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Background: Some recipients of ChAdOx1 nCoV-19 COVID-19 Vaccine AstraZeneca develop antibody-mediated vaccine-induced thrombotic thrombocytopenia (VITT), associated with cerebral venous and other unusual thrombosis resembling autoimmune heparin-induced thrombocytopenia. A prothrombotic predisposition is also observed in Covid-19. We explored whether antibodies against the SARS-CoV-2 spike protein induced by Covid-19 cross-react with platelet factor 4 (PF4/CXLC4), the protein targeted in both VITT and autoimmune heparin-induced thrombocytopenia.Methods: Immunogenic epitopes of PF4 and SARS-CoV-2 spike protein were compared via prediction tools and 3D modelling software (IMED, SIM, MacMYPOL). Sera from 222 PCR-confirmed Covid-19 patients from five European centers were tested by PF4/heparin ELISA, heparin-dependent and PF4-dependent platelet activation assays. Immunogenic reactivity of purified anti-PF4 and anti-PF4/heparin antibodies from patients with VITT were tested against recombinant SARS-CoV-2 spike protein. Results: Three motifs within the spike protein sequence share a potential immunogenic epitope with PF4. Nineteen of 222 (8.6%) Covid-19 patient sera tested positive in the IgG-specific PF4/heparin ELISA, none of which showed platelet activation in the heparin-dependent activation assay, including 10 (4.5%) of the 222 Covid-19 patients who developed thromboembolic complications. Purified anti-PF4 and anti-PF4/heparin antibodies from two VITT patients did not show cross-reactivity to recombinant SARS-CoV-2 spike protein. Conclusions: The antibody responses to PF4 in SARS-CoV-2 infection and after vaccination with COVID-19 Vaccine AstraZeneca differ. Antibodies against SARS-CoV-2 spike protein do not cross-react with PF4 or PF4/heparin complexes through molecular mimicry. These findings make it very unlikely that the intended vaccine-induced immune response against SARS-CoV-2 spike protein would itself induce VITT.

Purpose While more advanced COVID-19 necessitates medical interventions and hospitalization, patients with mild COVID-19 do not require this. Identifying patients at risk of progressing to advanced COVID-19 might guide treatment decisions, particularly for better prioritizing patients in need for hospitalization. Methods We developed a machine learning-based predictor for deriving a clinical score identifying patients with asymptomatic/mild COVID-19 at risk of progressing to advanced COVID-19. Clinical data from SARS-CoV-2 positive patients from the multicenter Lean European Open Survey on SARS-CoV-2 Infected Patients (LEOSS) were used for discovery (2020-03-16 to 2020-07-14) and validation (data from 2020-07-15 to 2021-02-16). Results The LEOSS dataset contains 473 baseline patient parameters measured at the first patient contact. After training the predictor model on a training dataset comprising 1233 patients, 20 of the 473 parameters were selected for the predictor model. From the predictor model, we delineated a composite predictive score (SACOV-19, Score for the prediction of an Advanced stage of COVID-19) with eleven variables. In the validation cohort (n = 2264 patients), we observed good prediction performance with an area under the curve (AUC) of 0.73 ± 0.01. Besides temperature, age, body mass index and smoking habit, variables indicating pulmonary involvement (respiration rate, oxygen saturation, dyspnea), inflammation (CRP, LDH, lymphocyte counts), and acute kidney injury at diagnosis were identified. For better interpretability, the predictor was translated into a web interface. Conclusion We present a machine learning-based predictor model and a clinical score for identifying patients at risk of developing advanced COVID-19.

Objectives Transjugular intrahepatic portosystemic shunt (TIPS) insertion is an established treatment to lower portal pressure. There are no obligatory evidence-based recommendations addressing procedure and anticoagulation. Therefore, a survey was performed to establish current practice at different German hospitals. Methods A three-page survey was sent out via postal mail to 76 different hospitals addressing the topics indication, contraindication, follow-up and anticoagulation. Results Forty-three hospitals completed the survey: the median number of TIPS/year was 28.6 ± 23. Ascites and hydrothorax were announced as the main indications. Bilirubin levels above 5 mg/dl, hepatic encephalopathy and cardiac disease were considered as absolute contraindications in most hospitals, but age was not. The biggest variations were reported with regard to anticoagulation after TIPS procedure. Four hospitals never used any anticoagulation; most hospitals reported the use of low molecular weight heparins for a period of days up to 4 weeks. But also aspirin or clopidogrel was used after TIPS insertion in eight different hospitals. Additionally, the standards for follow-up after TIPS insertion were different in the hospitals. Conclusions There is no consensus how to handle indication, contraindications and anticoagulation after the TIPS procedure. A national and international consensus is warranted to improve the outcome of TIPS patients and reduce secondary complications. In addition to compare results and efficacy in the future standard operation procedures as proposed here need to be put in place.

Abkürzung Erläuterung BR grenzwertig resektabel (Engl.: borderline resectable) BRCA 1/2 Brustkrebsgen1/2 (Engl.: Breast Cancer Associated Gene 1/2) BRPC Borderline-resezierbarer Bauchspeicheldrüsenkrebs (Engl.: Borderline resectable pancreatic cancer) CA19-9 Kohlenhydrat-Antigen 19-9 (Engl.: Carbohydrate-Antigen 19-9) CALGP Chirurgische Arbeitsgemeinschaft für Leber-, Galle-und Pankreaserkrankungen CAO-V Chirurgische Arbeitsgemeinschaft Onkologie CAPS Internationales Konsortium für Vorsorgeuntersuchungen beim Bauchspeicheldrüsenkrebs (Engl.: International Cancer of the Pancreas Screening Consortium) CDKN2A Cyclin-abhängiger Kinase-Inhibitor 2A (Engl.: Cyclin Dependent Kinase Inhibitor 2A) CDR Clinical Decision Rule CEA Karzinoembryonales Antigen (Engl.: Carcinoembryonic antigen) CGS Clinical Guideline Service CONKO Charité Onkologie CR Vollständiges Ansprechen (Engl.: Complete Response) CRM Zirkumferentieller Resektionsrand (Engl.: Circumferential resection margin) CT Computertomographie DEGRO Deutsche Gesellschaft für Radioonkologie DEGUM Deutsche Gesellschaft für Ultraschall in der Medizin DFS Krankheitsfreies Überleben (Engl.: Disease-free survival) * am häufigsten assoziierte Karzinome.

Many cohort studies have investigated the link between diet and plasma TMAO levels, reporting incongruent results, while gut microbiota were only recently included into analyses. In these studies, taxonomic data were recorded that are not a good proxy for TMA formation, as specific members of various taxa exhibit genes catalyzing this reaction, demanding function-based technologies for accurate quantification of TMA-synthesizing bacteria.