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SARS-CoV-2 vaccine ChAdOx1 nCoV-19 (AstraZeneca) causes a thromboembolic complication termed vaccine-induced immune thrombotic thrombocytopenia (VITT). Using biophysical techniques, mouse models, and analysis of VITT patient samples, we identified determinants of this vaccine-induced adverse reaction. Super-resolution microscopy visualized vaccine components forming antigenic complexes with platelet factor 4 (PF4) on platelet surfaces to which anti-PF4 antibodies obtained from VITT patients bound. PF4/vaccine complex formation was charge-driven and increased by addition of DNA. Proteomics identified substantial amounts of virus production-derived T-REx HEK293 proteins in the ethylenediaminetetraacetic acid (EDTA)-containing vaccine. Injected vaccine increased vascular leakage in mice, leading to systemic dissemination of vaccine components known to stimulate immune responses. Together, PF4/vaccine complex formation and the vaccine-stimulated proinflammatory milieu trigger a pronounced B-cell response that results in the formation of high-avidity anti-PF4 antibodies in VITT patients. The resulting high-titer anti-PF4 antibodies potently activated platelets in the presence of PF4 or DNA and polyphosphate polyanions. Anti-PF4 VITT patient antibodies also stimulated neutrophils to release neutrophil extracellular traps (NETs) in a platelet PF4-dependent manner. Biomarkers of procoagulant NETs were elevated in VITT patient serum, and NETs were visualized in abundance by immunohistochemistry in cerebral vein thrombi obtained from VITT patients. Together, vaccine-induced PF4/adenovirus aggregates and proinflammatory reactions stimulate pathologic anti-PF4 antibody production that drives thrombosis in VITT. The data support a 2-step mechanism underlying VITT that resembles the pathogenesis of (autoimmune) heparin-induced thrombocytopenia.

Zusammenfassung Hintergrund Sexualisierte Handlungen zwischen gleichaltrigen Kindern sind in der Regel Ausdruck eines normalen, altersgerechten Verhaltens. Doch auch zwischen Minderjährigen gibt es sexualisierte Gewalt, die über das altersentsprechende Interesse hinausgeht und in der medizinischen Literatur bislang wenig Beachtung fand. Methode Es wurde eine selektive Literaturrecherche in der Datenbank PubMed sowie mithilfe des Suchdienstes Google Scholar durchgeführt. Außerdem wurde eine retrospektive Analyse eigener Fälle durchgeführt. Ergebnisse Die erfassten Studien ergaben Prävalenzen von 6 bis 50,7 % für unerwünschte sexuelle Kontakte. SchülerIn an einer Highschool und weiblich zu sein oder einen Migrationshintergrund zu haben, wurde als Risikofaktor für sexuelle Übergriffe identifiziert. Mehr als die Hälfte (54 %) der Täterinnen und bis zu 16 % der Täter waren zuvor selber von Missbrauch und/oder Vernachlässigung betroffen. In der eigenen Erhebung gaben 37 % der Mädchen an, penovaginal penetriert worden zu sein, während 60 % der Jungen eine penoanale Penetration angaben. In keinem Fall konnten objektivierbare Verletzungen festgestellt werden. Schlussfolgerung Auch wenn bei der medizinischen Untersuchung von minderjährigen Geschädigten nach Sexualdelikten nur äußerst selten eindeutige Befunde festzustellen sind, sollte jede/jeder MedizinerIn Kenntnis über die Wertigkeit und Bedeutung von kindlichen Genitalbefunden haben. Weiterhin gilt es, den fließenden Übergang von „Doktorspielen“ zu sexualisierter Gewalt zwischen Minderjährigen korrekt zu erkennen.

ZusammenfassungEs wird von einem 13 Jahre alt gewordenen weiblichen Orang-Utan berichtet, der 4 Tage vor dem Tod an einer akuten Enterokolitis erkrankte. Die tierärztliche Ultraschalluntersuchung einen Tag vor dem Tod erbrachte den Nachweis von vermehrter Flüssigkeit im Zäkum und einer abschnittsweise verdickten Kolonwand. Nach dem für die Veterinärmediziner und die Zoomitarbeiter unerwarteten Todeseintritt erfolgte eine Obduktion durch Rechtsmediziner der Universitätsmedizin Rostock mit Unterstützung von Ärzten weiterer Fachrichtungen. Dabei wurde als Todesursache eine akute Escherichia-coli-Enterokolitis mit massiver Blutung in den Darm festgestellt. Begünstigend oder ursächlich für die letale Enterokolitis dürften wahrscheinlich zahlreiche rezidivierende Durchfallerkrankungen in der Anamnese des Orang-Utans als Folge eines Verweigerns des Stillens durch die Mutter nach der Geburt gewesen sein.

A 49-year old man was found dead at home next to a glass containing a dried, white, crystalline substance and near a bag containing pills with the imprint XANAX, the trade name of alprazolam. A comprehensive screening of material collected during the autopsy revealed the presence of etizolam and caffeine in lethal concentrations (0.77 μg/mL and 190 μg/mL) but no trace of alprazolam. Benzodiazepine analogue etizolam is rarely prescribed in Germany, and as a result there are not many reports about fatal cases. It has anxiolytic, hypnotic, sedative and muscle-relaxant properties and is used for the short-term treatment of anxiety and panic attacks. The purine alkaloid caffeine, conversely, is the most widely used central nervous system stimulant. The following report outlines potentially the first reported case of a lethal combination of the downer etizolam and the upper caffeine in medical literature.

Robert Conrad, Salus in manu feminae. Studien zur Herrschaftsteilhabe der Kaiserin Richenza (1087/89 – 1141) (Historische Studien 512). Husum: Matthiesen Verlag 2020. 651 S., 26 Abb. ISBN 978-3-7868-1512-9. Geb. € 79,–

Virchows Archiv (2022). doi:10.1007/s00428-022-03319-2, Published by Springer, Berlin

The lancet / Regional health. Europe 15, 100330 (2022). doi:10.1016/j.lanepe.2022.100330, Published by Elsevier, [Amsterdam]

Cannabis is the most frequently abused recreational drug worldwide. Its major psychoactive component, ∆9-tetrahydrocannabinol (∆9-THC), interacts with specific cannabinoid (CB) receptors in the brain. Until today distinct neuropathological alterations have not been described.

The neurotoxic consequences of amphetamines, methamphetamine, and their derivatives, especially MDMA (“ecstasy”), have been described in various animal species as well as in humans. The underlying pathogenetic mechanisms are not yet fully resolved. Furthermore, it is still unclear how to transmit the animal data to the human abusers and whether persistent neurotoxicity also develops in humans.

Older autopsy studies of drug deaths predominantly focused on cerebrovascular complications or the consequences of hypoxic-ischemic conditions which were considered as unspecific secondary findings. However, subsequent systematic neuropathological studies have shown profound morphological CNS alterations. The major findings encompassed hypoxic-ischemic-independent neuronal loss, reduction of GFAP-positive astrocytes, widespread areas of demyelination and axonal damage with concomitant microglia activation, disturbances of various constituents of the BBB as well as reactive and degenerative cerebrovascular alterations.

This chapter summarizes the neuropathological findings seen in drug abusers and briefly outlines implications for future research.

Neuroimaging studies with computed tomography (CT), diffusion tensor imaging (DIT), magnetic resonance imaging (MRI), positron emission tomography (PET), proton magnetic resonance spectroscopy (MRS), and single photon emission computed tomography (SPECT) revealed numerous alterations in different brain regions of drug abusers. The alterations encompassed, e.g., brain atrophy, neurochemical abnormalities, perfusions deficits, focal demyelinations, and hyperintense lesions as well as microstructural abnormalities in the white matter. However, the underlying cause or possible neuropathological correlates of the majority of the observed findings are still unclear.

BACKGROUND: The use of fresh-frozen (FF) specimens represents the gold standard for biomechanical investigations. Since FF specimens are often difficult to obtain, chemical-fixed specimens (formalin (FA), Thiel (TH)) are also used. OBJECTIVE: Since fixation methods can alter the mechanical properties of bone tissue, the purpose of this study was to examine their influence on the fracture force of lumbar vertebral bodies (VB). METHODS: First the VB were subdivided into three focus groups: FF, TH, and FA. After removing the soft tissue and the processus transverses of all VB, the endplates were planned with a thin layer of epoxy resin, in order to apply a constant strain to the surface and sub-surface. The VB were subjected to axial compression tests in order to determine fracture force. Lastly a standardized compression fracture was generated. RESULTS: The mean values of the fracture force of the focus groups were 4529.5 N (FF), 3211.3N (TH) and 2947.9N (FA). Consequently a significant difference between the FF and the other two groups could be demonstrated (p< 0.05). CONCLUSION: The preliminary tests showed that the fraction force of fresh-frozen VB were significantly higher than TH/FA-fixed VB. Therefore, these fixation methods could potentially have an influence on the biomechanical properties of VB. This leads to the assumption that if load-to-failure tests are performed, it is probably recommended to use fresh-frozen specimens.

Autoimmune pathology of acute disseminated encephalomyelitis (ADEM) is generally restricted to the brain. Our objective is to expand the phenotype of ADEM. A four-year-old girl was admitted to the pediatric emergency room of a university medical center five days after a common upper respiratory tract infection. Acute symptoms were fever, leg pain, and headaches. She developed meningeal signs, and her level of consciousness dropped rapidly. Epileptic seizure activity started, and she became comatose, requiring intubation and mechanical ventilation. Serial brain magnetic resonance imaging (MRI) illustrated the fulminant development of ADEM. Treatment escalation with high-dose corticosteroids, immunoglobulins, and plasma exchange did not lead to clinical improvement. On day ten, the patient developed treatment-refractory cardiogenic shock and passed away. The postmortem assessment confirmed ADEM and revealed acute lymphocytic myocarditis, likely explaining the acute cardiac failure. Human metapneumovirus and picornavirus were detected in the tracheal secrete by PCR. Data sources–medical chart of the patient. This case is consistent with evidence from experimental findings of an association of ADEM with myocarditis as a postinfectious systemic autoimmune response, with life-threatening involvement of the brain and heart.

Gliomas are the most common primary brain tumors and often become apparent through symptomatic epileptic seizures. Glial cells express the inwardly rectifying K+ channel Kir4.1 playing a major role in K+ buffering, and are presumably involved in facilitating epileptic hyperexcitability. We therefore aimed to investigate the molecular and functional expression of Kir4.1 channels in cultured rat and human glioma cells. Quantitative PCR showed reduced expression of Kir4.1 in rat C6 and F98 cells as compared to control. In human U-87MG cells and in patient-derived low-passage glioblastoma cultures, Kir4.1 expression was also reduced as compared to autopsy controls. Testing Kir4.1 function using whole-cell patch-clamp experiments on rat C6 and two human low-passage glioblastoma cell lines (HROG38 and HROG05), we found a significantly depolarized resting membrane potential (RMP) in HROG05 (-29 ± 2 mV, n = 11) compared to C6 (-71 ± 1 mV, n = 12, P < 0.05) and HROG38 (-60 ± 2 mV, n = 12, P < 0.05). Sustained K+ inward or outward currents were sensitive to Ba2+ added to the bath solution in HROG38 and C6 cells, but not in HROG05 cells, consistent with RMP depolarization. While immunocytochemistry confirmed Kir4.1 in all three cell lines including HROG05, we found that aquaporin-4 and Kir5.1 were also significantly reduced suggesting that the Ba2+-sensitive K+ current is generally impaired in glioma tissue. In summary, we demonstrated that glioma cells differentially express functional inwardly rectifying K+ channels suggesting that impaired K+ buffering in cells lacking functional Ba2+-sensitive K+ currents may be a risk factor for increased excitability and thereby contribute to the differential epileptogenicity of gliomas.

Background: High primary stability is the fundamental prerequisite for safe osseointegration of cementless intervertebral disc prosthesis. The aim of our study was to determine the primary stability of intervertebral disc prosthesis with two different anchoring concepts – keel and spike anchoring. Methods: 10 human cadaveric lumbar spine specimens with an ActivL intervertebral disc prosthesis (5 x keel anchoring, 5 x spike anchoring) were tested on a spine simulator. Under axial load, moments of flexion, extension, left and right bending and axial rotation were applied on the lumbar spine specimens through a defined three-dimensional movement program as per ISO 2631 and ISO/CD 18192-1.3 standards. Micro-motion of the implant was measured in every axis for both anchor types and compared using statistical test for significance after calculating 95% confidence intervals. Results: In the transverse axis, the keel anchoring concept showed lower mean values of micro-motion , which was statistically significant (p0.05). The highest micro-motion values were observed in the longitudinal axis. Both concepts showed values around the threshold of primary stability (150 μm) with the spike concept showing lower mean values, but without a statistically significant difference.Conclusions: Both types of anchors met the criteria of primary stability. The keel anchoring shows a slight advantage compared to anchoring with spikes. Direct postoperative active mobilization doesn’t seem to compromise the primary stability of the prosthesis.

In der Revision eines Strafprozesses in Deutschland 2013 trug ein Privatgutachter die kontrovers diskutierte Auffassung vor, dass eine Frau durch eine Luftembolie infolge eines vaginalen Geschlechtsverkehrs mit ausschlieslich peniler Penetration und Verletzung der Vaginalwand verstorben war. Dabei habe der Gutachter die Diagnose Jahre nach dem Tod der Frau durch histologische Untersuchungen der Lungen und der Vaginalverletzungen gestellt. Die Haufigkeit der Diagnose „Luftembolie infolge vaginaler Verletzungen durch intravaginalen Geschlechtsverkehr“ und die Modalitat der Diagnosestellung wurden uberpruft. Es erfolgte eine selektive Literaturrecherche. Weiterhin wurden Rundbriefe an alle rechtsmedizinischen Institute und an Direktoren bzw. Chefarzte von Frauenkliniken groser Stadte in Deutschland versandt. Im Schrifttum fanden sich 2 Kasuistiken, die bei kritischer Analyse nach dem Stand der Wissenschaft zum Publikationszeitpunkt Fehler bei der Diagnosestellung aufwiesen. Bei uber 300.000 durchgefuhrten Obduktionen in der Zeit von 1990 bis 2016 wurde von 26 rechtsmedizinischen Instituten Deutschlands, die den Rundbrief beantwortet hatten, in keinem Fall die Diagnose „Luftembolie infolge vaginaler Verletzungen durch intravaginalen Geschlechtsverkehr“ gestellt. Alle 32 berufserfahrenen Frauenarzte, die auf den Rundbrief geantwortet hatten, hatten in ihrem Berufsleben weder uberlebte noch letal verlaufende Falle einer Luftembolie nach vaginalen Verletzungen durch Geschlechtsverkehr therapiert oder davon Kenntnis erlangt. Fur eine Todesursachendiagnose „Luftembolie nach vaginalen Verletzungen“ besteht nach epidemiologischen Erhebungen und kritischer Analyse der bisherigen sehr wenigen Literaturfalle keine Evidenz. Bei der Diagnose einer letalen venosen Luftembolie sind zwingend wissenschaftliche Standards zu beachten. Eine Diagnosestellung allein durch histologische Untersuchungen war und ist nach dem Stand der Wissenschaft nicht moglich.

Pacemaker (PM) technology has developed tremendously in recent decades. We evaluated the extent of individual programming in current PMs. Over a 7-month period in 2016, all deceased persons taken to the Rostock crematorium were prospectively screened for cardiac implantable electronic devices (CIEDs) and these were interrogated in situ. Programming of patient data, leads, and study parameters including mode, lower rate, upper tracking or sensor rate (UTSR), ventricular refractory time, sleeping function, hysteresis, and PM-mediated tachycardia intervention were analyzed and compared with delivery settings. Alterations in atrial/ventricular capture management and atrial/ventricular sensing assurance as well as changes in sensitivity and lead output were evaluated. We examined 2297 subjects, of whom 154 (6.7%) had CIEDs, with 125 (81.2%) being PMs. Finally, 72 (57.6%) PMs were eligible for analysis with an operation time of 31.0 ± 27.0 months. We excluded 28 (18.2%) implantable cardioverter defibrillators (ICDs), 51 (41%) PMs presenting elective replacement indicator (ERI), two (1.6%) PMs with programming to insufficient function prior to death, and the left ventricle parameter of one (1.4%) cardiac resynchronization therapy pacemaker (CRT-P); further one CIED (0.6%) was not contactable. PMs offered in mean 75.2% of study parameters thereof 88.0% were to adjust manually, whereof 49.3% stayed unchanged to delivery mode. Lead output, UTSR, lower rate, and mode were the most frequently changed parameters (>85.7%, 65.3%, 54.2%, and 52.8%, respectively) compared with unmodified ventricular refractory time and hysteresis (91.7% and. 85.4%, respectively); 2.8% of PMs had out-of-the-box settings. The most frequent personalized data were last (88.9%) and first name (73.6%), while atrial and ventricular serial lead numbers were rarely entered (18.2% and 23.4%, respectively). The programming possibilities of PMs have advanced greatly. Nonetheless, improvements in individual PM programming are still needed as demonstrated by the findings in this study, e.g., PMs with manufacturer settings and lack of individual data.

Sufficient primary stability is mandatory for successful bony prosthetic incorporation. Therefore, defined micromotion values of 150 μm should not be exceeded as higher values might compromise the ingrowth of bone trabeculae to the implant surface. The aim of this study was to evaluate the primary stability of different cementless disc prosthesis in a cadaver model.Four different implants with different anchoring and bearing concept were tested with a target level of L4/5. 26 specimens were randomly allocated to 1 of the 4 different implants with 6 speciments in each group. Two groups were formed depending on the anchoring (spikes vs. fin) and bearing concept (non-/semi- vs. constrained). Each implant was tested regarding primary stability in a hydraulic simulator allowing simultaneous polyaxial segment movements and axial loading. The measurements were recorded on the lower plate of the prosthesis.The majority of the implants showed micromotion values below 200 μm in all planes. Only one prosthesis presented borderline longitudinal amplitudes that were significant higher than the other planes. Furthermore, significant differences were observed in the sagittal plane when comparing spike and keel anchoring. Spike anchoring implants showed superior tresults to keel anchoring implants (40 μm vs. 55 μm; p = .039), while the non-/semi-constrained bearing concept was more advantageous compared to constrained group (40 μm vs. 63 μm; p = .001).Spike anchoring and non-constrained implants might provide better primary stability.