Abusive Pediatric Thoracolumbar Fracture Due to Forced Hyperextension: Case Report, Biomechanical Considerations, and Review of the Literature.

Pediatric thoracolumbar fractures are rare due to the physiological differences which afford greater resilience to the immature spine. Most pediatric thoracolumbar fractures occur as the result of high energy trauma, such as motor vehicle accidents, and modes of reasonable accidental injuries are limited by age and developmental capabilities of the child. These fractures can occur as the result of inflicted blunt force trauma and child abuse, and in most cases, the mechanism of injury to the spine is not known. We report the death of a 29-month-old man due to blunt force trauma to the back and forced hyperextension of the thoracolumbar spine causing fracture of the fourth lumbar (L4) vertebral body. A complete forensic examination revealed a previous healing fracture of the anterior aspect of the L4 vertebral body, with acute disruption of the anterior longitudinal ligament overlying the fracture site, complete fracture of the vertebral body, and fatal retroperitoneal hemorrhage. We present a review of the biomechanical considerations of the pediatric spine, a survey of pediatric spinal fractures, and a review of the literature on pediatric abusive thoracolumbar fractures. In this case, there was never a provided explanation for how the injury occurred; however, understanding the biomechanics of the pediatric spine allowed for the determination of the mechanism, force required to produce this specific pattern of abusive spinal injury, and the manner of death.

Incidental Massive Hydrocephalus Associated With an Unruptured Choroid Plexus Arteriovenous Malformation and Complete Agenesis of the Corpus Callosum Found in an Adult at Autopsy.

Undiagnosed significant hydrocephalus is an uncommon finding at forensic autopsy as many cases present in life with complex neurological symptoms. We present a case of a 46-year-old man with no neurological deficits or history of head trauma that was incidentally found to have a massive hydrocephalus at autopsy. This was found to be associated with an unruptured arteriovenous malformation completely confined to the choroid plexus as well as complete agenesis of the corpus callosum. The arteriovenous malformation was found to form a calcified obstruction at the foramen of Monro analogous to a mass lesion, such as a colloid cyst of the third ventricle. The association of this malformation and agenesis of the corpus callosum has never been described. Histologic examination of the brain confirmed significant loss of white matter tracts and thinning of the cortical ribbon due to pressure atrophy of the ependymal lining without significant gliosis, cortical dysplasia, or evidence of other developmental malformations. Autopsy is a vital tool in the evaluation of such rare cases, enhances epidemiologic data, and increases the understanding of these pathophysiological associations.

Atherosclerotic and Hypertensive Cardiovascular Disease are Associated with Death at Sublethal Carboxyhemoglobin Levels: A Postmortem Study.

Residential fires are a significant cause for morbidity and mortality in the United States. Death is often the result of soot and smoke inhalation causing carbon monoxide (CO) toxicity. The approximate lethal level of carboxyhemoglobin (COHb) in healthy adults has been well described. However, a significant number of medical examiner cases involve infirmed decedents, often elderly, with complex cardiovascular disease burdens. It is well known that death in these cases will occur at sublethal levels of COHb; however, increased lethality has been largely documented via anecdotal experience and lacks quantification. Fifty-five cases were identified where death resulted from smoke and soot inhalation suffered in a residential fire. The control group, with no cardiovascular disease, had an age-adjusted mean COHb level of 61.6% at the time of death. Presence of hypertensive cardiovascular disease showed a 30% reduction in COHb (age-adjusted mean 43.2%), atherosclerotic disease showed a 33% reduction (age-adjusted mean 41.5%), and combined disease presentation accounted for 41% reduction (age-adjusted mean 36.3%). When controlling for age, atherosclerotic and hypertensive cardiovascular diseases were each associated with statistically significant decreases in COHb (p < 0.01). Increasing age was associated with decreased COHb levels at 2.8% per 10 years of life (p < 0.01), even when modeled with hypertensive and atherosclerotic disease. These findings carry important public health significance, as well as practical significance for the medical examiner when interpreting COHb levels in cases of suspected deaths due to smoke and soot inhalation.

Alternative lengthening of telomeres, ATRX loss and H3-K27M mutations in histologically defined pilocytic astrocytoma with anaplasia.

Anaplasia may be identified in a subset of tumors with a presumed pilocytic astrocytoma (PA) component or piloid features, which may be associated with aggressive behavior, but the biologic basis of this change remains unclear. Fifty-seven resections from 36 patients (23 M, 13 F, mean age 32 years, range 3-75) were included. A clinical diagnosis of NF1 was present in 8 (22%). Alternative lengthening of telomeres (ALT) was assessed by telomere-specific FISH and/or CISH. A combination of immunohistochemistry, DNA sequencing and FISH were used to study BRAF, ATRX, CDKN2A/p16, mutant IDH1 p.R132H and H3-K27M proteins. ALT was present in 25 (69%) cases and ATRX loss in 20 (57%), mostly in the expected association of ALT+/ATRX- (20/24, 83%) or ALT-/ATRX+ (11/11, 100%). BRAF duplication was present in 8 (of 26) (31%). H3-K27M was present in 5 of 32 (16%) cases, all with concurrent ATRX loss and ALT. ALT was also present in 9 (of 11) cases in the benign PA precursor, 7 of which also had ATRX loss in both the precursor and the anaplastic tumor. In a single pediatric case, ALT and ATRX loss developed in the anaplastic component only, and in another adult case, ALT was present in the PA-A component only, but ATRX was not tested. Features associated with worse prognosis included subtotal resection, adult vs. pediatric, presence of a PA precursor preceding a diagnosis of anaplasia, necrosis, presence of ALT and ATRX expression loss. ALT and ATRX loss, as well as alterations involving the MAPK pathway, are frequent in PA with anaplasia at the time of development of anaplasia or in their precursors. Additionally, a small subset of PA with anaplasia have H3-K27M mutations. These findings further support the concept that PA with anaplasia is a neoplasm with heterogeneous genetic features and alterations typical of both PA and diffuse gliomas.

Cardiac Involvement in Sarcoidosis Deaths in Wayne County, Michigan: A 20-Year Retrospective Study.

BACKGROUND: Sarcoidosis is a disease of unknown etiology characterized by the formation of noncaseating, nonnecrotizing granulomas in various organ systems. METHODS: Reviews of 84 cases of natural death with sarcoidosis between the years 1996 and 2017 autopsied at Wayne County. RESULTS: The median age of decedents was 44 years (29 - 59 years of age). Blacks comprised 95% of the cohort, and 52% were female. Sarcoidosis or direct sequelae were the cause of death in 79% of cases. Twenty-nine percent of patients had a documented history of sarcoidosis and 70% of patients had evidence of systemic sarcoidosis. The most common sites of involvement were lungs or hilar lymph nodes (92%), heart (45%), liver (39%), and spleen (30%). Decedents with cardiac involvement were more likely to have no documented history of sarcoidosis (87% vs. 59%, p=0.004), more likely to have died of a sarcoidosis-related cause (97% vs. 65%, p<0.001), and died at a younger mean age (41 years vs. 46 years, p=0.001). In addition, individuals with cardiac involvement commonly had concurrent multiorgan involvement including lungs (90%), lymph nodes (38%), liver (40%), spleen (32%), and kidneys (7%). CONCLUSIONS: Cardiac sarcoidosis is a uniquely poor prognostic factor and carries an increased risk of sudden death as shown by a disproportionate representation among medical examiner cases of sarcoidosis. Our findings suggest that approximately 40% may have asymptomatic cardiac involvement. The distribution of sarcoidosis within our cohort suggests that there is potentially a large undiagnosed and/or underdiagnosed demographic within large urban centers, such as Detroit, Michigan.

Gas Chromatography Mass Spectrometry (GC-MS) for Identification of Designer Stimulants Including 2C Amines, NBOMe Compounds, and Cathinones in Urine.

Phenethylamine derivatives are being increasingly exploited for recreational use as "designer" stimulants designed to mimic psychostimulant properties of amphetamine or other illicit substances like 3,4-methylenedioxymethamphetamine (MDMA [ecstasy]). Clandestine operations meticulously design phenethylamines so the user can bypass legal action when detected, as many of these are yet to be regulated by government authorities. Substituted phenethylamines or 2C amines, N-methoxybenzyl derivatives of the corresponding 2C amines commonly known as NBOMe compounds, and cathinones are among the most commonly abused phenethylamines. Current FDA-approved assays used in screening for illicit drug use lack the sensitivity needed to detect designer stimulants making it challenging for toxicologists to accurately identify these compounds. Gas chromatography mass spectrometry (GC-MS) is a sensitive method for identifying designer stimulants. This unit describes and compares two qualitative GC-MS methods for identifying 2C amines, NBOMe compounds, and cathinones in urine. © 2017 by John Wiley & Sons, Inc.

Sucrose increases the activation energy barrier for actin-myosin strong binding.

To determine the mechanism by which sucrose slows in vitro actin sliding velocities, V, we used stopped flow kinetics and a single molecule binding assay, SiMBA. We observed that in the absence of ATP, sucrose (880mM) slowed the rate of actin-myosin (A-M) strong binding by 71±8% with a smaller inhibitory effect observed on spontaneous rigor dissociation (21±3%). Similarly, in the presence of ATP, sucrose slowed strong binding associated with Pi release by 85±9% with a smaller inhibitory effect on ATP-induced A-M dissociation, kT (39±2%). Sucrose had no noticeable effect on any other step in the ATPase reaction. In SiMBA, sucrose had a relatively small effect on the diffusion coefficient for actin fragments (25±2%), and with stopped flow we showed that sucrose increased the activation energy barrier for A-M strong binding by 37±3%, indicating that sucrose inhibits the rate of A-M strong binding by slowing bond formation more than diffusional searching. The inhibitory effects of sucrose on the rate of A-M rigor binding (71%) are comparable in magnitude to sucrose's effects on both V (79±33% decrease) and maximal actin-activated ATPase, kcat, (81±16% decrease), indicating that the rate of A-M strong bond formation significantly influences both kcat and V.

The myosin duty ratio tunes the calcium sensitivity and cooperative activation of the thin filament.

In striated muscle, calcium binding to the thin filament (TF) regulatory complex activates actin-myosin ATPase activity, and actin-myosin kinetics in turn regulates TF activation. However, a quantitative description of the effects of actin-myosin kinetics on the calcium sensitivity (pCa50) and cooperativity (nH) of TF activation is lacking. With the assumption that TF structural transitions and TF-myosin binding transitions are inextricably coupled, we advanced the principles established by Kad et al. [Kad, N., et al. (2005) Proc. Natl. Acad. Sci. U.S.A. 102, 16990-16995] and Sich et al. [Sich, N. M., et al. (2011) J. Biol. Chem. 285, 39150-39159] to develop a simple model of TF regulation, which predicts that pCa50 varies linearly with duty ratio and that nH is maximal near physiological duty ratios. Using in vitro motility to determine the calcium sensitivity of TF sliding velocities, we measured pCa50 and nH at different myosin densities and in the presence of ATPase inhibitors. The observed effects of myosin density and actin-myosin duty ratio on pCa50 and nH are consistent with our model predictions. In striated muscle, pCa50 must match cytosolic calcium concentrations and a maximal nH optimizes calcium responsiveness. Our results indicate that pCa50 and nH can be predictably tuned through TF-myosin ATPase kinetics and that drugs and disease states that alter ATPase kinetics can, through their effects on calcium sensitivity, alter the efficiency of muscle contraction.