Association of Persistent Postconcussion Symptoms With Pediatric Quality of Life.

IMPORTANCE: Persistent postconcussion symptoms (PPCS) pose long-term challenges and can negatively affect patients' health-related quality of life (HRQoL). To date, no large comprehensive study has addressed the association between PPCS and HRQoL. OBJECTIVES: To determine the association between HRQoL and PPCS at 4 weeks after concussion and assess the degree of impairment of HRQoL in the subsequent 12 weeks. DESIGN, SETTING, AND PARTICIPANTS: In a prospective, multicenter cohort study (Predicting Persistent Postconcussive Problems in Pediatrics [5P]) from August 14, 2013, to September 30, 2014, children aged 5 to 18 years who presented to the emergency department within 48 hours after head injury and were considered to have an acute concussion were enrolled across 9 pediatric emergency departments within the Pediatric Emergency Research Canada Network. Persistent postconcussion symptoms were defined as 3 or more persistent symptoms on the validated Post-Concussion Symptom Inventory at 4 weeks. Linear mixed effects random coefficients models evaluated the association between PPCS and HRQoL, adjusting for potential confounders including age, sex, prior concussions, migraine, anxiety, learning disability, depression, and sleep disorder. MAIN OUTCOMES AND MEASURES: The primary outcome was HRQoL assessed with the validated Pediatric Quality of Life Inventory version 4.0 (PedsQL-4.0) at 4, 8, and 12 weeks after head injury. RESULTS: Of 2006 children enrolled (median age, 11.8 years [interquartile range, 8.9-14.6 years]; 1241 boys and 765 girls), 1667 (83.1%) completed the PedsQL-4.0 at all 3 time points. Of these 1667 children, the 510 with PPCS (30.6%) had lower total PedsQL-4.0 scores (mean, 70.0) than did those without PPCS (mean, 80.3; mean difference, -10.3; 95% CI, -9.4 to -11.2). Patients with PPCS also had significantly lower physical, emotional, social, and school PedsQL-4.0 subscores at 4, 8, and 12 weeks. Patients with PPCS had lower HRQoL than published healthy norms at 4 weeks (mean difference, 13.89; 95% CI, 11.55-16.23), 8 weeks (mean difference, 11.63; 95% CI, 9.34-13.93), and 12 weeks (mean difference, 9.38; 95% CI, 7.01-11.75; P < .001). Patients who recovered from concussion also had lower HRQoL than norms at 4 weeks (mean difference, 3.56; 95% CI, 1.28-5.85) and 8 weeks (mean difference, 2.75; 95% CI, 0.48-5.02; P < .05). School functioning PedsQL-4.0 subscores were significantly lower for all children regardless of PPCS status at all time points. CONCLUSIONS AND RELEVANCE: Children with PPCS have lower HRQoL compared with those who have recovered from concussion, yet deficits in HRQoL are pervasive across all domains and may persist for months even in children whose symptoms have resolved. Future interventional research should target the effect of concussion on HRQoL.

Junctional diversity prevents negative selection of an antigen-specific T cell repertoire.

Endogenous mouse mammary tumor proviruses (MMTV; Mtv loci) deletes Vbeta6 expressing T cells in the thymus of Mtv-7(+) DBA/2 (H2(d)) mice through negative selection. We found that in Mtv-7(-) BALB/c (H2(d)) mice, Vbeta6 is a dominant V gene used in T cell responses to an 18 amino acid long peptide antigen: EYKEYAEYAEYAEYAEYA [abbreviated as K5 or EYK(EYA)(5)]. It was therefore surprising to find that despite the deletion of Vbeta6+ T cells, vigorous K5 specific T cell responses that use Vbeta6 can be raised in DBA/2 mice. Sequence analysis of Vbeta6 junctional diversity in K5 specific T cell lines revealed that the DBA/2 K5 repertoire compensates for the loss of most Vbeta6 T cells by overusing and amplifying Vbeta6+ T cells escaping central deletion and peripheral tolerization. In order to address the inability of some Vbeta6 T cells to recognize Mtv-7(+) we analyzed a panel of BALB/c Vbeta6 expressing T cell hybridomas. This data supported the argument that certain Vbeta6 junctional sequences preclude Mtv recognition and allows their escape from central deletion in DBA/2 mice. These cells are not anergic and can be activated with cognate peptide antigen in periphery. We suggest that junctional diversity at the V region of some of the T cell receptors does not allow these cells to recognize self-superantigens with high enough affinity and thus they escape negative selection in the thymus. These results for the first time provide a molecular explanation of how the immune system compensates for "hole in the repertoire" caused by deletion of the majority of T cells carrying certain V region segments.

Peptide growth factors in tracheal aspirates of mechanically ventilated preterm neonates.

Basic fibroblast growth factor (bFGF or FGF-2), vascular endothelial growth factor (VEGF), and endothelin-1 (ET-1) are peptide growth factors (PGF) mediating normal lung development, maturation, injury, and repair. These PGF may therefore be involved in the pathogenesis of bronchopulmonary dysplasia (BPD). We hypothesized that elevated levels of these PGF in tracheal aspirates would be associated with a) BPD and/or death; b) markers of cell injury and apoptosis; and c) chorioamnionitis, a risk factor for BPD. Tracheal aspirates collected in 29 preterm (<34 wk gestation, 500-2000 g birth weight), mechanically ventilated infants on d 1 of life were assayed for PGF and histone-associated DNA fragments by ELISA and for LDH by enzyme assay. Clinical and pathologic examination was performed for chorioamnionitis. BPD was defined as oxygen requirement/mechanical ventilation at 28 d postnatal age. The birth weight (mean +/- SE) was 1009 +/- 85 g and median gestational age was 26 wk (range, 22-33). Eighteen infants died or developed BPD. bFGF levels were elevated in infants who died or developed BPD [median (25%,75%) level of 36 (23, 44) pg/mL versus 14 (6, 30) in the survivors without BPD, p = 0.01]. bFGF levels correlated with apoptosis (r = 0.73, p < 0.001) and LDH levels (r = 0.59, p < 0.001). VEGF and ET-1 levels were not associated with apoptosis or with BPD/death. PGF levels were not associated with chorioamnionitis. We conclude that elevated bFGF levels in the preterm trachea correlate with BPD/death and markers of cell injury and apoptosis but not with chorioamnionitis. We speculate that bFGF may play a role in the development of BPD.