[Information on Death Certificates: Comparison Between Inpatient and Outpatient Sectors]. / Angaben auf Todesbescheinigungen ­ Vergleich des hospitalen und ambulanten Bereichs.

The death of a person and the circumstances of death are documented on the death certificate in Germany. The path of the corpse to burial as well as the quality of the cause of death statistics are significantly influenced by the information in the official death certificate. The quality of the information in the death certificates has been repeatedly criticized. The aim of the present study was to identify typical sources of error in death certificates and to obtain information on whether qualitative differences exist between death certificates completed in the outpatient and inpatient sectors. A retrospective evaluation was performed of 218 death certificates of deaths examined by the Institute of Legal Medicine as part of a second postmortem examination prior to cremation. Of these, 118 death certificates were issued in the hospital and 100 death certificates were issued on an outpatient basis by the family physician or a physician on duty in the outpatient sector. All but one of the death certificates issued on an outpatient basis were legible. The information on the underlying disease was plausible. More than one-third of the epicrises had no significant findings or were not completed at all. The entry on the immediate causes of death in the designated field on the death certificate (Ia in the causal chain) were inadequate in one third of the cases. The error rate in the entries was higher in outpatient than in inpatient deaths. In the future, therefore, it will be necessary to prepare for the special situation of a post-mortem examination by means of further and advanced training events and to convey the importance of the diagnoses determined in the process, in order to eliminate these avoidable sources of error.

Fatal outcome of SARS-CoV-2 infection (B1.1.7) in a 4-year-old child.

This case report highlights details of a case of critical acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) with B1.1.7 variant in a 4-year-old girl who died due to pneumonia and pulmonary hemorrhage. The girl was referred to our University ECMO Center from another University hospital for veno-arterial extracorporeal membrane oxygenation (VA-ECMO). In the clinical course, superinfection with Pseudomonas aeruginosa was detected. Virological evidence of herpes simplex sepsis was also obtained in blood samples on her day of death. Transcription polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection in lung tissue. Postmortem computed tomography showed pulmonary hemorrhage with inhomogeneous density values in both lungs. Lung tissue showed no ventilated areas. Autopsy revealed a massively congested lung with evidence of acute respiratory distress syndrome (ARDS) and pneumonia with multiple abscesses. Histopathology showed a mixture of diffuse alveolar injury with hyaline membranes, massive hemorrhage, and bronchopneumonia with multiple granulocytic abscesses. Cardiac examination revealed pericarditis. Suspicion of myocarditis or myocardial infarction could not be confirmed microscopically. To our knowledge, this is the first autopsy-based case report of the death of a previously healthy child due to the new variant B 1.1.7 in Germany.

Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study.

BACKGROUND: The new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. OBJECTIVE: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. DESIGN: Prospective cohort study. SETTING: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19. PATIENTS: The first 12 consecutive COVID-19-positive deaths. MEASUREMENTS: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. RESULTS: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. LIMITATION: Limited sample size. CONCLUSION: The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it. PRIMARY FUNDING SOURCE: University Medical Center Hamburg-Eppendorf.

The handling of SARS-CoV-2 associated deaths - infectivity of the body.

The body of a deceased with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is considered infectious. In this study, we present the results of infectivity testing of the body and testing of mortuary staff for SARS-CoV-2. We performed real-time quantitative polymerase chain reaction (RT-qPCR) for SARS-CoV-2 on 33 decedents with ante mortem confirmed SARS-CoV-2 infection. Swabs of the body surface from five different body regions and from the body bag or coffin were examined. A subset of the swabs was brought into cell culture. In addition, screening of 25 Institute of Legal Medicine (ILM) personnel for ongoing or past SARS-CoV-2 infection was performed at two different time points during the pandemic. Swabs from all locations of the body surface and the body environment were negative in cases of negative post mortem nasopharyngeal testing (n=9). When the post mortem nasopharyngeal swab tested positive (n=24), between 0 and 5 of the body surface swabs were also positive, primarily the perioral region. In six of the cases, the body bag also yielded a positive result. The longest postmortem interval with positive SARS-CoV-2 RT-qPCR at the body surface was nine days. In no case viable SARS-CoV-2 was found on the skin of the bodies or the body bags. One employee (autopsy technician) had possible occupational infection with SARS-CoV-2; all other employees were tested negative for SARS-CoV-2 RNA or antibody twice. Our data indicate that with adequate management of general safety precautions, transmission of SARS-CoV-2 through autopsies and handling of bodies is unlikely.

Cerebellar heterotopia of infancy in sudden infant death syndrome: an observational neuropathological study of four cases.

Sudden infant death syndrome (SIDS) is the sudden unexpected death of an infant < 1 year of age that remains unexplained after comprehensive workup including complete autopsy and investigation of the circumstances of death. The triple risk hypothesis posits that SIDS results as a combination of both intrinsic and extrinsic factors on the background of a predisposing vulnerability. Neuropathological examination in the past has focussed mainly on the brainstem as the major player in respiratory control, where subtle findings have been linked to the chain of events leading to death in SIDS. The cerebellum has received less attention, probably due to an assumed negligible role in central cardiorespiratory control. We report four cases of SIDS in which neuropathological investigation revealed cerebellar heterotopia of infancy, a distinct malformation of the cerebellum, and discuss the potential impact of this condition on the aetiology and pathogenesis of SIDS.

Cases of asphyxia in children and adolescents: a retrospective analysis of fatal accidents, suicides, and homicides from 1998 to 2017 in Hamburg, Germany.

PURPOSE: Injury-related asphyxia is one of the most common causes of death in children in Germany. However, only a few systematic studies have analyzed the causes and circumstances of asphyxia in children and adolescents. METHODS: All cases of asphyxia in children and adolescents (0-21 years of age) among the Hamburg Legal Medical Department's autopsy cases from 1998 to 2017 were retrospectively analyzed with special focus on how often external findings were completely absent. RESULTS: Among 249 cases of fatal asphyxia, 68% were accidents, 14% were suicides, and 13% were homicides. Most of the cases involved boys. Adolescents and young adults aged 15-21 years represented the main age group. Drowning was the leading mechanism of asphyxia. Younger age was associated with less frequent detection of external signs of asphyxia in the postmortem external examination. Petechial hemorrhages were the most common visible external indication of asphyxia. No external findings indicative of asphyxia were present in 14% of the cases. CONCLUSION: Asphyxia in children and adolescents often involves accidents. However, postmortem external examination alone is insufficient to identify asphyxia and the manner of death.

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

The affiliation of the author Martin Aepfelbacher was incorrectly assigned in the manuscript. Martin Aepfelbacher is affiliated to the Institute of Microbiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, instead.

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

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

Pregnancy-related and maternal deaths in Hamburg, Germany: an autopsy study from 1984 - 2018.

Maternal deaths are rare events in industrial nations due to high quality medical services. These are often unexpected deaths occurring during pregnancy and labor, thus often requiring forensic autopsies. Our analysis will provide an overview of the expected range of causes of death. A retrospective analysis was carried out on all autopsies performed at the Department of Legal Medicine in Hamburg, Germany, over the last 34 years. Autopsies were carried out on 57 cases of maternal death over the 34- year period, i.e. 1 or 2 cases per year. The average age of women was 30 years. Approximately two thirds of deaths occurred during pregnancy. Cardiovascular events accounted for the leading causes of death from natural causes, suicides were the leading causes of non-natural death. Maternal deaths remained consistently rare over the examination period. There was a wide range of causes of death involving natural and non-natural causes.

The use of HIV post-exposure prophylaxis in forensic medicine following incidents of sexual violence in Hamburg, Germany: a retrospective study.

In Hamburg, Germany, the initiation of HIV post-exposure prophylaxis (HIV PEP) in cases of sexual violence is often carried out by forensic medical specialists (FMS) using the city's unique Hamburg Model. FMS-provided three-day HIV PEP starter packs include a combination of raltegravir and emtricitabine/tenofovir. This study aimed to investigate the practice of offering HIV PEP, reasons for discontinuing treatment, patient compliance, and whether or not potential perpetrators were tested for HIV. We conducted a retrospective study of forensic clinical examinations carried out by the Hamburg Department of Legal Medicine following incidents of sexual violence from 2009 to 2016. One thousand two hundred eighteen incidents of sexual violence were reviewed. In 18% of these cases, HIV PEP was initially prescribed by the FMS. HIV PEP indication depended on the examination occurring within 24 h after the incident, no/unknown condom use, the occurrence of ejaculation, the presence of any injury, and the perpetrator being from population at high risk for HIV. Half of the HIV PEP recipients returned for a reevaluation of the HIV PEP indication by an infectious disease specialist, and just 16% completed the full month of treatment. Only 131 potential perpetrators were tested for HIV, with one found to be HIV positive. No HIV seroconversion was registered among the study sample. Provision of HIV PEP by an FMS after sexual assault ensures appropriate and prompt care for victims. However, patient compliance and completion rates are low. HIV testing of perpetrators must be carried out much more rigorously.

Sudden death from acute epiglottitis in a toddler.

The bacterium Haemophilus influenzae type b (Hib) can cause severe and life-threatening infections such as epiglottitis and meningitis. The course of the disease can be very rapid, resulting in sudden death. The incidence of Hib-induced epiglottitis in children has declined since the introduction of vaccinations in countries where such vaccinations are routinely administered. We herein present a case involving a 2.5-year-old boy who died suddenly at home. He had developed acute-onset throat and abdominal pain and a high fever. Despite an emergency cricothyrotomy due to a complicated intubation because of a massively swollen epiglottis, the efforts to resuscitate the child were unsuccessful. He was a previously healthy toddler, but he had not yet been vaccinated. Microbiologic analysis revealed the pathogenic bacterium Hib. The main autopsy finding was acute epiglottitis with swelling and cherry-red coloring of the epiglottis. Postmortem cultures of the cerebrospinal fluid and heart blood also revealed Hib as the pathogenic agent. Acute pneumonia was also diagnosed microscopically. The present report describes a rare case of Hib-induced acute epiglottitis and presents the key findings of forensic investigations in this type of disease.

Autopsy in undergraduate medical education--what do students really learn?

Forensic medicine can provide access to autopsies for students in undergraduate medical education. Previous qualitative studies reported that attending autopsies promotes learning and is helpful in organising information in the context of self-directed learning, covering cognitive, emotional and societal issues. In the present study, learning outcome regarding specific pathophysiological learning objectives of students who attended an autopsy elective (intervention group, n = 32) was estimated in comparison to peer students who signed up for the course but were not selected (control group A, n = 47) and students who had not signed up (control group B, n = 186). Learning outcome (expressed as a percent knowledge gain) was measured by means of comparative self-assessments (CSA). Furthermore, group interviews were conducted to evaluate the attending students' perceptions and experiences of the course. In the intervention group, the percent knowledge gain for learning objectives reflecting pathophysiological mechanisms was about twice as high than that in the control groups, while all three groups showed comparable knowledge gain for learning objectives covered by mandatory courses that were held during the study period. Results of mandatory post-course assessments showed no statistically significant differences between the intervention and control groups. Therefore, the knowledge gain regarding learning objectives not covered by mandatory courses that was observed in the intervention group reflected the additional benefit of attending the autopsy course. Group interviews with the participants revealed gain of integrated knowledge and understanding of pathophysiological relations as important issues, while negative effects were reported infrequently. Our findings suggest that attendance of a series of autopsies fosters learning and understanding of important issues in medical education and should therefore be part of undergraduate medical curricula wherever possible.

Sudden unexpected death in infancy (SUDI) in the early neonatal period: the role of bed-sharing.

The incidence of sudden infant death syndrome (SIDS) has declined substantially, but the proportion of sudden unexpected death in infancy (SUDI) in neonates, <7 days old, has increased among all SUDI cases in the first year of life. The aim of this study was to analyze circumstances and common features of SUDI cases during the first 7 days of life. Data have been gathered retrospectively from Departments of Legal Medicine in Germany and Austria by using a standardized questionnaire. 19 out of 46 children died within 24 h after birth. A possible reason for this could be a lack of awareness of the needs of the newborn on the part of an exhausted mother. Fifty-two percent of the incidents occurred while the mother and her newborn were still hospitalized in a birth clinic. Forty-eight percent of the infants had been sleeping in the parents' bed with mother and/or father. In 11 % of the cases, there was a sofa-sharing situation. Bed-sharing seems to increase the risk for SIDS in the newborn period as well as the risk for accidental suffocation/asphyxia of the baby. Therefore, mothers should not be instructed to bed-share. Particularly during the first 24 h after birth, it may be advisable to check mothers and infants regularly.

Glucocorticoids induce a maladaptive epithelial stress response to aggravate acute kidney injury.

Acute kidney injury (AKI) is a frequent and challenging clinical condition associated with high morbidity and mortality and represents a common complication in critically ill patients with COVID-19. In AKI, renal tubular epithelial cells (TECs) are a primary site of damage, and recovery from AKI depends on TEC plasticity. However, the molecular mechanisms underlying adaptation and maladaptation of TECs in AKI remain largely unclear. Here, our study of an autopsy cohort of patients with COVID-19 provided evidence that injury of TECs by myoglobin, released as a consequence of rhabdomyolysis, is a major pathophysiological mechanism for AKI in severe COVID-19. Analyses of human kidney biopsies, mouse models of myoglobinuric and gentamicin-induced AKI, and mouse kidney tubuloids showed that TEC injury resulted in activation of the glucocorticoid receptor by endogenous glucocorticoids, which aggravated tubular damage. The detrimental effect of endogenous glucocorticoids on injured TECs was exacerbated by the administration of a widely clinically used synthetic glucocorticoid, dexamethasone, as indicated by experiments in mouse models of myoglobinuric- and folic acid-induced AKI, human and mouse kidney tubuloids, and human kidney slice cultures. Mechanistically, studies in mouse models of AKI, mouse tubuloids, and human kidney slice cultures demonstrated that glucocorticoid receptor signaling in injured TECs orchestrated a maladaptive transcriptional program to hinder DNA repair, amplify injury-induced DNA double-strand break formation, and dampen mTOR activity and mitochondrial bioenergetics. This study identifies glucocorticoid receptor activation as a mechanism of epithelial maladaptation, which is functionally important for AKI.

[One and a half years of e-scooters in Hamburg]. / Eineinhalb Jahre E-Scooter ­ Zwischenbilanz in Hamburg: Teil 1: alkoholbedingte Auffälligkeiten im Straßenverkehr.

Background: Since electric scooters were introduced as an urban means of transportation in Hamburg in June 2019, a high number of violations of the current laws regarding alcohol consumption by e­scooter riders have been recorded. Objective: The aim of this study is to obtain an overview of traffic offences committed by e­scooter drivers under the influence of alcohol, to classify their relevance in relation to other road user groups, and to draw a first interim balance with respect to their frequency after 1.5 years. Material and methods: The data of all e­scooter drivers (n = 342) examined concerning their blood alcohol values analyzed at the Institute of Legal Medicine of the University Medical Centre Hamburg-Eppendorf between 15.06.2019 and 31.12.2020 were retrospectively evaluated with respect to their demographic information and the medical examination results. These were brought into context with the total number of offences against the road traffic regulations with subsequent blood alcohol measurement. Results: 9.6% of the total number of offences against the road traffic regulations in connection with subsequent determination of the blood alcohol concentration were committed by e­scooter drivers. 87.7% of those examined were male. The blood alcohol concentration was above the limit of 1.10 ‰ for absolute driving incapacity when using a passenger car in 76.9% of those examined. An accumulation of cases was particularly noticeable at night and at weekends.Due to imprecise records, a certain number of unreported e­scooter incidents can be assumed among the unspecified motor vehicles. Conclusion: As e­scooter drivers make up a considerable proportion of drunken road users and the accidents mostly occur at night and at weekends, increased education and, if necessary, a driving ban at these times would seem to make sense.

Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage.

Recent studies of severe acute inflammatory lung disease including COVID-19 identify macrophages to drive pulmonary hyperinflammation and long-term damage such as fibrosis. Here, we report on the development of a first-in-class, carbohydrate-coupled inhibitor of microRNA-21 (RCS-21), as a therapeutic means against pulmonary hyperinflammation and fibrosis. MicroRNA-21 is among the strongest upregulated microRNAs in human COVID-19 and in mice with acute inflammatory lung damage, and it is the strongest expressed microRNA in pulmonary macrophages. Chemical linkage of a microRNA-21 inhibitor to trimannose achieves rapid and specific delivery to macrophages upon inhalation in mice. RCS-21 reverses pathological activation of macrophages and prevents pulmonary dysfunction and fibrosis after acute lung damage in mice. In human lung tissue infected with SARS-CoV-2 ex vivo, RCS-21 effectively prevents the exaggerated inflammatory response. Our data imply trimannose-coupling for effective and selective delivery of inhaled oligonucleotides to pulmonary macrophages and report on a first mannose-coupled candidate therapeutic for COVID-19.

Young COVID-19 Patients Show a Higher Degree of Microglial Activation When Compared to Controls.

The severe acute respiratory syndrome-corona virus type 2 (SARS-CoV-2) is the cause of human coronavirus disease 2019 (COVID-19). Since its identification in late 2019 SARS-CoV-2 has spread rapidly around the world creating a global pandemic. Although considered mainly a respiratory disease, COVID-19 also encompasses a variety of neuropsychiatric symptoms. How infection with SARS-CoV-2 leads to brain damage has remained largely elusive so far. In particular, it has remained unclear, whether signs of immune cell and / or innate immune and reactive astrogliosis are due to direct effects of the virus or may be an expression of a non-specific reaction of the brain to a severe life-threatening disease with a considerable proportion of patients requiring intensive care and invasive ventilation activation. Therefore, we designed a case-control-study of ten patients who died of COVID-19 and ten age-matched non-COVID-19-controls to quantitatively assess microglial and astroglial response. To minimize possible effects of severe systemic inflammation and / or invasive therapeutic measures we included only patients without any clinical or pathomorphological indication of sepsis and who had not been subjected to invasive intensive care treatment. Our results show a significantly higher degree of microglia activation in younger COVID-19 patients, while the difference was less and not significant for older COVID-19 patients. The difference in the degree of reactive gliosis increased with age but was not influenced by COVID-19. These preliminary data warrants further investigation of larger patient cohorts using additional immunohistochemical markers for different microglial phenotypes.

Contamination of personal protective equipment during COVID-19 autopsies.

Confronted with an emerging infectious disease at the beginning of the COVID-19 pandemic, the medical community faced concerns regarding the safety of autopsies on those who died of the disease. This attitude has changed, and autopsies are now recognized as indispensable tools for understanding COVID-19, but the true risk of infection to autopsy staff is nevertheless still debated. To clarify the rate of SARS-CoV-2 contamination in personal protective equipment (PPE), swabs were taken at nine points in the PPE of one physician and one assistant after each of 11 full autopsies performed at four centers. Swabs were also obtained from three minimally invasive autopsies (MIAs) conducted at a fifth center. Lung/bronchus swabs of the deceased served as positive controls, and SARS-CoV-2 RNA was detected by real-time RT-PCR. In 9 of 11 full autopsies, PPE samples tested RNA positive through PCR, accounting for 41 of the 198 PPE samples taken (21%). The main contaminated items of the PPE were gloves (64% positive), aprons (50% positive), and the tops of shoes (36% positive) while the fronts of safety goggles, for example, were positive in only 4.5% of the samples, and all the face masks were negative. In MIAs, viral RNA was observed in one sample from a glove but not in other swabs. Infectious virus isolation in cell culture was performed on RNA-positive swabs from the full autopsies. Of all the RNA-positive PPE samples, 21% of the glove samples, taken in 3 of 11 full autopsies, tested positive for infectious virus. In conclusion, PPE was contaminated with viral RNA in 82% of autopsies. In 27% of autopsies, PPE was found to be contaminated even with infectious virus, representing a potential risk of infection to autopsy staff. Adequate PPE and hygiene measures, including appropriate waste deposition, are therefore essential to ensure a safe work environment.