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1.
BACKGROUND AND OBJECTIVE: Concerns about the risk of transfusion therapy are driving towards new strategies which are designed to minimize exposure to allogeneic blood products. We aimed to find out whether it is possible to support the phase of thrombocytopenia following high-dose chemotherapy (HDC) and circulating progenitor cells (CPC) transplantation by autologous platelet concentrates (PC). DESIGN AND METHODS: PC were collected from 32 patients undergoing HDC and CPC transplantation for stage II/III breast cancer. A single plateletpheresis was performed at rebound after high-dose cyclophosphamide, when platelet count exceeded 250 x 10(9)/L. PC were cryopreserved in 5% DMSO after controlled-rate freezing and stored in liquid nitrogen. In vitro studies of cryopreserved platelets (aggregation, ATP release and change of mean platelet volume induced by EDTA) were performed. When platelet counts dropped below 20 x 10(9)/L following HDC (thiotepa 600 mg/m2, L-PAM 160 mg/m2) and CPC transplant (CD34+ cells > 5 x 10(6)/kg), PC were thawed in a 37 degrees C water bath, centrifuged to remove DMSO, resuspended in autologous plasma and reinfused within one hour. RESULTS: Large quantities of platelets were harvested in all patients (median 6.6 x 10(11), range 4.8-12.2). In vitro studies showed preserved platelet function as compared to both fresh platelets and standard PC. Twenty-eight out of 32 patients received autologous PC. At the time of transfusion most of the patients were febrile (> 38 degrees C) and had mucositis > G2. The median number of platelets reinfused was 3.8 x 10(11) (range 2.0-8.1) with a median loss during the freeze-thaw-wash procedure of 37%. Autotransfusion was able to maintain platelet count above 20 x 10(9)/L in most patients, with a corrected count increment > 7.5 in 20 cases. Four patients required one additional allogeneic transfusion, two because of a poor increment and two due to a late-occurring epistaxis. No side effects related to PC infusion were recorded. Sixteen control patients who received the same HDC and a similar number of CD34+ cells required a total of 17 allogeneic PC units (1 patient did not require platelet transfusion). INTERPRETATION AND CONCLUSIONS: Our data demonstrate that large doses of autologous platelets can easily be collected and safely administered to support the period of thrombocytopenia in patients undergoing HDC and CPC transplantation. Autologous PC in these patients can abrogate the risks deriving from allogeneic platelet transfusion.  相似文献   

2.
We carried out a randomized, single-blind, cross-over trial to compare the antiemetic effect, for both acute and delayed emesis, of granisetron plus dexamethasone (GRN+Dx) with that of high-dose metoclopramide plus dexamethasone (HDMP+Dx). Fifty-four patients with primary or metastatic lung cancer, given single-dose cisplatin (> 80 mg/m2) chemotherapy more than twice, were enrolled in this study. They were treated with both HDMP+Dx and GRN+Dx in two consecutive chemotherapy courses. On day 1, patients experienced a mean of 2.5 (SD = 4.3) and 0.1 (SD = 0.4) episodes of vomiting in the HDMP+Dx and the GRN+Dx groups, respectively (P = 0.0008). Complete response rate on day 1 was 45 and 90% in the HDMP+Dx and the GRN+Dx groups, respectively (P = 0.0001). Patients treated with GRN+Dx had a tendency to suffer more episodes of vomiting than the HDMP+Dx group on days 2-5, but it was not statistically significant. Twenty-four patients (57%) preferred the GRN+Dx treatment and 14 patients (33%), HDMP+Dx. In the HDMP+Dx group, nine patients (21%) had an extrapyramidal reaction, and 5 patients (12%) had constipation that lasted for at least two days. In contrast, no patients had extrapyramidal reactions, and 18 patients (43%) had constipation in the GRN+Dx group (P < 0.01). GRN+Dx was more effective than HDMP+Dx only in preventing the acute emesis induced by cisplatin. An effective treatment for delayed emesis is still needed.  相似文献   

3.
In a case control study, serum levels of thrombopoietin (TPO) were determined by a sandwich ELISA in 20 patients (median age, 7 years; range, 2-56 years) with various malignancies who received high-dose chemotherapy and a stem cell rescue operation. The patients received two different transplant modalities: (a) 12 patients received purified autologous peripheral blood CD34+ cells; and (b) 8 patients received cells in the CD34(-) fraction, which still contains many CD34+ cells. No significant differences were observed between the two groups with regard to the duration required to achieve an absolute granulocyte count of >0.5 x 10(9)/liter, the duration of dependence on platelet transfusion, or the number of platelet transfusions. In both groups, the serum TPO levels were inversely correlated with the circulating platelet count. Multivariate analysis demonstrated that significant determinants of the serum TPO level included the circulating platelet count (standardized regression coefficient = -0.5179), transplantation with cells in the CD34(-) fraction (0.2414), solid tumor (0.1420), and the age of the patient (-0.1236; r2 = 0.3021; P < 0.0001). These results suggest that the mode of stem cell support (ie., the presence of accessory cells in the inoculum), age, or the type of preceding chemotherapy affects serum TPO levels after transplantation.  相似文献   

4.
BACKGROUND/AIMS: Spontaneous gastroduodenal perforation is a rare and lethal complication in cancer patients receiving chemotherapy. METHODOLOGY: Data of 9 patients with spontaneous gastroduodenal perforation occurring during chemotherapy were reviewed. RESULTS: All 9 patients were male with an average age of 54.4+/-2.5 years. The primary malignancies included 5 head and neck cancers, 2 esophageal cancers, 1 malignant lymphoma, and 1 hepatocellular carcinoma. Abdominal pain was the most common symptom. The average interval between the onset of symptoms and surgery was 2.9+/-0.7 days (range: 16 hours to 7 days). Perforation was located on the duodenum (6 patients) and on the lower part of the body of the stomach (3 patients). Simple closure of the perforation was performed on 8 patients, and subtotal gastrectomy on 1 patient. Culture of the ascitic fluid of 8 patients revealed E. coli, Klebsiella pneumoniae, streptococcus viridans, and enterococcus. Four patients (44.4%) had post-operative complications. The 30-day post-operative mortality was 44.4% (4/9). Three patients died of sepsis with multiple organ failure, and 1 died of hepatic failure. Age, anaemia, leukopenia, serum albumin levels, impaired renal or liver functions are not significant operative risk factors. Pre-operative shock is a significant factor in predicting operative mortality and complications. CONCLUSIONS: High index with suspicion of the disease with early treatment may improve survival of cancer patients with spontaneous gastroduodenal perforation.  相似文献   

5.
4-Hydroperoxycyclophosphamide (4-HC), a commonly used marrow-purging agent, is active against many tumors, but is also toxic to normal marrow progenitors. Amifostine (WR-2721) is a sulfhydryl compound with chemoprotectant activity. Preclinical studies using suspensions of bone marrow and breast cancer cells demonstrated that ex vivo treatment with amifostine followed by 4-HC resulted in protection of marrow progenitors, with no compromise in the antitumor effect of 4-HC. This fact stimulated the development of a clinical trial. Bone marrow was harvested from 15 poor-prognosis breast cancer patients and randomly assigned to ex vivo treatment with amifostine followed by 4-HC (amifostine + 4-HC), or treatment with 4-HC alone. High-dose chemotherapy was then administered followed by infusion of the purged autologous bone marrow support (ABMS). Leukocyte engraftment, defined as a white blood cell count > or = 1 x 10(9)/L, was achieved in an average of 26 days for patients whose marrow was purged with amifostine + 4-HC versus 36 days for patients whose marrow was purged with 4-HC alone (P = .032). The average number of platelet transfusions (12 v 29; P = .017) and days of antibiotic therapy (28 v 40; P = .012) were significantly less for patients whose marrow was exposed to amifostine + 4-HC, compared with 4-HC alone. Unpurged backup marrow fractions were infused into three patients whose marrow was purged with 4-HC alone, because of inadequate marrow recovery. None of the patients who received amifostine + 4-HC-purged marrow required a backup marrow fraction. Complete remissions were achieved in 83% of patients with measurable disease, with no difference between the two cohorts. Forty-three percent of patients remained alive and progression-free at a mean of 13 months posttransplant. There was no significant difference in the rate or pattern of relapse for patients whose marrow was purged with amifostine + 4-HC compared with those whose marrow was purged with 4-HC alone. Ex vivo treatment of marrow with amifostine significantly shortens the time to marrow recovery, thereby reducing the risk of myelosuppressive complications in breast cancer patients receiving high-dose chemotherapy and 4-HC-purged ABMS. Since supportive care requirements are also significantly decreased, amifostine may reduce the cost of such therapy.  相似文献   

6.
100 cancer chemotherapy patients were interviewed, rated the severity of pre- and posttreatment nausea and emesis, and completed the State-Trait Anxiety Inventory. In addition, scores on the Millon Behavioral Health Inventory were obtained for 59 Ss. 33% of the Ss reported having experienced anticipatory nausea, and 11% reported having experienced anticipatory vomiting. Ss who experienced anticipatory nausea had more posttreatment nausea and vomiting, were more depressed, and were characteristically more anxious than other Ss. Future despair, social alienation, inhibited personality style, gastrointestinal susceptibility, chronic tension, and confident personality style were variables that best distinguished Ss who experienced anticipatory nausea. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

7.
Based on the single-agent activity of both paclitaxel and cyclophosphamide in the treatment of non-Hodgkin's lymphoma (NHL), we conducted a phase II study to evaluate the efficacy of the combination of the two drugs in patients with refractory and relapsed aggressive NHL. All patients received 900 mg/m2 bolus of cyclophosphamide intravenously daily for 3 consecutive days with a concurrent infusion of 150 mg/m2 of paclitaxel over 72 h (50 mg/m2/d). 24 h after the completion of chemotherapy, patients received subcutaneous injections of 5 microg/kg of granulocyte-colony stimulating factor (G-CSF) daily until white cell count recovery. Treatment was repeated every 3 weeks. Patients who had at least a partial response (PR) after two courses continued to receive a maximum of four courses. Patients with responding disease were allowed to undergo high-dose chemotherapy followed by stem-cell/bone marrow transplantation if they were eligible. Of the 77 patients who were eligible for the study, 74 (96%) were evaluable for toxicity and treatment response. The overall response rate was 45% (95% CI 33-57%). Patients who received treatment after their disease relapsed from a complete response (CR) had an 81% response rate (38% CRs), whereas those with primary refractory disease had a 22% response rate. Toxicities of > grade 2 included alopecia (100%) and stomatitis (25%). Neutropenic fever of grade > 2 occurred after 18% of the courses, and platelet count of < or = 20 x 10(9)/l developed after 20% of the courses. Thus, the combination of paclitaxel plus high-dose cyclophosphamide is an effective new regimen in the treatment of refractory and relapsed NHL.  相似文献   

8.
AIM: To evaluate the prevalence of iron overload in chronic hepatitis C and its relationship with liver histology. PATIENTS AND METHODS: Serum iron, unsaturated iron binding capacity and ferritin levels were determined in 204 consecutive anti-hepatitis C virus positive subjects, whereas hepatic iron concentration, hepatic histological grading and staging, hepatitis C virus genotypes were further assessed in a subgroup of 50 patients who underwent liver biopsy for chronic hepatitis. RESULTS: An increase in the serum markers of iron metabolism was more frequently found in subjects with aminotransferase activities above the normal range, whereas hepatic iron overload, established by direct hepatic iron determination, was found only in 9/50 (18%) patients with chronic hepatitis C. No serum iron marker could reliably predict hepatic iron stores. Patients with mild iron overload usually showed active hepatitis and fibrosis, whereas iron overload was not present in patients without fibrosis or with very mild fibrosis. Two out of nine patients with iron overload were shown to be beta thalassaemia heterozygous, and two were heterozygous carriers of a putative haemochromatosis gene mutation (His63Asp). CONCLUSIONS: Many anti-hepatitis C virus positive patients with elevated aminotransferase activities have serum ferritin levels above the normal range, but only a minority of patients with chronic hepatitis C have a mild iron overload. In chronic hepatitis C, a relationship does exist between hepatic iron content and liver fibrosis.  相似文献   

9.
Nausea and vomiting in anticipation of chemotherapy often develop in patients undergoing cancer treatment. In this study, deep muscle relaxation hypnosis controlled these conditioned reactions in 6 female patients (aged 24–56 yrs). Anticipatory emesis recurred when hypnosis was not used. During subsequent sessions in which hypnosis was reinstated, anticipatory emesis was again controlled. (18 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

10.
OBJECTIVE: To determine the incidence of ovarian failure after cyclophosphamide (CYC) treatment for systemic lupus erythematosus (SLE) and to identify the risk factors for this complication. METHODS: The records of 70 premenopausal female SLE patients treated with CYC were reviewed retrospectively. Information on demographic features, autoantibody profiles, and CYC treatment was obtained, and comparisons were made between those who developed ovarian failure and those who did not. Data on the CYC-treated patients were also compared with data on 2 control groups of non-CYC-treated SLE patients. RESULTS: Eighteen patients developed ovarian failure after CYC treatment, for an overall incidence of 26%. The incidence of ovarian failure showed a linear trend of increase with increasing age at the start of CYC (P = 0.007). The cumulative CYC dose was significantly higher in the patients with ovarian failure than in those without (28.3 gm versus 15.4 gm; P = 0.004). The risk of ovarian failure also showed a linear trend of increase with increasing cumulative CYC dose (P < 0.001). Using multiple logistic regression, the age at the time of CYC treatment initiation (beta = 0.37, SE = 0.11, P = 0.001) and the cumulative dose of CYC received (beta = 0.69, SE = 0.29, P = 0.02) were found to be independent risk factors for CYC-induced ovarian failure. CONCLUSION: In our population of female SLE patients, CYC-induced ovarian toxicity is a significant problem, particularly in patients above the age of 40. The age at the start of CYC therapy and the cumulative dose are the major determinants for the development of this complication. For older patients with SLE in whom the use of CYC is warranted, a shorter course and lower dosage should be considered.  相似文献   

11.
Two studies were conducted to investigate the use of cognitive/attentional distraction (via commercially available video games) to control conditioned nausea in pediatric cancer patients receiving chemotherapy. The first study compared the nausea severity in children who played video games during chemotherapy-related procedures with that of control-group children who did not play video games. The second study used a combined ABAB withdrawal and repeated measures analysis of variance design that incorporated baseline and intervention assessments within a single session. In both studies, video game-playing resulted in significantly less nausea. The introduction and withdrawal of the opportunity to play video games produced significant changes (reduction and exacerbation, respectively) in nausea. Although video games also reduced self-reported anxiety, the effects were weaker than those for nausea. Pulse rate and systolic/diastolic blood pressure were not consistently affected. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

12.
The broad spectrum of activity of ciprofloxacin makes it an ideal drug for the prophylaxis of bacterial infections in patients undergoing high-dose chemotherapy (HDC) with autologous stem cell rescue. We present two cases of ciprofloxacin-associated acute renal failure (ARF) in patients undergoing HDC. Maintaining a high index of suspicion for this complication will allow a prompt diagnosis, with discontinuation of the drug usually resulting in a reversal of renal failure. Renal biopsy usually reveals changes compatible with interstitial nephritis, but is not always possible in these patients due to severe thrombocytopenia following HDC. A brief course of steroid therapy may be beneficial although the role of glucocorticoids is difficult to ascertain in the absence of data regarding its efficiency in this clinical setting.  相似文献   

13.
A 13-year-old boy with a paratesticular embryonal rhabdomyosarcoma and a large thrombus into the inferior vena cava reaching the suprahepatic vein is presented. We used cardiopulmonary bypass with deep hypothermic circulatory arrest to realize a complete exeresis of the tumor and thrombus, followed by systemic chemotherapy and radiotherapy. Ten years later the patient is alive and doing well without any sequelae.  相似文献   

14.
Three patients are described who developed a severe neuropathy after chemotherapy with high dose cis-diamine-(1,1-cyclobutane dicarboxylato) platinum (carboplatin). This toxic side effect, which is unusual at conventional doses, might become more frequent as increasing doses are administered to overcome drug resistance in cancer treatment, and might limit its use at very high doses before haematopoietic stem cell transplantation.  相似文献   

15.
BACKGROUND: Nitrogen balance in patients who need high-dose administration of insulin has not been evaluated clinically. The purpose of this study was to compare the difference in nitrogen balance between burn patients who received high-dose administration of insulin and those who did not. METHODS: This study was performed in 19 severely burned adults with no liver or kidney failure. Patients were divided into two groups on the basis of the mean ratio of administered insulin and calorie intake (I/C) for the initial 4 weeks, a high I/C group (n = 9) and a low I/C group (n = 10). There were no significant differences between the two groups regarding age, percentage of area burned, and body weight. Nitrogen balance, blood urea nitrogen, and urine urea nitrogen were measured in all patients. Plasma concentrations of glucose, insulin, glucagon, cortisol, and urinary excretion of 3-methyl-histidine were measured in 12 patients (six in each group). RESULTS: Until day 10 both groups exhibited similar changes in plasma concentrations of glucose, insulin, glucagon, and cortisol. Subsequently, plasma concentrations of insulin and glucagon began to decrease in the low I/C group, whereas a high level was sustained in the high I/C group (p < 0.05). Plasma glucose and cortisol measurements showed no significant differences between the two groups. Blood urea nitrogen levels and urinary excretion of 3-methyl-histidine were not different between the two groups. Urine urea nitrogen excretion in the high I/C group, however, was significantly lower than that in the low I/C group from day 8 (p < 0.05). Thus the high I/C group achieved positive nitrogen balance more quickly than the low I/C group. Paradoxically, however, the high I/C group was at higher risk of septic complications and exhibited higher mortality than the low I/C group (p < 0.05). CONCLUSIONS: These results indicate that an improvement in nitrogen balance, which is accepted as a good thing in the management of critically ill patients, is not necessarily good in the high I/C group and that residual nitrogen was retained within the body in the high I/C group.  相似文献   

16.
A retrospective analysis of the outcome for 283 haematological patients who relapsed after high dose chemotherapy and autologous stem cell transplantation during a five year period from 1989 to 1994 is presented. The patients were treated in accordance with local regimes at 20 Nordic transplantation centers and included patients with acute leukemia (157 patients), multiple myeloma (16 patients) and lymphoma (110 patients). Two hundred and twenty-nine patients with relapse or progressive disease were given chemo- and/or radiotherapy and the response was evaluated after 90 days. Fifty-four patients (24%) obtained a complete remission and 44 patients (19%) partial remission. The overall median survival after relapse was five months. In the group who received salvage treatment the median survival was seven months, and for the 54 patients in complete remission the median survival was 15 months. We found that survival after relapse depends upon primary disease, the time from transplantation to relapse and whether salvage therapy was initiated.  相似文献   

17.
BACKGROUND: Intravenous antiemetic combinations containing a 5-HT3 receptor antagonist (like metoclopramide, ondansetron, or granisetron) with dexamethasone have become the standard therapy for the treatment of acute chemotherapy-induced vomiting. Intravenous antiemetics, however, can be more costly and take more time to prepare and deliver, and therefore are not preferred for home, outpatient, or office use. The objective of this study was to determine the antiemetic activity and safety of the oral combination antiemetic regimen of metoclopramide, dexamethasone, and diphenhydramine in patients with small cell lung cancer receiving standard outpatient chemotherapy programs. METHODS: Fifty-two patients receiving initial cisplatin (60 mg/m2) or cyclophosphamide (600-1500 mg/m2) plus doxorubicin (30-45 mg/m2) received an oral regimen of metoclopramide (3 mg/kg x 2 then 2 mg/kg x 2 or 4 doses), dexamethasone (20 mg) and diphenhydramine (50 mg x 2 or 3 doses) (oral MDD), beginning 30 minutes before chemotherapy. RESULTS: Vomiting was prevented in 15 of 21 (76%) patients (95% confidence interval [CI], 53%-92%) receiving cisplatin and 21 of 31 (71%) individuals (95% CI, 52%-86%) given cyclophosphamide plus doxorubicin. Adverse effects were mild and transient and included sedation, loose stools, akathisia, and hiccoughs. CONCLUSIONS: The oral MDD antiemetic regimen prevented acute emesis in 73% of the patients entered and was well tolerated in this population of patients with small cell lung cancer.  相似文献   

18.
Busulfan, a bifunctional alkylating agent, is a mainstay of myeloablative preparative regimens before hematopoietic stem cell transplantation. The apparent oral clearance of busulfan expressed relative to body surface area is 2-3-fold higher in children 1-4 years old than it is in adults. The first step in busulfan elimination is the formation of a tetrahydrothiophenium ion (THT+) in a glutathione S-transferase-catalyzed reaction. We present computer simulations that demonstrate that the ratio of the AUC of THT+ to that of busulfan over 6 h [(AUC(THT+)/AUC(BU))(0-->6)] is highly correlated (r2 = 0.805) with the determinants of THT+ formation and is virtually independent of the determinants of its elimination (r2 = 0.0201). We compared (AUC(THT+)/AUC(BU))(0-->6) determined in 14 children (0.5-4 years) to that of 11 adults (12-54 years) and found a 1.5-fold elevation in the area ratio (P = 0.0098) and a similarly significant increase in busulfan apparent oral clearance expressed relative to body surface area (P = 0.042). The only common explanation for the elevated busulfan apparent oral clearance and (AUC(THT+)/AUC(BU))(0-->6) is an enhanced ability of children to metabolize busulfan through glutathione conjugation.  相似文献   

19.
BB-10010 is a variant of the human form of macrophage inflammatory protein-1alpha (MIP-1alpha), which has been shown in mice to block the entry of hematopoietic stem cells into S-phase and to increase their self-renewal capacity during recovery from cytotoxic damage. Its use may constitute a novel approach for protecting the quality of the stem cell population and its capacity to regenerate after periods of cytotoxic treatment. Thirty patients with locally advanced or metastatic breast cancer were entered into the first randomized, parallel group controlled phase II study. This was designed to evaluate the potential myeloprotective effects of a 7-day regimen of BB-10010 administered to patients receiving six cycles of 5-fluorouracil (5-FU), adriamycin, and cyclophosphamide (FAC) chemotherapy. Patients were randomized, 10 receiving 100 microgram/kg BB-10010, 11 receiving 30 microgram/kg BB-10010, and nine control patients receiving no BB-10010. BB-10010 was well-tolerated in all patients with no severe adverse events related to the drug. Episodes of febrile neutropenia complicated only 4% of the treatment cycles and there was no difference in incidence between the treated and nontreated groups. Studies to assess the generation of progenitor cells in long-term bone marrow cultures were performed immediately preceding chemotherapy and at the end of six dosing cycles in 18 patients. Circulating neutrophils, platelets, CD 34(+) cells, and granulocyte/macrophage colony-forming cell (GM-CFC) levels were determined at serial time points in cycles 1, 3, and 6. The results showed similar hemoglobin and platelet kinetics in all three groups. On completion of the six treatment cycles, the average pretreatment neutrophil levels were reduced from 5.3 to 1.7 x 10(9)/L in the control patients and from 4.3 to 1.9 and 4.5 to 2.5 x 10(9)/L in the 30/100 microgram/kg BB-10010 groups, respectively. Relative to their pretreatment values, 50% of the patients receiving BB-10010 completed the treatment with neutrophil values significantly higher than any of the controls (P = .02). Mobilization of GM-CFC was enhanced by BB-10010 with an additional fivefold increase over that generated by chemotherapy alone, giving a maximal 25-fold increase over pretreatment values. Bone marrow progenitor assays before and after this standard regimen of chemotherapy indicated little long-term cumulative impairment to recovery from chemotherapy. Despite the limited cumulative damage to the bone marrow, which may have minimized the protective value of BB-10010 during this regimen of chemotherapy, better recovery of neutrophils in the later treatment cycles with BB-10010 was indicated in a number of patients.  相似文献   

20.
A clinical and economic evaluation of red blood cell (RBC) utilization in cancer patients during chemotherapy is described. Using a randomized sampling process, 100 patients who had received chemotherapy with or without cisplatin were selected (50 in each group). Multiple logistic regression was then used to identify risks factors for transfusion requirements. Twenty-five percent of patients in the cisplatin and 12% in the noncisplatin group received at least one blood transfusion during chemotherapy (p = .09). Depressed hemoglobin levels and cisplatin dosage were identified as risk factors for transfusion requirements. Combining all transfused patients revealed an overall cost of Can $599 (95% CI: $513-$683) per transfusion. The results of the current study indicated that anemia is a common complication of cancer chemotherapy that can be costly to manage.  相似文献   

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