The Role of the Kinin System and the Effect of Des-Arginine⁹-Bradykinin on Coagulation and Platelet Function in Critically Ill COVID-19 Patients: A Secondary Analysis of a Prospective Observational Study

The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the coagulation system is not fully understood. SARS-CoV-2 penetrates cells through angiotensin-converting enzyme 2 (ACE2) receptors, leading to its downregulation. Des-arginine9-bradykinin (DA9B) is degraded by ACE2 and causes vasodilation and increased vascular permeability. Furthermore, DA9B is associated with impaired platelet function. Therefore, the aim of this study was to evaluate the effects of DA9B on platelet function and coagulopathy in critically ill coronavirus disease 2019 (COVID-19) patients. In total, 29 polymerase-positive SARS-CoV-2 patients admitted to the intensive care unit of the University Hospital of Giessen and 29 healthy controls were included. Blood samples were taken, and platelet impedance aggregometry and rotational thromboelastometry were performed. Enzyme-linked immunosorbent assays measured the concentrations of DA9B, bradykinin, and angiotensin 2. Significantly increased concentrations of DA9B and angiotensin 2 were found in the COVID-19 patients. A negative effect of DA9B on platelet function and intrinsic coagulation was also found. A sub-analysis of moderate and severe acute respiratory distress syndrome patients revealed a negative association between DA9B and platelet counts and fibrinogen levels. DA9B provokes inhibitory effects on the intrinsic coagulation system in COVID-19 patients. This negative feedback seems reasonable as bradykinin, which is transformed to DA9B, is released after contact activation. Nevertheless, further studies are needed to confirm our findings

Ultrasound-accelerated thrombolysis in high-risk perioperative pulmonary embolism: two case reports and review of literature

Introduction!#!Treatment of high-risk pulmonary embolism (PE) in perioperative patients remains challenging. Systemic thrombolysis is associated with a high risk of major bleedings and intracranial haemorrhage. High mortality rates are reported for open pulmonary embolectomy. Therefore, postoperative surgical patients may benefit substantially from catheter-directed ultrasound-accelerated thrombolysis (USAT).!##!Case presentation!#!We report two cases of high-risk perioperative PE. Both patients developed severe haemodynamic instability leading to cardiac arrest. After the implantation of a veno-arterial extracorporeal membrane oxygenation (ECMO), they were both successfully treated with USAT. Adequate improvement of right ventricular function was achieved; thus, ECMO could be successfully weaned after 3 and 4 days, respectively. Both patients showed favourable outcomes and could be discharged to rehabilitation.!##!Conclusion!#!Current guidelines on treatment of PE offer no specific therapies for perioperative patients with high-risk PE. However, systemic thrombolysis is often excluded due to the perioperative setting and the risk of major bleeding. Catheter-directed thrombolysis was shown to utilise less thrombolytic agent while obtaining comparable thrombolytic effects. The risk for major bleeding (including intracranial haemorrhage) is also significantly lowered. Until further trials determining the value of adopted treatment strategies of high-risk PE in perioperative patients are available, USAT should be considered in similar cases

Cerebral Tissue Oxygen Saturation Is Enhanced in Patients following Transcatheter Aortic Valve Implantation: A Retrospective Study

Transcatheter aortic valve implantation (TAVI) has emerged as an alternative to surgical aortic valve replacement. The aim of this study was to evaluate whether a relevant alteration in cerebral tissue oxygen saturation (rSO2) could be detected following TAVI. Retrospective data analysis included 275 patients undergoing TAVI between October 2016 and December 2020. Overall, rSO2 significantly increased following TAVI (64.6 ± 10% vs. 68.1 ± 10%, p < 0.01). However, a significant rise was only observed in patients with a preoperative rSO2 < 60%. Of the hemodynamic confounders studied, hemoglobin, mean arterial pressure and blood pH were lowered, while central venous pressure and arterial partial pressure of carbon dioxide (PaCO2) were slightly elevated (PaCO2: 39 (36–43) mmHg vs. 42 (37–47) mmHg, p = 0.03; pH: 7.41 (7.3–7.4) vs. 7.36 (7.3–7.4), p < 0.01). Multivariate linear regression modeling identified only hemoglobin as a predictor of altered rSO2. Patients with a EuroScore II above 4% and an extended ICU stay were found to have lower rSO2, while no difference was observed in patients with postoperative delirium or between the implanted valve types. Further prospective studies that eliminate differences in potential confounding variables are necessary to confirm the rise in rSO2. Future research should provide more information on the value of cerebral oximetry for identifying high-risk patients who will require further clinical interventions in the setting of the TAVI procedure

Cerebral Tissue Oxygen Saturation Is Enhanced in Patients following Transcatheter Aortic Valve Implantation: A Retrospective Study

Transcatheter aortic valve implantation (TAVI) has emerged as an alternative to surgical aortic valve replacement. The aim of this study was to evaluate whether a relevant alteration in cerebral tissue oxygen saturation (rSO2) could be detected following TAVI. Retrospective data analysis included 275 patients undergoing TAVI between October 2016 and December 2020. Overall, rSO2 significantly increased following TAVI (64.6 ± 10% vs. 68.1 ± 10%, p 2 2) were slightly elevated (PaCO2: 39 (36–43) mmHg vs. 42 (37–47) mmHg, p = 0.03; pH: 7.41 (7.3–7.4) vs. 7.36 (7.3–7.4), p 2. Patients with a EuroScore II above 4% and an extended ICU stay were found to have lower rSO2, while no difference was observed in patients with postoperative delirium or between the implanted valve types. Further prospective studies that eliminate differences in potential confounding variables are necessary to confirm the rise in rSO2. Future research should provide more information on the value of cerebral oximetry for identifying high-risk patients who will require further clinical interventions in the setting of the TAVI procedure

SiPaGene: A new repository for instant online retrieval, sharing and meta-analyses of GeneChip^®expression data

Abstract Background Microarray expression profiling is becoming a routine technology for medical research and generates enormous amounts of data. However, reanalysis of public data and comparison with own results is laborious. Although many different tools exist, there is a need for more convenience and online analysis with restriction of access and user specific sharing options. Furthermore, most of the currently existing tools do not use the whole range of statistical power provided by the MAS5.0/GCOS algorithms. Description With a current focus on immunology, infection, inflammation, tissue regeneration and cancer we developed a database platform that can load preprocessed Affymetrix GeneChip expression data for immediate access. Group or subgroup comparisons can be calculated online, retrieved for candidate genes, transcriptional activity in various biological conditions and compared with different experiments. The system is based on Oracle 9i with algorithms in java and graphical user interfaces implemented as java servlets. Signals, detection calls, signal log ratios, change calls and corresponding p-values were calculated with MAS5.0/GCOS algorithms. MIAME information and gene annotations are provided via links to GEO and EntrezGene. Users access via https protocol their own, shared or public data. Sharing is comparison- and user-specific with different levels of rights. Arrays for group comparisons can be selected individually. Twenty-two different group comparison parameters can be applied in user-defined combinations on single or multiple group comparisons. Identified genes can be reviewed online or downloaded. Optimized selection criteria were developed and reliability was demonstrated with the "Latin Square" data set. Currently more than 1,000 arrays, 10,000 pairwise comparisons and 500 group comparisons are presented with public or restricted access by different research networks or individual users. Conclusion SiPaGene is a repository and a high quality tool for primary analysis of GeneChips. It exploits the MAS5.0/GCOS pairwise comparison algorithm, enables restricted access and user specific sharing. It does not aim for a complete representation of all public arrays but for high quality analysis with stepwise integration of reference signatures for detailed meta-analyses. Development of additional tools like functional annotation networks based on expression information will be future steps towards a systematic biological analysis of expression profiles.</p

Minimized Extracorporeal Circulation Is Associated with Reduced Plasma Levels of Free-Circulating Mitochondrial DNA Compared to Conventional Cardiopulmonary Bypass: A Secondary Analysis of an Exploratory, Prospective, Interventional Study

The use of minimized extracorporeal circulation (MiECC) during cardiac surgery is associated with a reduced inflammatory reaction compared to conventional cardiopulmonary bypass (cCPB). Since it is unknown if MiECC also reduces the amount of free-circulating mitochondrial DNA (mtDNA), this study aims to compare MiECC-induced mtDNA release to that of cCPB as well as to identify potential relations between the plasma levels of mtDNA and an adverse outcome. Overall, 45 patients undergoing cardiac surgery with either cCPB or MiECC were included in the study. MtDNA encoding for NADH dehydrogenase 1 was quantified with quantitative polymerase chain reaction. The plasma amount of mtDNA was significantly lower in patients undergoing cardiac surgery with MiECC compared to cCPB (MiECC: 161.8 (65.5–501.9); cCPB 190.8 (82–705.7); p p 650 copies/µL after the commencement of CPB had a 5-fold higher risk for postoperative atrial fibrillation independently of the type of cardiopulmonary bypass. An amount of mtDNA being higher than 650 copies/µL showed moderate predictive power (AUROC 0.71 (0.53–071)) for the identification of postoperative atrial fibrillation. In conclusion, plasma levels of mtDNA were lower in patients undergoing cardiac surgery with MiECC compared to cCPB. The amount of mtDNA at the beginning of the CPB was associated with postoperative atrial fibrillation independent of the type of cardiopulmonary bypass

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion