Research Spotlight

Kelly, R.J., Ajani, J.A., Kuzdzal, J., Zander, T., Van Cutsem, E., Piessen, G., Mendez, G., Feliciano, J., Motoyama, S., Lièvre, A., Uronis, H., Elimova, E., Grootscholten, C., Geboes, K., Zafar, S., Snow, S., Ko, A.H., Feeney, K., Schenker, M., Kocon, P., Zhang, J., Zhu, L., Lei, M., Singh, P., Kondo, K., Cleary, J.M. and Moehler, M. (2021). “Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer.” N Engl J Med 384(13): 1191-1203.

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BACKGROUND: No adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageal junction cancer. METHODS: We conducted CheckMate 577, a global, randomized, double-blind, placebo-controlled phase 3 trial to evaluate a checkpoint inhibitor as adjuvant therapy in patients with esophageal or gastroesophageal junction cancer. Adults with resected (R0) stage II or III esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy and had residual pathological disease were randomly assigned in a 2:1 ratio to receive nivolumab (at a dose of 240 mg every 2 weeks for 16 weeks, followed by nivolumab at a dose of 480 mg every 4 weeks) or matching placebo. The maximum duration of the trial intervention period was 1 year. The primary end point was disease-free survival. RESULTS: The median follow-up was 24.4 months. Among the 532 patients who received nivolumab, the median disease-free survival was 22.4 months (95% confidence interval [CI], 16.6 to 34.0), as compared with 11.0 months (95% CI, 8.3 to 14.3) among the 262 patients who received placebo (hazard ratio for disease recurrence or death, 0.69; 96.4% CI, 0.56 to 0.86; P<0.001). Disease-free survival favored nivolumab across multiple prespecified subgroups. Grade 3 or 4 adverse events that were considered by the investigators to be related to the active drug or placebo occurred in 71 of 532 patients (13%) in the nivolumab group and 15 of 260 patients (6%) in the placebo group. The trial regimen was discontinued because of adverse events related to the active drug or placebo in 9% of the patients in the nivolumab group and 3% of those in the placebo group. CONCLUSIONS: Among patients with resected esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy, disease-free survival was significantly longer among those who received nivolumab adjuvant therapy than among those who received placebo. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 577 ClinicalTrials.gov number, NCT02743494.).

Kastelz, A., Fernhall, B., Wang, E., Tzvetanov, I., Spaggiari, M., Shetty, A., Gallon, L., Hachaj, G., Kaplan, B. and Benedetti, E. (2021). “Personalized physical rehabilitation program and employment in kidney transplant recipients: A randomized trial.” Transpl Int Mar 18. [Epub ahead of print].

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INTRODUCTION: Kidney transplantation is the preferred treatment for kidney failure however after transplant, reduced physical function, poor self-perceptions and unemployment are common concerns that remain. METHODS: This randomized controlled trial compared the effects of a 12 month exercise rehabilitation program (intervention) to standard care alone (control) in kidney transplant recipients. The exercise intervention consisted of a 2 day/week, 60 minute personalized, one-on-one, resistance based exercise trainings. RESULTS: Eighty participants completed the study (52 intervention vs. 28 control). For individuals unemployed at baseline there was a 52.3% increase in employment compared to 13.3 % increase in the control group after 12 months (p=<0.0001). For those already employed at baseline, 100% of individuals maintained employment in both groups after 12 months (p=0.4742). For all comers, there was a positive trend for Global Physical Health (p=0.0034), Global Mental Health (p=0.0064), and Physical Function (p=0.0075), with the intervention group showing greater improvements. DISCUSSION/CONCLUSION: These findings suggest the implementation of an exercise rehabilitation program post kidney transplant can be beneficial to increase employment for individuals previously unemployed, improve self-perceived health, physical function, and mental health, overall contributing to better health outcomes in kidney transplant recipients. (Clinicaltrials.gov number: NCT02409901 ).

Kalantar-Zadeh, K., McCullough, P.A., Agarwal, S.K., Beddhu, S., Boaz, M., Bruchfeld, A., Chauveau, P., Chen, J., de Sequera, P., Gedney, N., Golper, T.A., Gupta, M., Harris, T., Hartwell, L., Liakopoulos, V., Kopple, J.D., Kovesdy, C.P., Macdougall, I.C., Mann, J.F.E., Molony, D., Norris, K.C., Perlmutter, J., Rhee, C.M., Riella, L.V., Weisbord, S.D., Zoccali, C. and Goldsmith, D. (2021). “Nomenclature in nephrology: preserving ‘renal’ and ‘nephro’ in the glossary of kidney health and disease.” J Nephrol Mar 13. [Epub ahead of print].

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A recently published nomenclature by a “Kidney Disease Improving Global Outcomes” (KDIGO) Consensus Conference suggested that the word “kidney” should be used in medical writings instead of “renal” or “nephro” when referring to kidney disease and kidney health. Whereas the decade-old move to use “kidney” more frequently should be supported when communicating with the public-at-large, such as the World Kidney Day, or in English speaking countries in communications with patients, care-partners, and non-medical persons, our point of view is that “renal” or “nephro” should not be removed from scientific and technical writings. Instead, the terms can coexist and be used in their relevant contexts. Cardiologists use “heart” and “cardio” as appropriate such as “heart failure” and “cardiac care units” and have not replaced “cardiovascular” with “heartvessel”, for instance. Likewise, in nephrology, we consider that “chronic kidney disease” and “continuous renal replacement therapy” should coexist. We suggest that in scientific writings and technical communications, the words “renal” and “nephro” and their derivatives are more appropriate and should be freely used without any pressure by medical journals to compel patients, care-partners, healthcare providers, researchers and other stakeholders to change their selected words and terminologies. We call to embrace the terms “kidney”, “renal” and “nephro” as they are used in different contexts and ask that scientific and medical journals not impose terminology restrictions for kidney disease and kidney health. The choice should be at the discretion of the authors, in the different contexts including in scientific journals.

Jalil, B.A., Ijaz, M., Khan, A.M. and Ledbetter, T.G. (2021). “A young man presenting with encephalopathy and seizures secondary to SARS-CoV-2.” BMJ Case Rep 14(3).

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COVID-19 has now emerged from a respiratory illness to a systemic viral illness with multisystem involvement. There is still a lot to learn about this illness as new disease associations with COVID-19 emerge consistently. We present a unique case of a neurological manifestation of a patient with structural brain disease who was COVID-19 positive and developed mental status changes, new-onset seizures and findings suggestive of viral meningitis on lumbar puncture. We also review the literature and discuss our case in the context of the other cases reported. We highlight the value of considering seizures and encephalopathy as one of the presenting features of COVID-19 disease.

Jackson, M.L., Ferdinands, J., Nowalk, M.P., Zimmerman, R.K., Kieke, B., Gaglani, M., Murthy, K., Petrie, J.G., Martin, E.T., Chung, J.R., Flannery, B. and Jackson, L.A. (2021). “Differences between Frequentist and Bayesian inference in routine surveillance for influenza vaccine effectiveness: a test-negative case-control study.” BMC Public Health 21(1): 516.

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BACKGROUND: Routine influenza vaccine effectiveness (VE) surveillance networks use frequentist methods to estimate VE. With data from more than a decade of VE surveillance from diverse global populations now available, using Bayesian methods to explicitly account for this knowledge may be beneficial. This study explores differences between Bayesian vs. frequentist inference in multiple seasons with varying VE. METHODS: We used data from the United States Influenza Vaccine Effectiveness (US Flu VE) Network. Ambulatory care patients with acute respiratory illness were enrolled during seasons of varying observed VE based on traditional frequentist methods. We estimated VE against A(H1N1)pdm in 2015/16, dominated by A(H1N1)pdm; against A(H3N2) in 2017/18, dominated by A(H3N2); and compared VE for live attenuated influenza vaccine (LAIV) vs. inactivated influenza vaccine (IIV) among children aged 2-17 years in 2013/14, also dominated by A(H1N1)pdm. VE was estimated using both frequentist and Bayesian methods using the test-negative design. For the Bayesian estimates, prior VE distributions were based on data from all published test-negative studies of the same influenza type/subtype available prior to the season of interest. RESULTS: Across the three seasons, 16,342 subjects were included in the analyses. For 2015/16, frequentist and Bayesian VE estimates were essentially identical (41% each). For 2017/18, frequentist and Bayesian estimates of VE against A(H3N2) viruses were also nearly identical (26% vs. 23%, respectively), even though the presence of apparent antigenic match could potentially have pulled Bayesian estimates upward. Precision of estimates was similar between methods in both seasons. Frequentist and Bayesian estimates diverged for children in 2013/14. Under the frequentist approach, LAIV effectiveness was 62 percentage points lower than IIV, while LAIV was only 27 percentage points lower than IIV under the Bayesian approach. CONCLUSION: Bayesian estimates of influenza VE can differ from frequentist estimates to a clinically meaningful degree when VE diverges substantially from previous seasons.