211 research outputs found

    A semiquantitative metric for evaluating clinical actionability of incidental or secondary findings from genome-scale sequencing

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    As genome-scale sequencing is increasingly applied in clinical scenarios, a wide variety of genomic findings will be discovered as secondary or incidental findings, and there is debate about how they should be handled. The clinical actionability of such findings varies, necessitating standardized frameworks for a priori decision making about their analysis

    Rethinking the definition of major trauma: The need for trauma intervention outperforms Injury Severity Score and Revised Trauma Score in 38 adult and pediatric trauma centers

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    BACKGROUND Patients\u27 trauma burdens are a combination of anatomic damage, physiologic derangement, and the resultant depletion of reserve. Typically, Injury Severity Score (ISS) \u3e15 defines major anatomic injury and Revised Trauma Score (RTS) \u3c7.84 defines major physiologic derangement, but there is no standard definition for reserve. The Need For Trauma Intervention (NFTI) identifies severely depleted reserves (NFTI+) with emergent interventions and/or early mortality. We hypothesized NFTI would have stronger associations with outcomes and better model fit than ISS and RTS. METHODS Thirty-eight adult and pediatric U.S. trauma centers submitted data for 88,488 encounters. Mixed models tested ISS greater than 15, RTS less than 7.84, and NFTI\u27s associations with complications, survivors\u27 discharge to continuing care, and survivors\u27 length of stay (LOS). RESULTS The NFTI had stronger associations with complications and LOS than ISS and RTS (odds ratios [99.5% confidence interval]: NFTI = 9.44 [8.46-10.53]; ISS = 5.94 [5.36-6.60], RTS = 4.79 [4.29-5.34]; LOS incidence rate ratios (99.5% confidence interval): NFTI = 3.15 [3.08-3.22], ISS = 2.87 [2.80-2.94], RTS = 2.37 [2.30-2.45]). NFTI was more strongly associated with continuing care discharge but not significantly more than ISS (relative risk [99.5% confidence interval]: NFTI = 2.59 [2.52-2.66], ISS = 2.51 [2.44-2.59], RTS = 2.37 [2.28-2.46]). Cross-validation revealed that in all cases NFTI\u27s model provided a much better fit than ISS greater than 15 or RTS less than 7.84. CONCLUSION In this multicenter study, NFTI had better model fit and stronger associations with the outcomes than ISS and RTS. By determining depletion of reserve via resource consumption, NFTI+ may be a better definition of major trauma than the standard definitions of ISS greater than 15 and RTS less than 7.84. Using NFTI may improve retrospective triage monitoring and statistical risk adjustments. LEVEL OF EVIDENCE Prognostic, level IV

    Pediatric Low-Grade Gliomas: Next Biologically Driven Steps.

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    Despite the fact that they are not typically life-threatening, low-grade gliomas (LGGs) remain a significant clinical challenge in pediatric neuro-oncology due to comorbidities associated with these tumors and/or their treatments, and their propensity to multiply recurs. LGGs, in total the most common brain tumors arising in childhood, can often become a chronic problem requiring decades of management. The Second International Consensus Conference on Pediatric Low-Grade Gliomas held in Padua, Italy in 2016 was convened in an attempt to advance the pace of translating biological discoveries on LGGs into meaningful clinical benefit. Topics discussed included: the implications of our growing biological understanding of the genomics underlying these tumors; the assessment of the model systems available; the implications of the molecular and histopathologic differences between adult and pediatric diffuse gliomas; and steps needed to expedite targeted therapy into late-stage clinical trials for newly diagnosed cases. Methods for the diagnostic assessment of alterations in the Ras/mitogen-activated protein kinase pathway, typical for these tumors, were also considered. While the overall tone was positive, with a consensus that progress is being and will continue to be made, the scale of the challenge presented by this complex group of tumors was also acknowledged. The conclusions and recommendations of the meeting panel are provided here as an outline of current thinking and a basis for further discussion

    Pediatric low-grade gliomas: Implications of the biologic era

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    For the past decade, it has been recognized that pediatric low-grade gliomas (LGGs) and glial-neuronal tumors carry distinct molecular alterations with resultant aberrant intracellular signaling in the Ras-mitogen-activated protein kinase pathway. The conclusions and recommendations of a consensus conference of how best to integrate the growing body of molecular genetic information into tumor classifcations and, more importantly, for future treatment of pediatric LGGs are summarized here. There is uniform agreement that molecular characterization must be incorporated into classifcation and is increasingly critical for appropriate management. Moleculartargeted therapies should be integrated expeditiously, but also carefully into the management of these tumors and success measured not only by radiographic responses or stability, but also by functional outcomes. These trials need to be carried out with the caveat that the long-term impact of molecularly targeted therapy on the developing nervous system, especially with long duration treatment, is essentially unknown
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