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Dennis E.L.,University of Southern California | Ellis M.U.,University of California at Los Angeles | Jin Y.,University of Southern California | Moran L.,University of California at Los Angeles | And 10 more authors.
Journal of Neuroscience | Year: 2015

Traumatic brain injury (TBI) often results in traumatic axonal injury and white matter(WM)damage, particularly to the corpus callosum (CC). Damage to the CC can lead to impaired performance on neurocognitive tasks, but there is a high degree of heterogeneity in impairment following TBI. Here we examined the relation between CC microstructure and function in pediatric TBI. We used high angular resolution diffusion-weighted imaging (DWI) to evaluate the structural integrity of the CC in humans following brain injury in a sample of 32 children (23 males and 9 females) with moderate-to-severe TBI (msTBI) at 1–5 months postinjury, compared with well matched healthy control children. We assessed CC function through interhemispheric transfer time (IHTT) as measured using eventrelated potentials (ERPs), and related this to DWI measures of WM integrity. Finally, the relation between DWI and IHTT results was supported by additional results of neurocognitive performance assessed using a single composite performance scale. Half of the msTBI participants (16 participants) had significantly slower IHTTs than the control group. This slow IHTT group demonstrated lower CC integrity (lower fractional anisotropy and higher mean diffusivity) and poorer neurocognitive functioning than both the control group and the msTBI group with normal IHTTs. Lower fractional anisotropy—a common sign of impaired WM—and slower IHTTs also predicted poor neurocognitive function. This study reveals that there is a subset of pediatric msTBI patients during the post-acute phase of injury who have markedly impaired CC functioning and structural integrity that is associated with poor neurocognitive functioning. © 2015, the authors. Source

Dennis E.L.,University of Southern California | Jin Y.,University of Southern California | Villalon-Reina J.E.,University of Southern California | Zhan L.,University of Southern California | And 8 more authors.
NeuroImage: Clinical | Year: 2015

Traumatic brain injury (TBI) is the leading cause of death and disability in children and can lead to a wide range of impairments. Brain imaging methods such as DTI (diffusion tensor imaging) are uniquely sensitive to the white matter (WM) damage that is common in TBI. However, higher-level analyses using tractography are complicated by the damage and decreased FA (fractional anisotropy) characteristic of TBI, which can result in premature tract endings. We used the newly developed autoMATE (automated multi-atlas tract extraction) method to identify differences in WM integrity. 63 pediatric patients aged 8-19 years with moderate/severe TBI were examined with cross sectional scanning at one or two time points after injury: a post-acute assessment 1-5 months post-injury and a chronic assessment 13-19 months post-injury. A battery of cognitive function tests was performed in the same time periods. 56 children were examined in the first phase, 28 TBI patients and 28 healthy controls. In the second phase 34 children were studied, 17 TBI patients and 17 controls (27 participants completed both post-acute and chronic phases). We did not find any significant group differences in the post-acute phase. Chronically, we found extensive group differences, mainly for mean and radial diffusivity (MD and RD). In the chronic phase, we found higher MD and RD across a wide range of WM. Additionally, we found correlations between these WM integrity measures and cognitive deficits. This suggests a distributed pattern of WM disruption that continues over the first year following a TBI in children. © 2015 Published by Elsevier Inc. Source

Huang J.S.,University of California at San Diego | Dillon L.,University of California at San Diego | Terrones L.,University of California at San Diego | Schubert L.,Rady Childrens Hospital | And 7 more authors.
Pediatric Blood and Cancer | Year: 2014

Background: Children surviving acute lymphoblastic leukemia (ALL) are at increased risk for overweight and obesity over that of the general population. Whether a generic or tailored approach to weight management is needed for cancer survivors has yet to be tested. Procedure: Thirty-eight youth 8-18 years with BMI≥85% who had survived ALL were recruited for a randomized clinical trial evaluating a weight management intervention (WMI) tailored for childhood ALL survivors (Fit4Life). Fit4Life recipients received a 4-month web, phone, and text message-delivered WMI tailored for cancer survivorship. Controls received a general WMI delivered via phone and mail. Assessments were performed at baseline and 4 months. Outcome data were analyzed according to assigned treatment condition over time. Results: Most (80%, (70%, 100%) [median (IQR)]) of the assigned curriculum was received by Fit4Life participants as compared to 50% (40%, 65%) among controls. Fit4Life recipients ≥14 years demonstrated less weight gain (P=0.05) and increased moderate-to-vigorous physical activity (P<0.01) while all Fit4Life recipients reported reduced negative mood (P<0.05) over time as compared to control counterparts. Conclusions: We demonstrated acceptable feasibility of a WMI tailored for overweight and obese children surviving ALL utilizing a multimodal technology approach. Improved weight, weight-related behavior, and psychological outcomes were demonstrated among Fit4Life intervention as compared to youth receiving a generic WMI. Data from this pilot trial may be used to design a larger trial to determine whether youth of all ages also can derive a benefit from a cancer survivor-tailored WMI and whether short-term outcomes translate into improved long-term outcomes for childhood ALL survivors. © 2014 Wiley Periodicals, Inc. Source

McKamy S.,Miller Childrens Hospital | Hernandez E.,Loma Linda University | Jahng M.,Miller Childrens Hospital | Moriwaki T.,Lucile Packard Childrens Hospital | And 2 more authors.
Journal of Pediatrics | Year: 2011

Objective: To determine the incidence of vancomycin-associated nephrotoxicity in children and to examine potential risk factors for nephrotoxicity, including average serum trough concentrations ≥15 mg/L. Study design: Patients ≥1 week old to ≤19 years with normal baseline serum creatinine values who received vancomycin for ≥48 hours between December 2007 and April 2009 were retrospectively evaluated. Nephrotoxicity was defined as a serum creatinine increase of ≥0.5 mg/dL or ≥50% baseline increase over 2 days. Patients with average serum trough concentrations ≥15 mg/L were compared with a lower trough group. Results: Nephrotoxicity occurred in 14% of 167 patients. More patients who attained high average (≥15 mg/L) rather than low average (<15 mg/L) vancomycin troughs had nephrotoxicity (28% versus 7.3%, P = .0001). Using multivariable regression analysis, patients with high troughs and those receiving furosemide in the intensive care unit were more likely to have nephrotoxicity (OR, 3.27 [95% CI, 1.19 to 8.95], P = .021, and odds ratio, 9.45 [95% confidence interval, 3.44 to 26.00], P < .0001, respectively). Conclusions: Renal function and serum troughs in children receiving vancomycin, especially those with targeted troughs of ≥15 mg/L, in intensive care, and receiving furosemide, should be closely monitored. © 2011 Mosby Inc. All rights reserved. Source

Randolph A.G.,Perioperative and Pain Medicine | Randolph A.G.,Harvard University | Vaughn F.,National Disaster Medical System | Sullivan R.,Perioperative and Pain Medicine | And 17 more authors.
Pediatrics | Year: 2011

BACKGROUND: The 2009 pandemic influenza A (H1N1) (pH1N1) virus continues to circulate worldwide. Determining the roles of chronic conditions and bacterial coinfection in mortality is difficult because of the limited data for children with pH1N1-related critical illness. METHODS: We identified children (<21 years old) with confirmed or probable pH1N1 admitted to 35 US PICUs from April 15, 2009, through April 15, 2010. We collected data on demographics, baseline health, laboratory results, treatments, and outcomes. RESULTS: Of 838 children with pH1N1 admitted to a PICU, the median age was 6 years, 58% were male, 70% had ≥1 chronic health condition, and 88.2% received oseltamivir (5.8% started before PICU admission). Most patients had respiratory failure with 564 (67.3%) receiving mechanical ventilation; 162 (19.3%) received vasopressors, and 75 (8.9%) died. Overall, 71 (8.5%) of the patients had a presumed diagnosis of early (within 72 hours after PICU admission) Staphylococcus aureus coinfection of the lung with 48% methicillin-resistant S aureus (MRSA). In multivariable analyses, preexisting neurologic conditions or immunosuppression, encephalitis (1.7% of cases), myocarditis (1.4% of cases), early presumed MRSA lung coinfection, and female gender were mortality risk factors. Among 251 previously healthy children, only early presumed MRSA coinfection of the lung (relative risk: 8 [95% confidence interval: 3.1-20.6]; P < .0001) remained a mortality risk factor. CONCLUSIONS: Children with preexisting neurologic conditions and immune compromise were at increased risk of pH1N1-associated death after PICU admission. Secondary complications of pH1N1, including myocarditis, encephalitis, and clinical diagnosis of early presumed MRSA coinfection of the lung, were mortality risk factors. Copyright © 2011 by the American Academy of Pediatrics. Source

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