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2.
Elife ; 92020 08 17.
Статья в английский | MEDLINE | ID: covidwho-2155739

Реферат

Temporal inference from laboratory testing results and triangulation with clinical outcomes extracted from unstructured electronic health record (EHR) provider notes is integral to advancing precision medicine. Here, we studied 246 SARS-CoV-2 PCR-positive (COVIDpos) patients and propensity-matched 2460 SARS-CoV-2 PCR-negative (COVIDneg) patients subjected to around 700,000 lab tests cumulatively across 194 assays. Compared to COVIDneg patients at the time of diagnostic testing, COVIDpos patients tended to have higher plasma fibrinogen levels and lower platelet counts. However, as the infection evolves, COVIDpos patients distinctively show declining fibrinogen, increasing platelet counts, and lower white blood cell counts. Augmented curation of EHRs suggests that only a minority of COVIDpos patients develop thromboembolism, and rarely, disseminated intravascular coagulopathy (DIC), with patients generally not displaying platelet reductions typical of consumptive coagulopathies. These temporal trends provide fine-grained resolution into COVID-19 associated coagulopathy (CAC) and set the stage for personalizing thromboprophylaxis.


Тема - темы
Betacoronavirus/isolation & purification , Blood Coagulation Disorders/diagnosis , Blood Coagulation Tests , Blood Coagulation , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Aged , Betacoronavirus/pathogenicity , Biomarkers/blood , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/virology , COVID-19 , COVID-19 Testing , Coronavirus Infections/blood , Coronavirus Infections/virology , Disease Progression , Female , Fibrinogen/metabolism , Host Microbial Interactions , Humans , Leukocyte Count , Longitudinal Studies , Male , Middle Aged , Pandemics , Platelet Count , Pneumonia, Viral/blood , Pneumonia, Viral/virology , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies , SARS-CoV-2 , Time Factors
4.
BMJ Open ; 12(11): e063856, 2022 11 04.
Статья в английский | MEDLINE | ID: covidwho-2108284

Реферат

INTRODUCTION: Hypercoagulation is one the main features of COVID-19. It is induced by the hyperinflammatory response that shifts the balance of haemostasis towards pro-coagulation. Interleukin-6 (IL-6) antagonist therapy has been recommended in certain subgroups of critically ill patients with COVID-19 to modulate inflammatory response. The interaction between immune response and haemostasis is well recognised. Therefore, our objective is to evaluate whether the modulation of the inflammatory response by IL-6 antagonist inflicts any changes in whole blood coagulation as assessed by viscoelastic methods in critically ill patients with COVID-19. METHODS AND ANALYSIS: In this prospective observational study, we are going to collect data on inflammatory parameters and blood coagulation using the ClotPro® device. The primary outcome is the change of the fibrinolytic system measured by the Lysis Time and Lysis onset time before and after immunomodulation therapy. Data will be collected before the IL-6 antagonist administration at baseline (T0) then after 24, 48 hours, then on day 5 and 7 (T1-4, respectively). Secondary outcomes include changes in other parameters related to inflammation, blood coagulation and biomarkers of endothelial injury. ETHICS AND DISSEMINATION: Ethical approval was given by the Medical Research Council of Hungary (1405-3/2022/EÜG). All participants provided written consent. The results of the study will be disseminated through peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05218369; Clinicaltrials.gov.


Тема - темы
COVID-19 , Humans , Blood Coagulation , COVID-19/drug therapy , Critical Illness/therapy , Interleukin-6 , Multicenter Studies as Topic , Observational Studies as Topic , Prospective Studies
5.
Blood ; 140(8): 809-814, 2022 08 25.
Статья в английский | MEDLINE | ID: covidwho-2083050

Реферат

Coronavirus disease-19 (COVID-19) includes a thromboinflammatory syndrome that may manifest with microvascular and macrovascular thrombosis. Patients with COVID-19 have a higher incidence of venous thromboembolism than other hospitalized patients. Three randomized control trials suggesting benefit of therapeutic heparin in hospitalized noncritically ill patients with COVID-19 have led to conditional guideline recommendations for this treatment. By contrast, prophylactic-dose heparin is recommended for critically ill patients. Unprecedented collaboration and rapidly funded research have improved care of hospitalized patients with COVID-19.


Тема - темы
COVID-19 , Venous Thromboembolism , Anticoagulants/pharmacology , Anticoagulants/therapeutic use , Blood Coagulation , COVID-19/complications , Heparin/pharmacology , Heparin/therapeutic use , Humans , Venous Thromboembolism/drug therapy , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology
6.
Kidney360 ; 1(7): 718-719, 2020 Jul 30.
Статья в английский | MEDLINE | ID: covidwho-1772606
7.
Thromb Res ; 219: 40-48, 2022 Nov.
Статья в английский | MEDLINE | ID: covidwho-2008145

Реферат

BACKGROUND: Thromboembolic events are common complications of COVID-19. Clinical study results on safety and efficacy of anticoagulation in COVID-19 are controversial. MATERIAL AND METHODS: This report updates our systematic review and random-effects meta-analysis on randomized controlled trials (RCTs) comparing standard prophylactic anticoagulation and intermediate or therapeutic anticoagulation in COVID-19 patients. We searched eligible studies for the update up to 4 February 2022 by weekly monitoring of RCTs in the Cochrane COVID-19 Study Register. Certainty of evidence was assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: For this update we included five new trials; a total of 13 RCTs with 7364 patients. Certainty of evidence was very low to low. We are uncertain whether low-dose prophylactic anticoagulation is favoured over placebo or no anticoagulation in the outpatient- or post-discharge-setting. In hospitalized patients with moderate and severe COVID-19, intermediate-dose anticoagulation may have little or no effect on thrombotic events or death (RR 1.03, 95 % CI 0.86-1.24), but may increase severe bleeding non-significantly (RR 1.48, 95 % CI 0.53-4.15). Therapeutic-dose anticoagulation may decrease thrombotic events or deaths in hospitalized patients with moderate COVID-19 (RR 0.64, 95 % CI 0.38-1.07; fixed-effect model RR 0.72, 95 % CI 0.57-0.91), but may have little or no effect in patients with severe disease (RR 0.98, 95 % CI 0.86-1.12). With therapeutic-dose anticoagulation, the risk of major bleeding may increase regardless of COVID-19 severity (RR 1.78, 95 % CI 1.15-2.74). CONCLUSIONS: Hospitalized, moderately ill COVID-19 patients may benefit from therapeutic-dose anticoagulation, while critically ill patients may not. Risk of major bleeding must be considered.


Тема - темы
COVID-19 , Thromboembolism , Thrombosis , Anticoagulants/adverse effects , Blood Coagulation , COVID-19/complications , COVID-19/drug therapy , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Humans , Thromboembolism/drug therapy , Thromboembolism/etiology , Thromboembolism/prevention & control , Thrombosis/chemically induced , Thrombosis/etiology
8.
J Hypertens ; 40(9): 1844, 2022 09 01.
Статья в английский | MEDLINE | ID: covidwho-1997085
9.
Clin Lab ; 68(8)2022 Aug 01.
Статья в английский | MEDLINE | ID: covidwho-1979624

Реферат

BACKGROUND: Protein S is a central regulator of coagulation as it critically participates in down-regulation of both extrinsic and intrinsic pathways of the coagulation cascade. In this review, we aim to provide an update on protein S and its anticoagulant functions as a central hemostatic regulator. METHODS: Electronic databases including, Google, Google Scholar, PMC, PubMed, Science Direct, and Scopus were rigorously searched using the terms protein S, hemostasis, natural anticoagulants, regulators of coagulation, and coagulation inhibitors for the completion of this descriptive review. RESULTS: Literature review shows that protein S is a potent cofactor for activated protein C (APC) in the regulation of the intrinsic pathway and a cofactor for tissue factor pathway inhibitor (TFPI) in the regulation of the extrinsic pathway. The strong association between protein S deficiency either hereditary or acquired and increased risk for venous thrombosis indicates the important and central role of protein S in controlling the initiation and propagation phase of coagulation cascade and that protein S is an important determinant for optimal activity of both APC and TFPI in coagulation regulation. CONCLUSIONS: Available evidence suggests that the role of protein S in the down-regulation of blood coagulation is mainly mediated through its high affinity binding to negatively charged phospholipid surfaces. This high affinity binding to negatively charged phospholipids helps bring the anticoagulant proteins to the membranes, resulting in efficient and targeted regulation of coagulation. In the shade of current COVID-19 pandemic, protein S deficiency has been found to be a leading cause of thrombotic complications associated with COVID-19.


Тема - темы
Blood Coagulation , Protein S Deficiency , Protein S , Anticoagulants/pharmacology , COVID-19 , Humans , Protein S/physiology
10.
Sci Rep ; 12(1): 13155, 2022 08 01.
Статья в английский | MEDLINE | ID: covidwho-1967619

Реферат

There has been growing attention toward the predictive value of the coagulation parameters abnormalities in COVID-19. The aim of the study was to investigate the role of coagulation parameters namely Prothrombin concentration (PC), activated Partial thromboplastin Time (aPTT), D-Dimer (DD), Anti Thrombin III (ATIII) and fibrinogen (Fg) together with hematological, and biochemical parameters in predicting the severity of COVID-19 patients and estimating their relation to clinical outcomes in hospitalized and severe COVID-19 Patients. In a prospective study, a total of 267 newly diagnosed COVID-19 patients were enrolled. They were divided into two groups; hospitalized group which included 144 patients and non-hospitalized group that included 123 patients. According to severity, the patients were divided into severe group which included 71 patients and non-severe group that included 196 patients who were admitted to ward or not hospitalized. Clinical evaluation, measurement of coagulation parameters, biochemical indices, outcome and survival data were recorded. Hospitalized and severe patients were older and commonly presented with dyspnea (P ≤ 0.001). Differences in coagulation parameters were highly significant in hospitalized and severe groups in almost all parameters, same for inflammatory markers. D-dimer, AT-III and LDH showed excellent independently prediction of severity risk. With a cut-off of > 2.0 ng/L, the sensitivity and specificity of D dimer in predicting severity were 76% and 93%, respectively. Patients with coagulation abnormalities showed worse survival than those without (p = 0.002). Early assessment and dynamic monitoring of coagulation parameters may be a benchmark in the prediction of COVID-19 severity and death.


Тема - темы
Blood Coagulation Disorders , COVID-19 , Blood Coagulation , Fibrin Fibrinogen Degradation Products , Humans , Partial Thromboplastin Time , Prospective Studies
11.
Methods Mol Biol ; 2511: 345-354, 2022.
Статья в английский | MEDLINE | ID: covidwho-1941388

Реферат

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent driving the current COVID-19 pandemic. The acute respiratory distress that occurs in some severe COVID-19 cases has been linked with hypercoagulation or thrombotic events as well as a worse prognosis and increased risk of death. Thus, point-of-care devices that can be used for early detection of coagulation abnormalities would assist in COVID-19 management. This chapter describes the use of the Roche Diagnostics CoaguChek® XS test kit for potential use in COVID-19 personalized medicine approaches.


Тема - темы
COVID-19 , Blood Coagulation , COVID-19/diagnosis , Humans , Pandemics , Point-of-Care Systems , SARS-CoV-2
12.
BMJ ; 378: o1670, 2022 07 08.
Статья в английский | MEDLINE | ID: covidwho-1932686
13.
Ther Adv Cardiovasc Dis ; 16: 17539447221105013, 2022.
Статья в английский | MEDLINE | ID: covidwho-1910188

Реферат

INTRODUCTION: Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in COVID-19 disease is associated with widespread inflammation and a prothrombotic state, resulting in frequent venous thromboembolic (VTE) events. It is currently unknown whether anticoagulation is protective for VTE events. Therefore, we conducted a systematic review to identify predictors of VTE in COVID-19. METHODS: We searched PubMed, EMBASE, Google Scholar, and Ovid databases for relevant observational studies of VTE in COVID-19 disease. The effect size for predictors of VTE was calculated using a random-effects model and presented as forest plots. Heterogeneity among studies was expressed as Q statistics and I2. Bias was assessed using the Newcastle Ottawa Scale for all identified observational studies. Publication bias was assessed with funnel plot analysis. RESULTS: We identified 28 studies involving 6053 patients with suspected or confirmed COVID-19. The overall pooled prevalence of VTE events was 20.7%. Male sex was associated with a higher risk of VTE events, whereas prior history of VTE, smoking, and cancer were not. VTE events were significantly higher in severely ill patients, mechanically ventilated patients, those requiring intensive care admission, and those with a low PaO2/FiO2 ratio (P/F ratio). Chronic comorbidities, including cardiovascular disease, heart failure, renal disease, and pulmonary disease, did not increase the risk of VTE events. Patients with VTE had higher leukocyte counts and higher levels of D-dimer, C-reactive protein, and procalcitonin. The occurrence of VTE was associated with increased length of stay but did not impact mortality. Therapeutic and prophylactic doses of anticoagulation were not protective against VTE. CONCLUSION: VTE in COVID-19 is associated with male gender and severe disease but not with traditional risk factors for VTE. The occurrence of VTE does not appear to be mitigated by either prophylactic or therapeutic anticoagulation. The occurrence of VTE in this population is associated with an increased length of stay but does not appear to impact mortality.


Тема - темы
COVID-19 , Venous Thromboembolism , Anticoagulants/therapeutic use , Blood Coagulation , COVID-19/complications , COVID-19/diagnosis , Humans , Male , SARS-CoV-2 , Venous Thromboembolism/diagnosis , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology
14.
Front Immunol ; 13: 837629, 2022.
Статья в английский | MEDLINE | ID: covidwho-1902997

Реферат

Both qualitative and quantitative platelet abnormalities are common in patients with coronavirus disease 2019 (COVID-19) and they correlate with clinical severity and mortality. Activated platelets contribute to the prothrombotic state in COVID-19 patients. Several groups have shown immune-mediated activation of platelets in critically ill COVID-19 patients. Vaccine-induced immune thrombotic thrombocytopenia is an autoimmune condition characterized by thrombocytopenia and life-threatening thrombotic events in the arterial and venous circulation. Although the initial trigger has yet to be determined, activation of platelets by immune complexes through Fc gamma RIIA results in platelet consumption and thrombosis. A better understanding of platelet activation in COVID-19 as well as in vaccine-induced thrombotic complications will have therapeutic implications. In this review, we focused on the role of immune-mediated platelet activation in thrombotic complications during COVID-19 infection and vaccine-induced immune thrombotic thrombocytopenia.


Тема - темы
Blood Platelets/physiology , COVID-19/immunology , Purpura, Thrombotic Thrombocytopenic/immunology , SARS-CoV-2/physiology , Animals , Blood Coagulation , Humans , Platelet Activation , Vaccination/adverse effects
15.
Saudi Med J ; 43(6): 541-550, 2022 Jun.
Статья в английский | MEDLINE | ID: covidwho-1903983

Реферат

OBJECTIVES: To reducing the risk of venous thromboembolic (VTE) events and subsequent mortality in covid-19 patients is still a matter of research. This systematic review and meta-analysis serve the purpose of comparing the mortality associated with the intensity of anticoagulation in patients admitted with covid-19. METHODS: A total of 7120 patients were recruited in 11 studies comparing using prophylactic anticoagulants against therapeutic anticoagulants. RESULTS: Our study showed that using prophylactic anticoagulants was associated with a 42% reduction in mortality compared to therapeutic anticoagulants (OR 0.58 (95% CI:0.676-0.499), p=0.000). Also, we assessed mortality in patients using no anticoagulants against using prophylactic anticoagulants. A total of 6069 patients were recruited in 4 studies in which 2 studies significantly favored prophylactic anticoagulants in terms of reducing mortality. Cumulatively, the meta-analysis showed that using prophylactic anticoagulants was associated with a 5% reduction in mortality but without any statistical significance: (OR 1.049 [95% CI 1.237 - 0.865]) (p=0.626). CONCLUSION: Our meta-analysis favors using prophylactic anticoagulation in covid-19 patients reduces all-cause mortality in comparison to therapeutic anticoagulation however the impact on mortality when compared with no anticoagulation was not significant.PROSPERO Number: CRD42021257320.


Тема - темы
COVID-19 , Thromboembolism , Venous Thromboembolism , Anticoagulants/therapeutic use , Blood Coagulation , COVID-19/drug therapy , Humans , SARS-CoV-2 , Thromboembolism/prevention & control , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
16.
Sci Rep ; 12(1): 637, 2022 01 12.
Статья в английский | MEDLINE | ID: covidwho-1900545

Реферат

Convalescent plasma is used to treat COVID-19. There are theoretical concerns about the impact of pro-coagulant factors in convalescent plasma on the coagulation cascade particularly among patients with severe COVID-19. The aim of this study was to evaluate the coagulation profile of COVID-19 convalescent plasma. Clotting times and coagulation factor assays were compared between fresh frozen plasma, COVID-19 convalescent plasma, and pathogen-reduced COVID-19 convalescent plasma. Measurements included prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, D-dimer, von Willebrand factor activity, von Willebrand factor antigen, coagulation factors II, V, VII-XII, protein S activity, protein C antigen, and alpha-2 plasmin inhibitor. Clotting times and coagulation factor assays were not different between COVID-19 convalescent plasma and fresh frozen plasma, except for protein C antigen. When compared to fresh frozen plasma and regular convalescent plasma, pathogen reduction treatment increased activated partial thromboplastin time and thrombin time, while reducing fibrinogen, coagulation factor II, V, VIII, IX, X, XI, XII, protein S activity, and alpha-2 plasmin inhibitor. The coagulation profiles of human COVID-19 convalescent plasma and standard fresh frozen plasma are not different. Pathogen reduced COVID-19 convalescent plasma is associated with reduction of coagulation factors and a slight prolongation of coagulation times, as anticipated. A key limitation of the study is that the COVID-19 disease course of the convalesced donors was not characterized.


Тема - темы
Blood Coagulation , COVID-19/blood , COVID-19/therapy , Adult , Blood Coagulation Tests , Blood Preservation , Blood Transfusion , Female , Humans , Immunization, Passive , Male , Middle Aged
17.
Zhonghua Jie He He Hu Xi Za Zhi ; 45(6): 588-592, 2022 Jun 12.
Статья в Китайский | MEDLINE | ID: covidwho-1879503

Реферат

In the past year, significant progress has been made in the field of venous thromboembolism (VTE) including risk assessment and anticoagulation prevention, diagnostic strategies and model exploration, new drug development and disease management. Particularly, major breakthroughs have been made in the prevention of VTE with FXI inhibitors and the prevention of novel coronavirus pneumonia with coagulation alterations and anticoagulation interventions. Here, we reviewed the progress and achievements in the field of VTE in the past year, aiming to provide evidence and ideas for the diagnosis, treatment and future studies of VTE.


Тема - темы
COVID-19 , Venous Thromboembolism , Anticoagulants/therapeutic use , Blood Coagulation , Humans , Risk Factors , SARS-CoV-2 , Venous Thromboembolism/diagnosis
18.
Circ J ; 86(7): 1137-1142, 2022 06 24.
Статья в английский | MEDLINE | ID: covidwho-1879294

Реферат

BACKGROUND: The potential benefit of therapeutic-dose anticoagulation for critically ill patients with coronavirus disease 2019 (COVID-19) is still controversial.Methods and Results: In the CLOT-COVID study, 225 patients with severe COVID-19 on admission requiring mechanical ventilation or extracorporeal membrane oxygenation were divided into patients with therapeutic-dose anticoagulation (N=110) and those with prophylactic-dose anticoagulation (N=115). There was no significant difference in the incidence of thrombosis between the groups (9.1% vs. 7.8%, P=0.73). CONCLUSIONS: Among a cohort of critically ill patients with COVID-19, approximately half received therapeutic-dose anticoagulation, although it did not show a potential benefit compared with prophylactic-dose anticoagulation.


Тема - темы
COVID-19 , Thrombosis , Anticoagulants/therapeutic use , Blood Coagulation , Critical Illness/therapy , Humans , Thrombosis/drug therapy , Thrombosis/etiology , Thrombosis/prevention & control
19.
Blood Adv ; 6(11): 3367-3377, 2022 06 14.
Статья в английский | MEDLINE | ID: covidwho-1879216

Реферат

Coagulation activation is a prominent feature of severe acute respiratory syndrome coronavirus 2 (COVID-19) infection. Activation of the contact system and intrinsic pathway has increasingly been implicated in the prothrombotic state observed in both sterile and infectious inflammatory conditions. We therefore sought to assess activation of the contact system and intrinsic pathway in individuals with COVID-19 infection. Baseline plasma levels of protease:serpin complexes indicative of activation of the contact and intrinsic pathways were measured in samples from inpatients with COVID-19 and healthy individuals. Cleaved kininogen, a surrogate for bradykinin release, was measured by enzyme-linked immunosorbent assay, and extrinsic pathway activation was assessed by microvesicle tissue factor-mediated factor Xa (FXa; MVTF) generation. Samples were collected within 24 hours of COVID-19 diagnosis. Thirty patients with COVID-19 and 30 age- and sex-matched controls were enrolled. Contact system and intrinsic pathway activation in COVID-19 was demonstrated by increased plasma levels of FXIIa:C1 esterase inhibitor (C1), kallikrein:C1, FXIa:C1, FXIa:α1-antitrypsin, and FIXa:antithrombin (AT). MVTF levels were also increased in patients with COVID-19. Because FIXa:AT levels were associated with both contact/intrinsic pathway complexes and MVTF, activation of FIX likely occurs through both contact/intrinsic and extrinsic pathways. Among the protease:serpin complexes measured, FIXa:AT complexes were uniquely associated with clinical indices of disease severity, specifically total length of hospitalization, length of intensive care unit stay, and extent of lung computed tomography changes. We conclude that the contact/intrinsic pathway may contribute to the pathogenesis of the prothrombotic state in COVID-19. Larger prospective studies are required to confirm whether FIXa:AT complexes are a clinically useful biomarker of adverse clinical outcomes.


Тема - темы
COVID-19 , Antithrombin III , Antithrombins , Blood Coagulation , COVID-19 Testing , Factor Xa , Humans , Kallikreins/metabolism
20.
Int J Hematol ; 115(6): 826-837, 2022 Jun.
Статья в английский | MEDLINE | ID: covidwho-1872733

Реферат

Coagulation and fibrinolytic mechanisms are enhanced in patients with coronavirus (COVID-19), but disturbances in the balance of both functions in COVID-19 patients remain unclear. We assessed global coagulation and fibrinolysis in plasma from 167 COVID-19 patients (mild/moderate/severe: 62/88/17, respectively) on admission using clot-fibrinolysis waveform analysis (CFWA). Maximum coagulation velocity (|min1|) and maximum fibrinolysis velocity (|FL-min1|) were expressed as ratios relative to normal plasma. Ten patients (6.0%) developed thrombosis, 5 (3.0%) had bleeding tendency, and 13 (7.8%) died during admission. FDP levels increased with severity of COVID-19 symptoms (mild/moderate/severe; median 2.7/4.9/9.9 µg/mL, respectively). The |min1| ratios were elevated in all categories (1.27/1.61/1.58) in keeping with enhanced coagulation potential, with significant differences between mild cases and moderate to severe cases. The |FL-min1| ratios were also elevated in all groups (1.19/1.39/1.40), reflecting enhanced fibrinolytic potential. These data identified coagulation dominance in moderate to severe cases, but balanced coagulation and fibrinolysis in mild cases. There were significant differences in FDP and TAT, but no significant differences in |min1| or |FL-min1| ratios, between patients with and without thrombosis. CFWA monitoring of coagulation and fibrinolysis dynamics could provide valuable data for understanding hemostatic changes and disease status in COVID-19 patients.


Тема - темы
COVID-19 , Thrombosis , Blood Coagulation , Fibrinolysis , Hemostasis , Humans , Thrombosis/etiology
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