiveness of this device in this patient population.

Froehler, M. T., J. L. Saver, O. O. Zaidat, R. Jahan, M. A. Aziz-Sultan, R. P. Klucznik, D. C. Haussen, F. R. Hellinger, Jr., D. R. Yavagal, T. L. Yao, D. S. Liebeskind, A. P. Jadhav, R. Gupta, A. E. Hassan, C. O. Martin, H. Bozorgchami, R. Kaushal, R. G. Nogueira, R. H. Gandhi, E. C. Peterson, S. R. Dashti, C. A. Given, 2nd, B. P. Mehta, V. Deshmukh, S. Starkman, I. Linfante, S. H. McPherson, P. Kvamme, T. J. Grobelny, M. S. Hussain, I. Thacker, N. Vora, P. R. Chen, S. J. Monteith, R. D. Ecker, C. M. Schirmer, E. Sauvageau, A. Abou-Chebl, C. P. Derdeyn, L. Maidan, A. Badruddin, A. H. Siddiqui, T. M. Dumont, A. Alhajeri, M. A. Taqi, K. Asi, J. Carpenter, A. Boulos, G. Jindal, A. S. Puri, R. Chitale, E. M. Deshaies, D. H. Robinson, D. F. Kallmes, B. W. Baxter, M. A. Jumaa, P. Sunenshine, A. Majjhoo, J. D. English, S. Suzuki, R. D. Fessler, J. E. Delgado Almandoz, J. C. Martin and N. H. Mueller-Kronast (2017). “Interhospital Transfer Before Thrombectomy Is Associated With Delayed Treatment and Worse Outcome in the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke).” Circulation 136(24): 2311-2321.

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BACKGROUND: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. METHODS: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0-2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. RESULTS: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients (P<0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06-1.79; P=0.02). Likewise, excellent outcome (modified Rankin Score 0-1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13-1.92; P=0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer; P=0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes, but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers. If bypass is limited to a 20-mile radius from onset, then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier. CONCLUSIONS: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes.