Genetic Variants Associated With Unexplained Sudden Cardiac Death in Adult White and African American Individuals.

Importance: Unexplained sudden cardiac death (SCD) describes SCD with no cause identified. Genetic testing helps to diagnose inherited cardiac diseases in unexplained SCD; however, the associations between pathogenic or likely pathogenic (P/LP) variants of inherited cardiomyopathies (CMs) and arrhythmia syndromes and the risk of unexplained SCD in both White and African American adults living the United States has never been systematically examined. Objective: To investigate cases of unexplained SCD to determine the frequency of P/LP genetic variants of inherited CMs and arrhythmia syndromes. Design, Setting, and Participants: This genetic association study included 683 African American and White adults who died of unexplained SCD and were included in an autopsy registry. Overall, 413 individuals had DNA of acceptable quality for genetic sequencing. Data were collected from January 1995 to December 2015. A total of 30 CM genes and 38 arrhythmia genes were sequenced, and variants in these genes, curated as P/LP, were examined to study their frequency. Data analysis was performed from June 2018 to March 2021. Main Outcomes and Measures: The frequency of P/LP variants for CM or arrhythmia in individuals with unexplained SCD. Results: The median (interquartile range) age at death of the 413 included individuals was 41 (29-48) years, 259 (62.7%) were men, and 208 (50.4%) were African American adults. A total of 76 patients (18.4%) with unexplained SCD carried variants considered P/LP for CM and arrhythmia genes. In total, 52 patients (12.6%) had 49 P/LP variants for CM, 22 (5.3%) carried 23 P/LP variants for arrhythmia, and 2 (0.5%) had P/LP variants for both CM and arrhythmia. Overall, 41 P/LP variants for hypertrophic CM were found in 45 patients (10.9%), 9 P/LP variants for dilated CM were found in 11 patients (2.7%), and 10 P/LP variants for long QT syndrome were found in 11 patients (2.7%). No significant difference was found in clinical and heart characteristics between individuals with or without P/LP variants. African American and White patients were equally likely to harbor P/LP variants. Conclusions and Relevance: In this large genetic association study of community cases of unexplained SCD, nearly 20% of patients carried P/LP variants, suggesting that genetics may contribute to a significant number of cases of unexplained SCD. Our findings regarding both the association of unexplained SCD with CM genes and race-specific genetic variants suggest new avenues of study for this poorly understood entity.

Survey of coyotes, red foxes and wolves from Wyoming, USA, for Echinococcus granulosus s. l.

The paraphyletic group Echinococcus granulosus sensu lato is comprised of parasitic tapeworms of wild and domestic canids such as wolves (Canis lupus) and coyotes (Canis latrans), which serve as definitive hosts, and ungulates, which are the intermediate hosts. Members of this tapeworm group are characterized by both cosmopolitan distribution and zoonotic disease potential. This survey (conducted from 2012 through 2017) was designed to provide insight into the prevalence and distribution of this parasite in wild canids in Wyoming. Echinococcus sp. infections were documented in 14 of 22 gray wolves (63.6%), 1 of 182 coyotes (0.55%) and 0 of 5 red foxes (Vulpes fulva). Echinococcus granulosus s. l. was confirmed in 4 of these 14 specimens obtained from wolves with two parasite specimens corresponding morphologically with E. canadensis (G8/G10). These results suggest that wolves serve as the major definitive host of E. granulosus s. l. in Wyoming, while coyotes do not play an equivalent role. Limited sample size precludes evaluation of the importance of the red fox as a favorable definitive host. Whereas this study documents the occurrence of E. granulosus s. l. in Wyoming, the zoonotic disease risk does not appear to be high. Education remains the key to disease prevention, coupled with good hygienic practices by humans and anthelmintic treatment of domestic dogs exhibiting elevated risk of exposure.

Temporal trends and autopsy findings of SUDEP based on medico-legal investigations in the United States.

OBJECTIVE: To determine time trends and distinguishing autopsy findings of sudden unexpected death in epilepsy (SUDEP) in the United States. METHODS: We identified decedents where epilepsy/seizure was listed as cause/contributor to death or comorbid condition on the death certificate among all decedents who underwent medico-legal investigation at 3 medical examiner (ME) offices across the country: New York City (2009-2016), San Diego County (2008-2016), and Maryland (2000-2016). After reviewing all available reports, deaths classified as definite/probable/near SUDEP or SUDEP plus were included for analysis. Mann-Kendall trend test was used to analyze temporal trends in SUDEP rate for 2009-2016. Definite SUDEPs were compared to sex- and age ±2 years-matched non-SUDEP deaths with a history of epilepsy regarding autopsy findings, circumstances, and comorbidities. RESULTS: A total of 1,086 SUDEP cases were identified. There was a decreasing trend in ME-investigated SUDEP incidence between 2009 and 2016 (z = -2.2, S = -42, p = 0.028) among 3 regions. There was a 28% reduction in ME-investigated SUDEP incidence from 2009 to 2012 to 2013-2016 (confidence interval, 17%-38%, p < 0.0001). We found no correlation between SUDEP rates and the month of year or day of week. There was no difference between SUDEP and non-SUDEP deaths regarding neurodevelopmental abnormalities, pulmonary congestion/edema, and myocardial fibrosis. CONCLUSIONS: There was a decreasing monotonic trend in ME-investigated SUDEP incidence over 8 years, with a 28% reduction in incidence from 2009-2012 to 2013-2016. Unlike SIDS and sudden cardiac death, we found no correlation between SUDEP and the season of year or day of week. No autopsy findings distinguished SUDEP from non-SUDEP deaths.

Socioeconomic disparities in SUDEP in the US.

OBJECTIVE: To determine the impact of socioeconomic status (SES) on sudden unexpected death in epilepsy (SUDEP) rates. METHODS: We queried all decedents presented for medico-legal investigation at 3 medical examiner (ME) offices across the country (New York City, Maryland, San Diego County) in 2009 to 2010 and 2014 to 2015. We identified all decedents for whom epilepsy/seizure was listed as cause/contributor to death or comorbid condition on the death certificate. We then reviewed all available reports. Decedents determined to have SUDEP were included for analysis. We used median income in the ZIP code of residence as a surrogate for SES. For each region, zip code regions were ranked by median household income and divided into quartiles based on total population for 2 time periods. Region-, age-, and income-adjusted epilepsy prevalence was estimated in each zip code. SUDEP rates in the highest and lowest SES quartiles were evaluated to determine disparity. Examined SUDEP rates in 2 time periods were also compared. RESULTS: There were 159 and 43 SUDEP cases in the lowest and highest SES quartiles. ME-investigated SUDEP rate ratio between the lowest and highest SES quartiles was 2.6 (95% confidence interval [CI] 1.7-4.1, p < 0.0001) in 2009 to 2010 and 3.3 (95% CI 1.9-6.0, p < 0.0001) in 2014 to 2015. There was a significant decline in overall SUDEP rate between the 2 study periods (36% decrease, 95% CI 22%-48%, p < 0.0001). CONCLUSION: ME-investigated SUDEP incidence was significantly higher in people with the lowest SES compared to the highest SES. The difference persisted over a 5-year period despite decreased overall SUDEP rates.

Prevalence of long gun use in Maryland firearm suicides.

BACKGROUND: Firearms account for the majority of US suicides, largely due to lethality and accessibility. Under Federal and Maryland law, long guns are less regulated than handguns which is a concern for increased suicide risk. This study uses Maryland data to ascertain the impact of long guns on suicides in the state. We hypothesize that the prevalence of long gun use among firearm suicides will be increased in rural and young populations. METHODS: This is a cross sectional study using police and medical examiner narratives to identify firearm type involved in all 3931 Maryland gun suicides from 2003 to 2018. Proportions of firearm suicides utilizing long guns were calculated. Urban-rural differences were determined using the National Center for Health Statistics' classification system. Logistic regression was used to calculate odds ratios of long gun to handgun suicides across the urban-rural spectrum, controlling for decedent demographics. RESULTS: From 2003 to 2018, 28.4% of Maryland gun suicides used long guns. The proportion of long guns used was highest in the most rural counties, where 51.6% of firearm suicides were by long gun, compared to 16.8% in the most urban counties. Long guns were disproportionately used by the young. For decedents 18 or younger, 44.6% used long guns, compared to 20.2% in those 65 or older. Compared to the most urban counties, firearm suicide decedents in the most rural counties were 3.74x more likely to use long guns (OR = 3.74; 95% CI 2.19, 6.40; p < .001) after adjusting for demographics, intoxication, and hunting season. CONCLUSIONS: Long guns are used in a large proportion of Maryland firearm suicides, particularly in rural areas and disproportionately in youth suicides. Long guns must be considered as part of access to lethal means or policy strategies in efforts to reduce the burden of firearm suicide.

A Pilot Study Comparing Postmortem and Antemortem CT for the Identification of Unknowns: Could a Forensic Pathologist Do It?

Forensic pathologists are commonly tasked with identifying human remains. Although DNA analysis remains the gold standard in identification, time and cost make it particularly prohibitive. Radiological examination, more specifically analog imaging, is more cost-effective and has been widely used in the medical examiner setting as a means of identification. In the United States, CT imaging is a fairly new imaging modality in the forensic setting, but in more recent years, offices are acquiring CT scans or collaborating with local hospitals to utilize the technology. To broaden the spectrum of potential identifying characteristics, we collected 20 cases with antemortem and postmortem CT images. The results were qualitatively assessed by a forensic pathologist and a nonmedically trained intern, and all cases were correctly identified. This study demonstrates that identification of human remains using visual comparison could be performed with ease by a forensic pathologist with limited CT experience.

Elevator-Related Deaths.

Elevators are mechanical transportation devices used to move vertically between different levels of a building. When first developed, elevators lacked the safety features. When safety mechanisms were developed, elevators became a common feature of multistory buildings. Despite their well-regarded safety record, elevators are not without the potential for danger of injury or death. Persons at-risk for elevator-related death include maintenance and construction workers, other employees, and those who are prone to risky behavior. Deaths may be related to asphyxia, blunt force, avulsion injuries, and various forms of environmental trauma. In this review, we report on 48 elevator-related deaths that occurred in nine different medicolegal death investigation jurisdictions within the United States over an approximately 30-year period. The data represents a cross-section of the different types of elevator-related deaths that may be encountered. The review also presents an overview of preventive strategies for the purpose of avoiding future elevator-related fatalities.

Causes of Sudden Unexpected Death in Schizophrenia Patients: A Forensic Autopsy Population Study.

BACKGROUND: Schizophrenia is a detrimental psychiatric disorder, with an increased mortality from natural and nonnatural causes. METHODS: This study was a retrospective review of autopsy cases of all the individuals with history of schizophrenia investigated by the Office of the Chief Medical Examiner, State of Maryland, for a 5-year period from 2008 to 2012. RESULT: A total of 391 schizophrenia patients were autopsied at the Office of the Chief Medical Examiner because they died suddenly and unexpectedly. Their age ranged from 15 to 100 years with the mean age of 49.5 years. Of the 391 deaths, 191 (48.8%) were white, 185 (47.3%) were African American, and 15 (3.9%) were either Hispanic or Asian. The male and female ratio was 1.5:1. The majority of deaths (64.2%) were caused by natural diseases, 12.0% deaths were accidents, 11.5% deaths were suicides, and 9.7% deaths were homicides. The manner of death remained undetermined in 38 cases (9.7%). Of the 251 natural deaths, 198 cases (78.9%) were owing to cardiovascular diseases. Cause of death was listed as cardiac arrhythmia in 11 cases. This diagnosis of cardiac arrhythmia was made by exclusion based on death scene investigation, review of medical history, complete autopsy, and toxicological tests. Drug intoxication was the second most common cause of death. CONCLUSIONS: The study shows high fatality caused by cardiovascular diseases and drug intoxication among schizophrenia patients, which calls attention of the medical community to closely monitor the high risk factors of sudden death among schizophrenia patients.

African-American and Caucasian participation in postmortem human brain donation for neuropsychiatric research.

Increased African-American research participation is critical to the applicability and generalizability of biomedical research, as population diversity continues to increase both domestically and abroad. Yet numerous studies document historical origins of mistrust, as well as other barriers that may contribute to resistance in the African-American community towards participation in biomedical research. However, a growing body of more recent scientific evidence suggests that African-Americans value research and are willing to participate when asked. In the present study, we set out to determine factors associated with research participation of African-American families in postmortem human brain tissue donation for neuropsychiatric disorders as compared with Caucasian families, from same-day medical examiner autopsy referrals. We retrospectively reviewed brain donation rates, as well as demographic and clinical factors associated with donation in 1,421 consecutive referrals to three medical examiner's offices from 2010-2015. Overall, 69.7% of all next-of-kin contacted agreed to brain donation. While Caucasian families consented to donate brain tissue at a significantly higher rate (74.1%) than African-American families (57.0%) (p<0.001), African-American brain donation rates were as high as 60.5% in referrals from Maryland. Neither African-American nor Caucasian donors differed significantly from non-donors on any demographic or clinical factors ascertained, including age, sex, diagnosis of the donor, or in the relationship of the next-of-kin being contacted (p>0.05). However, Caucasian donors were significantly older, had more years of education, were more likely to be referred for study due to a psychiatric diagnosis, more likely to have comorbid substance abuse, and more likely to have died via suicide, as compared with African-American donors (p<0.05). When African-American participants are identified and approached, African-American families as well as Caucasian families are indeed willing to donate brain tissue on the spot for neuropsychiatric research, which supports the belief that African-American attitudes towards biomedical research may be more favorable than previously thought.

Amyloid ß toxic conformer has dynamic localization in the human inferior parietal cortex in absence of amyloid plaques.

Amyloid ß (Aß) plays a critical role in the pathogenesis of Alzheimer's disease. Nevertheless, its distribution and clearance before Aß plaque formation needs to be elucidated. Using an optimized immunofluorescent staining method, we examined the distribution of Aß in the post-mortem parietal cortex of 35 subjects, 30 to 65 years of age, APOE ε3/ε3, without AD lesions. We used 11A1, an antibody against an Aß conformer which forms neurotoxic oligomers. 11A1 immunoreactivity (IR) was present in cortical neurons, pericapillary spaces, astrocytes and the extracellular compartment at 30 years of age. The percentage of neurons with 11A1 IR did not change with age, but the number and percentage of astrocytes with 11A1 IR gradually increased. Notably, the percentage of pericapillary spaces labeled with 11A1 IR declined significantly in the 5th decade of the life, at the same time that 11A1 IR increased in the extracellular space. Our findings indicate that the Aß toxic conformer is normally present in various cell types and brain parenchyma, and appears to be constitutively produced, degraded, and cleared from the inferior parietal cortex. The decrease in pericapillary Aß and the concomitant increase of extracellular Aß may reflect an age-associated impairment in Aß clearance from the brain.

Dead in the water: Epilepsy-related drowning or sudden unexpected death in epilepsy?

OBJECTIVE: Both drowning and sudden unexpected death in epilepsy (SUDEP) are diagnoses of exclusion with predominantly nonspecific autopsy findings. We hypothesized that people with epilepsy found dead in water with no clear sign of submersion could be misdiagnosed as SUDEP. METHODS: All reported seizure-related deaths undergoing medicolegal investigation in three medical examiner's offices (New York City, Maryland, San Diego County) over different time periods were reviewed to identify epilepsy-related drownings and SUDEPs. Drowning cases that fulfilled inclusion criteria were divided into two groups according to the circumstances of death: definite drowning and possible drowning. The SUDEP group included two sex- and age (±2 years)-matched definite SUDEP/definite SUDEP plus cases for each drowning case. RESULTS: Of 1346 deaths reviewed, we identified 36 definite (76.6%) and 11 possible drowning deaths (23.4%), most of which occurred in a bathtub (72.3%). There were drowning-related findings, including fluid within the sphenoid sinuses, foam in the airways, clear fluid in the stomach content, and lung hyperinflation in 58.3% (21/36) of the definite drowning group, 45.5% (5/11) of the possible drowning group, and 4.3% of the SUDEP group (4/92). There was no difference in the presence of pulmonary edema/congestion between the definite drowning group, possible drowning group, and SUDEP group. The definite drowning group had a higher mean combined lung weight than the SUDEP group, but there was no difference in mean lung weights between the possible drowning and SUDEP groups or between the possible drowning and definite drowning groups. SIGNIFICANCE: No distinguishable autopsy finding could be found between SUDEPs and epilepsy-related drownings when there were no drowning-related signs and no clear evidence of submersion. SUDEP could be the cause of death in such possible drowning cases. As most drowning cases occurred in the bathtub, supervision and specific bathing precautions could be effective prevention strategies.

Standard Death Certificates Versus Enhanced Surveillance to Identify Heroin Overdose-Related Deaths.

OBJECTIVES: To compare 2 approaches to identifying heroin-related deaths in cases of overdose: standard death certificates and enhanced surveillance. METHODS: We reviewed Maryland death certificates from 2012 to 2015 in cases of overdose to determine specific mentions of heroin. Counts were compared with estimates obtained through an enhanced surveillance approach that included a protocol considering cause of death, toxicology, and scene investigation findings. RESULTS: Death certificates identified 1130 heroin-related deaths. Enhanced surveillance identified 2182 cases, nearly double the number found through the standard approach. The major factors supporting enhanced surveillance in identifying cases were the presence of morphine, either alone or in combination with quinine, and scene investigation information suggesting heroin use. CONCLUSIONS: Death certificates, the primary source of state and national data on overdose deaths, may underestimate the contribution of heroin to drug-related mortality. Enhanced surveillance efforts should be considered to allow a better understanding of the contribution of heroin to the overdose crisis. Public Health Implications. If enhanced surveillance can be incorporated into the death certificate process, national data on overdoses may better reflect the contribution of heroin to the opioid crisis.

Estimating Sex Using Metric Analysis of the Scapula by Postmortem Computed Tomography.

Postmortem computed tomography (CT) has been extensively used in the last decade for identification purposes and in various anthropologic studies. Postmortem CT measurements of scapulae, analyzed using logistic discriminant function developed in this study, showed 94.5% accuracy in estimating sex. Data analyzed using the Dabbs and Moore-Jansen (2010) discriminant function and the discriminant function generated in this study provided nearly identical results with disagreement in only one case. Height and weight were not statically significant in sex prediction. The results of this study show that data obtained from volume rendered postmortem CT images can be considered reliable and treated as a practical option to standard anthropological methods, especially in mass fatalities as a rapid triage tool for sex determination.

Urban-Rural Differences in Suicide in the State of Maryland: The Role of Firearms.

OBJECTIVES: To assess whether the use of firearms explains rural-urban differences in suicide rates. METHODS: We performed a retrospective analysis on all 6196 well-characterized adult suicides in Maryland from 2003 through 2015. We computed rate ratios by using census data and then stratified by sex, with adjustment for age and race. RESULTS: Suicide rates were higher in rural compared with urban counties. However, the higher rural suicide rates were limited to firearm suicides (incident rate ratio [IRR] = 1.66; 95% confidence interval [CI] = 1.20, 2.31). Nonfirearm suicide rates were not significantly higher in rural settings. Furthermore, 89% of firearm suicides occurred in men and the higher rural firearm suicide rate was limited to men (IRR = 1.36; 95% CI = 1.09, 1.69). Women were significantly less likely to complete suicide in rural areas (IRR = 0.63; 95% CI = 0.43, 0.94), regardless of method. CONCLUSIONS: Male firearm use drives the increased rate of suicide in rural areas. The opposite associations between urbanicity and suicide in men and women may be driven by the male preference for firearms as a method for committing suicide.

Pathology of Chronic Total Occlusion in Bare-Metal Versus Drug-Eluting Stents: Implications for Revascularization.

OBJECTIVES: The aim of this study was to explore the pathology of in-stent chronic total occlusion (IS-CTO) in bare-metal (BMS) versus drug-eluting stents (DES). BACKGROUND: Despite a relatively high prevalence of IS-CTO, little is known about the underlying etiology and histopathologic characteristics of the occlusion. METHODS: From CVPath Institute's stent registry of human native coronary arteries, the authors identified 56 lesions (32 BMS and 24 DES) from 54 patients with IS-CTO. Sections of stented coronary arteries were examined for histological features of IS-CTO. The underlying mechanisms of IS-CTO were determined along with the histopathological characteristics. RESULTS: The pathological prevalence of IS-CTO was significantly higher in BMS versus DES cases at autopsy (11.7% vs. 5.9%; p = 0.01). The most frequent etiology of IS-CTO was acute thrombotic occlusion (51% in BMS vs. 67% in DES), followed by restenosis (31% vs. 8%) and neoatherosclerotic rupture (9% vs. 4%). The proximal lumen pattern was abrupt in 67% of BMS and in 57% of DES, whereas the distal lumen was tapered in 68% of BMS and in 74% of DES. BMS showed longer fibrous cap of IS-CTO than DES in both proximal (4.6 mm vs. 1.6 mm; p = 0.06) and distal (5.3 mm vs. 2.0 mm; p = 0.06). CONCLUSIONS: At autopsy, IS-CTO was observed more frequently in BMS versus DES, with acute thrombotic occlusion being the most frequent cause, followed by restenosis (especially in BMS) and neoatherosclerotic rupture. Our findings shed new light upon the frequency, mechanisms, and pathology of IS-CTO.

Evaluation of Acute Alcohol Intoxication as the Primary Cause of Death: A Diagnostic Challenge for Forensic Pathologists.

Deaths caused by acute alcohol intoxication (AAI) remain a major public health issue. This study is retrospective and descriptive: an 8-year case analysis of deaths due to AAI in Maryland. Study showed that of 150 AAI deaths, the death rate among Hispanics (10.41/100,000 population) was significantly higher than all the non-Hispanics combined (1.88/100,000 population). The majority of individuals were young adults, overweight, and binge drinkers. The obese group showed significantly lower mean heart and peripheral blood alcohol concentration (BAC) (0.36%, 0.37%) than the normal weight group (0.45%, 0.42%). Based on the PBAC and urine AC ratio, 49.6% deaths likely occurred close to peak phase, followed by postabsorptive phase (31.6%) and absorptive phase (18.8%). Our results indicate that forensic pathologists should evaluate postmortem BAC in the light of individual's age, drinking history, body weight, possible phase of alcohol intoxication, and other autopsy findings when certifying AAI as primary cause of death.

Drug Intoxication and the Need to Autopsy: A Diagnosis of Exclusion?

The recent surge in drug deaths has focused attention on the diagnosis of drug intoxication as a cause of death. In Maryland, the Department of Vital Records has shown an increase from 649 intoxication deaths in 2012 to 1259 in 2015. Preliminary data for 2016 document 1892 of these deaths. Many of the medicolegal death investigation offices in the United States are facing potential loss of accreditation. There is limited capacity to add more staff due to a lack of appropriately trained pathologists and budget constraints. The diagnosis of this intoxication and the need to autopsy all of these cases is a matter of debate, as many death investigation offices look for alternative means to maintain accreditation. The alternative to adding more staff is to reduce the autopsy caseload. Can this be done without compromising the intent of the medical examiner system and the law? Balancing this with being fiscally responsible may be a very real challenge and one that will test many death investigation systems due to this pandemic of drug deaths. If there is a need to reduce the autopsy caseload, it should be in cases other than where the diagnosis is one of exclusion.

Public Figures, Professional Ethics, and the Media.

Death certificates and autopsy reports contain personal identifying information and clinical information protected under the Health Insurance Portability and Accountability Act (HIPAA) of 1996. These documents are used, for example, by the families of the deceased for settling estates, bereavement and closure, and genetic counseling of relatives. Insurance companies, public health and law enforcement officials, and the legal community also have legitimate claims to this information. Critical ethical questions have not yet been settled about whether and when this information should be public and under which circumstances making this kind of information public incurs benefits, harms, or both. Additional considerations include which organizations-the media, academic institutions, or government agencies, for example-are best suited to interpret these questions and respond to them.