The next-generation coronavirus diagnostic techniques with particular emphasis on the SARS-CoV-2.

The potential zoonotic coronaviruses (SARS-CoV, MERS-CoV, and SARS-CoV-2) are of global health concerns. Early diagnosis is the milestone in their mitigation, control, and eradication. Many diagnostic techniques are showing great success and have many advantages, such as the rapid turnover of the results, high accuracy, and high specificity and sensitivity. However, some of these techniques have several pitfalls if samples were not collected, processed, and transported in the standard ways and if these techniques were not practiced with extreme caution and precision. This may lead to false-negative/positive results. This may affect the downstream management of the affected cases. These techniques require regular fine-tuning, upgrading, and optimization. The continuous evolution of new strains and viruses belong to the coronaviruses is hampering the success of many classical techniques. There are urgent needs for next generations of coronaviruses diagnostic assays that overcome these pitfalls. This new generation of diagnostic tests should be able to do simultaneous, multiplex, and high-throughput detection of various coronavirus in one reaction. Furthermore, the development of novel assays and techniques that enable the in situ detection of the virus on the environmental samples, especially air, water, and surfaces, should be given considerable attention in the future. These approaches will have a substantial positive impact on the mitigation and eradication of coronaviruses, including the current SARS-CoV-2 pandemic.

Vascular Imaging of Matrix Metalloproteinase Activity as an Informative Preclinical Biomarker of Drug-induced Vascular Injury.

Lack of biomarkers specific to and either predictive or diagnostic of drug-induced vascular injury (DIVI) continues to be a major obstacle during drug development. Biomarkers derived from physiologic responses to vessel injury, such as inflammation and vascular remodeling, could make good candidates; however, they characteristically lack specificity for vasculature. We evaluated whether vascular remodeling-associated protease activity, as well as changes to vessel permeability resulting from DIVI, could be visualized ex vivo in affected vessels, thereby allowing for visual monitoring of the pathology to address specificity. We found that visualization of matrix metalloproteinase activation accompanied by increased vascular leakage in the mesentery of rats treated with agents known to induce vascular injury correlated well with incidence and severity of histopathological findings and associated inflammation as well as with circulating levels of tissue inhibitors of metalloproteinase 1 and neutrophil gelatinase-associated lipocalin. The weight of evidence approach reported here shows promise as a composite DIVI preclinical tool by means of complementing noninvasive monitoring of circulating biomarkers of inflammation with direct imaging of affected vasculature and thus lending specificity to its interpretation. These findings are supportive of a potential strategy that relies on translational imaging tools in conjunction with circulating biomarker data for high-specificity monitoring of VI both preclinically and clinically.

[Consideration of guidelines, recommendations and quality indicators for treatment of stroke in the dataset "Emergency Department" of DIVI]. / Berücksichtigung von Leitlinien, Empfehlungen und Qualitätsindikatoren zur Schlaganfalltherapie im Datensatz Notaufnahme der DIVI.

BACKGROUND: The dataset "Emergency Department" of the German Interdisciplinary Association of Critical Care and Emergency Medicine (DIVI) has been developed during several expert meetings. Its goal is an all-encompassing documentation of the early clinical treatment of patients in emergency departments. Using the example of the index disease acute ischemic stroke (stroke), the aim was to analyze how far this approach has been fulfilled. MATERIAL AND METHODS: In this study German, European and US American guidelines were used to analyze the extent of coverage of the datasets on current emergency department guidelines and recommendations from professional societies. In addition, it was examined whether the dataset includes recommended quality indicators (QI) for quality management (QM) and in a third step it was examined to what extent national provisions for billing are included. In each case a differentiation was made whether the respective rationale was primary, i.e. directly apparent or whether it was merely secondarily depicted by expertise. In the evaluation an additional differentiation was made between the level of recommendations and further quality relevant criteria. RESULTS: The modular design of the emergency department dataset comprising 676 data fields is briefly described. A total of 401 individual fields, divided into basic documentation, monitoring and specific neurological documentation of the treatment of stroke patients were considered. For 247 data fields a rationale was found. Partially overlapping, 78.9 % of 214 medical recommendations in 3 guidelines and 85.8 % of the 106 identified quality indicators were primarily covered. Of the 67 requirements for billing of performance of services, 55.5 % are primarily part of the emergency department dataset. Through appropriate expertise and documentation by a board certified neurologist, the results can be improved to almost 100 %. CONCLUSION: The index disease stroke illustrates that the emergency department dataset of the DIVI covers medical guidelines, especially 100 % of the German guidelines with a grade of recommendation. All necessary information to document the specialized stroke treatment procedure in the German diagnosis-related groups (DRG) system is also covered. The dataset is also suitable as a documentation tool of quality management, for example, to participate in the registry of the German Stroke Society (ADSR). Best results are obtained if the dataset is applied by a physician specialized in the treatment of patients with stroke (e.g. board certified neurologist). Finally the results show that changes in medical guidelines and recommendations for quality management as well as billing-relevant content should be implemented in the development of datasets for documentation to avoid duplicate documentation.

Evaluation of von Willebrand factor and von Willebrand factor propeptide in models of vascular endothelial cell activation, perturbation, and/or injury.

Pharmacologically, vasoactive agents targeting endothelial and/or smooth muscle cells (SMC) are known to cause acute drug-induced vascular injury (DIVI) and the resulting pathology is due to endothelial cell (EC) perturbation, activation, and/or injury. Alteration in EC structure and/or function may be a critical event in vascular injury and, therefore, evaluation of the circulatory kinetic profile and secretory pattern of EC-specific proteins such as VWF and VWFpp could serve as acute vascular injury biomarkers. In rat and dog models of DIVI, this profile was determined using pharmacologically diverse agents associated with functional stimulation/perturbation (DDAVP), pathological activation (lipopolysaccharide [LPS]/endotoxin), and structural damage (fenoldopam [FD], dopamine [DA], and potassium channel opener (PCO) ZD6169). In rats, FD caused moderate DIVI and time-related increase in plasma VWF levels ∼33% while in control rats VWF increased ∼5%. In dogs, VWF levels transiently increased ∼30% when there was morphologic evidence of DIVI by DA or ZD6169. However, in dogs, VWFpp increased >60-fold (LPS) and >6-fold (DDAVP), respectively. This was in comparison to smaller dynamic 1.38-fold (LPS) and 0.54-fold (DDAVP) increases seen in plasma VWF. Furthermore, DA was associated with a dose-dependent increase in plasma VWFpp. In summary, VWF and VWFpp can discriminate between physiological and pathological perturbation, activation, and injury to ECs.