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 November 15th 2019

Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial.

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

Thuijs, D., A. P. Kappetein, P. W. Serruys, F. W. Mohr, M. C. Morice, M. J. Mack, D. R. Holmes, Jr., N. Curzen, P. Davierwala, T. Noack, M. Milojevic, K. D. Dawkins, B. R. da Costa, P. Juni and S. J. Head (2019). “Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial.” Lancet 394(10206): 1325-1334.

Full text of this article.

BACKGROUND: The Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) trial was a non-inferiority trial that compared percutaneous coronary intervention (PCI) using first-generation paclitaxel-eluting stents with coronary artery bypass grafting (CABG) in patients with de-novo three-vessel and left main coronary artery disease, and reported results up to 5 years. We now report 10-year all-cause death results. METHODS: The SYNTAX Extended Survival (SYNTAXES) study is an investigator-driven extension of follow-up of a multicentre, randomised controlled trial done in 85 hospitals across 18 North American and European countries. Patients with de-novo three-vessel and left main coronary artery disease were randomly assigned (1:1) to the PCI group or CABG group. Patients with a history of PCI or CABG, acute myocardial infarction, or an indication for concomitant cardiac surgery were excluded. The primary endpoint of the SYNTAXES study was 10-year all-cause death, which was assessed according to the intention-to-treat principle. Prespecified subgroup analyses were performed according to the presence or absence of left main coronary artery disease and diabetes, and according to coronary complexity defined by core laboratory SYNTAX score tertiles. This study is registered with ClinicalTrials.gov, NCT03417050. FINDINGS: From March, 2005, to April, 2007, 1800 patients were randomly assigned to the PCI (n=903) or CABG (n=897) group. Vital status information at 10 years was complete for 841 (93%) patients in the PCI group and 848 (95%) patients in the CABG group. At 10 years, 244 (27%) patients had died after PCI and 211 (24%) after CABG (hazard ratio 1.17 [95% CI 0.97-1.41], p=0.092). Among patients with three-vessel disease, 151 (28%) of 546 had died after PCI versus 113 (21%) of 549 after CABG (hazard ratio 1.41 [95% CI 1.10-1.80]), and among patients with left main coronary artery disease, 93 (26%) of 357 had died after PCI versus 98 (28%) of 348 after CABG (0.90 [0.68-1.20], pinteraction=0.019). There was no treatment-by-subgroup interaction with diabetes (pinteraction=0.66) and no linear trend across SYNTAX score tertiles (ptrend=0.30). INTERPRETATION: At 10 years, no significant difference existed in all-cause death between PCI using first-generation paclitaxel-eluting stents and CABG. However, CABG provided a significant survival benefit in patients with three-vessel disease, but not in patients with left main coronary artery disease. FUNDING: German Foundation of Heart Research (SYNTAXES study, 5-10-year follow-up) and Boston Scientific Corporation (SYNTAX study, 0-5-year follow-up).


Posted November 15th 2019

Randomized Trial of Medical versus Surgical Treatment for Refractory Heartburn.

Stuart Spechler M.D.
Stuart Spechler M.D.

Spechler, S. J., J. G. Hunter, K. M. Jones, R. Lee, B. R. Smith, H. Mashimo, V. M. Sanchez, K. B. Dunbar, T. H. Pham, U. K. Murthy, T. Kim, C. S. Jackson, J. M. Wallen, E. C. von Rosenvinge, J. P. Pearl, L. Laine, A. W. Kim, A. M. Kaz, R. P. Tatum, Z. F. Gellad, S. Lagoo-Deenadayalan, J. H. Rubenstein, A. A. Ghaferi, W. K. Lo, R. S. Fernando, B. S. Chan, S. C. Paski, D. Provenzale, D. O. Castell, D. Lieberman, R. F. Souza, W. D. Chey, S. R. Warren, A. Davis-Karim, S. D. Melton, R. M. Genta, T. Serpi, K. Biswas and G. D. Huang (2019). “Randomized Trial of Medical versus Surgical Treatment for Refractory Heartburn.” New England Journal of Medicine 381(16): 1513-1523.

Full text of this article.

BACKGROUND: Heartburn that persists despite proton-pump inhibitor (PPI) treatment is a frequent clinical problem with multiple potential causes. Treatments for PPI-refractory heartburn are of unproven efficacy and focus on controlling gastroesophageal reflux with reflux-reducing medication (e.g., baclofen) or antireflux surgery or on dampening visceral hypersensitivity with neuromodulators (e.g., desipramine). METHODS: Patients who were referred to Veterans Affairs (VA) gastroenterology clinics for PPI-refractory heartburn received 20 mg of omeprazole twice daily for 2 weeks, and those with persistent heartburn underwent endoscopy, esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance-pH monitoring. If patients were found to have reflux-related heartburn, we randomly assigned them to receive surgical treatment (laparoscopic Nissen fundoplication), active medical treatment (omeprazole plus baclofen, with desipramine added depending on symptoms), or control medical treatment (omeprazole plus placebo). The primary outcome was treatment success, defined as a decrease of 50% or more in the Gastroesophageal Reflux Disease (GERD)-Health Related Quality of Life score (range, 0 to 50, with higher scores indicating worse symptoms) at 1 year. RESULTS: A total of 366 patients (mean age, 48.5 years; 280 men) were enrolled. Prerandomization procedures excluded 288 patients: 42 had relief of their heartburn during the 2-week omeprazole trial, 70 did not complete trial procedures, 54 were excluded for other reasons, 23 had non-GERD esophageal disorders, and 99 had functional heartburn (not due to GERD or other histopathologic, motility, or structural abnormality). The remaining 78 patients underwent randomization. The incidence of treatment success with surgery (18 of 27 patients, 67%) was significantly superior to that with active medical treatment (7 of 25 patients, 28%; P = 0.007) or control medical treatment (3 of 26 patients, 12%; P<0.001). The difference in the incidence of treatment success between the active medical group and the control medical group was 16 percentage points (95% confidence interval, -5 to 38; P = 0.17). CONCLUSIONS: Among patients referred to VA gastroenterology clinics for PPI-refractory heartburn, systematic workup revealed truly PPI-refractory and reflux-related heartburn in a minority of patients. For that highly selected subgroup, surgery was superior to medical treatment. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT01265550.).


Posted November 15th 2019

Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction.

Milton Packer M.D.
Milton Packer M.D.

Solomon, S. D., J. J. V. McMurray, I. S. Anand, J. Ge, C. S. P. Lam, A. P. Maggioni, F. Martinez, M. Packer, M. A. Pfeffer, B. Pieske, M. M. Redfield, J. L. Rouleau, D. J. van Veldhuisen, F. Zannad, M. R. Zile, A. S. Desai, B. Claggett, P. S. Jhund, S. A. Boytsov, J. Comin-Colet, J. Cleland, H. D. Dungen, E. Goncalvesova, T. Katova, J. F. Kerr Saraiva, M. Lelonek, B. Merkely, M. Senni, S. J. Shah, J. Zhou, A. R. Rizkala, J. Gong, V. C. Shi and M. P. Lefkowitz (2019). “Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction.” New England Journal of Medicine 381(17): 1609-1620.

Full text of this article.

BACKGROUND: The angiotensin receptor-neprilysin inhibitor sacubitril-valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients with heart failure and reduced ejection fraction. The effect of angiotensin receptor-neprilysin inhibition in patients with heart failure with preserved ejection fraction is unclear. METHODS: We randomly assigned 4822 patients with New York Heart Association (NYHA) class II to IV heart failure, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The primary outcome was a composite of total hospitalizations for heart failure and death from cardiovascular causes. Primary outcome components, secondary outcomes (including NYHA class change, worsening renal function, and change in Kansas City Cardiomyopathy Questionnaire [KCCQ] clinical summary score [scale, 0 to 100, with higher scores indicating fewer symptoms and physical limitations]), and safety were also assessed. RESULTS: There were 894 primary events in 526 patients in the sacubitril-valsartan group and 1009 primary events in 557 patients in the valsartan group (rate ratio, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P = 0.06). The incidence of death from cardiovascular causes was 8.5% in the sacubitril-valsartan group and 8.9% in the valsartan group (hazard ratio, 0.95; 95% CI, 0.79 to 1.16); there were 690 and 797 total hospitalizations for heart failure, respectively (rate ratio, 0.85; 95% CI, 0.72 to 1.00). NYHA class improved in 15.0% of the patients in the sacubitril-valsartan group and in 12.6% of those in the valsartan group (odds ratio, 1.45; 95% CI, 1.13 to 1.86); renal function worsened in 1.4% and 2.7%, respectively (hazard ratio, 0.50; 95% CI, 0.33 to 0.77). The mean change in the KCCQ clinical summary score at 8 months was 1.0 point (95% CI, 0.0 to 2.1) higher in the sacubitril-valsartan group. Patients in the sacubitril-valsartan group had a higher incidence of hypotension and angioedema and a lower incidence of hyperkalemia. Among 12 prespecified subgroups, there was suggestion of heterogeneity with possible benefit with sacubitril-valsartan in patients with lower ejection fraction and in women. CONCLUSIONS: Sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among patients with heart failure and an ejection fraction of 45% or higher. (Funded by Novartis; PARAGON-HF ClinicalTrials.gov number, NCT01920711.).


Posted November 15th 2019

Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma.

Charles L. Cowey M.D.
Charles L. Cowey M.D.

Larkin, J., V. Chiarion-Sileni, R. Gonzalez, J. J. Grob, P. Rutkowski, C. D. Lao, C. L. Cowey, D. Schadendorf, J. Wagstaff, R. Dummer, P. F. Ferrucci, M. Smylie, D. Hogg, A. Hill, I. Marquez-Rodas, J. Haanen, M. Guidoboni, M. Maio, P. Schoffski, M. S. Carlino, C. Lebbe, G. McArthur, P. A. Ascierto, G. A. Daniels, G. V. Long, L. Bastholt, J. I. Rizzo, A. Balogh, A. Moshyk, F. S. Hodi and J. D. Wolchok (2019). “Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma.” New England Journal of Medicine 381(16): 1535-1546.

Full text of this article.

BACKGROUND: Nivolumab plus ipilimumab or nivolumab alone resulted in longer progression-free and overall survival than ipilimumab alone in a trial involving patients with advanced melanoma. We now report 5-year outcomes in the trial. METHODS: We randomly assigned patients with previously untreated advanced melanoma to receive one of the following regimens: nivolumab (at a dose of 1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram every 2 weeks); nivolumab (3 mg per kilogram every 2 weeks) plus ipilimumab-matched placebo; or ipilimumab (3 mg per kilogram every 3 weeks for four doses) plus nivolumab-matched placebo. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group, as compared with the ipilimumab group. RESULTS: At a minimum follow-up of 60 months, the median overall survival was more than 60.0 months (median not reached) in the nivolumab-plus-ipilimumab group and 36.9 months in the nivolumab group, as compared with 19.9 months in the ipilimumab group (hazard ratio for death with nivolumab plus ipilimumab vs. ipilimumab, 0.52; hazard ratio for death with nivolumab vs. ipilimumab, 0.63). Overall survival at 5 years was 52% in the nivolumab-plus-ipilimumab group and 44% in the nivolumab group, as compared with 26% in the ipilimumab group. No sustained deterioration of health-related quality of life was observed during or after treatment with nivolumab plus ipilimumab or with nivolumab alone. No new late toxic effects were noted. CONCLUSIONS: Among patients with advanced melanoma, sustained long-term overall survival at 5 years was observed in a greater percentage of patients who received nivolumab plus ipilimumab or nivolumab alone than in those who received ipilimumab alone, with no apparent loss of quality of life in the patients who received regimens containing nivolumab. (Funded by Bristol-Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).


Posted November 15th 2019

The Changing Paradigm of Ethics in Uterus Transplantation: A Systematic Review.

Liza Johannesson, M.D.
Liza Johannesson, M.D.

Ngaage, L. M., S. Ike, A. Elegbede, C. J. Vercler, S. Gebran, F. Liang, E. M. Rada, C. Cooney, G. Brandacher, R. J. Redett, L. Johannesson and Y. M. Rasko (2019). “The Changing Paradigm of Ethics in Uterus Transplantation: A Systematic Review.” Transplant International Nov 1. [Epub ahead of print].

Full text of this article.

BACKGROUND: The first uterus transplantation was performed in 2000. As key milestones are reached (longlasting graft survival in 2011, and first birth from a transplanted womb in 2014), the ethical debate around uterus transplant evolves. METHODS: We performed a systematic review of articles on uterus transplantation. Ethical themes were extracted and categorised according to four bioethical principles. Papers were divided into time periods separated by key events in uterus transplant history: Phase I (first technical achievement, 2002-11), Phase II (clinical achievement, 2012-14), and Phase III (after the first childbirth, 2015-18). RESULTS: Eighty-one articles were included. The majority of ethics papers were published in Phase III (65%, p<0.0001), i.e. after the first birth. 80% of papers discussed non-maleficence making it the most discussed principle. The first birth acted as a pivotal point: non-maleficence was discussed by a lower proportion of articles (p=0.0073), as was beneficence (p=0.0309). However, discussion of justice increased to become the most discussed principle of the time period (p=0.0085). CONCLUSIONS: The ethical debate surrounding uterus transplantation has evolved around landmark events that signify scientific progress. As safety and efficacy become evident, the focus of ethical debate shifts from clinical equipoise to socioeconomic challenges and equitable access to uterus transplantation.