The impact of hyperfibrinogenemia on short-term outcomes after acute ischemic stroke (AIS) is still not well understood.We investigated the association between hyperfibrinogenemia upon hospital admission and the short-term prognosis of AIS patients.A total of 3,212 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included in the present study. Hyperfibrinogenemia was defined as having a serum fibrinogen＞4.0g/L. Cox proportional hazard and logistic regression models were used to estimate the effect of hyperfibrinogenemia on all-cause in-hospital mortality and poor discharge outcome (modified Rankin Scale score≥3) in AIS patients.During hospitalization, 106 patients (3.3%) died from all-cause and 1226 (38.2%) patients experienced poor functional outcome at discharge. Multivariable model adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, white blood cell count and other covariates, showed that hyperfibrinogenemia was associated with a 1.76-fold increase in the risk of in-hospital mortality (hazard ratio [HR] 1.76; 95% confidence interval [CI], 1.10-2.81; P-value=0.019). However, there was no significant association between hyperfibrinogenemia and poor outcome at discharge (adjusted odds ratios[OR]1.15; 95% CI 0.86-1.53; P-value=0.338). Sensitivity and subgroup analyses also confirmed a significant association between hyperfibrinogenemia and in-hospital mortality.In patients with AIS, hyperfibrinogenemia at the time of admission was independently associated with increased in-hospital mortality.
Objectives Treating red blood cells (RBCs) with dithiothreitol (DTT) is a wildly-recommended to overcome the interference of the daratumumab (DARA) with blood compatibility testing. Nevertheless, DTT can be hard to obtain in the clinical laboratory, while its use in routine practice may be time-consuming. In the following study, we explored the feasibility of using a commercial 2-mercaptoethanol (2-ME) working solution or the time-saving Polybrene method to mitigate DARA interference.Methods Antibody screening and cross-matching were performed using 2-ME or DTT-based indirect antiglobulin tests (IATs) and Polybrene method (with human IgG anti-E same IATs titer as DARA as positive control) on 37 samples. Most clinically important blood group antigens on RBCs were detected after treatment with 2-ME or DTT.Results Treating RBCs with 2-ME eliminates the DARA interference with the antibody screening or cross-matching; yet, K antigen is denatured during treatment. DARA does not interfere with antibody screening and cross-matching via Polybrene method, while 2+ agglutinations of anti-E antibody with the same titer (IATs method) as DARA could be observed in the positive controls via this method.Conclusion 2-ME-based IATs or Polybrene method could replace DTT-based IATs to mitigate DARA interference.
Background Identifying genetic variants of the ABO gene may reveal new biologic mechanisms underlying variant phenotypes of the ABO blood group. We report the molecular genetic analysis of 322 apparently unrelated ABO subgroup individuals in an estimated 2.1 million donors. Study Design and Methods We performed phenotype investigations by serology studies, analyzed the DNA sequence of the ABO gene by direct sequencing or sequencing after cloning, and evaluated promoter activity by reporter assays. Results In 62 rare ABO alleles, we identified 29 novel ABO subgroup alleles in 43 apparently unrelated subgroup individuals and their four available pedigrees. Of these alleles, one was a deletion‐mutation allele, four were hybrid alleles, and 24 were point‐mutation alleles. Most of the point mutations were detected in Exons 6 to 7, while several others were also detected in Exons 1 to 5 or splicing regions. One ABO promoter mutation, −35 to −18 del, was found and verified to reduce promoter activity, as determined by dual luciferase assays. Two mutations, 7 G > T and 52 C > T , carrying the premature terminal codons E 3 X and R 18 X in the 5′‐region, were found to be associated with the very weak ABO subgroups “ A el” and “ B el.” Conclusion Twenty‐nine ABO subgroup alleles were newly linked to different kinds of ABO variations. We provide the first evidence that promoter abnormality is involved in the formation of weak ABO phenotypes. We also described the first naturally occurring ABO alleles with premature terminal codons in the 5′‐region that led to A el and B el phenotypes.
Abstract Background Treating red blood cells (RBCs) with dithiothreitol (DTT) is a wildly-recommended to overcome the interference of anti-CD38 immunotherapy with blood compatibility testing. Nevertheless, DTT can be hard to obtain in clinical laboratory, while its use in routine practice may be time-consuming. In the following study, we explored the feasibility of using a commercial 2-mercaptoethanol (2-ME) working solution or the time-saving polybrene method to mitigate the daratumumab (DARA) interference. Materials and Methods Antibody screening and cross-matching were performed using 2-ME or DTT-based indirect antiglobulin tests (IATs) and polybrene method (human IgG anti-E same IATs titer as DARA as positive control) on 37 samples, and these samples were from patients enrolled in the “Several methods resolve the interference of anti-CD38 monoclonal antibody on blood compatibility tests” clinical trial ( www.chictr.org.cn identifier: ChiCTR2000040761). Most clinically important blood group antigens on RBCs were detected after treatment with 2-ME or DTT. Hemoglobin values were compared after 69 units RBCs were transfused with compatible cross-matching results by a 2-ME-based method or polybrene test. Results Treating RBCs with 2-ME eliminates the DARA interference with the antibody screening or cross-matching; yet, K antigen is denatured during treatment. DARA with 2+ agglutinations of anti-E control does not interfere with antibody screening and cross-matching via polybrene method. After RBCs transfusion with a negative cross-matching test by 2-ME-based IATs or polybrene method, hemoglobin significantly increased without adverse transfusion reactions. Conclusion 2-ME-based IATs or polybrene method could be used to mitigate DARA interference as DTT.
Alzheimer's disease (AD) is characterized by β-amyloid (Aβ) plaques consisted primarily of aggregated Aβ proteins and neurofibrillary tangles formed by hyperphosphorylated tau protein. Both Aβ and hyperphosphorylated tau are toxic both in vivo and in vitro. Immunotherapy targeting Aβ seems to provide a promising approach to reduce the toxic species in the brain. However, there is little evidence from clinical trials so far indicating the efficacy of Aβ immunotherapy in cognitive improvement. Immunization with tau peptides or anti-tau antibodies could remove the tau aggregates and improve the cognitive function in preclinical study, which provides a novel strategy of AD therapy. In this article, we will summarize the immunotherapeutic strategies targeting either Aβ or tau.
B(x) is a very rare ABO blood group phenotype and the molecular mechanism underlying it still remains largely unknown. This study reports two novel B(x) alleles in two Chinese individuals.Serologic investigations including serum transferase activity assay were performed with standard methods. DNA sequences of all seven exons and exon-intron boundaries of ABO gene were analyzed using genomic DNA by polymerase chain reaction and direct DNA sequencing or sequencing after gene cloning.B(x) phenotypes were diagnosed in these two individuals. DNA analysis revealed that the ABO gene of the two B(x) individuals was heterozygous of O01/B alleles. Two novel heterozygous mutations 905A>G and 541T>C were identified, respectively, which resulted in the amino acid changes D302G and W181R in the B glycosyltransferases. The mutations were not found in 120 randomly selected samples.Amino acid substitutions resulted from novel mutations 905A>G and 541T>C on ABO gene change highly conserved regions of the enzyme and may reduce the activity of the glycosyltransferases, leading to the B(x) phenotype.
Supplementary Data 1 Exon19 of the mother's SLC4A1 gene, code Diego antigen Dia/Dia Supplementary Data 2 Exon19 of the neonate's SLC4A1 gene, code Diego antigen Dia/Dib Supplementary Data 3 Serologic result of the neonate Column 1: The serum of the newborn reacted positively to type A red blood cells. Column 2: The serum of the newborn reacted positively to type O red blood cells. Column 3: The RBC eluate of the newborn reacted positively to type A red blood cells. Column 4: The RBC eluate of the newborn reacted positively to type O red blood cells. Column 5: DAT of the newborn was positive. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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