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BACKGROUND: The healthy donor effect (HDE) is a selection bias caused by the health criteria blood donors must meet. It obscures investigations of beneficial/adverse health effects of blood donation and complicates the generalizability of findings from blood donor cohorts. To further characterize the HDE we investigated how self-reported health and lifestyle are associated with becoming a blood donor, lapsing, and donation intensity. Furthermore, we examined differences in mortality based on donor status.STUDY DESIGN AND METHODS: The Danish National Health Survey was linked to the Scandinavian Donations and Transfusions (SCANDAT) database and Danish register data. Logistic- and normal regression was used to compare baseline characteristics and participation. Poisson regression was used to investigate future donation choices. Donation intensity was explored by the Anderson-Gill model and Poisson regression. Mortality was investigated using Poisson regression.RESULTS: Blood donors were more likely to participate in the surveys, OR = 2.45 95% confidence interval (2.40-2.49) than non-donors. Among survey participants, better self-reported health and healthier lifestyle were associated with being or becoming a blood donor, donor retention, and to some extent donation intensity, for example, current smoking conveyed lower likelihood of becoming a donor, OR = 0.70 (0.66-0.75). We observed lower mortality for donors and survey participants, respectively, compared with non-participating non-donors.CONCLUSION: We provide evidence that blood donation is associated with increased likelihood to participate in health surveys, possibly a manifestation of the HDE. Furthermore, becoming a blood donor, donor retention, and donation intensity was associated with better self-reported health and healthier lifestyles.

Familial clustering of the skin disease primary hyperhidrosis suggests a genetic component to the disease. The human leucocyte antigen (HLA) is implicated in a range of diseases, including many comorbidities to hyperhidrosis. No study has investigated whether the HLA genes are involved in the pathogenesis of hyperhidrosis. We, therefore, compared HLA alleles in individuals with and without hyperhidrosis in this study of 65 000 blood donors. In this retrospective cohort study, we retrieved information on individuals with and without hyperhidrosis using self-reported questionnaires, the Danish National Patient Registry and the Danish National Prescription Registry on participants recruited to the Danish Blood Donor Study between 2010 and 2019. Association tests using logistic regression were conducted for each HLA allele corrected for sex, age, body mass index, smoking and principal components. Overall, 145 of 65 795 (0.2%) participants had hospital diagnosed hyperhidrosis. Similarly, 1379 of 15 530 (8.9%) participants had moderate-severe self-reported hyperhidrosis, of whom 447 (2.9%) had severe self-reported hyperhidrosis. Altogether, 28 participants had both hospital diagnosed and moderate-severe self-reported hyperhidrosis. Severe self-reported hyperhidrosis was associated with HLA-A*80:01 (adjusted odds ratio 26.97; 95% confidence interval 5.32-136.70; n = 7; P

BackgroundPeople experiencing homelessness (PEH) and associated shelter workers may be at higher risk of infection with “Severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2). The aim of this study was to determine the prevalence of SARS-CoV-2 among PEH and shelter workers in Denmark.Design and methodsIn November 2020, we conducted a nationwide cross-sectional seroprevalence study among PEH and shelter workers at 21 recruitment sites in Denmark. The assessment included a point-of-care test for antibodies against SARS-CoV-2, followed by a questionnaire. The seroprevalence was compared to that of geographically matched blood donors considered as a proxy for the background population, tested using a total Ig ELISA assay.ResultsWe included 827 participants in the study, of whom 819 provided their SARS-CoV-2 antibody results. Of those, 628 were PEH (median age 50.8 (IQR 40.9-59.1) years, 35.5% female) and 191 were shelter workers (median age 46.6 (IQR 36.1-55.0) years and 74.5% female). The overall seroprevalence was 6.7% and was similar among PEH and shelter workers (6.8% vs 6.3%, p=0.87); and 12.2% among all participants who engaged in sex work. The overall participant seroprevalence was significantly higher than that of the background population (2.9%, p InterpretationsThe prevalence of SARS-CoV-2 antibodies was more than twice as high among PEH and associated shelter workers, compared to the background population. The subset of the study participants who were also sex workers were at particularly high risk of COVID-19 infection.FundingTrygFonden and HelseFonden.

Clonal hematopoiesis of indeterminate potential (CHIP) is suspected of being a risk factor for patients with cancer. This study aimed to assess the clinical consequences of CHIP in patients with lymphoma intended for high-dose chemotherapy and autologous stem-cell transplantation (ASCT) in a population-based setting. We identified 892 lymphoma patients who had undergone stem cell harvest at all transplant centers in Denmark. A total of 565 patients had an available harvest sample, which was analysed for CHIP by next-generation sequencing, and the median follow-up was 9.1 years. Of the patients who were intended for immediate ASCT, 25.5% (112/440) carried at least one CHIP mutation. In contrast to previous single-center studies CHIP was not associated with inferior overall survival (OS) in multivariate analyses. However, patients with mutations in genes of the DNA repair pathway (PPM1D, TP53, RAD21, BRCC3) had a significant inferior OS (HR after 1 year of follow-up 2.79, 95% confidence interval 1.71–4.56; p < 0.0001), which also was evident in multivariate analysis (p = 0.00067). These patients had also increased rates of therapy-related leukemia and admission to intensive care. Furthermore, in patients who did not undergo immediate ASCT, a significant inferior OS of individuals with DNA repair mutations was also identified (p = 0.003).

Background: Somatic driver mutations in hematopoietic cells may lead to clonal hematopoiesis of indeterminate potential (CHIP). In patients with lymphoma CHIP has been associated with increased risk of therapy-related myeloid neoplasms (tMN) and inferior survival after autologous stem cell transplantation as demonstrated in a large single center study and in a case-control study (Gibson CJ et al., JCO 2017 and Berger G et al., Blood 2018). Here, we investigated the clinical impact of clonal hematopoiesis in a nation-wide population-based cohort of Danish lymphoma patients undergoing autologous transplant with prospective data from four national patient registries. Methods: Patients with lymphoma who had undergone leukapheresis at all danish transplant centers from 2000 to 2012 were identified. DNA and RNA was extracted from mobilized peripheral blood products. Targeted sequencing of all samples was performed using an Illumina TruSeq Custom Amplicon panel (Illumina, San Diego, CA, USA) designed to cover >95% of mutations associated with CHIP (ASXL1, ASXL2, BCOR, BRCC3, CBL, CREBBP, DNMT3A, ETV6, GNB1, IDH1, IDH2, JAK2, KRAS, NRAS, PPM1D, RAD21, SF3B1, SRSF2, TET2, TP53). To allow detection of low-level mutations and secure variant calling, unique molecular identifiers (UMI's) were used. Filtering of variants was done by stringent criteria consistent with earlier studies. Assessment of mutations was performed blinded to the patients' clinical data. Prospective clinical patient data was obtained for all patients from four national registries, including the Danish Lymphoma Registry (diagnosis, involvement, lymphoma treatment, relapse and death), the Danish National Patient Registry (hospital admission diagnoses and treatments), the Danish Cancer Registry (primary and secondary cancer diagnoses) and the Danish Pathology Database (histopathological examinations and diagnoses), respectively. Results: Samples from 574 patients were included. The median age was 55.5 years (IQR: 45.3 - 62.2) and the median follow-up time for survivors was 9.2 years (IQR: 7.1 - 11.2). The lymphoma subtypes were typical of patients selected for autologous transplantation; diffuse large B-cell lymphoma (191 pts), follicular lymphoma (102 pts), mantle cell lymphoma (88 pts), Hodgkin's lymphoma (80 pts), peripheral T-cell lymphoma (77 pts) and other histologies (36 pts). Of the 574 patients analyzed, 191 (33.3%) of the patients had somatic mutations meeting CHIP criteria (total mutations called=210). The most commonly mutated genes were DNMT3A (n=59, 28%), TET2 (n=48, 23%), PPM1D (n=34, 16%), ASXL1 (n=21, 10%) and TP53 (n=18, 8%). As expected CHIP mutations were more frequent in patients above 60 years (p=0.002). Prevalence of CHIP was associated with an inferior overall survival (p=0.004) and event-free survival (p=0.03). It was also associated with increased risk of biopsy-confirmed tMN (p=0.03) and higher probability of receiving blood transfusions after autologous transplant (p=0.027). Especially patients with mutations in DNA damage response genes PPM1D and TP53 (found in 48 pts, 8.3%) had a significantly increased risk of adverse outcomes. Both overall survival and event-free survival were significantly poorer with the presence of DNA damage pathway mutations (p The impact of low-level mutations and statistical modelling of interactions between parallel outcomes will be presented at the meeting. Conclusion: To our knowledge this is the first population-based study of clonal hematopoiesis in patients with lymphoma. We find that CHIP and particularly mutations in DNA damage response genes (PPM1D/TP53) are associated with increased mortality, which confirms findings from single center studies. These data support the evaluation of CHIP for risk assessment in lymphoma patients before high-dose chemotherapy. Our study also identifies increased rates of several clinically relevant adverse outcomes (severe infections, blood transfusions and secondary cancers) in lymphoma patients with clonal hematopoiesis. Figure 1. Figure 1. Disclosures Grønbæk: Janssen Pharma: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Otsuka Pharma: Membership on an entity's Board of Directors or advisory committees.

Udgivelsesdato: 2010-Mar-17 Abstract Objectives. We have previously shown that repeated intracoronary infusion of bone marrow cells (BMSC) did not improve left ventricular (LV) ejection fraction in patients with chronic ischemic heart failure. However, the impact of BMSC therapy on LV diastolic filling has remained uncertain. Design. Thirty two patients with LV ejection fraction less than 40% were studied. Each patient underwent three baseline echocardiograms to ensure stable LV filling. Infusion of BMSC was given at baseline and again after four months. Echocardiograms were repeated four, eight and 12 months after the first intervention. Main outcome measures were the ratio of transmitral flow (E) velocity to early mitral annulus (e') velocity (E/e'), left atrial (LA) volume and plasma levels of N-terminal pro-brain natriuretic peptide (NT- pro-BNP). Results. During the initial observational period there were no changes in main outcome. After treatment with intracoronary BMSC a significant decrease was observed in E/e' ratio (14.7+/-6.7 vs. 13.2+/-7.7, p=0.04), LA volume (90+/-25 ml vs. 80+/-26 ml, p=0.006) and plasma NT-pro-BNP (p=0.03). The effect was greatest in patients who received the largest amount of CD34(+) cells. Conclusion. In this non-randomised study repeated intracoronary BMSC infusions had a beneficial effect on LV filling in patients with chronic ischemic heart failure. Randomised studies are warranted.

Background: It has been suggested that myocardial regeneration may be achieved by a single intracoronary bone marrow derived stem cell infusion in selected patients with ischaemic heart disease. The effect is uncertain in patients with chronic ischaemic heart failure and it is not known whether repeated infusions would have additional positive effects. Aims: To assess whether two treatments of intracoronary infusion of bone marrow stem cells, administered 4 months apart, could improve left ventricular (LV) systolic function in patients with chronic ischaemic heart failure. Methods: The study was prospective and non-randomised, comprising an observational baseline period of 4 months followed by an interventional period of 12 months. Intracoronary bone marrow cell infusion was performed at the end of the baseline period and repeated 4 months later. Results: 32 patients were included. LV ejection fraction remained unchanged (33±9% vs. 34±10% after 8 months, p=0.30). Likewise, there was no significant change in LV end-systolic volume, wall motion score index (WMSI) or contractile reserve. At 12 months, a decrease in target vessel WMSI was seen (2.17±0.34 vs. 2.06±0.46, p=0.02). Furthermore, NYHA class improved (p