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  • 1
    In: BMC Ecology, Springer Science and Business Media LLC, Vol. 16, No. 1 ( 2016-12)
    Materialart: Online-Ressource
    ISSN: 1472-6785
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2016
    ZDB Id: 2050430-5
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: Blood, American Society of Hematology, Vol. 114, No. 18 ( 2009-10-29), p. 3742-3747
    Kurzfassung: Vaso-occlusive crisis (VOC) is the primary cause of hospitalization of patients with sickle-cell disease. Treatment mainly consists of intravenous morphine, which has many dose-related side effects. Nonsteroidal antiinflammatory drugs have been proposed to provide pain relief and decrease the need for opioids. Nevertheless, only a few underpowered trials of nonsteroidal antiinflammatory drugs for sickle-cell VOC have been conducted, and conflicting results were reported. We conducted a phase 3, double-blind, randomized, placebo-controlled trial with ketoprofen (300 mg/day for 5 days), a nonselective cyclooxygenase inhibitor, for severe VOC in adults. A total of 66 VOC episodes were included. The primary efficacy outcome was VOC duration. The secondary end points were morphine consumption, pain relief, and treatment failure. Seven VOC episodes in each group were excluded from the analysis because of treatment failures. No significant between-group differences were observed for the primary outcome or the secondary end points. Thus, although ketoprofen was well-tolerated, it had no significant efficacy as treatment of VOC requiring hospitalization. These findings argue against its systematic use in this setting.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2009
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    Online-Ressource
    Online-Ressource
    American Society of Hematology ; 2006
    In:  Blood Vol. 108, No. 11 ( 2006-11-16), p. 3354-3354
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 3354-3354
    Kurzfassung: Background: Patients suffering from β-thalassemia (TM), sickle cell disease (SCD), and myelodysplastic syndromes (MDS) undergoing chronic blood transfusions are at risk for iron overload which, if not treated by iron chelation therapy (ICT), can cause serious organ damage and reduce life expectancy. Deferoxamine (DFO) is the standard of care for the depletion of excess body iron. It has to be infused for 8–10 hours, 5–7 times a week. Although the clinical need for ICT is clearly established, less is known about the economic burden of DFO treatment. Aim: To estimate the total annual costs of DFO ICT in treatment centers in France. Methods: A cross-sectional study with a prospective recruitment. Among 278 consecutive patients receiving regular transfusions for TM, SCD or MDS who consulted between October 2005 and February 2006 in 24 French centers, 161 were on ICT. 124 patients were treated with DFO alone for more than 1 year. Among them, 67 aged 14 years or more agreed to participate. Resources used were collected through patient and physician questionnaires. Unit costs (2004/2005 €) were applied according to French economic guidelines. Results: DFO was administered via subcutaneous (sc) infusion for 70% of patients, mainly nightly and with a mean duration of 10 hours. Other ways of administering DFO included intravenous (iv) infusion (15%), sc bolus (9%) and combined sc and iv treatment (5%). Patient characteristics are summarized in the table below. TM (n=24) SCD (n=17) MDS (n=26) *Cardiac, liver and endocrine diseases, lens opacities, osteoporosis Median age (min-max), years 30 (15–70) 32 (14–57) 69 (45–85) Sex, M/F 11/13 6/11 14/12 Organ dysfunction potentially related to hemosiderosis* (%) 75 47 54 Ferritin level (median), ng/mL 1049 2653 2627 DFO nb/week (mean) 3.7 4.5 4 Dose (mean) 40 17 43 For all patients, the estimated mean weighted annual cost of infusions is 16009 € (SD ± 13867). Costs are similar for the three diseases. ICT delivery equipment (infusion set and pump) and nursing administration, drug cost, DFO adverse events monitoring, periodic exams and treatment of infused ICT-related adverse events represent respectively 56.5%, 38.5%, 0.3%, 3.7% and 0.9% of total direct cost. The estimated annual mean cost of the drug alone was 6160 € (SD ± 4145). Average cost for DFO adverse events management is low at 151.5€ (SD ± 1224), essentially due to one patient complication. Costs of periodic exams are also low due to the fact that exams are not strictly performed annually as recommended. These estimates of the total annual costs of DFO ICT are likely to be underestimating the overall cost of DFO therapy because treatment costs of the clinical consequences of poor adherence to DFO and lost productivity were not collected in the study. Conclusions: ISOSFER demonstrated that total direct costs of ICT are substantial and well exceed the cost of DFO alone. The cost of DFO administration constitutes a significant portion of the total cost of iron chelation (54%). These data are comparable to other analyses published from US (43% of the total costs, n=155) and Swiss (45%, n=17) databases.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2006
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 954-954
    Kurzfassung: Background: Delayed haemolytic transfusion reaction (DHTR) may be a life-threatening complication in sickle cell disease (SCD) patients. DHTR is characterized by a marked drop in hemoglobin (Hb) and is frequently accompanied with intensification of the disease symptoms. Pathogenesis of DHTR is not completely understood as autologous RBCs are probably destroyed and allo-antibodies against transfused RBCs in the course of the accident are not always detected. Here we describe a case of serious DHTR and analyse lymphocyte subsets and cytokine transcripts. Case report: A 33-year-old man with SCD was scheduled for hip replacement. He was poly-immunized (anti-RH2, -RH23, -RH30, -FY1, -FY3,-MNS3, -YT2) and had history of 2 DHTR. He received 7 units of crossmatch-compatible blood at day 0 of surgery. On days 5 and 8, sera were still compatible with samples of units received at day 0. Direct antiglobulin test (DAT) and eluate were negative. Hb remained stable at 6 g.dl−1. On day 14, the patient presented pain, fever and signs of hemolysis including a drop in Hb to 3.5 g.dl−1, LDH at 12460 U per L, bilirubin at 111 μmol/L and renal failure. Serological and eluate evaluation revealed the presence of antibodies against all RBCs tested (including units previously transfused at day 0), DAT positive with anti-C3 and anti-IgG. Hb dropped to 2.5 g.dl−1, the patient presenting neurologic symptoms. Because of the life-threatening anemia, he received 4 units that were compatible only with the known antibodies, associated with corticoids and cyclophosphamide. An anti-MNS5 was finally detected explaining partly the positive reactions against all RBCs tested. Then, additional U-negative units were transfused. The patient gradually improved symptomatically and was discharged from the high dependency unit on day 30. Hb level reached 6 g.dl−1. As compared to day 0, vigorous expansion (ten times) of Natural Killer subset (CD56+, CD16+) was observed on day 14 during hemolysis. This expansion was correlated to an increase of IL-10 transcripts whereas IL-2 and IFNγ transcripts were not detected. After treatment (day 32) lymphocyte subsets returned to the day 0 level and IL10 transcripts disappeared. Conclusion : This case report confirms that DHTR can be induced by transfusion of crossmatch-compatible units. In this poly-immunized SCD patient, transfusion has elicited production of auto-antibodies. The observed expansion of Natural Killer cells during the hemolysis suggests that Natural Killer cells could participate, through an ADCC mechanism, to the destruction of both transfused and autologous RBCs. The involvement of IL-10 on Natural Killer FcγRIIIa receptor expression and Natural Killer cytotoxicity will be discussed.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2005
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    In: Blood, American Society of Hematology, Vol. 116, No. 12 ( 2010-09-23), p. 2152-2159
    Kurzfassung: Sickle cell disease is characterized by painful vaso-occlusive crises during which abnormal interactions between erythroid adhesion molecules and vessel-wall proteins are thought to play a critical role. Hydroxyurea, the only drug with proven benefit in sickle cell disease, diminishes these interactions, but its mechanism of action is not fully understood. We report that, under hydroxyurea, expression of the unique erythroid laminin receptor Lu/BCAM was increased, but red blood cell adhesion to laminin decreased. Because Lu/BCAM phosphorylation is known to activate cell adhesion to laminin, it was evaluated and found to be dramatically lower in hydroxyurea-treated patients. Analysis of the protein kinase A pathway showed decreased intracellular levels of the upstream effector cyclic adenosine monophosphate during hydroxyurea treatment. Using a cellular model expressing recombinant Lu/BCAM, we showed that hydroxyurea led to decreased intracellular cyclic adenosine monophosphate levels and diminished Lu/BCAM phosphorylation and cell adhesion. We provide evidence that hydroxyurea could reduce abnormal sickle red blood cell adhesion to the vascular wall by regulating the activation state of adhesion molecules independently of their expression level.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2010
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 3037-3037
    Kurzfassung: Background: Delayed hemolytic transfusion reaction (DHTR) is a life-threatening complication in sickle cell disease (SCD). Some features are characteristic: destruction of both donor and recipient red blood cells (RBCs), hemolysis exacerbation by further transfusions, recurrence of SCD complications, reported cases without demonstrable RBC antibodies. We carried out a prospective study to clarify mechanisms of DHTR without demonstrable antibody and associated features. In this matter, we considered that study of phosphatidylserine exposure (PS) was important as PS-exposure signed eryptosis or suicidal erythrocyte death1, a process of membrane shedding leading to clearance of apoptotic erythrocytes by macrophages through their PS-receptors. Patients and methods: 48 SCD patients were included. Transfusion occurred for different SCD indications. Adverse events were monitored. Analyses were performed at 5 time points (day 0 and around days 1, 5, 10 and 20 post-transfusion) including hemolysis parameters, % of HbA and HbS, and research of antibodies against RBCs by antibody-screening in plasma and eluate, cross-matching between donor RBCs and both plasma and eluate, direct antiglobulin test with anti-IgG, IgM, IgA, C3d/C3b (DAT). Amount of PS-RBCs was determined by flow cytometry as Annexin V-positive RBCs, in vivo, on patient samples and in vitro, on healthy blood donor RBCs previously incubated 48H in the J0 plasma of the patients. Results and discussion: Transfusion outcome was known for all patients, 31 patients could be completely studied at the biological level. Three patients experienced DHTR, confirmed by complete disappearance of HbA at days 13, 7 and 10 respectively and by biological parameters of hemolysis. Two cases occurred without demonstrable antibody, in the third case, RBC antibodies could not be eliminated as DAT became positive with IgG. In vivo, a significant fold increase of PS-RBCs was observed for the 3 DHTR patients around day 10 (3.74±2.0, p=0.009) and day 17 (4.85±1.4, p=0.007). This result shows that DHTR, with no consideration of the mechanism, is a risk factor for recurrence of SCD complications as PS-RBCs are involved in vaso-occlusive crisis (VOC)2. In vitro, PS-RBCs % increases significantly (p & lt;0.01) after incubation of donor RBCs into J0 plasma of the 15 patients transfused for VOC (12.8±9.9%) compared with J0 plasma of patients transfused for other indications (4.7±4.6%). The increase is significantly higher (p & lt;0.05) with plasma of the 2 VOC patients who experienced DHTR without demonstrable antibody (37.1±6.7%) compared with other transfused VOC patients. This result indicates that transfused RBCs can suffer from the in vivo environment of SCD patients who encountered VOC and their survival be compromised by enhancing the normal physiological clearance of apoptotic RBCs. Conclusion: In this study, we clearly demonstrate that DHTR can occur without demonstrable antibody. Based on PS-exposure results, we propose the following scenario of DHTR features: RBCs transfused in a high oxidative stress environment (VOC) suffer from accelerated eryptosis. Hemolysis reaction of transfused RBCs promotes a cascade of events that increases release of oxidative stress mediators and more destruction of autologous RBCs that are already fragile. A further transfusion will trigger a new wave of hemolysis with amplified consequences. The only way to stop the loop is to stop transfusion. It remains to determine the mediators which accelerate eryptosis of transfused RBCs in order to propose the adapted prevention such as cytoprotective drugs.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2008
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 12-12
    Kurzfassung: INTRODUCTION Besides many problematics the Covid-19 pandemic has triggered, one issue remains the care of chronically ill patients. Regarding sickle cell disease (SCD), patients often present co-morbidities that could predispose them to poor outcome if they get infected. Vaso-occlusive crisis (VOC), a characteristic manifestation of SCD, is the first cause of patients 'hospitalizations. Here, we describe how our sickle cell referral center has managed outpatient care, with the constant preoccupation of minimizing risks for our patients and avoid them unnecessary trips to heavily burdened hospital settings. DESCRIPTION OF SETTING With the outbreak of Covid-19, our primary obsession was to provide continuous care for our patients, while ensuring their safety. All appointments were canceled when possible and patients were instructed to comply with the national lock down procedures. A hotline and helpdesk were setup as the first stage of our structure. When patients described symptoms of VOC and/or light breathing difficulties, they were enlisted for daily monitoring. This stage two consisted of calling patients daily with a specific set of questions, regarding management and improvement or deterioration of their symptoms. A dedicated team of dentists, who all volunteered and received specific training, managed both stage 1 and 2, along with nurses. SCD specialists supervised these two stages for medical decisions. All symptoms were recorded and reported. If symptoms disappeared, the patient's name was discarded from the list. If there was a worsening or no improvement of the patient's condition, he was moved to stage three by the SCD expert, with the deployment of homecare service. A whole network was then setup, with the delivery of oxygen supply at the patient's house, dispatch of a medical prescription to a neighboring pharmacy and daily visits from homecare service providers. Both opioids and parenteral treatments were prescribed and monitoring was performed daily (blood pressure, temperature, respiratory rate, pain, etc...). On the first visit, a blood sample was sent to a laboratory, to allow calculation of the PRESEV score (Bartolucci et al., 2016). This score, established by team members and colleagues, assesses the risk of acute chest syndrome (ACS). Moreover, it has just been validated by a multicenter international study (PRESEV II - under writing process). In case the PRESEV score was ≤ 5, home hospitalization was pursued. In case this score was ≥11, the patient was sent to hospital for constant monitoring and full comprehensive care. For low and intermediate scores, the patient was referred to hospital for any aggravation. The helpdesk was in constant interaction with nurses and providers of homecare services and status and evolution of the patient's global condition was reported daily for medical decisions. In addition, patients with home hospitalization care were called daily by the helpdesk, to ensure proper care and satisfaction. When home hospitalization was over, the patient automatically came back to stage two for a daily follow-up until full recovery. Early discharged patients could either re-integrate stage 2 or 3 for daily monitoring until full recovery. Out of the 305 patients included in this system, with a total of 2068 calls between March 23rd and May 29th. Seventy five were included for home hospitalization. Mean age was 36 years old [±9], sex ratio was 45/30 (female/male), mean homecare follow up was 6 days (±3), 16 patients also had Covid-19. Thirteen patients (17.3%) were hospitalized: one for an acute chest syndrome, two for a Covid-19 infection and nine for VOC management. Only one patient was in ICU due to a salmonella septicemia. No death was reported. PERSPECTIVES The Covid-19 pandemic has highlighted the need for profound reshaping of healthcare systems worldwide. In this particular context, the structure we have installed, DREPADOM, allowed follow up and monitoring of two profiles of patients: at-risk population of SCD patients and Covid-19 positive SCD patients. With the ongoing situation, our delocalized hospitalization system has proven interesting enough to enter a new phase: DREPADOM was selected as part of a public call for tenders, for financial support to make the structure permanent (DREPADOM - APRES). Disclosures Habibi: Pfizer: Consultancy; Bluebird: Consultancy; Addmedica: Consultancy; Novartis: Consultancy. Bartolucci:GBT: Consultancy; Roche: Consultancy; Emmaus: Consultancy; Innovhem: Other; Addmedica: Research Funding; HEMANEXT: Consultancy; Novartis: Consultancy; ADDMEDICA: Consultancy; Fabre Foundation: Research Funding; Novartis: Research Funding; Bluebird: Consultancy; AGIOS: Consultancy; Bluebird: Research Funding.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2020
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    Online-Ressource
    Online-Ressource
    American Thoracic Society ; 2003
    In:  American Journal of Respiratory and Critical Care Medicine Vol. 168, No. 11 ( 2003-12-01), p. 1373-1377
    In: American Journal of Respiratory and Critical Care Medicine, American Thoracic Society, Vol. 168, No. 11 ( 2003-12-01), p. 1373-1377
    Materialart: Online-Ressource
    ISSN: 1073-449X , 1535-4970
    RVK:
    Sprache: Englisch
    Verlag: American Thoracic Society
    Publikationsdatum: 2003
    ZDB Id: 1468352-0
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 242-242
    Kurzfassung: Abstract 242 Introduction Hydroxyurea (HU) has proved its efficacy in reducing vaso-occlusive events in patients with SCD and increasing life expectancy. However, effects on fertility in adult males represent a major issue for acceptance and adherence, as HU has been reported to impair spermatogenesis through direct cytotoxic effects and hypogonadism. There are only limited data in the literature in this field and mainly retrospective. Patients and methods 49 adult patients aged 20–52 years with homozygous SCD eligible for first line HU treatment were enrolled after informed consent between June 2010 and April 2012 in this prospective study: HYDREP.The main objective was to compare at Day 0 and 180 of HU treatment the semen parameters according to the WHO (1999) criteria(volume, sperm concentration, viability, forward motility and morphology ). Vaso-occlusive events and other complications, number of transfusions during the 6 months preceding and following HU initiation were recorded. Hematological, biochemical, hormonal parameters, HU dosage were recorded at Day 0, Day 90 and 180. HU was begun at 15mg/Kg dose (Platt *) and modulated following haematological tolerance and renal function. Results and discussion Preliminary results concern the 24/49 patients, who complete the 6 months protocol. A statistically significant impairment in all sperm parameters was observed, after a 6 months HU therapy, with great variations between individuals, which are to be explained by complementary tests. These preliminary deleterious findings must be interpreted with caution as in our experience 1) spermatogenesis may recover after drug withdrawal 2) Repeated vaso-occlusive events are also potentially deleterious on fertility (Berthaut **)and 3)this study must be completed with a survey on effective fertility seen in men treated with HU. Thus, regarding to the great benefit offered by HU on prognosis allowing a real “life project” in young symptomatic adults with SCD, it is worth providing each patient of the most accurate information on fertility as an essential prerequisite for their adhesion to HU treatment. Conclusion Sperm cryopreservation is advised before beginning a treatment with HU. Prospective follow up studies of HU male cohort regarding fertility are warranted. Health education has a major role to play to increase HU compliance especially in view of these results. Disclosures: No relevant conflicts of interest to declare.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2012
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    In: American Journal of Hematology, Wiley, Vol. 89, No. 3 ( 2014-03), p. 267-272
    Kurzfassung: Strokes are one of the most severe complications of sickle‐cell disease. Most studies have been restricted to children with sickle‐cell disease. To better understand the characteristics and follow‐up of strokes occurring from childhood to adulthood, we undertook a retrospective cohort study of 69 stroke patients among the 2,875 patients consulting at the French Adult Sickle‐Cell Disease Referral Center. Between 1970 and 2008, they had experienced 104 strokes: 80 ischemic, 22 hemorrhagic, and 2 intracranial sinus thromboses. Coma and/or fatal outcomes underscored the severity of strokes in sickle‐cell disease patients. Hemorrhagic strokes occurred mostly in adults and carried a higher risk of death than ischemic stroke. The mechanisms underlying sickle‐cell disease associated strokes were reevaluated and etiologies were determined for first stroke and recurrences, in childhood and adulthood. Sickle‐cell disease vasculopathy concerned only SS patients and remains their most frequent stroke etiology. Cardioembolism, vaso‐occlusive crisis and triggering factors were other etiologies identified in adults. Recurrences occurred in 19 SS patients only after a first ischemic stroke. SC patients' strokes occurred in adulthood and were associated with cardiovascular risk factors. Our findings provide novel information about cerebrovascular pathologies throughout the lives of sickle‐cell disease patients and suggest the need for different diagnostic and therapeutic management approaches in those different settings. Am. J. Hematol. 89:267–272, 2014. © 2013 Wiley Periodicals, Inc.
    Materialart: Online-Ressource
    ISSN: 0361-8609 , 1096-8652
    URL: Issue
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2014
    ZDB Id: 1492749-4
    Standort Signatur Einschränkungen Verfügbarkeit
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