Fries D.


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A Snapshot of Coagulopathy After Cardiopulmonary Bypass.

Tue, 19/07/2016 - 1:16pm

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A Snapshot of Coagulopathy After Cardiopulmonary Bypass.

Clin Appl Thromb Hemost. 2016 Jun 5;

Authors: Höfer J, Fries D, Solomon C, Velik-Salchner C, Ausserer J

Abstract
Cardiac surgery involving cardiopulmonary bypass (CPB) is often associated with important blood loss, allogeneic blood product usage, morbidity, and mortality. Coagulopathy during CPB is complex, and the current lack of uniformity for triggers and hemostatic agents has led to a wide variability in bleeding treatment. The aim of this review is to provide a simplified picture of the data available on patients' coagulation status at the end of CPB in order to provide relevant information for the development of tailored transfusion algorithms. A nonsystematic literature review was carried out to identify changes in coagulation parameters during CPB. Both prothrombin time and activated partial thromboplastin time increased during CPB, by a median of 33.3% and 17.9%, respectively. However, there was marked variability across the published studies, indicating these tests may be unreliable for guiding hemostatic therapy. Some thrombin generation (TG) parameters were affected, as indicated by a median increase in TG lag time of 55.0%, a decrease in TG peak of 17.5%, and only a slight decrease in endogenous thrombin potential of 7%. The most affected parameters were fibrinogen levels and platelet count/function. Both plasma fibrinogen concentration and FIBTEM maximum clot firmness decreased during CPB (median change of 36.4% and 33.3%, respectively) as did platelet count (44.5%) and platelet component (34.2%). This review provides initial information regarding changes in coagulation parameters during CPB but highlights the variability in the reported results. Further studies are warranted to guide physicians on the parameters most appropriate to guide hemostatic therapy.

PMID: 27268940 [PubMed - as supplied by publisher]

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Fibrinogen concentrate improves clot strength in patients with haematological malignancies requiring platelet transfusion.

Tue, 19/07/2016 - 1:16pm

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Fibrinogen concentrate improves clot strength in patients with haematological malignancies requiring platelet transfusion.

Transfus Med. 2016 May 30;

Authors: Munk-Andersen H, Schenk B, Larsen OH, Fries D, Fenger-Eriksen C

Abstract
BACKGROUND: Patients with bone marrow failure secondary to chemotherapy often develop thrombocytopenia and require platelet transfusion. Fibrinogen plays an important role in platelet aggregation and the establishment of the primary haemostatic plug.
OBJECTIVES: To compare the effects of in vivo platelet transfusion on clot firmness in thrombocytopenic patients with in vitro-performed fibrinogen concentrate substitution.
MATERIALS AND METHODS: Thirty patients with haematological malignancy admitted for platelet transfusion were included. Haemostatic effects from platelet transfusion and ex vivo addition of fibrinogen concentrate at three different doses were evaluated by thromboelastometry, with clot firmness as the primary endpoint (A30 ExTEM assay). Secondary endpoints were other thromboelastometry parameters, thrombin generation parameters, activated partial thromboplastin time (APTT), prothrombin time PT, fibrinogen and factor XIII levels and a clinical bleeding score.
RESULTS: Twenty patients (66%) had clinical bleeding signs by prior to transfusion. Platelets increased from 17 (range, 1-109) to 40 (range 2-139) × 10(9)  L(-1) following transfusion, with a median corrected count increment of 16·7 (range, 0·8-43·5). The A30 value increased significantly by platelet transfusion from 35 ± 11 to 47 ± 10 mm, with no changes in thrombin generation. Fibrinogen concentrate dose-dependently increased A 30 (to 43 ± 10, 49 ± 9 and 50 ± 9 mm, respectively) and reduced parameters of thrombin generation at high doses. Platelet transfusion, together with fibrinogen concentrate, further increased clot firmness. APTT and PT were within normal range, whereas fibrinogen levels were slightly elevated.
CONCLUSION: Fibrinogen concentrate increased clot firmness to the same degree as platelet transfusion in patients with low platelet count requiring platelet transfusion.

PMID: 27238953 [PubMed - as supplied by publisher]

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The endothelial glycocalyx and its disruption, protection and regeneration: a narrative review.

Tue, 19/07/2016 - 1:16pm

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The endothelial glycocalyx and its disruption, protection and regeneration: a narrative review.

Scand J Trauma Resusc Emerg Med. 2016;24:48

Authors: Schött U, Solomon C, Fries D, Bentzer P

Abstract
The glycocalyx is a carbohydrate-rich layer that lines the luminal side of the vascular endothelium. Its soluble components exist in a dynamic equilibrium with the bloodstream and play an important role in maintaining endothelial layer integrity. However, the glycocalyx can be easily damaged and is extremely vulnerable to insults from a variety of sources, including inflammation, trauma, haemorrhagic shock, hypovolemia and ischaemia-reperfusion. Damage to the glycocalyx commonly precedes further damage to the vascular endothelium. Preclinical research has identified a number of different factors capable of protecting or regenerating the glycocalyx. Initial investigations suggest that plasma may convey protective and regenerative effects. However, it remains unclear which exact components or properties of plasma are responsible for this protective effect. Studies have reported protective effects for several plasma proteins individually, including antithrombin, orosomucoid and albumin; the latter of which may be of particular interest, due to the high levels of albumin present in plasma. A further possibility is that plasma is simply a better intravascular volume expander than other resuscitation fluids. It has also been proposed that the protective effects are mediated indirectly via plasma resuscitation-induced changes in gene expression. Further work is needed to determine the importance of specific plasma proteins or other factors for glycocalyx protection, particularly in a clinical setting.

PMID: 27068016 [PubMed - in process]

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In search for in vivo methods to visualize clot forming in cut vessels and interrupted flow.

Tue, 19/07/2016 - 1:16pm

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In search for in vivo methods to visualize clot forming in cut vessels and interrupted flow.

Br J Anaesth. 2016 Apr;116(4):554-5

Authors: Solomon C, White NJ, Hochleitner G, Hermann M, Fries D

PMID: 26994233 [PubMed - in process]

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Biopsychronology: A Method Using Live Tissue Staining to Image Cell Function in the Kidney.

Tue, 19/07/2016 - 1:16pm

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Biopsychronology: A Method Using Live Tissue Staining to Image Cell Function in the Kidney.

Methods Mol Biol. 2016;1397:81-90

Authors: Ashraf MI, Fries D, Streif W, Aigner F, Hengster P, Troppmair J, Hermann M

Abstract
Methods to monitor the status of a graft prior to transplantation are highly desirable to avoid unnecessary surgical interventions and follow-up treatments and to optimize the clinical outcome as delayed graft function may lead to costly and lengthy follow-up treatments or even organ loss. As a promising step in this direction we present a method which combines the use of fine needle biopsies, the staining of living cells with dyes suitable to monitor mitochondrial status/cellular integrity, and live confocal real-time analysis.This approach provides information about the functional and structural intactness of an organ within a few minutes. To confirm the feasibility of this approach, we recently published a pilot study using rodent kidneys. The results demonstrated that this method is suitable to monitor organ damage caused by ischemia or short periods of reperfusion. This procedure required minimal time for sample preparation and data acquisition and is suitable for recording damage resulting from unphysiological stress to the organ.

PMID: 26676129 [PubMed - in process]

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Influence of Acute Normobaric Hypoxia on Hemostasis in Volunteers with and without Acute Mountain Sickness.

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Influence of Acute Normobaric Hypoxia on Hemostasis in Volunteers with and without Acute Mountain Sickness.

Biomed Res Int. 2015;2015:593938

Authors: Schaber M, Leichtfried V, Fries D, Wille M, Gatterer H, Faulhaber M, Würtinger P, Schobersberger W

Abstract
INTRODUCTION: The aim of the present study was to investigate whether a 12-hour exposure in a normobaric hypoxic chamber would induce changes in the hemostatic system and a procoagulant state in volunteers suffering from acute mountain sickness (AMS) and healthy controls.
MATERIALS AND METHODS: 37 healthy participants were passively exposed to 12.6% FiO2 (simulated altitude hypoxia of 4,500 m). AMS development was investigated by the Lake Louise Score (LLS). Prothrombin time, activated partial thromboplastin time, fibrinogen, and platelet count were measured and specific methods (i.e., thromboelastometry and a thrombin generation test) were used.
RESULTS: AMS prevalence was 62.2% (LLS cut off of 3). For the whole group, paired sample t-tests showed significant increase in the maximal concentration of generated thrombin. ROTEM measurements revealed a significant shortening of coagulation time and an increase of maximal clot firmness (InTEM test). A significant increase in maximum clot firmness could be shown (FibTEM test).
CONCLUSIONS: All significant changes in coagulation parameters after exposure remained within normal reference ranges. No differences with regard to measured parameters of the hemostatic system between AMS-positive and -negative subjects were observed. Therefore, the hypothesis of the acute activation of coagulation by hypoxia can be rejected.

PMID: 26451374 [PubMed - in process]

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Rediscovering the wound hematoma as a site of hemostasis during major arterial hemorrhage.

Tue, 19/07/2016 - 1:16pm

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Rediscovering the wound hematoma as a site of hemostasis during major arterial hemorrhage.

J Thromb Haemost. 2015 Dec;13(12):2202-9

Authors: White NJ, Mehic E, Wang X, Chien D, Lim E, St John AE, Stern SA, Mourad PD, Rieger M, Fries D, Martinowitz U

Abstract
BACKGROUND: Treatments for major internal bleeding after injury include permissive hypotension to decrease the rate of blood loss, intravenous infusion of plasma or clotting factors to improve clot formation, and rapid surgical hemostasis or arterial embolization to control bleeding vessels. Yet, little is known regarding major internal arterial hemostasis, or how these commonly used treatments might influence hemostasis.
OBJECTIVES: (i) To use a swine model of femoral artery bleeding to understand the perivascular hemostatic response to contained arterial hemorrhage. (ii) To directly confirm the association between hemodynamics and bleeding velocity. (iii) To observe the feasibility of delivering an activated clotting factor directly to internal sites of bleeding using a simplified angiographic approach.
METHODS: Ultrasound was used to measure bleeding velocity and in vivo clot formation by elastography in a swine model of contained femoral artery bleeding with fluid resuscitation. A swine model of internal pelvic and axillary artery hemorrhage was also used to demonstrate the feasibility of local delivery of an activated clotting factor.
RESULTS: In this model, clots formed slowly within the peri-wound hematoma, but eventually contained the bleeding. Central hemodynamics correlated positively with bleeding velocity. Infusion of recombinant human activated factor VII into the injured artery near the site of major internal hemorrhage in the pelvis and axillae was feasible.
CONCLUSIONS: We rediscovered that clot formation within the peri-wound hematoma is an integral component of hemostasis and a feasible target for the treatment of major internal bleeding using activated clotting factors delivered using a simplified angiographic approach.

PMID: 26414624 [PubMed - in process]

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Injectable hemostatic adjuncts in trauma: Fibrinogen and the FIinTIC study.

Tue, 19/07/2016 - 1:16pm

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Injectable hemostatic adjuncts in trauma: Fibrinogen and the FIinTIC study.

J Trauma Acute Care Surg. 2015 Jun;78(6 Suppl 1):S76-82

Authors: Maegele M, Zinser M, Schlimp C, Schöchl H, Fries D

PMID: 26002269 [PubMed - indexed for MEDLINE]

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Perioperatively acquired disorders of coagulation.

Tue, 19/07/2016 - 1:16pm

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Perioperatively acquired disorders of coagulation.

Curr Opin Anaesthesiol. 2015 Apr;28(2):113-22

Authors: Grottke O, Fries D, Nascimento B

Abstract
PURPOSE OF REVIEW: To provide an overview of acquired coagulopathies that can occur in various perioperative clinical settings. Also described are coagulation disturbances linked to antithrombotic medications and currently available strategies to reverse their antithrombotic effects in situations of severe hemorrhage.
RECENT FINDINGS: Recent studies highlight the link between low fibrinogen and decreased fibrin polymerization in the development of acquired coagulopathy. Particularly, fibrin(ogen) deficits are observable after cardiopulmonary bypass in cardiac surgery, on arrival at the emergency room in trauma patients, and with ongoing bleeding after child birth. Regarding antithrombotic therapy, although new oral anticoagulants offer the possibility of efficacy and relative safety compared with vitamin K antagonists, reversal of their anticoagulant effect with nonspecific agents, including prothrombin complex concentrate, has provided conflicting results. Specific antidotes, currently being developed, are not yet licensed for clinical use, but initial results are promising.
SUMMARY: Targeted hemostatic therapy aims to correct coagulopathies in specific clinical settings, and reduce the need for allogeneic transfusions, thus preventing massive transfusion and its deleterious outcomes. Although there are specific guidelines for reversing anticoagulation in patients treated with antiplatelet agents or warfarin, there is currently little evidence to advocate comprehensive recommendations to treat drug-induced coagulopathy associated with new oral anticoagulants.

PMID: 25734869 [PubMed - indexed for MEDLINE]

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Point-of-care testing in critically ill patients.

Tue, 19/07/2016 - 1:16pm

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Point-of-care testing in critically ill patients.

Semin Thromb Hemost. 2015 Feb;41(1):75-83

Authors: Fries D, Streif W

Abstract
Point-of-care (POC) testing in hemostasis has experienced a significant increase in the spectrum of available tests and the number of tests performed. Short turn-around time and observation of rapid changes in test results are facilitated. The quality control process in POC testing must encompass a preanalytic (collection), analytic (measurement), and postanalytic (clinical response) phase. Erroneous interpretation of findings and difficult quality controls can outweigh the advantages of POC testing.Only a limited number of hemostatic POC tests have proven useful so far: prothrombin time POC-monitoring of oral vitamin K antagonists; activated clotting time POC-monitoring of high-dose heparin therapy; platelet function analyzer (PFA; Siemens, Marburg, Germany) closure time (CT)-detection of von Willebrand disease and severe platelet function defects; whole blood aggregometry (WBA) Multiplate (Roche Diagnostics, Rotkreuz, Switzerland), and the VerifyNow system (Accumetrics, San Diego, CA)-detection of platelet dysfunction due to antiplatelet drugs; thromboelastography-continuous observation of clot formation and fibrinolysis. The use of various agonists in WBA and thromboelastography (TEG) requires some expertise. In experienced hands the PFA CT and WBA and TEG are recommended combinations.Application of POC testing depends strictly on whether it improves medical care and patient outcome. More POC test systems are in the research pipeline, but only a few will resist the ravages of time.

PMID: 25611850 [PubMed - indexed for MEDLINE]

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Efficacy of argatroban in critically ill patients with heparin resistance: a retrospective analysis.

Tue, 19/07/2016 - 1:16pm

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Efficacy of argatroban in critically ill patients with heparin resistance: a retrospective analysis.

Semin Thromb Hemost. 2015 Feb;41(1):61-7

Authors: Treichl B, Bachler M, Lorenz I, Friesenecker B, Oswald E, Schlimp CJ, Pedross F, Fries D

Abstract
The patients who do not respond even to very high dosages of heparin are assumed to suffer from heparin resistance. The aim of this study was to investigate whether critically ill patients suffering from heparin resistance generally have low antithrombin III (AT) levels, and if the direct thrombin inhibitor argatroban in that case can be an effective option to achieve prophylactic anticoagulation. The study was conducted at the Department for General and Surgical Intensive Care Medicine at the University Hospital Innsbruck. We retrospectively included all patients between 2008 and 2012, who received argatroban because of poor response to high-dosage heparin prophylaxis. The period under observation lasted in total for 9 days, 2 days of anticoagulation with unfractionated heparin (UFH) and 7 days with argatroban. The primary objective was to investigate if after 7 (± 1) hours of switching to argatroban the activated partial thromboplastin time (aPTT) levels were in a prophylactic range of 45 to 55 seconds. Further objectives were to assess the AT level, side effects such as bleeding or thromboembolism, platelet count, correlation between organ function and argatroban dose as well as any need for allogeneic blood products. The study population, consisting of 5 women and 15 men with a mean (± standard deviation, SD) age of 54.6 ± 16.3 years, differed in many clinical aspects. A median (interquartile range) heparin dose of 1,000, 819 to 1,125 IU/h was administered for 2 days and failed in providing a prophylactic anticoagulation measured by the aPTT. The mean aPTT level with heparin treatment was 38.5 seconds (± 4.7) its change within that period was not significant. After switching to argatroban, the mean increase of the aPTT levels in all study patients amounted from 38.5 to 48.3 seconds (p < 0.001). The rise in aPTT clearly reaches sufficient prophylactic anticoagulant levels. The maintenance of prophylactic aPTT levels was achieved over the period of 1 week. There was neither a correlation found between low-AT levels and occurrence of heparin resistance, nor between the simplified acute physiology score II and the administered argatroban dose (r = -0.224, p = 0.342). The results of the present study indicate that argatroban is an effective alternative therapy, especially in critically ill patients, to achieve prophylactic anticoagulation when heparin resistance occurs.

PMID: 25594496 [PubMed - indexed for MEDLINE]

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Usefulness of standard plasma coagulation tests in the management of perioperative coagulopathic bleeding: is there any evidence?

Tue, 19/07/2016 - 1:16pm

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Usefulness of standard plasma coagulation tests in the management of perioperative coagulopathic bleeding: is there any evidence?

Br J Anaesth. 2015 Feb;114(2):217-24

Authors: Haas T, Fries D, Tanaka KA, Asmis L, Curry NS, Schöchl H

Abstract
Standard laboratory coagulation tests (SLTs) such as prothrombin time/international normalized ratio or partial thromboplastin time are frequently used to assess coagulopathy and to guide haemostatic interventions. However, this has been challenged by numerous reports, including the current European guidelines for perioperative bleeding management, which question the utility and reliability of SLTs in this setting. Furthermore, the arbitrary definition of coagulopathy (i.e. SLTs are prolonged by more than 1.5-fold) has been questioned. The present study aims to review the evidence for the usefulness of SLTs to assess coagulopathy and to guide bleeding management in the perioperative and massive bleeding setting. Medline was searched for investigations using results of SLTs as a means to determine coagulopathy or to guide bleeding management, and the outcomes (i.e. blood loss, transfusion requirements, mortality) were reported. A total of 11 guidelines for management of massive bleeding or perioperative bleeding and 64 studies investigating the usefulness of SLTs in this setting were identified and were included for final data synthesis. Referenced evidence for the usefulness of SLTs was found in only three prospective trials, investigating a total of 108 patients (whereby microvascular bleeding was a rare finding). Furthermore, no data from randomized controlled trials support the use of SLTs. In contrast, numerous investigations have challenged the reliability of SLTs to assess coagulopathy or guide bleeding management. There is actually no sound evidence from well-designed studies that confirm the usefulness of SLTs for diagnosis of coagulopathy or to guide haemostatic therapy.

PMID: 25204698 [PubMed - indexed for MEDLINE]

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Biopsychronology: live confocal imaging of biopsies to assess organ function.

Tue, 19/07/2016 - 1:16pm

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Biopsychronology: live confocal imaging of biopsies to assess organ function.

Transpl Int. 2014 Aug;27(8):868-76

Authors: Ashraf MI, Fries D, Streif W, Aigner F, Hengster P, Troppmair J, Hermann M

Abstract
Prolonged ischemia (I) times caused by organ procurement and transport are main contributors to a decrease in organ function, which is further enhanced during reperfusion (R). This combined damage, referred to as ischemia-reperfusion injury (IRI), is a main contributor to delayed graft function, which leads to costly and lengthy follow-up treatments or even organ loss. Methods to monitor the status of a graft prior to transplantation are therefore highly desirable to optimize the clinical outcome. Here, we propose the use of fine needle biopsies, which are analyzed by real-time live confocal microscopy. Such a combination provides information about the functional and structural integrity of an organ within a few minutes. To confirm the feasibility of this approach, we obtained fine needle biopsies from rodent kidneys and exposed them to various stress conditions. Following the addition of a range of live stains, biopsies were monitored for mitochondrial function, cell viability, and tissue integrity using confocal live cell imaging. Our data demonstrate that this procedure requires minimal time for sample preparation and data acquisition and is well suitable to record organ damage resulting from unphysiological stress.

PMID: 24750326 [PubMed - indexed for MEDLINE]

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Effects of hiking at moderate and low altitude on cardiovascular parameters in male patients with metabolic syndrome: Austrian Moderate Altitude Study.

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Effects of hiking at moderate and low altitude on cardiovascular parameters in male patients with metabolic syndrome: Austrian Moderate Altitude Study.

Wilderness Environ Med. 2014 Sep;25(3):329-34

Authors: Neumayr G, Fries D, Mittermayer M, Humpeler E, Klingler A, Schobersberger W, Spiesberger R, Pokan R, Schmid P, Berent R

Abstract
OBJECTIVE: Physical activity is a cornerstone in therapy for patients with metabolic syndrome. Walking and hiking in a mountain scenery represents an ideal approach to make them move. The Austrian Moderate Altitude Study (AMAS) 2000 main study is a randomized controlled trial to investigate the cardiovascular effects of hiking at moderate altitude on patients with metabolic syndrome compared with a control group at low altitude, to assess a potential altitude-specific effect.
METHODS: Seventy-one male patients with metabolic syndrome were randomly assigned to a moderate altitude group (at 1700 m), with 36 participants, or to a low altitude group (at 200 m), with 35 participants. The 3-week vacation program included 12 hiking tours (4 per week, average duration 2.5 hours, intensity 55% to 65% of heart rate maximum). Physical parameters, performance capacity, 24-hour blood pressure, and heart rate profiles were obtained before, during, and after the stay.
RESULTS: In both groups, we found a significant mean weight loss of -3.13 kg; changes in performance capacity were minor. Systolic, diastolic, and mean arterial pressures and circadian heart rate profiles were significantly reduced in both groups, with no differences between them. Consequently, the pressure-rate product was reduced as well. All study participants tolerated the vacation well without any adverse events.
CONCLUSIONS: A 3-week hiking vacation at moderate or low altitude is safe for patients with metabolic syndrome and provides several improvements in their cardiovascular parameters. The cardiovascular benefits achieved are more likely to be the result of regular physical activity than the altitude-specific effect of a mountain environment.

PMID: 24731832 [PubMed - indexed for MEDLINE]

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