Baylor Research Institute

Nakase-Richardson, R., M. N. Dahdah, E. Almeida, P. Ricketti, M. A. Silva, K. Calero, U. Magalang and D. J. Schwartz (2020). “Concordance between current American Academy of Sleep Medicine and Centers for Medicare and Medicare scoring criteria for obstructive sleep apnea in hospitalized persons with traumatic brain injury: a VA TBI Model System study.” J Clin Sleep Med 16(6): 879-888.

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STUDY OBJECTIVES: The objective of this study was to compare obstructive sleep apnea (OSA), demographic, and traumatic brain injury (TBI) characteristics across the American Academy of Sleep Medicine (AASM) and Centers for Medicare and Medicare (CMS) scoring rules in moderate to severe TBI undergoing inpatient neurorehabilitation. METHODS: This is a secondary analysis from a prospective clinical trial of sleep apnea at 6 TBI Model System study sites (n = 248). Scoring was completed by a centralized center using both the AASM and CMS criteria for OSA. Hospitalization and injury characteristics were abstracted from the medical record, and demographics were obtained by interview by trained research assistants using TBI Model System standard procedures. RESULTS: OSA was prevalent using the AASM (66%) and CMS (41.5%) criteria with moderate to strong agreement (weighted κ = 0.64; 95% confidence interval = 0.58-0.70). Significant differences were observed for participants meeting AASM and CMS criteria (concordant group) compared with those meeting criteria for AASM but not CMS (discordant group). At an apnea-hypopnea index ≥ 5 events/h, the discordant group (n = 61) had lower Emergency Department Glasgow Coma Scale Scores consistent with greater injury severity (median, 5 vs 13; P = .0050), younger age (median, 38 vs 58; P < .0001), and lower body mass index (median, 22.1 vs 24.8; P = .0007) compared with the concordant group (n = 103). At an apnea-hypopnea index ≥ 15 events/h, female sex but no other differences were noted, possibly because of the smaller sample size. CONCLUSIONS: The underestimation of sleep apnea using CMS criteria is consistent with prior literature; however, this is the first study to report the impact of the criteria in persons with moderate to severe TBI during a critical stage of neural recovery. Management of comorbidities in TBI has become an increasing focus for optimizing TBI outcomes. Given the chronic morbidity after moderate to severe TBI, the impact of CMS policy for OSA diagnosis for persons with chronic disability and young age are considerable.

Womack, K. B., R. Dubiel, L. Callender, C. Dunklin, M. Dahdah, T. S. Harris, Devous Md, Sr., S. B. Juengst, K. Bell, R. Diaz-Arrastia and K. Ding (2020). “(123)I-Iofluopane Single-Photon Emission Computed Tomography as an Imaging Biomarker of Pre-Synaptic Dopaminergic System after Moderate-to-Severe Traumatic Brain Injury.” J Neurotrauma June 3. [Epub ahead of print].

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Dopaminergic (DA) system function is frequently disrupted after traumatic brain injury (TBI). However, published interventions that target the DA system with the hope of enhancing functional outcomes are inconclusive, partially because of the lack of DA signaling biomarkers that can be used to select patients likely to benefit from DA-directed therapies or to monitor treatment efficacy. The aim of this study was to evaluate the feasibility of using (123)I-iofluopane single-photon emission computerized tomography (SPECT) to assess pre-synaptic DA system dysfunction after severe TBI. Eighteen patients with severe TBI were enrolled in this study. (123)I-iofluopane SPECT imaging was performed at baseline and again 2.5 h after a single dose of methylphenidate (MP) administered enterally. DA transporter (DAT) specific binding ratio (SBR) before and after MP was measured. Functional outcomes included the Disability Rating Scale, JFK Coma Recovery Scale-Revised, Functional Independence Measure, and Functional Assessment Measure. Thirteen of 18 patients completed the study. Average time from injury to SPECT scan was 48 days (standard deviation [SD], 24 days; median, 31). Baseline ioflupane striatal SBR was 1.51 ± 0.46 (median, 1.67). A 43.1% (SD, 16; median, 46.5) displacement of ioflupane from pre-synaptic DAT was observed after MP administration. Baseline SBR positively correlated with functional status at baseline and 4 weeks after completion of the study. Serum MP levels correlated with relative change in SBR (r(s) = 0.60; p = 0.04). Our findings suggest that (123)I-iofluopane SPECT is a promising tool to determine the severity of pre-synaptic DA terminal disruption and for monitoring pharmacokinetics and pharmacodynamics of therapeutic interventions targeting the DA system.

Upchurch, K., M. Wiest, J. Cardenas, J. Skinner, D. Nattami, B. Lanier, M. Millard, H. Joo, J. Turner and S. Oh (2020). “Whole blood transcriptional variations between responders and non-responders in asthma patients receiving omalizumab.” Clin Exp Allergy May 29. [Epub ahead of print].

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BACKGROUND: Anti-IgE (omalizumab) has been used for the treatment of moderate-to-severe asthma that is not controlled by inhaled steroids. Despite its success, it does not always provide patients with significant clinical benefits. OBJECTIVE: To investigate transcriptional variations between omalizumab responders and non-responders and to study the mechanisms of action of omalizumab. METHODS: The whole blood transcriptomes of moderate-to-severe adult asthma patients (N=45: 34 responders and 11 non-responders) were analyzed over the course of omalizumab treatment. Non-asthmatic healthy controls (N=17) were used as controls. RESULTS: Transcriptome variations between responders and non-responders were identified using genes significant (FDR<0.05) in at least one comparison of each patient response status and time point compared to control subjects. Using gene ontology and network analysis, eight clusters of genes were identified. Longitudinal analyses of individual clusters revealed that responders could maintain changes induced with omalizumab treatment and become more similar to the control subjects, while non-responders tend to remain more similar to their pre-treatment baseline. Further analysis of an inflammatory gene cluster revealed that genes associated with neutrophil/eosinophil activities were upregulated in non-responders and, more importantly, omalizumab did not significantly alter their expression levels. The application of modular analysis supported our findings and further revealed variations between responders and non-responders. CONCLUSION & CLINICAL RELEVANCE: This study provides not only transcriptional variations between omalizumab responders and non-responders, but also molecular insights for controlling asthma by omalizumab.

Nakase-Richardson, R., D. J. Schwartz, J. M. Ketchum, L. Drasher-Phillips, M. N. Dahdah, K. R. Monden, K. Bell, J. Hoffman, J. Whyte, J. Bogner, K. Calero and U. Magalang (2020). “Comparison of diagnostic sleep studies in hospitalized neurorehabilitation patients with moderate to severe traumatic brain injury.” Chest May 6;S0012-3692(20)30863-1. [Epub ahead of print].

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BACKGROUND: Obstructive sleep apnea is prevalent during a time of critical neural repair following traumatic brain injury (TBI). The diagnostic utility of existing sleep studies is needed to inform clinical management during acute recovery from TBI. RESEARCH QUESTION: This study aimed to evaluate the non-inferiority and diagnostic accuracy of a portable Level 3 sleep study relative to Level 1 polysomnography in hospitalized neurorehabilitation patients with traumatic brain injury. STUDY DESIGN: and Methods: This is a prospective clinical trial conducted at six TBI Model System study sites between 05/2017 and 02/2019. Of 896 admissions, 449 were screened and eligible for the trial with 345 consented. Additional screening left 263 eligible for and completing simultaneous administration of both Level 1 and 3 sleep studies with final analyses completed on n=214 (median age=42; ED Glasgow Coma Scale=6; time to PSG=52 days). RESULTS: Agreement was moderate to strong (weighted kappa = 0.78, 95% CI = 0.72, 0.83) with the misclassification commonly occurring with mild sleep apnea due to underestimation of AHI. A majority of those with moderate to severe sleep apnea were correctly classified (n=54/72). Non-inferiority was not demonstrated: the minimum tolerable specificity of 0.5 was achieved across all AHI cutoff scores (LCL range = 0.807-0.943) but the minimum tolerable sensitivity of 0.8 was not (LCL range = 0.665-0.764). INTERPRETATION: While the non-inferiority of Level 3 portable diagnostic testing relative to Level 1 was not established, there was strong agreement across sleep apnea indices. A majority of those with moderate to severe sleep apnea were correctly identified; however, there was risk of misclassification with Level 3 sleep studies underestimating disease severity for those with moderate to severe AHI and disease presence for those with mild AHI during early TBI neurorehabilitation.

Mistry, P., M. Balwani, D. Barbouth, T. A. Burrow, E. I. Ginns, O. Goker-Alpan, G. A. Grabowski, R. V. Kartha, P. S. Kishnani, H. Lau, C. U. Lee, G. Lopez, G. Maegawa, S. Packman, C. Prada, B. Rosenbloom, T. R. Lal, R. Schiffmann, N. Weinreb and E. Sidransky (2020). “Gaucher disease and SARS-CoV-2 infection: Emerging management challenges.” Mol Genet Metab 130(3): 164-169.

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The 2020 SARS-CoV-2 pandemic has introduced many unanticipated challenges related to the treatment and support of patients with rare disease. Like with GD, other inborn errors of metabolism likely have unique aspects that must be considered during these uncertain times. Prospective plans for patient management and for collecting and communicating disease parameters real-time are essential for providing optimal care during the current pandemic and potentially in the future. [No abstract; excerpt from article].