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1.
目的 探讨西罗莫司对肝移植术后钙调素类免疫抑制剂相关肾功能损害病人的肾功能的改善作用及安全性.方法 对11例肝移植术后出现钙调素类免疫抑制剂相关肾损害病人进行西罗莫司转换治疗,同时减少或完全停止钙调素类免疫抑制剂的应用.观察转换治疗后病人的肾功能、肝功能、急性排斥反应的发生及药物副作用等情况.结果 随访至今所有病人均存活,随访时间6~23个月.转化治疗后所有病人的肾功能均有不同程度的改善,6个月后血肌酐从(163.8±47.9)μmol/L降为(108.1±26.6)μtmol/L(P<0.05);除1例病人出现转氨酶升高,加用钙调素类免疫抑制剂后恢复正常外,其余病人肝功能无明显变化;药物副作用有高脂血症、贫血、溃疡型口疮等.结论 西罗莫司可以安全地应用于肝移植术后钙调素类免疫抑制剂相关肾功能损害的病人,改善病人的肾功能,同时对移植肝功能无明显影响.  相似文献   

2.
目的 探讨西罗莫司替换钙调磷酸酶抑制剂治疗肝移植术后肾功能不全的安全性和有效性.方法 北将肝移植术后发生肾功能不全的62例患者随机分为对照组和转换组.对照组29例,继续采用Tac(或CsA)、MMF及Pred的方案,血Tac(或CsA)浓度调整在治疗窗范围的下限;转换组33例,用SRL替换原方案中的Tac(或CsA),SRL的起始用量为2 mg/d,以后根据血SRL浓度及不良反应作相应调整,Tac(或CsA)减少至原用量的1/3~1/2,3 d后停用,MMF和Pred的用法不变.转换治疗后,对患者的肝肾功能、急性排斥反应及存活率进行随访监测,并观察患者在转换治疗期间发生的不良反应.结果 共有49例患者痊愈或者好转,13例死亡,对照组死亡8例,转换组死亡5例.随访9~51个月,转换组存活患者肝功能稳定,均未发生急性排斥反应.两组存活患者肾功能恢复后均未再出现反复,且转换组患者肾功能恢复时间明显缩短,治疗效果较好.转换组存活患者未发生严重不良反应,与对照组肺部感染发生率的比较,差异无统计学意义(P>0.05).结论 肝移植术后并发肾功能不全时,采用西罗莫司替换原免疫抑制方案中的CNI治疗是安全有效的.  相似文献   

3.
目的 探讨以钙调磷酸酶抑制剂(CNI)为主要免疫抑制方案的肾移植受者术后远期发生各类并发症时,应用两罗莫司(SRL)转换治疗方案的有效性及安全性.方法 肾移植术后远期38例采用CNI的患者因发生各类并发症而转换为SRL治疗,其中慢性移植肾肾病(CAN)17例、肿瘤10例、糖尿病3例、移植肾动脉狭窄(TRAS)球囊扩张术后2例、CNI毒性肝损害2例、丙型肝炎病毒(HCV)感染2例、面容改变1例及马兜铃酸肾病1例.SRL首剂负荷剂量为4~6 mg,维持剂量为1~2 mg/d,血SRL浓度维持在4~8 μg/L.使用SRL当天,CNI的用量减少一半,并在达到血SRL目标浓度的2~4周内逐渐撤除.转换后对患者随访了3~46个月,动态观察血常规、血肌酐、血糖、血脂及尿蛋白等指标,观察不良反应及监测急性排斥反应、移植肾功能丧失和肺部感染等并发症的发生.结果 转换治疗后.17例CAN患者中12例肾功能明显好转,血肌酐水平由转换前的(195.8±40.0)μmol/L降至(159.1±37.5)μmol/L(P<0.05);10例肿瘤患者中7例存活良好,2例发生肿瘤远处转移,1例死亡,血肌酐水平由转换前的(102.8±28.0)μmol/L降至转换后3个月的(77.8±25.6)μmol/L(P<0.05);2例TRAS球囊扩张术后患者肾功能恢复正常,TRAS未再发生;3例糖尿病患者血糖水平有所改善;2例CNI肝毒性者转换后肝功能恢复正常;2例HCV感染者肝功能稳定,病毒RNA拷贝水平下降;1例面容改变者症状明显好转;1例马兜铃酸肾病者未发生肿瘤.转换治疗后,所有患者均未发生急性排斥反应,不良反应主要为高脂血症3例、蛋白尿3例及白细胞减少1例.结论 肾移植术后采用CNI者发生CAN等远期并发症时,将CNI转换为西罗莫司治疗是安全,有效的.  相似文献   

4.
目的 总结出现钙调磷酸酶抑制剂(CNI)相关并发症的患者采用西罗莫司(SRL)单药转换治疗的体会.方法 肝移植患者14例,其中因CNI类药物致肾功能受损而行转换治疗者13例,因移植后血糖升高而行转换治疗者1例.转换治疗前,患者采用他克莫司(Tac)和糖皮质激素预防排斥反应,部分患者还加用霉酚酸酯.进行转换治疗后,初次给予SRL 4 mg/d;1周内给予SRL 1~2 mg/d,同时Tac的用量减至原来的一半;治疗1周后,根据血SRL浓度调整其剂量,维持血SRL浓度谷值为5~10μg/L,于转换治疗后1~2周完全撤除Tac.观察患者转换治疗后并发症的改善情况,肾功能、肝功能和急性排斥反应的发生情况及药物不良反应等.结果 转换治疗前,13例肾功能受损者的血肌酐为(158.3±41.6)μmol/L,随访结束时降低到(103.7±21.2)μmol/L;另1例血糖升高者在转换治疗后血糖得到有效控制,胰岛素用量由转换前的80 IU/L减少至24 IU/L.转换治疗后6个月内,14例中有2例(14.3%)发生急性排斥反应,治疗后均逆转.随访过程中,4例出现血脂升高,4例出现贫血或血小板减少,5例出现溃疡型口疮,但无患者因SRL不良反应而终止转换治疗.结论 肝移植术后出现CNI相关并发症的患者可以采用SRL单药转换治疗.  相似文献   

5.
目的探讨肝移植后并发他克莫司(FK506)所致肾功能损害时使用西罗莫司的有效性和安全性。方法13例患者肝移植术后均采用以FK506为主的免疫抑制方案预防排斥反应,发生肾功能损害后,停用FK506,或FK506用量减半,同时加用西罗莫司。治疗期间监测患者的血肌酐和尿素氮水平、血西罗莫司和,FK506浓度、肝脏功能及排斥反应的发生情况。结果所有患者在使用西罗莫司后肾脏功能迅速改善,血肌酐水平由(147.6±92.8)μmol/L降到(106.1±71.6)μmol/L(P <0.05);除1例发生急性排斥反应外,其余患者在治疗期间均未发生排斥反应;用药期间的不良反应有高脂血症(4例)及白细胞减少(2例),经对症处理好转。迄今随访4~15个月,肾功能未再出现异常。结论肝移植术后发生药物性肾功能损害时,使用西罗莫司治疗是安全和有效的。  相似文献   

6.
目的 观察慢性肾功能损伤的肝移植受者转换为西罗莫司治疗的疗效.方法 应用钙调磷酸酶抑制剂(CNI)并伴有慢性肾功能损伤的肝移植受者23例(其中19例应用他克莫司,4例应用环孢素A)转换为西罗莫司(SRL)治疗.SRL的起始剂量为4mg/d,次日为2 mg/d,应用高压液相色谱法测定全血SRL浓度,当血SRL浓度达5~8 μg/L后,停用CNI类药物,同时服用吗替麦考酚酯,1 g/d.记录受者入组前的基础血清肌酐(Cr)、肌酐清除率、肾小球滤过率(GFR),并分别于用药后第1、3、6、12和24个月时监测血SRL浓度、Cr、肌酐清除率、GFR,同时监测受者体重、血压、血细胞计数、肝功能和肝脏生化指标、血脂、尿蛋白.于用药后12个月时行肝脏穿刺活检确认有无排斥反应.结果 23例平均随访29.4个月,随访期内死亡2例,另21例于用药后1、3、6、12和24月时的Cr分别为(147.40±23.36)、(152.60±20.08)、(150.20±22.64)、(137.60±18.09)、(138.30±17.04)μmol/L,与Cr的基础值[(158.91±29.13)μmol/L]相比较,1、12、24个月时的差异有统计学意义(P<0.05).用药后1、3、6、12和24月时的肌酐清除率分别为(0.97±0.18)、(0.99±0.14)、(1.00±0.17)、(1.07±0.29)、(1.14±0.12)ml/s,与基础肌酐清除率[(0.91±0.14)ml/s]相比较,1、12、24个月时的差异有统计学意义(P<0.05).用药后1、3、6、12和24月时的GFR分别为(0.80±0.15)、(0.78±0.11)、(0.75±0.12)、(0.84±0.10)、(0.94±0.13),与基础GFR[(0.71±0.11)ml/s]相比较,1、12、24个月时的差异有统计学意义(P<0.05).应用SRL后第1、3、6、12和24个月时,Cr≤123μmol/L者所占的比例分别为38.1%、33.3%、28.6%、47.6%和52.4%.随访期内无受者发生排斥反应.结论 慢性肾功能损伤的肝移植受者转换为西罗莫司治疗可改善其肾功能.转换治疗未增加排斥反应的发生率.  相似文献   

7.
目的 探讨肝移植术后应用西罗莫司的抗排斥替换治疗效果。方法 回顾性分析50例肝移植或肝肾联合移植患者替换西罗莫司前后肝肾功能的改善情况及副作用和排斥反应的发生率。34例联合应用小剂量FK506,9例联合应用骁悉,2例联合应用新山地明。5例术后远期患者,替换前仅用FK506,替换后单用西罗莫司。结果 24例患者因肝功能不良而替换西罗莫司,其中16例(66.7%)肝功能明显改善;18例患者肾功能不良,其中13例(72.2%)在2个月内肾功能明显好转;8例患者因大剂量应用FK506但其浓度未达到6ng/ml而替换西罗莫司,移植术后肝肾功能恢复良好,未出现排斥反应。本组中应用西罗莫司后出现急性排斥反应3例(6%),改用FK506后急性排斥反应治愈。11例(22%)出现白细胞及血小板减少,9例(18%)胆固醇和甘油三酯升高。这些副作用均在西罗莫司应用1月后出现,当停药或对症处理后消失。本组中未出现肝动脉血栓形成、伤口愈合不良等并发症。结论 肝移植术后应用钙调磷酸酶抑制剂发生肝肾功能不良或不能达到理想药物浓度时,西罗莫司是有效的抗排斥替代药物。  相似文献   

8.
目的探讨西罗莫司联合常规免疫抑制方案治疗慢性移植物肾病(CAN)的安全性和有效性。方法回顾性分析1999年9月至2014年9月在温州医科大学附属第一医院肾移植术后发生CAN并采用西罗莫司联合常规免疫抑制方案治疗的56例患者资料。观察西罗莫司联合治疗前及治疗后1、3、6、12个月血清肌酐、肾小球滤过率、肝功能、血脂、血常规和尿常规等结果,观察联合治疗1年内急性排斥反应、感染和移植肾失功等发生情况。采用重复测量资料方差分析比较西罗莫司联合治疗前、后各时间点血清肌酐和肾小球滤过率。P0.05为差异有统计学意义。结果截至2015年12月,56例CAN患者接受西罗莫司联合治疗方案后平均随访时间(24±11)个月。西罗莫司联合治疗前患者平均血清肌酐和肾小球滤过率分别为(134±57)μmol/L和(61±21)m L/min,联合治疗后血清肌酐下降,肾小球滤过率上升。联合治疗后3、6、12个月与联合治疗前相比,差异均有统计学意义(P均0.05);56例患者联合治疗后12个月均未发生急性排斥反应、感染、死亡及移植肾失功。6例患者联合治疗前已出现新发恶性肿瘤,联合治疗后肿瘤未见明显转移或病情进展;其余患者未见新发恶性肿瘤。新发高脂血症35例,经对症治疗后缓解。无新发肝功能异常和新发血糖异常患者。结论西罗莫司联合常规免疫抑制方案治疗CAN患者是安全、有效的,可以改善移植肾功能,但需要注意患者血脂变化。  相似文献   

9.
目的 探讨肝癌肝移植受者术后采用以西罗莫司联合两剂激素为主的免疫抑制方案的安全性和有效性.方法 2004年3月至2006年10月间,共为92例超出米兰标准的中晚期肝癌患者施行了肝移植.其中89例纳入研究.前54例患者采用以他克莫司为主的免疫抑制方案,后35例患者采用以西罗莫司为主的新免疫抑制方案.术后对两组受者均进行了随访.随访时检测受者的肝肾功能、血糖和血脂水平等生化指标,监测受者感染、急性排斥反应、肿瘤复发、存活率及药物副作用等表现,并对两组免疫抑制方案的效果进行了分析和比较.结果 两组间1年肿瘤复发率、3个月内感染发牛率、术后1个月高血糖发生率及术后1年肾功能损害和高脂血症发生率的比较,差异均有统计学意义(P<0.05);其它指标的比较,无显著性差异.结论 肝癌肝移植受者采用以西罗莫司联合两剂激素为主的免疫抑制方案是安全和有效的.该方案在有效抑制排斥反应的同时可显著降低受者的肿瘤复发率,还可减少感染发生率、高血糖及.肾功能损害,但增加了高脂血症发生率.  相似文献   

10.
亲体部分肝移植治疗Wilson病20例报告   总被引:2,自引:0,他引:2  
目的探讨亲体部分肝移植治疗肝豆状核变性病 (Wilson病 )的价值。方法 2 0 0 1年 1月至 2 0 0 3年 10月 ,我院连续为 2 0例Wilson病患者成功施行亲体部分肝移植术 ,男性 8例 ,女性 12例 ,年龄 7~ 2 0岁 ,平均 11 1岁。 3例是暴发性肝功能衰竭 ,17例慢性进行性肝损害。供肝者为患者父亲或母亲。结果供受体手术顺利 ,术后 1个月肝功能和铜蓝蛋白恢复正常水平。 19例病人健康存活 ,1例术后 72d死于排斥反应。术后并发症包括 :醒状昏迷 1例 ,肝动脉血栓形成 1例 ,创面胆漏 1例 ,平均随访 18 9个月。结论亲体部分肝移植是治疗Wilson病并发肝功能衰竭的有效疗法。  相似文献   

11.
BACKGROUND: While providing potent immunosuppression for liver transplant recipients, calcineurin inhibitors (CNI) exhibit nephrotoxicity as a major side effect. The purpose of this study was to evaluate the safety and efficacy of conversion from CNI to sirolimus (SRL) among liver transplant recipients with CNI-induced chronic nephrotoxicity. METHODS: Between January 2004 and June 2005, we performed conversion in 16 recipients after a median period of 8.5 months after liver transplantation. The indication for conversion was CNI-related nephrotoxicity with a serum creatinine (sCr) value >132.6 umol/L. Renal function was measured before and after conversion to SRL. Clinical and laboratory data related to the clinical course of the patients were recorded to investigate the safety and efficacy of conversion. RESULTS: Sixteen patients were converted to SRL after developing nephrotoxicity. Their renal function improved gradually after conversion. The levels of sCr decreased significantly within the first 30 days (164.1 +/- 12.48 micromol/L to 130.1 +/- 5.573 micromol/L), and over the next 60 days after conversion (97.86 +/- 11.69 micromol/L to 90.7 +/- 8.95 micromol/L) (P < .01). Similarly, the mean glomerular filtration rate (GFR) increased significantly during the same period. Four recipients experienced hypercholesterolemia, 1 with ankle edema, and 1 with acute rejection. The median follow-up was 2.4 years. No patient discontinued SRL due to side effects. No patient needed dialysis or kidney transplantation during the study period. CONCLUSIONS: SRL is a safe, effective replacement agent as primary immunosuppressive therapy following withdrawal of CNIs in liver transplant recipients with CNI-induced chronic nephrotoxicity.  相似文献   

12.
Calcineurin inhibitors (CNIs) have become the cornerstone of immunosuppressive regimens following heart transplantation, but their use is associated with nephrotoxicity. We evaluated a CNI elimination protocol in 14 patients with renal impairment at 48.3 +/- 36.0 months after heart transplantation. The mean serum creatinine was 321 +/- 107 micromol/L; cyclosporine (n=13) or tacrolimus (n=1) was discontinued with sirolimus commenced immediately, initially aiming for a target trough level of 16 (12 to 20) ng/mL. If patients were not receiving mycophenolate (MMF) this was initiated at 1 g bid. The transfer period was covered with a tapering course of corticosteroids. In addition to monitoring clinical status, hematology, biochemistry, and sirolimus levels, graft function was assessed by echocardiography, ECG, and, where indicated, endomyocardial biopsy. Renal function improved in 12 patients (with 6 having a greater than 40% decrease in serum creatinine), remained unchanged in 1, and deteriorated in 1. Two patients who were converted at 15 and 139 months after transplantation experienced grade 3A rejection. One patient experienced a fall in ejection fraction without histologic evidence of rejection. Sirolimus was discontinued in three patients because of side effects: bone marrow suppression, presumed lymphocytic pneumonitis, and generalized acneform rash complicated by an axillary abcess; 50% of patients continue on sirolimus. In conclusion, withdrawal of CNIs after heart transplantation resulted in an improvement in renal function in most patients: 43% experienced a substantial improvement. CNI elimination protocols need to be refined to reduce the risk of breakthrough rejection and to minimize side effects while protecting renal function after heart transplantation.  相似文献   

13.
Reports on the use of sirolimus (SRL) in pancreas transplantation are still limited. The aim of this study was to evaluate the outcome of SRL conversion in pancreas transplant patients. Among 247 patients undergoing simultaneous kidney-pancreas or solitary pancreas transplantation, 33 (13%) were converted to SRL. The reasons for conversion were calcineurin inhibitors (CNI) nephrotoxicity (n = 24; 73%), severe neurotoxicity owing to CNI (n = 1; 3%), severe and/or recurrent acute rejection episodes (n = 7; 21%), gastrointestinal (GI) side effects of mycophenolate mofetil (MMF; n = 5; 15%), and hyperglycemia (n = 4; 12%).Before conversion, all patients were maintained on a CNI, MMF, and low-dose steroids. They were gradually converted to SRL associated with either CNI or MMF withdrawal. Sixty-three percent (n = 15) of patients who were converted owing to CNI nephrotoxicity, showed stable or improved renal function. At 12 months after conversion, serum creatinine levels were significantly decreased in this group (2.2 ± 0.5 vs 1.6 ± 0.3 mg/dL; P = .001) and C-peptide values increased (2.9 ± 1.1.1 vs 3.1 ± 1.3 nmol/L; P = .018). The only patient with leucoencephalopathy showed improved neurologic status after SRL conversion. All patients converted to SRL because of GI side effects of MMF showed improvements, and none of those converted because of hyperglycemia experienced improvement. There were no episodes of acute rejection after conversion.We concluded that conversion to SRL in pancreas transplantation should be considered an important alternative strategy, particularly for CNI nephrotoxicity and neurotoxicity, and in cases of severe diarrhea due to MMF.  相似文献   

14.
METHODS: We reviewed our prospectively maintained database of 2005 liver transplantations. Therapy was either started de novo or converted from calcineurin inhibitors (CNIs) to sirolimus as the main immunosuppressive agent for nephrotoxicity or rejection. Glomerular filtration rate (GFR) was determined with iodine 125-labeled sodium isthalamate (Glofil-125), and serum creatinine concentration was obtained before and 3 months after transplantation, and yearly in both groups. Sirolimus levels were 10 to 15 ng/mL in patients at less than 3 months after transplantations and 5 to 10 ng/mL in the remaining patients. All patients received mycophenolate mofetil as maintenance therapy. RESULTS: Data for 29 patients in the de novo group and 35 in the conversion group were reviewed. Patients in the de novo group demonstrated an acute cellular rejection rate of 17.2%, 40% of which were steroid resistant. In this group, 48.2% discontinuation of sirolimus was necessary because of adverse effects. Patients in the conversion group demonstrated an acute cellular rejection rate of 2.8% and a 34.3% rate of sirolimus discontinuation. Seventeen (56.7%) patients at 1 year and 8 (44.4%) patients at 2 years demonstrated continued improvement in GFR. In the conversion group, case-control analysis did not demonstrate a significant difference in GFR and serum creatinine concentration (P > .05) at 1 and 2 years after conversion. At the time of review, no patients in the conversion group required hemodialysis. CONCLUSIONS: Conversion to sirolimus therapy is an effective strategy in improving renal function in patients with CNI-induced nephrotoxicity and can be done without increased rejection. Most of our patients (65.7%) tolerated sirolimus conversion. Of these, 56.7% and 44.4% demonstrated continued increase in GFR with the CNI-free regimen at 1 and 2 years, respectively. Long-term, large-population, prospective, randomized, controlled studies should further validate these results.  相似文献   

15.
Renal failure, mainly due to calcineurin inhibitor (CNI) nephrotoxicity, is the most common complication following orthotopic liver transplantation (ltx). The aim of this study was to evaluate the incidence and course of renal failure in adult ltx patients. Severe acute renal failure in early postoperative period due to impaired hemodynamics and CNI nephrotoxicity, occurred in 14 patients, 3 of whom required dialysis. The creatinine clearance after ltx showed a tendency to decrease, but there was no statistically significant difference (P >.05) in the change in serum creatinine clearance levels between patients treated with tacrolimus (TAC) versus Cyclosporine (CsA) during the first 2 years of follow-up. Fourteen patients required conversion of their regimen because of CNI nephrotoxicity namely, dose reduction (n = 7) or discontinuation of CNI therapy with the replacement by mycophenolate mofetil (MMF) (n = 5) or SRL (n = 5). Dose reduction or CNI withdrawal significantly improved the creatinine clearance (P <.05) without affecting lives graft function. No episode of acute rejection was observed after conversion. Neither conversion of CsA to TAC nor the reverse maneuver significantly influenced the serum creatinine level (P >.05). Reduction of the CNI dose or CNI discontinuation or replacement with MMF or SRL in patients with stable liver but impaired renal function is safe, resulting in a significant improvement in renal function.  相似文献   

16.
Background: Calcineurin inhibitors (CNI) are the main immunosuppressive drugs in solid organ transplantation. However, their use is hampered by side effects like nephrotoxicity. We report an exceptional experience with three children treated with sirolimus after combined liver and kidney transplantation with prolonged renal failure and CNI-associated nephrotoxicity. Patients and results: Two girls experienced prolonged renal graft failure after combined liver-kidney transplantation for 11 and 12 weeks. Repeated biopsies did not show any rejection but did exhibit tubular damage and acute CNI-toxicity. A boy with hyperoxaluria after liver and (a third) renal transplantation experienced acute renal graft failure after an early steroid-resistant rejection. All children were switched to sirolimus-based immunosuppression and cessation of CNI therapy, which was followed by rapid improvement of renal function. Rejection of liver or kidney did not occur after CNI withdrawal. Sirolimus was commenced with 3 mg/m2/day in two doses and resulted in reasonable drug exposure. However, drug monitoring was required to adjust sirolimus dosage. Summary: Prolonged renal failure after transplantation with severe CNI toxicity may be salvaged successfully with sirolimus-based immunosuppression.  相似文献   

17.
Calcineurin inhibitor (CNI) immunosuppressive therapy post-liver transplantation (OLT) is important to reduce graft rejection episodes. However, these drugs show important side effects, particularly renal dysfunction (RDF). Changing from CNI to a nonnephrotoxic drug, as mammalian target of rapamycin (mTOR) inhibitor may solve the problem. Our objective was to evaluate renal function (RF) among liver transplant patients initially receiving CNI, among whom the patients with RDF were converted completely or partially to an mTOR inhibitor like everolimus (EVE). We performed a prospective study in liver transplant patients from 2000 to 2009. Creatinine levels and creatinine clearances (Cockroft-Gault) expressed as mean values ± standard deviations were measured pre- and postswitch for comparisons using Wilcoxon nonparametric tests. Six patients were converted fully or partially to EVE. Their mean age at the moment of introducing the new therapy was 52.2 ± 13.6 years (range = 28-60). Immunosuppression time prior to switching from CNI to EVE was 23.8 ± 26.6 months (range = 6-70). Postconversion follow-up was 25.8 ± 16.5 months (range = 8-42). All patients showed improvement in RF. The creatinine level improvement was significant (P = .03) namely, from a mean of 2.26 ± 0.49 to 1.21 ± 0.57 mg/dL. Glomerular filtration rate improved from a mean of 40 ± 15.13 to 72.60 ± 17.3 mL/min/m2 (P = .03). Conversion from CNI to EVE improved creatinine concentrations and creatinine clearances with long-term effects free of graft rejection.  相似文献   

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