Deaths From Alcoholic and Diabetic Ketoacidosis at Autopsy-A Comparison Study.

Diabetes mellitus and alcoholism are common disorders that may result in sudden death. Ketoacidosis may occur in both conditions. Diagnosis is based on history, and post-mortem findings including biochemistry and toxicology. This study compares deaths from alcoholic and diabetic ketoacidosis from two centres with large autopsy workloads. In the study period 9332 deaths were autopsies with 151 deaths diagnosed as ketoacidosis (1.6%) with 82 (0.9 %) being diabetic ketoacidosis (DKA) and 48 (0.5%) alcoholic ketoacidosis (AKA) deaths. There were more male deaths in each group. The median age for DKA deaths was 51 years (range 19-79). The median age for AKA deaths was 55 years (range was 34-78). The BMI range in DKA deaths was 12.5 to 40.4 kg/m2, with a median of 21.9. The comparative figures for AKA deaths was a range of 11.3 - 38.3 with a median of 20.2. Acetone concentrations were statistically higher in diabetic compared with alcoholic deaths, mean of 33.7 mg/100 mL in DKA cases versus mean of 16.9 mg/100 mL in AKA cases. Both DKA and AKA deaths are seen more commonly in males than female and are typically people with low BMIs in their 50s.

The Goudge Inquiry and Forensic Pathology in Canada.

Aims: This article analyses the effects of The Inquiry into Pediatric Forensic Pathology in Ontario, commonly known as the Goudge Inquiry, and its effects upon forensic pathology in Canada. Methods: The Goudge Inquiry was a Government of Ontario public inquiry that examined the delivery of pediatric forensic pathology services to the Ontario Coroner's Office and the Canadian criminal justice system. The inquiry was conducted by Mr. Justice Goudge, a court of Appeal Judge and made substantial recommendations of improving forensic pathology in a Coroner system and its role in delivering evidence to the criminal justice system. This article reviews the inquiry and discusses the effect of the inquiry on the development of forensic pathology in Canada and academic literature about the inquiry. Results: The Inquiry has had important effects on the role of all expert witnesses in the courts and is the most substantial examination of forensic pathology by any judicial inquiry. Conclusions: The Goudge Inquiry has been considered a significant success, being described as transformative.

Subnuclear renal tubular vacuoles in alcohol use disorder.

Subnuclear vacuoles in the proximal renal tubules have been reported as a histologic sign of ketoacidosis. Originally described in diabetic ketoacidosis, renal vacuoles can be found in other ketogenic states such as alcoholic ketoacidosis (AKA), starvation, and hypothermia, underpinned by deranged fatty acid metabolism. A retrospective analysis of 133 deaths associated with alcohol use disorder (AUD) examined at autopsy between 2017 and 2020 was undertaken. This study aimed to determine the prevalence of subnuclear vacuoles in deaths of those with AUD and their specificity for deaths from AKA, and to elucidate what demographic, biochemical, and pathologic findings are associated with subnuclear vacuoles. In each case, vitreous humor biochemistry including electrolytes, glucose, and beta-hydroxybutyrate (BHB) was analyzed alongside postmortem hemoglobin A1c and renal and liver histology. Renal histology was graded for the presence of vacuoles as absent (0), scanty (1), or easily identifiable (2). Liver histology was graded for steatosis and for fibrosis if Masson trichrome staining was available. Vacuoles were commonly seen in the deaths of those with AUD. They were seen in deaths due to AKA but were not specific to that cause of death. With vacuoles present, lower vitreous sodium (139 vs. 142 mmol/L; p = 0.005), higher vitreous BHB (1.50 vs. 1.39 mmol/L; p = 0.04), severe hepatic steatosis, and severe hepatic fibrosis were seen, compared with those without renal vacuoles.

Evaluating small vessel neutrophils as a marker for sepsis.

A retrospective case-control study of 100 sepsis autopsy cases and 103 controls over a 9-year period was conducted to analyze patterns of neutrophils in small caliber vessels of the liver, heart, and lungs in relation to sepsis as the cause of death. Data extracted included demographics of the decedent, cause of death, presence of conditions that could interfere with an inflammatory response, history of hospitalization, and results of microbiology cultures. Histologic sections of the liver, heart, and lungs were assessed. Organs were scored for neutrophilic inflammation based upon a predetermined grading system. Scores of 0, 1, and 2 were assigned according to mild, moderate, and florid neutrophilic presence, respectively; a total score was also assigned based on the sum of the scores from all three organs. Comparing the histologic grading between cases and controls found a statistical difference with the neutrophil grading in the liver (p < 0.001), lung (p < 0.001), and heart (p < 0.001) and between the combined total scores (p < 0.001). Combined neutrophilic scores of 4 and greater showed high specificities (90% to 100%) for sepsis-related deaths. Examining the percentage of sepsis cases as the histologic neutrophilic score increased found a positive slope in all three organs. However, only the linear regression looking at the lung (p = 0.03) and the combined score (p = 0.001) were statistically significant. Despite the above results, sepsis cases with low scores and controls with moderate and florid neutrophilic infiltrates were also seen.

Utility of Postmortem Vitreous Beta-Hydroxybutyrate Testing for Distinguishing Sudden from Prolonged Deaths and for Diagnosing Ketoacidosis.

A retrospective, cross-sectional analysis of vitreous beta-hydroxybutyrate (BHB) on 967 forensic cases over a two-year period was conducted. Cases were sorted into six categories of death: (i) sudden traumatic/non-natural (ST), (ii) sudden natural (SN), (iii) prolonged traumatic/non-natural (PT), (iv) prolonged natural (PN), (v) diabetic ketoacidosis (DKA), and (vi) alcoholic ketoacidosis (AKA). The mean BHB for all cases was 1.67 mmol/L (17.4 mg/dL; range: 0.11-18.02 mmol/L). The numbers of DKA, AKA, PN, PT, SN, and ST deaths were 21, 5, 155, 258, 275, and 253, respectively. Their mean vitreous BHBs were as follows: 11.04 mmol/L (DKA), 8.88 mmol/L (AKA), 1.56 mmol/L (PN), 1.55 mmol/L (PT), 1.26 mmol/L (SN), and 1.38 mmol/L (ST). There was a statistically significant difference between the mean BHBs of the PN and SN death groups (p < 0.001), as well as between those of the PT and ST death groups (p = 0.004). Given the overlapping ranges seen between the prolonged and sudden death groups, the identified differences did not hold clinical significance. In addition, we sought to determine a threshold value for vitreous BHB to definitely diagnose cases of ketoacidosis. BHB threshold concentrations between 2.5 and 5 mmol/L produced sensitivities >92% and specificities >96%. A receiver operator characteristic curve found 3.43 mmol/L to be the optimal cutoff value, demonstrating a specificity of 98.3% and a sensitivity of 96.2%.

Opioid-Related Deaths in Eastern Ontario from 2011 to 2016.

There has been a growing opioid crisis in the United States and Canada. The aim of this study was to analyze trends in opioid-related deaths from the Eastern Ontario Regional Forensic Pathology Unit so that prevention strategies for these deaths can be developed. The analyses included examining the opioids involved and demographic characteristics of the individuals in these deaths so that possible risk factors for opioid-related deaths could be identified. A retrospective cross-sectional analysis of the full autopsy and toxicology data between 2011 and 2016 was conducted. Trends regarding the opioids involved in the death, all opioids reported in the toxicology reports and certain nonopioid drugs reported in the toxicology reports were examined. The distribution of opioid-related death by age-group and manner of death was also conducted. Two hundred seventy-four opioid-related deaths met the inclusion criteria and were examined. The majority of individuals overdosing were male. The most frequent age range for opioid-related deaths was 45 to 54 years with increasing deaths among individuals aged 55 years and older over the period studied. Fentanyl was responsible for most deaths overall when single or multiple opioids were involved. However, hydromorphone involvement was the only opioid to have a statistically significant increase over the time period. Analysis of nonopioid-related drugs revealed extensive use of antidepressants, benzodiazepines, and their metabolites. Accident was the most common manner of death throughout all age groups except for those aged 65 years or older, where suicide was most common.

Fat Embolism, Fat Embolism Syndrome and the Autopsy.

Fat embolism is common following trauma and is a common autopsy finding in these cases. It may also be seen in non-traumatic cases and is seen in children as well as adults. In comparison fat embolism syndrome (FES) only occurs in a small number of trauma and non-trauma cases. Clinical diagnosis is based on characteristic clinical and laboratory findings. Fat embolism exerts its effect by mechanical blockage of vessels and/or by biochemical means including breakdown of fat to free fatty acids causing an inflammatory response. Fat embolism can be identified at autopsy on microscopy of the lungs using fat stains conducted on frozen tissue, including on formalin fixed but not processed tissue. With FES fat emboli can be seen in other organs including the brain, kidney and myocardium. Fat can also be identified with post-fixation staining, typically with osmium tetroxide. Scoring systems have been developed to try and determine the severity of fat embolism in lung tissue. Fat embolism is also common following resuscitation. When no resuscitation has taken place, the presence of fat on lung histology has been used as proof of vitality. Diagnosis of fat embolism syndrome at autopsy requires analysis of the history, clinical and laboratory findings along with autopsy investigations to determine its relevance, but is an important diagnosis to make which is not always identified clinically. This paper reviews the history, clinical and laboratory findings and diagnosis of fat embolism and fat embolism syndrome at autopsy.

Deaths from Environmental Hypoxia and Raised Carbon Dioxide.

This paper reviews deaths in which there is an environment that is low in oxygen and/or has elevated levels of carbon dioxide. These deaths present problems to autopsy pathologists, as the autopsy is typically negative and postmortem toxicology cannot be used to detect the effects of hypoxia and raised levels of carbon dioxide. Deaths from hypoxia and raised carbon dioxide may be encountered in work-and nonwork-related environments. Typically these are accidents, but suicides may be encountered and criminal charges may follow these events. Environments that have been associated with these events include mines, tunnels, sewers, and pits. Transportation incidents may also be associated with hypoxic events, particularly aircraft and submarines. When an atmosphere low in oxygen is entered, collapse can be rapid, or immediate if the environmental oxygen is below 6%. Environments rich in carbon dioxide can also cause death, even with a high oxygen concentration. Such environments may be encountered in industrial settings, but also occur in natural disasters such as the Lake Nyos disaster. The identification of these deaths typically requires a coordinated investigation with safety inspectors and other experts in industrial- and work-related deaths.

Fatty Liver and the Forensic Pathologist.

Fatty liver is a common finding in clinical practice and at autopsy. It is most commonly seen associated with alcohol abuse and in non-alcoholic fatty liver disease (NAFLD). It may also be seen in many other conditions in both adults and children. It is now recognized that NAFLD, like alcoholic liver disease, may lead to end stage liver disease. Nonalcoholic fatty liver disease is associated with increased mortality from other disorders, particularly cardiovascular diseases. Fatty liver may be seen in many conditions that concern autopsy pathologists, including drug toxicity, anorexia, hepatic ischemia, and heatstroke. In infants, steatosis is common in sudden unexpected deaths. Fatty liver has been associated with sudden death and this review examines the pathology and role of fatty liver in sudden death. Acad Forensic Pathol. 2018 8(2): 296-310.

The Utility and Scope of Forensic Histopathology.

Forensic histopathology is the use of histology to aid in the identification of disease and injuries in forensic pathology practice. The value of routine microscopy has been challenged in various studies and discussions have taken place in forensic journals about how useful microscopic diagnosis is in medicolegal autopsies. This paper reviews the literature on the value of histological examination in forensic practice and discusses routine histochemical stains that can be used in postmortem examinations to aid in the diagnosis and add value by confirming or refuting macroscopic findings.

Histologic Changes In Recreational Drug Misuse.

Use of recreational drugs is associated with a number of histologic changes. These may be related to the method of administration or due to systemic effects of the drugs. This paper reviews the histopathological features seen following recreational drug use. With injection, there may be local effects from abscess formation and systemic effects may result in amyloidosis. Injections have been associated with necrotizing fasciitis, anthrax, and clostridial infections. Systemic effects include infective endocarditis, with the risk of embolization, and abscesses may be seen in organs in the absence of infective endocarditis. Viral complications of injection include hepatitis and human immunodeficiency virus (HIV) infection. Injecting crushed tablets can result in intravascular granulomata in the lungs. Smoking drugs is associated with intraalveolar changes, including blackand brown-pigmented macrophages in crack cocaine and cannabis smoking, respectively. Snorting may result in intraalveolar granulomata forming when crush tablets are used and there may be systemic granulomata. Stimulants are associated with cardiovascular and cerebrovascular pathology, including contraction band necrosis and myocardial fibrosis, as well as coronary artery dissection. Stimulants may cause hyperpyrexia and rhabdomyolysis, which may be associated with changes in multiple organs including myoglobin casts in the kidney. Opioids cause respiratory depression and this can be associated with inhalational pneumonia and hypoxia in other organs if there is resuscitation and a period of survival. Ketamine use has been associated with changes in the urothelium and the liver. This paper reviews histology changes that may be seen in drug-related deaths using illustrative cases.

Ten Percent of SIDS Cases are Murder - or are They?

Sudden infant death syndrome (SIDS) has been used as a cause of death for over four decades. It has allowed deaths of infants to be registered as natural. Within this group of deaths, a certain number have been recognized to be homicides from inflicted smothering rather than being natural or accidental deaths. Research has been conducted using confidential inquires to determine how frequent homicide is in cases called SIDS. This paper traces the history of quoted rates of homicide. Early work suggested the figure was between 2-10% of all SIDS cases, though other workers have suggested figures as high as 20-40%. With the fall in the rate of infant deaths following the "Back to Sleep" campaigns, these figures have been reevaluated. If the higher figures were correct that 20-40% of SIDS were homicides, the fall in infant deaths would be expected to be less than it has been. Current data suggests a much lower figure than 10% of current cases, with much lower overall rates of infant deaths. As well as 10% of SIDS cases having been stated to be homicides, a related question is whether multiple deaths classified as SIDS are really homicides. The paper discusses the maxim that one death is a tragedy, two is suspicious, and three deaths indicate homicide. The paper also looks at court cases and the approach that has been made in prosecutions of sudden unexpected death in infancy as multiple murder.

A Brief History of the Expert Witness.

Expert witnesses are now an accepted part of criminal and civil trials. The use of expert witnesses and the admissibility of their science has developed over the last 250 years, when the concept of allowing an expert witness to give opinion evidence on the facts of other witnesses was allowed by Lord Mansfield in the case of Folkes v. Chadd in 1782. This paper briefly describes how court procedures have changed over the centuries before opinion evidence was admitted and then traces the history of the expert witness in England, USA, and Canada, examining issues of admissibility and duties of the expert from the 18th century to the 21st century. The paper further describes the change in admissibility with US decisions in Frye and Daubert and how they have affected courts in the UK and Canada. Also described are recent decisions in the UK on duties of experts and immunity from suit.

A Brief History of the Literature on Postmortem Changes to the 19th Century.

The fact that the body changes following death must have been known for the whole history of mankind. But myth and superstition surrounded the changes. This led to such entities as the ordeal of the bier being used as criminal proof, even though other forms of trial by ordeal had long been abandoned. The scientific literature in the English language did not start until the late 18th century and was still surrounded with ignorance and some superstition. The main concern of the early writers was the correct determination of death. In the 19th century, an understanding of postmortem changes developed and the first attempts to accurately classify sequences of putrefaction were made. This paper analyzes the early forensic medicine writing and the progress of knowledge to the later 19th century, through examination of forensic medicine textbooks published in the English language.