X-ray analytic microscopy with CT-guided sample extraction to analyze potential projectile fragments in a dead serow.

In forensic pathology, it is important to detect and recover as evidence residual metal particles and projectiles when evaluating potential gunshot wounds. This process can be challenging when the bullets are fragmented. This report presents our experience using multiple modalities to analyze the wound of an illegally killed Japanese serow (Capricornis crispus) found in a mountainous region without its head and hind limbs. We performed postmortem computed tomography (PMCT) and necropsy that showed a distant-range gunshot wound of the neck likely created by a centerfire rifle. A postmortem cut through the neck and absent head precluded a complete evaluation. To determine the composition of the metal-like fragments in the neck, sampling and metal analysis were performed in two ways. Samples extracted from the exposed wound surface without CT guidance were analyzed directly using inductively coupled plasma mass spectrometry (ICP-MS). Samples from the bone, muscles, and cervical cord extracted under CT guidance were analyzed using x-ray analytic microscopy (XGT-9000, HORIBA, Kyoto, Japan). In wound surface samples, silicon and iron were detected as the main components on ICP-MS, suggesting that the materials were gravel. The samples taken under CT guidance and analyzed with XGT-9000 revealed that the high-density CT areas were mainly composed of lead. Combining CT-guided sample extraction and XGT-9000 can be useful for retrieving true projectile fragments and avoiding the confusion created by erroneously sampling non-projectile surface materials.

Can computed tomography replace or supplement autopsy?

Postmortem computed tomography (PMCT) has been integrated into the practice of many forensic pathologists. To evaluate the utility of PMCT in supplementing and/or supplanting medicolegal autopsy, we conducted a prospective double-blind comparison of abnormal findings reported by the autopsy pathologist with those reported by a radiologist reviewing the PMCT. We reviewed 890 cases: 167 with blunt force injury (BFI), 63 with pediatric trauma (under 5 years), 203 firearm injuries, and 457 drug poisoning deaths. Autopsy and radiology reports were coded using the Abbreviated Injury Scale and abnormal findings and cause of death (COD) were compared for congruence in consensus conferences with novel pathologists and radiologists. Overall sensitivity for recognizing abnormal findings was 71% for PMCT and 74.6% for autopsy. Sensitivities for PMCT/autopsy were 74%/73.1% for BFI, 61.5%/71.4% for pediatric trauma, 84.9%/83.7% for firearm injuries, and 56.5%/66.4% for drug poisoning deaths. COD assigned by reviewing PMCT/autopsy was correct in 88%/95.8% of BFI cases, 99%/99.5% of firearm fatalities, 82.5%/98.5% of pediatric trauma deaths, and 84%/100% of drug poisoning deaths of individuals younger than 50. Both autopsy and PMCT were imperfect in recognizing injuries. However, both methods identified the most important findings and are sufficient to establish COD in cases of BFI, pediatric trauma, firearm injuries and drug poisoning in individuals younger than 50. Ideally, all forensic pathologists would have access to a CT scanner and a consulting radiologist. This would allow a flexible approach that meets the diagnostic needs of each case and best serves decedents' families and other stakeholders.

Escalating costs of self-injury mortality in the 21st century United States: an interstate observational study.

BACKGROUND: Estimating the economic costs of self-injury mortality (SIM) can inform health planning and clinical and public health interventions, serve as a basis for their evaluation, and provide the foundation for broadly disseminating evidence-based policies and practices. SIM is operationalized as a composite of all registered suicides at any age, and 80% of drug overdose (intoxication) deaths medicolegally classified as 'accidents,' and 90% of corresponding undetermined (intent) deaths in the age group 15 years and older. It is the long-term practice of the United States (US) Centers for Disease Control and Prevention (CDC) to subsume poisoning (drug and nondrug) deaths under the injury rubric. This study aimed to estimate magnitude and change in SIM and suicide costs in 2019 dollars for the United States (US), including the 50 states and the District of Columbia. METHODS: Cost estimates were generated from underlying cause-of-death data for 1999/2000 and 2018/2019 from the US Centers for Disease Control and Prevention's (CDC's) Wide-ranging ONline Data for Epidemiologic Research (WONDER). Estimation utilized the updated version of Medical and Work Loss Cost Estimation Methods for CDC's Web-based Injury Statistics Query and Reporting System (WISQARS). Exposures were medical expenditures, lost work productivity, and future quality of life loss. Main outcome measures were disaggregated, annual-averaged total and per capita costs of SIM and suicide for the nation and states in 1999/2000 and 2018/2019. RESULTS: 40,834 annual-averaged self-injury deaths in 1999/2000 and 101,325 in 2018/2019 were identified. Estimated national costs of SIM rose by 143% from $0.46 trillion to $1.12 trillion. Ratios of quality of life and work losses to medical spending in 2019 US dollars in 2018/2019 were 1,476 and 526, respectively, versus 1,419 and 526 in 1999/2000. Total national suicide costs increased 58%-from $318.6 billion to $502.7 billion. National per capita costs of SIM doubled from $1,638 to $3,413 over the observation period; costs of the suicide component rose from $1,137 to $1,534. States in the top quintile for per capita SIM, those whose cost increases exceeded 152%, concentrated in the Great Lakes, Southeast, Mideast and New England. States in the bottom quintile, those with per capita cost increases below 70%, were located in the Far West, Southwest, Plains, and Rocky Mountain regions. West Virginia exhibited the largest increase at 263% and Nevada the smallest at 22%. Percentage per capita cost increases for suicide were smaller than for SIM. Only the Far West, Southwest and Mideast were not represented in the top quintile, which comprised states with increases of 50% or greater. The bottom quintile comprised states with per capita suicide cost increases below 24%. Regions represented were the Far West, Southeast, Mideast and New England. North Dakota and Nevada occupied the extremes on the cost change continuum at 75% and - 1%, respectively. CONCLUSION: The scale and surge in the economic costs of SIM to society are large. Federal and state prevention and intervention programs should be financed with a clear understanding of the total costs-fiscal, social, and personal-incurred by deaths due to self-injurious behaviors.

Activation and On-Scene Intervals for Severe Trauma EMS Interventions: An Analysis of the NEMSIS Database.

Objective: Time to care is a determinant of trauma patient outcomes, and timely delivery of trauma care to severely injured patients is critical in reducing mortality. Numerous studies have analyzed access to care using prehospital intervals from a Carr et al. meta-analysis of studies from 1975 to 2005. Carr et al.'s research sought to determine national mean activation and on-scene intervals for trauma patients using contemporary emergency medical services (EMS) records. Since the Carr et al. meta-analysis was published, the National Highway Traffic Safety Administration (NHTSA) created and refined the National Emergency Medical Services Information System (NEMSIS) database. We sought to perform a modern analysis of prehospital intervals to establish current standards and temporal patterns.Methods: We utilized NEMSIS to analyze EMS data of trauma patients from 2016 to 2019. The dataset comprises more than 94 million EMS records, which we filtered to select for severe trauma and stratified by type of transport and rurality to calculate mean activation and on-scene intervals. Furthermore, we explored the impact of basic life support (BLS) and advanced life support (ALS) of ground units on activation and on-scene time intervals.Results: Mean activation and on-scene intervals for ground transport were statistically different when stratified by rurality. Urban, suburban, and rural ground activation intervals were 2.60 ± 3.94, 2.88 ± 3.89, and 3.33 ± 4.58 minutes, respectively. On-scene intervals were 15.50 ± 10.46, 17.56 ± 11.27, and 18.07 ± 16.13 minutes, respectively. Mean helicopter transport activation time was 13.75 ± 7.44 minutes and on-scene time was 19.42 ± 16.09 minutes. This analysis provides an empirically defined mean for activation and on-scene times for trauma patients based on transport type and rurality. Results from this analysis proved to be significantly longer than the previous analysis, except for helicopter transport on-scene time. Shorter mean intervals were seen in ALS compared to BLS for activation intervals, however ALS on-scene intervals were marginally longer than BLS.Conclusions: With the increasing sophistication of geospatial technologies employed to analyze access to care, these intervals are the most accurate and up-to-date and should be included in access to care models.

Accuracy of forensic pathologists in incorporating post-mortem CT (PMCT) in forensic death investigation.

Post-mortem computed tomography (PMCT) is now performed routinely in some medical examiner's offices, and the images are typically interpreted by forensic pathologists. In this study, the question of whether pathologists appropriately identify significant PMCT findings and incorporate them into the death investigation report and the cause and manner of death (COD and MOD) statements was addressed. We retrospectively reviewed 200 cases where PMCT was performed. The cases were divided into four categories: (1) full autopsy without radiology consultation (n = 77), (2) external exam without radiology consultation (n = 79), (3) full autopsy with radiology consultation (n = 26), (4) external exam with radiology consultation (n = 18). A radiologist (not the consult radiologist) read the PMCT images, and a pathologist (not the case pathologist) reviewed the case pathologist's post-mortem examination report in tandem to determine any PMCT findings omitted from the report. Omitted findings were classified into error types according to a modified Goldman classification including Major 1: Unrecognized fatal injury or pathology that would change COD and/or MOD, and Major 2: Unrecognized fatal injury or pathology that would not change COD and/or MOD. A total of 13 Major errors were identified (6.5%), and none definitively changed the MOD. All four Major-1 errors which could change the COD were found in Category 2. Of 9 Major-2 errors, 2 occurred in Category 1, 6 occurred in Category 2, and 1 occurred in Category 4. In conclusion, forensic pathologists who routinely utilize computed tomography (CT) interpret CT images well enough to reliably certify the COD and MOD.

Association of State Social and Environmental Factors With Rates of Self-injury Mortality and Suicide in the United States.

Importance: Self-injury mortality (SIM) combines suicides and the preponderance of drug misuse-related overdose fatalities. Identifying social and environmental factors associated with SIM and suicide may inform etiologic understanding and intervention design. Objective: To identify factors associated with interstate SIM and suicide rate variation and to assess potential for differential suicide misclassification. Design, Setting, and Participants: This cross-sectional study used a partial panel time series with underlying cause-of-death data from 50 US states and the District of Columbia for 1999-2000, 2007-2008, 2013-2014 and 2018-2019. Applying data from the Centers for Disease Control and Prevention, SIM includes all suicides and the preponderance of unintentional and undetermined drug intoxication deaths, reflecting self-harm behaviors. Data were analyzed from February to June 2021. Exposures: Exposures included inequity, isolation, demographic characteristics, injury mechanism, health care access, and medicolegal death investigation system type. Main Outcomes and Measures: The main outcome, SIM, was assessed using unstandardized regression coefficients of interstate variation associations, identified by the least absolute shrinkage and selection operator; ratios of crude SIM to suicide rates per 100 000 population were assessed for potential differential suicide misclassification. Results: A total of 101 325 SIMs were identified, including 74 506 (73.5%) among males and 26 819 (26.5%) among females. SIM to suicide rate ratios trended upwards, with an accelerating increase in overdose fatalities classified as unintentional or undetermined (SIM to suicide rate ratio, 1999-2000: 1.39; 95% CI, 1.38-1.41; 2018-2019: 2.12; 95% CI, 2.11-2.14). Eight states recorded a SIM to suicide rate ratio less than 1.50 in 2018-2019 vs 39 states in 1999-2000. Northeastern states concentrated in the highest category (range, 2.10-6.00); only the West remained unrepresented. Least absolute shrinkage and selection operator identified 8 factors associated with the SIM rate in 2018-2019: centralized medical examiner system (ß = 4.362), labor underutilization rate (ß = 0.728), manufacturing employment (ß = -0.056), homelessness rate (ß = -0.125), percentage nonreligious (ß = 0.041), non-Hispanic White race and ethnicity (ß = 0.087), prescribed opioids for 30 days or more (ß = 0.117), and percentage without health insurance (ß = -0.013) and 5 factors associated with the suicide rate: percentage male (ß = 1.046), military veteran (ß = 0.747), rural (ß = 0.031), firearm ownership (ß = 0.030), and pain reliever misuse (ß = 1.131). Conclusions and Relevance: These findings suggest that SIM rates were associated with modifiable, upstream factors. Although embedded in SIM, suicide unexpectedly deviated in proposed social and environmental determinants. Heterogeneity in medicolegal death investigation processes and data assurance needs further characterization, with the goal of providing the highest-quality reports for developing and tracking public health policies and practices.

Fatal self-injury in the United States, 1999-2018: Unmasking a national mental health crisis.

BACKGROUND: Suicides by any method, plus 'nonsuicide' fatalities from drug self-intoxication (estimated from selected forensically undetermined and 'accidental' deaths), together represent self-injury mortality (SIM)-fatalities due to mental disorders or distress. SIM is especially important to examine given frequent undercounting of suicides amongst drug overdose deaths. We report suicide and SIM trends in the United States of America (US) during 1999-2018, portray interstate rate trends, and examine spatiotemporal (spacetime) diffusion or spread of the drug self-intoxication component of SIM, with attention to potential for differential suicide misclassification. METHODS: For this state-based, cross-sectional, panel time series, we used de-identified manner and underlying cause-of-death data for the 50 states and District of Columbia (DC) from CDC's Wide-ranging Online Data for Epidemiologic Research. Procedures comprised joinpoint regression to describe national trends; Spearman's rank-order correlation coefficient to assess interstate SIM and suicide rate congruence; and spacetime hierarchical modelling of the 'nonsuicide' SIM component. FINDINGS: The national annual average percentage change over the observation period in the SIM rate was 4.3% (95% CI: 3.3%, 5.4%; p<0.001) versus 1.8% (95% CI: 1.6%, 2.0%; p<0.001) for the suicide rate. By 2017/2018, all states except Nebraska (19.9) posted a SIM rate of at least 21.0 deaths per 100,000 population-the floor of the rate range for the top 5 ranking states in 1999/2000. The rank-order correlation coefficient for SIM and suicide rates was 0.82 (p<0.001) in 1999/2000 versus 0.34 (p = 0.02) by 2017/2018. Seven states in the West posted a ≥ 5.0% reduction in their standardised mortality ratios of 'nonsuicide' drug fatalities, relative to the national ratio, and 6 states from the other 3 major regions a >6.0% increase (p<0.05). INTERPRETATION: Depiction of rising SIM trends across states and major regions unmasks a burgeoning national mental health crisis. Geographic variation is plausibly a partial product of local heterogeneity in toxic drug availability and the quality of medicolegal death investigations. Like COVID-19, the nation will only be able to prevent SIM by responding with collective, comprehensive, systemic approaches. Injury surveillance and prevention, mental health, and societal well-being are poorly served by the continuing segregation of substance use disorders from other mental disorders in clinical medicine and public health practice. FUNDING: This study was partially funded by the National Centre for Injury Prevention and Control, US Centers for Disease Control and Prevention (R49CE002093) and the US National Institute on Drug Abuse (1UM1DA049412-01; 1R21DA046521-01A1).

Overcoming the limitations of 'accident' as a manner of death for drug overdose mortality: case for a death certificate checkbox.

Collectively, the epidemic increases in the United States of opioid-related deaths and suicides during the first two decades of the 21st century have exposed shortcomings in current forensic and epidemiological approaches for determining and codifying manner of death-a vital function fulfilled by medical examiners, coroners and nosologists-the foundation for the National Violent Death Reporting System (NVDRS), an incident-based surveillance system providing individual-level information on decedent characteristics, manner, cause and circumstances of suicide, homicide and other violent injury deaths. Drug intoxication deaths are generally classified as 'accidents' or unintentional, a fundamental mischaracterisation; most arose from repetitive self-harm behaviours related to substance acquisition and misuse. Moreover, given the burden of affirmative evidence required to determine suicide, many of these 'accidents' likely reflected unrecognised intentional acts-that is, suicides. Addition of a simple checkbox for self-injury mortality on the death certificate would enrich the National Death Index and NVDRS, and in turn, inform prevention and clinical research, and enhance the evaluation of prevention programmes and therapeutic regimens.

Design and Construction of a Biosafety Level 3 Autopsy Laboratory.

CONTEXT.­: Autopsy pathologists, including medical examiners, provide valuable public health support for infectious disease deaths through surveillance for deaths of public health concern including emerging infections, identifying causative organisms for unexplained deaths, and providing insights into the pathology and pathogenesis of novel or unusual infections. However, autopsy poses biosafety risks to workers within and outside the laboratory. The highest rates of laboratory-acquired infections occur in autopsy workers. OBJECTIVE.­: To design and construct an appropriately biosafe autopsy laboratory. DESIGN.­: We conducted a biosafety risk assessment for autopsy workers using the process developed by the US Centers for Disease Control and Prevention and National Institutes of Health and applied these findings as the basis of laboratory design and construction. RESULTS.­: Autopsy workers are unpredictably exposed to a variety of infectious organisms, including hepatitis C virus, HIV, and Mycobacterium tuberculosis. Hazardous autopsy procedures include using and encountering sharp objects and the generation of aerosols from dissection, fluid aspiration, rinsing tissues, and dividing bone with an oscillating saw. CONCLUSIONS.­: Exposure to blood-borne and airborne pathogens from procedures that can cause cutaneous inoculation and inhalation of aerosols indicates that human autopsies should be performed at biosafety level 3. We designed a large, entirely biosafety level 3 medical examiner autopsy laboratory using design principles and characteristics that can be scaled to accommodate smaller academic or other hospital-based autopsy spaces. Containment was achieved through a concentric ring design, with access control at interface zones. As new autopsy laboratories are planned, we strongly recommend that they be designed to function uniformly at biosafety level 3.

Postmortem Computed Tomography in Firearm Homicides: A Retrospective Case Series.

Postmortem computed tomography (PMCT) is integrated into the evaluation of decedents in several American medical examiner offices and medicolegal death investigative centers in many other countries. We retrospectively investigated the value of PMCT in a series of firearm homicide cases from a statewide centralized medical examiner's office that occurred during 2016. Autopsies were performed or supervised by board-certified forensic pathologists who reviewed the PMCT scans prior to autopsy. PMCT scans were re-evaluated by a forensic radiologist blinded to the autopsy findings and scored by body region (head-neck, thoracoabdominal, and extremities). Injury discrepancies were scored using a modified Goldman classification and analyzed with McNemar's test. We included 60 males and 20 females (median age 31 years, range 3-73). Based on PMCT, 56 (79.1%) cases had injuries relevant to the cause of death in a single body region (24 head-neck region, 32 thoracoabdominal region). Out of these 56 cases, 9 had a missed major diagnosis by PMCT outside that region, including 6 extremity injuries visible during standard external examination. Yet all had evident lethal firearm injury. We showed that PMCT identifies major firearm injuries in homicide victims and excludes injuries related to the cause of death in other regions when a single body region is injured. Although PMCT has a known limited sensitivity for soft tissue and vascular pathology, it can be combined with external examination to potentially reduce or focus dissections in some of these cases depending on the circumstances and medicolegal needs.

Evaluating the Potential for Unintentional Occupational Exposure to Fentanyl and Fentanyl Analogues Among Medicolegal Death Investigators and Autopsy Technicians.

Recent increases in deaths in the United States from synthetic opioids such as fentanyl and fentanyl analogues (fentanyls) have raised concerns about possible occupational exposures to these potent agents. Medicolegal death investigators and autopsy suite staff might perform job tasks involving exposure to fentanyls. The potential for exposure to fentanyls among medicolegal death investigators and autopsy technicians at a state medical examiner's office was evaluated through review of caseload characteristics, injury and illness logs, and procedures and policies and discussions with management and employee representatives. The evaluation showed that this medical examiner's office had low potential for work-related exposure to fentanyls; its standard operating procedures and personal protective equipment requirements should reduce the potential for occupational exposure. Medicolegal death investigation agencies can develop and implement guidance to control exposures and provide workforce education and training to reduce the potential for work-related exposure to fentanyls.

Unrecognised self-injury mortality (SIM) trends among racial/ethnic minorities and women in the USA.

AIM: To assess whether an enhanced category combining suicides with nonsuicide drug self-intoxication fatalities more effectively captures the burden of self-injury mortality (SIM) in the USA among US non-Hispanic black and Hispanic populations and women irrespective of race/ethnicity. METHODS: This observational study used deidentified national mortality data for 2008-2017 from the CDC's Web-based Injury Statistics Query and Reporting System. SIM comprised suicides by any method and age at death plus estimated nonsuicide drug self-intoxication deaths at age ≥15 years. Measures were crude SIM and suicide rates; SIM-to-suicide rate ratios; and indices of premature mortality. RESULTS: While the suicide rate increased by 29% for blacks, 36% for Hispanics and 25% for non-Hispanic whites between 2008 and 2017, corresponding SIM rate increases were larger at 109%, 69% and 55% (p<0.0001). SIM:suicide rate ratio gaps were widest among blacks but similar for the other two groups. Gaps were wider for females than males, especially black females whose ratios measured ≥3.71 across the observation period versus <3.00 for white and Hispanic counterparts. Total lost years of life for Hispanic, white and black SIM decedents in 2017 were projected to be 42.6, 37.1 and 32.4, respectively. CONCLUSION: Application of SIM exposed substantial excess burdens from substance poisoning relative to suicide for minorities, particularly non-Hispanic blacks and for women generally. Results underscored the need to define, develop, implement and evaluate comprehensive strategies to address common antecedents of self-injurious behaviours.

Protocols, practices, and needs for investigating sudden unexpected infant deaths.

Understanding case identification practices, protocols, and training needs of medical examiners and coroners (MEC) may inform efforts to improve cause-of-death certification. We surveyed a U.S.-representative sample of MECs and described investigation practices and protocols used in certifying sudden unexpected infant deaths (SUID). We also identified MEC training and resource needs. Of the 377 respondents, use of the SUID Investigation Reporting Form or an equivalent was 89% for large, 87% for medium, and 52% for small jurisdictions. Routine completion of infant medical history, witness interviews, autopsy, photos or videos, and family social history for infant death investigations was ≥80%, but routine scene re-creation with a doll was 30% in small, 64% in medium, and 59% in large offices. Seventy percent of MECs reported infant death investigation training needs. Increased training and use of standardized practices may improve SUID cause-of-death certification, allowing us to better understand SUID.

Multi-Institutional Multidisciplinary Injury Mortality Investigation in the Civilian Pre-Hospital Environment (MIMIC): a methodology for reliably measuring prehospital time and distance to definitive care.

The detailed study of prehospital injury death is critical to advancing trauma and emergency care, as circumstance and causality have significant implications for the development of mitigation strategies. Though there is no true 'Golden Hour,' the time from injury to care is a critical element in the analysis matrix, particularly in patients with severe injury. Currently, there is no standard method for the assessment of time to definitive care after injury among prehospital deaths. This article describes a methodology to estimate total prehospital time and distance for trauma patients transported via ground emergency medical services and helicopter emergency medical services using a geographic information system. Data generated using this method, along with medical examiner and field investigation reports, will be used to estimate the potential survivability of prehospital trauma deaths occurring in five US states and the District of Columbia as part of the Multi-Institutional Multidisciplinary Injury Mortality Investigation in the Civilian Pre-Hospital Environment study. One goal of this work is to develop standard metrics for the assessment of total prehospital time and distance, which can be used in the future for more complex spatial analyses to gain a deeper understanding of trauma center access. Results will be used to identify high priority areas for research and development in injury prevention, trauma system performance improvement, and public health.

The Opioid Epidemic: Moving Toward an Integrated, Holistic Analytical Response.

In many jurisdictions, public safety and public health entities are working together to enhance the timeliness and accuracy of the analytical characterization and toxicology testing of novel synthetic opioids. The improved sharing and early detection of these analytical data are intended to inform surveillance, interdiction efforts, patient intervention and treatment, all of which are critical to curbing the opioid epidemic. Forensic practitioners working to identify novel synthetic opioids struggle to provide timely results when encountering new or unknown substances, such as the fentanyl analogs. These compounds, which mimic heroin in pharmacologic effect but can be far more potent, are inconsistently present in chemical identification libraries, and are currently largely unavailable as reference materials for analytical comparison. Additionally, federal, state and local governments as well as nongovernmental organizations require potency, toxicity and potential-for-abuse data to evaluate the potential health risks of emerging drug threats. Subsequent scheduling efforts and criminal prosecutions also require these thorough drug characterization studies. Pilot programs have demonstrated that early communication of real-time drug toxicity and analytical data significantly impacts the successful response to emerging opioids. High-quality, real-time, national-level data on chemical composition, toxicological test data, drug toxicity and overdoses, and analysis of seized materials by law enforcement are needed to track drug trends. However, the USA still lacks a national system to coordinate and communicate toxicology, medical and medical examiner and coroner data with the broader medical and law enforcement communities. Opportunities to address these gaps as well as recent advancements collected through interagency efforts and technical workshops in the toxicology and analytical chemistry communities are presented here. Opportunities for partnership, increased communication and expanding best practices to move toward an integrated, holistic analytical response are also explored.

Upregulation of P2Y2R, Active uPA, and PAI-1 Are Essential Components of Hantavirus Cardiopulmonary Syndrome.

Sin Nombre virus (SNV) causes hantavirus cardiopulmonary pulmonary syndrome (HCPS) with the loss of pulmonary vascular endothelial integrity, and pulmonary edema without causing cytopathic effects on the vascular endothelium. HCPS is associated primarily with a dysregulated immune response. We previously found occult signs of hemostatic imbalance in the form of a sharp >30-100 fold increase in the expression of plasminogen activator inhibitor type 1 (PAI-1), in serial blood plasma draws of terminal stage-patients. However, the mechanism of the increase in PAI-1 remains unclear. PAI-1 is a primary inhibitor of fibrinolysis caused by tissue plasminogen activator (tPA) and urokinase plasminogen activator plasma (uPA). Here, we investigate factors that contribute to PAI-1 upregulation during HCPS. Using zymography, we found evidence of PAI-1-refractory uPA activity and no tPA activity in plasma samples drawn from HCPS patients. The sole prevalence of uPA activity suggested that severe inflammation drove PAI-1 activity. We have recently reported that the P2Y2 receptor (P2Y2R) mediates SNV infectivity by interacting in cis with ß3 integrins, which activates the latter during infection. P2Y2R is a known effector for several biological processes relevant to HCPS pathogenesis, such as upregulation of tissue factor (TF), a primary initiator of the coagulation cascade, stimulating vascular permeability and leukocyte homing to sites of infection. As P2Y2R is prone to upregulation under conditions of inflammation, we compared the expression level of P2Y2R in formalin fixed tissues of HCPS decedents using a TaqMan assay and immunohistochemistry. Our TaqMan results show that the expression of P2Y2R is upregulated significantly in HCPS cases compared to non- HCPS controls (P < 0.001). Immunohistochemistry showed that lung macrophages were the primary reservoir of high and coincident localization of P2Y2R, uPA, PAI-1, and TF antigens. We also observed increased staining for SNV antigens in the same tissue segments where P2Y2R expression was upregulated. Conversely, sections of low P2Y2R expression showed weak manifestations of macrophages, SNV, PAI-1, and TF. Coincident localization of P2Y2R and PAI-1 on macrophage deposits suggests an inflammation-dependent mechanism of increasing pro-coagulant activity in HCPS in the absence of tissue injury.

Method overtness, forensic autopsy, and the evidentiary suicide note: A multilevel National Violent Death Reporting System analysis.

OBJECTIVE: Higher prevalence of suicide notes could signify more conservatism in accounting and greater proneness to undercounting of suicide by method. We tested two hypotheses: (1) an evidentiary suicide note is more likely to accompany suicides by drug-intoxication and by other poisoning, as less violent and less forensically overt methods, than suicides by firearm and hanging/suffocation; and (2) performance of a forensic autopsy attenuates any observed association between overtness of method and the reported presence of a note. METHODS: This multilevel (individual/county), multivariable analysis employed a generalized linear mixed model (GLMM). Representing the 17 states participating in the United States National Violent Death Reporting System throughout 2011-2013, the study population comprised registered suicides, aged 15 years and older. Decedents totaled 32,151. The outcome measure was relative odds of an authenticated suicide note. RESULTS: An authenticated suicide note was documented in 31% of the suicide cases. Inspection of the full multivariable model showed a suicide note was more likely to manifest among drug intoxication (adjusted odds ratio [OR], 1.70; 95% CI, 1.56, 1.85) and other poisoning suicides (OR, 2.12; 1.85, 2.42) than firearm suicides, the referent. Respective excesses were larger when there was no autopsy or autopsy status was unknown (OR, 1.86; 95% CI, 1.61, 2.14) and (OR, 2.25; 95% CI, 1.86, 2.72) relative to the comparisons with a forensic autopsy (OR, 1.62, 95% CI, 1.45, 1.82 and OR, 2.01; 95% CI, 1.66, 2.43). Hanging/suffocation suicides did not differ from the firearm referent given an autopsy. CONCLUSIONS: Suicide requires substantial affirmative evidence to establish manner of death, and affirmation of drug intoxication suicides appears to demand an especially high burden of proof. Findings and their implications argue for more stringent investigative standards, better training, and more resources to support comprehensive and accurate case ascertainment, as the foundation for developing evidence-based suicide prevention initiatives.

The Role of Postmortem Computed Tomography in the Evaluation of Strangulation Deaths.

We explored the value of postmortem computed tomography (PMCT) to augment autopsy in evaluating strangulation fatalities. A literature search identified 16 studies describing autopsy findings in 576 deaths and two studies describing autopsy and PMCT findings in six deaths. Similar cases were identified from our institution, yielding 130 deaths with autopsy findings and 14 deaths with both autopsy and PMCT findings. The presence of laryngohyoid fracture and soft tissue hemorrhage was compared from autopsy and autopsy+PMCT cases. The detection rates of fractures in autopsy and autopsy+PMCT cases were not significantly different. PMCT identified all fractures observed at autopsy and five fractures not identified. While PMCT may not detect soft tissue injuries in decomposed remains or subtle internal hemorrhages in neck injury, it is equally able to detect bony injuries as autopsy and might surpass autopsy in detecting subtle fractures. We conclude PMCT is useful to supplement autopsy in strangulation cases.

Discerning suicide in drug intoxication deaths: Paucity and primacy of suicide notes and psychiatric history.

OBJECTIVE: A paucity of corroborative psychological and psychiatric evidence may be inhibiting detection of drug intoxication suicides in the United States. We evaluated the relative importance of suicide notes and psychiatric history in the classification of suicide by drug intoxication versus firearm (gunshot wound) plus hanging/suffocation-the other two major, but overtly violent methods. METHODS: This observational multilevel (individual/county), multivariable study employed a generalized linear mixed model (GLMM) to analyze pooled suicides and undetermined intent deaths, as possible suicides, among the population aged 15 years and older in the 17 states participating in the National Violent Death Reporting System throughout 2011-2013. The outcome measure was relative odds of suicide versus undetermined classification, adjusted for demographics, precipitating circumstances, and investigation characteristics. RESULTS: A suicide note, prior suicide attempt, or affective disorder was documented in less than one-third of suicides and one-quarter of undetermined deaths. The prevalence gaps were larger among drug intoxication cases than gunshot/hanging cases. The latter were more likely than intoxication cases to be classified as suicide versus undetermined manner of death (adjusted odds ratio [OR], 41.14; 95% CI, 34.43-49.15), as were cases documenting a suicide note (OR, 33.90; 95% CI, 26.11-44.05), prior suicide attempt (OR, 2.42; 95% CI, 2.11-2.77), or depression (OR, 1.61; 95% CI, 1.38 to 1.88), or bipolar disorder (OR, 1.41; 95% CI, 1.10-1.81). Stratification by mechanism/cause intensified the association between a note and suicide classification for intoxication cases (OR, 45.43; 95% CI, 31.06-66.58). Prior suicide attempt (OR, 2.64; 95% CI, 2.19-3.18) and depression (OR, 1.48; 95% CI, 1.17-1.87) were associated with suicide classification in intoxication but not gunshot/hanging cases. CONCLUSIONS: Without psychological/psychiatric evidence contributing to manner of death classification, suicide by drug intoxication in the US is likely profoundly under-reported. Findings harbor adverse implications for surveillance, etiologic understanding, and prevention of suicides and drug deaths.