Research Spotlight

Baylor Health Sciences Library brings to you each month the latest published research from the Baylor Scott & White community. 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@baylorhealth.edu. 214-828-8989.


Posted October 15th 2018

The Name of the Dog.

Taimur Safdur M.D.

Taimur Safdur M.D.

Safder, T. (2018). “The Name of the Dog.” N Engl J Med 379(14): 1299-1301.

Full text of this article.

It was July 1, my first day of residency, and a queasy feeling lodged in my stomach as I donned my new white coat. It was different from the previous ones I’d worn — not just longer, but heavier. I was carrying in my pockets everything I thought I needed as a freshly minted doctor: my three favorite pens, a glossy Littmann Cardiology III stethoscope, copies of studies related to my patient with cirrhosis, and of course my trusty purple Sabatine’s Pocket Medicine. Before the day was over, my bodily-fluid–covered white coat would have made a fitting prop for a CSI episode, my attending physician wasn’t nearly as impressed as I’d hoped with the studies I waved in front of her, and worst of all, I had lost all three of my pens. But with the aid of my pockets, I’d gotten through. I’d played my part reasonably well most of the day, but the moment when my attending had brought me up short with a question kept replaying in my mind. During morning rounds, I had presented a patient who was admitted for chest pain after walking his dog. My attending had asked, “What was the name of his dog?” (Excerpt from text of this commentary, p. 1299-1300; no abstract available.)


Posted October 15th 2018

Transcatheter Mitral-Valve Repair in Patients with Heart Failure.

Michael J. Mack M.D.

Michael J. Mack M.D.

Stone, G. W., J. Lindenfeld, W. T. Abraham, S. Kar, D. S. Lim, J. M. Mishell, B. Whisenant, P. A. Grayburn, M. Rinaldi, S. R. Kapadia, V. Rajagopal, I. J. Sarembock, A. Brieke, S. O. Marx, D. J. Cohen, N. J. Weissman and M. J. Mack (2018). “Transcatheter Mitral-Valve Repair in Patients with Heart Failure.” N Engl J Med Sep 23. [Epub ahead of print].

Full text of this article.

BACKGROUND: Among patients with heart failure who have mitral regurgitation due to left ventricular dysfunction, the prognosis is poor. Transcatheter mitral-valve repair may improve their clinical outcomes. METHODS: At 78 sites in the United States and Canada, we enrolled patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy. Patients were randomly assigned to transcatheter mitral-valve repair plus medical therapy (device group) or medical therapy alone (control group). The primary effectiveness end point was all hospitalizations for heart failure within 24 months of follow-up. The primary safety end point was freedom from device-related complications at 12 months; the rate for this end point was compared with a prespecified objective performance goal of 88.0%. RESULTS: Of the 614 patients who were enrolled in the trial, 302 were assigned to the device group and 312 to the control group. The annualized rate of all hospitalizations for heart failure within 24 months was 35.8% per patient-year in the device group as compared with 67.9% per patient-year in the control group (hazard ratio, 0.53; 95% confidence interval [CI], 0.40 to 0.70; P<0.001). The rate of freedom from device-related complications at 12 months was 96.6% (lower 95% confidence limit, 94.8%; P<0.001 for comparison with the performance goal). Death from any cause within 24 months occurred in 29.1% of the patients in the device group as compared with 46.1% in the control group (hazard ratio, 0.62; 95% CI, 0.46 to 0.82; P<0.001). CONCLUSIONS: Among patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy, transcatheter mitral-valve repair resulted in a lower rate of hospitalization for heart failure and lower all-cause mortality within 24 months of follow-up than medical therapy alone. The rate of freedom from device-related complications exceeded a prespecified safety threshold. (Funded by Abbott; COAPT ClinicalTrials.gov number, NCT01626079.)


Posted October 15th 2018

Blinded outcomes and angina assessment of coronary bioresorbable scaffolds: 30-day and 1-year results from the ABSORB IV randomised trial.

James W. Choi M.D.

James W. Choi M.D.

Stone, G. W., S. G. Ellis, T. Gori, D. C. Metzger, B. Stein, M. Erickson, J. Torzewski, J. Williams, Jr., W. Lawson, T. M. Broderick, A. Kabour, G. Piegari, J. Cavendish, B. Bertolet, J. W. Choi, S. O. Marx, P. Genereux and D. J. Kereiakes (2018). “Blinded outcomes and angina assessment of coronary bioresorbable scaffolds: 30-day and 1-year results from the ABSORB IV randomised trial.” Lancet Sep 24. [Epub ahead of print].

Full text of this article.

BACKGROUND: Previous studies showed more adverse events with coronary bioresorbable vascular scaffolds (BVS) than with metallic drug-eluting stents (DES), although in one randomised trial angina was reduced with BVS. However, these early studies were unmasked, lesions smaller than intended for the scaffold were frequently enrolled, implantation technique was suboptimal, and patients with myocardial infarction, in whom BVS might be well suited, were excluded. METHODS: In the active-controlled, blinded, multicentre, randomised ABSORB IV trial, patients with stable coronary artery disease or acute coronary syndromes aged 18 years or older were recruited from 147 hospitals in five countries (the USA, Germany, Australia, Singapore, and Canada). Enrolled patients were randomly assigned (1:1) to receive polymeric everolimus-eluting BVS (Absorb; Abbott Vascular, Santa Clara, CA, USA) with optimised implantation technique or cobalt-chromium everolimus-eluting stents (EES; Xience; Abbott Vascular, Santa Clara, CA, USA). Randomisation was stratified by diabetic status, whether patients would have been eligible for enrolment in the previous ABSORB III trial, and site. Patients and clinical assessors were masked to randomisation. The primary endpoint was target lesion failure (cardiac death, target vessel myocardial infarction, or ischaemia-driven target lesion revascularisation) at 30 days, tested for non-inferiority with a 2.9% margin for the risk difference. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT02173379, and is closed to accrual. FINDINGS: Between Aug 15, 2014, and March 31, 2017, we screened 18 722 patients for eligibility, 2604 of whom were enrolled. 1296 patients were assigned to BVS, and 1308 patients were assigned to EES. Follow-up data at 30 days and 1 year, respectively, were available for 1288 and 1254 patients with BVS and for 1303 and 1272 patients with EES. Biomarker-positive acute coronary syndromes were present in 622 (24%) of 2602 patients, and, by angiographic core laboratory analysis, 78 (3%) of 2893 of lesions were in very small vessels. Target lesion failure at 30 days occurred in 64 (5.0%) patients assigned to BVS and 48 (3.7%) patients assigned to EES (difference 1.3%, upper 97.5% confidence limit 2.89; one-sided pnon-inferiority=0.0244). Target lesion failure at 1 year occurred in 98 (7.8%) patients assigned to BVS and 82 (6.4%) patients assigned to EES (difference 1.4%, upper 97.5% confidence limit 3.4; one-sided pnon-inferiority=0.0006). Angina, adjudicated by a central events committee at 1 year, occurred in 270 (20.3%) patients assigned to BVS and 274 (20.5%) patients assigned to EES (difference -0.3%, 95% CI -3.4% to 2.9%; one-sided pnon-inferiority=0.0008; two-sided psuperiority=0.8603). Device thrombosis within 1 year occurred in nine (0.7%) patients assigned to BVS and four (0.3%) patients assigned to EES (p=0.1586). INTERPRETATION: Polymeric BVS implanted with optimised technique in an expanded patient population resulted in non-inferior 30-day and 1-year rates of target lesion failure and angina compared with metallic DES. FUNDING: Abbott Vascular.


Posted October 15th 2018

Association Between Preoperative Proteinuria and Postoperative Acute Kidney Injury and Readmission.

Laurel A. Copeland Ph.D.

Laurel A. Copeland Ph.D.

Wahl, T. S., L. A. Graham, M. S. Morris, J. S. Richman, R. H. Hollis, C. E. Jones, K. M. Itani, T. H. Wagner, H. J. Mull, J. C. Whittle, G. L. Telford, A. K. Rosen, L. A. Copeland, E. A. Burns and M. T. Hawn (2018). “Association Between Preoperative Proteinuria and Postoperative Acute Kidney Injury and Readmission.” JAMA Surg 153(9): e182009. [Epub ahead of print Sep 19].

Full text of this article.

Importance: Proteinuria indicates renal dysfunction and is a risk factor for morbidity among medical patients, but less is understood among surgical populations. There is a paucity of studies investigating how preoperative proteinuria is associated with surgical outcomes, including postoperative acute kidney injury (AKI) and readmission. Objective: To assess preoperative urine protein levels as a biomarker for adverse surgical outcomes. Design, Setting, and Participants: A retrospective, population-based study was conducted in a cohort of patients with and without known preoperative renal dysfunction undergoing elective inpatient surgery performed at 119 Veterans Affairs facilities from October 1, 2007, to September 30, 2014. Data analysis was conducted from April 4 to December 1, 2016. Preoperative dialysis, septic, cardiac, ophthalmology, transplantation, and urologic cases were excluded. Exposures: Preoperative proteinuria as assessed by urinalysis using the closest value within 6 months of surgery: negative (0 mg/dL), trace (15-29 mg/dL), 1+ (30-100 mg/dL), 2+ (101-300 mg/dL), 3+ (301-1000 mg/dL), and 4+ (>1000 mg/dL). Main Outcomes and Measures: Primary outcome was postoperative predischarge AKI and 30-day postdischarge unplanned readmission. Secondary outcomes included any 30-day postoperative outcome. Results: Of 346676 surgeries, 153767 met inclusion criteria, with the majority including orthopedic (37%), general (29%), and vascular procedures (14%). Evidence of proteinuria was shown in 43.8% of the population (trace: 20.6%, 1+: 16.0%, 2+: 5.5%, 3+: 1.6%) with 20.4%, 14.9%, 4.3%, and 0.9%, respectively, of the patients having a normal preoperative estimated glomerular filtration rate (eGFR). In unadjusted analysis, preoperative proteinuria was significantly associated with postoperative AKI (negative: 8.6%, trace: 12%, 1+: 14.5%, 2+: 21.2%, 3+: 27.6%; P < .001) and readmission (9.3%, 11.3%, 13.3%, 15.8%, 17.5%, respectively, P < .001). After adjustment, preoperative proteinuria was associated with postoperative AKI in a dose-dependent relationship (trace: odds ratio [OR], 1.2; 95% CI, 1.1-1.3, to 3+: OR, 2.0; 95% CI, 1.8-2.2) and 30-day unplanned readmission (trace: OR, 1.0; 95% CI, 1.0-1.1, to 3+: OR, 1.3; 95% CI, 1.1-1.4). Preoperative proteinuria was associated with AKI independent of eGFR. Conclusions and Relevance: Proteinuria was associated with postoperative AKI and 30-day unplanned readmission independent of preoperative eGFR. Simple urine assessment for proteinuria may identify patients at higher risk of AKI and readmission to guide perioperative management.


Posted October 15th 2018

Acidic Bile Salts Induce Epithelial to Mesenchymal Transition via VEGF Signaling in Non-Neoplastic Barrett’s Cells.

Qiuyang D. Zhang Ph.D.

Qiuyang D. Zhang Ph.D.

Zhang, Q., A. T. Agoston, T. H. Pham, W. Zhang, X. Zhang, X. Huo, S. Peng, M. Bajpai, K. Das, R. D. Odze, S. J. Spechler and R. F. Souza (2018). “Acidic Bile Salts Induce Epithelial to Mesenchymal Transition via VEGF Signaling in Non-Neoplastic Barrett’s Cells.” Gastroenterology Sep 27. [Epub ahead of print].

Full text of this article.

BACKGROUND & AIMS: Metaplastic glands buried under squamous epithelium are frequently detected in patients with Barrett’s esophagus (BE). This sub-squamous intestinal metaplasia (SSIM) might be responsible for cancers that develop despite endoscopic surveillance, and for metaplasia recurrences after endoscopic ablation. To determine whether reflux induces BE cells to undergo epithelial to mesenchymal transition (EMT) that produces SSIM, we assessed EMT in BE cells exposed to acidic bile salts, and in rat and human esophageal tissues. METHODS: We compared markers of EMT and cell motility in transwell and 3-dimensional organotypic culture systems among dysplastic BE epithelial cell lines, nondysplastic telomerase-immortalized BE cell lines (BAR-T), and BAR-T cells exposed acutely or for 20 weeks (BEC-20W) to acidic bile salts. VEGFA was inhibited with a neutralizing antibody or CRISPR-Cas9n and VEGFR2 was inhibited with SU1498 or shRNA, and cells were analyzed by immunohistochemistry, quantitative PCR, or immunoblotting for markers of VEGF signaling and EMT; cell motility was assessed by transwell. We used immunohistochemistry and quantitative PCR to assess EMT markers in the columnar-lined esophagus of rats with surgically induced reflux esophagitis and in esophagectomy specimens from patients with BE. RESULTS: We detected features of EMT (decreased cadherin 1 [CDH1]; increased fibronectin 1, vimentin, and MMP2; and increased motility) in dysplastic BE epithelial cell lines and in BEC-20W cells, but not in unexposed BAR-T cells. Acute acidic bile salt exposure induced expression of the zinc finger E-box binding homeobox 1/2 (ZEB1/2) in BAR-T cells, which reduced their expression of CDH1 and increased motility; inhibitors of VEGF signaling blocked these effects. Columnar-lined esophagus of rats with reflux esophagitis had increased expression of ZEB1/2 and decreased expression of CDH1 compared with controls. Dysplastic BE tissues also had significantly increased levels of ZEB1 and significantly decreased levels of CDH1 compared with non-dysplastic BE tissues. CONCLUSIONS: In BE cell lines, acidic bile salts induce EMT via VEGF signaling, which increases expression of ZEB1/2, repressors of CDH1. These observations suggest that reflux induces EMT in metaplastic BE tissues, which promotes development of SSIM.