Protocol of Investigation on Sudden Death at Autopsy, Including Molecular, Genetic and Toxicology Testing

The role of the autopsy: 1) Whether the death is ascribable to a natural or unnatural cause and when natural, if cardiac or extra-cardiac;2) The nosology of the cardiac diseases and the mechanism of cardiac death, whether arrhythmic or mechanical;3) If the cardiac disease is inherited, screening and counselling of the next of kin is required. About 30% of sudden deaths is ascribable to genetically determined morbid entities, mostly transmissible with the autosomal dominant pattern of inheritance, so that 50% of the first degree relatives are genetically affected (“carriers”) and exposed at risk;4) If toxic or illicit drug abuse was involved.

Liver pathology in COVID-19 related death and leading role of autopsy in the pandemic

BACKGROUND Information on liver involvement in patients with coronavirus disease 2019 is currently fragmented.AIM To highlight the pathological changes found during the autopsy of severe acute respiratory syndrome coronavirus 2 positive patients.METHODS A systematic literature search on PubMed was carried out until June 21,2022.RESULTS A literature review reveals that pre-existing liver disease and elevation of liver enzyme in these patients are not common;liver enzyme elevations tend to be seen in those in critical conditions.Despite the poor expression of viral receptors in the liver,it seems that the virus is able to infect this organ and therefore cause liver damage.Unfortunately,to date,the search for the virus inside the liver is not frequent(16%of the cases)and only a small number show the presence of the virus.In most of the autopsy cases,macroscopic assessment is lacking,while microscopic evaluation of livers has revealed the frequent presence of congestion(42.7%)and steatosis(41.6%).Less frequent is the finding of hepatic inflammation or necrosis(19%)and portal inflammation(18%).The presence of microthrombi,frequently found in the lungs,is infrequent in the liver,with only 12%of cases presenting thrombotic formations within the vascular tree.CONCLUSION To date,the greatest problem in interpreting these modifications remains the association of the damage with the direct action of the virus,rather than with the inflammation or alterations induced by hypoxia and hypovolemia in patients undergoing oxygen therapy and decompensated patients.

Understanding the Unique Characteristics of Suicide in China: National Psychological Autopsy Study

Objective To compare the characteristics of suicides in the four main demographic groups： urban males, urban females, rural males and rural females in order to help clarify the demographic pattern of suicides in China. Methods A detailed psychological autopsy survey instrument was independently administered to 895 suicide victims in family members and close associates from 23 geographically representative locations from around the country. Results Pesticide ingestion accounted for 58% （519） of all suicides and 61% （3181519） of deaths were due to unsuccessful medical resuscitation. A substantial proportion （37%） of suicide victims did not have a mental illness. Among the 563 victims with mental illness, only 13% （76/563） received psychiatric treatment. Compared to other demographic groups, young rural females who died from suicide had the highest rate of pesticide ingestion （79%）, the lowest prevalence of mental illness （39%）, and the highest acute stress from precipitating life events just prior to the suicide. Contusion Many suicides in China are impulsive acts of deliberate self-harm following acute interpersonal crises. Prevention of suicides in China must focus on improving awareness of psychological problems, improving mental health services, providing alternative social support networks for managing acute interpersonal conflicts, limiting access to pesticides, and improving the resuscitation skills of primary care providers.

Peritoneal bleeding due to percutaneous transhepatic gallbladder drainage:An autopsy report

A 77-year-old man underwent percutaneous transhepatic gallbladder drainage(PTGBD) for acute cholecystitis as a preoperative procedure;however,he suddenly suffered cardiopulmonary arrest 4 h after the PTGBD and died.There were three centesis scars for the PTGBD,and only one pathway from the most dorsal centesis scar reached the gallbladder.Microscopically,the PTGBD pathway crossed and injured the intrahepatic arterial wall,and hepatic parenchymal bleeding extended along the PTGBD pathway to the inferior surface of the liver.Blood flowed to the peritoneal cavity through a small gap between the liver and gallbladder.Consequently,the PTGBD caused lethal bleeding.When the percutaneous transhepatic cholangio drainage/PTGBD pathway runs close to vessels near the liver surface,it might be necessary to deal with the possibility of rapid and lethal peritoneal bleeding.

Prevalence of pulmonary embolism at autopsy among elderly patients in a Chinese general hospital

Objectives To investigate the prevalence and characteristics of pulmonary embolism （PE） at autopsy in a Chinese general hospital over a period of 10 years, and to evaluate the antemortem achievement of the prophylaxis, diagnosis, and treatment of PE. Methods All medical records of deaths from the West Branch of the Chinese People＇s Liberation Army （PLA） General Hospital were retrospectively re- viewed, for the period of January 1, 2006 to December 31, 2015. Cases in which autopsies had been performed were identified and further analyzed. The numbers and detailed characteristics of patients who had PEs were noted. Prophylactic measures, along with diagnosis and treatment of PE, were recorded, if performed. Results During the 10-year period, 1057 patients died in the study hospital and 278 necrop- sies were performed （autopsy rate： 26.3%）. Nine patients were found to have PE （3.2%）, and in seven of these patients （2.5%）, the PE was considered to be fatal. Embolisms were found in the trunk and bilateral main branches of the pulmonary artery tree in all seven of the fatal PE cases. Right intracardiac thrombosis was detected in five of the nine PE patients （55.6%）. All patients with PE had been hospitalized in medical departments, and only one had undergone surgery during hospitalization. Antemortem prophylaxis was performed in two of the nine PE cases （22.2%）. None of the 9 patients had received a clinical diagnosis of PE before death. Conclusions The incidence of and death rate associated with PE may vary among different races and regions. Continuous monitoring of PE by means of necropsy in certain representative medical institutions is necessary.

Liquid Chromatography-tandem Mass Spectrometry for Analysis of Acylcarnitines in Dried Blood Specimens Collected at Autopsy from Neonatal Intensive Care Unit

Objective To investigate the feasibility of analyzing acylcarnitine in dry filter-paper blood spots by liquid chromatography-tandem mass spectrometry(LC-MS/MS) which could be applied to detect inborn errors of metabolism in neonates.Methods We obtained filter-paper blood from 26 dead infants from a neonatal intensive care unit(NICU) between October 1,2008 and September 30,2009.Acylcarnitine and amino acid profiles were obtained with LC-MS/MS.Four infants underwent routine autopsy.The postmortem blood specimens were compared with newborn blood specimens,and with specimens obtained from older infants with metabolic disorders.Results Of all the 26 patients,5(19.2%) were diagnosed as having different kinds of diseases:3 with methylmalonic acidemia(the concentration of C3,and the ratio of C3/C16,C3/C2 increased),1 with maple syrup urine disease(the concentration of leucine and isoleucine increased),and 1 with isovaleric aci-demia(the concentration of C5 increased).Conclusions Postmortem metabolic test can explain infant deaths and provide estimates of deaths attributable to inborn errors of metabolism in NICU.LC-MS/MS is suitable for analysis of postmortem specimens and can be considered for routine application in NICU autopsy.

An autopsy case of metastatic extramammary Paget’s disease treated with multimodality treatment including anti-HER2 therapy: What is the clinical and pathological significance of trastuzumab to the patient?

Advanced Extramammary Paget’s disease (AEMPD) shows a poor prognosis despite multimodality therapy. In recent years, it is suggested that anti-HER2 therapy may be promising for HER2-positive AEMPD. We herein present an autopsy case of a patient with AEMPD treated with multimodality treatment including anti-HER2 therapy. A 78-year-old man who diagnosed with AEMPD died after surgery and systemic chemotherapy including anti-HER2 therapy (trastuzumab). The metastatic skin lesions were immnohistologically HER2-positive. While the patients were administrated trastuzumab plus taxan (docetaxel, and paclitaxel) regimen, the metastatic skin lesion decreased, however, brain metastases were found in his brain and trastuzumab is discontinued. The skin metastasis rapidly spread over his body, leading to weakness, and he eventually died. At autopsy, the lesions of EMPD were extended distant organs including brain, although each metastasis was small and asymptomatic. The wide lesion of skin metastasis was exacerbated after discontinuation of trastuzumab, and transudate was observed due to the extensive necrosis and erosion. Our autopsy findings showed one progressive pattern of AEMPD, and indicated what is the clinical and pathological significance of anti HER2 therapy for HER2-positive AEMPD.

Verbal Autopsy of Stillbirths and Neonatal Deaths in a Rural Area of Burkina Faso

Introduction: In developing countries, many neonatal deaths still occur at home and the causes of these deaths are not ascertained. Objective: To identify the causes of stillbirths and neonatal deaths that occur at home and the factors that have contributed to these deaths. Materials and Method: We have used the method of verbal autopsy to investigate the stillbirths and neonatal deaths in nine villages in the health area of Namsiguia, health district of Ouahigouya, Burkina Faso, during the period January 1, 2007 to December 8, 2012. Results: Over these six years, we have recorded 19 stillbirths and 36 neonatal deaths among 1507 live births, demonstrating a neonatal mortality rate of 28.8 per1000 and a rate of stillbirths of 12.6 per 1000. The average age of newborns at death was 5.6 days and the sex-ratio was 1.6. The major cause of stillbirths was antenatal hypoxia and birth asphyxia (42.1%). The direct causes of neonatal deaths were neonatal sepsis (41.7%), preterm birth (19.4%) and hypoxia and birth asphyxia (11.1%). There were 42.1% deliveries and 58.3% neonatal deaths, which occurred at home. We have noted 89.5% fresh stillbirths. Death occurred more often during the early neonatal period (55.5%). Factors significantly associated with neonatal death were, lack of school education of mothers (OR = 4), precocious marriage of the mother (OR = 8), poor follow-up of pregnancies (OR = 3), birth at home (OR = 4), low socioeconomic level (OR = 6), and low geographical access to the health facility (OR = 4). Conclusions: Strengthening of the health infrastructure and improving their accessibility, reinforcement of the staff for high quality care, and communication for a change in behavior in rural communities, will contribute toward reducing neonatal mortality in the area of health of Namsiguia.

An autopsy case showing massive fibrinoid necrosis of the portal tracts of the liver with cholangiographic findings similar to those of primary sclerosing cholangitis

An 81-year-old Japanese man with jaundice was strongly suspected clinically of having primary sclerosing cholangitis based on clinical examinations and later died of hepatic failure. The entire course of the disease lasted about 10 mo. The autopsy revealed extensive fibrinoid necrosis in the liver, kidney, spleen, pancreas, lung, lymph nodes, and pleura. Particularly extensive fibrinoid necrosis in the portal tracts of the liver induced severe stenoses of the intrahepatic bile ducts, resulting in cholestasis in association with prominent liver injury. There were no findings indicating primary sclerosing cholangitis. The hepatic lesions in this case did not coincide with any known disease including collagen diseases. To clarify the cause of irregular stenoses of the intrahepatic biliary trees on cholangiographic findings, we postulate that some form of immunological derangement might be involved in pathogenesis of fibrinoid necrosis. However, the true etiology remains unknown.

Immunohistochemistry panel segregates molecular types of hepatocellular carcinoma in Brazilian autopsy cases

AIM: To assess the distribution of proteins coded by genes reported as relevant for the molecular classification of hepatocellular carcinoma (HCC).METHODS: In this retrospective cross-sectional study, the following clinicopathological data were analyzed in 80 autopsied HCC patients: sex, age, ethnicity, alcohol intake, infection with hepatitis B and/or C virus, infection with human immunodeficiency virus, prior treatment, basic and immediate causes of death, liver weight, presence of cirrhosis, number and size of nodules, gross pattern, histological grade and variants, architectural pattern, invasion of large veins, and presence and location of extrahepatic metastases. The protein products of genes known to be involved in molecular pathogenesis of HCC, including epidermal growth factor receptor (EGFR), MET, keratin 19 (K19), vimentin, beta-catenin, mechanistic target of rapamycin (mTOR), extracellular signaling-related kinase (ERK)1, ERK2, Ki67, cyclin D1, caspase 3 and p53, were detected by immunohistochemistry on tissue microarrays. The expression levels were scored and statistically assessed for correlation with HCC parameters.RESULTS: Infection with hepatitis C virus was identified in 49% of the 80 autopsy patients, cirrhosis in 90%, advanced tumors in 95%, and extrahepatic metastases in 38%. Expression of K19, p53 and ERK1 correlated to high-grade lesions. Expression of ERK1, nuclear beta-catenin, cyclin D1 and ERK2 correlated to higher rates of cell proliferation as determined by Ki67. Expression of MET, EGFR (> 0) and caspase 3 correlated with lower histological grades. Expression of EGFR correlated to that of caspase 3, and overexpression of EGFR (≥ 200/300) was observed in low-grade tumors more frequently (grades 1 and 2: 67% vs grade 3: 27% and grade 4: 30%). Expression of ERK1 was associated with that of K19 and vimentin, whereas expression of ERK2 was associated with that of cyclin D1, MET and membrane beta-catenin. Expression of vimentin was strongly correlated with that of K19.CONCLUSION: Expression of K19, p53, ERK1, ERK2, vimentin and nuclear beta-catenin was related to higher-grade markers, as opposed to expression/overexpression of EGFR, MET and caspase 3.

Evaluating the quality of evidence for diagnosing ischemic heart disease from verbal autopsy in Indonesia

BACKGROUND Mortality and cause of death data are fundamental to health policy development.Civil Registration and Vital Statistics systems are the ideal data source,but the system is still under development in Indonesia.A national Sample Registration System(SRS)has provided nationally representative mortality data from 128 subdistricts since 2014.Verbal autopsy(VA)is used in the SRS to obtain causes of death.The quality of VA data must be evaluated as part of the SRS data quality assessment.AIM To assess the strength of evidence used in the assignment of Ischaemic Heart Disease(IHD)as causes of death from VA.METHODS The sample frame for this study is the 4,070 deaths that had IHD assigned as the underlying cause in the SRS 2016 database.From these,400 cases were randomly selected.A data extraction form and data entry template were designed to collect relevant data about IHD from VA questionnaires.A standardised categorisation was designed to assess the strength of evidence used to infer IHD as a cause of death.A pilot test of 50 cases was carried out.IBM SPSS software was used in this study.RESULTS Strong evidence of IHD as a cause of death was assigned based on surgery for coronary heart disease,chest pain and two out of:sudden death,history of heart disease,medical diagnosis of heart disease,or terminal shortness of breath.More than half(53%)of the questionnaires contained strong evidence.For deaths outside health facilities,VA questionnaires for male deaths contained acceptable evidence in significantly higher proportions as compared to those for female deaths.(P<0.001).Nearly half of all IHD deaths were concentrated in the 50-69 year age group(48.40%),and a further 36.10%were aged 70 years or more.Nearly two-thirds of the deceased were male(58.40%).Smoking behaviour was found in 44.11%of IHD deaths,but this figure was 73.82%among males.CONCLUSION More than half of the VA questionnaires from the study sample were found to contain strong evidence to infer IHD as the cause of death.Results from medical records such as electrocardiograms,coronary angiographies,and load tests could have improved the strength of evidence and contributed to IHD cause of death diagnosis.

An autopsy case of granulocyte-colony-stimulating-factor- producing extrahepatic bile duct carcinoma

A 79-year-old man was referred to this department due to the presence of extrahepatic bile duct carcinoma with a tumor at the left chest wall. The lesion was suspected to be a metastasis of bile duct carcinoma to the left wall, however, computed tomography (CT) revealed no regional lymph node or liver metastases. In addition, cytological and pathological examinations did not show malignancy. At the time of admission, the white blood cell count was 21 460 cells/μL (neutrophils, 18 240 cells/μL) and this elevated to 106 040 before death. In addition, serum granulocyte colony-stimulating factor (G-CSF) was elevated. At 28 d after admission, the patient died. An autopsy showed a poorly differentiated adenocarcinoma with sarcomatous change, which had slightly invaded into the pancreas around the bile duct, and was found in the distal bile duct with multiple metastases to the chest wall, lung, kidney, adrenal body, liver, mesentery, vertebra and mediastinal and para-aortic lymph nodes, without locoregional lymph node and liver metastasis. The cancer cells showed positive immunohistochemical staining for anti-G-CSF antibody. This is believed to be the first report of an extrahepatic bile duct carcinoma that produces G-CSF. Since G-CSF-producing carcinoma and sarcomatous change of the biliary tract leads to poor prognosis, early diagnosis and treatment are needed. When infection is ruled out, the G-CSF in serum should be examined. In addition, examinations such as bonescintigraphy and chest CT should also be considered for distant metastasis.

Autopsy study of anatomical features of the posterior gastric artery for surgical contribution

AIM： To investigate features of the posterior gastric arten/（PGA） with respect to incidence, location and size by using autopsy subjects. METHODS： Autopsies were performed on 72 cadavers of adults with no history of abdominal operations. The localization of the PGA, the distance between the root of the splenic artery and the origin of the PGA, and the external diameter of the PGA were examined. RESULTS： The PGA was recognized in all patients. In 70 （97.2%） cadavers, the PGA branched from the splenic artery, and one female in this group had two PGAs. In 1 （1.4%） patient, the PGA originated from the root of the celiac trunk and in another （1.4%） patient, the PGA branched from the superior polar artery. Overall, the PGA extended for a length of 5.8-12.2 （mean, 8.4） cm from the root of the splenic artery, and the external diameter of the PGA was 1.2-3.2 （mean, 2） mm. CONCLUSION： The anatomical features of the PGA can be readily observed and characterized by autopsy. This study has provided valuable information on the features of the PGA useful in the planning of surgical treatment.

Forensic Pathological Expertise of Medical Tangle Analysis of 139 Autopsy Cases

In this article , we report 139 autopsy cases of medical tangle , which were examined by the Department of Forensic Pathology, Faculty of Medicine, Tongji Medical University from Jan. 1972 to Dec. 1992.The emphasis is put on analyses of the status of medical tangle autopsy in forensic pathology, involved medical departments , distribution of victim's age and sex , differences between clinical diagnosis and autoptical conclusion, the composition and causes of medical tangle. The associated problems in forensic pathological autopsy are also discussed.

Aka Canturk Oral Autopsy Method for the Dental Identification of Fetus and Infant Cases

Forensic research requires the application of reliable identification methods for unidentified individuals, among which the dental analysis has prime importance. The most significant source of dental evidence is oral autopsy applications, which consist of an examination and evidence collection from the oral cavity of a deceased individual. Oral autopsies show variations depending on the age of the person due to rigor mortis. The oral autopsy of a child may require an easier operation than adults, and thus, the procedures are usually simpler for fetus or infant cases. The aim of this study is to propose the theoretical and experimental aspects of an oral autopsy protocol for a special age group of fetus or infant cases, which is a method for extracting tooth germs in their developmental stages for identification purposes and entitled by the authors’ names as the “Aka-Canturk Oral Autopsy Method”.

Autopsy Findings in a Case of Ellis Van Creveld Syndrome with Review of Literature

Ellis Van Creveld (EVC) syndrome is one of the congenital anomalies not compatible with life. It is also known as chondroectodermal dysplasia. The most common manifestations of this syndrome are short ribs, postaxial polydactyly, growth retardation, and ectodermal and cardiac defects. It has an incidence of one in every 60,000 live births and equal sex predisposition. In our case, perinatal autopsy was performed in a stillborn baby of 32 weeks of gestation having syndactyly, polydactyly and short forearms to know the cause of death and the diagnosis emerged as EVC syndrome. It is important to diagnose EVC syndrome as it is transmitted as an autosomal recessive disorder, so genetic counseling is required to make parents aware of the risk of recurrence.

Autopsy-Based Study of Abdominal Traffic Trauma Death after Emergency Room Arrival

We experienced the autopsy cases that the deceased was alive in emergency room on arrival. Bleeding is the leading cause of preventable death after injury. This retrospective study aimed to characterize opportunities for performance improvements identified in patients who died from traffic trauma and were considered by the quality improvement of education system. We focused the abdominal traffic trauma injury. An autopsy-based cross-sectional study was conducted. A purposive sampling technique was applied to select the study sample of 41 post-mortems of road traffic accident. 16 patients (39.0%) were abdominal trauma injury. The mean period of survival after meeting with accident was 13.5 hours, and compared abdominal trauma death was 27.4 hours longer. In road traffic accidents, the most injured abdominal organs were the liver followed by mesentery. We thought that delayed treatment was associated with immediate diagnostic imaging, and so expected to expand trauma management examination.

Rapidly deforming gastric carcinosarcoma with osteoblastic component:An autopsy case report

Carcinosarcomas are rare,malignant,biphasic tumors simultaneously comprising carcinoma and sarcoma in a single tumor.We present an extremely rare case of gastric carcinosarcoma with an osteoblastic component that drastically changed its shape within 2 mo.A 59-year-old male patient presented to the emergency outpatient unit with a complaint of black stool.Gastrointestinal endoscopy showed an ulcerated mass in the cardia of the lesser curvature of the stomach.Biopsy specimens revealed only adenocarcinoma.Two months later,the ulcerated lesion drastically changed its shape into an exophytic tumor.Total gastrectomy was performed.In the resected specimen,the gastric tumor contained both adenocarcinoma and sarcoma components with lace-like osteoid.The patient died 7 mo after the operation,and an autopsy was performed.In the autopsy,widespread metastases were present in the liver,lung,lymph nodes and peritoneum.In this report,we describe a case of gastric carcinosarcoma and presume its tumorigenesis based on the autopsy findings.

Psychological Autopsy. A Possible Innovative Revision of the MAPI: Psychological Autopsy Structured on Individual Cases (PASIC)

The aim of this research is to propose an innovative technique of the psychological autopsy.Compared to the classic MAPI model,our procedure is structured on each single case by adapting the interview to the environmental circumstances,the socio-cultural characteristics of the subject examined and to the weapon used in the criminal act.We believe that this approach improves both confidence and compliance of the interviewee and the chances of obtaining information that could escape a standardized investigation.In one of the cold cases we studied,this new protocol led to the discovery of biological material coming from the crime scene,which had been secretly hidden by the subject for over 50 years.The aim of our work was also to coordinate the activity of the interviewer,trying to avoid repetition in the interviews that could lead to an alteration of the answers to the questions asked.In the first phase,questions with open-ended responses were preferred.In later stages,we asked specifically worded questions.We were careful not to formulate questions that had already been asked.It must be emphasized that for each case of psychological autopsy only one operator handled the interview.

Study of hypoechoic nodule diagnosis of BPH in outer gland of the prostate by TRUS and autopsy

To investigate the possibility of benign prostatic hyperplasia (BPH) in prostatic outer gland by transrectal ultrasound (TRUS) and autopsy examination.Methods Fifty-nine patients were biopsied by TRUS guided in sagittal and longitudinal sections,respectively,because hypoechoic nodules were found in the outer glands of the prostates.The specimens were stained by HE methods.The whole prostate specimens obtained from 16 men at autopsy were studied.Sonogram of the specimens was investigated by putting them in water.Them the specimens were sliced down perpendicularly to the urethra,histologically processed and stained by HE methods.Results Pathologically,22 of the 59 specimens were of benign prostate hyperplasia (BPH),29 of prostate cancer (PCa),1 of prostatic intraepithelial neoplasia (PIN) and 7 of tuberculosis (TB).A clear-cut interface between inner gland and outer gland,and multiple calculi and cysts were found on sonogram.Pathological diagnosis of BPH of the outer glands was made in all HE-stained autopsied specimens with varying degrees of hyperplasia of the glands,small muscles and stroma.Conclusion It is suggested that hypoechoic nodules in outer gland of the prostate by TRUS on sonogram may be benign hyperplastic nodules besides PCa,PIN,and TB.10 refs,5 figs.