Browsing by Author "Sun, Jessica"
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Item Open Access Brain structural connectivity increases concurrent with functional improvement: evidence from diffusion tensor MRI in children with cerebral palsy during therapy.(NeuroImage. Clinical, 2015-01-09) Englander, Zoë A; Sun, Jessica; Laura Case; Mikati, Mohamad A; Kurtzberg, Joanne; Song, Allen WCerebral Palsy (CP) refers to a heterogeneous group of permanent but non-progressive movement disorders caused by injury to the developing fetal or infant brain (Bax et al., 2005). Because of its serious long-term consequences, effective interventions that can help improve motor function, independence, and quality of life are critically needed. Our ongoing longitudinal clinical trial to treat children with CP is specifically designed to meet this challenge. To maximize the potential for functional improvement, all children in this trial received autologous cord blood transfusions (with order randomized with a placebo administration over 2 years) in conjunction with more standard physical and occupational therapies. As a part of this trial, magnetic resonance imaging (MRI) is used to improve our understanding of how these interventions affect brain development, and to develop biomarkers of treatment efficacy. In this report, diffusion tensor imaging (DTI) and subsequent brain connectome analyses were performed in a subset of children enrolled in the clinical trial (n = 17), who all exhibited positive but varying degrees of functional improvement over the first 2-year period of the study. Strong correlations between increases in white matter (WM) connectivity and functional improvement were demonstrated; however no significant relationships between either of these factors with the age of the child at time of enrollment were identified. Thus, our data indicate that increases in brain connectivity reflect improved functional abilities in children with CP. In future work, this potential biomarker can be used to help differentiate the underlying mechanisms of functional improvement, as well as to identify treatments that can best facilitate functional improvement upon un-blinding of the timing of autologous cord blood transfusions at the completion of this study.Item Open Access Differences in quality between privately and publicly banked umbilical cord blood units: a pilot study of autologous cord blood infusion in children with acquired neurologic disorders.(Transfusion, 2010-09) Sun, Jessica; Allison, June; McLaughlin, Colleen; Sledge, Linda; Waters-Pick, Barbara; Wease, Stephen; Kurtzberg, JoanneBackground
A pilot study was conducted to determine the safety and feasibility of intravenous administration of autologous umbilical cord blood (CB) in young children with acquired neurologic disorders. Most CB units (CBUs) were electively stored in private CB banks. Unlike public banks, which utilize specific criteria and thresholds for banking, private banks generally store all collected CBUs.Study design and methods
CBUs of eligible patients containing more than 1 × 10⁷ cells/kg were shipped to Duke from the banks of origin after confirming identity by HLA typing. On the day of infusion, CBUs were thawed and washed in dextran-albumin and infused intravenously. Patients were medicated with acetaminophen, diphenhydramine, and methylprednisolone before transfusion. Data regarding patients, infusions, and CBUs were collected retrospectively. Characteristics of CBUs were compared to existing data from CBUs publicly banked at the Carolinas Cord Blood Bank.Results
From March 2004 to December 2009, 184 children received 198 CB infusions. Three patients had infusion reactions, all responsive to medical therapy and stopping the infusion. Median precryopreservation volume (60 mL vs. 89 mL, p < 0.0001), total nucleated cell count (4.7 × 10⁸ vs. 10.8 × 10⁸, p < 0.0001), and CD34 count (1.8 × 10⁶ vs. 3.0 × 10⁶, p < 0.0001) were significantly lower than publicly stored CBUs. Postthaw sterility cultures were positive in 7.6% of infused CBUs.Conclusion
IV infusion of autologous CB is safe and feasible in young children with neurologic injuries. Quality parameters of privately banked CBUs are inferior to those stored in public banks. If efficacy of autologous CB is established clinically, the quality of autologous units should be held to the same standards as those stored in public banks.Item Open Access Diffuse reduction of white matter connectivity in cerebral palsy with specific vulnerability of long range fiber tracts.(NeuroImage. Clinical, 2013-01) Englander, Zoë A; Pizoli, Carolyn E; Batrachenko, Anastasiya; Sun, Jessica; Worley, Gordon; Mikati, Mohamad A; Kurtzberg, Joanne; Song, Allen WCerebral palsy (CP) is a heterogeneous group of non-progressive motor disorders caused by injury to the developing fetal or infant brain. Although the defining feature of CP is motor impairment, numerous other neurodevelopmental disabilities are associated with CP and contribute greatly to its morbidity. The relationship between brain structure and neurodevelopmental outcomes in CP is complex, and current evidence suggests that motor and developmental outcomes are related to the spatial pattern and extent of brain injury. Given that multiple disabilities are frequently associated with CP, and that there is increasing burden of neurodevelopmental disability with increasing motor severity, global white matter (WM) connectivity was examined in a cohort of 17 children with bilateral CP to test the hypothesis that increased global WM damage will be seen in the group of severely affected (Gross Motor Function Classification Scale (GMFCS) level of IV) as compared to moderately affected (GMFCS of II or III) individuals. Diffusion tensor tractography was performed and the resulting fibers between anatomically defined brain regions were quantified and analyzed in relation to GMFCS levels. Overall, a reduction in total WM connectivity throughout the brain in severe versus moderate CP was observed, including but not limited to regions associated with the sensorimotor system. Our results also show a diffuse and significant reduction in global inter-regional connectivity between severity groups, represented by inter-regional fiber count, throughout the brain. Furthermore, it was also observed that there is a significant difference (p = 0.02) in long-range connectivity in patients with severe CP as compared to those with moderate CP, whereas short-range connectivity was similar between groups. This new finding, which has not been previously reported in the CP literature, demonstrates that CP may involve distributed, network-level structural disruptions.Item Open Access Expanded Access Protocol of Umbilical Cord Blood Infusion for Children with Neurological Conditions: An Update.(Stem cells translational medicine, 2021-09) McLaughlin, Colleen; West, Tara; Hollowell, Rachel; Skergan, Natalie; Giguere, Paige; Vinesett, Richard; Arbuckle, Erin; Cash, Jayne; Hoyle, Kerry; Crane, Sydney; Moore, Lettie; Waters-Pick, Barbara; Hawkins, Tiffany; Prasad, Vinod; Sun, Jessica; Kurtzberg, JoanneItem Open Access Optimizing donor selection for public cord blood banking: influence of maternal, infant, and collection characteristics on cord blood unit quality.(Transfusion, 2014-02) Page, Kristin M; Mendizabal, Adam; Betz-Stablein, Brigid; Wease, Stephen; Shoulars, Kevin; Gentry, Tracy; Prasad, Vinod K; Sun, Jessica; Carter, Shelly; Balber, Andrew E; Kurtzberg, JoanneBackground
Banked unrelated donor umbilical cord blood (CB) has improved access to hematopoietic stem cell transplantation for patients without a suitably matched donor. In a resource-limited environment, ensuring that the public inventory is enriched with high-quality cord blood units (CBUs) addressing the needs of a diverse group of patients is a priority. Identification of donor characteristics correlating with higher CBU quality could guide operational strategies to increase the yield of banked high-quality CBUs.Study design and methods
Characteristics of 5267 CBUs donated to the Carolinas Cord Blood Bank, a public bank participating in the National Cord Blood Inventory, were retrospectively analyzed. Eligible CBUs, collected by trained personnel, were processed using standard procedures. Routine quality and potency metrics (postprocessing total nucleated cell count [post-TNCC], CD34+, colony-forming units [CFUs]) were correlated with maternal, infant, and collection characteristics.Results
High-quality CBUs were defined as those with higher post-TNCC (>1.25 × 10(9)) with CD34+ and CFUs in the upper quartile. Factors associated with higher CD34+ or CFU content included a shorter interval from collection to processing (<10 hr), younger gestational age (34-37 weeks; CD34+ and CFUs), Caucasian race, higher birthweight (>3500 g), and larger collection volumes (>80 mL).Conclusions
We describe characteristics identifying high-quality CBUs, which can be used to inform strategies for CBU collection for public banks. Efforts should be made to prioritize collections from larger babies born before 38 weeks of gestation. CBUs should be rapidly transported to the processing laboratory. The lower quality of CBUs from non-Caucasian donors highlights the challenges of building a racially diverse public CB inventory.Item Open Access White Matter Tract Changes Associated with Clinical Improvement in an Open-Label Trial Assessing Autologous Umbilical Cord Blood for Treatment of Young Children with Autism.(Stem cells translational medicine, 2019-02) Carpenter, Kimberly LH; Major, Samantha; Tallman, Catherine; Chen, Lyon W; Franz, Lauren; Sun, Jessica; Kurtzberg, Joanne; Song, Allen; Dawson, GeraldineAutism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by social communication deficits and the presence of restricted interests and repetitive behaviors. We have previously reported significant improvements in behavior, including increased social functioning, improved communication abilities, and decreased clinical symptoms in children with ASD, following treatment with a single infusion of autologous cord blood in a phase I open-label trial. In the current study, we aimed to understand whether these improvements were associated with concurrent changes in brain structural connectivity. Twenty-five 2- to 6-year-old children with ASD participated in this trial. Clinical outcome measures included the Vineland Adaptive Behavior Scales-II Socialization Subscale, Expressive One-Word Picture Vocabulary Test-4, and the Clinical Global Impression-Improvement Scale. Structural connectivity was measured at baseline and at 6 months in a subset of 19 children with 25-direction diffusion tensor imaging and deterministic tractography. Behavioral improvements were associated with increased white matter connectivity in frontal, temporal, and subcortical regions (hippocampus and basal ganglia) that have been previously shown to show anatomical, connectivity, and functional abnormalities in ASD. The current results suggest that improvements in social communication skills and a reduction in symptoms in children with ASD following treatment with autologous cord blood infusion were associated with increased structural connectivity in brain networks supporting social, communication, and language abilities. Stem Cells Translational Medicine 2019;8:138&10.