Summary Background We used the RNActive® technology platform (CureVac N.V., Tübingen, Germany) to prepare CVnCoV, a COVID-19 vaccine containing sequence-optimized mRNA coding for a stabilized form of SARS-CoV‑2 spike (S) protein encapsulated in lipid nanoparticles (LNP). Methods This is an interim analysis of a dosage escalation phase 1 study in healthy 18–60-year-old volunteers in Hannover, Munich and Tübingen, Germany, and Ghent, Belgium. After giving 2 intramuscular doses of CVnCoV or placebo 28 days apart we assessed solicited local and systemic adverse events (AE) for 7 days and unsolicited AEs for 28 days after each vaccination. Immunogenicity was measured as enzyme-linked immunosorbent assay (ELISA) IgG antibodies to SARS-CoV‑2 S‑protein and receptor binding domain (RBD), and SARS-CoV‑2 neutralizing titers (MN50). Results In 245 volunteers who received 2 CVnCoV vaccinations (2 μg, n = 47, 4 μg, n = 48, 6 μg, n = 46, 8 μg, n = 44, 12 μg, n = 28) or placebo (n = 32) there were no vaccine-related serious AEs. Dosage-dependent increases in frequency and severity of solicited systemic AEs, and to a lesser extent local AEs, were mainly mild or moderate and transient in duration. Dosage-dependent increases in IgG antibodies to S‑protein and RBD and MN50 were evident in all groups 2 weeks after the second dose when 100% (23/23) seroconverted to S‑protein or RBD, and 83% (19/23) seroconverted for MN50 in the 12 μg group. Responses to 12 μg were comparable to those observed in convalescent sera from known COVID-19 patients. Conclusion In this study 2 CVnCoV doses were safe, with acceptable reactogenicity and 12 μg dosages elicited levels of immune responses that overlapped those observed in convalescent sera.

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Background: Gilles de la Tourette syndrome (TS) is a chronic neuropsychiatric disorder characterized by motor and vocal tics. First-line treatments for tics are antipsychotics and tic-specific behavioral therapies. However, due to a lack of trained therapists and adverse events of antipsychotic medication many patients seek alternative treatment options including cannabis. Based on the favorable results obtained from case studies on different cannabis-based medicines as well as two small randomized controlled trials using delta-9-tetrahydrocannabinol (THC), we hypothesize that the cannabis extract nabiximols can be regarded as a promising new and safe treatment strategy in TS.Objective: To test in a double blind randomized clinical trial, whether treatment with the cannabis extract nabiximols is superior to placebo in patients with chronic tic disorders.Patients and Methods: This is a multicenter, randomized, double-blind, placebo controlled, parallel-group, phase IIIb trial, which aims to enroll 96 adult patients with chronic tic disorders (TS or chronic motor tic disorder) across 6 centers throughout Germany. Patients will be randomized with a 2:1 ratio into a nabiximols and a placebo arm. The primary efficacy endpoint is defined as tic reduction of at least 30% (compared to baseline) according to the Total Tic Score of the Yale Global Tic Severity Scale (YGTSS-TTS) after 13 weeks of treatment. In addition, several secondary endpoints will be assessed including changes in different psychiatric comorbidities, quality of life, driving ability, and safety assessments.Discussion: This will be the first large, controlled study investigating efficacy and safety of a cannabis-based medicine in patients with TS. Based on available data using different cannabis-based medicines, we expect not only a reduction of tics, but also an improvement of psychiatric comorbidities. If the cannabis extract nabiximols is proven to be safe and effective, it will be a valuable alternative treatment option. The results of this study will be of high health-economic relevance, because a substantial number of patients uses cannabis (illegally) as self-medication.Conclusion: The CANNA-TICS trial will clarify whether nabiximols is efficacious and safe in the treatment of patients with chronic tic disorders.Clinical Trial Registration: This trial is registered at clinicaltrialsregister.eu (Eudra-CT 2016-000564-42) and clinicaltrials.gov (NCT03087201).

A score based on preoperative creatinine, leukocyte, and platelet values allowed early estimation of postoperative 30- and 90-day outcomes and intraoperative transfusion requirements in liver transplantation. Results might help to improve timely logistic and personal strategies.

Introduction Despite advances in perioperative management and surgical technique, postoperative liver failure remains a feared complication after hepatic resection. Various supportive treatment options are under current discussion, but lack of structured evaluation. We therefore established a porcine model of major liver resection to study regeneration after partial hepatectomy in a reliable and well-defined pre-clinical setting. Methods Major hepatectomy was performed on seven minipigs with the intention to set up a non-lethal but relevant transient impairment of liver function. For steady postoperative vascular access (e.g. for blood withdrawal, measurement of venous pressure), permanent catheters were implanted into the internal jugular and portal veins, respectively. Animals were followed up for 30 days; clinical and laboratory results were recorded in detail. Monitoring was enhanced by non-invasive determination of the maximum liver function capacity (LiMAx test). Results and conclusions The established porcine model appeared suitable for evaluation of postoperative liver regeneration. Clinical characteristics and progression of liver function impairment as well as subsequent recovery were comparable to courses known from surgery in humans. Laboratory parameters (e.g. liver enzymes, bilirubin, INR, coagulation factor II) showed relevant derangements during postoperative days (POD) 0 to 3 followed by normalization until POD 7. Application of the LiMAx test was feasible in minipigs, again showing values comparable to humans and kinetics in line with obtained laboratory parameters. The exteriorized portal vein catheters enabled intra- and postoperative monitoring of portal venous pressures as well as easy access for blood withdrawal without relevant risk of postoperative complications.

The antibody response of mice infected with Plasmodium vinckei after treatment with chloroquine either alone or in combination with interferon-gamma (IFN-gamma) was determined. Sequential serum samples were drawn from BALB/c mice receiving either 240 micrograms chloroquine on the day of infection or 120 micrograms chloroquine plus 10(4) units IFN-gamma daily for 11 days beginning on day 3 prior to infection. Mice treated with additional IFN-gamma showed an early induction of IgG2a response and a reduction in IgG1 antibodies as detected by the immunofluorescence technique at between 10 and 16 days after infection as compared with mice treated with chloroquine alone. Thus, IFN-gamma may partly exert its antimalarial activity via the induction of IgG2a antibody formation. At 4-6 weeks after infection, when mice from both groups resisted homologous re-infection, the predominant antibody isotypes found in both groups were IgG1 and IgG2a. Serum samples obtained from mice in both treatment groups at 6 weeks after infection were used for serum transfer experiments. When parasitised erythrocytes were preincubated with such immune serum, a retardation of the course of parasitaemia by 2 days was observed.

Purpose To determine the nature and frequency of duplicate prescriptions (DPs) in the emergency department (ED) by utilization of a novel categorization of DPs which differentiates between appropriate DPs (ADPs) and potentially inappropriate DPs (PIDPs). Methods In this retrospective cohort study, adult patients who presented to the ED for internal medicine of a large university hospital in northern Germany in 2018 and 2019 were screened for the presence of DPs. Descriptive statistical methods were used to characterize the nature and frequency of PIDPs compared to the frequency of ADPs. Results A total of 4208 patients were enrolled into the study. The median age of the study population was 63 years (interquartile range (IQR) 48–77), 53.9% were female. The patients took a median of 5 drugs (IQR 3–9). 10.9% of the study population were affected by at least one PIDP (at least one grade-1 PIDP: 6.1%; at least one grade-2 PIDP: 4.5%; at least one grade-3 PIDP: 1.1%). Non-opioid analgesics accounted for the majority of grade-1 PIDPs, while inhalatives were most frequently responsible for grade-2 and grade-3 PIDPs. Nearly half of the study population (48.6%) displayed at least one ADP. Conclusion PIDPs pose a frequent pharmacological challenge in the ED. The medication review should comprise a systematic screening for PIDPs with a particular focus on non-opioid analgesics and inhalatives. ADPs were detected more frequently than PIDPs, questioning the predominant notion in the medical literature that DPs are exclusively deleterious.

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