Academic Forensic Pathology

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.

The dramatic increase in drug-related deaths in the last decade has presented fiduciary and logistical difficulties to medicolegal jurisdictions of all types and sizes. New Hampshire, with a centralized state medical examiner system of death investigation, has been confronted with the task of investigating these drug-related deaths against the backdrop of statutory hurdles inhibiting a nimble response to the situation. This has led to a collaborative approach with law enforcement and the state Department of Justice in terms of triaging drug deaths to full autopsy versus external examination with toxicology testing. Preliminary data suggest that between 11 and 13% of suspected drug deaths have an alternative cause of death revealed by autopsy. Positive toxicological findings were documented in 97.5% of cases in which only an external examination was performed; however, some of these cases may have had undetected, significant internal findings that could have accounted for an alternative cause of death if an autopsy had been performed. While the case triage system described has temporarily addressed the acute problem, the issue of the medical examiner's appropriate role in the adequate evaluation of public health and safety remains extant. Furthermore, noncompliance with the National Association of Medical Examiners inspection and accreditation standards puts this agency, and others facing the same issues, at risk of losing full accreditation status until such resource issues are addressed by legislators and other stakeholders in the quality of medicolegal death investigation in the United States.

In recent years, there has been a substantial increase in opioid use and abuse, and in opioid-related fatal overdoses. The increase in opioid use has resulted at least in part from individuals transitioning from prescribed opioids to heroin and fentanyl, which can cause significant respiratory depression that can progress to apnea and death. Heroin and fentanyl may be used individually, together, or in combination with other substances such as ethanol, benzodiazepines, or other drugs that can have additional deleterious effects on respiration. Suspicion that a death is drug-related begins with the decedent's medical and social history, and scene investigation, where drugs and drug paraphernalia may be encountered, and examination of the decedent, which may reveal needle punctures and needle track marks. At autopsy, the most significant internal finding that is reflective of opioid toxicity is pulmonary edema and congestion, and frothy watery fluid is often present in the airways. Various medical ailments such as heart and lung disease and obesity may limit an individual's physiologic reserve, rendering them more susceptible to the toxic effects of opioids and other drugs. Although many opioids will be detected on routine toxicology testing, more specialized testing may be warranted for opioid analogs, or other uncommon, synthetic, or semisynthetic drugs.

Hundreds of synthetic substances have been introduced into the illicit drug market over the last ten years, but none of these drugs has had as poisonous a consequence as the emergence of the synthetic fentanyl analogs. Initially, pharmaceutical grade or illicit fentanyl was mixed with heroin, allegedly to boost the potency of the heroin. Then, the amounts of fentanyl spiked gradually increased until the proportion of fentanyl was greater than the proportion of heroin. Ultimately, many overdose cases began consisting of only fentanyl. The emergence of numerous synthetic fentanyl analogs, including acetylfentanyl, butyrylfentanyl, acrylfentanyl, furanylfentanyl and β-hydroxythiofentanyl, which are manufactured in China, were made available to the illicit drug traffickers over the Internet. In July of 2016, the most potent commercially available opioid, carfentanil, started appearing in illicit drug submissions and medical examiner death investigation cases in Northeast Ohio. Postmortem femoral blood carfentanil concentrations are in the picogram per milliliter (pg/mL) range, which is extremely low, and tests the limits of detection for most analytical forensic toxicology laboratories. The interpretation of these low carfentanil blood concentrations in antemortem and postmortem specimens is made difficult due to the overlap in the concentrations between these specimen types. The presence of these powerful synthetic fentanyl analogs presents a challenge to forensic toxicology laboratories preparing to analyze for these substances.

The United States continues to grapple with an epidemic of opiate/opioid drugs. This crisis initially manifested itself in the use and abuse of opioid pain relievers and has since seen an increase in illicit opiate/opioid drug use mortality. Cuyahoga County (metropolitan Cleveland) has been an area where the crisis has been particularly acute; this paper updates our previous experience. Most notable in the evolution of the drug epidemic has been an increase in mortality associated with fentanyl and an alarming rise in overall deaths, largely attributable to the emergence of fentanyl (a 64% increase in total overdose deaths from 2015 to 2016, with fentanyl increasing 324%). Fentanyl is a synthetic opioid with use in medical analgesia and anesthesia; however, most of the current supply is of clandestinely manufactured origin. Also of concern is the recent appearance of illicit fentanyl analogues, which are briefly described in this report. White males continue to be the most frequent overdose victims in the current crisis. A decrease of age appears to have taken place with the emergence of fentanyl with the most common age group being between 30 and 44 years of age. The majority of decedents are nonurban residents. Educationally, most of these decedents have a high school diploma or less schooling and a significant percentage consists of manual laborers. Medical examiners are an important source of information necessary to develop prevention and interdiction strategies. Challenges faced regarding adequate funding, instrumentation, and staffing are being felt.

Opioid-related deaths have transitioned over the past 15 years, beginning with a steady increase in the incidence of fatal prescription overdoses, followed by a dramatic increase in deaths caused by illicit opioids, namely heroin and fentanyl. These trends in drug-related deaths are identified by medical examiners and coroners who serve an important role in public health surveillance. Medicolegal death investigators, being first responders, often recognize spates of drug-related deaths in real time. While few jurisdictions are unaffected by the epidemic, some medicolegal death investigators may have less experience detecting fatal opioid overdoses. This review will outline many of the medical, behavioral, and physical indicators of a deadly prescription or illicit opioid overdose. All aspects of a thorough medicolegal death investigation will be discussed, including the proper documentation of the scene and evidence handling. Investigative questions and follow-up procedures will also be reviewed.

The medical examiner/coroner (ME/C) death scene investigation systems of the United States play a pivotal role in the current public health crisis created by the expanding drug dependency epidemic in the United States. The first point of recognition of a drug-related death in a community is often the local ME/C agency. This circumstance places these entities in an ideal position to provide surveillance data regarding the epidemiology of drug-related deaths occurring within the jurisdiction of the agency. The ability to surveil for the distribution and determinants among drug-related deaths at the first point of contact enhances the capacity to recognize actionable trends at the local, state, and national levels, including the ability to identify secular (longer-term) trends among various drugs and population subgroups, as well as activity spikes (outbreaks) associated with high-potency formulations and drug combinations.

In this article, we describe the development and implementation of an online website that provides public access to a wide array of drug-related death surveillance resources and tools. The website gives users access to a detailed dataset that includes information regarding specific drugs, demographic information pertaining to the decedent, and to investigational findings related to the circumstances of the death. A unique aspect of the database is that it is populated by ME/C agencies and accessed by the public with no intermediary agency, so that the lag time between the identification and investigation of the death as drug-related and community knowledge of the circumstances of the death is minimized.

Wide dissemination of accurate drug death surveillance information in an easily accessible and customizable format promotes societal awareness of the drug death epidemic, but also provides information to public health, law enforcement, regulatory, and other community-based organizations that can benefit from the most up-to-date knowledge. We envision a national system of surveillance at the regional ME/C level that would allow for optimal information dissemination and sharing. Such a system would likely allow for more efficacious allocation of resources at the regional and national level.

The Virginia Prescription Monitoring Program (VPMP) has been in effect since 2002, providing reports for prescribers, pharmacists, and other stakeholders in the growing opioid epidemic. The Office of the Chief Medical Examiner is one such stakeholder and has found great efficacy in the program in investigating suspected drug-related deaths. This review examines the origins of the VPMP, its benefits, and limitations for use during death investigation.

As drug- and opiate/opioid-related deaths continue to rise in the Midwest, we must look at how the type of death investigation in these areas is affected and taxed by the increase. Many states with a large rural component rely on a local coroner system, where death investigation lacks uniformity and requirements for coroner investigative personnel are extremely variable. This has mixed implications for communities and potentially affects law enforcement and prosecution, data collection, and public policy. Both coroner and medical examiner systems benefit from strong leadership, properly trained personnel, and fiscal support. However, operational differences amongst jurisdictions should be addressed so that all stakeholders ultimately receive optimal data. This paper discusses the coroner system of death investigation in one Midwest state (Ohio) in the context of the region's burgeoning opiate/opioid epidemic and suggests opportunities for improvement.

As the opiate/opioid crisis has worsened in the United States, one of the law enforcement responses has involved increased efforts to prosecute the individuals responsible for the distribution of illicit drugs that result in overdoses. When mixed intoxications occur, the controlling decision for prosecution is Burrage v. United States (2014), which provides guidance on the types of evidence required for establishment of causation. In many types of legal proceedings, forensic pathologists are called to provide expert testimony, although they may be unaware of the burden of proof that is required in a given case. This paper seeks to elaborate upon the burden of proof in drug overdose prosecutions with the guidance of Burrage and offer insight into the expectations and limitations involved in these cases.

From 2000 to 2014, drug overdose deaths increased 137% in the United States, and 61% of these deaths included some form of opiate. The vast majority of opiate-related drug fatalities include multiple drugs, although there is scant data quantitatively describing the exact drugs that contribute to deaths due to multiple drugs. In the present study, we sought to quantitatively identify the drugs that occur with opiates in accidental multidrug-related fatalities. We retrospectively explored fatal drug trends in four Michigan counties, with a focus on profiling drugs present concurrently with opiates. Blood and urine toxicology reports for mixed drug fatalities (N=180) were analyzed using frequent item analysis approaches to identify common analyte trends in opiate-related fatalities. Within our cohort, the most prevalent serum analytes included caffeine (n=147), morphine (n=90), alprazolam (n=69), gabapentin (n=46), and tetrahydrocannabinol (n=44). In 100% of cases where gabapentin was present (n=46), an opiate was also present in the serum or urine. The average gabapentin serum concentration was 13.56 μg/mL (SEM =0.33 μg/mL), with a range of 0.5-88.7 μg/mL. Gabapentin was found at very high frequency in accidental mixed drug fatalities. Gabapentin concentrations were generally within the normal therapeutic range (2-20 μg/mL). It is unknown whether a synergistic effect with opioids may contribute to central respiratory depression. Further research is warranted to determine any contributory role of gabapentin in these deaths. Confirmed interactions could have broad implications for future reporting by forensic pathologists as well as prescribing practices by clinicians.

Sudden death in infants due to primary cardiac tumors is extremely rare. Herein we describe a case of an 8-month-old male infant, without any previous medical history, who died in a hospital in the city of Medellín-Antioquia, Colombia. The family stated that approximately 15 minutes after he received a bottle, the baby became cyanotic and subsequently lost consciousness. He was taken to the hospital immediately; however, he arrived lifeless. As this was a sudden death case, the child was referred to the Institute of Legal Medicine and Forensic Sciences in the city of Medellín to clarify the cause, manner, and mechanism of death.

The forensic autopsy revealed a eutrophic infant with central and peripheral cyanosis, without signs of trauma, and the internal examination found a single cardiac tumor in the anterior wall of the left ventricle. The mass was white and whorled; histological evaluation diagnosed a fibroma.

The manner of death was natural due to a cardiogenic shock caused by a primary tumor.

In the summer of 2015, many individuals visiting the Little Wolf River in Waupaca County were exposed to the pathogenic fungus, Blastomyces. Over time, 59 confirmed and 39 probable cases were reported to the Wisconsin Department of Health Services (W-DHS), making this one of the largest outbreaks in recent state history. Though most instances of blastomycosis are not associated with common source outbreaks, cases such as this highlight the need for vigilance regarding this preventable cause of death. In the state of Wisconsin, an average of 118.6 cases (range, 84-174) of confirmed blastomycosis are diagnosed annually; the majority of these cases are sporadic rather than outbreak-associated. In the current study, we review characteristics of blastomycosis cases diagnosed at our academic medical center, as well as examine statewide W-DHS data, in order to familiarize pathologists with the epidemiologic and histologic characteristics of this disease.

The diagnosis of adrenal insufficiency is often delayed, as the presenting symptoms of fatigue, abdominal pain, and anorexia are vague and nonspecific. However, timely diagnosis and treatment with replacement steroids are needed to prevent fatal adrenal crisis. While the most common cause of primary adrenal insufficiency in childhood is congenital adrenal hyperplasia, a significant minority (13-23%) is caused by autoimmune destruction of the gland. We present a case of a 4-year-old, previously healthy child who had a one-day history of nausea and vomiting, and was found unresponsive by her caretaker. Despite emergency rescue and transport to the hospital, she was pronounced dead. At autopsy, the adrenal glands were atrophied. Histologic examination revealed lymphocytic infiltration of the adrenal glands consistent with autoimmune adrenal insufficiency. Fecal viral antigen testing was positive for rotavirus. The cause of death was determined to be adrenal crisis in the setting of rotavirus gastroenteritis due to adrenal insufficiency (Addison disease).

Huntington disease (HD) is a neurodegenerative disorder with a worldwide prevalence of four to ten per 100 000. It is characterized by choreiform movements, behavioral/psychiatric disturbances, and eventual cognitive decline. Symptoms usually present between 30 and 50 years of age and the diagnosis is based on the combination of clinical symptoms, family history, and genetic testing. A variation of HD, juvenile Huntington disease (JHD), presents earlier, with more severe symptoms and with a worse prognosis. Symptoms are different in JHD, with personality changes and learning difficulties being the predominant presenting features. Seizures are common in JHD, and chorea is uncommon; movement disorders at presentation of JHD are predominantly nonchoreiform. The inheritance pattern for both HD and JHD is autosomal dominant and the disease is caused by an elongation of the CAG repeat in the huntingtin gene.

There are many published case reports of Huntington disease that were confirmed at autopsy, but to our knowledge, there are no reports in the literature where the diagnosis of Huntington disease was first made at autopsy. We present a case of a 28-year-old African-American male who was in a state of neglect due to a lifetime of abuse, cognitive difficulties, and seizures, whose cause of death was pneumonia.

The gross autopsy findings included bilateral caudate nucleus atrophy and lateral ventricular dilation. Microscopically, severe bilateral neuronal loss and gliosis of the caudate and putamen nuclei were seen. Genetic testing for the number of CAG repeats confirmed the diagnosis and was consistent with JHD.