Hematopoietic stem cell transplantation for CD40 ligand deficiency: Results from an EBMT/ESID-IEWP-SCETIDE-PIDTC study

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HLA -A, -C, -B, -DRB1, -DQB1 and -DPB1 allele and haplotype frequencies in 4514 healthy Norwegians

We report HLA-A, -C, -B, -DRB1, -DQB1 and -DPB1 allele frequencies and estimated haplotype frequencies from 4514 healthy Norwegians who volunteered to participate in the Norwegian Bone Marrow Donor Registry. HLA genotyping was conducted on a Next Generation Sequencing platform. Data were analyzed using Arlequin and Pypop software. No significant deviations from Hardy-Weinberg Equilibrium were noted at any of the loci studied. We discuss the representability for the Norwegian population and argue that the presented HLA data could serve as a Norwegian reference panel.     

Do no harm: no psychological harm from colorectal cancer screening

Background:

Participation in cancer screening programmes might cause worries in the population outweighting the benefits of reduced mortality. The present study aimed to investigate possible psychological harm of participation in a colorectal cancer (CRC) screening pilot in Norway.

Methods:

In a prospective, randomised trial participants (aged 50–74 years) were invited to either flexible sigmoidoscopy (FS) screening, faecal immunochemical test (FIT), or no screening (the control group; 1 : 1: 1). Three thousand two hundred and thirteen screening participants (42% of screened individuals) completed the Hospital Anxiety and Depression Scale questionnaire as well as the SF-12—a health-related quality of life (HRQOL) questionnaire when invited to screening and when receiving the screening result. A control group was invited to complete the questionnaires only. Two thousand six hundred and eighteen control participants (35% of invited individuals) completed the questionnaire.

Results:

A positive screening result did not increase participants'' level of anxiety or depression, or decrease participants'' level of HRQOL. Participants who received a negative result reported decreased anxiety and improvement on some HRQOL dimensions. However, no change was considered to be of clinical relevance.

Conclusion:

The current study showed no clinically relevant psychological harm of receiving a positive CRC screening result or of participating in FS or FIT screening, in a Norwegian population.     

Nephrotoxic potency of antisera to three rat glomerular basement membrane glycoproteins.

In a previous article, we cited studies which have allowed us to isolate diverse glycoproteins of the rat glomerular basement membrane (GMB) and to study their biochemical structures and antigenicity. This present study attempts to examine, using the heterologous nephrotoxic nephritis model (Masugi's nephritis) the nephrotoxicity of immune sera prepared from three of these glycoproteins: one fairly rich in collagen-like structures (A3), another lacking collagen-like structures (A1), and a third of intermediate composition (A2). The results obtained are discussed in relation to those already published concerning the nature of the GBM antigen(s) responsible for the nephrotoxicity of the sera.     

Autologous bone marrow transplantation for acute leukemia using transplant chemopurified with metabolite of oxazaphosphorines (ASTA Z 7557, INN mafosfamide)

Summary The contamination of autologous marrow with clonogenic tumor cells has been the main argument against ABMT in acute leukemia.In a preclinical study we evaluated an active cyclophosphamide derivative named ASTA Z 7557. We observed that the toxic effect of this drug on CFU-GM growth was dependent on nucleated cell concentration as well as on red blood cell contamination. The potency of the drug was in close relationship with the incubation temperature.The growth of leukemic CFU was inhibited with an ASTA Z dose higher than 30 g/ml. In our system, beyond 40 g/ml more than 95% of committed stem cells are destroyed.Fifteen patients had autotransplant because of AML for 10 patients and because of ALL for 5 patients (4 patients were grafted in relapse and 11 patients in remission).We demonstrated that the marrow take was possible although the inoculum is CFU-GM depleted.Five of the 10 AML patients are alive and remain disease-free at 45 +, 65 +, 190 +, 345+ and 570 + days from ABMT without any maintenance treatment. Four of the 5 ALL patients are alive, three of them in complete remission (404+, 110+, 250+ days).The number of patients reported in this clinical study was relatively small and more cases should be evaluated to be conclusive. Nevertheless the feasibility of chemopurified ABMT was demonstrated.     

FDG-PET, 99mTc-HMPAO white blood cell SPET and bone scintigraphy in the evaluation of painful total knee arthroplasties

Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET), technetium-99m hexamethylpropylene amine oxime (HMPAO)-labelled white blood cell (WBC) scintigraphy and bone scintigraphy were used in the evaluation of total knee arthroplasties (TKAs). We prospectively included 21 patients who had a three-phase bone scan for exclusion of infection of TKAs. Four hours after injection of 185 MBq ^99mTc-HMPAO-labelled WBCs, planar and single-photon emission tomographic (SPET) imaging was performed. Planar imaging was repeated at 24 h p.i. Consecutively images of the knees were obtained with a dedicated PET system 60 min following the injection of 370 MBq of FDG. Focal tracer uptake was scored on SPET and PET visually (0=no uptake, 4=intense uptake). In addition, SUV (standardised uptake value) per voxel was calculated from attenuation-corrected PET images using the MLAA algorithm. Focal uptake at the bone-prosthesis interface was used as the criterion for infection before and after correlation with the third phase of the bone scan. Final diagnosis was based on operative findings, culture and clinical outcome. In the infected TKAs, the WBC scan showed focal activity of grade 2 (n=2), 3 (n=1) or 4 (n=2). PET scan revealed focal activity of grade 4 (n=5) or 3 (n=1). WBC scan alone had a specificity for infection of 53% [positive predictive value (PPV) 42%, sensitivity 100%], compared with 73% for PET scan (PPV 60%, sensitivity 100%). Considering only lesions at the bone-prosthesis interface that were also present on the third phase of the bone scan, we found a specificity of 93% (PPV 83%) for WBC scan. Using these criteria, a specificity of 80% (PPV 67%) was obtained for PET scan. Two out of three false-positive PET scans were due to loosening of the TKA. It is concluded that WBC scintigraphy in combination with bone scintigraphy has a high specificity in the detection of infected TKAs. FDG-PET seems to offer no additional benefit.