The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics

Schons M, Pilgram L, Reese J-P, et al. The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics. European Journal of Epidemiology . 2022.The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON's goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36-62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON's design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities.Trial registration https://clinicaltrials.gov/ct2/show/NCT04768998 . https://clinicaltrials.gov/ct2/show/NCT04747366 . https://clinicaltrials.gov/ct2/show/NCT04679584. © 2022. The Author(s)

Glycation Leads to Increased Polysialylation and Promotes the Metastatic Potential of Neuroblastoma Cells

Neuroblastoma is the second most frequent extracranial tumor, affecting young children worldwide. One hallmark of tumors such as neuroblastomas, is the expression of polysialic acid, which interferes with adhesion and may promote invasion and metastasis. Since tumor cells use glycolysis for energy production, they thereby produce as side product methylglyoxal (MGO), which reacts with proteins to advanced glycation end products in a mechanism called glycation. Here we analyzed the expression of (poly) sialic acid and adhesion of Kelly neuroblastoma cells after glycation with MGO. We found that both sialylation and polysialylation is increased after glycation. Furthermore, glycated Kelly neuroblastoma cells had a much higher potential for migration and invasion compared with non-glycated cells

The grim truth in Murphýs law: Routine subgaleal suction drain may cause rapid and fatal brain damage

Purpose: Cranioplasty is most commonly performed after decompressive hemicraniectomy and serves on the one hand for protection of the underlying brain tissue, on the other hand this surgery is also indicated for cosmetic reasons. In addition, patients may experience clinical improvement after this procedure, which can be explained by normalization of the CSF (Cerebrospinal fluid) and cerebral blood flow. However, this (usually underestimated) procedure is associated with one of the the highest complication rates in neurosurgery. Results: We report a case with a fatal outcome after routine cranioplasty utilizing PEEK (polyetheretherketone) implant due to a cerebrospinal fluid fistula. Conclusion: Cranioplasty after decompressive hemicraniectomy can restore aesthetics, ensures protection, and often leads to neurologic improvement in patients. However, it is one of the procedures with the highest complication rates in neurosurgery, and it should not be underestimated. The use of a drain with suction can have fatal consequences, especially when dural integrity is compromised and when there is intracranial room for considerable volume shift, e.g. after hemispheric infarction

Emerging magnetic order in platinum atomic contacts and chains

The development of atomic-scale structures revealing novel transport phenomena is a major goal of nanotechnology. Examples include chains of atoms that form while stretching a transition metal contact or the predicted formation of magnetic order in these chains, the existence of which is still debated. Here we report an experimental study of the magneto-conductance (MC) and anisotropic MC with atomic-size contacts and mono-atomic chains of the nonmagnetic metal platinum. We find a pronounced and diverse MC behaviour, the amplitude and functional dependence change when stretching the contact by subatomic distances. These findings can be interpreted as a signature of local magnetic order in the chain, which may be of particular importance for the application of atomic-sized contacts in spintronic devices of the smallest possible size

Electrophilic Functionalization of a Hexaphosphabenzene Ligand in [(Cp*Mo)₂(μ,η⁶ : ⁶‐P₆)]

The electrophilic functionalization of the triple-decker sandwich complex [{Cp*Mo}2(μ,η6:6-P6)] (A) and its mono-oxidized counterpart [{Cp*Mo}2(μ,η6:6-P6)][SbF6] (B) with reactive main-group electrophiles as well as radical scavengers is shown to be a reliable method for the selective functionalization of the hexaphosphabenzene ligand. Depending on the electrophile used, the regioselectivity of the functionalization can be adjusted. Using group 16 electrophiles, the trisubstituted compounds [{Cp*Mo}2{(μ,η3 : 3-P3)(μ,η1 : 1 : 1 : 1-1,3-(SePh)2-2-Br-P3)}][TEF] (1), [{Cp*Mo}2(μ,η3 : 3-P3)(μ,η1 : 1 : 1 : 1-1,2,3-(EPh)3-P3)][SbF6] (E=S (2), Se (3)) as well as the side product [{Cp*Mo}2(μ,η4:4-P4)(μ,η1 : 1-P(SPh)2)][SbF6] (4) are obtained. By switching to phosphenium ions as group 15 electrophiles, the ring-inserted products [{Cp*Mo}2(μ,η3 : 3 : 2 : 2-P7R2)][TEF] (R=Cy (5), iPr (6)) are isolated, showing an unprecedented P7R2 structural motif. Furthermore, the reaction with MeOTf yields the dimeric [{Cp*Mo}4(1,4-Me2-μ4,η1 : 1 : 1 : 1 : 1 : 1-P6)(μ,η3 : 3-P3)2][TEF]2 (7) as the first example of a complex featuring two interconnected cyclo-P6 middle deck ligands. Finally, by combination of the methylation step with Ph2Se2, the mixed group 14/16 complex [{Cp*Mo}2{(μ,η3 : 3-P3)(μ,η1 : 1 : 1 : 11,2-(SePh)2-3-Me-P3)}][OTf] (8) is obtained

Glycation Leads to Increased Invasion of Glioblastoma Cells

Glioblastoma (GBM) is a highly aggressive and invasive brain tumor with a poor prognosis despite extensive treatment. The switch to aerobic glycolysis, known as the Warburg effect, in cancer cells leads to an increased production of methylglyoxal (MGO), a potent glycation agent with pro-tumorigenic characteristics. MGO non-enzymatically reacts with proteins, DNA, and lipids, leading to alterations in the signaling pathways, genomic instability, and cellular dysfunction. In this study, we investigated the impact of MGO on the LN229 and U251 (WHO grade IV, GBM) cell lines and the U343 (WHO grade III) glioma cell line, along with primary human astrocytes (hA). The results showed that increasing concentrations of MGO led to glycation, the accumulation of advanced glycation end-products, and decreasing cell viability in all cell lines. The invasiveness of the GBM cell lines increased under the influence of physiological MGO concentrations (0.3 mmol/L), resulting in a more aggressive phenotype, whereas glycation decreased the invasion potential of hA. In addition, glycation had differential effects on the ECM components that are involved in the invasion progress, upregulating TGFβ, brevican, and tenascin C in the GBM cell lines LN229 and U251. These findings highlight the importance of further studies on the prevention of glycation through MGO scavengers or glyoxalase 1 activators as a potential therapeutic strategy against glioma and GBM

Makroskopische und mikroskopische Veränderungen des N. vestibulocochlearis nach Gamma-Knife-Therapie

We report on a case in which macroscopic and microscopic changes of the vestibulocochlear nerve could be observed after radiosurgery of an intrameatal vestibular schwannoma. This case shows for the first time a morphological correlate for undesirable effects after radiosurgical treatment of a vestibular schwannoma and indicates that despite a certain distance to the actual tumor, degenerative changes in neural structures can be expected

Neurofibromatosis Type 1 Gene Alterations Define Specific Features of a Subset of Glioblastomas

Neurofibromatosis type 1 (NF1) gene mutations or alterations occur within neurofibromatosis type 1 as well as in many different malignant tumours on the somatic level. In glioblastoma, NF1 loss of function plays a major role in inducing the mesenchymal (MES) subtype and, therefore defining the most aggressive glioblastoma. This is associated with an immune signature and mediated via the NF1–MAPK–FOSL1 axis. Specifically, increased invasion seems to be regulated via mutations in the leucine-rich domain (LRD) of the NF1 gene product neurofibromin. Novel targets for therapy may arise from neurofibromin deficiency-associated cellular mechanisms that are summarised in this review

Distal Flow Diversion with Anti-Thrombotically Coated and Bare Metal Low-Profile Flow Diverters—A Comparison

Background and purpose: The establishment of low-profile flow diverting stents (FDS), for example, the Silk Vista Baby (SVB) and the p48MW, facilitated endovascular treatment of peripheral cerebral aneurysms. This study therefore aims to compare the performance and outcomes of the SVB with those of the p48MW HPC, with a special focus on hemodynamic aspects of peripheral segments and bifurcations. Materials and methods: The study cohort comprises 108 patients, who were either treated with the SVB or the p48MW HPC between June 2018 and April 2021. Results: Sixty patients received a SVB and forty-eight patients a p48MW HPC. The SVB was used predominantly in the AcomA-complex, and the p48MW HPC in the MCA bifurcation. Immediately after implantation, significant hemodynamic downgrading (OKM A2-A3, B1-B3, C3) was achieved in 60% in the SVB group vs. 75.1% in the p48MW HPC group. At the second follow-up, after an average of 8.8 and 10.9 months, respectively, OKM D1 was observed in 64.4% of the SVB group vs. 27.3% in the p48MW HPC group. Only 1.7% vs. 6.8% of the aneurysms remained morphologically unaltered (OKM A1). Adverse events with persisting neurologic sequalae at last follow-up were largely comparable in both groups (5.0% vs. 4.2%). Conclusion: Immediately after implantation, the p48MW HPC had a more profound hemodynamic impact than the SVB; however, early complete occlusions were achieved in a greater proportion of lesions after implantation of the uncoated SVB