354 research outputs found

    EVALUACIÓN DE RESULTADOS QUIRÚRGICOS DESDE LA PERSPECTIVA DEL PACIENTE

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    RESUMENMedir la calidad de vida relacionada a salud y los síntomas de los pacientes es un problema difícil. Las medición de los problemas de salud mediante escalas o cuestionarios se ha desarrollado para crear los Instrumentos de Evaluación desde la Perspectiva del Paciente o PRO's por su nombre en inglés: Patient-reported outcomes. Los PROs evalúan la calidad de vida en forma genérica o específica en un continuo, entregando instrumentos que pueden evaluar la gravedad de una enfermedad o el impacto de una intervención desde la perspectiva del paciente en frecuentes escenarios clínicos. El objetivo de la presente revisión es entregar a clínicos e investigadores una introducción hacia los PROs y resumir sus principales propiedades.SUMMARYQuantifying health-related quality of life and specific patient symptoms it is a difficult problem. Health measurement scales has developed to include rigorous techniques to develop patient-reported outcome measures (PROs). PROs assess objectively the QoL in a continuum, providing instruments to measure the severity of a given disease or the impact of a therapeutic intervention from patient perspective in different clinical problems. The following review aims to introduce the PROs to clinicians and researchers and summarize its main properties

    Afucosylated IgG responses in humans – structural clues to the regulation of humoral immunity

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    Healthy immune responses require efficient protection without excessive inflammation. Recent discoveries on the degree of fucosylation of a human N-linked glycan at a conserved site in the immunoglobulin IgG-Fc domain might add an additional regulatory layer to adaptive humoral immunity. Specifically, afucosylation of IgG-Fc enhances the interaction of IgG with FcγRIII and thereby its activity. Although plasma IgG is generally fucosylated, afucosylated IgG is raised in responses to enveloped viruses and Plasmodium falciparum proteins expressed on infected erythrocytes, as well as during alloimmune responses. Moreover, while afucosylation can exacerbate some infectious diseases (e.g., COVID-19), it also correlates with traits of protective immunity against malaria and HIV-1. Herein we discuss the implications of IgG afucosylation for health and disease, as well as for vaccination

    Are measurable residual disease results after consolidation therapy useful in children with acute lymphoblastic leukemia?

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    Measurable residual disease (MRD) is regularly tested at later timepoints after the end of first consolidation (EOC) in children with acute lymphoblastic leukemia (ALL). The question remains whether this is useful for detecting (molecular) relapse. We investigated the clinical relevance of MRD after EOC in intermediate risk patients treated on DCOG-ALL-10 (n = 271) and DCOG-ALL-9 (n = 122), with MRD &lt;0.05% at EOC. EOC MRD-negative patients (n = 178) had excellent outcomes, irrespective of MRD results at later timepoints; 6-year cumulative incidence of relapse (6-y CIR) of 7.4% (95% CI, 3.9%–12.3%) for those with MRD negativity at all later timepoints compared to 3.8% (95% CI, 0.3%–16.8%) for those with one or more later timepoints being positive (p = 0.51). Patients with positive EOC MRD (n = 91) of whom the subsequent timepoints were MRD negative (n = 43), had comparable good outcomes, 6-y CIR of 7.0% (95% CI, 1.8%–17.2%). In contrast, patients being MRD positive at EOC and MRD positive at one or more subsequent timepoints (n = 48) had a higher risk of relapse, 6-y CIR 29.4% (95% CI, 17.2%–42.8%), p &lt; 0.001. These findings were confirmed in the validation cohort of ALL-9 as well as using the updated EuroMRD guidelines. In EOC MRD-negative patients, subsequent MRD measurements can be abandoned. For EOC MRD-positive patients the subsequent MRD measurement might be informative for further risk stratification.</p

    A prominent lack of IgG1-Fc fucosylation of platelet alloantibodies in pregnancy.

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    To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Immunoglobulin G (IgG) formed during pregnancy against human platelet antigens (HPAs) of the fetus mediates fetal or neonatal alloimmune thrombocytopenia (FNAIT). Because antibody titer or isotype does not strictly correlate with disease severity, we investigated by mass spectrometry variations in the glycosylation at Asn297 in the IgG Fc because the composition of this glycan can be highly variable, affecting binding to phagocyte IgG-Fc receptors (FcγR). We found markedly decreased levels of core fucosylation of anti-HPA-1a-specific IgG1 from FNAIT patients (n = 48), but not in total serum IgG1. Antibodies with a low amount of fucose displayed higher binding affinity to FcγRIIIa and FcγRIIIb, but not to FcγRIIa, compared with antibodies with a high amount of Fc fucose. Consequently, these antibodies with a low amount of Fc fucose showed enhanced phagocytosis of platelets using FcγRIIIb(+) polymorphonuclear cells or FcγRIIIa(+) monocytes as effector cells, but not with FcγRIIIa(-) monocytes. In addition, the degree of anti-HPA-1a fucosylation correlated positively with the neonatal platelet counts in FNAIT, and negatively to the clinical disease severity. In contrast to the FNAIT patients, no changes in core fucosylation were observed for anti-HLA antibodies in refractory thrombocytopenia (post platelet transfusion), indicating that the level of fucosylation may be antigen dependent and/or related to the immune milieu defined by pregnancy.Sanquin/PPOC-09- 025 Landsteiner Foundation for Blood Transfusion/0721 info:eu-repo/grantAgreement/EC/FP7/27853

    Real-world performance of a clinical droplet digital polymerase chain reaction assay for non-invasive foetal blood group and platelet antigen genotyping of alloimmunized pregnant women with antibodies directed against RhD, RhE, Rhc, RhC, K1, HPA-1a or HPA-5b:A 1-year experience

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    Background and Objectives: To test the performance of a new droplet digital polymerase chain reaction (ddPCR) non-invasive foetal blood group and platelet antigen genotyping assay in the setting of a Dutch reference laboratory for foetal blood group and platelet antigen genotyping. Our population comprised 229 consecutive alloimmunized pregnant women who presented between April 2022 and March 2023 with 250 requests for non-invasive foetal RHD, RHE, RHc, RHC, K1, HPA-1a or HPA-5b blood group and platelet antigen genotyping. Materials and Methods: Samples were genotyped for blood group and platelet antigen alleles along with methylated RASSF1a (mRASSF1a) and sex-determining region of Y (SRY) and DYS14 as positive foetal controls. Negative blood group and platelet antigen results were issued only when foetal controls were positive; otherwise, such samples were classified as inconclusive. Results: The assay achieved a success rate of 98.4% (246 of 250) because one case was lost to follow-up, one case was solved with quantitative polymerase chain reaction (qPCR) and one case precluded foetal typing due to RHD variant mothers. Only 10 cases needed a second sample and one case a third for a valid final result. We identified 116 maternal–foetal blood group and platelet antigen incompatibilities. Conclusion: Clinical non-invasive foetal blood group and platelet antigen typing of alloimmunized pregnant women via ddPCR is successful and represents an improvement over qPCR because of the addition of a foetal control and because ddPCR circumvents potential interference from maternal cell-free DNA (cfDNA) background for foetal HPA-1 and K1.</p

    Reduction of anti-K-mediated hemolytic disease of newborns after the introduction of a matched transfusion policy:A nation-wide policy change evaluation study in the Netherlands

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    Background: During pregnancy, maternal red blood cell (RBC) antibodies can lead to life-threatening fetal hemolysis and anemia. Women can become immunized by a pregnancy or an unmatched transfusion. Our aim was to quantify the effect of a nationwide K-matched transfusion policy for women of childbearing age potential to prevent K-immunization in pregnancy. Study Design and Methods: In this nation-wide policy change evaluation study we determined the occurrence of RBC antibodies before and after introduction of a K-matched transfusion policy and evaluated the cause K alloimmunization 10 years after introduction of this measure. K-matched transfusion for females under 45 years of age is advised in the Dutch transfusion guideline since 2004. We used laboratory data from pregnancies with RBC antibodies identified in the period 1999-2018 obtained as part of a population-based screening program in the Netherlands. Results: Tests of 36 286 pregnancies produced a positive antibody screening result which concerned anti-K in 1550 pregnancies. The occurrence of anti-K decreased from 67.9 to 20.2 per 100 000 pregnancies. The relative risk reduction was 0.70 which largely exceeded the relative risk reduction of 0.27 for antibodies against RBC antigens for which no preventive matching is required. The number of pregnancies at risk for anti-K-mediated disease decreased from 9.7 to 4.2 per 100 000 pregnancies. Conclusions: A K-matched transfusion policy is associated with a major decrease in a number of pregnant women with anti-K and pregnancies at risk for anti-K-mediated disease. A relatively simple measure is now shown to impact prevention of hemolytic disease in the fetus and newborn
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