Baylor Research Institute

Schiattarella, G. G., A. Sannino, E. Toscano, F. Cattaneo, B. Trimarco, G. Esposito and C. Perrino (2016). “Cardiovascular effects of histone deacetylase inhibitors epigenetic therapies: Systematic review of 62 studies and new hypotheses for future research.” Int J Cardiol 219: 396-403.

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Based on the available published clinical trials reporting cardiovascular effects of HDACi therapy in cancer patients, 62 studies for a total patient population of 3268 were included to perform a systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) requirements. A further analysis was conducted to evaluate cardiovascular effects of the different drugs among the HDACi class. Overall, only a minority of studies reported cardiovascular effect of HDACi, and showed mild but frequent cardiovascular side effects after HDACi treatment in cancer patients.

Schiffmann, R. and B. Banwell (2016). “Brain mri and motor function in leukodystrophies.” Neurology 87(8): 748-749.

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There is a need to develop clinical outcome measures for future treatment trials, particularly for pediatric studies and for studies of rare disorders for which such outcome metrics are neither currently well-defined nor validated.1 Patient-reported outcome measures should reflect outcomes that are meaningful to patient-perceived quality of life and sensitive to patient-identified change over time. Physician-reported outcome measures are typically quantifiable and consistently applied across multiple study sites by different investigators, which requires that the metrics be well-defined and that investigator training be rigorous. While clinically relevant outcomes are considered the “gold standard,” and are often the mandated primary outcome of federally funded research, many slowly progressive disorders do not demonstrate clinically apparent change over the time course of a clinical trial. Thus, there is a need for biomarkers, such as neuroimaging measures, that may be more sensitive to change over the typical 2- to 5-year period of a trial. Key to the applicability of such surrogate measures, however, is that they ultimately correlate with changes in neurologic function.

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].

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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.

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.

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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.

Gensous, N., N. Schmitt, C. Richez, H. Ueno and P. Blanco (2016). “T follicular helper cells, interleukin-21 and systemic lupus erythematosus.” Rheumatology (Oxford): 2016 Aug [Epub ahead of print].

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SLE is a chronic systemic autoimmune disease characterized by a breakdown of tolerance to nuclear antigens and generation of high-affinity pathogenic autoantibodies. These autoantibodies form, with autoantigens, immune complexes that are involved in organ and tissue damages. Understanding how the production of these pathogenic autoantibodies arises is of prime importance. T follicular helper cells (Tfh) and IL-21 have emerged as central players in this process. This article reviews the pathogenic role of Tfh cells and IL-21 in SLE.