Although allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment for patients with Fanconi anemia (FA), published series mostly refer to single-center experience ...with limited numbers of patients. We analyzed results in 795 patients with FA who underwent first HSCT between May 1972 and January 2010. With a 6-year median follow-up, overall survival was 49% at 20 years (95% confidence interval, 38-65 years). Better outcome was observed for patients transplanted before the age of 10 years, before clonal evolution (ie, myelodysplastic syndrome or acute myeloid leukemia), from a matched family donor, after a conditioning regimen without irradiation, the latter including fludarabine. Chronic graft-versus-host disease and secondary malignancy were deleterious when considered as time-dependent covariates. Age more than 10 years at time of HSCT, clonal evolution as an indication for transplantation, peripheral blood as source of stem cells, and chronic graft-versus-host disease were found to be independently associated with the risk for secondary malignancy. Changes in transplant protocols have significantly improved the outcome of patients with FA, who should be transplanted at a young age, with bone marrow as the source of stem cells.
Key Points
This study concerns the interactional work involved in the accomplishment of video-mediated homework support and is based on a single case analysis of an instructional encounter between a tutor and ...an upper-secondary student working together on mathematical assignments. In addition to communicating through video, the participants use an online digital platform that constitutes a shared workspace and interface between the participants, who are situated in geographically disparate locations. A crucial feature of the setting is the unequal distribution of epistemically rich artefacts, such as the maths book, to which the tutee has sole access. Drawing on ethnomethodology and multimodal interaction analysis, the analyses show how the interaction is shaped by and contingent upon the affordances of the online platform and the particular circumstances of the video-mediated setting. The findings reveal how the participants work together to establish shared points of reference from which they embark on collaborative problem-solving trajectories while establishing the problem to be worked upon and its interpretation, as well as negotiating proper presentations of solutions. Additionally, the way in which the participants overcome the interactional and epistemic challenges implicated by the unequal access to crucial epistemic resources is shown.
A multicentre study evaluating the presence of glycosil phosphatidyl-inositol (GPI)-negative populations was performed in 85 children with acquired aplastic anemia (AA). A GPI-negative population was ...observed in 41% of patients at diagnosis, 48% during immune-suppressive therapy (IST), and 45% in patients off-therapy. No association was found between the presence of a GPI-negative population at diagnosis and the response to IST. In addition, the response rate to IST did not differ between the patients who were GPI-positive at diagnosis and later developed GPI-negative populations and the 11 patients who remained GPI-positive. Two patients with a GPI-negative population >10%, and laboratory signs of hemolysis without hemoglobinuria were considered affected by paroxysmal nocturnal hemoglobinuria (PNH) secondary to AA; no thrombotic event was reported. Excluding the 2 patients with a GPI-negative population greater than 10%, we did not observe a significant correlation between LDH levels and GPI-negative population size. In this study monitoring for laboratory signs of hemolysis was sufficient to diagnose PNH in AA patients. The presence of minor GPI-negative populations at diagnosis in our series did not influence the therapeutic response. As occasionally the appearance of a GPI-negative population was observed at cyclosporine (CSA) tapering or AA relapse, a possible role of GPI-negative population monitoring during IST modulation may need further investigation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A prolonged preoperatory aPTT in children is often the cause of a delay of scheduled surgeries and the repetition of multiple blood tests, with the consequent wasting of resources and significant ...discomfort for children and parents. The aim of this review is to analyze the situations in which an isolated prolongation of aPTT is found during preoperative evaluation in children, especially when it is due to the presence of antiphospholipid antibodies, providing the readers with the keys to interpret this situation and the possibility to correctly evaluate the hemorrhagic risk of a patient.
Diamond-Blackfan anemia is an autosomal dominant disease due to mutations in nine ribosomal protein encoding genes. Because most mutations are loss of function and detected by direct sequencing of ...coding exons, we reasoned that part of the approximately 50% mutation negative patients may have carried a copy number variant of ribosomal protein genes. As a proof of concept, we designed a multiplex ligation-dependent probe amplification assay targeted to screen the six genes that are most frequently mutated in Diamond-Blackfan anemia patients: RPS17, RPS19, RPS26, RPL5, RPL11, and RPL35A. Using this assay we showed that deletions represent approximately 20% of all mutations. The combination of sequencing and multiplex ligation-dependent probe amplification analysis of these six genes allows the genetic characterization of approximately 65% of patients, showing that Diamond-Blackfan anemia is indisputably a ribosomopathy.
Hemophilia Care in the Pediatric Age Bertamino, Marta; Riccardi, Francesca; Banov, Laura ...
Journal of clinical medicine,
05/2017, Letnik:
6, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Hemophilia is the most common of the severe bleeding disorders and if not properly managed since early infancy can lead to chronic disease and lifelong disabilities. However, it enjoys the most ...efficacious and safe treatment among the most prevalent monogenic disorders. Hemophilia should be considered in the neonatal period in the case of unusual bleeding or in the case of positive family history. Later, hemophilia should be suspected mainly in males because of abnormal bruising/bleeding or unusual bleeding following invasive procedures-for example, tonsillectomy or circumcision. Prophylactic treatment that is started early with clotting-factor concentrates has been shown to prevent hemophilic arthropathy and is, therefore, the gold standard of care for hemophilia A and B in most countries with adequate resources. Central venous access catheters and arterovenous fistulas play an important role in the management of hemophilia children requiring repeated and/or urgent administration of coagulation factor concentrates. During childhood and adolescence, personalized treatment strategies that suit the patient and his lifestyle are essential to ensure optimal outcomes. Physical activity is important and can contribute to better coordination, endurance, flexibility and strength. The present article focuses also on questions frequently posed to pediatric hematologists like vaccinations, day-care/school access and dental care.
Acquired aplastic anemia (AA) is a rare heterogeneous disease characterized by pancytopenia and hypoplastic bone marrow. The incidence is 2–3/million inhabitants/year, in Europe, but higher in East ...Asia. Survival in severe aplastic anemia (SAA) has markedly improved in the past 2decades because of advances in hematopoietic stem cell transplantation, immunosuppressive and biologic drugs, and supportive care. In SAA hematopoietic stem cell transplant (HSCT) from a matched sibling donor (MSD) is the treatment of choice. If a MSD is not available, the options include immunosuppressive therapy (IST) or unrelated donor HSCT. The objective of this guideline is to provide healthcare professionals with clear guidance on the diagnosis and management of pediatric patients with AA. A preliminary, evidence-based document issued by a group of pediatric hematologists was discussed, modified and approved during a series of “Consensus Conferences” according to procedures previously validated by the AIEOP Board. The guidelines highlight the importance of referring pediatric patients with AA to pediatric centers with long experience in diagnosis, differential diagnosis, management, supportive care and follow-up of AA.
Fanconi anemia is an inherited disease characterized by congenital malformations, pancytopenia, cancer predisposition, and sensitivity to cross-linking agents. The molecular diagnosis of Fanconi ...anemia is relatively complex for several aspects including genetic heterogeneity with mutations in at least 16 different genes. In this paper, we report the mutations identified in 100 unrelated probands enrolled into the National Network of the Italian Association of Pediatric Hematoly and Oncology. In approximately half of these cases, mutational screening was carried out after retroviral complementation analyses or protein analysis. In the other half, the analysis was performed on the most frequently mutated genes or using a next generation sequencing approach. We identified 108 distinct variants of the FANCA, FANCG, FANCC, FANCD2, and FANCB genes in 85, 9, 3, 2, and 1 families, respectively. Despite the relatively high number of private mutations, 45 of which are novel Fanconi anemia alleles, 26% of the FANCA alleles are due to 5 distinct mutations. Most of the mutations are large genomic deletions and nonsense or frameshift mutations, although we identified a series of missense mutations, whose pathogenetic role was not always certain. The molecular diagnosis of Fanconi anemia is still a tiered procedure that requires identifying candidate genes to avoid useless sequencing. Introduction of next generation sequencing strategies will greatly improve the diagnostic process, allowing a rapid analysis of all the genes.
The study targets how reported speech is used as an interactional resource for building and legitimatizing a particular version of events in the context of peer disputes. Several unfolding multiparty ...storytelling events within a group of preadolescent girls in a Swedish school setting are analyzed, primarily highlighting the interactional use of previous talk in building credibility for particular affective and moral stances, as well as blame accusations during disputes. Overall, the study highlights different ways that reported speech can function as a resource for legitimizing negative assessments of opposite parties, building alliances, and taking sanctioning actions toward peers.
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