Research Spotlight

Lehman, L. L., J. C. Khoury, J. M. Taylor, S. Yeramaneni, H. Sucharew, K. Alwell, C. J. Moomaw, K. Peariso, M. Flaherty, P. Khatri, J. P. Broderick, B. M. Kissela and D. O. Kleindorfer (2018). “Pediatric Stroke Rates Over 17 Years: Report From a Population-Based Study.” J Child Neurol 33(7): 463-467.

Full text of this article.

We previously published rates of pediatric stroke using our population-based Greater Cincinnati Northern Kentucky Stroke Study (GCNK) for periods July 1993-June 1994 and 1999. We report population-based rates from 2 additional study periods: 2005 and 2010. We identified all pediatric strokes for residents of the GCNK region that occurred in July 1, 1993-June 30, 1994, and calendar years 1999, 2005, and 2010. Stroke cases were ascertained by screening discharge ICD-9 codes, and verified by a physician. Pediatric stroke was defined as stroke in those <20 years of age. Stroke rates by study period, overall, by age and by race, were calculated. Eleven children died within 30 days, yielding an all-cause case fatality rate of 15.7% (95% confidence interval 1.1%, 26.4%) with 3 (27.3%) ischemic, 6 (54.5%) hemorrhagic, and 2 (18.2%) unknown stroke type. The pediatric stroke rate of 4.4 per 100 000 in the GCNK study region has not changed over 17 years.

Kearns, N. T., J. K. Peterson, L. Smurr Walters, W. T. Jackson, J. M. Miguelez and T. Ryan (2018). “Development and Psychometric Validation of Capacity Assessment of Prosthetic Performance for the Upper Limb (CAPPFUL).” Arch Phys Med Rehabil. May 16. [Epub ahead of print].

Full text of this article.

OBJECTIVES: (1) Develop a performance-based measure for adult upper limb (UL) prosthetic functioning through broad (i.e. overall performance) and functional domain-specific (e.g., control skills) assessment of commonplace activities; (2) conduct initial psychometric evaluation of the Capacity Assessment of Prosthetic Performance for the Upper Limb (CAPPFUL). DESIGN: Internal consistency of CAPPFUL and interrater reliability for task, functional domain, and full scale (sub)scores among three independent raters were estimated. Known-group validity was examined comparing scores by amputation level. Convergent validity was assessed between CAPPFUL and two hand dexterity/function tests; discriminant validity against self-reported disability. SETTING: Six prosthetic rehabilitation centers across the United States. PARTICIPANTS: Subjects (n = 60) with UL amputation utilizing a prosthesis. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Not applicable. RESULTS: Interrater reliability was excellent for scoring on the task, domain, and full scale scores (ICCs = .88-.99). Internal consistency was good (alpha = .79-.82). Generally, subjects with higher amputation levels scored lower (worse) than subjects with lower amputation levels. CAPPFUL demonstrated strong correlations with measures of hand dexterity/functioning (rs = -.58-.72); moderate correlation to self-reported disability (r = -.35). CONCLUSIONS: CAPPFUL was designed as a versatile, low burden measure of prosthesis performance for any UL functional prosthetic device type and any UL amputation level. CAPPFUL assesses overall performance, as well as five functional performance domains, during completion of 11 tasks that require movement in all planes while manipulating everyday objects requiring multiple grasp patterns. Psychometric evaluation indicates good interrater reliability, internal consistency, known-group validity, and convergent and discriminant validity.RE

Kale, P. and A. Afzal (2018). “Stage B Heart Failure: To Strain or Not to Strain.” JACC Cardiovasc Imaging. May 11.[Epub ahead of print].

Full text of this article.

Heart failure (HF) has been considered a progressive disorder than can be represented as a clinical continuum. In 2005, American College of Cardiology/American Heart Association updated the guidelines for management of HF and identified 4 states of heart failure with clinical recommendations for each stage. These guidelines helped address some of the confusion stemming from the symptom severity-based New York Heart Association functional classification. Symptom severity can change drastically over a short period either from medical therapy or absence of it, which can create confusion on treatment recommendations based solely on New York Heart Association functional classification. In the current schema, Stage B heart failure (SBHF) includes patients with Stage A HF who have structural heart disease but no current or prior symptoms of HF. It has been estimated that the number of patients in Stage B is about 2 times higher than Stages C and D combined. (Brief excerpt from this commentary, in press; no abstract available.)

Jin, Y., K. Chen, A. De Paepe, E. Hellqvist, A. D. Krstic, L. Metang, C. Gustafsson, R. E. Davis, Y. M. Levy, R. Surapaneni, A. Wallblom, H. Nahi, R. Mansson and Y. C. Lin (2018). “Active enhancer and chromatin accessibility landscapes chart the regulatory network of primary multiple myeloma.” Blood 131(19): 2138-2150.

Full text of this article.

Multiple myeloma (MM) is an aggressive cancer that originates from antibody-secreting plasma cells. Although genetically and transcriptionally well characterized, the aberrant gene regulatory networks that underpin this disease remain poorly understood. Here, we mapped regulatory elements, open chromatin, and transcription factor (TF) footprints in primary MM cells. In comparison with normal antibody-secreting cells, MM cells displayed consistent changes in enhancer activity that are connected to superenhancer (SE)-mediated deregulation of TF genes. MM cells also displayed widespread decompaction of heterochromatin that was associated with activation of regulatory elements and in a major subset of patients’ deregulation of the cyclic adenosine monophosphate pathway. Finally, building SE-associated TF-based regulatory networks allowed identification of several novel TFs that are central to MM biology. Taken together, these findings significantly add to our understanding of the aberrant gene regulatory network that underpins MM.

Jaggi, P., A. Mejias, Z. Xu, H. Yin, M. Moore-Clingenpeel, B. Smith, J. C. Burns, A. H. Tremoulet, A. Jordan-Villegas, D. Chaussabel, K. Texter, V. Pascual and O. Ramilo (2018). “Whole blood transcriptional profiles as a prognostic tool in complete and incomplete Kawasaki Disease.” PLoS One 13(5): e0197858. May 29. [eCollection 2018].

Full text of this article.

BACKGROUND: Early identification of children with Kawasaki Disease (KD) is key for timely initiation of intravenous immunoglobulin (IVIG) therapy. However, the diagnosis of the disease remains challenging, especially in children with an incomplete presentation (inKD). Moreover, we currently lack objective tools for identification of non-response (NR) to IVIG. METHODS: Children with KD were enrolled and samples obtained before IVIG treatment and sequentially at 24 h and 4-6 weeks post-IVIG in a subset of patients. We also enrolled children with other febrile illnesses [adenovirus (AdV); group A streptococcus (GAS)] and healthy controls (HC) for comparative analyses. Blood transcriptional profiles were analyzed to define: a) the cKD and inKD biosignature, b) compare the KD signature with other febrile illnesses and, c) identify biomarkers predictive of clinical outcomes. RESULTS: We identified a cKD biosignature (n = 39; HC, n = 16) that was validated in two additional cohorts of children with cKD (n = 37; HC, n = 20) and inKD (n = 13; HC, n = 8) and was characterized by overexpression of inflammation, platelets, apoptosis and neutrophil genes, and underexpression of T and NK cell genes. Classifier genes discriminated KD from adenovirus with higher sensitivity and specificity (92% and 100%, respectively) than for GAS (75% and 87%, respectively). We identified a genomic score (MDTH) that was higher at baseline in IVIG-NR [median 12,290 vs. 5,572 in responders, p = 0.009] and independently predicted IVIG-NR. CONCLUSION: A reproducible biosignature from KD patients was identified, and was similar in children with cKD and inKD. A genomic score allowed early identification of children at higher risk for non-response to IVIG.