Baylor Research Institute

Henry, C., C. Boethel, L. A. Copeland, S. Ghamande, A. C. Arroliga and H. D. White (2017). “Clinical utility of testing for legionella pneumonia in central texas.” Ann Am Thorac Soc 14(1): 65-69.

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RATIONALE: Legionella pneumophila is an uncommon cause of community-acquired pneumonia in the south central region of the United States, and regular testing may not be cost effective in areas of low incidence. OBJECTIVES: To evaluate the incidence of Legionella in central Texas and to determine the cost effectiveness of Legionella urinary antigen testing. METHODS: We performed a single-center retrospective cohort study of patients admitted with pneumonia between January 2001 and December 2013. Patients were identified by Binax Legionella urinary antigen and International Classification of Disease, Ninth Revision codes. Demographic characteristics and clinical history of the confirmed Legionella pneumonia cases were obtained by chart review. Descriptive statistics were used to describe patient characteristics. MEASUREMENTS AND MAIN RESULTS: Over 12 years, 5,807 patients with 11,377 admissions for pneumonia were tested for Legionella urinary antigen. A positive Legionella urinary antigen was found in 17 patients. Cumulative incidence during the study period was 0.23%. Among the Legionella-positive patients, intensive care unit admission and median length of stay were 58.8% and 8.5 days, respectively. Most patients (64.7%) met American Thoracic Society criteria for severe pneumonia. All patients empirically received either a macrolide or fluoroquinolone covering Legionella. There were two in-hospital and three total 90-day deaths in those with a positive urinary antigen. The estimated cost of screening this population with Legionella urinary antigen was $214,438 over 13 years. CONCLUSIONS: This study reveals the low incidence of Legionella pneumonia in central Texas. Use of guideline-concordant antibiotic treatment provides coverage for Legionella. We speculate that testing in a low-prevalence area would not influence outcomes or be cost effective.

Schiffmann, R., M. Fuller, L. A. Clarke and J. M. Aerts (2016). “Is it fabry disease?” Genet Med 18(12): 1181-1185.

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Fabry disease is caused by mutations in the GLA gene that lower alpha-galactosidase A activity to less than 25-30% of the mean normal level. Several GLA variants have been identified that are associated with relatively elevated residual alpha-galactosidase A. The challenge is to determine which GLA variants can cause clinical manifestations related to Fabry disease. Here, we review the various types of GLA variants and recommend that pathogenicity be considered only when associated with elevated globotriaosylceramide in disease-relevant organs and tissues as analyzed by mass spectrometry. This criterion is necessary to ensure that very costly and specific therapy is provided only when appropriate.

Desnick, R. J., N. W. Barton, S. Furbish, G. A. Grabowski, S. Karlsson, E. H. Kolodny, J. A. Medin, G. J. Murray, P. K. Mistry, M. C. Patterson, R. Schiffmann and N. J. Weinreb (2016). “Roscoe owen brady, md: Remembrances of co-investigators and colleagues.” Mol Genet Metab: 2016 Nov [Epub ahead of print].

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To celebrate the research visions and accomplishments of the late Roscoe O. Brady (1923-2016), remembrance commentaries were requested from several of his postdoctoral research fellows and colleagues. These commentaries not only reflect on the accomplishments of Dr. Brady, but they also share some of the backstories and experiences working in the Brady laboratory. They provide insights and perspectives on Brady’s research activities, and especially on his efforts to develop an effective treatment for patients with Type 1 Gaucher disease. These remembrances illuminate Brady’s efforts to implement the latest scientific advances with an outstanding team of young co-investigators to develop and demonstrate the safety and effectiveness of the first enzyme replacement therapy for a lysosomal storage disease. Brady’s pursuit and persistence in accomplishing his research objectives provide insights into this remarkably successful physician scientist who paved the way for the development of treatments for patients with other lysosomal storage diseases.

Ewing, M., G. A. Funk, A. M. Warren, N. Rapier, M. Reynolds, M. Bennett, C. Mastropieri and M. L. Foreman (2016). “Improving national trauma data bank(r) coding data reliability for traumatic injury using a prospective systems approach.” Health Informatics J 22(4): 1076-1082.

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Trauma centers manage an active Trauma Registry from which research, quality improvement, and epidemiologic information are extracted to ensure optimal care of the trauma patient. We evaluated coding procedures using the Relational Trauma Scoring System to determine the relative accuracy of the Relational Trauma Scoring System for coding diagnoses in comparison to the standard retrospective chart-based format. Charts from 150 patients admitted to a level I trauma service were abstracted using standard methods. These charts were then randomized and abstracted by trauma nurse clinicians with coding software aide. For charts scored pre-training, percent correct for the trauma nurse clinicians ranged from 52 to 64 percent, while the registrars scored 51 percent correct. After training, percentage correct for the trauma nurse clinicians increased to a range of 80-86 percent. Our research has demonstrated implementable changes that can significantly increase the accuracy of data from trauma centers.

Gideon, H. P., J. A. Skinner, N. Baldwin, J. L. Flynn and P. L. Lin (2016). “Early whole blood transcriptional signatures are associated with severity of lung inflammation in cynomolgus macaques with mycobacterium tuberculosis infection.” J Immunol 197(12): 4817-4828.

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Whole blood transcriptional profiling offers great diagnostic and prognostic potential. Although studies identified signatures for pulmonary tuberculosis (TB) and transcripts that predict the risk for developing active TB in humans, the early transcriptional changes immediately following Mycobacterium tuberculosis infection have not been evaluated. We evaluated the gene expression changes in the cynomolgus macaque model of TB, which recapitulates all clinical aspects of human M. tuberculosis infection, using a human microarray and analytics platform. We performed genome-wide blood transcriptional analysis on 38 macaques at 11 postinfection time points during the first 6 mo of M. tuberculosis infection. Of 6371 differentially expressed transcripts between preinfection and postinfection, the greatest change in transcriptional activity occurred 20-56 d postinfection, during which fluctuation of innate and adaptive immune response-related transcripts was observed. Modest transcriptional differences between active TB and latent infection were observed over the time course with substantial overlap. The pattern of module activity previously published for human active TB was similar in macaques with active disease. Blood transcript activity was highly correlated with lung inflammation (lung [18F]fluorodeoxyglucose [FDG] avidity) measured by positron emission tomography and computed tomography at early time points postinfection. The differential signatures between animals with high and low lung FDG were stronger than between clinical outcomes. Analysis of preinfection signatures of macaques revealed that IFN signatures could influence eventual clinical outcomes and lung FDG avidity, even before infection. Our data support that transcriptional changes in the macaque model are translatable to human M. tuberculosis infection and offer important insights into early events of M. tuberculosis infection.