High-Energy Skeletal Trauma in the Elderly

Switzer, Julie A.; Gammon, Steven R.

doi:10.2106/jbjs.k.01166

Cited by 37 publications

(13 citation statements)

References 105 publications

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“…We then examined the effect of NO on mTOR signaling downstream of the BRAF inhibitor Vemurafenib (PLX4032/RG7204) (42, 43) since it is used clinically in treatment of melanoma. Cells were treated with Vemurafenib and the exogenous NO donor DEANONOate, or a combination of both for 3 hours.…”

Section: Resultsmentioning

confidence: 99%

Inducible Nitric Oxide Synthase Drives mTOR Pathway Activation and Proliferation of Human Melanoma by Reversible Nitrosylation of TSC2

et al. 2014

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Melanoma is one of the cancers of fastest-rising incidence in the world. iNOS is overexpressed in melanoma and other cancers, and previous data suggest that iNOS and nitric oxide (NO) drive survival and proliferation of human melanoma cells. However, specific mechanisms through which this occurs are poorly defined. One candidate is the PI3K/AKT/mTOR pathway, which plays a major role in proliferation, angiogenesis, and metastasis of melanoma and other cancers. We used the chick embryo chorioallantoic membrane (CAM) assay to test the hypothesis that melanoma growth is regulated by iNOS-dependent mTOR pathway activation. Both pharmacologic inhibition and siRNA-mediated gene silencing of iNOS suppressed melanoma proliferation and in vivo growth on the CAM in human melanoma models. This was associated with strong downregulation of mTOR pathway activation by Western blot analysis of p-mTOR, p-P70S6K, p-S6RP, and p-4EBP1. iNOS expression and NO were associated with reversible nitrosylation of TSC2, and inhibited dimerization of TSC2 with its inhibitory partner TSC1, enhancing GTPase activity of its target Rheb, a critical activator of mTOR signaling. Immunohistochemical analysis of tumor specimens from stage III melanoma patients showed a significant correlation between iNOS expression levels and expression of mTOR pathway members. Exogenously-supplied NO was also sufficient to reverse mTOR pathway inhibition by the B-Raf inhibitor Vemurafenib. In summary, covalent modification of TSC2 by iNOS-derived NO is associated with impaired TSC2/TSC1 dimerization, mTOR pathway activation, and proliferation of human melanoma. This model is consistent with the known association of iNOS overexpression and poor prognosis in melanoma and other cancers.

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Section: Resultsmentioning

confidence: 99%

Inducible Nitric Oxide Synthase Drives mTOR Pathway Activation and Proliferation of Human Melanoma by Reversible Nitrosylation of TSC2

et al. 2014

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“…Although this study was exploring fatal low free falls across all ages, the sample of fatal cases was heavily skewed (median 84 years) toward the elderly. This age distribution of primarily elderly individuals was expected given the changes bone undergoes with advancing age (i.e., mineralization ) means elderly individuals are potentially more susceptible to severe injury from fairly low‐energy mechanisms of BFT , such as these falls. Within that context, it is of particular medico‐legal interest, and thus important to note, that young and middle‐aged adults (i.e., those with healthy skeletal biology ) are, although rare occurrences, still capable of dying from low‐energy BFT mechanisms such as these falls.…”

Section: Discussionmentioning

confidence: 99%

Skeletal Trauma Resulting From Fatal Low (≤3 m) Free Falls: An Analysis of Fracture Patterns and Morphologies

Rowbotham

Blau

Hislop-Jambrich³

et al. 2017

Journal of Forensic Sciences

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The skeletal trauma resulting from fatal low (≤3 m) free falls is poorly researched and understood by forensic practitioners. The aim of this study was to identify the types of skeletal trauma resulting from low falls through investigating fracture patterns and morphologies. Skeletal trauma was analyzed using full-body postmortem computed tomography scans of 145 individuals who died from a low free fall. Trauma was then contextualized to the variables that influence how a person falls using multiple logistic regression. Results showed fracture patterning primarily involved the axial skeleton and that there were a number of patterns significantly associated with the height fallen, pre-existing health conditions, and age. Analysis of fracture morphologies showed 108 possible fracture types, six of which were significantly associated with the height fallen. Understanding the skeletal trauma characteristic of low free falls will further inform anthropological interpretations of trauma in cases where a fall may be considered the possible mechanism.

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“…There has been data to show a linear relationship to number of rib fractures with increased mortality and pneumonia rates in this group as well. There is a large amount of literature which focuses on outcomes in elderly patients who have sustained trauma and if treated early and aggressively can be rescued even in the extremes of cases [13,14]. In our cohort of patients age had negligible impact on the decision to provide operative repair in this series, as 25% of the study cohort was over the age of 65.…”

Section: Resultsmentioning

confidence: 91%

Untitled

2018

Trauma Cases Rev

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Introduction: Non-operative management of rib fractures can lead to significant morbidity such as chronic pain, and dyspnea. Up to 40% may also fail to return to work. Over the last decade rib fixation has made resurgence and there are emerging data supporting early fixation in patients that fail aggressive pain control even in non-flail segments. We describe our early experience with early rib fixation in a small cohort of patients with severe chest wall injury.

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High-Energy Skeletal Trauma in the Elderly

Cited by 37 publications

References 105 publications

Inducible Nitric Oxide Synthase Drives mTOR Pathway Activation and Proliferation of Human Melanoma by Reversible Nitrosylation of TSC2

Inducible Nitric Oxide Synthase Drives mTOR Pathway Activation and Proliferation of Human Melanoma by Reversible Nitrosylation of TSC2

Skeletal Trauma Resulting From Fatal Low (≤3 m) Free Falls: An Analysis of Fracture Patterns and Morphologies

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