Research Spotlight

Baylor Health Sciences Library brings to you each month the latest published research from the Baylor Scott & White and Texas A&M College of Dentistry communities. Each newly published article features the researcher, the abstract, and link to the full text. For information on including your own research, please contact John Fullinwider, john.fullinwider@BSWHealth.org for BSWH or Sudha Ramakrishnan, sudharamakrishnan@tamu.edu, for COD.


Posted March 15th 2020

Pembrolizumab for Early Triple-Negative Breast Cancer.

Joyce O'Shaughnessy M.D.
Joyce O’Shaughnessy M.D.

Schmid, P., J. Cortes, L. Pusztai, H. McArthur, S. Kummel, J. Bergh, C. Denkert, Y. H. Park, R. Hui, N. Harbeck, M. Takahashi, T. Foukakis, P. A. Fasching, F. Cardoso, M. Untch, L. Jia, V. Karantza, J. Zhao, G. Aktan, R. Dent and J. O’Shaughnessy (2020). “Pembrolizumab for Early Triple-Negative Breast Cancer.” New England Journal of Medicine 382(9): 810-821.

Full text of this article.

BACKGROUND: Previous trials showed promising antitumor activity and an acceptable safety profile associated with pembrolizumab in patients with early triple-negative breast cancer. Whether the addition of pembrolizumab to neoadjuvant chemotherapy would significantly increase the percentage of patients with early triple-negative breast cancer who have a pathological complete response (defined as no invasive cancer in the breast and negative nodes) at definitive surgery is unclear. METHODS: In this phase 3 trial, we randomly assigned (in a 2:1 ratio) patients with previously untreated stage II or stage III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) every 3 weeks plus paclitaxel and carboplatin (784 patients; the pembrolizumab-chemotherapy group) or placebo every 3 weeks plus paclitaxel and carboplatin (390 patients; the placebo-chemotherapy group); the two groups then received an additional four cycles of pembrolizumab or placebo, and both groups received doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After definitive surgery, the patients received adjuvant pembrolizumab or placebo every 3 weeks for up to nine cycles. The primary end points were a pathological complete response at the time of definitive surgery and event-free survival in the intention-to-treat population. RESULTS: At the first interim analysis, among the first 602 patients who underwent randomization, the percentage of patients with a pathological complete response was 64.8% (95% confidence interval [CI], 59.9 to 69.5) in the pembrolizumab-chemotherapy group and 51.2% (95% CI, 44.1 to 58.3) in the placebo-chemotherapy group (estimated treatment difference, 13.6 percentage points; 95% CI, 5.4 to 21.8; P<0.001). After a median follow-up of 15.5 months (range, 2.7 to 25.0), 58 of 784 patients (7.4%) in the pembrolizumab-chemotherapy group and 46 of 390 patients (11.8%) in the placebo-chemotherapy group had disease progression that precluded definitive surgery, had local or distant recurrence or a second primary tumor, or died from any cause (hazard ratio, 0.63; 95% CI, 0.43 to 0.93). Across all treatment phases, the incidence of treatment-related adverse events of grade 3 or higher was 78.0% in the pembrolizumab-chemotherapy group and 73.0% in the placebo-chemotherapy group, including death in 0.4% (3 patients) and 0.3% (1 patient), respectively. CONCLUSIONS: Among patients with early triple-negative breast cancer, the percentage with a pathological complete response was significantly higher among those who received pembrolizumab plus neoadjuvant chemotherapy than among those who received placebo plus neoadjuvant chemotherapy. (Funded by Merck Sharp & Dohme [a subsidiary of Merck]; KEYNOTE-522 ClinicalTrials.gov number, NCT03036488.).


Posted March 15th 2020

Five-Year Outcomes of Transcatheter or Surgical Aortic-Valve Replacement.

Michael J. Mack M.D.
Michael J. Mack M.D.

Makkar, R. R., V. H. Thourani, M. J. Mack, S. K. Kodali, S. Kapadia, J. G. Webb, S. H. Yoon, A. Trento, L. G. Svensson, H. C. Herrmann, W. Y. Szeto, D. C. Miller, L. Satler, D. J. Cohen, T. M. Dewey, V. Babaliaros, M. R. Williams, D. J. Kereiakes, A. Zajarias, K. L. Greason, B. K. Whisenant, R. W. Hodson, D. L. Brown, W. F. Fearon, M. J. Russo, P. Pibarot, R. T. Hahn, W. A. Jaber, E. Rogers, K. Xu, J. Wheeler, M. C. Alu, C. R. Smith and M. B. Leon (2020). “Five-Year Outcomes of Transcatheter or Surgical Aortic-Valve Replacement.” New England Journal of Medicine 382(9): 799-809.

Full text of this article.

BACKGROUND: There are scant data on long-term clinical outcomes and bioprosthetic-valve function after transcatheter aortic-valve replacement (TAVR) as compared with surgical aortic-valve replacement in patients with severe aortic stenosis and intermediate surgical risk. METHODS: We enrolled 2032 intermediate-risk patients with severe, symptomatic aortic stenosis at 57 centers. Patients were stratified according to intended transfemoral or transthoracic access (76.3% and 23.7%, respectively) and were randomly assigned to undergo either TAVR or surgical replacement. Clinical, echocardiographic, and health-status outcomes were followed for 5 years. The primary end point was death from any cause or disabling stroke. RESULTS: At 5 years, there was no significant difference in the incidence of death from any cause or disabling stroke between the TAVR group and the surgery group (47.9% and 43.4%, respectively; hazard ratio, 1.09; 95% confidence interval [CI], 0.95 to 1.25; P = 0.21). Results were similar for the transfemoral-access cohort (44.5% and 42.0%, respectively; hazard ratio, 1.02; 95% CI, 0.87 to 1.20), but the incidence of death or disabling stroke was higher after TAVR than after surgery in the transthoracic-access cohort (59.3% vs. 48.3%; hazard ratio, 1.32; 95% CI, 1.02 to 1.71). At 5 years, more patients in the TAVR group than in the surgery group had at least mild paravalvular aortic regurgitation (33.3% vs. 6.3%). Repeat hospitalizations were more frequent after TAVR than after surgery (33.3% vs. 25.2%), as were aortic-valve reinterventions (3.2% vs. 0.8%). Improvement in health status at 5 years was similar for TAVR and surgery. CONCLUSIONS: Among patients with aortic stenosis who were at intermediate surgical risk, there was no significant difference in the incidence of death or disabling stroke at 5 years after TAVR as compared with surgical aortic-valve replacement. (Funded by Edwards Lifesciences; PARTNER 2 ClinicalTrials.gov number, NCT01314313.).


Posted March 15th 2020

Broad immune activation underlies shared set point signatures for vaccine responsiveness in healthy individuals and disease activity in patients with lupus.

Romain Banchereau, Ph.D.
Romain Banchereau, Ph.D

Kotliarov, Y., R. Sparks, A. J. Martins, M. P. Mule, Y. Lu, M. Goswami, L. Kardava, R. Banchereau, V. Pascual, A. Biancotto, J. Chen, P. L. Schwartzberg, N. Bansal, C. C. Liu, F. Cheung, S. Moir and J. S. Tsang (2020). “Broad immune activation underlies shared set point signatures for vaccine responsiveness in healthy individuals and disease activity in patients with lupus.” Nature Medicine Feb 24. [Epub ahead of print].

Full text of this article.

Responses to vaccination and to diseases vary widely across individuals, which may be partly due to baseline immune variations. Identifying such baseline predictors of immune responses and their biological basis is of broad interest, given their potential importance for cancer immunotherapy, disease outcomes, vaccination and infection responses. Here we uncover baseline blood transcriptional signatures predictive of antibody responses to both influenza and yellow fever vaccinations in healthy subjects. These same signatures evaluated at clinical quiescence are correlated with disease activity in patients with systemic lupus erythematosus with plasmablast-associated flares. CITE-seq profiling of 82 surface proteins and transcriptomes of 53,201 single cells from healthy high and low influenza vaccination responders revealed that our signatures reflect the extent of activation in a plasmacytoid dendritic cell-type I IFN-T/B lymphocyte network. Our findings raise the prospect that modulating such immune baseline states may improve vaccine responsiveness and mitigate undesirable autoimmune disease activity.


Posted March 15th 2020

Coherence between sleep detection by actigraphy and polysomnography in a multi-center, in-patient cohort of individuals with traumatic brain injury.

Marie Dahdah, Ph.D.
Marie Dahdah, Ph.D.

Zeitzer, J. M., F. Hon, J. Whyte, K. R. Monden, J. Bogner, M. Dahdah, L. Wittine, K. R. Bell and R. Nakase-Richardson (2020). “Coherence between sleep detection by actigraphy and polysomnography in a multi-center, in-patient cohort of individuals with traumatic brain injury.” PM & R Mar 3. [Epub ahead of print].

Full text of this article.

INTRODUCTION: Sleep is increasingly recognizes as a crucial component to rapid and successful rehabilitation, especially from traumatic brain injuries (TBI). Assessment of longitudinal patterns of sleep in a hospital setting, however, are difficult and often the expertise or equipment to conduct such studies are not available. Actigraphy (wrist worn accelerometry) has been used for many years as a simple proxy measurement of sleep patterns, but its use has not been thoroughly validated in individuals with TBI. OBJECTIVE: To determine the validity of different sensitivity settings of actigraphy analysis to optimize its use as a proxy for recording sleep patterns in individuals with a traumatic brain injury (TBI). DESIGN: Comparison of actigraphy to criterion standard polysomnographic (PSG)-determination of sleep on a single overnight study. SETTING: Six rehabilitation hospitals in the TBI Model System. PARTICIPANTS: 227 consecutive, medically stable individuals with a TBI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Concordance between PSG- and actigraphy-determined sleep using different sensitivity threshold settings (low, medium, high, automated). RESULTS: Bland-Altman plots revealed increasing error with increasing amounts of wake during the sleep episode. Precision-recall statistics indicate that with less sensitive actigraphy thresholds, episodes identified as “wake” are usually ‘wake’, but many true episodes of ‘wake’ are missed. With more sensitive actigraphy thresholds, more episodes of ‘wake’ are identified, but only some of these are true episodes of ‘wake’. CONCLUSIONS: In hospitalized patients with TBI and poor sleep, actigraphy underestimates the level of sleep disruption and has poor concordance with PSG-determined sleep. Alternate methods of scoring sleep from actigraphy data are necessary in this population.


Posted March 15th 2020

Retrograde Chronic Total Occlusion Percutaneous Coronary Intervention via Saphenous Vein Graft.

James W. Choi M.D.
James W. Choi M.D.

Xenogiannis, I., F. Gkargkoulas, D. Karmpaliotis, O. Krestyaninov, D. Khelimskii, F. A. Jaffer, J. J. Khatri, D. E. Kandzari, R. M. Wyman, A. H. Doing, P. Dattilo, C. Toma, R. W. Yeh, H. Tamez, J. W. Choi, W. Jaber, H. Samady, A. M. Sheikh, S. Potluri, M. Patel, E. Mahmud, B. Elbaruni, M. P. Love, M. Koutouzis, I. Tsiafoutis, B. K. Jefferson, T. Patel, B. Uretsky, J. W. Moses, N. J. Lembo, M. Parikh, A. J. Kirtane, Z. A. Ali, A. B. Hall, M. S. Megaly, E. Vemmou, I. Nikolakopoulos, B. V. Rangan, P. W. Morley, B. Bou Dargham, S. Abdullah, S. Garcia, S. Banerjee, M. N. Burke, E. S. Brilakis and K. Alaswad (2020). “Retrograde Chronic Total Occlusion Percutaneous Coronary Intervention via Saphenous Vein Graft.” JACC Cardiovasc Interv 13(4): 517-526.

Full text of this article.

OBJECTIVES: The aim of this study was to examine the use of saphenous vein grafts (SVGs) for retrograde crossing during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). BACKGROUND: The use of SVGs for retrograde crossing during CTO PCI has received limited study. METHODS: A total of 1,615 retrograde CTO PCIs performed between 2012 and 2019 at 25 centers were examined. Clinical, angiographic, and technical characteristics and procedural outcomes were compared among retrograde cases via SVGs (SVG group) versus other collateral vessels (non-SVG group). RESULTS: Retrograde CTO PCI via SVGs was performed in 189 cases (12%). Patients in the SVG group were older (mean age 70 +/- 9 years vs. 64 +/- 10 years; p < 0.01) and had higher rates of prior myocardial infarction (62% vs. 51%; p < 0.01) and prior PCI (81% vs. 70%; p < 0.01). They were more likely to have moderate or severe calcification (81% vs. 65%; p < 0.01) and moderate or severe tortuosity (53% vs. 44%; p = 0.02) and had similar J-CTO (Multicenter CTO Registry in Japan) scores (3.2 +/- 1.0 vs. 3.1 +/- 1.1; p = 0.13) but higher PROGRESS-CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) scores (4.7 +/- 1.7 vs. 3.1 +/- 1.1; p < 0.01). Technical (85% vs. 78%; p = 0.04) and procedural (81% vs. 74%; p = 0.04) success rates were higher in the SVG group, with no difference in in-hospital major adverse events (6.4% vs. 4.4%; p = 0.22). Contrast volume was lower in the SVG group (225 ml [173 to 325 ml] vs. 292 ml [202 to 400 ml]; p < 0.01). CONCLUSIONS: Use of SVGs for retrograde crossing is associated with higher rates of technical and procedural success and similar rates of in-hospital major adverse cardiac events compared with retrograde CTO PCI via other collateral vessels.