John Bæch

Storage time of allogeneic red blood cells is associated with risk of severe postoperative infection after coronary artery bypass grafting

OBJECTIVE The storage time of allogeneic red blood cells (RBCs) has been linked with the risk of severe postoperative infections following cardiac surgery. However, existing data are sparse and inconsistent. We therefore examined the association between the age of transfused RBCs and development of severe postoperative infection following coronary artery bypass grafting (CABG) in a large population-based cohort study. METHODS The study included patients undergoing CABG with or without concomitant cardiac surgery between June 2003 and July 2008 in the North and Central Denmark regions. Data on demography, perioperative variables, allogeneic blood transfusion and severe postoperative infections (deep sternal wound infection, bacteremia or septicemia) were retrieved from medical databases and medical records. We used logistic regression analyses to compute the crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for the association between storage time of transfused RBCs and the risk of severe infection. RESULTS A total of 4240 patients were included in the final analyses, and 1748 of these patients (41%) were transfused with RBCs. Among transfused patients, 953 were exclusively transfused with RBC stored for < 14 days and 548 were exclusively transfused with RBC stored for ≥ 14 days. Severe infection was identified in 165 patients (3.9%). The adjusted ORs for severe infection among all transfused patients and patients transfused with RBCs stored exclusively for either < 14 days or ≥ 14 days were 1.6 (95% CI: 0.9-2.8), 1.1 (95% CI: 0.6-2.1), and 2.3 (95% CI: 1.2-4.2), respectively, when compared with non-transfused patients. There was a dose-response relationship between the number of transfused RBC units and the risk of severe infection among patients exclusively transfused with RBCs stored for ≥ 14 days. CONCLUSION Although the risk of possible confounding could not be eliminated entirely in this observational study, the findings add further support for the hypothesis that storage time of RBCs is positively associated with the risk of transfusion-related severe postoperative infection in patients undergoing CABG.

Promoter polymorphisms in the chitinase 3-like 1 gene influence the serum concentration of YKL-40 in Danish patients with rheumatoid arthritis and in healthy subjects

IntroductionThe present study investigates the association between single nucleotide polymorphisms (SNPs) in the chitinase 3-like 1 (CHI3L1) gene and serum concentrations of YKL-40 in Danish patients with rheumatoid arthritis (RA) and healthy controls as well as the association with RA in the Danish population. The CHI3L1 gene is located on chromosome 1q32.1 and encodes the YKL-40 glycoprotein. YKL-40 concentrations are elevated in the serum of patients with RA compared to healthy subjects, and YKL-40 has been suggested to be an auto-antigen and may play a role in development of RA and in inflammation.MethodsEight SNPs in the CHI3L1 gene and promotor were genotyped in 308 patients with RA and 605 controls (healthy blood donors) using TaqMan allele discrimination assays. Serum concentrations of YKL-40 were determined by an enzyme-linked immunosorbent assay (ELISA).ResultsWe found significant association between the serum concentrations of YKL-40 and polymorphism in the CHI3L1 gene among both patients with RA and controls. The g.-131(C > G) polymorphism (rs4950928) was most strongly associated with age adjusted serum concentrations of YKL-40 in patients with RA (P < 2.4e-8) and controls (P < 2.2e-16). No significant allelic- or genotypic association with RA was found in this Danish cohort.ConclusionsWe suggest that the g.-131(C > G) promoter polymorphism has a substantial impact on serum concentrations of YKL-40 in patients with RA and healthy subjects. However, the polymorphism does not seem to confer risk to RA itself. The effect of CHI3L1 polymorphism on clinical outcome or the response to treatment in patients with RA remains to be investigated.

Validation of the Nordic Flow Cytometry Standard for CD34+ Cell Enumeration in Blood and Autografts: Report from the Third Workshop

Following two workshops on standardization of enumeration of CD34+ cells in blood and leukapheresis products, the Nordic Stem Cell Laboratory Group (NSCL-G) evaluated the Milan/Mulhouse/Nordic standard in clinical practice during the third workshop (WS-III). This report documents an acceptable interlaboratory variation in the most clinically active laboratories, with a coefficient of variation (CV) below 0.19 in 7 of 8 analyses performed. The introduction of a pan-CD45 antibody in the analysis did not improve the CV. Comparison of two different CD34 class II antibodies on a total of 99 samples and procedures with and without washing on a total of 96 samples revealed a significant correlation (r2 >0.99) for all analyses. Finally, subset analysis of uncommitted and lineage-specific progenitors revealed major gating difficulties, indicating that further improvements are necessary. In an analysis of more than 600 patients undergoing mobilization and harvest of blood progenitors, with about 500 patients autografted, we found a significant correlation between blood levels of CD34+ cells and recovery of CD34+ cells from each harvest as well as between CD34+ cell number reinfused and time to neutrophil and platelet recovery. This report documents for the first time that the very simple Milan/Mulhouse method (termed The Nordic Standard) can be used by a group of laboratories to obtain important clinical information. Consequently, we consider this method as the conventional method in quality assessment of autografts, which should provide a benchmark for development of second-generation improvements.

Routine noninvasive prenatal screening for fetal RHD in plasma of RhD-negative pregnant women—2 years of screening experience from Denmark

Prenatal and postnatal RhD prophylaxis reduces the risk of RhD immunization in pregnancies of RhD‐negative women. Based on the result from prenatal screening for the fetal RHD gene, prenatal RhD prophylaxis in Denmark is targeted to RhD‐negative women who carry an RhD‐positive fetus. Here, we present a 2‐year evaluation of a nationwide prenatal RHD screening.

Frequencies of HNA‐1, HNA‐3, HNA‐4, and HNA‐5 in the Danish and Zambian populations determined using a novel TaqMan real time polymerase chain reaction method

In this study, we report a novel real time polymerase chain reaction (Q-PCR) method using TaqMan probes for human neutrophil antigens (HNA)-1, -3, -4, and -5 genotyping. The method was validated in a Caucasian Danish population, a Zambian population, and in clinical samples using three different methods: an in-house polymerase chain reaction with sequence-specific primers (PCR-SSP) method, a commercial available PCR-SSP kit and a novel Q-PCR method. We observed no discrepancy in the genotype frequencies determined by the PCR-SSP methods and the TaqMan assay in the populations studied. In tests of a family of Nigerian origin and in samples carrying the rare SLC44A2*1:2 genotype, different results were produced by the commercial PCR-SSP kit and the real-time TaqMan assay. The TaqMan-based genotyping method was rapid and reproducible, allowing high-throughput HNA-1, -3, -4, and -5 genotyping.

Failure of metal-backed patellar arthroplasty. 47 AGC total knees followed for at least 1 year

A prospective series of 47 total knee arthroplasties in 44 patients with gonarthrosis were followed for at least 1 year to detect patellar complications. In five knees the metal-backed patellar component failed, in one knee the cement fractured, and in one knee there was a spontaneous fracture of the patella. We regard this failure rate as unacceptable.

Stable Phenotype Of B‐Cell Subsets Following Cryopreservation and Thawing of Normal Human Lymphocytes Stored in a Tissue Biobank

Cryopreservation is an acknowledged procedure to store vital cells for future biomarker analyses. Few studies, however, have analyzed the impact of the cryopreservation on phenotyping.

Cell of origin associated classification of B-cell malignancies by gene signatures of the normal B-cell hierarchy

Abstract Recent findings have suggested biological classification of B-cell malignancies as exemplified by the “activated B-cell-like” (ABC), the “germinal-center B-cell-like” (GCB) and primary mediastinal B-cell lymphoma (PMBL) subtypes of diffuse large B-cell lymphoma and “recurrent translocation and cyclin D” (TC) classification of multiple myeloma. Biological classification of B-cell derived cancers may be refined by a direct and systematic strategy where identification and characterization of normal B-cell differentiation subsets are used to define the cancer cell of origin phenotype. Here we propose a strategy combining multiparametric flow cytometry, global gene expression profiling and biostatistical modeling to generate B-cell subset specific gene signatures from sorted normal human immature, naive, germinal centrocytes and centroblasts, post-germinal memory B-cells, plasmablasts and plasma cells from available lymphoid tissues including lymph nodes, tonsils, thymus, peripheral blood and bone marrow. This strategy will provide an accurate image of the stage of differentiation, which prospectively can be used to classify any B-cell malignancy and eventually purify tumor cells. This report briefly describes the current models of the normal B-cell subset differentiation in multiple tissues and the pathogenesis of malignancies originating from the normal germinal B-cell hierarchy.

Inherited Inflammatory Response Genes Are Associated with B-Cell Non-Hodgkin’s Lymphoma Risk and Survival

Background Malignant B-cell clones are affected by both acquired genetic alterations and by inherited genetic variations changing the inflammatory tumour microenvironment. Methods We investigated 50 inflammatory response gene polymorphisms in 355 B-cell non-Hodgkin’s lymphoma (B-NHL) samples encompassing 216 diffuse large B cell lymphoma (DLBCL) and 139 follicular lymphoma (FL) and 307 controls. The effect of single genes and haplotypes were investigated and gene-expression analysis was applied for selected genes. Since interaction between risk genes can have a large impact on phenotype, two-way gene-gene interaction analysis was included. Results We found inherited SNPs in genes critical for inflammatory pathways; TLR9, IL4, TAP2, IL2RA, FCGR2A, TNFA, IL10RB, GALNT12, IL12A and IL1B were significantly associated with disease risk and SELE, IL1RN, TNFA, TAP2, MBL2, IL5, CX3CR1, CHI3L1 and IL12A were, associated with overall survival (OS) in specific diagnostic entities of B-NHL. We discovered noteworthy interactions between DLBCL risk alleles on IL10 and IL4RA and FL risk alleles on IL4RA and IL4. In relation to OS, a highly significant interaction was observed in DLBCL for IL4RA (rs1805010) * IL10 (rs1800890) (HR = 0.11 (0.02–0.50)). Finally, we explored the expression of risk genes from the gene-gene interaction analysis in normal B-cell subtypes showing a different expression of IL4RA, IL10, IL10RB genes supporting a pathogenetic effect of these interactions in the germinal center. Conclusions The present findings support the importance of inflammatory genes in B-cell lymphomas. We found association between polymorphic sites in inflammatory response genes and risk as well as outcome in B-NHL and suggest an effect of gene-gene interactions during the stepwise oncogenesis.

Circulating tumor necrosis factor-α and YKL-40 level is associated with remission status following salvage therapy in relapsed non-Hodgkin lymphoma

1 Department of Hematology, 4 Department of Clinical Immunology and 5 Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark, 2 Department of Hematology and 7 Department of Medicine and Oncology, Herlev University Hospital, Herlev, Denmark, 3 Department of Hematology, Roskilde University Hospital, Roskilde, Denmark and 6 Department of Clinical Medicine, Aalborg University, Aalborg, Denmark