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1.
Cancer has been shown to be an independent risk factor for the development of venous thromboembolism (VTE; deep vein thrombosis and pulmonary embolism). Thromboprophylaxis reduces the incidence of VTE in patients with cancer; however, active cancer places patients at high risk for recurrent VTE, necessitating extended prophylactic regimens. Extended prophylaxis in patients with cancer can be problematic because of increased risk for bleeding. Oral anticoagulants, such as warfarin, have been the standard of care for extended prophylaxis, but maintaining a clinically effective level of anticoagulation can be difficult because of a wide range of drug interactions, a narrow therapeutic window, and an increased risk of bleeding complications, particularly in patients with cancer. Recent evidence indicates that long-term prophylaxis with low-molecular-weight heparins (LMWHs) is an effective and safe alternative to oral anticoagulation in patients with VTE and cancer, reducing the risk for recurrent VTE by up to 52%. LMWHs can also be seen as cost-effective for long-term prophylaxis, because higher drug acquisition costs are offset by the potential for reduced hospital stays, reduced need for coagulation monitoring, and fewer bleeding complications. Some studies suggest that LMWHs may also have direct antitumor effects and improve survival rates, most notably in patients with non-metastatic disease. Further clinical research is needed to evaluate the potential survival benefits of LMWH therapy in patients with cancer.  相似文献   

2.
Venous thromboembolism (VTE) is a common complication in cancer patients that results in significant morbidity and mortality. Long-term treatment options for cancer patients who experience VTE include vitamin K antagonists (VKAs), low molecular weight heparins (LMWHs), and inferior vena caval (IVC) filters. Cancer patients have a two- to fourfold higher risk for experiencing recurrent VTE and major bleeding during chronic VKA therapy than patients without malignancies. Recent randomized clinical trials have shown that LMWHs rather than oral VKAs are preferred for initial chronic treatment of VTE in patients with advanced cancer. One factor potentially limiting the broader use of LMWH for chronic therapy in the United States is its higher acquisition cost. Efficacy, cost, drug availability, patient comorbidities, and concomitant medications all need to be considered when selecting chronic VTE therapy. Cancer patients with VTE should be treated for as long as their disease is active to minimize the incidence of recurrence. Use of IVC filters should generally be reserved for patients at high risk for recurrent VTE who have contraindications to anticoagulation. Several new anticoagulants are being investigated that promise greater therapeutic choices and potentially better outcomes for cancer patients with VTE.  相似文献   

3.
《Annals of oncology》2019,30(6):897-907
Anticoagulation for cancer-associated venous thromboembolism (VTE) can be challenging due to complications—including bleeding and potential drug–drug interactions with chemotherapy—associated with vitamin K antagonists and inconvenience of low-molecular-weight heparin (LMWH). Direct oral anticoagulants (DOACs) could partially overcome these issues, but until recently there were no large clinical trials assessing their efficacy and safety in cancer patients. This review summarizes clinical treatment guidelines, prior clinical and real-world evidence for anticoagulant choice, recent clinical trials assessing DOACs for cancer-associated VTE (i.e. Hokusai-VTE Cancer, SELECT-D, CARAVAGGIO, and ADAM VTE), and special considerations for DOAC use. Based on established data, clinical guidelines recommend patients with cancer-associated VTE receive LMWH treatment of at least 3–6 months. Nevertheless, LMWH is underused and associated with poor compliance and persistence in these patients relative to oral anticoagulants. Clinical data supporting DOAC use in cancer patients are becoming available. In Hokusai-VTE Cancer, edoxaban was noninferior to dalteparin for the composite of recurrent VTE and major bleeding (12.8% versus 13.5%), with numerically lower recurrent VTE (7.9% versus 11.3%) and significantly higher major bleeding (6.9% versus 4.0%); only patients with gastrointestinal cancer had significantly higher risk of bleeding with edoxaban. In SELECT-D, rivaroxaban had numerically lower VTE recurrence (4% versus 11%), comparable major bleeding (6% versus 4%), and numerically higher clinically relevant nonmajor bleeding (13% versus 4%) versus dalteparin. Most bleeding events were gastrointestinal or urologic; patients with esophageal/gastroesophageal cancer had higher rates of major bleeding with rivaroxaban (36% versus 11%). For comparison of apixaban versus dalteparin, CARAVAGGIO is ongoing, and preliminary results from ADAM VTE are favorable. This review concludes that DOACs appear to be reasonable alternatives to LMWH for treatment of cancer-associated VTE. In patients with gastrointestinal cancer, DOAC use should be considered on a case-by-case basis with consideration of the relative risks and benefits.  相似文献   

4.
The increased risk of thrombosis-related morbidity and mortality in patients with cancer remains, even in the face of anticoagulant therapy. Moreover, recurrent venous thromboembolism (VTE) complicates the management of cancer and adversely affects quality of life and survival. Until recently, initial therapy with unfractionated heparin or low-molecular-weight heparin (LMWH) followed by long-term therapy with an oral anticoagulant was the standard of care for the secondary prevention of acute thromboembolism in most patients. However, according to the results of the CLOT trial (Randomized Comparison of Low-Molecular-Weight Heparin Versus Oral Anticoagulant Therapy for the Prevention of Recurrent VTE in Patients With Cancer), extended LMWH therapy with dalteparin represents an alternative to standard oral anticoagulation. In terms of efficacy, the incidence of recurrent VTE in patients receiving dalteparin was half that of those receiving warfarin (27 of 336 patients vs 53 of 336 patients, respectively), for a 52% relative risk reduction. The incidence of major bleeding in this trial was not significantly different in the two arms. Although this LMWH regimen is supported by the latest practice guidelines of the American College of Chest Physicians, the question of whether long-term treatment with LMWH in cancer patients actually affects survival apart from the benefits of thromboprophylaxis remains to be answered.  相似文献   

5.
The treatment of venous thromboembolism (VTE) in patients with cancer is challenging because these patients have increased risks of both recurrent VTE and major bleeding, along with patient‐specific and cancer‐related factors that influence the approach to treatment. Historically, anticoagulant therapy with low‐molecular‐weight heparin (LMWH), given for both initial and long‐term treatment, has been the preferred approach recommended by practice guidelines. Most recently, the National Comprehensive Cancer Network (NCCN) guidelines indicate that the direct oral anticoagulants (DOACs) apixaban, edoxaban, or rivaroxaban are preferred for patients without gastric or gastroesophageal lesions. DOACs have been associated with an increased risk of major bleeding in patients with gastrointestinal and possibly genitourinary cancers, and DOACs should either not be used (especially in those with intact intraluminal tumors) or be used with caution in patients with these cancers. Fatal or life‐threatening bleeding occurs with similar frequency with DOACs or LMWH, and most major bleeding with DOACs can be managed with transfusion and standard measures. The patient''s willingness and ability to comply with LMWH injections, and their treatment preference, should also be considered. Patients with cancer who have VTE should be treated with anticoagulation for a minimum of 6 months. Anticoagulation should be continued indefinitely while cancer is active or under treatment or if there are persistent risk factors for recurrent VTE. This article summarizes the evidence from clinical trials of LMWH and DOACs that underpins the NCCN guideline recommendations, addresses several controversies and caveats regarding anticoagulant treatment, and offers evidence‐based, practical suggestions on patient selection for treatment with DOACs.Implications for PracticeSeveral randomized trials support the addition of direct oral anticoagulants (DOACs) to the therapeutic armamentarium for cancer‐associated venous thromboembolism (VTE). These agents come with unique risks and patient‐ and cancer‐specific variables that must be evaluated during the course of a patient''s cancer care. This narrative review discusses findings from clinical trials of low‐molecular‐weight heparin and DOACs for the treatment of cancer‐associated VTE, evidence that supports the recent National Comprehensive Cancer Network guideline recommendations. A personalized approach to treatment is proposed that addresses patient selection for treatment with DOACs, factors that influence efficacy and safety, controversies and caveats, and suggestions for their resolution in clinical practice.  相似文献   

6.
Patients with cancer have long been recognised to be at high risk of venous thromboembolism (VTE), although the condition remains under diagnosed and under treated in these patients. As a consequence, the morbidity and mortality due to deep venous thrombosis and pulmonary embolism remains unacceptably high in this group. Furthermore, the management of VTE in the presence of malignancy is complex, due both to the effects of the cancer itself and its treatments. Conventional long-term management of VTE involves the use of vitamin K antagonists (VKAs), such as warfarin, to reduce the risk of recurrence. However, this approach is associated with a range of practical difficulties including the need for regular laboratory monitoring, the potential for drug interactions, in addition to the risk of treatment resistance and bleeding in patients with cancer. Recent research indicates that the use of low molecular weight heparin (LMWH) therapy instead of VKAs may be beneficial in these patients. In particular, evidence from a large clinical trial of the LMWH dalteparin indicates that this agent offers an effective alternative to VKAs in the long-term management of VTE, that is free from the practical problems associated with the use of VKAs and without increasing the risk of bleeding.  相似文献   

7.
Patients undergoing major abdominal surgery for malignancy are at particularly high risk of developing VTE. Extra protection against this can be given to patients with cancer by using a higher dose of LMWH than normally used for prophylaxis, with no increase in bleeding complications. Despite thromboprophylaxis with high-dose LMWH for the first postoperative week, the rate of late VTE is estimated to be between 10% and 20%. A meta-analysis of two studies using dalteparin or enoxaparin has shown that prolonging thromboprophylaxis for a further 3 weeks significantly reduces the risk of late occurring VTE by 62%. Thromboprophylaxis with LMWH for at least one month should be considered in patients undergoing surgery for malignant disease.  相似文献   

8.
The risk of venous thromboembolism (VTE) is increased in association with malignancy, and has a potential to produce significant morbidity and mortality. Treatment of such patients with anticoagulants is associated with both benefit and a high rate of complications. In the early phase, the treatment is usually achieved with low molecular weight heparin (LMWH), which has a number of advantages over unfractionated heparin (UFH): once or twice daily administration, no necessary laboratory monitoring, lesser risk of bleeding and no drugs interactions. Nevertheless, the UFH is the anticoagulant of choice when a rapid anticoagulant effect or stop of anticoagulant effect is required, in the treatment of massive pulmonary embolism or severe renal insufficiency. Prolonged anticoagulation with LMWH (over 3 or 6 months) appears to be beneficial on survival for such patients. The subject of anticoagulation in patients with primary or secondary brain tumours is controversial. The long-term anticoagulation mainly use LMWH or vitamin K antagonist. The last ones are more difficult to use because of an unpredictable response with higher rate of recurrence and bleeding. The optimal duration of treatment is not known but the patients should be treated for at least 6 months, even at least 12 months after a second episode of venous thromboembolism. On the primary prevention in high-risk surgical oncology, the LMWH are at least as effective and safer as UFH when the optimal dose was administered. For the medical patients, the use of prophylactic anticoagulant treatment is less clear except the patients who are bedridden for prolonged periods of time. For the secondary prevention, the LMWH seems to be more effective over vitamin K antagonists. For these patients, the anticoagulant therapy is recommended indefinitely or until cancer is resolved.  相似文献   

9.
Background  Venous thromboembolism (VTE) is one of the most common complications in cancer patients. It is not only associated with both reduced survival and a high number of recurrences, but an idiopathic VTE also increases the likelihood of a cancer diagnosis. Methods  Between January 2000 and October 2005 we reviewed the medical history of 88 patients who were admitted to a tertiary hospital and presented both a diagnosis of VTE and any type of tumour. The information collected included the type of tumour, the temporal association between tumour diagnosis and VTE, anticoagulation treatment applied and percentage of recurrences. Results  Ten patients (11.4%) presented the VTE prior to the cancer diagnosis; only half of them underwent a posterior tumour screening routine. Fifteen patients (17%) were diagnosed simultaneously and 71% presented the VTE after the tumour was detected. In 47 patients (53.4%) no risk factors for VTEs were detected. Twenty-nine patients (31.7%) presented a recurrent VTE, mainly during chemotherapy treatment (66%). Less than half of the patients (47.57%) were receiving treatment with low-molecular-weight heparins (LMWH). Conclusions  Idiopathic VTEs may be the first manifestation of an occult neoplasia, but tumour screening is scheduled in only a few patients. Regarding the high incidence of recurrent VTE in cancer populations, a high percentage is attributed to the underuse of LMWH, whose efficacy in preventing recurrent phenomena is superior to oral dicumarinics.  相似文献   

10.
《Bulletin du cancer》2014,101(3):295-301
Low-molecular-weight heparins (LMWH) are the reference curative treatment of venous thromboembolism (VTE) in patients with cancer. All international guidelines recommend the long-term use of LMWH given their demonstrated superiority compared to vitamin-K antagonists (VKA) in reducing VTE recurrence in this patient population without increased risk of bleeding. However, several studies consistently show a lack of adherence to treatment recommendations, which are applied at the very best in 50% of cases. This results in a loss of chance for patients with fragile prognosis and in whom VTE represents the second cause of death. Given the expected benefit and the increased VTE prevalence in patients with cancer, full awareness is necessary to implement programs aiming at improving the therapeutic management of cancer-associated VTE. This requires multidisciplinary consideration by qualified physicians involved in the management of patients with cancer-associated VTE such as oncologists, internists and those specialized in vascular disease and hemostasis.  相似文献   

11.
The occurrence of thromboembolism in patients with cancer complicates their management. Patients with cancer who have established venous thrombosis are at increased risk of recurrent venous thromboembolism and anticoagulant-associated bleeding compared with non-cancer patients. Low-molecular-weight heparins have largely replaced unfractionated heparin as the initial treatment for acute thrombosis and have the advantage that they can be administered at home. The use of oral anticoagulant for the long-term secondary prevention of recurrent venous thromboembolism can be problematic in the cancer patient due to unpredictable changes in the dose response because of poor nutrition, infection, concomitant medications and impaired hepatic function. A large randomised clinical trial has shown that 6 months of treatment with the low-molecular-weight heparin dalteparin in place of 6 months of oral anticoagulant therapy significantly reduces the risk of recurrent thrombosis (50% reduction in risk; p = 0.0017) in cancer patients without an increase in bleeding.  相似文献   

12.
静脉血栓栓塞(VTE)是恶性肿瘤患者常见并发症,是仅次于肿瘤本身引起患者死亡的第二位原因。血栓有时可作为隐匿性癌的初始表现。血栓形成参与了肿瘤的进展、血管生成和转移等机制。恶性肿瘤患者合并血栓栓塞不仅增加治疗难度,而且降低患者的生存质量并缩短生存时间。抗凝治疗不仅能有效的治疗血栓,而且具有一定的抗肿瘤作用。低分子肝素(LMWH)作为预防和治疗静脉血栓栓塞有效的和安全的首选药物,其优点包括延长生存时间和改善生活质量,减少静脉血栓栓塞的发生率。推荐在院的及接受手术治疗的肿瘤患者预防性使用LMWH。LMWH应作为已确诊的和存在再发可能的VTE的肿瘤患者的一线治疗。  相似文献   

13.
恶性肿瘤与静脉血栓栓塞的研究进展   总被引:1,自引:0,他引:1  
静脉血栓栓塞(VTE)是恶性肿瘤患者常见并发症,是仅次于肿瘤本身引起患者死亡的第二位原因。血栓有时可作为隐匿性癌的初始表现。血栓形成参与了肿瘤的进展、血管生成和转移等机制。恶性肿瘤患者合并血栓栓塞不仅增加治疗难度,而且降低患者的生存质量并缩短生存时间。抗凝治疗不仅能有效的治疗血栓,而且具有一定的抗肿瘤作用。低分子肝素(LMWH)作为预防和治疗静脉血栓栓塞有效的和安全的首选药物,其优点包括延长生存时间和改善生活质量,减少静脉血栓栓塞的发生率。推荐在院的及接受手术治疗的肿瘤患者预防性使用LMWH。LMWH应作为已确诊的和存在再发可能的VTE的肿瘤患者的一线治疗。  相似文献   

14.
Cancer patients are at increased risk of thromboembolic complications, which are commonly referred to as Trousseau’s syndrome. Besides the potentially dramatic effects of the tumor on the coagulation and fibrinolytic systems, various supportive measures and more specific cancer treatments, such as surgery or chemotherapy contribute to the pathophysiology of cancer-associated venous thromboembolism (VTE). Clinical trials have shown that long-term therapy with low-molecular-weight heparin (LMWH) is superior to secondary prophylaxis with vitamin K antagonists in the treatment of patients with cancer-associated VTE. Based on currently available clinical evidence it is not clear which cancer patient should be offered primary thromboprophylaxis with LMWH. In this respect, the individual risk profile which is substantially influenced by the general condition of the patient and possible co-morbidities have to be taken into account. Recent experimental and clinical studies have suggested that LMWH affects tumor biology at various levels and may thus be potentially beneficial as an adjunct in cancer therapy.  相似文献   

15.
Opinion statement Venous thromboembolic disease (VTE) is a common complication of malignancies affecting the central nervous system (CNS), both in the perioperative period and throughout the disease course. Until recently, the perceived risk of intracranial hemorrhage in patients with CNS malignancies was felt to be a relative contraindication to systemic anticoagulation, and most patients were managed with nonpharmacologic methods in both the prophylactic and treatment setting. However, several studies of the safety and efficacy of anticoagulation in both neurosurgical and cancer patients have challenged the previous dogma, and routine use of unfractionated heparin or low molecular weight heparin (LMWH) for VTE prophylaxis in patients undergoing craniotomy for CNS malignancy is recommended. Likewise, treatment of established VTE in this population with heparins is recommended, at least initially, followed by long-term treatment either with heparin or oral warfarin. Complications of inferior vena cava (IVC) filters, used as an alternative to systemic anticoagulation, appear to be more common in brain tumor patients with VTE, lending further support to treatment with systemic anticoagulation when possible. We advocate a multimodality approach utilizing compression stockings, intermittent compression devices, and heparin in the perioperative setting as the best proven method to reduce the risk of VTE. In the absence of a strict contraindication to systemic anticoagulation, such as previous intracranial hemorrhage or profound thrombocytopenia, LMWH is recommended in brain tumor patients with newly diagnosed VTE, followed by long-term warfarin or LMWH.  相似文献   

16.
The association between cancer and venous thromboembolism (VTE) is well established. Importantly, VTE is a significant cause of mortality in cancer patients. Although long-term warfarin (Coumadin(trade mark); Bristol-Myers Squibb; New York, NY) therapy is the mainstay of treatment for cancer patients with VTE, there are many practical problems with its use in this population. In particular, achieving therapeutic drug levels is difficult in cancer patients due to the increased risk of drug interactions, malnutrition, vomiting, and liver dysfunction in these patients. Moreover, cancer patients are at an increased risk of adverse effects of warfarin therapy. In contrast, low-molecular-weight heparins (LMWHs) are associated with a lower risk of adverse events compared with warfarin in patients with cancer. These agents also offer practical advantages compared with warfarin, including more predictable anticoagulant effects and ease of administration in addition to possible antineoplastic effects. Several LMWHs have demonstrated superior efficacy to warfarin in the secondary prevention of VTE. In particular, the LMWH, dalteparin (Fragmin; Pfizer; New York, NY), has recently been shown to have superior efficacy to warfarin in a large trial of patients with cancer and VTE without increasing the risk of bleeding. A randomized trial of dalteparin has also shown improved response rates and survival in patients with small cell lung cancer. In view of the availability of more effective and reliable alternatives to warfarin therapy in cancer patients, it is appropriate to reassess the role of warfarin therapy in patients with cancer and VTE. Further evaluation of the LMWHs for effects on cancer outcome is indicated.  相似文献   

17.

Background.

Evidence-based treatment guidelines recommend low molecular weight heparin (LMWH) monotherapy for cancer-associated venous thromboembolism (VTE). This analysis assessed the first-line treatment strategies for VTE in patients with advanced solid tumors.

Methods.

Using administrative data from advanced lung, prostate, colon, or breast cancer patients diagnosed between January 2000 and December 2007 at four HMOs with integrated delivery systems, patients with an inpatient or outpatient VTE diagnosed within 2 years after cancer diagnosis and an outpatient purchase of warfarin, LMWH, and/or fondaparinux anticoagulant within 7 days of the VTE diagnosis were identified. First-line outpatient VTE pharmacological treatment and factors independently associated with receipt/non-receipt of LMWH monotherapy were assessed.

Results.

Overall, 25% of the 1,089 eligible patients received LMWH monotherapy as primary VTE treatment. The percentage increased steadily over time from 18% among patients diagnosed in 2000 to 31% among those diagnosed in 2007. Factors associated with LMWH monotherapy included VTE diagnosis year, chemotherapy within 60 days prior to VTE diagnosis, history of VTE prior to cancer diagnosis, and invasive surgery in the 90 days following VTE diagnosis. Colorectal and prostate cancer patients versus lung cancer patients and stage III versus stage IV patients were less likely to be treated with LMWH monotherapy.

Conclusions.

Adoption of LMWH monotherapy as initial treatment for cancer-associated VTE was low but increased steadily over the study period. Future studies should explore reasons underlying the underutilization of this preferred evidence-based treatment as well as the comparative effectiveness of LMWH versus warfarin-based anticoagulation in real-world cancer patients with VTE.  相似文献   

18.
Venous thromboembolism (VTE) constitutes an important health problem in developed countries. Owing to their underlying malignancies, people with cancer are at particularly high risk of VTE. The level of this risk is influenced by several factors, including type of cancer and the presence or absence of metastases. However, different types of oncology treatment can also further increase the thrombotic risk. Consequently, primary and secondary thromboprophylaxis in people with cancer should be considered as part of any integrated oncology treatment. Moreover, recent exciting studies have suggested that low molecular weight heparins (LMWH) may also influence overall survival in people with cancer. Clearly, these findings raise the likelihood that the use of LMWH in oncology practice may increase significantly in the near future. However, it is important to appreciate that the use of thromboprophylaxis in people with cancer is complicated by a number of specific problems. In this overview, we have systematically addressed the difficult clinical issues that are involved in the selection of appropriate primary and secondary thromboprophylaxis for people with cancer.  相似文献   

19.
Gary H. Lyman MD  MPH 《Cancer》2009,115(24):5637-5650
Venous thromboembolism (VTE) is a frequent complication of cancer and cancer treatment and is associated with multiple clinical consequences, including recurrent VTE, bleeding, and an increase in the risk of death. Although the risks associated with VTE have been well recognized in surgical cancer patients, there is also considerable and increasing risk in medical cancer patients. VTE risk factors in medical cancer patients include the type and stage of cancer, major comorbid illnesses, current hospitalization, active chemotherapy, hormone therapy, and antiangiogenic agents. Low‐molecular‐weight heparins (LMWHs) are recommended commonly for the prevention of VTE in hospitalized cancer patients and in higher risk ambulatory cancer patients because of their favorable risk‐to‐benefit profile. These agents have demonstrated effectiveness in both the primary and secondary prevention of VTE in medical cancer patients. Extended‐duration anticoagulant therapy is often recommended to reduce the risk of VTE recurrence in patients with cancer. LMWHs are often used for long‐term prophylaxis because of a reduced need for coagulation monitoring, few major bleeding episodes, and once‐daily dosing. Despite clinical and practical benefits, a substantial proportion of medical cancer patients do not receive VTE prophylaxis. To improve the appropriate prevention and treatment of VTE in cancer patients, guidelines have been published recently by the American Society of Clinical Oncology and the National Comprehensive Cancer Network. Widespread dissemination and application of these guidelines are encouraged to improve the appropriate use of these agents and to improve clinical outcomes in medical cancer patients at risk for VTE and its complications. Cancer 2009. © 2009 American Cancer Society.  相似文献   

20.
AIMS: To review the epidemiology and pathogenesis of venous thromboembolism (VTE) in surgical cancer patients, in addition to the use of thromboprophylaxis in major abdominal surgery, such as low-molecular-weight heparin (LMWH) and fondaparinux. METHODS: Systematic review of the literature, focussing on risk factors for VTE, parenteral methods of thromboprophylaxis, approaches to prolonged prophylaxis, and effects on patient survival. FINDINGS: Patients with cancer undergoing abdominal surgery are at substantially higher risk for VTE than patients without cancer. Furthermore, prolonged thromboprophylaxis for up to 4 weeks is more effective than short-term administration in these high-risk patients. The concurrent use of graduated compression stockings has a synergistic effect on the reduction in VTE risk. CONCLUSIONS: Thromboprophylaxis with LMWH has been shown to minimise the incidence of thromboembolic events, and is a well-established therapy worldwide. The American College of Chest Physicians recommends the routine use of thromboprophylaxis, with LMWH or unfractionated heparin, in patients with cancer who are undergoing surgical procedures, and the appropriate use of these thromboprophylactic agents has significant implications for the clinical care and quality of life of surgical patients with cancer.  相似文献   

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