cord-006192-bqwchhwk 1988 cord-006860-a3b8hyyr 1996 Dept of Pediatrics, University Hospitals Kiel and Mtinster, Germany Resistance to activated protein C (APCR), in the majority of cases associated with the Arg 506 Gin point mutation in the factor V gene is present in more than 50 % of patients < 60 years of age with unexplained thrombophilia. The regular APC resistance test is not applicable to plasma from Orally anticoagulated (OAC) or heparinized patients due to decreased levels of vitamin K-dependent clotting factors and to thrombin inhibition by antithrombin, respectively. On admission an extensive coagulation screen yielded the following results (n/normal, t/elevated, I/reduced, +/positive, -/negative): PT t, aPTT t, Tr n, factor II, V, VIII n, factor VII, IX, XI, XII /,, fibrinogan t, ATIII n, protein C, S *, activated protein C sensitivity ratio 1.92 ($), FV-Leidenmutation PCR -, fibrinolytic system n, TAT t, Ft÷2 t, lupus anticoagulant +, heparin induced platelet antibodies +; no diagnosis of a specific autoimmuna disorder could be made. cord-010328-uxpedpz8 2020 In this study, source plasma from donation centers in various locations of the Southwestern quarter of the United States was surveyed for antibody titers to hepatitis A virus (HAV), measles virus (MeV), and cytomegalovirus (CMV). Safety measures implemented nearly two decades ago-collaborative, industry-wide epidemiological surveillance of the donor population, judicious selection of donors, rigorous testing of plasma by serological and molecular (e.g., nucleic acid testing) methods and validation of manufacturing methods for virus clearance capacity-provide a high degree of confidence that IG products, regardless of plasma origin, safely deliver a diverse, natural combination of human polyclonal antibodies 1,2 . The analyses of individual units originating from select pools served to demonstrate that a number of centers in the US Southwest are capable of consistently generating plasma with elevated anti-HAV Ig titers. cord-018142-xt71w4nr 2006 cord-018492-d34tyar7 2019 cord-018845-r88bhiac 2010 cord-031907-ilhr3iu5 2020 L.M., and the National Institutes of Health (R35GM119623) to T.R.G. The addition of a size exclusion chromatography step to various urinary extracellular vesicle concentrating methods reveals differences in the small RNA profile Introduction: Urinary extracellular vesicles (EVs) and their RNA cargo are a novel source of biomarkers for various diseases, however non-vesicular RNA (e.g. associated with proteins) is also present within urine. We then evaluated efficiency of heart targeting for eAAV9 or eAAV6 and standard AAV9 or AAV6 encoding for EGFP, mCherry or firefly luciferase in different human cell lines in vitro, in black mouse and in passive immunity nude mouse model in vivo using flow cytometry, confocal microscopy, Langendorff perfusion system and Methods: HLHS patients (n = 3) after Glenn procedure and swine (n = 3) after PAB were given RV injections of allogeneic/xenogeneic MSCs. Donor-specific, HLA-I+, exosomes were isolated from plasma. cord-261653-0vtghtp7 2020 Thus, the present narrative overviews the strategy developed by our team to identify and recruit COVID-19 survivors to donate convalescent plasma at the Mayo Clinic Blood Donor Center in Rochester, Minnesota. Rochester, Minnesota required a strategy to interface with the community of recovering COVID-19 patients and recruit eligible convalescent plasma donors. Overall, this recruitment strategy utilized a simple survey, an algorithm for triaging donors, a workflow for connecting donors with Mayo Clinic Blood Donor Center, a team of physician navigators (including medical students) to screen eligible donors, and a support center for donor questions. Our web-based recruitment survey and all e-mail communications to interested potential donors contained the e-mail address for our convalescent plasma service center. The service center team used available resources from the US FDA, Mayo Clinic, and the blood banking community to support questions regarding donor eligibility and COVID-19 testing. cord-262776-6k7tcgfs 2004 cord-266147-s8rxzm0t 2007 cord-270908-9snyt2n1 2006 cord-271764-um001ffd 2020 cord-274150-ukdha3ap 2020 Given its rapid acquisition, convalescent plasma therapy has been considered as an emergency intervention in several pandemics, including the Spanish flu, severe acute respiratory syndrome coronavirus (SARS-CoV-1), and West Nile virus, and more recently, Ebola virus [7] [8] [9] . Although large-scale randomized controlled trials have not yet been performed, and most studies did not evaluate neutralizing activities of used convalescent plasma, previous experiences on convalescent plasma therapy for the treatment of emerging infectious diseases provide us with important historical precedents that this intervention might be useful for confronting the COVID-19 epidemics. To evaluate the efficacy and adverse effects of convalescent plasma therapy for patients with COVID19 , an open-label, multicenter, randomized clinical trial was performed in seven medical centers in Wuhan, China. Some patients who recover from viral diseases may not have high titers of neutralizing antibodies, which are crucial for the effectiveness of convalescent plasma therapy [13, 14] . cord-277811-j58qvyum 2011 cord-280221-s6oxq772 2020 cord-282252-07uzz649 2020 The basic concept for use of convalescent plasma in COVID-19 is as a delivery system for viral neutralizing antibodies, that is to confer passive immunity. Considering the aforementioned limitations and the potential risks, appropriate triage systems should be utilized; hence, plasma therapy use is currently restricted only to critically ill patients. The FDA recommends two clinical indications for the current usage of convalescent plasma therapy in COVID-19 patients(12) Scenario A (Severe disease) which is defined as one or more of the following: On April 3, 2020, the FDA cleared the path for the use of this potential lifesaving therapy under any of the following three routes[1] enrollment in a clinical trial, [2] via the national expanded access treatment protocol, and [3] under a single patient emergency investigational new drug application (eIND). Lacking a vaccine and with limited antiviral options against SARS-CoV-2, this is an ideal time to try convalescent plasma therapy in COVID-19 patients. Treatment of 5 Critically Ill Patients with COVID-19 with Convalescent Plasma Effectiveness of convalescent plasma therapy in severe COVID-19 patients cord-284208-8fsqgkw5 2008 cord-284582-xwedgllw 2020 cord-294585-dl5v9p50 2009 However, because blood contains numerous labile proteins and fragile cells, and because there is a wide array of potentially infectious agents, no single method of pathogen-inactivation will likely preserve all blood components, yet effectively remove all viruses, bacteria, spores, protozoa and prions. Riboflavin/ultraviolet light treatment has been evaluated in preclinical studies and found to result in reduction of infectivity by many pathogens including west Nile virus, intracellular HIV, bacteria and protozoa. Therapeutic efficacy and safety of platelets treated with a photochemical process for pathogen inactivation: the SPRINT Trial Clinical safety of platelets photochemically treated with amotosalen HCl and ultraviolet A light for pathogen inactivation: the SPRINT trial Fresh frozen plasma prepared with amotosalen HCl (S-59) photochemical pathogen inactivation: transfusion of patients with congenital coagulation factor deficiencies Therapeutic efficacy and safety of red blood cells treated with a chemical process (S-303) for pathogen inactivation: a Phase III clinical trial in cardiac surgery patients cord-294684-wfsdjs1f 2020 cord-304616-k92fa15l 2020 cord-305074-wz17u4e7 2020 cord-305130-vz72ldbo 2020 cord-319013-oytqcifa 2020 In the first retrospective, randomized controlled trial published to date, 39 patients in New York with severe COVID-19 were transfused with 2 units of ABO-type matched CP with anti-Spike antibody titers of Ն1:320 (measured by a two-step Spike proteindirected ELISA). CP (9 to 13 ml/kg from donors with S-RBD IgG titer of Ն1:640) was associated with a negative SARS-CoV-2 PCR test at 72 h in 87.2% of the CP group versus 37.5% of the BSC group, but clinical improvement at 28 days was statistically different only in patients with severe, but not in life-threatening, disease (104) . Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol Anti-SARS-CoV-2 virus antibody levels in convalescent plasma of six donors who have recovered from COVID-19 cord-321697-yua3apfi 2020 This article highlights the involvement of circulating CFNAs in local and systemic processes dealing with the question, whether specific patterns of CFNAs in blood, their detection, quantity and quality (such as their methylation status) might be instrumental to predict a disease development/progression and could be further utilised for accompanying diagnostics, targeted prevention, creation of individualised therapy algorithms, therapy monitoring and prognosis. Especially severe, prolonged and/ or chronic stress of any origin such as exercise-induced oxidative stress [22] (see "Physical activity and exercise-induced oxidative stress" section), hormonal stress [23] , emotional stress and psychological burden [24] [25] [26] [27] as well as metabolic stress, e.g. in diabetes mellitus [28, 29] (see also below "Association between diabetes mellitus and carcinogenesis: diagnostic and therapeutic potential of cell-free nucleic acids" section) and hyperhomocysteinaemia [30, 31] amongst others, is associated with highly increased ROS production and insufficient repair capacity-both linked to oxidative damage of mitochondria and consequent mitochondrial dysfunction leading to the development of cardiovascular impairments [32] [33] [34] , neuro/degenerative pathologies [34] [35] [36] [37] , impaired healing [34] and malignant cell transformation [34, [38] [39] [40] [41] [42] . cord-322714-s0wge7o4 2020 cord-323656-bzefn894 2020 cord-324908-ptlpsnfo 2020 16 Public Health of England and the International Severe Acute Respiratory and Emerging Infection Consortium 17 put forward that convalescent plasma could be a promising specific treatment for serious Middle East respiratory syndrome (MERS), and further evaluation is needed in human clinical trials. Although many studies have reported the efficacy and safety of convalescent plasma infusion in the treatment of various infections, due to the lack of large-scale, randomized, well-designed, and prospective clinical trials, we tend to consider convalescent plasma as an "empirical" therapy. Mortality in the treatment group was significantly lower than in the nontreatment group ( controlled trial reported that patients who received immune plasma and standard care for severe influenza showed a nonsignificant reduction in the mortality rate. In conclusion, the transfusion of up to 500 mL of convalescent plasma with unknown levels of neutralizing antibodies in 84 patients with confirmed Ebola virus infection was not associated with a significant improvement in survival. cord-326176-n0xo3e53 2008 cord-328352-l1q4uvxl 2020 cord-329228-yjvw2ee1 2006 cord-335316-x2t5h5gu 2020 cord-336177-p7b7yw28 2020 cord-349031-tbof9yqi 2020 cord-351328-ly72scru 2020 cord-352985-5ccrkfsa 2020