Autopsy Information Research Articles

Autopsy doesn’t always tell all: The importance of exhuming skeletal remains of cemetery unidentified decedents

The process of personal identification differs according to the state of preservation of the corpse, becoming more complicated when dealing with remains altered by taphonomic variables. Since 2015, the staff of the Laboratory of Forensic Anthropology and Odontology (LABANOF) of the University of Milan has been engaged in recovering the skeletons of 36 unknown people from the cemeteries of the city of Milan, to redraw their biological profiles and give them back the possibility of being identified. Of the 36 starting skeletons, 7 have been identified and therefore are not the object of this study, 25 individuals were previously subjected to an autopsy examination and 4 skeletons were studied for the first time in the present work. The post-mortem data of all the individuals who had previously undergone autopsy and had not yet been identified (n = 25) have been retrieved from the archives of the Institute of Forensic Medicine in Milan and allowed for a comparison with those obtained from the new anthropological study of each exhumed skeleton. The authors aim to present the three most interesting cases to better highlight the results that emerged from the comparison. The autopsy information alone lacked important details. In all cases, the anthropological examination proved to be capable of detailing the biological profile of the unknowns even after a long period of inhumation (even more than 20 years). The limitations of instrumental investigations in achieving the goal single-handedly and the importance of recovering the unknown skeletons from cemeteries for identification purposes are discussed.

Prevalence of concealed arrhythmogenic substrate for sudden cardiac arrest in the general population

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): US National Heart Lung and Blood institute National Institute of Health. Background Individuals who present with SCA as the first manifestation of heart disease (Concealed Substrate) present the greatest challenge for clinical risk stratification but population-based information in the current era is lacking. We hypothesized that improved awareness and access to health care has resulted in a reduction in prevalence of Concealed Substrate. Purpose We compared the overall prevalence, secular trends and SCA etiologies of Concealed Substrate in two geographically distinct US populations. Methods Consecutive cases of SCA were ascertained prospectively from 2 large ongoing US studies, the Population Cohort A (PopulationCohortA, 2002-2018) and Population Cohort B (PopulationCohortB, 2015-2022), total population 1.85 million residents. All out-of-hospital SCA events attended by emergency medical services were determined following an established multi-source ascertainment and adjudication process, and detailed lifetime clinical record evaluation conducted for each individual. This included the comprehensive electronic health record, evaluation of SCA survivors as well as all available autopsy information. Concealed Substrate cases were defined as SCA with no prior heart disease diagnosis. Results From a total of 5708 SCA cases (age 66.5 ± 18.2, female 35%), n=3390 (age 64.3 ± 18.8, female 34%) were identified in PopulationCohortA and n=2318 (age 71.6 ± 15.7, female 36%) in PopulationCohortB. In PopulationCohortA, prevalence of Concealed Substrate was 39% (n=1282, age 58.6 ± 21.7, 32% female) and decreased modestly over time (Figure; 37% in 2002-06 vs. to 33% in 2014-18; p=0.001). In PopulationCohortB, overall prevalence of Concealed Substrate was 41% (n=949, age 68.3 ± 17.6, 33% female) and did not change significantly over time (Figure; 2015-2022; p=0.06). Etiology of SCA was determined in a subgroup of overall cases (n=3210, 56%) of which n=2727 (85%) were ischemic SCA and n=483 (15%) non-ischemic SCA. Non-ischemic SCA was more commonly identified in Concealed Substrate (29% vs. 11%; p<0001) and ischemic SCA was more common in Revealed Substrate (89% vs. 72%; p<0.0001). Conclusion There was a modest reduction in prevalence over time, 33-41% of individuals continued to present with Concealed Substrate, with higher likelihood of non-ischemic SCA. These findings suggest that widely available and inexpensive tests such as the 12-lead ECG warrant further evaluation as a pre-screening method in the general population.

A fatal case of poisoning with a cathinone derivative: α-PiHP and its post-mortem distribution in body fluids and organ tissues.

New psychoactive substances (NPS) continue to appear on the drug market and alpha-pyrrolidinoisohexanophenone (α-PiHP) is one of the most popular cathinone derivatives. In this paper, we report a case of death caused by α-PiHP. Based on the toxicological results of the studied case along with autopsy, histopathological findings and crime-scene information, fatal intoxication with α-PiHP was accepted as the final cause of death. α-PiHP and its metabolite (OH-α-PiHP) were detected and quantified in all post-mortem materials (blood collected from the heart, the femoral vein and the dural venous sinuses, vitreous humour, cerebrospinal fluid, cerebral cortex, brainstem, cerebellum, bile, liver, kidney, heart, pancreas, spleen, thyroid gland, lung, adipose tissue, stomach and intestine). To date, this is the first case of determination of α-PiHP and its metabolite in post-mortem specimens. In our opinion, α-PiHP and its metabolite concentration database can be helpful in the interpretation of fatal cases.

Child and adolescent mortality associated with pesticide toxicity in Cape Town, South Africa, 2010–2019: a retrospective case review

BackgroundPoisoning of children after exposure to pesticides is a major public health concern, particularly in countries with poorer urban populations, such as South Africa. This may stem from the illegal distribution and domestic use of street pesticides, which are highly hazardous agricultural pesticides. The aim of this study was to profile paediatric deaths due to acute pesticide poisoning in the west-metropole of Cape Town, South Africa; to identify whether the active ingredients were highly hazardous pesticides according to the FAO and WHO; and to inform policy and public health interventions to prevent future exposures and mortality.MethodsA retrospective and descriptive analysis of forensic post-mortem records (2010 to 2019) was conducted to identify cases of paediatric deaths (< 18 years old) in the west metropole of Cape Town, involving pesticide poisoning admitted to the Salt River mortuary (one out of 16 mortuaries in the Western Cape province). Demographic, circumstantial, autopsy, and toxicological information was captured. Descriptive statistics, together with chi-square tests, Fisher’s probability tests, and Mann–Whitney U tests were used to analyse the data.ResultsIn total, 54 paediatric pesticide deaths were identified, including 22 (40.7%) males and 32 (59.3%) females, out of 5,181 paediatric unnatural deaths admitted over the 10-year period. The median age of the decedents was 8.3 years (range: 1 day to 17.9 years), with the majority under five years (42.6%) or between 15 and 18 years old (40.7%). All incidents occurred in peri-urban areas of Cape Town, with most individuals being admitted to hospital (88.9%) for a median survival time of 4.8 h. Toxicological analysis was requested in 50 cases (92.6%) with the organophosphate pesticides terbufos (n = 29), methamidophos (n = 2) and diazinon (n = 2) detected most frequently. Adolescent (15–18 years) suicides (29.6%) and accidental child deaths (< 4 years) (18.5%) were common.ConclusionsTerbufos and methamidophos are highly hazardous pesticide (HHP) active ingredients registered in South Africa for agricultural uses, yet commonly sold as street pesticides for domestic use in lower socioeconomic areas. Reducing access and availability of toxic pesticides, especially through the illegal selling of street pesticides, and providing low toxic alternatives to poorer communities, may support mortality reduction initiatives. Mortality and toxicology data provide important, often overlooked, surveillance tools for informing policy and public health interventions to reduce toxic pesticide harm in local communities.

Causes of Death in Patients with Sickle Cell Disease from a Large Population-Based Cohort

Background Mortality rates and causes of death in children with sickle cell disease (SCD) have changed significantly over the past several decades. With ongoing improvements in standards of care, modern mortality rates and causes of death must be updated. Children's Healthcare of Atlanta (CHOA) houses one of the largest pediatric SCD programs in the country. This analysis reviews causes of death in children with SCD who were treated at CHOA between June 2010-June 2022. Methods We reviewed the CHOA's Sickle Cell Clinical Database (SCCD) for deceased patients. Demographics, SCD genotype, date and age at death, healthcare utilization, hydroxyurea (HU) use, chronic transfusion therapy (CTT), and bone marrow transplant (BMT) were obtained from the SCCD. Cause of death and history of significant comorbidities were abstracted from the medical record, death certificates and/or autopsy reports. Results A total of 4022 unique patients with SCD were seen at CHOA from June 2010- June 2022. Fifty-seven patients died during this period. All but 1 patient had been seen in the CHOA Sickle Cell Outpatient Clinic at least once. That patient received SCD care at a different institution, died from complications of a non-SCD related disease following transfer to CHOA, and was excluded from analysis. SCD-related causes accounted for 22 (39%) deaths. Acute SCD-related causes included bone marrow fat emboli, acute chest syndrome or pneumonia, cerebral hemorrhage in a person with history of stroke and moyamoya, and pulmonary hypertensive crisis. Of the infectious causes included Streptococcus pneumoniae, gram negative bacteria, unspecified streptococcal meningitis (by verbal report), and due to presumed septic shock complicated by severe anemia. Viral infections included respiratory syncytial virus, COVID-19 with severe anemia, and Parvovirus B-19 complicated by bone marrow fat emboli. Death due to complications of treatment included ceftriaxone-induced hemolysis and severe intrathoracic hemorrhage after apheresis catheter removal for treatment of ACS. BMT-associated complications included adenovirus infection after transplant with a matched unrelated donor and Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis after haploidentical transplant (see Figure 1). Non-SCD comorbidities or accidents accounted for 15 (27%) deaths. These included heart disease, advanced cancer or complications of cancer (including E. coli sepsis in a child with relapsed neuroblastoma), accidents, one due to motor vehicle accident and one drowning. Gastrointestinal causes included bleeding from undiagnosed inflammatory bowel disease and liver failure leading to coagulopathy and intracranial hemorrhage. There was a case of severe anemia related to systemic lupus erythematosus. The causes of death were unknown in the remaining 19 (34%) of individuals. Six (11%) were under 18 years of age. Five died at home or out of state and had no autopsy information, one had autopsy declined by the coroner. Of those who were 18 years of age or older, 7 (53%) were lost to follow-up, 3 (23%) had transitioned to adult care, and 3 (23%) were still being treated at CHOA. There were more deaths in the 0-2 year and 15-17 year groups, and the most among adults (n = 19, 34%). Death from congenital heart disease was more frequent in children 0-5 years old. Pneumococcal sepsis were in children 5-7 years old, after stopping penicillin and before the second Pneumovax vaccine. Other bacterial infections were evenly distributed by age. Non-infectious SCD-related deaths were more likely to occur in patients 12 years and older (n = 6, 86%) (Figure 2). Conclusions Continuing from a previous study by Lai et al. (2020) which reported the 10-year mortality rate at CHOA, this study described the causes of death of SCD patients during a 12-year period. Of direct SCD-related causes, bone marrow fat embolism was the most common and was also present in a patient who also had Parvovirus-B19 infection. Severe anemia was present in several patients at the time of death, associated with ceftriaxone-induced hemolysis, presumed septic shock, COVID-19, systemic lupus erythematosus, as well as G or intracranial hemorrhage. Patients beginning transition to adult care are at risk of becoming lost to follow-up and may experience difficulties transitioning to adult care. Future analyses will include review of regional hospital where available, and CDC's National Death Index. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The key role of examining the placenta in establishing a probable cause for stillbirth

IntroductionAutopsy is regarded as the “gold standard” to determine probable causes of stillbirths. However, autopsy is expensive and not readily available in low- and middle-income countries. Therefore, we assessed how the clinical cause of death is modified by adding placental histology and autopsy findings. MethodData from the Safe Passage Study was used where 7060 pregnant women were followed prospectively. Following a stillbirth, each case was discussed and classified at weekly perinatal mortality meetings. This classification was later adapted to the WHO ICD PM system. Clinical information was presented first, and a possible cause of death decided upon and noted. The placental histology was then presented and, again, a possible cause of death, using the placental and clinical information, was decided upon and noted, followed by autopsy information. Diagnoses were then compared to determine how often the additional information changed the initial clinical findings. ResultsClinical information, placental histology, and autopsy results were available in 47 stillbirths. There were major amendments from the clinical only diagnoses when placental histology was added. Forty cases were classified as due to M1: complications of placenta, cord, and membranes, when placental histology was added compared to 7 cases with clinical classification only, and M5: No maternal condition identified decreased from 30 cases to 3 cases. Autopsy findings confirmed the clinical and placental histology findings. DiscussionClinical information together with examination of the placenta revealed sufficient information to diagnose the most probable cause of death in 40 of 47 cases of stillbirth (85%).

Causes of neonatal mortality using verbal autopsies in rural Southern Nepal, 2010-2017.

The burden of neonatal mortality remains high worldwide, particularly in South Asia. Verbal Autopsy is a method used to identify cause of death (COD) where vital registration capabilities are lacking. This study examines the causes of neonatal mortality in a large study population in rural Southern Nepal. The data used is from a larger cluster-randomized community-based trial. The study includes 984 neonatal deaths with complete verbal autopsy information which occurred between 2010 and 2017. The InterVA-5 software was used to identify COD. COD included severe infection (sepsis, pneumonia, meningitis/encephalitis), intrapartum related events (identified as birth asphyxia), congenital malformations, and other. The neonatal mortality rate was 31.2 neonatal deaths per 1000 live births. The causes of neonatal mortality were identified as prematurity (40%), intrapartum related events (35%), severe infection (19%), congenital abnormalities (4%), and other (2%). A high proportion, 42.5% of neonatal deaths occurred in the first 24 hours after birth. Over half (56.4%) of deaths occurred at home. This large prospective study identifies population level neonatal causes of death in rural Southern Nepal, which can contribute to national and regional COD estimates. Interventions to decrease neonatal mortality should focus on preventative measures and ensuring the delivery of high risk infants at a healthcare facility in the presence of a skilled birth attendant.

Postmortem reference concentrations of elements in blood and urine

To establish postmortem reference concentrations of elements. Fatal intoxications, both accidental and intentional, are a global issue. In the western world intoxications with pharmaceuticals dominate, but in other parts of the world other substances are more common. Intoxication with elemental compounds is generally considered to be uncommon. In a forensic setting, elemental intoxications are of great importance when investigating both accidental, suicidal, and homicidal deaths. Arsenic, for example, is a classical poison which also has relevance in the modern era. Unlike for pharmaceuticals, postmortem reference concentrations for elements are scarce. For many elements it is therefore unknown if, and to what extent, they are affected by postmortem redistribution. The current study presents normal postmortem reference concentrations of 68 elements in femoral blood and urine. In addition, possible sources of error such as contamination from collection tubes, preservative potassium fluoride solution and storage time are evaluated. Paired blood and urine samples from 120 cases of death by suicidal hanging in Sweden were collected. 20 cases from each of the six local units of forensic medicine were used to account for possible regional differences. Additionally, the included cases reflected both short and long storage times. To account for possible elemental contamination from collection tubes and the added potassium fluoride solution, multiple batches of tubes and multiple samples of potassium fluoride solution were also analysed. Concentrations of elements were determined by double focusing sector field ICP-MS. Key descriptive statistics for all 68 elements are provided (including mean, median and percentiles) in blood and urine. Forensic highlights include blood concentrations of total arsenic (mean: 4.25 μg/g), thallium (mean: 0.14 μg/g) and antimony (mean: 14.82 μg/g). For several elements in blood and urine ( n = 24 and n = 25, respectively) a majority of elemental concentrations were below the limit of detection. The contribution of contamination from collection tubes were minor compared to the overall mean elemental concentrations in both blood and urine. Though the added solution of potassium fluoride contained a large assortment of elements, given the small amounts of this solution added to samples, the overall contribution is minor for most elements relative to the overall mean. However, there was a significant difference between samples with short and long storage time for 22 elements in blood and 17 elements in urine. These differences reflected both increases and decreases in concentration. Relative to antemortem elemental concentrations the postmortem concentrations show both increases and decreases. Of special note are markedly higher concentrations for several elements in blood (such as cadmium, chromium, manganese and antimony) compared to several antemortem populations. In general, it can be assumed the phenomenon of postmortem redistribution is as large for elements as it is for drugs and other substances. When evaluating individual concentrations, it is important to be aware of potential sources of contamination and the potential influence of storage time. Concentrations indicating overexposure must be evaluated together with autopsy findings and case circumstances to form a holistic view of the case as a whole. The present study provides an important tool when evaluating postmortem elemental concentrations. It fills a needed gap between large antemortem population studies and postmortem case reports or small case series of elemental intoxications. Together with the forensic autopsy and circumstantial information the present references will aid in diagnosing cases of potential elemental overexposure.

A retrospective autopsy study of 42 cases of stillbirth in Avicenna Research Institute

BackgroundAccording to the World Health Organization about 2.6 million deaths were reported worldwide in 2015. More than 98% of stillbirths occur in developing countries. At present, the causes of many cases of stillbirth are unknown due to the lack of necessary data and autopsies in Iran. The aim of this study was to investigate the most plausible cause of stillbirth by evaluating clinical records and autopsies.MethodsA cross-sectional study of 42 stillbirth autopsies in Avicenna Research Institute from 2012 to 2019, was conducted. Data were extracted from a checklist prepared by the project researchers. The checklist contains maternal demographic information, medical history and maternal illness, pregnancy risk factors, placenta and stillbirth information. Collected data were reviewed and classified according to the ReCoDe (Relevant Condition at Death) system.ResultsIn the present study, based on ReCoDe classification, related causes of 95.2% of stillbirths were identified and 4.8% were in the unclassified group. The most common causes were:Fetal causes (64.3%), umbilical cord (14.3%), placenta (7.1%), amniotic fluid (4.8%), maternal medical conditions (2.4%). The causes of about 70% of stillbirth in Iran are unexplained, but in this study, using autopsy results and ReCoDe classification, only 4.8% of stillbirth causes remained unexplained.ConclusionsIn our study, unknown cases were rare after autopsy. But considering the limitations and costs of autopsy, we need to design the guideline to specify cases who need an autopsy.Fetal autopsy, placental examination and clinical information could reduce the proportion of stillbirths that remain unexplained.

More than half of all sudden cardiac deaths occur in persons without a history of cardiovascular disease: A study of 54,028 deaths in Denmark

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Copenhagen University Hospital, Rigshospitalet Background Sudden cardiac death (SCD) is a major public health problem accounting for a large proportion of global mortality. Previous studies suggest that SCD often occurs in the general population in persons not previously diagnosed with cardiovascular disease. It is evidently challenging to identify high-risk persons in an overwhelmingly large population of mainly healthy individuals and studies are needed to further characterize these SCD cases. Purpose To estimate SCD burden in patients not previously diagnosed with cardiovascular disease and to characterize these SCD cases. Methods All deaths in Denmark (population of 5.5 million) in 2010 were manually reviewed case-by-case. Autopsy reports, death certificates, and information from nationwide health registries were systematically examined to identify all SCD in 2010. The Danish National Patient Register contains information on all in- and outpatient activities at Danish hospitals and emergency departments and was used to identify all SCD cases with a previous cardiovascular diagnosis. Results There were 54,028 deaths in Denmark in 2010, of which 6,867 (13%) were categorized as SCD. Overall incidence rate of SCD was 124 (95%-CI: 121-127) per 100,000 person-years. Of all SCD, 59% were not diagnosed with cardiovascular disease prior to death. SCD incidence in persons with and without a history of cardiovascular disease was 790 (95%-CI: 762-820) and 78 (95%-CI: 75-80) per 100,000 person-years, respectively. This corresponds to an incidence rate ratio of 10 (95%-CI: 10-11). SCD cases with no previously diagnosed cardiovascular diseases were younger (median age 75 vs. 80 years, p&amp;lt;0.001), more often female (45 vs. 42%, p=0.019), and on average had a lower household income (p=0.002) (Table 1). SCD cases not diagnosed with cardiovascular disease prior to death in general had fewer comorbidities, except for psychiatric diseases, which were more common in the undiagnosed group (Table 1). Conclusion In this large and nationwide study of all SCD in Denmark in 2010, more than half of all SCD occurred in persons without a history of cardiovascular disease. This suggests that SCD is often first manifestation of disease. We currently do not have accurate tools for SCD risk stratification in the general population and future research is needed to identify modifiable and easily measured risk factors of SCD in the general population.

In Reply.

In Reply.—We thank the Centers for Disease Control and Prevention's (CDC's) Infectious Diseases Pathology Branch laboratory for performing these tests and for sharing the full extent of its workup.The investigating forensic pathologist is in the best position to integrate all of the autopsy, laboratory, and clinical information to determine the cause of death. The CDC unfortunately overstepped its role with patient B by diagnosing the death as “attributable directly” to clostridial sepsis “based on the composite histological, immunohistochemical, and molecular findings.” It misinterpreted common postmortem findings, including bacterial overgrowth. This is what causes bodies to putrefy after death as the intestinal flora spread throughout the body, and this is why there was no associated inflammation. The autopsy on patient B was done 2 days after his death. Practicing forensic pathologists routinely see this type of postmortem bacterial overgrowth at autopsy. In fact, studies have used the postmortem growth of clostridium to attempt to determine the postmortem interval.1,2 This bacterial invasion is not the cause of death but a consequence of death.3 The adrenal glands undergo early autolysis and it is common to see some “hemorrhage” after death. Clostridium septicum is a very small component of the human colon flora and rarely causes infection.4,5 It has been described to cause sepsis with colonic malignancies that offer a portal of entry into the circulation.6 Both forensic pathologists who certified these deaths spoke directly with the parents to confirm the clinical histories and did not rely upon tertiary accounts.The clinical history and cardiac findings simply do not support a diagnosis of clostridial sepsis. The clostridial “diagnosis” was not included in the report because it was a postmortem artifact; it was not an “important finding” or an “alternate cause of death.”For patient A, we agree that for completeness the parvovirus B (PVB) results should have been included in our report. We note that the CDC also did not diagnose this death as caused by PVB19 myocarditis. It noted in its report that “the significance of this finding is unclear as parvovirus-19 likely has long-term persistence in heart tissues, and is frequently detected in heart tissues from autopsies with no clinical or histopathologic evidence of myocarditis.1,2”4,7,8 In a study4 using 84 persons who died by suicide as a control group, PVB genomes were detected by polymerase chain reaction in 44% of the hearts. The authors concluded “that a positive PVB polymerase chain reaction test in cardiac autopsy specimens most likely represents a persistent infection with no or limited association to myocarditis. Hence, caution should be taken when interpreting the results for establishing the cause of death.”4 The histologic features in patient A were not those of viral myocarditis, nor would the ischemic injury be explained by such an infection. Thus, we conclude that the detection of the PVB genome is an incidental finding.

Contextual information in medicolegal death investigation decision-making: Manner of death determination for cases of a single gunshot wound

To explore the role of contextual information in determining manner of death, four cases involving single gunshot wounds were presented to participants (n = 252) involved in medicolegal death investigation. The participants received identical autopsy information but different contextual information. The data demonstrated that participants tended to rely on contextual information more than autopsy information: In the suicide context, participants across the four cases reached 153 final decisions of suicide (and 25 of homicide), whereas in the homicide context, participants reached only 10 final decisions of suicide (and 181 of homicide) --all while examining identical autopsy information. The impact of the contextual information was so powerful that many participants changed initial autopsy-based conclusions to align with the contextual information. Given the significant role and impact that contextual information has on expert decision making, one must consider what, how, and when contextual information should be used.

Evaluation of histopathological findings of cardiac deaths in forensic autopsies.

The vast majority of sudden and unexpected natural deaths are related to cardiovascular diseases, especially coronary artery diseases. In this study, we aimed to reveal the epidemiological differences between men and women and to investigate the most common pathologies that cause cardiac deaths. Five thousand seven hundred sixty-eight autopsy cases that were done in 2016 were reviewed for the autopsy information and histopathological findings. Of the 5768 autopsies performed, 866 were due to cardiac causes. Eight hundred thirty-two cases were reviewed due to lack of autopsy information in 34 cases. One hundred sixteen (13.9%) were female, and 716 (86.1%) were male. Coronary artery disease was detected in 760 of 832 cases. There were findings of acute or previous myocardial infarction in 595 (71.5%), perivascular and interstitial fibrosis in 159 (19.1%), myocardial rupture and tamponade in 31 (%3.7), valvular disease in 6 (0.7%), cardiomyopathy in 4 (0.5%), and congenital heart disease in 3 (0.4%). In the study, it was observed that the mean age of death due to cardiac pathology other than coronary artery disease was significantly lower than deaths due to coronary artery disease (p < 0.05). The presence of coronary artery disease in men was found to be significantly higher than in women (p < 0.001). In our study, it was found that deaths due to coronary artery disease are seen at an older age than cardiac deaths other than coronary artery disease. In addition, in line with current knowledge, it has been confirmed that the mortality rate of coronary artery disease is higher in men than in women.

Nationwide burden of sudden cardiac death: A study of 54,028 deaths in Denmark.

A large proportion of all deaths are sudden cardiac deaths (SCDs). Reliable estimates of nationwide incidence of SCD, however, are missing. The goals of this study were to estimate SCD burden across all age groups in Denmark and to compare it with the estimates of other common causes of death. All deaths in Denmark (population of 5.5 million) in 2010 were manually reviewed case by case. Autopsy reports, death certificates, and information from nationwide health registries were systematically examined to identify all SCD cases in 2010. According to the level of detail of the available information, all deaths were categorized as either non-SCD, definite SCD, probable SCD, or possible SCD. There were 54,028 deaths in Denmark in 2010, of which 6867 (13%) were categorized as SCD (591 (9%) definite SCD, 1568 (23%) probable SCD, and 4708 (68%) possible SCD). The incidence rate of definite SCD was 11 (95% confidence interval 10-12) per 100,000 person-years. Including definite, probable, and possible SCD cases, the highest possible overall SCD incidence rate was 124 (95% confidence interval 121-127) per 100,000 person-years. Estimated SCD burden was similar to or greater than the estimates of all other common causes of death. Of all SCD cases, 49% were not diagnosed with cardiovascular disease before death. SCD accounted for up to 13% of all deaths. Almost half of all SCD cases occurred in persons without a history of cardiovascular disease. Consequently, the optimization of risk stratification and prevention of SCD in the general population should be given high priority.

Pathogenesis of COVID-19; Acute Auto-inflammatory Disease (Endotheliopathica & Leukocytoclastica COVIDicus).

The pathogenesis of the COVID19 pandemic, that has killed one million nine hundred people and infected more the 90 million until end of 2020, has been studied by many researchers. Here, we try to explain its biological behavior based on our recent autopsy information and review of literature. In this study, patients with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) result were considered eligible for enrollment. Histopathological examinations were done on 13 people who were hospitalized in Afzalipour hospital, Kerman, Iran. Clinical and laboratory data were reviewed. Tissue examination was done by light microscopy, immunohistochemistry and electron microscopy. The most frequent co-morbidity in the patients was cardiovascular disease. The common initial symptoms of COVID-19 infection were dyspnea and cough. In all cases, the number of white blood cells was higher than the normal range. Common histopathological findings were variable degrees of vasculitis as degenerative to necrotic changes of endothelium and trafficking of inflammatory cells in the vessel wall with fibrinoid necrosis. Tissue damage included interstitial acute inflammatory cells reaction with degenerative to necrotic changes of the parenchymal cells. CD34 and Factor VIII immunohistochemistry staining showed endothelial cell degeneration to necrosis at the vessel wall and infiltration by inflammatory cells. Electron microscopic features confirmed the degenerative damages in the endothelial cells. Our histopathological studies suggest that the main focus of the viral damage is the endothelial cells (endotheliopathica) in involved organs. Also, our findings suggest that degeneration of leukocytes occurs at the site of inflammation and release of cytokines (leukocytoclastica) resulting in a cytokine storm.

Case-control analysis of prehospital death and prolonged field care survival during recent US military combat operations.

Quantification of medical interventions administered during prolonged field care (PFC) is necessary to inform training and planning. Retrospective cohort study of Department of Defense Trauma Registry casualties with maximum Abbreviated Injury Scale (MAIS) score of 2 or greater and prehospital records during combat operations 2007 to 2015; US military nonsurvivors were linked to Armed Forces Medical Examiner System data. Medical interventions administered to survivors of 4 hours to 72 hours of PFC and nonsurvivors who died prehospital were compared by frequency-matching on mechanism (explosive, firearm, other), injury type (penetrating, blunt) and injured body regions with MAIS score of 3 or greater. Covariates for adjustment included age, sex, military Service, shock, Glasgow Coma Scale, transport team, MAIS and Injury Severity Score (ISS). Sensitivity analysis focused on US military subgroup with AIS/ISS assigned to nonsurvivors after autopsy. The total inception cohort included 16,202 casualties (5,269 US military, 10,809 non-US military), 64% Afghanistan, 36% Iraq. Of US military, 734 deaths occurred within 30 days, nearly 90% occurred within 4 hours of injury. There were 3,222 casualties (1,111 US military, 2,111 non-US military) documented for prehospital care and died prehospital (691) or survived 4 hours to 72 hours of PFC (2,531). Twenty-five percent (815/3,222) received advanced airway, 18% (583) ventilatory support, 9% (281) tourniquet. Twenty-three percent (725) received blood transfusions within 24 hours. Of the matched cohort (1,233 survivors, 490 nonsurvivors), differences were observed in care (survivors received more warming, intravenous fluids, sedation, mechanical ventilation, narcotics, antibiotics; nonsurvivors received more intubations, tourniquets, intraosseous fluids, cardiopulmonary resuscitation). Sensitivity analysis focused on US military (732 survivors, 379 nonsurvivors) showed no significant differences in prehospital interventions. Without autopsy information, the ISS of nonsurvivors significantly underestimated injury severity. Tourniquets, blood transfusion, airway, and ventilatory support are frequently required interventions for the seriously injured. Prolonged field care should direct resources, technology, and training to field technology for sustained resuscitation, airway, and breathing support in the austere environment. Prognostic, Level III.

Post-mortem distribution of mephedrone and its metabolites in body fluids and organ tissues of an intoxication case

New psychoactive substances (NPS) are substances that continue to appear on the drug market to bypass controlled substance legislation. Mephedrone or 4-methylmethcathinone is becoming the most popular new psychoactive substance among youth as a recreational drug. The present study describes the optimization and validation of a sensitive method that combined clean up procedure and LC–MS/MS technique designed to simultaneously determine the presence of Mephedrone and its two metabolites (normephedrone as active metabolite and dyhidromephedrone) in post-mortem specimens (body fluids and organ tissues). To date, this is the first determination of Mephedrone metabolites in post-mortem specimens. The validated method was applied to a fatal Mephedrone intoxication case. The distribution of the three analytes in different post-mortem matrices was presented. The toxicological results of the studied case are discussed, along with autopsy, histopathological evidence and crime-scene information. The toxicological results presented in the study provide new data relative to mephedrone and the distribution of its metabolites in post-mortem specimens. In our opinion, the metabolite concentration database must be developed because the metabolites may be linked to toxicity. The pattern of parent drug and its metabolites can be helpful in the interpretation of fatal cases involving mephedrone, which will contribute to the currently limited knowledge about mephedrone and metabolites concentrations.

Drugs, pesticides and metabolites in forensic post-mortem blood samples.

Forensic post-mortem toxicological data provide valuable information for the elucidation of cause of death. However, this is still not routine practice in Brazilian laboratories. This study investigated the presence of illicit and prescription drugs, pesticides and metabolites in 111 post-mortem blood samples from cases investigated by the Forensic Medical Institute of the Federal District, Brazil. Quantitative analysis was performed for 14 analytes using a validated programmed temperature vaporisation-large volume injection-gas chromatography-mass spectrometry method, which was also used as screening (qualitative analysis) for an additional 19 substances of forensic interest. At least one analyte was found in 61.2% of the samples, of which 34 were related to homicide, 15 to accidental death and 10 to suicide cases. The victims were 14-72 years old. The benzodiazepines diazepam, midazolam and 7-aminoflunitrazepan were detected in 46% of the positive samples (0.02-1.12 µg/mL; midazolam only qualitative). Cocaine was found in 34% (0.02-4.07 µg/mL), associated with substances commonly used as cocaine adulterants (e.g. caffeine, lidocaine and phenacetin). Three suicide cases involved the illegal rodenticide chumbinho, residues of which were found in the gastric content, and blood samples showed the presence of terbufos (0.03 and 0.04 µg/mL) and carbofuran (27.3 µg/mL). These results are discussed, along with autopsy and crime-scene information.

Predictors of mortality in treatment experienced HIV-infected patients in northern Tanzania.

While factors that drive early mortality among people living with HIV (PLWH) initiating antiretroviral therapy (ART) in sub-Saharan Africa (SSA) have been described, less is known about the predictors of long-term mortality for those with ART experience. PLWH and on ART attending two HIV treatment clinics in Moshi, Tanzania were enrolled from 2008 through 2009 and followed for 3.5 years. Demographic, psychosocial, and clinical information were collected at enrollment. Plasma HIV RNA measurements were collected annually. Cause of death was adjudicated by two independent reviewers based on verbal autopsy information and medical records. Bivariable and multivariable analyses were conducted using Cox proportional hazard models to identify predictors of mortality. The analysis included 403 participants. The median (IQR) age in years was 42 (36-48) and 277 (68.7%) participants were female. The proportion of participants virologically suppressed during the 4 collection time points was 88.5%, 94.7%, 91.5%, and 94.5%. During follow-up, 24 participants died; the overall mortality rate was 1.8 deaths per 100 person-years. Of the deaths, 14 (58.3%) were suspected to be HIV/AIDS related. Predictors of mortality (adjusted hazard ratio, 95% confidence interval) were male sex (2.63, 1.01-6.83), secondary or higher education (7.70, 3.02-19.60), receiving care at the regional referral hospital in comparison to the larger zonal referral hospital (6.33, 1.93-20.76), and moderate to severe depression symptoms (6.35, 1.69-23.87). As ART coverage continues to expand in SSA, HIV programs should recognize the need for interventions to promote HIV care engagement for men and the integration of mental health screening and treatment with HIV care. Facility-level barriers may contribute to challenges faced by PLWH as they progress through the HIV care continuum, and further understanding of these barriers is needed. The association of higher educational attainment with mortality merits further investigation.

Differentiating COVID-19 Pneumonia From Acute Respiratory Distress Syndrome and High Altitude Pulmonary Edema: Therapeutic Implications.

Differentiating COVID-19 Pneumonia From Acute Respiratory Distress Syndrome and High Altitude Pulmonary Edema: Therapeutic Implications.