Research Spotlight

Jacob, A., Shook, J. and Hutson, T. (2021). “The implementation of lenvatinib/everolimus or lenvatinib/pembrolizumab combinations in the treatment of metastatic renal cell carcinoma.” Expert Rev Anticancer Ther Jan 4. [ Epub ahead of print].

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Introduction: There are 400,000 new cases of Renal Cell Carcinoma (RCC) and 175,000 deaths worldwide every year. Currently available frontline therapies to treat RCC have less toxicity than previously employed therapeutic agents, but drug resistance is still a clinically significant problem. Drug resistance occurs through angiogenic escape by the activation of pathways that are independent of the VEGF targets of most first-line therapies. The lenvatinib/everolimus and lenvatinib/pembrolizumab are part of a new generation of combinations that can combat this method of resistance to extend both progression-free survival and overall survival in patients with metastatic RCC. Areas covered: This article discusses the evolution of current data on the efficacy and safety of these two combinations and future directions for their implementation in the treatment of advanced renal cell carcinoma. Expert opinion: Future research will focus on these combinations in contrast with other currently approved regimens. Once specific biomarkers that predict response to treatment are identified, the future of treatment of RCC will involve specifically tailored therapies for a patient’s genotype. Therapies unique only to the patient undergoing treatment will increase both efficacy and safety of new treatments, and that is the truly exciting future that awaits this field.

Huynh, P., Konda, V., Sanguansataya, S., Ward, M.A. and Leeds, S.G. (2020). “Mind the Gap: Current Treatment Alternatives for GERD Patients Failing Medical Treatment and Not Ready for a Fundoplication.” Surg Laparosc Endosc Percutan Tech Dec 16. [Epub ahead of print].

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BACKGROUND: Gastroesophageal reflux disease is associated with Barrett esophagus, esophageal adenocarcinoma, and significantly impacts quality of life. Medical management is the first line therapy with surgical fundoplication as an alternative therapy. However, a small portion of patients who fail medical therapy are referred for surgical consultation. This creates a “gap” in therapy for those patients dissatisfied with medical therapy but are not getting referred for surgical consultation. Three procedures have been designed to address these patients. These include radiofrequency ablation (RFA) of the lower esophageal sphincter, transoral incisionless fundoplication (TIF), and magnetic sphincter augmentation. MATERIALS AND METHODS: A Pubmed literature review was conducted of all publications for RFA, TIF, and MSA. Four most common endpoints for the 3 procedures were compared at different intervals of follow-up. These include percent of patients off proton pump inhibitors (PPIs), GERD-HRQL score, DeMeester score, and percent of time with pH <4. A second query was performed for patients treated with PPI and fundoplications to match the same 4 endpoints as a control. RESULTS: Variable freedom from PPI was reported at 1 year for RFA with a weighted mean of 62%, TIF with a weighted mean of 61%, MSA with a weighted mean of 85%, and fundoplications with a weighted mean of 84%. All procedures including PPIs improved quality-of-life scores but were not equal. Fundoplication had the best improvement followed by MSA, TIF, RFA, and PPI, respectively. DeMeester scores are variable after all procedures and PPIs. All MSA studies showed normalization of pH, whereas only 4 of 17 RFA studies and 3 of 11 TIF studies reported normalization of pH. CONCLUSIONS: Our literature review compares 3 rival procedures to treat "gap" patients for gastroesophageal reflux disease with 4 common endpoints. Magnetic sphincter augmentation appears to have the most reproducible and linear outcomes but is the most invasive of the 3 procedures. MSA outcomes most closely mirrors that of fundoplication.

Hughes, K., Middleton, D.B., Nowalk, M.P., Balasubramani, G.K., Martin, E.T., Gaglani, M., Talbot, H.K., Patel, M.M., Ferdinands, J.M., Zimmerman, R.K. and Silveira, F.P. (2021). “Effectiveness of Influenza Vaccine for Preventing Laboratory-Confirmed Influenza Hospitalizations in Immunocompromised Adults.” Clin Infect Dis Jan 3;ciaa1927. [Epub ahead of print].

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BACKGROUND: Yearly influenza immunization is recommended for immunocompromised (IC) individuals, although immune responses are lower than that for the non-immunocompromised and the data on vaccine effectiveness (VE) in the IC is scarce. We evaluated VE against influenza-associated hospitalization among IC adults. METHODS: We analyzed data from adults ≥ 18 years hospitalized with acute respiratory illness (ARI) during the 2017-2018 influenza season at 10 hospitals in the United States. IC adults were identified using pre-specified case-definitions, utilizing electronic medical record data. VE was evaluated with a test-negative case-control design using multivariable logistic regression with PCR-confirmed influenza as the outcome and vaccination status as the exposure, adjusting for age, enrolling site, illness onset date, race, days from onset to specimen collection, self-reported health, and self-reported hospitalizations. RESULTS: Of 3,524 adults hospitalized with ARI, 1,210 (34.3%) had an immunocompromising condition. IC adults were more likely to be vaccinated than non-IC (69.5% vs 65.2%), and less likely to have influenza (22% vs 27.8%). The mean age did not differ among IC and non-IC (61.4 vs 60.8 years old). The overall VE against influenza hospitalization, including immunocompetent adults, was 33% (95% CI, 21% to 44%). VE among IC vs non-IC adults was lower at 5% (-29% to 31%) vs. 41% (27% to 52%) (p<0.05 for interaction term). CONCLUSIONS: VE in one influenza season was very low among IC individuals. Future efforts should include evaluation of VE among the different immunocompromising conditions and whether enhanced vaccines improve the suboptimal effectiveness among the immunocompromised.

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.

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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.

Hobson, D.T.G., Kinman, C.L., Gaskins, J.T., Francis, S.L., McKenzie, C.M., Stewart, J.R., Gupta, A.S. and Meriwether, K.V. (2021). “Comparative analyses of attitude, knowledge, and recollection of preoperative counseling regarding pelvic mesh among women with or without a mesh-related complication.” Arch Gynecol Obstet Jan 3. [Epub ahead of print].

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PURPOSE: Our objective was to compare the recollection of preoperative counseling regarding mesh for pelvic organ prolapse (POP) and/or stress urinary incontinence (SUI) among women with or without a mesh-related complication (MRC). We hypothesized that the patients who had MRC would better recollect counseling regarding complications associated with mesh. METHODS: We conducted a retrospective cohort study among women who had prior implantation of synthetic, non-absorbable mesh for POP and/or SUI at least 3 months prior who presented with or without a MRC. The primary outcome was the proportion of women who recalled being counseled preoperatively about the risk of mesh exposure. RESULTS: Ninety-six women were included in the final analysis (50 MRC; 46 no MRC). MRC women presented further in time from the index surgery [median 69 months [IQR 26-115] vs 12 months (IQR 6-64), p < 0.01]. After adjustment for time since surgery and age, MRC women were significantly less likely to recall being counseled about the possibility of any MRC [19/50 (38%) vs 32/44 (73%), aOR 0.29, 95% CI 0.11-0.79, p = 0.01]. They were also less likely to report they would undergo the same surgery again 5-point Likert scale [median 3 (IQR 1-4) vs 5 (IQR 3-5), 5-point Likert scale, p < 0.01], less satisfied with their mesh surgery [median 1 (IQR 1-3) vs 5 (IQR 3-5), 5-point Likert scale, p < 0.01] and recommended improved preoperative counseling [27/50 (54%) vs 6/46 (13%), p < 0.01]. CONCLUSION: Women who experienced MRC were less likely to recall being counseled about the possibility of MRC and report more unmet needs regarding perioperative counseling than women without MRC.