Association of Coronary Microvascular Rarefaction and Myocardial Fibrosis With Coronary Artery Disease.

BACKGROUND: To evaluate, in a cohort study, whether coronary microvasculature and myocardial structure differ between people with and without coronary artery disease (CAD). METHODS AND RESULTS: We performed histological analysis of left ventricle free wall obtained at autopsy from 25 men and 23 women with ≥1 coronary artery with ≥75% area stenosis, and 25 men and 25 women without (no or minimal) CAD, matched for sex and age, who died suddenly from noncardiac causes. Decedents with myocardial infarction or other cardiac abnormality were excluded. Decedents with and without CAD had similar height and weight. Heart weight of decedents with CAD was higher than that of decedents without CAD (mean, 391 versus 364 g; mean difference, 27 g [95% CI, 0.3-54.0], P=0.048). Decedents with CAD had lower arteriole density (mean, 1.4 per mm2 versus 1.8 per mm2; mean difference, -0.4 per mm2 [95% CI, -0.6 to -0.2], P=0.0001), lower capillary length density (mean, 3164 versus 3701 mm/mm3; mean difference, -537 [95% CI, -787 to -286], P<0.0001), and higher total myocardial fibrosis (mean, 7.5% versus 5.7%; mean difference, 1.7% [95% CI, 1.0-2.5], P<0.0001), than decedents without CAD. CONCLUSIONS: CAD was associated with coronary microvascular rarefaction and increased myocardial fibrosis. The association of CAD with coronary microvascular rarefaction and increased myocardial fibrosis may contribute to the increased risks of death, myocardial infarction and heart failure that accompany CAD, and may attenuate the impact of percutaneous coronary intervention on cardiovascular risk in people with stable angina.

Moving from the unknown to the known: a multidisciplinary approach to the identification of skeletal remains from Sandy Point, Australia.

When human remains are inadvertently located, case-related circumstantial information is used to generate an identification hypothesis, and the preservation of the remains typically informs which identification methods may then be used to validate that hypothesis. What happens, however, when there is no contextual information to generate an identification hypothesis? This paper presents the case of a near-complete human skeleton discovered at Sandy Point in Victoria, Australia. The circumstances of the case did not facilitate an identification hypothesis, and with no hypothesis to triage the identification process, all possible identification methods were employed. Preservation of the individual meant neither a visual nor a fingerprint identification was possible, and the lack of an identification hypothesis meant there was no antemortem reference data to compare with the postmortem DNA or dental information. Consequently, in addition to historical research, novel methods, such as radiocarbon dating and genetic intelligence, were utilized to complement information provided by the forensic anthropology and odontology analyses, which ultimately resulted in the identification. This example highlights the complexity of cases of unidentified skeletal remains and emphasizes the fact that identification is a process that necessarily requires a multidisciplinary and collaborative approach. Key points: Human skeletal remains were recovered from Sandy Point, Victoria.The absence of circumstantial information and the poor preservation (i.e. skeletonized) of the remains precluded the formation of an identification hypothesis, rendering the identification process complex.Only through the integration of anthropology, odontology, molecular biology, radiocarbon dating, historical research, and genealogy were the remains able to be identified as Mr. Christopher Luke Moore, who drowned in 1928.Human identification is a process that necessarily requires a multidisciplinary and collaborative approach.

Distribution of prostatic markers in glands of the female urethra and anterior vaginal wall-a rapid autopsy study.

BACKGROUND: There are varying reports of immunohistochemically detected prostatic marker protein distribution in glands associated with the female urethra that may be related to tissue integrity at the time of fixation. AIM: In this study we used tissue derived from rapid autopsies of female patients to determine the distribution of glandular structures expressing prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAP) along the female urethra and in surrounding tissues, including the anterior vaginal wall (AVW). METHODS: Tissue blocks from 7 donors that contained the entire urethra and adjacent AVW were analyzed. These tissue samples were fixed within 4-12 hours of death and divided into 5-mm transverse slices that were paraffin embedded. Sections cut from each slice were immunolabeled for PSA or PSAP and a neighboring section was stained with hematoxylin and eosin. The sections were reviewed by light microscopy and analyzed using QuPath software. OBSERVATIONS: In tissue from all donors, glandular structures expressing PSA and/or PSAP were located within the wall of the urethra and were present along its whole length. RESULTS: In the proximal half of the urethra from all donors, small glands expressing PSAP, but not PSA, were observed adjacent to the and emptying into the lumen. In the distal half of the urethra from 5 of the 7 donors, tubuloacinar structures lined by a glandular epithelium expressed both PSA and PSAP. In addition, columnar cells at the surface of structures with a multilayered transitional epithelium in the distal half of the urethra from all donors expressed PSAP. No glands expressing PSA or PSAP were found in tissues surrounding the urethra, including the AVW. CLINICAL IMPLICATIONS: Greater understanding of the distribution of urethral glands expressing prostatic proteins in female patients is important because these glands are reported to contribute to the female sexual response and to urethral pathology, including urethral cysts, diverticula, and adenocarcinoma. STRENGTHS AND LIMITATIONS: Strengths of the present study include the use of rapid autopsy to minimize protein degradation and autolysis, and the preparation of large tissue sections to demonstrate precise anatomical relations within all the tissues surrounding the urethral lumen. Limitations include the sample size and that all donors had advanced malignancy and had undergone previous therapy which may have had unknown tissue effects. CONCLUSION: Proximal and distal glands expressing prostate-specific proteins were observed in tissue from all donors, and these glands were located only within the wall of the urethra.

Quadriceps tendon malalignment is an independent anatomical deformity which is the primary abnormality associated with lateral facet patellofemoral joint osteoarthritis.

PURPOSE: The purposes of this study are to, firstly, develop techniques to accurately identify extensor mechanism malalignment by measuring the alignment of the quadriceps tendon (QTA) with computerized tomography (CT) scans. Secondly, to investigate correlations between QTA and lower limb bony anatomical variations within a representative normal population. Lastly, to evaluate the clinical significance of QTA by establishing its potential connection with lateral facet patellofemoral joint osteoarthritis (LFPFJOA). METHOD: CT scans were orientated to a mechanical axis reference frame and three techniques developed to measure the alignment of the quadriceps tendon. Multiple measurement of bony alignment from the hip to the ankle were performed on each scan. A series of 110 cadaveric CT scans were measured to determine normal values, reproducibility, and correlations with bony anatomy. Secondly, a comparison between 2 groups of 25 patients, 1 group with LFPFJOA and 1 group with isolated medial OA and no LFPFJOA. RESULTS: From the cadaveric study, it was determined that the alignment of the quadriceps tendon is on average 4.3° (SD 3.9) varus and the apex of the tendon is 9.1 mm (SD 7.7 mm) lateral to the trochlear groove and externally rotated 1.9° (SD 12.4°) from the centre of the femoral shaft. There was no association between the quadriceps tendon alignment and any other bony measurements including tibial tubercle trochlear groove distance (TTTG), coronal alignment, trochlear groove alignment and femoral neck anteversion. A lateralized QTA was significantly associated with LFPFJOA. QTA in the LFPFJOA group was 9.6° varus (SD 2.8°), 21.3 mm (SD 6.6) lateralised and 17.3° ER (SD 11°) compared to 5.5° (SD 2.3°), 10.7 mm (SD 4.9) and 3.3° (SD 7.2°), respectively, in the control group (p < 0.001). A significant association with LFPFJOA was also found for TTTG (17.2 mm (SD 5.7) vs 12.1 mm (SD 4.3), p < 0.01). Logistic regression analysis confirmed the QTA as having the stronger association with LFPFJOA than TTTG (AUC 0.87 to 0.92 for QTA vs 0.79 for TTTG). CONCLUSION: These studies have confirmed the ability to accurately determine QTA on CT scans. The normal values indicate that the QTA is highly variable and unrelated to bony anatomy. The comparative study has determined that QTA is clinically relevant and a lateralised QTA is the dominant predictor of severe LFPFJOA. This deformity should be considered when assessing patella maltracking associated with patella osteoarthritis, patella instability and arthroplasty. LEVEL OF EVIDENCE: III (retrospective cohort study).

BRCA1 and BRCA2 carriers with breast, ovarian and prostate cancer demonstrate a different pattern of metastatic disease compared with non-carriers: results from a rapid autopsy programme.

AIM: To catalogue and compare the pattern of metastatic disease in germline BRCA1/2 pathogenic mutation carriers and non-carriers with breast, ovarian and prostate cancer from a rapid autopsy programme. METHODS AND RESULTS: The number of metastases in the major body systems and the proportion of participants with metastases were documented in 50 participants (19 germline mutation carriers). Analysis was conducted on the participants' pattern of disease for the different cancers and mutation subgroups. The four commonly affected organ systems were the digestive (liver only) (82%), respiratory (76%), gastrointestinal (65%) and reticuloendothelial (42%). There were significant differences in the pattern of metastatic breast cancer in BRCA1/2 germline carriers compared with non-carriers. Breast cancer carriers had significantly fewer organ systems involved (median n = 3, range = 1-3) compared with non-carriers (median n = 9, range = 1-7) (P = 0.03). BRCA1/2 carriers with ovarian carcinomas had significantly more organ systems with metastatic carcinoma (median n = 10, range = 3-8) than non-carriers (median n = 5, range = 3-5) (P < 0.001). There were no significant differences in the number of involved systems in BRCA2 carriers compared with non-carriers with prostate cancer (P = 1.0). There was an absence of locoregional disease (6.5%) compared with distant disease (93.5%) among the three cancer subtypes (P < 0.001). The majority of metastatic deposits (97%) collected during the autopsy were identified by recent diagnostic imaging. CONCLUSION: Even though a major limitation of this study is that our numbers are small, especially in the breast cancer carrier group, the metastatic patterns of breast and ovarian cancers may be impacted by BRCA1/2 carrier status, suggesting that tumours derived from patients with these mutations use different mechanisms of dissemination. The findings may focus clinical diagnostic imaging for monitoring metastases where whole-body imaging resources are scant.

Fatal Intoxications from a Combination of 4-Fluoroamphetamine and 25C-NBOMe.

Six fatalities have occurred from the ingestion of a combination of new psychoactive substances (NPSs), 4-fluoroamphetamine (4FA) and 2-(4-chloro-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25C-NBOMe) over a 9-month period. Four of these fatalities (one older female and three young males) were from direct adverse effects of drugs, and one each from a fall while being intoxicated and during restraint. All cases were subject to full postmortem examinations that included collection of femoral blood. The four drug-caused fatalities had postmortem blood concentrations for 4FA and 25C-NBOMe of 330-682 ng/L (median 417) and 1.4-12 ng/mL (median 4.3), respectively. The other two cases (both young males) where death was considered to have been caused indirectly by drug intoxication had 4FA and 25C-NBOMe postmortem concentrations of 21 and 123 ng/mL, and 1.8 and 4.5 ng/mL, respectively. None of these cases showed concentrations of drugs that suggested use of high recreational doses. In one drug-caused death, capsules and a brown powder obtained from the scene were found to contain a mixture of these two NPSs. With the exception of one drug-caused death, other drugs were detected; however, the effects of the two NPSs together were regarded as the primary triggers for the deaths. There were no consistent symptoms or pathology in these cases; however, agitation/aggression was observed in two cases prior to their collapse, with seizures in possibly three cases. Pulmonary and/or cerebral edema was noted in three cases. Potentially significant natural disease (a mildly enlarged heart) was only observed in one drug-caused case. These cases illustrate a possible increased risk of sudden death with this combination of drugs, both of which can elevate serotonin concentrations as well as act as strong stimulants. These cases also illustrate the difficulty in detecting NPS in cases where no prior information is available that might suggest their use.

Stimulant use in suicides: A systematic review.

Suicide remains a global public health concern and the increased supply and use of synthetic stimulants globally may have implications for the burden of suicides attributable to substance use. This systematic review investigated any potential associations of stimulant use detected in post-mortem biological specimens and suicides. We conducted a systematic review and narrative synthesis (CRD42021237966). Medline, EMBASE, TOXLINE, and Scopus databases were searched for terms related to forensic toxicology, post-mortem toxicology, suicide and stimulants. The primary outcome was to estimate the prevalence of stimulant use in suicides. There were 26 studies whichcontributed to prevalence measures; in studies reporting at the individual compound level, suicides involved cocaine (0.1-23%), caffeine (3.2-22%), 3,4-methylenedioxymethamphetamine (0.1-17%), amphetamine (0.2-9.3%), methamphetamine (3.1-7%), and phentermine (0.9-1%). Overall, stimulant use in suicides was over-represented compared to estimates of stimulant use in the general population and has increased over time. Thirteen case reports used to contextualise suicides involving stimulants found no examples of cocaine or methamphetamine mono-intoxication of suicidal intent. This suggests mechanisms other than acute toxicity involved in stimulant-associated suicide. Future research by in-depth psychological autopsies of suicides involving stimulants, in combination with segmental hair analysis to determine the chronicity of stimulant exposure, may contribute to a better understanding of the burden of suicide attributable to stimulant use.

Postmortem Interrogation of Cardiac Implantable Electronic Devices: A 15-Year Experience.

OBJECTIVES: This study sought to define the feasibility and utility of postmortem cardiac implantable electronic device (CIED) interrogation. BACKGROUND: The diagnostic yield of routine postmortem interrogation of CIEDs including pacemakers, defibrillators, and implantable loop recorders has not been established. METHODS: The study reviewed all CIED interrogations in deceased individuals undergoing medicolegal investigation of sudden or unexplained death by the Victorian Institute of Forensic Medicine between 2005 and 2020. RESULTS: A total of 260 patients (68.8% male, median age 72.8 years [interquartile range: 62.7-82.2 years]) underwent CIED interrogation (202 pacemakers, 56 defibrillators, and 2 loop recorders) for investigation of sudden (n = 162) or unexplained (n = 98) death. CIEDs were implanted for median of 2.0 years (interquartile range: 0.7-5.0 years), with 19 devices at elective replacement indicator and 5 at end of life. Interrogation was successful in 256 (98.5%) cases. Potential CIED malfunction was identified in 20 (7.7%) cases, including untreated ventricular arrhythmias (n = 13) and lead failures (n = 3, 2 resulting in untreated ventricular arrhythmia). Interrogation directly informed cause of death in 131 (50.4%) cases. A total of 72 (27.7%) patients had abnormalities recorded in 30 days preceding death: nonsustained ventricular tachycardia (n = 26), rapid atrial fibrillation (n = 17), elective replacement indicator or end-of-life status (n = 22), intrathoracic impedance alarms (n = 3), lead issues (n = 3), or therapy delivered (n = 1). In 6 cases in which the patient was found deceased after a prolonged period, interrogation determined time of death. In 1 case, CIED interrogation was the primary means of patient identification. CONCLUSIONS: Postmortem CIED interrogation frequently contributes important information regarding critical device malfunction, premortem abnormalities, mechanism, and time of death or patient identity. Device interrogation should be considered for select patients with CIEDs undergoing autopsy.

Post-mortem CT lung findings at a medicolegal institute in SARS-CoV-2 RT-PCR positive cases with autopsy correlation.

CoVID-19 is a novel viral infection with now well-established clinical radiological findings. There is limited data on post-mortem imaging. We explore the proposition that PMCT could be used as screening test. In an 11-week period, 39 deceased persons were referred for medicolegal investigation with pre-existing or subsequent nasopharyngeal swabs showing positivity on SARS-CoV-2 RT-PCR testing. All 39 had routine whole-body CT scans on admission and 12 underwent medicolegal autopsy. These cases were contrasted with 4 others which were negative on nasopharyngeal swabs despite PMCT findings suggestive of CoVID-19 pneumonia (designated false positive). Nine of the 12 autopsies showed lung histology consistent with those reported in CoVID-19 pneumonia. Typical clinical CoVID-19 lung findings on PMCT were only detected in 5 (42%). In 3 of the 4 false positive cases, lung findings showed non-COVID-19 histology but in 1, findings were identical. PMCT CoVID-19 findings in the lungs are therefore not specific and may not be detected in all cases due to obscuration by expected agonal CT findings or other pathologies that pre-dated SARS-CoV-2 infection. PMCT findings may otherwise be subtle. Although PMCT may hint at CoVID-19, we believe that nasopharyngeal swabs are still required for definitive diagnosis. Even with positive swabs, clinical CoVID-19 lung findings on PMCT are often not detected. PMCT findings can be subtle, extreme or obscured by agonal changes. Given this range of PMCT changes, the challenge for pathologists is to determine whether death has been caused by, or merely associated with, SARS-CoV-2 infection.

Evolution of late-stage metastatic melanoma is dominated by aneuploidy and whole genome doubling.

Although melanoma is initiated by acquisition of point mutations and limited focal copy number alterations in melanocytes-of-origin, the nature of genetic changes that characterise lethal metastatic disease is poorly understood. Here, we analyze the evolution of human melanoma progressing from early to late disease in 13 patients by sampling their tumours at multiple sites and times. Whole exome and genome sequencing data from 88 tumour samples reveals only limited gain of point mutations generally, with net mutational loss in some metastases. In contrast, melanoma evolution is dominated by whole genome doubling and large-scale aneuploidy, in which widespread loss of heterozygosity sculpts the burden of point mutations, neoantigens and structural variants even in treatment-naïve and primary cutaneous melanomas in some patients. These results imply that dysregulation of genomic integrity is a key driver of selective clonal advantage during melanoma progression.

Survey on postmortem screening and management of COVID-19 related deaths.

The COVID-19 pandemic is associated with a high case fatality rate in some countries even thought the majority of cases are asymptomatic. Scientific studies on this novel virus is limited and there is uncertainty regarding the best practices for death investigations both in terms of detection of the disease as well as autopsy safety. An online survey was conducted to identify how different institutions responded to the screening and management of dead bodies during the early phase of the pandemic from January to May. A questionnaire was developed using Google Forms and data was collected from 14 different forensic and pathological institutions in 9 countries. None of the institutions had performed any screening prior to March. Four institutions stated that screening was done routinely. In total, 322 cases had been screened using RT-PCR, out of which 40 positive cases were detected among four institutions. The commonest types of samples obtained were nasopharyngeal and oropharyngeal swabs which also had the highest rates of positivity followed by tracheal swab. Blood, swabs from cut surfaces of lung and lung tissue also gave positive results in some cases. Majority of the positive cases were > 65 years with a history suggestive of respiratory infection and were clinically suspected to have COVID-19 before death. Except for one institution which performed limited dissections, standard autopsies were conducted on all positive cases. Disposal of bodies involved the use of sealed body bags and labelling as COVID positive. Funeral rites were restricted and none of the institutions advocated cremation. There were no reports of disease transmission to those who handled COVID positive bodies.

Postmortem Drug Redistribution: A Compilation of Postmortem/Antemortem Drug Concentration Ratios.

Postmortem drug redistribution (PMR) is a well-known phenomenon in forensic toxicology with implications for medico-legal death investigations. Paired antemortem (AM) specimen and postmortem (PM) mortuary admission femoral blood drug concentrations from 811 coronial cases were used to construct a retrospective compilation of PM/AM drug concentration ratios for 42 parent drugs and metabolites. The median PM/AM ratios for all antidepressants were > 1 and consistent with PMR In contrast, the median PM/AM ratios of most benzodiazepines were < 1. The antipsychotics were varied (0.63-3.3) and suggest the mixed effects of PMR and drug instability. Amphetamines exhibited no trends (0.90-0.95) and are likely confounded by many factors. The PM/AM ratios of cardiovascular drugs, opioids and other drugs are also reported. This research represents an expansive retrospective compilation of paired AM and PM drug concentrations for many toxicologically relevant drugs. While the median PM/AM ratios demonstrate some drug-dependent trends, there was no obvious relationship between AM specimens and PM femoral blood taken at mortuary admission.

Time-Dependent Changes in THC Concentrations in Deceased Persons.

Changes in the concentrations of Δ9-tetrahydrocannabinol (THC) in the postmortem period were investigated in a series of cases by comparing concentrations in blood taken on receipt of the body in the mortuary (admission specimen, AD) with the concentrations obtained in blood taken at autopsy some time later and also from blood specimens taken antemortem. Overall, the median THC concentration in AD blood was 13.7 ng/mL (n = 239, range LOQ-220), while the median concentration at autopsy was 13.8 ng/mL (n = 106, range LOQ-810) and 1.9 ng/mL (n = 147, range LOQ-48) antemortem. Fourteen cases had all three specimens taken from the same decedent. The corresponding AM, AD and PM median concentrations were 4.0 (range LOQ-48), 15.5 (range 4.0-176) and 4.4 ng/mL (LOQ-56), respectively. The median elapsed times from AM to AD and AD to PM were 33 and 97.5 h, respectively. In contrast, acetaminophen showed no change in blood concentration from AM to AD (6.8 and 6.0 mg/L, respectively). These data show large increases in THC concentration in the early postmortem period, followed by a decline, although the median blood concentrations at autopsy were similar to that obtained antemortem. In contrast, when blood was taken from the femoral region, subclavian and heart ventricles sites, in the same case, the THC concentrations, while variable, showed overall no significant difference. These dynamic changes reflect complex phenomenon occurring in deceased persons and will further serve to increase the uncertainty over any interpretation of postmortem THC concentrations.

Odds of culpability associated with use of impairing drugs in injured drivers in Victoria, Australia.

Culpability analysis was conducted on 5000 drivers injured as a result of a vehicular collision and in whom comprehensive toxicology testing in blood was conducted. The sample included 1000 drivers for each of 5 years from approximately 5000-6000 drivers injured and taken to hospital in the State of Victoria. Logistic regression was used to investigate differences in the odds of culpability associated with alcohol and drug use and other selected crash attributes using the drug-free driver as the reference group. Adjusted odds ratios were obtained from multivariable logistic regression models in which other potentially explanatory driver and crash attributes were included. Drivers with alcohol present showed large increases in the odds of culpability similar to that seen in other studies investigating associations between blood alcohol concentration and crash risk. Methylamphetamine also showed a large increase in the odds of culpability (OR 19) compared to the reference group at both below and above 0.1 mg/L, whereas those drivers with Δ9-tetrahydrocannabinol (THC) present showed only modest increase in odds when all concentrations were assessed (OR 1.9, 95 %CI 1.2-3.1). Benzodiazepines in drivers also gave an increase in odds (3.2, 95 %CI 1.6-6.1), but not other medicinal drugs such as antidepressants, antipsychotics and opioids. Drivers that had combinations of impairing drugs generally gave a large increase in odds, particularly combinations of alcohol with THC or benzodiazepines, and those drivers using both THC and methamphetamine.

A Lethal Blow to the Chest as an Underdiagnosed Cause of Sudden Death in United Kingdom Sports (Football, Cricket, Rugby).

Nonpenetrating blunt force trauma to the front of the chest can lead to commotio cordis, a cardiac rhythm disturbance, which can result in cardiac arrest and death. The condition is particularly noted during sport. No series of such cases has been published in the UK. This study is a retrospective analysis of a database of 6000 cases of sudden cardiac death examining commotio cordis in the setting of collapse and death shortly following a blow to the precordium where no structural heart disease was identified at autopsy. Of the 17 cases, 16 were male, and 11 were 18 years old or younger. Eleven occurred whilst playing sport while 6 involved physical interaction including assault. The most common circumstance of death involved a youth being struck in the chest by a ball during sporting activity. In conclusion, this study demonstrates that cases of commotio cordis in the UK follow a similar circumstantial and age profile to those reported in the United States, and indicates that ball sports such as football, cricket, and rugby expose young participants to a similar risk. There is currently no nation-wide registry of deaths occurring during sporting activity in the UK, and although the true incidence of this condition is not currently known, it is most probably under-recognised and underdiagnosed.

Difference in the characteristics of mortality reports during a heatwave period: retrospective analysis comparing deaths during a heatwave in January 2014 with the same period a year earlier.

OBJECTIVES: To describe the characteristics of deaths reported to the Coroners Court of Victoria (CCOV) during Victoria's last heatwave (14-17 January 2014) and subsequent 4 days (18-21 January) using medicolegal data obtained from both the police investigation report and the pathologist's report. DESIGN, SETTING AND PARTICIPANTS: A single-jurisdiction population-based retrospective analysis of consecutive heat-related deaths (HRDs) reported to the CCOV between 14 and 21 January 2014 with a historical comparison group. MAIN OUTCOME MEASURES: Descriptive statistics were used to summarise case demographics, causes of death and the types of investigations performed. The cases from 2014 were subgrouped into HRD and non-HRD. RESULTS: Of the 222 cases during the study period in 2014, 94 (42.3%) were HRDs and 128 (57.7%) were non-HRDs. HRDs were significantly older than non-HRDs (70.5 years: SD=13.8 vs 61.0 years: SD=22.4, t(220)=3.60, p<0.001, 95% CI 4.3 to 14.6). The most common primary cause of death in HRDs was circulatory system disease (n=57, 60.6%), which was significantly higher when compared with non-HRDs (n=39, 30.5%; χ2=20.1, p<0.001, OR 3.5, 95% CI 2.0 to 6.2). HRDs required significantly greater toxicology investigation (89.4% (n=84) vs 71.9% (n=92); χ2=10.9, p<0.001, OR 3.3, 95% CI 1.54 to 7.03) and greater vitreous biochemistry testing (40.4% (n=38) vs 16.4% (n=21); χ2=16.0, p<0.001, OR 3.5, 95% CI 1.9 to 6.5). CONCLUSIONS: A heatwave places a significant burden on death investigation services. The inclusion of additional laboratory tests and more detailed circumstantial information are essential if the factors that contribute to HRDs are to be identified.

Cannabis as a cause of death: A review.

Synthetic cannabinoids have caused a large number of emergency presentations to hospitals for adverse cardiovascular events including numerous deaths, particularly for the more potent analogs acting on the CB1 receptor. While smoked cannabis use is often associated with significant changes in heart rate and cardiac output, amongst other physiological changes, it has been rarely considered in the forensic literature as a significant contributory or causal factor in sudden unexpected death. A review of case reports of admissions to hospitals for cardiovascular events was undertaken together with a review of epidemiological studies, and case reports of sudden death attributed, at least in part, to use of this drug. These publications show that use of cannabis is not without its risks of occasional serious medical emergencies and sudden death, with reports of at least 35 persons presenting with significant cardiovascular emergencies who had recently smoked a cannabis preparation. At least 13 deaths from a cardiovascular mechanism have been reported from use of this drug which is very likely to be an under-estimate of the true incidence of its contribution to sudden death. In addition, many cases of stroke and vascular arteritis have also been reported with the latter often involving a limb amputation. While it is a drug with widespread usage among the community with relatively few deaths when faced with a circumstance of very recent use (within a few hours), a positive blood concentration of THC and a possible cardiac-related or cerebrovascular cause of death this drug should be considered, at least, a contributory cause of death in cases of sudden or unexpected death.

Major haemorrhage fatalities in the Australian national coronial database.

OBJECTIVE: The aim of the study is to describe the epidemiology of major bleeding fatalities. METHODS: A case series analysis of Australia's National Coronial Information System was conducted. Keywords were used to search for closed cases of major haemorrhage in the state of Victoria for the period 1 January 2009 to 31 December 2011. Coroners' findings, autopsy reports and police reports of cases were reviewed. Demographic data were extracted, and cases were assigned to a clinical bleeding context. RESULTS: A total of 427 cases of major bleeding causing death were identified. The cohort was predominately men (69%), with a median age of 63 years (interquartile range 45-77 years). Trauma accounted for 38%, gastrointestinal haemorrhage 28%, surgical/procedural bleeding 14%, ruptured/leaking aneurysms 12% and other 8%. Most events began in homes (46%), hospitals (22%) and at the roadside (17%). Of those whose haemorrhage began in the community, 69% did not survive to hospital. CONCLUSIONS: Major bleeding fatalities occurred across a diverse range of contexts, with trauma and gastrointestinal bleeding accounting for most deaths. The majority of patients did not survive to reach hospital. Major haemorrhage occurring entirely outside hospital may be underrecognised from analyses of datasets based primarily on traumatic or in-hospital bleeding. These findings have implications for management of pre-hospital resuscitation and development of clinical practice guidelines for identification and management of major bleeding in the community.

The effect of post-mortem computed tomography angiography (PMCTA) using water-soluble, iodine-based radiographic contrast on histological analysis of the liver, kidneys and left ventricle of the heart.

The purpose of this study was to investigate the impact of post-mortem computed-tomography angiography (PMCTA) on the histology of the liver, kidneys and heart. Multiple tissue cores were collected from the liver, left and right kidneys and left ventricle utilizing CT-guided biopsy. Subsequent whole body PMCTA was performed using a solution of polyethylene glycol and iodinated radiographic contrast, and an embalming pump. Corresponding biopsy cores were collected at autopsy, and blinded histology analysis assessing for PMCTA-induced histology artefact was performed. The blinded analysis of pre-PMCTA and post-PMCTA biopsy samples demonstrated that whole body PMCTA had no effect on the histological analyses of the liver (0%, CI = 0-13.7%), left ventricle of the heart (0%, CI = 0-36.9%) and right kidney (0%, CI = 13.2%), however likely caused increased Bowman's capsule spaces in the left kidney of one case (4%, CI = 0.01-20.4%). Other artefactual histological changes identified included eosinophilic material in the liver, whiter interstitium and dilated tubules in kidney samples, and autolysis-related changes, however these could not be categorically attributed to the PMCTA procedure. PMCTA causes zero or minimal effect to the histological examination of the liver, left kidney, right kidney and left ventricle, and as such performing PMCTA prior to autopsy is unlikely to impact autopsy histological results in these organs.