To determine the effect of cognitive activity level on duration of post-concussion symptoms. METHODS:We conducted a prospective cohort study of patients who presented to a Sports Concussion Clinic within 3 weeks of injury between October 2009 and July 2011. At each visit, patients completed a scale that recorded their average level of cognitive activity since the previous visit. The product of cognitive activity level and days between visits (cognitive activity-days) was calculated and divided into quartiles. Kaplan-Meier Product Limit method was used to generate curves of symptom duration based on cognitive activity level. To adjust for other possible predictors of concussion recovery, we constructed a Cox proportional hazard model with cognitive activity-days as the main predictor. RESULTS:Of the 335 patients included in the study, 62% were male, 19% reported a loss of consciousness, and 37% reported experiencing amnesia at the time of injury. The mean age of participants was 15 years (range, 8-23) and the mean number of previous concussions was 0.76; 39% of athletes had sustained a previous concussion. The mean Post-Concussion Symptom Scale score at the initial visit was 30 (SD, 26). The overall mean duration of symptoms was 43 days (SD, 53). Of all variables assessed, only total symptom burden at initial visit and cognitive activity level were independently associated with duration of symptoms.CONCLUSIONS: Increased cognitive activity is associated with longer recovery from concussion. This study supports the use of cognitive rest and adds to the current consensus opinion. Pediatrics 2014;133:e299-e304 AUTHORS:

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Objectives To evaluate the test characteristics of clinical examination (CE) with the addition of bedside emergency ultrasound (CE+EUS) compared to CE alone in determining skin and soft tissue infections (SSTIs) that require drainage in pediatric patients. Methods This was a prospective study of CE+EUS as a diagnostic test for the evaluation of patients 2 months to 19 years of age evaluated for SSTIs in a pediatric emergency department (ED). Two physicians clinically and independently evaluated each lesion, and the reliability of the CE for diagnosing lesions requiring drainage was calculated. Trained pediatric emergency physicians (EPs) performed US following their CEs. The authors determined and compared the test characteristics for evaluating a SSTI requiring drainage for CE alone and for CE+EUS for those lesions in which the two EPs agreed and were certain regarding their CE diagnosis (clinically evident). The performance of CE+EUS was evaluated in those lesions in which the two EPs either disagreed or were uncertain of their diagnosis (not clinically evident). The reference standard for determining if a lesion required drainage was defined as pus expressed at the time of the ED visit, or within two days by follow-up assessment. Results Three hundred and eighty-seven lesions underwent CE+EUS and were analyzed. CE agreement between physicians was fair (K = 0.38). For the 228 lesions for which physicians agreed and were certain of their diagnoses, sensitivity was 94.7% for CE and 93.1% for CE+EUS (difference −1.7%, 95% CI = −3.4% to 0%). The specificity of CE was 84.2% compared to 81.4% for CE+EUS (difference −2.8%, 95% CI = −9.7% to 4.1%). For lesions not clinically evident based on CE, the sensitivity of CE was 43.7%, compared with 77.6% for CE+EUS (difference 33.9%, 95% CI = 1.2% to 66.6%). The specificity of CE for this group was 42.0%, compared with 61.3% for CE+EUS (difference 19.3%, 95% CI = −13.8% to 52.4%). Conclusions For clinically evident lesions, the addition of US did not significantly improve the already highly accurate CE for diagnosing lesions requiring drainage in this study population. However, there were many lesions that were not clinically evident, and in these cases, US may improve the accuracy of the CE.

Improper regulation of B cell responses leads to excessive production of antibodies and contributes to the development of autoimmune disease. T helper 17 (Th17) cells also drive the development of autoimmune disease, but the role of B cells in shaping Th17 cell-mediated immune responses, as well as the reciprocal regulation of B cell responses by IL-17 family cytokines, remains unclear. The aim of this study was to characterize the regulation of IL-17A and IL-17F in a model of T cell-dependent B cell activation. Stimulation of primary human B cell and peripheral blood mononuclear cell (BT) co-cultures with α-IgM and a non-mitogenic concentration of superantigens for three days promoted a Th17 cell response as evidenced by increased expression of Th17-related gene transcripts, including Il17f, Il21, Il22, and Il23r, in CD4 T cells, as well as the secretion of IL-17A and IL-17F protein. We tested the ability of 144 pharmacologic modulators representing 91 different targets or pathways to regulate IL-17A and IL-17F production in these stimulated BT co-cultures. IL-17A production was found to be preferentially sensitive to inhibition of the PI3K/mTOR pathway, while prostaglandin EP receptor agonists, including PGE2, increased IL-17A concentrations. In contrast, the production of IL-17F was inhibited by PGE2, but selectively increased by TLR2 and TLR5 agonists. These results indicate that IL-17A regulation is distinct from IL-17F in stimulated BT co-cultures and that this co-culture approach can be used to identify pathway mechanisms and novel agents that selectively inhibit production of IL-17A or IL-17F.