Research Spotlight

Carroll, J.D., Mack, M.J., Vemulapalli, S., Herrmann, H.C., Gleason, T.G., Hanzel, G., Deeb, G.M., Thourani, V.H., Cohen, D.J., Desai, N., Kirtane, A.J., Fitzgerald, S., Michaels, J., Krohn, C., Masoudi, F.A., Brindis, R.G. and Bavaria, J.E. (2021). “STS-ACC TVT Registry of Transcatheter Aortic Valve Replacement.” Ann Thorac Surg 111(2): 701-722.

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The STS-ACC TVT Registry (Society of Thoracic Surgeons-American College of Cardiology Transcatheter Valve Therapy Registry) from 2011 to 2019 has collected data on 276,316 patients undergoing transcatheter aortic valve replacement (TAVR) at sites in all U.S. states. Volumes have increased every year, exceeding surgical aortic valve replacement in 2019 (72,991 vs. 57,626), and it is now performed in all U.S. states. TAVR now extends from extreme- to low-risk patients. This is the first presentation on 8,395 low-risk patients treated in 2019. In 2019, for the entire cohort, femoral access increased to 95.3%, hospital stay was 2 days, and 90.3% were discharged home. Since 2011, the 30-day mortality rate has decreased (7.2% to 2.5%), stroke has started to decrease (2.75% to 2.3%), but pacemaker need is unchanged (10.9% to 10.8%). Alive with acceptable patient-reported outcomes is achieved in 8 of 10 patients at 1 year. The Registry is a national resource to improve care and analyze TAVR’s evolution. Real-world outcomes, site performance, and the impact of coronavirus disease 2019 will be subsequently studied. (STS/ACC Transcatheter Valve Therapy Registry [TVT Registry]; NCT01737528).

Linz, W., Arunachalam, P., George, E., Yadegar, T. and Robinson, P. (2021). “Telapheresis: A new paradigm for “saw and evaluated”.” J Clin Apher Feb 3. [Epub ahead of print].

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Medical record documentation guidelines from the American Society of Apheresis (ASFA) recommend that an apheresis physician of record “saw and evaluated”1 the apheresis patient. However, the guidelines do not specify by what means the patient should be seen or evaluated. Since that recommendation in 2005, advancing telecommunication technologies have catalyzed the development of “telapheresis”2 which allows physicians to see and evaluate patients with the aid of an onsite apheresis operator. This can be accomplished in a simple, inexpensive, and HIPAA (Health Insurance Portability and Accountability Act) compliant manner through devices supported by many institution’s existing telecommunications infrastructure and software such as Microsoft Teams. [No abstract; excerpt from article].

Spigel, D., Jotte, R., Nemunaitis, J., Shum, M., Schneider, J., Goldschmidt, J., Eisenstein, J., Berz, D., Seneviratne, L., Socoteanu, M., Bhanderi, V., Konduri, K., Xia, M., Wang, H., Hozak, R.R., Gueorguieva, I., Ferry, D., Gandhi, L., Chao, B.H. and Rybkin, I. (2021). “Randomized Phase 2 Studies of Checkpoint Inhibitors Alone or in Combination With Pegilodecakin in Patients With Metastatic NSCLC (CYPRESS 1 and CYPRESS 2).” J Thorac Oncol 16(2): 327-333.

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INTRODUCTION: Checkpoint inhibitors (CPIs) have been approved to treat metastatic NSCLC. Pegilodecakin + CPI suggested promising efficacy in phase 1 IVY, providing rationale for randomized phase 2 trials CYPRESS 1 and CYPRESS 2. METHODS: CYPRESS 1 (N = 101) and CYPRESS 2 (N = 52) included Eastern Cooperative Oncology Group performance status of 0 to 1 and first-line/second-line metastatic NSCLC, respectively, without known EGFR/ALK mutations. Patients were randomized 1:1; control arms received pembrolizumab (CYPRESS 1) or nivolumab (CYPRESS 2); experimental arms received pegilodecakin + CPI. Patients had programmed death-ligand 1 tumor proportion score of greater than or equal to 50% (CYPRESS 1) or 0% to 49% (CYPRESS 2). Primary end point was objective response rate (ORR) per investigator. Secondary end points included progression-free survival (PFS), overall survival (OS), and safety. Exploratory end points included immune activation biomarkers. RESULTS: Median follow-up for CYPRESS 1 and CYPRESS 2 was 10.0 and 11.6 months, respectively. Results for pegilodecakin + pembrolizumab versus pembrolizumab were as follows: ORR per investigator 47% versus 44% (OR = 1.1, 95% confidence interval [CI]: 0.5-2.5); median PFS 6.3 versus 6.1 months (hazard ratio [HR] = 0.937, 95% CI: 0.54-1.625); and median OS 16.3 months versus not reached (HR = 1.507, 95% CI: 0.708-3.209). Results per blinded independent central review were consistent. Treatment discontinuation rate owing to adverse events (AEs) doubled in the experimental arm (32% versus 15%). AEs with grade greater than or equal to 3 treatment-related AEs (62% versus 19%) included anemia (20% versus 0%) and thrombocytopenia (12% versus 2%). Results for pegilodecakin + nivolumab versus nivolumab were as follows: ORR per investigator 15% versus 12% (OR = 1.2, 95% CI: 0.3-5.9); median PFS 1.9 versus 1.9 months (HR = 1.006, 95% CI: 0.519-1.951); and median OS 6.7 versus 10.7 months (HR = 1.871, 95% CI: 0.772-4.532). AEs with grade greater than or equal to 3 treatment-related AEs (70.4% versus 16.7%) included anemia (40.7% versus 0%), fatigue (18% versus 0%), and thrombocytopenia (14.8% versus 0%). Biomarker data suggested activation of immunostimulatory signals of interleukin-10R pathway in pegilodecakin-containing arms. CONCLUSIONS: Despite evidence of biological effect in peripheral blood, adding pegilodecakin to CPI did not improve ORR, PFS, or OS, in first-line/second-line NSCLC. Pegilodecakin + CPI has been found to have overall higher toxicity compared with CPI alone, leading to doubling of treatment discontinuation rate owing to AEs.

Langer, C.J., Gajra, A., Gridelli, C., Konduri, K., Morgensztern, D., Spigel, D., Talbot, D., Thomas, M., Weiss, J., Pilot, R., Bhore, R., Wolfsteiner, M., Ong, T.J. and Socinski, M. (2020). “nab-Paclitaxel/Carboplatin in Vulnerable Populations With Advanced Non-Small Cell Lung Cancer: Pooled Analysis.” Front Oncol 10: 485587.

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INTRODUCTION: Despite improvements in the treatment of advanced non-small cell lung cancer (NSCLC), certain patient populations remain underrepresented in clinical trials. Many patients have benefited from platinum doublets, including nab-paclitaxel-based regimens, but there are patients with comorbidities who particularly require careful balancing of efficacy and safety. Clinical trial data are limited for patients who are elderly or have renal impairment, diabetes, or impaired performance status. METHODS: To better understand outcomes in these patient populations, we performed a pooled analysis using data from the ABOUND clinical trial program (ABOUND.SQM, ABOUND.PS2, ABOUND.70+) and the key phase III trial of nab-paclitaxel/carboplatin in advanced NSCLC. The populations included in this pooled analysis consisted of elderly patients (≥ 70 years) and patients with renal impairment (eGFR < 60 ml/min/1.73 m(2)), diabetes, or poor performance status (ECOG PS 2). RESULTS: Median progression-free survival (PFS) ranged from 4.1 months in patients with ECOG PS 2 (95% CI, 2.04-5.09 months) to 7.7 months in patients with diabetes (95% CI, 5.88-10.12 months). PFS for elderly patients and patients with renal impairment was 6.9 months each (95% CI, 6.01-7.98 months and 4.47-9.79 months, respectively). Median overall survival (OS) was 18.2 months (95% CI, 10.94-28.22 months), 17.4 months (95% CI, 14.59-20.14 months), and 16.1 months (95% CI, 14.09-18.50 months) in patients with renal impairment, patients with diabetes, and elderly patients, respectively. Patients with ECOG PS 2 exhibited the shortest median OS: 5.6 months (95% CI, 3.98-11.37 months). Overall response rates were 56.9%, 54.6%, 45.9%, and 29.4% in patients with diabetes, elderly patients, patients with renal impairment, and patients with ECOG PS 2, respectively. Most treatment-related adverse events were hematologic. The most common grade 3/4 hematologic adverse events in patients with renal impairment, elderly patients, patients with diabetes, and patients with poor performance status included neutropenia, anemia, and thrombocytopenia. CONCLUSIONS: Although survival data in patients with ECOG PS 2 were notably inferior to the other cohorts, our findings are consistent with those previously reported in the population-specific studies of the ABOUND trials and lend additional support for the use of nab-paclitaxel-based regimens in historically understudied and vulnerable populations.

Oguayo, C.C., Chu, J. and Jones, A.L. (2021). “A Community Orthopaedic Residency Approach to Education and Training During the COVID-19 Pandemic.” J Am Acad Orthop Surg Glob Res Rev 5(1).

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BACKGROUND: The COVID-19 pandemic has rapidly affected all facets of everyday life including the practice of medicine. Hospital systems and medical practices have evolved to protect patients, physicians, and staff and conserve personal protective equipment and resources. Orthopaedic practices have been specifically affected by social distancing and stay at home guidelines, limiting in-office practice and elective surgery restrictions. This, in turn, has had an effect on resident education. Previous literature has been published regarding how academic programs have adjusted to these changes. However, the effects on smaller orthopaedic residencies with nonacademic faculty has not been discussed. The orthopaedic residency at Baylor University Medical Center of Dallas is a fifteen-resident program with a combination of hospital employed and private practice faculty. We adjusted our resident education in mid-March 2020 to keep residents safe while trying to maximize surgical and clinical education and outside research. GOALS: Our goals were to come up with a plan allowed for continuing high-level patient care and resident education while protecting residents and limiting burnout. MODEL: We devised a four-team system with five-day call periods. Interactions between teams were strictly minimized. We also moved to a web-based academic curriculum and devised a system for safe resident participation in surgical cases. The model has been adjusted based on attending and resident feedback. CONCLUSION: Until we develop effective treatments or vaccination for COVID-19, there is a possibility that it will be an ongoing threat. Resident education must also adapt to the changing environment while continuing to provide residents safe opportunities for patient care, didactic education, and research. We believe we have come up with a sustainable, adaptable model for resident education during this challenging time.