Multifactorial White Matter Damage in the Acute Phase and Pre-Existing Conditions May Drive Cognitive Dysfunction after SARS-CoV-2 Infection: Neuropathology-Based Evidence.

BACKGROUND: There is an urgent need to better understand the mechanisms underlying acute and long-term neurological symptoms after COVID-19. Neuropathological studies can contribute to a better understanding of some of these mechanisms. METHODS: We conducted a detailed postmortem neuropathological analysis of 32 patients who died due to COVID-19 during 2020 and 2021 in Austria. RESULTS: All cases showed diffuse white matter damage with a diffuse microglial activation of a variable severity, including one case of hemorrhagic leukoencephalopathy. Some cases revealed mild inflammatory changes, including olfactory neuritis (25%), nodular brainstem encephalitis (31%), and cranial nerve neuritis (6%), which were similar to those observed in non-COVID-19 severely ill patients. One previously immunosuppressed patient developed acute herpes simplex encephalitis. Acute vascular pathologies (acute infarcts 22%, vascular thrombosis 12%, diffuse hypoxic-ischemic brain damage 40%) and pre-existing small vessel diseases (34%) were frequent findings. Moreover, silent neurodegenerative pathologies in elderly persons were common (AD neuropathologic changes 32%, age-related neuronal and glial tau pathologies 22%, Lewy bodies 9%, argyrophilic grain disease 12.5%, TDP43 pathology 6%). CONCLUSIONS: Our results support some previous neuropathological findings of apparently multifactorial and most likely indirect brain damage in the context of SARS-CoV-2 infection rather than virus-specific damage, and they are in line with the recent experimental data on SARS-CoV-2-related diffuse white matter damage, microglial activation, and cytokine release.

Neuropathological Variability within a Spectrum of NMDAR-Encephalitis.

OBJECTIVE: To describe the neuropathological features of N-methyl-D-aspartate receptor (NMDAR)-encephalitis in an archival autopsy cohort. METHODS: We examined four autopsies from patients with NMDAR-encephalitis; two patients were untreated, three had comorbidities: small cell lung cancer, brain post-transplant lymphoproliferative disease (PTLD), and overlapping demyelination. RESULTS: The two untreated patients had inflammatory infiltrates predominantly composed of perivascular and parenchymal CD3+ /CD8- T cells and CD79a+ B cells/plasma cells in basal ganglia, amygdala, and hippocampus with surrounding white matter. The hippocampi showed a significant decrease of NMDAR-immunoreactivity that correlated with disease severity. The patient with NMDAR-encephalitis and immunosuppression for kidney transplantation developed a brain monomorphic PTLD. Inflammatory changes were compatible with NMDAR-encephalitis. Additionally, plasma cells accumulated in the vicinity of the necrotic tumor along with macrophages and activated microglia that strongly expressed pro-inflammatory activation markers HLA-DR, CD68, and IL18. The fourth patient developed demyelinating lesions in the setting of a relapse 4 years after NMDAR-encephalitis. These lesions exhibited the hallmarks of classic multiple sclerosis with radially expanding lesions and remyelinated shadow plaques without complement or immunoglobulin deposition, compatible with a pattern I demyelination. INTERPRETATION: The topographic distribution of inflammation in patients with NMDAR-encephalitis reflects the clinical symptoms of movement disorders, abnormal behavior, and memory dysfunction with inflammation dominantly observed in basal ganglia, amygdala, and hippocampus, and loss of NMDAR-immunoreactivity correlates with disease severity. Co-occurring pathologies influence the spatial distribution, composition, and intensity of inflammation, which may modify patients' clinical presentation and outcome. ANN NEUROL 2021;90:725-737.

Stable isotope and trace element studies on gladiators and contemporary Romans from Ephesus (Turkey, 2nd and 3rd Ct. AD)--mplications for differences in diet.

The gladiator cemetery discovered in Ephesus (Turkey) in 1993 dates to the 2nd and 3rd century AD. The aim of this study is to reconstruct diverse diet, social stratification, and migration of the inhabitants of Roman Ephesus and the distinct group of gladiators. Stable carbon, nitrogen, and sulphur isotope analysis were applied, and inorganic bone elements (strontium, calcium) were determined. In total, 53 individuals, including 22 gladiators, were analysed. All individuals consumed C3 plants like wheat and barley as staple food. A few individuals show indication of consumption of C4 plants. The δ13C values of one female from the gladiator cemetery and one gladiator differ from all other individuals. Their δ34S values indicate that they probably migrated from another geographical region or consumed different foods. The δ15N values are relatively low in comparison to other sites from Roman times. A probable cause for the depletion of 15N in Ephesus could be the frequent consumption of legumes. The Sr/Ca-ratios of the gladiators were significantly higher than the values of the contemporary Roman inhabitants. Since the Sr/Ca-ratio reflects the main Ca-supplier in the diet, the elevated values of the gladiators might suggest a frequent use of a plant ash beverage, as mentioned in ancient texts.

Does the prior application of the field kit bullet hole testing kit 3 on a suspected bullet hole bias the analysis of atomic absorption spectrophotometry?

Forensic ballistics is the study of bullet trajectory and consists of determining gunshot residue (GSR) to identify bullet holes. Among several highly sensitive methods, atomic absorption spectrophotometry (AAS) is employed to analyze GSR in the laboratory. However, it is sometimes necessary to identify bullet holes immediately at a crime scene. The purpose of this examination was to determine whether the use of the field test Bullet Hole Testing Kit 3 (BTK3) on a suspected bullet hole would influence the outcome of AAS-analysis: Three commonly encountered firearms (Glock17, Tokarev, and Colt) were fired at skin, wood, and cloth. AAS-analysis was performed with and without previous BTK3 application. The results clearly indicate that there is no significant interaction on the grounds of BTK3 use (BTK3 vs. no-BTK3 [kit_nokit] [Pb: p = 0.1309; Sb: p = 0.9111], material*kit_nokit [Pb: p = 0.5960; Sb: p = 0.9930], distance*kit_nokit [Pb: p = 0.4014; Sb: p = 0.9184], and firearm type*kit_nokit [Pb: p = 0.9662; Sb: p = 0.9885]); hence, applying this field kit does not falsify later AAS outcomes.

Citrate content of bone for time since death estimation: results from burials with different physical characteristics and known PMI.

A recently introduced method to determine the postmortem interval (PMI) based on quantification of the citrate content in bone was applied on the temporal bones and femora of 20 individuals buried in wooden coffins (WO) and body bags (BB), respectively. Concerning known vs. calculated PMI, a significant difference between the temporal and the femur bone samples of the same individuals was observed in the BB group (p = 0.012). In contrast, differences were insignificant for the WO group (p = 0.400). Moreover, similar levels of underestimation of PMIs resulted from the analysis of the femora for both burial groups (p = 0.247). Also, there was consistently less citrate preserved in the flat temporal bones as compared to the femora, indicating that the cortical layer of the long bones should be preferentially employed for citrate-based PMI estimations. The results call for additional research on subsurface-buried and surface-deposited remains to enhance the accuracy of the published PMI equation.

Investigations on human and animal remains from a medieval shaft well in Ayasuluk/Ephesos (Turkey).

In course of the archaeological survey of Ayasuluk/Ephesos region (Turkey), a shaft well situated at the area of an extensive medieval bathing complex was excavated. In the stratum corresponding to the reign Mehmed II the well-preserved skeletons of two humans, an equine and a canine were recovered. Anthropological analysis of the human skeletons indentified two males aged 22 (± 3) and 36 (± 5) years. The skeleton of the younger individual showed signs of various antemortal conditions, including a well-healed fraction of right arc of the fifth lumbar vertebra, and a marked asymmetry of the shoulder joints. The older individual exhibited significant peri/postmortem injuries at the elbows, with evident signs of peeling and external burning. Also, the few elements of the cranium recovered showed also indications of burning. Archaeozoological characterization of the complete skeletons of the equine and canine established evidence of well cared-for animals of high value. The time of disposal of this group coincides with uprising of the formerly ruling Aydnoullar clan against the Ottomans in power. The human individuals recovered from the well may have been members of Aydnoullar tribe or men in service of the latter, suffering severe torture and/or mutilation for siding with the rebels after defeat.

Micromorphological changes in cardiac tissue of drug-related deaths with emphasis on chronic illicit opioid abuse.

AIMS: The main intention of this retrospective study was to investigate whether chronic illicit drug abuse, especially the intravenous use of opioids (heroin), could potentially trigger the development of myocardial fibrosis in drug addicts. DESIGN: A retrospective case-control study was performed using myocardial tissue samples from both drug-related deaths (DRD) with verifiable opioid abuse and non-drug-related deaths in the same age group. SETTING: Department of Forensic Medicine, Medical University of Vienna, Austria (1993-94). PARTICIPANTS: Myocardial specimens were retrieved from 76 deceased intravenous opioid users and compared to those of 23 deceased non-drug users. MEASUREMENTS: Drug quantification was carried out using the enzyme-multiplied immunoassay technique (EMIT), followed by [gas chromatography-mass spectrometry (GC-MS), MAT 112(®) ], and analysed using the Integrator 3390A by Hewlett Packard(®) and LABCOM.1 computer (MSS-G.G.). The amount of fibrous connective tissue (FCT) in the myocardium was determined by using the morphometric software LUCIA Net version 1.16.2(©) , Laboratory Imaging, with NIS Elements 3.0(®) . FINDINGS: Drug analysis revealed that 67.11% were polydrug users and the same proportion was classified as heroin addicts (6-monoacetylmorphine, 6-MAM)-32.89% were users of pure heroin. In 76.32% of DRD cases, codeine was detected. Only 2.63% consumed cocaine. The mean morphine concentrations were 389.03 ng/g in the cerebellum and 275.52 ng/g in the medulla oblongata, respectively. Morphometric analysis exhibited a strong correlation between DRD and myocardial fibrosis. The mean proportion of FCT content in the drug group was 7.6 ± 2.9% (females: 6.30 ± 2.19%; males: 7.91 ± 3.01%) in contrast to 5.2 ± 1.7% (females: 4.45 ± 1.23%; males: 5.50 ± 1.78%) in the control group, indicating a significant difference (P = 0.0012), and a significant difference in the amount of FCT between females and males (P = 0.0383). There was no significant interaction of age and FCT (P = 0.8472). CONCLUSIONS: There is a long-term risk of cardiac dysfunction following chronic illicit drug abuse with opioids as a principal component. Regular cardiological examination of patients receiving substitution treatment with morphine is strongly recommended.

Iatrogenic death: A review of cases from 1990-2000 investigated at the Department of Forensic Medicine, Vienna.

Medical malpractice is a global problem which can have considerable financial and legal consequences for the community as well as personal consequences for those involved. Austria does not record any statistical and epidemiological data concerning medical malpractice cases. Data from 7,211 autopsy cases from the Department of Forensic Medicine in Vienna covering the period from 1990 to 2000 were analyzed. Fifty-five autopsy reports that were filed as suspected medical malpractice were recorded and analyzed. Thirty cases were classified as surgical incidents, 19 cases as negligence, and 6 cases as medication incidents. Out of a total of 40 cases from available court files, 36 cases were dropped, there were 2 acquittals and only two resulted in convictions. The number of instances of medical malpractice leading to iatrogenic deaths in Austria seems to be very low in comparison to other countries. The possibility that many cases go unnoticed needs to be taken into consideration.

Does weight force application to the lower torso have an influence on inferior vena cava and cardiovascular parameters?

OBJECTIVE: The aim of this study was to determine whether weight force application to the lower torso can lead to impairment of inferior vena cava (IVC) and cardiovascular parameters. METHODS: Using ultrasound sonography and impedance cardiography, the effects of a weight force application of 5, 10, 15, and 25 kg to the lower torso, placed in prone position, on IVC diameter and maximal blood flow, mean artery pressure, stroke volume, heart rate, cardiac index, cardiac output, oxygen saturation (SpO(2)), and acceleration index were investigated in 6 healthy volunteers. RESULTS: The following parameters showed a statistically significant correlation with the amount of weight force applied: IVC diameter: r=-0.83, P < .001; IVC maximal blood flow: r=-0.76, P < .001; cardiac index: r=-0.33, P < .05; and cardiac output: r=-0.32, P < .05. CONCLUSION: Application of moderate weight force to the lower torso can lead to major changes in IVC parameters and minor changes in cardiovascular parameters.

Mortality in opioid-maintained patients after release from an addiction clinic.

AIM: To investigate the mortality rate in a cohort of 269 opioid-dependent patients and the outcome of survivors meeting DSM-IV criteria for opioid dependence. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients enrolled in synthetic opioid maintenance therapy during a time frame from 1998 to 1999 originally at the Addiction Clinic and then discharged to general practitioners. METHODS: Structured interviews (Europ-ASI), urinalysis at time of interview as well as autopsy findings from deceased patients. RESULTS: After six mailings, information from 147 (54.6%) patients was gained. 85 patients (31.6%) were interviewed. From these 76.5% (n = 65) were still enrolled in maintenance therapy, 18.8% (n = 16) were drug-free and 4.7% (n = 4) relapsed. From 29 fatalities, 37.9% died of intoxication with illicit substances, 34.5% related to AIDS and 27.6% of somatic complications. The Standardized Mortality Ratio (SMR) was 29.13 (95% CI = 19.27-44.04). A higher lifetime frequency of hospitalization, less working days and a lack of social relationships were factors associated with high mortality. CONCLUSIONS: The study confirms the high mortality rate in this patient group and supports the importance of maintenance therapy. Although great efforts were undertaken in locating patients, about 45% of the target group could not be located.

Is there a relationship between street heroin purity and drug-related emergencies and/or drug-related deaths? An analysis from Vienna, Austria.

This study examines the quality of street heroin seized in Vienna in 1999 and whether there was a relationship between the purity of street heroin and the number of heroin-related emergencies as well as the number of heroin-related deaths. Street heroin confiscated by the Viennese police, run-sheets of drug-related emergencies, and postmortem reports of drug-related deaths in Vienna in 1999 were analyzed. A total of 415 retail samples with a total weight of 128.02 g contained a median percentage of 6.5% diacetylmorphine (range: 0.0-47.0%). All the samples contained a diluent, mainly lactose, as well as adulterants, such as caffeine and/or paracetamol. During the study period, 75 heroin-related deaths and 387 heroin-related emergencies were registered in Vienna. Time-series analysis revealed no statistically significant relationship between the rate of heroin-related incidents and the diacetylmorphine concentration of street heroin samples confiscated in Vienna in 1999. The widely held belief that the number of heroin-related deaths could be explained simply through fluctuations in the purity of street heroin could not be substantiated, even though the results of this study do not rule out an association between the purity of heroin and heroin-related deaths/emergencies.

Discovery of decomposed and mummified corpses in the domestic setting--a marker of social isolation?

Mass media reports attribute the occurrence of decomposed or mummified corpses in a domestic setting mainly to an increasing social isolation of elderly people. Not much is known about the demographic and medical conditions under which individuals are found months or even years after death in their homes. For this study, autopsy reports of individuals found dead and mummified or decomposed between 1993 and 1997 with those from 1963 to 1967 were retrospectively analyzed. Between 1993 and 1997, a total number of 320 individuals were found decomposed at home compared to 412 such cases between 1963 and 1967. The proportion of individuals older than 64 years was significantly higher during the 1990s study period. Furthermore, the proportion of deaths attributable to natural causes was significantly lower during the 1990s, whereas the rate of suicides was nearly three times higher.