Denosumab

denosumab
  • 文章类型: Journal Article
    目的:本研究的目的是确定骨质疏松症药物对基于机会性CT的Hounsfield单位(HU)的影响。
    方法:对脊柱和非脊柱手术患者进行回顾性分析,这些患者接受romosozumab治疗3~12个月,特立帕肽3至12个月,特立帕肽治疗>12个月,denosumab持续>12个月,或阿仑膦酸钠治疗>12个月。在L1-4椎体中测量HU。使用单因素方差分析比较5种治疗方案中HU的平均变化。
    结果:总计,包括318名患者(70%为女性),平均年龄69岁,平均BMI为27kg/m2。使用romosozumab治疗3至12个月后,平均HU改善(p<0.001)存在显着差异(n=32),特立帕肽3至12个月(n=30),特立帕肽治疗>12个月(n=44),denosumab>12个月(n=123),和阿仑膦酸钠持续>12个月(n=100)。用romosozumab治疗平均10.5个月显著增加平均HU26%,从基线85到107(p=0.012)。使用特立帕肽治疗>12个月(平均23个月)的患者平均HU改善25%,从106到132(p=0.039)。与平均基线HU相比,使用特立帕肽治疗3至12个月后,差异无统计学意义(110至119,p=0.48),denosumab>12个月(105到107,p=0.68),或阿仑膦酸钠持续>12个月(111至113,p=0.80)。
    结论:使用romosozumab治疗平均10.5个月和特立帕肽治疗平均23个月的患者通过基于CT的机会性HU估计,脊柱骨矿物质密度改善。鉴于有效治疗的持续时间较短,romosozumab可能是优化骨质疏松患者的首选药物,为择期脊柱融合手术做准备。
    OBJECTIVE: The purpose of this study was to determine the effect of osteoporosis medications on opportunistic CT-based Hounsfield units (HU).
    METHODS: Spine and nonspine surgery patients were retrospectively identified who had been treated with romosozumab for 3 to 12 months, teriparatide for 3 to 12 months, teriparatide for > 12 months, denosumab for > 12 months, or alendronate for > 12 months. HU were measured in the L1-4 vertebral bodies. One-way ANOVA was used to compare the mean change in HU among the five treatment regimens.
    RESULTS: In total, 318 patients (70% women) were included, with a mean age of 69 years and mean BMI of 27 kg/m2. There was a significant difference in mean HU improvement (p < 0.001) following treatment with romosozumab for 3 to 12 months (n = 32), teriparatide for 3 to 12 months (n = 30), teriparatide for > 12 months (n = 44), denosumab for > 12 months (n = 123), and alendronate for > 12 months (n = 100). Treatment with romosozumab for a mean of 10.5 months significantly increased the mean HU by 26%, from a baseline of 85 to 107 (p = 0.012). Patients treated with teriparatide for > 12 months (mean 23 months) experienced a mean HU improvement of 25%, from 106 to 132 (p = 0.039). Compared with the mean baseline HU, there was no significant difference after treatment with teriparatide for 3 to 12 months (110 to 119, p = 0.48), denosumab for > 12 months (105 to 107, p = 0.68), or alendronate for > 12 months (111 to 113, p = 0.80).
    CONCLUSIONS: Patients treated with romosozumab for a mean of 10.5 months and teriparatide for a mean of 23 months experienced improved spinal bone mineral density as estimated by CT-based opportunistic HU. Given the shorter duration of effective treatment, romosozumab may be the preferred medication for optimization of osteoporotic patients in preparation for elective spine fusion surgery.
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  • 文章类型: Journal Article
    骨巨细胞瘤(GCTB)是一种局部侵袭性中间骨肿瘤。Denosumab已在GCTB治疗中显示出有效性;然而,denosumab降级对不可切除的GCTB的益处尚未得到很好的讨论.本研究调查了地诺单抗降阶梯治疗GCTB的有效性和安全性。9例无法切除的GCTB或无法切除的GCTB患者的病历,他在冈山大学医院(冈山,日本)在2014年4月至2021年12月之间进行了回顾性审查。denosumab治疗间隔逐渐延长至每8、12和24周。评估了标准和降级的denosumab治疗期间的影像学变化和临床症状。标准4周治疗的中位数为12个月后,denosumab间隔逐渐降低。成像显示,每周4次治疗获得的溶骨性病变的再骨化在每周8次和每周12次治疗中得以维持。标准治疗后,骨外肿块显著减少,而在降级治疗期间肿瘤减少持续。在24周治疗期间,2名患者保持稳定,2例患者出现局部复发。在标准治疗下,临床症状显着改善,在降级治疗期间仍保持改善。有严重的不良事件,包括颌骨坏死(2例),非典型股骨骨折(1例)和GCTB恶变(1例)。总之,在不可切除的GCTB患者中,每周12次降级的denosumab治疗显示出作为维持治疗的临床益处,除了持续稳定的肿瘤控制和改善临床症状与标准治疗。也可以进行24周治疗,仔细注意检测局部复发。
    Giant cell tumor of bone (GCTB) is a locally aggressive intermediate bone tumor. Denosumab has shown effectiveness in GCTB treatment; however, the benefits of denosumab de-escalation for unresectable GCTB have not been well discussed. The present study investigated the efficacy and safety of denosumab de-escalation for GCTB. The medical records of 9 patients with unresectable GCTB or resectable GCTB not eligible for resection, who received de-escalated denosumab treatment at Okayama University Hospital (Okayama, Japan) between April 2014 and December 2021, were retrospectively reviewed. The denosumab treatment interval was gradually extended to every 8, 12 and 24 weeks. The radiographic changes and clinical symptoms during standard and de-escalated denosumab therapy were assessed. The denosumab interval was de-escalated after a median of 12 months of a standard 4-weekly treatment. Imaging showed that the re-ossification of osteolytic lesions obtained with the 4-weekly treatment were sustained with 8- and 12-weekly treatments. The extraskeletal masses reduced significantly with standard treatment, while tumor reduction was sustained during de-escalated treatment. During the 24-weekly treatment, 2 patients remained stable, while 2 patients developed local recurrence. The clinical symptoms improved significantly with standard treatment and remained improved during de-escalated treatment. There were severe adverse events including osteonecrosis of the jaw (2 patients), atypical femoral fracture (1 patient) and malignant transformation of GCTB (1 patient). In conclusion, 12-weekly de-escalated denosumab treatment showed clinical benefits as a maintenance treatment in patients with unresectable GCTB, in addition to sustained stable tumor control and improved clinical symptoms with standard treatment. A 24-weekly treatment can also be administered, with careful attention paid to detecting local recurrence.
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  • 文章类型: Journal Article
    目的:探讨经皮椎体强化术(PVA)后骨质疏松性椎体压缩骨折(OVCF)患者抗骨质疏松药物的使用情况和再骨折发生率,并评价PVA后使用Denosumab对患者的实际治疗效果。这项研究旨在为脊柱外科医生提供来自现实世界场景的经验见解,以增强OVCF患者骨骼健康的管理。
    方法:本回顾性队列研究基于来自美国MarketScan和Optum数据库的数据。纳入了在2013年1月至2020年3月期间接受PVA治疗OVCF的55-90岁女性患者,并从手术后当天开始随访。接受至少一个剂量的denosumab的患者被纳入denosumab队列,并根据他们是否接受第二剂量的denosumab进一步分为治疗组和治疗组,随访从指数日开始(第一次denosumab剂量后225天)。在这项研究中,非治疗组作为对照组.PVA后再断裂发生率,使用抗骨质疏松药物的患者在总研究人群中的比例,分析denosumab队列中指数日之后的再骨折发生率。
    结果:来自MarketScan和Optum数据库的13,451名和21,420名患者,分别,包括在内。在denosumab队列中,在指数日之后的3年内临床骨质疏松性骨折的累积发生率在治疗组明显低于非治疗组(MarketScan数据库:23.0%vs39.0%,p=0.002;Optum数据库:28.2%对40.0%,p=0.023)。在治疗组的临床椎体骨折的累积发生率也低于在非治疗组,在MarketScan数据库中存在显著差异(14.4%vs25.5%,p=0.002),并且在Optum数据库中发现了数字差异(20.2%对27.5%,p=0.084)。术后6个月使用抗骨质疏松药物的患者比例较低,只有大约7%的人使用denosumab,13%-15%的人口服双膦酸盐。
    结论:绝经后妇女再骨折率高,PVA后使用抗骨质疏松药物的比例低。PVA后继续denosumab治疗与骨质疏松和临床椎体骨折的风险较低相关。因此,denosumab可能是PVA术后骨质疏松症患者的治疗选择。
    OBJECTIVE: To investigate the use of anti-osteoporotic agents and refracture incidence in patients with osteoporotic vertebral compression fracture (OVCF) following percutaneous vertebral augmentation (PVA) and to evaluate the real-world treatment of patients using denosumab following PVA. This study aims to provide spine surgeons with empirical insights derived from real-world scenarios to enhance the management of bone health in OVCF patients.
    METHODS: This retrospective cohort study was based on data from the MarketScan and Optum databases from the USA. Female patients aged 55-90 years who underwent PVA for OVCF between January 2013 and March 2020 were included and followed up from the day after surgery. Patients who received at least one dose of denosumab were included in the denosumab cohort and were further divided into the on-treatment and off-treatment groups according to whether they received a second dose of denosumab, with follow-up beginning on the index day (225 days after the first denosumab dose). In this study, the off-treatment group was considered as the control group. Refracture incidence after PVA, the proportion of patients using anti-osteoporotic agents in the total study population, and refracture incidence after the index day in the denosumab cohort were analyzed.
    RESULTS: A total of 13,451 and 21,420 patients from the MarketScan and Optum databases, respectively, were included. In the denosumab cohort, the cumulative incidence of clinical osteoporotic fractures within 3 years after the index day was significantly lower in the on-treatment group than in the off-treatment group (MarketScan database: 23.0% vs 39.0%, p = 0.002; Optum database: 28.2% vs 40.0%, p = 0.023). The cumulative incidence of clinical vertebral fractures was also lower in the on-treatment group than in the off-treatment group, with a significant difference in the MarketScan database (14.4% vs 25.5%, p = 0.002) and a numerical difference was found in the Optum database (20.2% vs 27.5%, p = 0.084).The proportion of patients using anti-osteoporotic agents was low at 6 months postoperatively, with only approximately 7% using denosumab and 13%-15% taking oral bisphosphonates.
    CONCLUSIONS: Postmenopausal women have a high refracture rate and a low proportion of anti-osteoporotic drug use after PVA. Continued denosumab treatment after PVA is associated with a lower risk of osteoporotic and clinical vertebral fractures. Therefore, denosumab may be a treatment option for patients with osteoporosis after PVA.
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  • 文章类型: English Abstract
    Objective: This study investigated the efficacy and safety of denosumab (DENOS) versus zoledronic acid (ZOL) in the bone disease treatment of newly diagnosed multiple myeloma. Methods: The clinical data of 80 patients with myeloma bone disease (MBD) at the Fifth Medical Center of PLA General Hospital between March 1, 2021 and June 30, 2023 were retrospectively reviewed. Eighteen patients with severe renal impairment (SRI, endogenous creatinine clearance rate<30 ml/min) were treated with DENOS, and 62 non-SRI patients were divided into DENOS (30 patients) and ZOL group (32 patients) . Results: Hypocalcemia was observed in 26 (33%) patients, and 22 patients developed hypocalcemia during the first treatment course. The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group [20% (6/30) vs 13% (4/32), P=0.028]. The incidence of hypocalcemia in SRI was 89% (16/18). Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min was significantly associated with hypocalcemia after DENOS administration (P<0.001). After 1 month of antiresorptive (AR) drug application, the decrease in the serum β-C-terminal cross-linked carboxy-telopeptide of collagen type I concentrations of SRI and non-SRI patients in the DENOS group were significantly higher than that in the ZOL group (68% vs 59% vs 27%, P<0.001). The increase in serum procollagen type Ⅰ N-terminal propeptide concentrations of patients with or without SRI in the DENOS group were significantly higher than that in the ZOL group (34% vs 20% vs 11%, P<0.05). The level of intact parathyroid hormone in each group increased after AR drug treatment. None of the patients developed osteonecrosis of the jaw and renal adverse events, and no statistically significant differences in the overall response rate, complete remission and stringent complete remission rates were found among the groups (P>0.05), and the median PFS and OS time were not reached (P>0.05) . Conclusions: In the treatment of MBD, DENOS minimizes nephrotoxicity and has strong AR effect. Hypocalcemia is a common adverse event but is usually mild or moderate and manageable.
    目的: 探讨地舒单抗(DENOS)与唑来膦酸(ZOL)治疗新诊断多发性骨髓瘤骨病(MBD)的疗效及安全性。 方法: 回顾性分析2021年3月1日至2023年6月30日解放军总医院第五医学中心血液病医学部收治的80例新诊断MBD患者的临床资料。18例伴重度肾损害(SRI)患者[内生肌酐清除率(CrCl)<30 ml/min]均接受DENOS治疗,62例非SRI患者分为DENOS组(30例)和ZOL组(32例)。 结果: 80例MBD患者中26例(33%)发生低钙血症,22例发生于第1次用药后。非SRI患者中DENOS组低钙血症发生率高于ZOL组[20%(6/30)对13%(4/32),P=0.028],SRI患者低钙血症发生率为89%(16/18)。多因素分析显示,CrCl<30 ml/min与DENOS治疗后低钙血症相关(P<0.001)。抗骨吸收药物治疗1个月后,DENOS组SRI、非SRI患者血清Ⅰ型胶原交联羧基端肽β特殊序列降低率大于ZOL组(68%对59%对27%,P<0.001),DENOS组SRI、非SRI患者血清Ⅰ型原胶原氨基端前肽升高率大于ZOL组(34%对20%对11%,P<0.05)。抗骨吸收药物治疗后各组全段甲状旁腺激素升高。所有患者均未发生抗骨吸收药物相关颌骨坏死及肾脏不良事件,各组血液学总有效率、完全缓解率、严格意义的完全缓解率差异均无统计学意义(P值均>0.05),中位无进展生存及总生存时间均未达到。 结论: DENOS治疗MBD具有较强的抗骨吸收作用和低肾毒性,低钙血症是常见不良反应,多为轻中度且可控。.
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  • 文章类型: Journal Article
    背景:denosumab(Dmab)广泛用于治疗绝经后骨质疏松症。它的停药有时伴有多处椎骨骨折。Romosozumab(Rmab)尚未测试其预防反弹现象的能力。
    方法:我们介绍了一名68岁绝经后骨质疏松症女性患者的病例,该患者在接受Rmab治疗后出现多处椎体骨折。添加Rmab并不能预防新发反弹相关的椎骨骨折。患者停用Rmab,重新开始Dmab。六个月后,没有出现新的椎骨骨折,骨矿物质密度增加,骨转换标志物仍然受到抑制。
    结论:我们的临床案例说明了Rmab预防Dmab停药导致的多发性椎体骨折级联反应的有效性。我们认为,用Rmab治疗可能不足以防止这种现象。用Dmab治疗或可能与Dmab和Rmab联合治疗可能是另一种治疗选择。
    BACKGROUND: Denosumab (Dmab) is widely used for the treatment of post-menopausal osteoporosis. Its discontinuation is sometimes accompanied by multiple vertebral fractures. Romosozumab (Rmab) has not been tested for its ability to prevent the rebound phenomenon.
    METHODS: We present the case of a 68-year-old female patient with post-menopausal osteoporosis under treatment with Rmab who presented with multiple vertebral fractures after denosumab discontinuation. The addition of Rmab did not prevent new-onset rebound-associated vertebral fractures. The patient discontinued Rmab and Dmab was re-initiated. After six months, no new vertebral fractures occurred, bone mineral density increased and bone turnover markers remained suppressed.
    CONCLUSIONS: Our clinical case illustrates the effectiveness of Rmab to prevent the multiple vertebral fracture cascade attributable to discontinuation of Dmab. We believe that treatment with Rmab might not be enough to prevent this phenomenon. Treatment with Dmab or possibly combination treatment with Dmab and Rmab could be another treatment option.
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  • 文章类型: Journal Article
    软骨母细胞瘤转移,虽然罕见,代表骨肿瘤的临床上有意义且特别重要的方面。了解其流行病学特征,病理特征,和治疗方式,尽管频率不高,全面的患者管理势在必行。这篇综述旨在阐明流行病学,分子机制,诊断挑战,以及与软骨母细胞瘤转移相关的治疗策略。模式,预后因素,并通过对病例研究和临床报告的分析探讨治疗结果.值得注意的是,我们强调了旨在改善患者结局的新兴治疗观点.据我们所知,以前没有累积处理这些问题的审查,突出了现有学术文献中的显著差距。通过阐明软骨母细胞瘤转移的细微差别,这篇综述有助于提高该领域的知识,并为改善患者护理的临床决策提供信息.
    Chondroblastoma metastasis, though rare, represents a clinically significant and notably important aspect of bone tumors. Understanding its epidemiological characteristics, pathological features, and treatment modalities, despite its infrequency, is imperative for comprehensive patient management. This review aims to elucidate the epidemiology, molecular mechanisms, diagnostic challenges, and therapeutic strategies associated with chondroblastoma metastasis. The patterns, prognostic factors, and treatment outcomes were explored through an analysis of case studies and clinical reports. Notably, we highlighted emerging therapeutic perspectives aimed at improving patient outcomes. To the best of our knowledge, there has been no previous review addressing these matters cumulatively, highlighting a significant gap in the existing scholarly literature. By shedding light on the nuances of chondroblastoma metastasis, this review contributes to the advancement of knowledge in this field and informs clinical decision-making for improved patient care.
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  • 文章类型: Case Reports
    在这个案例报告中,描述了一种新的N-乙酰氨基半乳糖转移酶3纯合突变(c.782G>A;p.R261Q),其与高磷酸盐血症性家族性肿瘤钙质沉着/骨增生-高磷酸盐血症综合征相关.病人有肘部,骨盆,和下肢疼痛以及髋关节和鹰嘴区域的硬块。观察到无机磷(Pi)和C反应蛋白的水平升高。用常规药物治疗后,我们测试了denosumab,这减少了,但没有使Pi正常化。
    In this case report, a novel N-acetylgalactosaminyltransferase 3 homozygous mutation (c.782 G>A; p.R261Q) associated with hyperphosphatemic familial tumoral calcinosis/hyperostosis-hyperphosphatemia syndrome is described. The patient had elbow, pelvis, and lower limb pain and a hard mass in the hip and olecranon regions. Increased levels of inorganic phosphorus (Pi) and C-reactive protein were observed. After treating the patient with conventional drugs, we tested denosumab, which reduced but did not normalize the Pi.
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  • 文章类型: Journal Article
    使用FAERS数据库中的数据全面分析与Denosumab(Prolia)治疗骨质疏松症相关的ADR,并更好地了解Denosumab(Prolia)治疗的潜在风险和副作用。
    Denosumab(Prolia)的数据是从FAERS数据库收集的,涵盖了2010年第一季度至2023年第三季度的时期。不相称性分析是通过计算报告优势比(ROR),比例报告比率(PRR),和贝叶斯分析置信度传播神经网络(BCPNN)来检测正信号。
    完全,从FAERS数据库收集了17,985,365份报告,1,97,807份Denosumab(Prolia)报告被确定为“主要可疑(PS)”ADR。Denosumab(Prolia)诱导的ADR发生在27个器官系统中。同时保留了38个满足三种算法的显著不成比例PT。也会发生意外的显着ADR,例如骨密度异常和不动。大多数ADR发生在Denosumab(Prolia)开始后的前30天内。
    基于美国FAERS数据库,Denosumab(Prolia)的高频ADR是低钙血症,骨密度异常,湿疹,回弹效应,脊柱畸形,等。本药的临床应用应集中于这部分ADR。还应注意新发现的ADR,比如不动的,更年期症状,等。,避免更严重的后果。队列研究,更详细和全面的案例信息,需要进行长期的临床研究来确认这些结果,并进一步了解Denosumab(Prolia)的安全性.
    UNASSIGNED: To comprehensively analyze the ADRs associated with Denosumab (Prolia) in the treatment of osteoporosis using data from the FAERS database, and gain a better understanding of the potential risks and side effects of Denosumab (Prolia) therapy.
    UNASSIGNED: Data of Denosumab (Prolia) were collected from the FAERS database covering the period from first quarter of 2010 to the third quarter of 2023. Disproportionality analysis was performed by calculating the reporting odds ratios (ROR), proportional reporting ratio (PRR), and Bayesian analysis confidence propagation neural network (BCPNN) to detect positive signals.
    UNASSIGNED: Totally, 17,985,365 reports were collected from the FAERS database, 1,97,807 reports of Denosumab (Prolia) were identified as the \"primary suspected (PS)\" ADRs. Denosumab (Prolia) induced ADRs occurred in 27 organ systems. 38 significant disproportionality PTs satisfying with the three algorithms were retained at the same time. Unexpected significant ADRs such as bone density abnormal and immobile also occur. The majority of the ADRs occurred within the first 30 days after Denosumab (Prolia) initiation.
    UNASSIGNED: Based on the American FAERS database, the high frequency ADRs of Denosumab (Prolia) were hypocalcaemia, bone density abnormal, eczema, rebound effect, spinal deformity, etc. Clinical use of this drug should focus on this part of ADRs. Attention should also be paid to newly discovered ADRs, such as immobile, menopausal symptoms, etc., to avoid more serious consequences. Cohort studies, more detailed and comprehensive case information, and long-term clinical investigations are needed to confirm these results and to further understand the safety profile of Denosumab (Prolia).
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  • 文章类型: Case Reports
    动脉瘤性骨囊肿(ABCs)是侵袭性和良性肿瘤,主要影响儿童和青少年。ABCs的标准治疗过程包括手术切除或刮除,并进行骨移植或水泥以修复缺陷。Denosumab,抑制核κB配体受体激活剂的单克隆抗体,用于治疗骨质疏松症,骨转移,和骨骼巨细胞瘤。
    本案例研究详细介绍了一名女性患者的治疗方法,年龄22岁,患有胫骨远端复发性侵袭性ABC。患者最初使用刮宫和病变填充进行治疗。然而,9个月后观察到骨质溶解的复发,这导致随后的干预措施包括在多个疗程中进行无水酒精硬化治疗.然而,这些干预措施未能实现骨化。在手术和硬化治疗不成功之后,病人服用了denosumab,这导致了积极的回应。定期的影像学和临床随访显示骨化和疼痛减轻的显着改善。在12个月的治疗过程中,访问频率逐渐减少。Further,随访和监测显示了局部控制和长期治疗的有效性。
    本病例报告强调了denosumab在手术或硬化治疗失败后治疗复发性侵袭性ABCs的能力。
    UNASSIGNED: Aneurysmal bone cysts (ABCs) are aggressive and benign tumors that primarily affect children and adolescents. The standard course of treatment for ABCs involves surgical excision or curettage with a bone transplant or cement to repair the deficiency. Denosumab, a monoclonal antibody that inhibits receptor activator of nuclear kappa B ligand, is used to treat osteoporosis, skeletal metastasis, and giant cell tumors of the bones.
    UNASSIGNED: This case study details the therapeutic treatment of a female patient, age 22, who had a recurring aggressive ABC of the distal tibia. The patient was initially treated using curettage and lesion filling. However, recurrence of the osteolysis was observed 9 months later that led to subsequent interventions involving absolute alcohol sclerotherapy in multiple sessions. However, these interventions failed to achieve ossification. Following unsuccessful surgical and sclerotherapy treatments, the patient was administered denosumab, which led to a positive response. Regular radiographic and clinical follow-up demonstrated significant improvements in ossification and pain reduction. During the course of the 12-month treatment, the frequency of visits was gradually reduced. Further, follow-up and monitoring revealed the effectiveness of the local control and long-term treatment.
    UNASSIGNED: This case report highlights the ability of denosumab to manage recurrent aggressive ABCs after surgical or sclerotherapy failure.
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