Alternative Cause Of Death Research Articles

Prevalence and Molecular Analysis of Encephalomyocarditis Virus-2 in the Hazel Dormouse.

The hazel dormouse (Muscardinus avellanarius) population in the UK continues to decline due to habitat loss, despite reintroductions of captive-bred individuals being conducted nationally for over 30years. Disease surveillance of captive-bred and wild dormice is performed to identify novel and existing disease threats which could impact populations. In this study, we firstly investigated cause of death in seven hazel dormice found dead in England, through next-generation sequencing identifying a virus closely related to a wood mouse encephalomyocarditis virus-2 (EMCV-2). Subsequently, lung tissue samples from 35 out of 44 hazel dormice tested positive for EMCV-2 RNA using a reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and Sanger sequencing methods developed in this study. Formalin-fixed tissues available for nine hazel dormice which tested positive for EMCV-2 RNA were examined microscopically. Three cases showed moderate interstitial pneumonia with minimal to mild lymphoplasmacytic myocarditis, but no evidence of encephalitis. However, the presence of possible alternative causes of death in these cases means that the lesions cannot be definitively attributed to EMCV-2. Here, we report the first detection of EMCV-2 in hazel dormice and conclude that EMCV-2 is likely to be endemic in the hazel dormouse population in England and may be associated with clinical disease.

A case-control study of antipsychotic use and pneumonia-related mortality in the United Kingdom.

There is increasing evidence linking antipsychotic use with pneumonia, but limited evidence of an effect on pneumonia-related outcomes such as mortality. In this study, we aimed to examine the association of pneumonia-related death with specific antipsychotic exposure. Deaths analysed were those reported to a UK-based drug-related deaths database, the National Programme on Substance Abuse Deaths (NPSAD), between 1997 and September 2020. We conducted a case-control study with cases defined as pneumonia-related deaths and controls as cases with alternative causes of death. Cases were analysed by considering drugs detected at post-mortem (PM) and by drugs prescribed to the deceased at the time of their death with calculated odds ratios (ORs) adjusted to account for confounders. There were 2467 PM cases and 40,128 controls; 1818 prescribed cases and 28,018 controls. Second generation antipsychotics (SGAs) were robustly associated with an increased risk of pneumonia-related death compared with those not prescribed or taking antipsychotics (PM detection adjusted OR [AOR] 1·34 [95% CI 1·15-1·55]; prescribed AOR 1·28 [95% CI 1·11-1·49]). First generation antipsychotics had no clear association with death from pneumonia (PM detection AOR 1·06 [95% CI 0·77-1·47]; prescribed AOR 0·91 [95% CI 0·71-1·17]). Amongst SGAs, olanzapine was associated with an increased risk of death due to pneumonia (PM detection AOR 1·49 [95% CI 1·22-1·82]; prescribed AOR 1·44 [95% CI 1·18-1·76]) as was quetiapine (PM detection AOR 1·34 [95% CI 1·07-1·66]; prescribed AOR 1·28 [95% CI 1·01-1·64]). Olanzapine and quetiapine were found to increase the risk of pneumonia-related death in this NPSAD sample to a clinically important extent.

Review of findings in a case series of NPS benzodiazepines in UK deaths

Review the other drugs present and circumstances in fatalities where NPS benzodiazepines have been detected in a case series from the UK. Determine the most frequent NPS benzodiazepines involved in deaths and concentrations where possible. Benzodiazepine-type New Psychoactive Substances (NPS) have been increasingly detected in toxicology casework worldwide. These NPS benzodiazepines are potentially more potent than traditional benzodiazepines and may present an increased risk to the user, especially if other CNS depressant drugs are taken. Also, concentration data are sometimes lacking that may be useful in determining additional toxicological significance to the cause of death. As part of routine post-mortem toxicology analysis, NPS benzodiazepines have been detected, and where able, measured in blood by LC-MS-MS. Data from 35 cases involving such drugs are presented, including other drug and alcohol findings as well as the context of the death (e.g. drug related death or alternative cause). The number and frequency of different NPS benzodiazepines has been compiled along with concentrations (where available) as well as other drug findings collated by drug type. Across the 35 fatalities, 7 different NPS benzodiazepines were detected. In decreasing order of frequency; flubromazolam (13 cases), bromazolam (12), etizolam (9), flualprazolam (5), flubromazepam (1), phenazepam (1) and bromazepam (1). 80% of cases had only one NPS benzodiazepine present with 20% of cases having two NPS benzodiazepines. All fatalities were either a drug related death–83% (including cases where other drugs were present that may have been more significant than the NPS benzodiazepines) or involved an alternative cause of death–17% (including hanging, hit by a train or other medical cause). Other drugs or alcohol were detected in all cases; traditional benzodiazepines (e.g. diazepam, lorazepam, clonazepam, alprazolam) were the most common (28 detections), followed by cocaine and antidepressants (21), methadone (16), heroin/morphine (15), pregabalin (14), codeine (12), other opioids (12), alcohol and cannabis (8), zopiclone (5), ibuprofen/paracetamol (4), ketamine, antipsychotics and anticonvulsants (3), antihistamines, amphetamines and erectile dysfunction drugs (2). In terms of concentrations (where measured), flualprazolam concentrations ranged 8.7-26 ng/mL (median 20 ng/mL, n = 5), flubromazolam concentrations ranged 2.9-45 ng/mL (median 13 ng/mL, n = 11) and etizolam concentrations ranged 4.6-95 ng/mL (median 37.5 ng/mL, n = 6). As drugs with CNS depressant capabilities, NPS benzodiazepines present a risk of toxicity to users, especially if other CNS depressant drugs are co-used. This risk is increased due to the availability of these drugs often as adulterants or in falsified traditional benzodiazepines (such as diazepam and alprazolam), whereby the user may not be aware of the constituent drugs in any product consumed and this was suspected to have occurred in some of the cases featured along with use of traditional benzodiazepines as well. The review shows that poly-drug use is a particular issue with these cases; principally traditional benzodiazepines, cocaine, heroin/morphine, antidepressants, methadone and other opiates and opioids. The concentrations of NPS benzodiazepines found, where measured, provide some data for toxicologists if investigating post-mortem casework and indicate a need for sensitive qualitative and quantitative techniques. The concentrations also overlap with available data for other (non-fatal) case types such as driving under the influence so “fatal” ranges do not seem to apply. NPS benzodiazepines have been detected in a number of drug related and non-drug related deaths in the UK supporting their prevalence worldwide. Toxicologists should ensure the necessary analytical capabilities to detect what could be low concentrations despite presenting potential toxicological significance to cause of death.

Dignified management of dead during COVID -19 pandemic - A commentary review

As per WHO guidelines, death due to COVID-19 can result from a clinically compatible illness in a probable or confirmed COVID-19 case unless an alternative cause of death that cannot be related to COVID (e.g., trauma). It also emphasized that there should be no period of complete recovery from COVID-19 between illness and death. Death caused due to COVID-19 may not be attributed to another disease (e.g. cancer) and should be counted independently of pre-existing conditions suspected of triggering a severe course of COVID-19.

Consider Alternative Causes of Death to SARS-CoV-2 Vaccination-Related Guillain-Barre Syndrome without Dysautonomia.

Consider Alternative Causes of Death to SARS-CoV-2 Vaccination-Related Guillain-Barre Syndrome without Dysautonomia.

Systematic Review of Excess Mortality in India during the Covid-19 Pandemic with Differentiation between Model-Based and Data-Based Mortality Estimates.

COVID-19 has proven to be the worst pandemic in the history of mankind. While the pandemic still continues to perplex scientists globally, attempts are being made to quantify the mortality caused by the pandemic. Official COVID-19 figures in India grossly understate the true scale of the pandemic in the country. Fatality rates help us understand the severity of a disease, identify at risk populations, and evaluate quality of healthcare. Official COVID-19 mortality figures in India grossly understate the true scale of the pandemic in the country. A COVID-19 death is defined for surveillance purposes as a death resulting from a clinically compatible illness in a probable or confirmed COVID-19 case, unless there is a clear alternative cause of death that cannot be related to COVID-19 disease (e.g., trauma) and excess mortality is defined as the difference in the total number of deaths in a crisis compared to those expected under normal conditions. We did a systematic review of multiple papers on PubMed, Medline, Embase, MedRxiV pre print on excess mortality. Differentiation between model based estimated excess mortality and data based excess mortality was studied. All the studies showed that the excess mortality was to the tune of almost three times the official figures. The model based excess mortality assumptions showed higher deaths as compared to the data based one. However, there were a lot of discrepancies in the data provided by various states along with variations observed between the two waves as well. Health survey data suggested higher mortality rate as compared to data compiled from the civil registration system. Additionally, in the second wave, a small but a significant number of deaths occurred due to non availability of oxygen and beds in the hospitals. Official COVID-19 deaths have entirely failed to capture the scale of pandemic excess mortality in India. If most excess deaths were, indeed, from COVID-19 then under ascertainment of COVID-19 deaths has been high, with around 8-10 excess deaths for every recorded COVID-19 death.

Localised release of matrix metallopeptidase 8 in fatal cerebral malaria.

ObjectiveCerebral malaria (CM) is a complication of Plasmodium falciparum malaria, in which progressive brain swelling is associated with sequestration of parasites and impaired barrier function of the cerebral microvascular endothelium. To test the hypothesis that localised release of matrix metallopeptidase 8 (MMP8) within the retina is implicated in microvascular leak in CM, we examined its expression and association with extravascular fibrinogen leak in a case–control study of post‐mortem retinal samples from 13 Malawian children who met the clinical case definition of CM during life. Cases were seven children who were found on post‐mortem examination to have ‘true‐CM’ (parasite sequestration in brain blood vessels), whilst controls were six children who had alternative causes of death (‘faux‐CM’, no parasite sequestration in blood vessels).MethodsWe used immunofluorescence microscopy and independent scoring, by two assessors blinded to the CM status, to assess MMP8 expression, extravascular fibrinogen as an indicator of vascular leak and their co‐localisation in the retinal microvasculature.ResultsIn ‘true‐CM’ subjects, MMP8 staining was invariably associated with sequestered parasites and a median of 88% (IQR = 74–91%) of capillaries showed MMP8 staining, compared with 14% (IQR = 3.8–24%) in ‘faux‐CM’ (P‐value = 0.001). 41% (IQR = 28–49%) of capillaries in ‘true‐CM’ subjects showed co‐localisation of extravascular fibrinogen leak and MMP8 staining, compared with 1.8% of capillaries in ‘faux‐CM’ (IQR = 0–3.9%, P‐value = 0.01). Vascular leak was rare in the absence of MMP8 staining.ConclusionMatrix metallopeptidase 8 was extensively expressed in retinal capillaries of Malawian children with malarial retinopathy and strongly associated with vascular leak. Our findings implicate MMP8 as a cause of the vascular endothelial barrier disruption in CM, which may precipitate fatal brain swelling.

Aspiration in lethal drug abuse\u2014a consequence of opioid intoxication

AimsThe primary objective of this study was to investigate whether the fatalities of opioid abuse are not only related to respiratory depression but also as a result of other side effects such as emesis, delayed gastric emptying, a reduction of the cough reflex, and impaired consciousness leading to the aspiration of gastric contents, a finding regularly observed in drug-related deaths.DesignA retrospective exploratory study analyzing heroin/morphine/methadone-related deaths submitted to court-ordered autopsy.SettingCenter for Forensic Medicine, Medical University of Vienna, Austria (2010–2015).ParticipantsTwo hundred thirty-four autopsy cases were included in the study: morphine (n = 200), heroin (n = 11), and methadone (n = 23) intoxication.FindingsAnalyses revealed that 41.88% of all deceased showed aspiration of gastric contents with equal gender distribution (p = 0.59). Aspiration was more frequent in younger deceased (χ2 = 8.7936; p = 0.012) and in deceased with higher body mass index (BMI) (χ2 = 6.2441; p = 0.044). Blood opioid concentration was lower in deceased with signs of aspiration than in non-aspirators (p = 0.013). Toxicological evaluation revealed a high degree of concomitant substance abuse (91%)—benzodiazepines (61.6%) and/or alcohol (21.8%).ConclusionsThere are lower opioid concentrations in deceased with signs of aspiration, a fact which strongly points to aspiration as alternative cause of death in opioid-related fatalities. Furthermore, this study highlights the common abuse of slow-release oral morphine in Vienna and discusses alternative medications in substitution programs (buprenorphine/naloxone or tamper-resistant slow-release oral morphine preparations), as they might reduce intravenous abuse and opioid-related deaths.

Dying with SARS-CoV-2 infection-an autopsy study of the first consecutive 80 cases in Hamburg, Germany.

Autopsies of deceased with a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can provide important insights into the novel disease and its course. Furthermore, autopsies are essential for the correct statistical recording of the coronavirus disease 2019 (COVID-19) deaths. In the northern German Federal State of Hamburg, all deaths of Hamburg citizens with ante- or postmortem PCR-confirmed SARS-CoV-2 infection have been autopsied since the outbreak of the pandemic in Germany. Our evaluation provides a systematic overview of the first 80 consecutive full autopsies. A proposal for the categorisation of deaths with SARS-CoV-2 infection is presented (category 1: definite COVID-19 death; category 2: probable COVID-19 death; category 3: possible COVID-19 death with an equal alternative cause of death; category 4: SARS-CoV-2 detection with cause of death not associated to COVID-19). In six cases, SARS-CoV-2 infection was diagnosed postmortem by a positive PCR test in a nasopharyngeal or lung tissue swab. In the other 74 cases, SARS-CoV-2 infection had already been known antemortem. The deceased were aged between 52 and 96 years (average 79.2 years, median 82.4 years). In the study cohort, 34 deceased were female (38%) and 46 male (62%). Overall, 38% of the deceased were overweight or obese. All deceased, except for two women, in whom no significant pre-existing conditions were found autoptically, had relevant comorbidities (in descending order of frequency): (1) diseases of the cardiovascular system, (2) lung diseases, (3) central nervous system diseases, (4) kidney diseases, and (5) diabetes mellitus. A total of 76 cases (95%) were classified as COVID-19 deaths, corresponding to categories 1–3. Four deaths (5%) were defined as non-COVID-19 deaths with virus-independent causes of death. In eight cases, pneumonia was combined with a fulminant pulmonary artery embolism. Peripheral pulmonary artery embolisms were found in nine other cases. Overall, deep vein thrombosis has been found in 40% of the cases. This study provides the largest overview of autopsies of SARS-CoV-2-infected patients presented so far.

Anoxia Effects in Asphyxiated Green Sea Turtles (Chelonia mydas) Caught in an Artisanal Fishing Net on the Coast of Brazil

Among studies of drowning in green sea turtles (Chelonia mydas), none have associated drowning with injuries of organs other than the lung. We describe the gross and microscopical findings in 23 green sea turtles found dead in a fishing net. Deprived of air, these animals experienced hypoxia and anoxia before dying, which caused congestion, hydropic degeneration and necrosis in several organs. There was no evidence of an alternative cause of death. These findings demonstrate a pattern characteristic of death by asphyxia caused by drowning.

Appearance/Image- and Performance-Enhancing Drug Users

Image- and performance-enhancing drugs include a wide range of substances used to promote physical changes to enhance appearance. Anabolic androgen steroids are the most widely used image- and performance-enhancing drugs along with a wide variety of additional substances. The aim of this study was to identify the pathological changes pertaining to the cardiovascular system possibly involved in the death and characterize the substances associated with steroid use and their possible role in the death. A series of deaths involving image- and performance-enhancing drug users were selected. Nandrolone and testosterone were the most frequently identified steroids. The most commonly illegal drugs found were tetrahydrocannabinol, cocaine, and methadone. Antidepressants, opioids, benzodiazepines, and barbiturates were also found. These findings highlight that results obtained from postmortem investigations should be meticulously evaluated to understand the weight that each identified substance may have played in the death process and exclude any alternative causes of death.

Does Twitter language reliably predict heart disease? A commentary on Eichstaedt et al. (2015a).

We comment on Eichstaedt et al.’s (2015a) claim to have shown that language patterns among Twitter users, aggregated at the level of US counties, predicted county-level mortality rates from atherosclerotic heart disease (AHD), with “negative” language being associated with higher rates of death from AHD and “positive” language associated with lower rates. First, we examine some of Eichstaedt et al.’s apparent assumptions about the nature of AHD, as well as some issues related to the secondary analysis of online data and to considering counties as communities. Next, using the data files supplied by Eichstaedt et al., we reproduce their regression- and correlation-based models, substituting mortality from an alternative cause of death—namely, suicide—as the outcome variable, and observe that the purported associations between “negative” and “positive” language and mortality are reversed when suicide is used as the outcome variable. We identify numerous other conceptual and methodological limitations that call into question the robustness and generalizability of Eichstaedt et al.’s claims, even when these are based on the results of their ridge regression/machine learning model. We conclude that there is no good evidence that analyzing Twitter data in bulk in this way can add anything useful to our ability to understand geographical variation in AHD mortality rates.

When is myocarditis indeed the cause of death?

Attribution of death to myocarditis continues to be a controversial issue in forensic pathology, despite the existence of established histopathological criteria as well as complementary investigations. The aim of the study was two-fold: (a) to retrospectively analyse the data obtained from a series of clinical and forensic autopsies in order to assess the number of cases with death attributed to myocarditis, and (b) to reevaluate these cases in order to assess how properly the histopathological diagnosis of myocarditis conformed to established criteria and therefore how accurately these were used on the basis of all postmortem investigation findings to conclude the cause of death. 2474 clinical and forensic autopsies were taken into consideration. Myocarditis was recorded as the official, underlying cause of death in 48 cases. Of those, 8 cases were considered to accurately conform to the histopathological Dallas criteria for the presence of myocarditis and could therefore be classified as cases of fatal myocarditis. In 19 out of 48 cases, description of focal myocarditis was considered to accurately fulfill the histopathological Dallas criteria for the presence of myocarditis. However, data provided by histological analysis and virology testing result reevaluation allowed alternative causes of death to be speculated. In another 21 out of 48 cases, description of focal myocardial inflammation was considered to inaccurately meet the histopathological Dallas criteria for the presence of myocarditis. The findings of our own study appear to be in agreement with previous observations in similar study groups and highlight that since myocarditis may occur in association with many diseases, a great deal of evidence is required before settling on categorical conclusions.

Ocena przebiegu klinicznego u chorych z ostrą zatorowością płucną i skrzeplinami w jamach prawego serca. Doświadczenia jednego ośrodka

Introduction. Assessment of the clinical course of patients with acute pulmonary embolism (PE) and a right heart thrombus (RiHT). Material and methods . The analysis included 13 consecutive patients with echocardiographically detected RiHT and acute PE who were treated in our department. The endpoints were 30-day all-cause mortality and 30-day acute PE-related mortality. When a clear alternative cause of death was reported, a non-acute PE-related death was diagnosed and this contributed to 30-day all-cause mortality. All other fatalities were classified as related to acute PE. Results. High risk acute PE was diagnosed in 4 of 13 patients, and intermediate risk acute PE was diagnosed in the remaining 9 patients. Thrombolysis was the first-choice treatment in 4 (31%) patients, 6 (46%) patients were only anticoagulated, and the remaining 3 (23%) patients underwent surgical treatment. The main indication for embolectomy was RiHT entrapped in a patent foramen ovale (PFO). Two patients died during the first 30 days; they were hemodynamically unstable and deaths occurred within 48 hours since the diagnosis. No hemodynamically stable patients died within 30 days since the diagnosis. Conclusions . Thirty-day mortality in patients with RiHT depended mostly on the patient’s clinical condition and was not related to the presence or morphology of the thrombus. Patients with shock or hypotension may possibly benefit more from primary invasive treatment compared to drug therapy.

Confronting an Upsurge in Opiate Deaths with Limited Resources.

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.

Vaccination and anaphylaxis: a forensic perspective.

AimTo review the available literature pertaining to fatalities following vaccine administration and, in particular, cases of vaccine-related fatal anaphylaxis.MethodThe MEDLINE database was systematically searched up to March 2016 to identify all relevant articles pertaining to fatal cases of anaphylaxis following vaccine administration.ResultsSix papers pertaining to fatal anaphylaxis following vaccination were found relevant. Mast cell tryptase and total IgE concentration was assessed exclusively in one case. Laryngeal edema was not detected in any of these cases, whereas eosinophil or mast cell infiltration was observed in lymphoid organs. In one case, immunohistochemical investigations using anti-tryptase antibodies allowed pulmonary mast cells and degranulating mast cells with tryptase-positive material outside to be identified.ConclusionIn any suspected IgE-mediated fatal anaphylactic cases, biochemical investigations should be systematically performed for forensic purposes. Splenic tissue should be routinely sampled for immunohistochemical investigations in all suspected anaphylaxis-related deaths and mast cell/eosinophil infiltrations should be systematically sought out in the spleen, myocardium, and coronary artery wall. The hypothesis of fatal anaphylaxis following vaccination should be formulated exclusively when circumstantial data, available medical records, laboratory investigations, and autopsy or histology findings converge in a consistent pattern. The reasonable exclusion of alternative causes of death after all postmortem investigations is also imperative in order to establish or rule out a cause-and-effect relationship between vaccine administration and any presumptive temporarily-related death.

Determining the Toxicological Significance of Pregabalin in Fatalities

Pregabalin has become more widely prescribed and abused in recent years but is still not always included in laboratory analysis. An LC-MS-MS method has been developed and applied to measure pregabalin in 93 postmortem cases, including drug-related deaths, alternative causes of death, and fatalities where pregabalin was likely to have contributed to death. Other drugs or alcohol was detected, and the most common drug types (in decreasing frequency) were antidepressants, opioids, benzodiazepines, opiates, alcohol, antipsychotics, cocaine, cardiac drugs, amphetamines, cannabis, anticonvulsants, and antihistamines. New psychoactive substances (methoxphenidine and synthetic cannabinoids) were only found in two cases. The results provide further data to assist in evaluating the significance of postmortem pregabalin concentrations and a toxicologically significant concentration of 25 mg/L is proposed. Pregabalin, especially with concomitant use of other CNS depressant drugs, presents a significant toxicological risk and existing laboratory protocols should be reviewed for their suitability to detect pregabalin.

A 3-year review of new psychoactive substances in casework

Following the initial popularity of mephedrone (4-methylmethcathinone) there has been a stream of new “recreational drugs” entering the global market. The lack of clinical studies on the effects and toxicity of these drugs has made interpretation of toxicological findings difficult. In an attempt to assist in a better understanding of the extent of their use and the fatalities that have been linked to these compounds we present our collated findings in post-mortem and criminal casework where these have been detected and/or implicated. Between January 2010 and December 2012 we have detected new psychoactive substances (NPS) in 203 cases, with 120 cases in 2012 alone. The drugs detected in in life or post-mortem blood and urine are, in order of decreasing frequency; mephedrone, 4-methylethcathinone, BZP, MDPV, TFMPP, methoxetamine, 4-fluoromethcathinone, 4-methylamphetamine, PMA, methylone, PMMA, naphyrone, alpha-methyltryptamine, butylone, MDAI, desoxypipradrol, D2PM, MPA, synthetic cannabinoids, 2-AI, 5-IAI, 5-MeODALT, MDPBP, 5/6-APB, pentedrone and pentylone. Other drugs or alcohol were detected in 84% of the cases including other NPS and in fatalities it should be noted that alternative causes of death (including mechanical suicide, accidental death and non-psychoactive drug overdose) accounted for the majority. Related to this was that of all fatalities involving cathinones, 41% of these were hangings or other mechanical suicides, this was a higher proportion than seen with other drugs found in such cases. The presence of multiple NPS and/or other stimulants was a particular feature in various cases, however, of the drug deaths only 7% solely involved NPS. Across all case types and including some cases investigated in 2013, NPS concentrations showed a wide range but these and selected cases are presented to assist toxicological interpretation in future cases.

The Postmortem Diagnosis of Alcoholic Ketoacidosis

The aim of this article is to review the forensic literature covering the postmortem investigations that are associated with alcoholic ketoacidosis fatalities and report the results of our own analyses. Eight cases of suspected alcoholic ketoacidosis that had undergone medico-legal investigations in our facility from 2011 to 2013 were retrospectively selected. A series of laboratory parameters were measured in whole femoral blood, postmortem serum from femoral blood, urine and vitreous humor in order to obtain a more general overview on the biochemical and metabolic changes that occur during alcoholic ketoacidosis. Most of the tested parameters were chosen among those that had been described in clinical and forensic literature associated with alcoholic ketoacidosis and its complications. Ketone bodies and carbohydrate-deficient transferrin levels were increased in all cases. Biochemical markers of generalized inflammation, volume depletion and undernourishment showed higher levels. Adaptive endocrine reactions involving insulin, glucagon, cortisol and triiodothyronine were also observed. Metabolic and biochemical disturbances characterizing alcoholic ketoacidosis can be reliably identified in the postmortem setting. The correlation of medical history, autopsy findings and biochemical results proves therefore decisive in identifying pre-existing disorders, excluding alternative causes of death and diagnosing alcoholic ketoacidosis as the cause of death.

The post-mortem relationship between beta-hydroxybutyrate (BHB), acetone and ethanol in ketoacidosis

A reduced blood pH (ketoacidosis) from the production of β-oxidative ketone bodies as a result of alcoholism (alcoholic ketoacidosis, AKA) or diabetes (diabetic ketoacidosis, DKA) can feature in many fatalities and analytical evidence can be used to support a pathological diagnosis, or provide a possible cause of death in the absence of other pathologically significant findings. Existing beliefs concerning the relationship of BHB concentrations, acetone and ethanol have been re-examined by analysis of BHB, acetone and ethanol in over 350 fatalities grouped into alcoholics, diabetics, alcoholic diabetics, coupled with speculative cases and those with an alternative cause of death. Uniquely, the concentrations of BHB were measured in post-mortem blood, urine and vitreous humour using selective GC–MS. The results showed that existing beliefs need to be re-evaluated. Ethanol is not always low (<10 mg/dL) or absent in cases of AKA. Also, the absence of acetone does not preclude a high BHB (>250 mg/L), therefore acetone can be used as an initial marker pathologically significant ketoacidosis. For blood and urine BHB concentrations the following interpretative ranges can be used (in mg/L); normal (<50 mg/L), raised (51–249 mg/L), high and pathologically significant (>250 mg/L). Initial data suggest vitreous humour BHB could be a useful alternative in the absence of blood (same interpretative ranges may also apply). Analytical recommendation for investigation of post-mortem ketoacidosis is also presented.