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Effective prophylaxis with rFVIIa in young haemophiliacs with inhibitors using a schedule similar to FVIII prophylaxis in non-inhibitor patients

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Health 2013年第7期5卷 1151-1157页

作者： Maria Fernanda Lopez-Fernandez Carmen Altisent Victor Jimenez-Yuste Faustino Garcia-Candel Carmen Sedano Ana Cid Eva Mingot ramiro nunez Maria Jose Paloma Inmaculada Soto Manuel Prieto Haematology Complejo Hospitalario Universitario A CorunaA CorunaSpain Haemophilia Unit Hospital Universitario Vall d’HebronBarcelonaSpain Haemophilia Unit Hospital UniversitarioMadridSpain Haemophilia Unit Hospital Universitario Virgen de la ArreixacaMurciaSpain Haematology Complejo Hospitalario Universitario Marques de ValdecillaSantanderSpain Congenital Coagulophaties Unit Hospital Universitario La FeValenciaSpain Haematology Hospital Universitario Carlos HayaMalagaSpain Haematology Hospital Universitario Virgen del RocíoSevillaSpain Haematology Hospital Virgen del CaminoPamplonaSpain Haematology Hospital General de AsturiasOviedoSpain Haematology Hospital General YagüeBurgosSpain

Objective: To assess the role of early prophylaxis with recombinant activated factor VII (rFVIIa) in young haemophiliacs with inhibitors and to determine whether it can reduce bleeding episodes and prevent joint damage. Patients and Methods: Ten severe haemophiliacs, less of three years old, with up to four joint bleeds and inhibitors to FVIII who started early prophylaxis with rFVIIa, were included. A number of haemorrhages/year/patient and haemarthroses/ year/patient were compared before the start of prophylaxis, which include both the time before (initial period) and after inhibitor diagnosis (inhibitor period), with those during prophylaxis (prophylaxis period). Results: The mean time of inhibitor diagnosis was 15.6 months (range: 2.3-34.1). The mean time between inhibitor diagnosis and the start of prophylaxis was 7.1 months (range: 0-23.2), shorter than the time of rFVIIa prophylaxis (mean: 10.3 months;range: 4.1-32.0). Bleeding episodes for the three time periods were 45, 36 and 17, respectively, or 0.29 and 0.51 haemorrhages/year/patient in the two periods prior to prophylaxis compared to 0.17 during prophylaxis. Total haemarthroses for the three-time periods were 7, 5 and 5, respectively. The haemarthroses/year/patient in the pre-prophylaxis period were 0.032 and 0.070, compared to0.049 inthe prophylaxis period. rFVIIa schedules were either 90 μg/kg three times weekly or 90 μg/kg daily. Conclusions: Early prophylaxis with rFVIIa may be efficacious in young haemophiliacs with inhibitors, reducing joint bleeds. After the risky period of inhibitor presence, they are able to continue rFVIII prophylaxis with success assured to prevent arthropathy.

关键词： rFVIIa Haemarthroses Haemophilia Inhibitors Prophylaxis

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Acute kidney injury in severely injured patients admitted to the Intensive Care Unit

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Military Medical Research 2021年第2期8卷 141-147页

作者： Alberto F.García ramiro Manzano-nunez Juan G.Bayona Maria P.Naranjo Dary Neicce Villa Manuel Moreno Sebastian Ossa Juan M.Martinez Nathalia Martinez Juan C.Puyana Division of Trauma and Acute Care Surgery Department of SurgeryFundación Valle del LiliCaliColombia Clinical Research Center Fundación Valle del LiliCaliColombia Escuela de Medicina Ciencias de la SaludUniversidad del RosarioCarrera 98#18-49760001BogotaColombia Méderi Hospital Universitario Mayor Colombia School of Medicine Universidad ICESI(ICESI University)CaliColombia Department of Surgery University of PittsburghPittsburghPAUSA

Background:Our objective was to identify possible associations between clinical and laboratory variables and the risk of developing acute kidney injury(AKI)in severely injured patients admitted to the Intensive Care Unit(ICU)for whom creatine kinase(CK)levels were available.Methods:For this retrospective observational study,we analyzed adult trauma patients admitted to the ICU from 2011 to 2015 at Fundación Valle del Lili(FVL)University Hospital.Our primary outcome was the incidence of AKI.Multivariate regression analysis was used to assess risk factors for this outcome.Results:A total of 315 patients were included.The trauma mechanisms were blunt(n=130),penetrating(n=66)and blast(n=44)trauma.The median[interquartile range,(IQR)of injury severity score(ISS)was 21(16–29).AKI developed in 75 patients(23.8%).Multivariate regression analysis revealed that the thoracic abbreviated injury scale(AIS)value(median(IQR)in the AKI group:3(0–4)],Acute Physiology and Chronic Health Evaluation(APACHE Ⅱ)score[median(IQR)in the AKI group:18(10–27)],CK greater than 5000 U/L,lactic acid concentration at admission,and dobutamine administration were independently associated with AKI.Conclusions:We found that age,APACHE Ⅱ score,thoracic trauma,lactic acidosis,and dobutamine administration were independently associated with AKI.Trauma surgeons need to be aware of the increased odds of AKI if one of these factors is identified during the evaluation and treatment of injured patients.

关键词： Rhabdomyolysis Wounds and injuries Acute kidney injury Critical care Trauma

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A new approach for the treatment of CLL using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles

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Nano Research 2016年第2期9卷 537-548页

作者： Sara Capolla Nelly Mezzaroba Sonia Zorzet Claudio Tripodo ramiro Mendoza-Maldonado Marilena Granzotto Francesca Vita Ruben Spretz Gustavo Larsen Sandra Noriega Eduardo Mansilla Michele Dal Bo Valter Gattei Gabriele Pozzato Luis nunez Paolo Macor Department of Life Sciences University of Trieste 34127 Trieste Italy Department of Human Pathology University of Palermo 90133 Sicilia Italy Molecular Oncology Unit National Laboratory Consorzio Interuniversitatio per le Biotecnologie (CIB) 34012 Trieste Italy Dipartimento Universitario Clinico di Scienze mediche Chirurgiche e della Salute University of Trieste 34149 Trieste Italy LNK Chemsolutions LLC Lincoln NE 68521 USA Bio-Target Inc. Chicago IL 60637 USA Centro Unico Coordinador de Ablacion e Implante Provincia de Buenos Aires (C.U.CA.I.B.A.) Ministry of Health La Plata Buenos AiresArgentina Clinical and Experimental Onco-Hematology Unit Centro di Riferimento Oncologico Istituto di Ricerca e Cura a Carattere Scientifico(I.R.C.C.S.) 33081 Aviano Italy Callerio Foundation Onlus Institutes of Biological Researches 34127 Trieste Italy

Current approaches for the treatment of chronic lymphocytic leukemia （CLL） have greatly improved the prognosis for survival, but some patients remain refractive to these therapeutic regimens. Hence, in addition to reducing the long-term side- effects of therapeutics for all leukemia patients, there is an urgent need for novel therapeutic strategies for difficult-to-treat leukemia cases. Due to the cytotoxicity of drugs, the major challenge currently is to deliver the therapeutic agents to neoplastic cells while preserving the viability of non-malignant ceils. In this study, we propose a therapeutic approach in which high doses of hydroxychloroquine and chlorambucil were loaded into biodegradable polymeric nanopartides coated with an anti-CD20 antibody.We first demonstrated the ability of the nanoparticles to target and internalize in tumor B-cells. Moreover, these nanoparticles could kill not only p53-mutated]deleted leukemia cells expressing a low amount of CD20, but also circulating primary ceils isolated from chronic lymphocytic leukemia patients. The safety of these nanoparticles was also demonstrated in healthy mice, and their therapeutic effects were shown in a new model of aggressive leukemia. These results showed that anti-CD20 nanoparticles containing hydroxychloroquine and chlorambucil can be effective in controlling aggressive leukemia and provided a rationale for adopting this approach for the treatment of other B-cell disorders.

关键词： chronic lymphocytic leukemia,immune targeted nanoparticles,treatment,xenograft model

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