A retrospective study of unexpected deaths with alcohol use disorder from Japanese forensic autopsy cases.

BACKGROUND: Alcohol use disorder (AUD) is an important target for prevention of alcohol-related problems. In this study, we analyzed forensic autopsy cases to reveal the characteristics of the living conditions and death situations of individuals with AUD. METHODS: We retrospectively investigated 486 cases with a history of alcohol consumption for which a forensic autopsy was performed from 2012 to 2021 in Yamaguchi prefecture. Judgement of AUD was made using DSM-5. Various factors were compared statistically between AUD and non-AUD cases. RESULTS: Of the 486 cases, 225 (46.2%) were judged to be AUD, including 89 (18.3%) with advanced AUD, 33 (6.8%) were judged not to be AUD, and a judgement could not be made in the remaining cases. AUD was associated with alcohol consumption prior to death. Only 14.3% of the advanced-AUD cases was in treatment for alcohol dependence. The rates of interpersonal, health, financial and legal problems, receipt of public assistance and an extremely cluttered or hoarding house status were higher in all AUD and advanced AUD cases. Living alone, smoking and BMI were also associated with AUD. CONCLUSIONS: Many cases of alcohol-related deaths may have AUD, and persons with AUD who undergo a forensic autopsy commonly have multiple socioeconomic factors that may be associated with isolation that is involved in exacerbation of AUD. Further studies of these associations are needed because early diagnosis and treatment of AUD and support for the patient may lead to reduction of alcohol-related deaths.

Stillbirth Associated With Anomalous Origin and Course of the Left Coronary Artery: A Report of 2 Cases.

Coronary artery anomalies and their potential sequelae are not well studied in association with stillbirth. Herein, we report the autopsy findings in two term stillborn fetuses with coronary artery anomalies. Both fetuses showed identical findings consisting of an abnormal origin of the left coronary artery from the right sinus of Valsalva and an interarterial course of the left coronary artery. Histologic vascular and myocardial changes were also present. These coronary artery findings are associated with sudden death in adults and neonates, and therefore, their potential to be a cause and/or contributor to fetal death is suspected.

An Autopsy Case of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Induced by Propylthiouracil.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a complication caused by antithyroid drugs, particularly propylthiouracil (PTU). Most patients experience organ failure due to the affects of the treatment regimen. We herein report the case of an 89-year-old woman whose severe AAV induced by PTU resulted in various instances of organ failure that eventually led to death after 9 years of PTU therapy. During autopsy, we identified five types of organ failure. As AAV is a potentially fatal disease, the development of various vasculitis symptoms during PTU therapy should therefore be carefully monitored.

Acanthosis nigricans - a potentially useful clue to the presence of significant occult disease at autopsy.

A 19-year-old male was found dead in his apartment. At autopsy he was morbidly obese (Body mass index; BMI - 40.5) with multiple areas of velvety pigmented thickening of the skin in folds around the neck, in the axillae, in the inframammary regions, over the anterior waistline and groin regions and over the dorsal aspects of the feet. These had the typical appearance of acanthosis nigricans. Internal examination revealed aspiration of gastric contents into the airways. Vitreous humour biochemistry showed markedly elevated levels of both glucose (62.9 mmol/L) and ß-hydroxybutyrate (13.54 mmol/L). Death was, therefore, due to aspiration pneumonia complicating diabetic ketoacidosis on a background of morbid obesity. The initial indicator of underlying diabetes, in conjunction with obesity had been acanthosis nigricans.

Prediction model for anabolic androgenic steroid positivity in forensic autopsy cases - a new tool to the autopsy room.

Non-prescription use of anabolic androgenic steroids (AAS) is associated with an increased risk of premature death. However, these substances are seldom screened in connection with forensic cause-of-death investigation, unless the forensic pathologist specifically suspects use, often based on a positive AAS use history. Since AAS use is often concealed from others, this practice may lead to mistargeting of these analyses and significant underestimation of the true number of AAS positive cases undergoing forensic autopsy. Thus, more accurate diagnostic tools are needed to identify these cases. The main objective of this study was to determine, whether a multivariable model could predict AAS urine assay positivity in forensic autopsies. We analyzed retrospectively the autopsy reports of all cases that had been screened for AAS during forensic cause-of-death investigation between 2016-2019 at the Finnish Institute for Health and Welfare forensic units (n = 46). Binary logistic regression with penalized maximum likelihood estimation was used to generate a nine-variable model combining circumferential and macroscopic autopsy-derived variables. The multivariable model predicted AAS assay positivity significantly better than a "conventional" model with anamnestic information about AAS use only (area under the receiver operating characteristic curve [AUC] = 0.968 vs. 0.802, p = 0.005). Temporal validation was conducted in an independent sample of AAS screened cases between 2020-2022 (n = 31), where the superiority of the multivariable model was replicated (AUC = 0.856 vs. 0.644, p = 0.004). Based on the model, a calculator predicting AAS assay positivity is released as a decision-aiding tool for forensic pathologists working in the autopsy room.

A novel conservative technique to allow oral opening and overcome rigor mortis during medicolegal autopsy.

This study presents a novel conservative technique to increase oral opening and overcome rigor mortis during medicolegal autopsy (MLA). The method proposes a myotomy of the temporalis and masseter muscles, taking advantage of the incisions of the cranial opening procedures, to achieve a significant oral opening (≥ 30 mm) in fresh cadavers with established rigor mortis without altering facial aesthetics. The study was performed on 48 individuals aged between 18 and 66 years (20 males and 28 females) who were autopsied at the Instituto Nacional de Patología Forense Dr. Sergio Sarita Valdez (Santo Domingo, Dominican Republic). The proposed technique not only allowed the oral access to all autopsied cadavers but also complied with current ethical standards for preserving facial aesthetics, taking into account the concerns of family members by allowing respectful viewing of the cadaver. This advancement not only contributes to the efficiency of oral autopsies but also influences public perception of forensic procedures and highlights the importance of ethical and aesthetic considerations in the context of MLAs. The proposed technique represents a significant step towards more respectful and ethical forensic practices, and offers practical advantages for a more complete and accurate assessment during MLA.

Between the hammer and the anvil: An unusual power hammer fatality.

Power hammers are mechanised forging devices that constitute a pivotal part of steel manufacturing. Power hammer-associated injuries are a rare occurrence. We report a noteworthy case of a 52-year-old man who sustained a high-energy penetrating injury while working with a power (counterblow) hammer. The man used a sizable disc-shaped metallic object to dislodge the forging wedged in the machine by applying the force of the striking ram on it. On impact, the object ejected and struck the man in the right lateral portion of the chest. The autopsy disclosed extensive damage to the thoracic and abdominal organs. The cause of death was opined to be exsanguination due to penetrating trauma of the heart and transection of the descending aorta. The investigation confirmed a breach of safety regulations. To the best of our knowledge, this is the first power (counterblow) hammer-related fatality in medico-legal literature.

Butane-related deaths in post-mortem investigations: A systematic review.

Volatile substance abuse is widespread among adolescents due to its easy availability and methods of consumption. Inhalant abuse represents a current problematic issue, causing significant morbidity and mortality due to direct toxicity on several target organs and displacement of gas which results in a lack of oxygen. This review aims to evaluate post-mortem and toxicological investigations in cases of suspected butane intoxication. We performed comprehensive research using the Preferred Reporting Items for Systematic Review (PRISMA) standards. Forty scientific papers fulfilled the inclusion criteria. A total of 58 cases of butane-related deaths were found. Among these, we found 11 cases of suicide (18%), 1 case of homicide (2%), 44 cases of accidental poisoning (76%), and 2 cases of work-related deaths (4%). Autopsy and post-mortem examinations were performed in 54 cases, whereas toxicological analyses were presented in 56 cases. In autopsy, pulmonary edema (51%) and poli-visceral congestion (59%) were the most common findings. When death by butane inhalation is hypothesized, autopsy and histological findings may be nonspecific, therefore toxicological investigations assume a crucial role along with attention to the methods used to collect biological samples.

A case of fatal poisoning caused by etomidate: evidence from pathological and toxicological analyses.

Etomidate is a nonbarbiturate sedative derived from imidazole. Prolonged and excessive use of etomidate can lead to the suppression of adrenocortical function, myoclonus, and even death. This report describes a rare case of a 47-year-old man who died from acute intoxication after oral ingestion of liquid containing etomidate. The cause of death was conclusively attributed to etomidate based on a comprehensive investigation, including autopsy, histopathological examination, toxicological analysis, and biochemical analysis. This is the first reported case of a fatality solely resulting from the oral ingestion of etomidate, which can provide valuable insights for future forensic investigations involving etomidate poisoning. Therefore, it is imperative to share this case with the scientific community.

Correlations and discrepancies between cardiac ultrasound, clinical diagnosis and the autopsy findings in early deceased patients with suspected cardiovascular emergencies.

Cardiac ultrasound (CUS), either focused cardiac ultrasound (FoCUS) or emergency echocardiography, is frequently used in cardiovascular (CV) emergencies. We assessed correlations and discrepancies between CUS, clinical diagnosis and the autopsy findings in early deceased patients with suspected CV emergencies. We retrospectively analysed clinical and autopsy data of 131 consecutive patients who died within 24 h of hospital admission. The type of CUS and its findings were analysed in relation to the clinical and autopsy diagnoses. CUS was performed in 58% of patients - FoCUS in 83%, emergency echocardiography in 12%, and both types of CUS in 5% of cases. CUS was performed more frequently in patients without a history of CV disease (64 vs. 40%, p = 0.08) and when the time between admission and death was longer (6 vs. 2 h, p = 0.021). In 7% of patients, CUS was inconclusive. In 10% of patients, the ante-mortem cause of death could not be determined, while discrepancies between the clinical and post-mortem diagnosis were found in 26% of cases. In the multivariate logistic regression model, only conclusive CUS [odds ratio (OR) 2.76, 95% confidence interval (CI) 1.30-7.39, p = 0.044] and chest pain at presentation (OR 30.19, 95%CI 5.65 -161.22, p < 0.001) were independently associated with congruent clinical and autopsy diagnosis. In a tertiary university hospital, FoCUS was used more frequently than emergency echocardiography in critically ill patients with suspected cardiac emergencies. Chest pain at presentation and a conclusive CUS were associated with concordant clinical and autopsy diagnoses.

Advanced Diagnostic Tools in Hypothermia-Related Fatalities-A Pathological Perspective.

BACKGROUND AND OBJECTIVES: Although classical gross features are known in hypothermia victims, they lack specific diagnosis features. The aim of our study was to reveal specific brain and lung pathological features in a group of hypothermia-related fatalities. MATERIALS AND METHODS: The study group comprised 107 cases from our files associated with hypothermia. Routine hematoxylin-eosin (H&E) staining and postmortem immunohistochemistry were performed. RESULTS: The microscopic cerebral exam revealed diffuse perineuronal and perivascular edema, gliosis, mononuclear cell infiltration, acute brain injuries, focal neuronal ischemia, lacunar infarction, and variable hemorrhages. Variable alveolar edema, pulmonary emphysema, intra-alveolar and/or pleural hemorrhage, and bronchopneumonia, as well as other pre-existing lesions, were identified in lung tissue samples. Glial cells displayed S100ß expression, while neurons showed moderate Hsp70 immunopositivity. Alveolar basal membranes exhibited diffuse ICAM-1 positive expression, while ICAM-1 and AQP-1 positivity was observed in the alveolar septum vascular endothelium. Statistical analysis revealed a significant correlation between S100ß and Hps70 immunoexpression and cerebral pathological features, between ICAM-1 immunoexpression and alveolar edema and pulmonary emphysema, and between AQP-1 immunoexpression and pulmonary emphysema. CONCLUSIONS: Our results add supplementary data to brain and lung pathological findings in hypothermia-related fatalities, with potential therapeutic value in hypothermia patients.

Sparse Asymmetry in Locus Coeruleus Pathology in Alzheimer's Disease.

 Tau accumulation in and neurodegeneration of locus coeruleus (LC) neurons is observed in Alzheimer's disease (AD). We investigated whether tangle and neuronal density in the rostral and caudal LC is characterized by an asymmetric pattern in 77 autopsy cases of the Rush Memory and Aging Project. We found left-right equivalence for tangle density across individuals with and without AD pathology. However, neuronal density, particularly in the caudal-rostral axis of the LC, is asymmetric among individuals with AD pathology. Asymmetry in LC neuronal density may signal advanced disease progression and should be considered in AD neuroimaging studies of LC neurodegeneration.

A fatal misdiagnosis of page kidney - case report.

Page kidney is a condition where external compression of the renal artery and renal parenchyma leads to subsequent ischaemia and activation of renin-angiotensin-aldosterone axis. A 42-year-old female with hirsutism, hypertension and diabetes was diagnosed with a right adrenal mass and underwent laparoscopic adrenalectomy. Her hypertension worsened postoperatively and was managed medically. Subsequently she developed a right flank pain on the fifth postoperative day and died suddenly the next day. Autopsy revealed a pale body with cushingoid appearance. Surgical scars were healthy. Internal examination of the abdomen revealed a haemoperitoneum of 500 ml together with a large subcapsular haematoma measuring 1000 ml surrounding the right kidney, compressing the right renal artery. Kidneys were pale and the right kidney was soft and friable. Cortical surface of the right kidney demonstrated a possible surgical puncture site with an overlying thrombus together with a contused inferior vena cava. Other organs were pale but appeared otherwise normal. Histology revealed diffuse cortical necrosis of right kidney and features of adult respiratory distress syndrome in the lungs. Haemorrhagic shock following laparoscopic adrenalectomy for right adrenal tumor was declared as the cause of death, contributed by the development of the Page kidney. Trauma of several aetiologies including laparoscopic abdominal surgery may contribute to Page kidney. It presents with flank pain, hypertension and renal mass. Since postoperative blood loss usually manifests as hypotension, resulting hypertension may mislead the attending clinicians. Once diagnosed, it can be managed with surgical drainage and antihypertensives.

Carnitine-acylcarnitine translocase deficiency: a case report with autopsy.

Fatty acid oxidation defects are a heterogeneous group of disorders related to the mitochondrial fatty acid oxidation pathway. Carnitine acylcarnitine translocase (CACT) is an enzyme responsible for the unidirectional transport of acylcarnitine across the inner mitochondrial membrane. This enzyme plays a crucial role in the oxidation of fatty acids. The autopsy pathology of the CACT deficiency is described in only a few cases. We describe the autopsy pathology of a child with CACT deficiency dominantly in the form of microvesicular steatosis of the hepatocytes, renal proximal tubular epithelia, cardiac myocytes, and rhabdomyocytes. The diagnosis was further confirmed on whole exome sequencing with compound heterozygous variants in the exon 1 (c.82G>T, p.Gly28Cys; likely pathogenic) and exon 5 (c.535G>A, p.Asp179Asn; uncertain significance) of the SLC25A20 gene. This case elucidates the histopathology of the liver and the detailed autopsy of a case of CACT deficiency from India.

Autopsy case of meningoencephalitis induced by nivolumab and ipilimumab in a patient being treated for non-small cell lung cancer.

A 75-year-old woman with stage IVB (cT2bN3M1b) lung adenocarcinoma was administered nivolumab, ipilimumab, carboplatin, and paclitaxel. Fourteen days after receiving chemotherapy, she experienced an impaired consciousness and a cerebrospinal fluid analysis revealed high protein levels and pleocytosis. She was diagnosed with nivolumab- and ipilimumab-induced encephalitis and was treated with corticosteroids which were tapered to 10 mg/day, with no symptom recurrence. She died 18 weeks after the initial presentation, as the cancer worsened. An autopsy showed encephalitis and CD8+ lymphocyte infiltration around the blood vessels. Thus, immune-related adverse events should be suspected and treatment should be initiated for patients presenting with an impaired consciousness when concurrently being treated with nivolumab and ipilimumab.

Forensic Pathology and Legal Issues in COVID-19: Case Report and Literature Review.

Autopsy investigations of deaths following nosocomial coronavirus disease 2019 (COVID-19) infection have enormous medical and social significance, as autopsies are essential for the correct statistical recording of COVID-19 deaths, presenting new lessons, which is important to policymakers and in the improvement of public health in general.  Our study is based on the presentation of a case of a road traffic accident involving an elderly 73-year-old female with a complication of nosocomial COVID-19 infection and death leading to forensic pathological investigation. This involved autopsy, histopathological examinations, and other tests, and highlighting the importance of medicolegal matters, including the legal and ethical practicalities encountered in healthcare. This article highlights the fact that patients who have sustained various traumatic injuries accompanied by nosocomial COVID-19 infection have higher risks of morbidity and mortality. The significance of the role of a Forensic Pathologist in dealing with the analysis of injuries and the performance of autopsies to determine the cause, mechanism, and manner of death. In addition, the important lesson of testing patients for COVID-19 more regularly during a long hospital admission period, to offer early treatment and isolation, including avoiding the further spread of the COVID-19 infection variants to patients and healthcare professionals, thereby minimising and preventing hospital-acquired infection and death is stressed.

A Multidisciplinary Approach to a Complex Fatal Attack Due to a Pack of Maremma Sheepdogs: Is It Always an Accident?

Deaths due to dog attacks are a worldwide issue. Fatal dog attacks may occur in various environments, including the dog owner's property. A lot of difficulties emerge when the attack involves a pack of dogs, of different species and sizes. In this case, it becomes much more difficult for forensic investigators to evaluate the event, especially regarding the identification of the dog or dogs that caused the death as well as the identification of the owner and the reconstruction of the dynamics for forensic purposes. In this paper, we analyze a specific case of an attack by a herd of Maremma sheepdogs. A crime scene investigation has been carried out. In the first phase of this case, the victim interacted with dogs that had non-aggressive attitudes. Then, after an escape attempt, she was assaulted by about 20 Maremma dogs of different sizes, leading to multiple injuries all over her body. The greatest difficulty was precisely that of reconstructing the dynamics due to the numerous injuries and dogs involved in the attack. The dynamics were divided into several stages following the analysis of the injuries found on the victim. This case study highlights how the forensic multidisciplinary approach has made it possible to precisely reconstruct the event. The analysis of the dogs' state of malnutrition and their suddenly aggressive attitude towards the victim revealed profiles of responsibility of the owner attributable to improper management and training of the animals to defend their property.

Alpha-methyltryptamine and 5-(2-methylaminopropyl)-benzofuran (5-MAPB) fatal co-intoxication: case report and review of literature.

The scientific literature contains little reliable data regarding new psychoactive substances and designer drugs, making it difficult to assess toxic blood levels and potentially lethal threshold. Here, we report a fatal co-intoxication involving two uncommon drugs ‒ alpha-methyltryptamine (AMT) and 5-(2-methylaminopropyl)-benzofuran (5-MAPB) ‒ combined with exposure to benzodiazepines, ephedrine, and norephedrine. AMT and 5-MAPB were quantified using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC/MS-MS), revealing concentrations of AMT 4690 ng/mL and 5-MAPB 101 ng/mL in postmortem peripheral blood. We additionally reviewed the literature to help interpret the likely roles of these molecules in the occurrence of death.

Comparative Study of Postmortem MRI and Pathological Findings in Malignant Brain Tumors.

This study compared magnetic resonance imaging (MRI) findings of postmortem brain specimens with neuropathological findings to evaluate the value of postmortem MRI. Postmortem MRI was performed on five formalin-fixed whole brains with malignant tumors. Postmortem T2-weighted images detected all neuropathological abnormalities as high-signal regions but also showed histological tumor invasion in areas without edema. Tumor lesions with high necrosis and edema showed high signal intensity on T2-weighted images; in three cases, lesion enlargement was detected on the final prenatal imaging and postmortem MRI. Disease progression immediately before death may have contributed to this difference. In conclusion, the correlation between MRI and neuropathological findings facilitates understanding of the mechanisms responsible for MRI abnormalities. Increased free water due to edema, necrosis, and brain tissue injury can explain the increased signal intensity observed on T2-weighted images. Postmortem MRI may contribute to effective pathology by identifying subtle abnormalities prior to brain dissection.