Research Spotlight

Posted September 15th 2016

Selenium Supplementation for Prevention of Colorectal Adenomas and Risk of Associated Type 2 Diabetes.

C. Richard Boland M.D.

C. Richard Boland M.D.

Thompson, P. A., E. L. Ashbeck, D. J. Roe, L. Fales, J. Buckmeier, F. Wang, A. Bhattacharyya, C. H. Hsu, H. H. Chow, D. J. Ahnen, C. R. Boland, R. I. Heigh, D. E. Fay, S. R. Hamilton, E. T. Jacobs, M. E. Martinez, D. S. Alberts and P. Lance (2016). “Selenium supplementation for prevention of colorectal adenomas and risk of associated type 2 diabetes.” J Natl Cancer Inst 108(12): 1-10.

Full text of this article.

BACKGROUND: Selenium supplementation may help to prevent colorectal cancer; as precursors of colorectal cancer, colorectal adenomas are a surrogate for colorectal cancer. Selenium supplementation may increase risk of type 2 diabetes (T2D). METHODS: The Selenium and Celecoxib (Sel/Cel) Trial was a randomized, placebo controlled trial of selenium 200 microg daily as selenized yeast and celecoxib 400 mg once daily, alone or together, for colorectal adenoma prevention. Men and women between age 40 and 80 years were eligible following colonoscopic removal of colorectal adenomas. The primary outcome was adenoma development. Celecoxib was suspended because of cardiovascular toxicity in other trials, but accrual continued to selenium and placebo. A total of 1621 participants were randomly assigned to selenium or placebo, of whom 1374 (84.8%) were available for analysis. All statistical tests were two-sided. RESULTS: In the respective placebo and selenium arms of 689 and 685 participants, adenoma detection after medians of 33.6 (range = 0.0-85.1 months) and 33.0 months (range = 0.0-82.6 months) were 42.8% and 44.1% (relative risk [RR] = 1.03, 95% confidence interval [CI] = 0.91 to 1.16, P = .68). In participants with baseline advanced adenomas, adenoma recurrence was reduced by 18% with selenium (RR = 0.82, 95% CI = 0.71 to 0.96, P = .01). In participants receiving selenium, the hazard ratio for new-onset T2D was 1.25 (95% CI = 0.74 to 2.11, P = .41), with a statistically significantly increased risk of selenium-associated T2D among older participants (RR = 2.21; 95% CI = 1.04 to 4.67, P = .03). CONCLUSIONS: Overall, selenium did not prevent colorectal adenomas and showed only modest benefit in patients with baseline advanced adenomas. With limited benefit and similar increases in T2D to other trials, selenium is not recommended for preventing colorectal adenomas in selenium-replete individuals.


Posted September 15th 2016

ABT-719 for the Prevention of Acute Kidney Injury in Patients Undergoing High-Risk Cardiac Surgery: A Randomized Phase 2b Clinical Trial.

Peter McCullough M.D.

Peter McCullough M.D.

McCullough, P. A., E. Bennett-Guerrero, L. S. Chawla, T. Beaver, R. L. Mehta, B. A. Molitoris, A. Eldred, G. Ball, H. J. Lee, M. T. Houser and S. Khan (2016). “Abt-719 for the prevention of acute kidney injury in patients undergoing high-risk cardiac surgery: A randomized phase 2b clinical trial.” J Am Heart Assoc 5(8): 1-11.

Full text of this article.

BACKGROUND: Patients undergoing cardiac surgeries with cardiopulmonary bypass (on-pump) have a high risk for acute kidney injury (AKI). We tested ABT-719, a novel alpha-melanocyte-stimulating hormone analog, for prevention of AKI in postoperative cardiac surgery patients. METHODS AND RESULTS: This phase 2b randomized, double-blind, placebo-controlled trial included adult patients with stable renal function undergoing high-risk on-pump cardiac surgery in the United States and Denmark. Participants received placebo (n=61) or cumulative ABT-719 doses of 800 (n=59), 1600 (n=61), or 2100 mug/kg (n=59). Primary outcome was development of AKI based on Acute Kidney Injury Network (AKIN) criteria, measured utilizing preoperative creatinine value and maximum value within 48 hours and urine output within the first 42 hours postsurgery. Secondary outcomes included incidence of AKI based on maximal changes from baseline in novel AKI biomarkers over a 72-hour period after clamp release and length of intensive care unit stays through 90 days postsurgery. A total of 65.5%, 62.7%, and 69.6% of patients in the 800-, 1600-, and 2100-mug/kg groups, respectively, developed AKI (stages 1, 2, and 3 combined) versus 65.5% in the placebo group (for each pair-wise comparison with placebo, P=0.966, 0.815, and 0.605, respectively). Adverse events occurred at a similar rate in all treatment groups. CONCLUSIONS: ABT-719 treatment did not lower AKI incidence using AKIN criteria, influence the elevations of novel biomarkers, or change 90-day outcomes in patients after cardiac surgery.


Posted September 15th 2016

Update on Leukodystrophies: A Historical Perspective and Adapted Definition.

Raphael Schiffmann M.D.

Raphael Schiffmann M.D.

Kevelam, S. H., M. E. Steenweg, S. Srivastava, G. Helman, S. Naidu, R. Schiffmann, S. Blaser, A. Vanderver, N. I. Wolf and M. S. van der Knaap (2016). “Update on leukodystrophies: A historical perspective and adapted definition.” Neuropediatrics: 2016 Aug [Epub ahead of print].

Full text of this article.

Leukodystrophies were defined in the 1980s as progressive genetic disorders primarily affecting myelin of the central nervous system. At that time, a limited number of such disorders and no associated gene defects were known. The majority of the leukodystrophy patients remained without a specific diagnosis. In the following two decades, magnetic resonance imaging pattern recognition revolutionized the field, allowing the definition of numerous novel leukodystrophies. Their genetic defects were usually identified through genetic linkage studies. This process required substantial numbers of cases and many rare disorders remained unclarified. As recently as 2010, 50% of the leukodystrophy patients remained unclassified. Since 2011, whole-exome sequencing has resulted in an exponential increase in numbers of known, distinct, genetically determined, ultrarare leukodystrophies. We performed a retrospective study concerning three historical cohorts of unclassified leukodystrophy patients and found that currently at least 80% of the patients can be molecularly classified. Based on the original definition of the leukodystrophies, numerous defects in proteins important in myelin structure, maintenance, and function were expected. By contrast, a high percentage of the newly identified gene defects affect the housekeeping process of mRNA translation, shedding new light on white matter pathobiology and requiring adaptation of the leukodystrophy definition.


Posted September 15th 2016

Effect of Transcatheter Mitral Annuloplasty With the Cardioband Device on 3-Dimensional Geometry of the Mitral Annulus.

Giovanni Filardo Ph.D.

Giovanni Filardo Ph.D.

Arsalan, M., E. Agricola, O. Alfieri, S. Baldus, A. Colombo, G. Filardo, C. Hammerstingl, M. Huntgeburth, F. Kreidel, K. H. Kuck, G. LaCanna, D. Messika-Zeitoun, F. Maisano, G. Nickenig, B. D. Pollock, B. J. Roberts, A. Vahanian and P. A. Grayburn (2016). “Effect of transcatheter mitral annuloplasty with the cardioband device on 3-dimensional geometry of the mitral annulus.” Am J Cardiol 118(5): 744-749.

Full text of this article.

This study was performed to assess the acute intraprocedural effects of transcatheter direct mitral annuloplasty using the Cardioband device on 3-dimensional (3D) anatomy of the mitral annulus. Of 45 patients with functional mitral regurgitation (MR) enrolled in a single arm, multicenter, prospective trial, 22 had complete pre- and post-implant 3D transesophageal echocardiography (TEE) images stored in native data format that allowed off-line 3D reconstruction. Images with the highest volume rate and best image quality were selected for analysis. Multiple measurements of annular geometry were compared from baseline to post-implant using paired t tests with Bonferroni correction to account for multiple comparisons. The device was successfully implanted in all patients, and MR was reduced to moderate in 2 patients, mild in 17 patients, and trace in 3 patients after final device cinching. Compared with preprocedural TEE, postprocedural TEE showed statistically significantly reductions in annular circumference (137 +/- 15 vs 128 +/- 17 mm; p = 0.042), intercommissural distance (42.4 +/- 4.3 vs 38.6 +/- 4.4 mm; p = 0.029), anteroposterior distance (40.0 +/- 5.4 vs 37.0 +/- 5.7 mm; p = 0.025), and aortic-mitral angle (117 +/- 8 degrees vs 112 +/- 8 degrees ; p = 0.032). This study demonstrates that transcatheter direct mitral annuloplasty with the Cardioband device results in acute remodeling of the mitral annulus with successful reduction of functional MR.


Posted September 15th 2016

Evaluation of a Physical Activity Behavior Change Program for Individuals With a Brain Injury.

Simon Driver Ph.D.

Simon Driver Ph.D.

Driver, S. and A. Woolsey (2016). “Evaluation of a physical activity behavior change program for individuals with a brain injury.” Arch Phys Med Rehabil 97(9 Suppl): S194-200.

Full text of this article.

OBJECTIVE: To investigate the effectiveness of a physical activity intervention for use within a comprehensive outpatient rehabilitation program for individuals with brain injury. DESIGN: Quasi-experimental comparison group design with 3-month follow-up. SETTING: Comprehensive outpatient rehabilitation clinic that is a transitional setting between acute inpatient rehabilitation and community dwelling. PARTICIPANTS: Individuals (N=47) with a brain injury were enrolled into either the intervention (n=22; 8 women, 14 men; mean age, 48.68y) or control group (n=25; 9 women, 16 men; mean age, 46.23y). INTERVENTION: Consisted of an 8-week informational and social/behavioral program that focused on enabling individuals to become independently active. The control group completed the standard of care typically available to patients in comprehensive outpatient rehabilitation. MAIN OUTCOME MEASURES: Behavioral Risk Factor Surveillance Survey self-report physical activity items, Exercise Self-Efficacy Scale, and Mayo-Portland Adaptability Inventory-4. RESULTS: The intervention group reported significantly (P<.001) greater weekly activity, self-efficacy, and rehabilitation outcomes at the completion of the program as well as at the 3-month follow-up when compared with the control group. Significantly, individuals in the experimental group reported increasing their weekly activity from 45 minutes preprogram to 72 minutes postprogram (d=2.12; 95% confidence interval, 1.78-2.52), and 67 minutes at 3-month follow-up. CONCLUSIONS: Findings suggest that the intervention may be effective in increasing the physical activity behaviors of individuals engaged in a comprehensive outpatient rehabilitation program after brain injury.