Hyperhidrosis and human leucocyte antigens in the Danish Blood Donor Study.

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 < .001). Moderate-severe self-reported hyperhidrosis and hospital diagnosed hyperhidrosis were not associated with any HLA. The association between hyperhidrosis and HLA-A*80:01 was based on a very small number of cases and not replicated in other patient subsets, and therefore likely a chance finding. Thus, this study suggests that genes other than the HLA are involved in the pathogenesis of hyperhidrosis.

Ultrasound-guidance of peripheral venous catheterization in apheresis minimizes the need for central venous catheters.

INTRODUCTION: Central venous catheters (CVC) can facilitate a reliable blood flow for apheresis procedures, but the placement is time-consuming and costly and the incidence of catheter-related complications is high. Ultrasound can aid nurses to insert peripheral venous catheters (PVC), which is safer for the patients. METHODS AND MATERIALS: We evaluated the use of CVC vs PVC for all apheresis procedures 3 years after the implementation of structured training of apheresis nurses to perform ultrasound-guided PVC. Ultrasound can visualize the needle tip and target vessel dynamically and guide peripheral venous catheterization with an increased success rate. Time consumption for PVC insertion was measured. RESULTS: In 10 months, we performed 1294 apheresis procedures on 227 patients, where 97.4% were performed with PVC. Hundred percent of extracorporeal photophoresis (off-line ECP) and peripheral blood stem cell collections on adults were performed with PVC. Patients who were treated with CVC (n = 8) were either children, had poor peripheral blood flow due to dehydration or admitted to an intensive care unit and had CVC for other reasons. Time consumption for PVC placement with ultrasound was 11 minutes on average. CONCLUSION: Training of apheresis nurses in ultrasound-guided peripheral venous catheterization can enable close to 100% of apheresis procedures to be performed by PVC.

RHD positive among C/E+ and D- blood donors in Denmark.

BACKGROUND: Many different partial and weak D types have been reported, and most of these are easily detected by serology. However, 17 Del types have also been described, with a very low expression of the D antigen, only detectable by absorption-elution techniques, and these may elicit the development of an anti-D. A genomic test of C/E+ and D- blood donors was initiated, to be able to categorize them correctly as D+ or -. STUDY DESIGN AND METHODS: We analyzed all C/E+ and D- donors within our donor population of 22,000 donors with an initial test for RHD Exon 10. In case of a positive reaction, the genotype was further analyzed by sequence-specific polymerase chain reaction or nucleotide sequencing of the RHD gene. CONCLUSIONS: Of 233 donors analyzed, seven were found positive for RHD Exon 10, and four of these were Del, corresponding to 1.7%. We report here a new mutation in the RHD gene. A correct assignment of all blood donors as D+ or D- is not possible using serotyping alone; genotyping offers the only exact categorization of all cases.

Clinical impact of clonal hematopoiesis in patients with lymphoma undergoing ASCT: a national population-based cohort study.

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).

Common, intermediate and well-documented HLA alleles in world populations: CIWD version 3.0.0.

A catalog of common, intermediate and well-documented (CIWD) HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQB1 and -DPB1 alleles has been compiled from over 8 million individuals using data from 20 unrelated hematopoietic stem cell volunteer donor registries. Individuals are divided into seven geographic/ancestral/ethnic groups and data are summarized for each group and for the total population. P (two-field) and G group assignments are divided into one of four frequency categories: common (≥1 in 10 000), intermediate (≥1 in 100 000), well-documented (≥5 occurrences) or not-CIWD. Overall 26% of alleles in IPD-IMGT/HLA version 3.31.0 at P group resolution fall into the three CIWD categories. The two-field catalog includes 18% (n = 545) common, 17% (n = 513) intermediate, and 65% (n = 1997) well-documented alleles. Full-field allele frequency data are provided but are limited in value by the variations in resolution used by the registries. A recommended CIWD list is based on the most frequent category in the total or any of the seven geographic/ancestral/ethnic groups. Data are also provided so users can compile a catalog specific to the population groups that they serve. Comparisons are made to three previous CWD reports representing more limited population groups. This catalog, CIWD version 3.0.0, is a step closer to the collection of global HLA frequencies and to a clearer view of HLA diversity in the human population as a whole.