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The long-term prognosis following herpes simplex virus (HSV) central nervous system (CNS) infection is still debated. We examined outcomes in all Danish residents who, during 2000-2016, tested PCR positive for HSV-1 (n=208) or HSV-2 (n=283) in the cerebrospinal fluid, compared to comparison cohorts from the general population (n=2080 and n=2830). One-year mortality was increased among HSV-1 patients (difference 19.3%; 95% CI: 13.6% to 25.0%) and HSV-2 patients (difference 5.3%; 95% CI: 2.5% to 8.1%), but thereafter mortality was not increased. After exclusion of persons diagnosed with cancer prior to study inclusion, one-year mortality difference for HSV-2 patients was 1.7% (-0.1% to 3.5%). After five years, HSV-1 patients had lower employment (difference -19.8%; 95% CI: -34.7% to -4.8%) and higher disability pension rates (difference 22.2%; 95% CI: 8.4% to 36.0%) than the comparison cohort, but similar number of inpatient days, outpatient visits, and sick leave. HSV-2 patients had employment and disability pension rates comparable to the comparison cohort, but more inpatient days (difference 1.5/year; 95% CI: -0.2 to 3.2), outpatient visits (difference 1.3/year; 95% CI: 0.3 to 3.2), and sick leave days (difference 9.1/year; 95% CI: 7.9 to 10.4). HSV-1 and HSV-2 CNS infections differ substantially with respect to prognosis. HSV-1 CNS infection is followed by increased short-term mortality and long-term risk of disability. HSV-2 CNS infection has no substantial impact on mortality or working capability but is associated with increased morbidity.

Several studies have demonstrated an association between rheumatoid arthritis (RA) and lymphoproliferative malignancies, but pathogenic mechanisms remain unclear. We investigated 1) the risk of lymphoproliferative malignancies and solid tumors in adults with RA identified in primary care and 2) the possible mediating role of blood eosinophilia in the clonal evolution of cancer in these patients. From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356,196 individuals with at least one differential cell count (DIFF) encompassing the eosinophil count between 2000-2007. From these, one DIFF was randomly chosen (the index DIFF). By linking to the Danish National Patient Register, we categorized the selected individuals according to known longstanding (≥3 years) or recent onset (<3 years) RA prior to the index DIFF. In addition, the cohort was stratified according to management in primary or secondary care. From the Danish Cancer Registry we ascertained malignancies within four years following the index DIFF. Using multivariable logistic regression, odds ratios (OR) were calculated and adjusted for sex, age, year, month, eosinophilia, comorbid conditions and C-reactive protein (CRP). 921 patients had recent onset RA and 2,578 had longer disease duration. Seventy three percent of RA patients were managed in primary care. After adjustment for sex, age, year, and month, neither recent onset nor long-standing RA was associated with incident lymphoproliferative malignancies or solid cancers. These risk estimates did not change when eosinophilia, CRP, and comorbidities were included in the models. In this large cohort of patients with RA of short or long duration recruited from a primary care resource, RA was not associated with an increased risk of lymphoproliferative or solid cancers during 4 years of follow-up, when the models were adjusted for confounders. Blood eosinophilia could not be identified as a mediator of cancer development in the present setting.

Primary myelofibrosis (MF) is a severe chronic myeloproliferative neoplasm, progressing towards a terminal stage with insufficient haematopoiesis and osteosclerotic manifestations. Whilst densitometry studies have showed MF patients to have elevated bone mineral density, data on bone geometry and micro-structure assessed with non-invasive methods are lacking. We measured areal bone mineral density (aBMD) using dual-energy X-ray absorptiometry (DXA). Bone geometry, volumetric BMD, and micro-architecture were measured using high-resolution peripheral quantitative computed tomography (HR-pQCT). We compared the structural parameters of bones by comparing 18 patients with MF and healthy controls matched for age, sex, and height. Blood was analysed for biochemical markers of bone turnover in patients with MF. There were no significant differences in measurements of bone geometry, volumetric bone mineral density, and micro-structure between MF patients and matched controls. Estimated bone stiffness and bone strength were similar between MF patients and controls. The level of pro-collagen type 1 N-terminal pro-peptide (P1NP) was significantly increased in MF, which may indicate extensive collagen synthesis, one of the major diagnostic criteria in MF. We conclude that bone mineral density, geometry, and micro-architecture in this cohort of MF patients are comparable with those in healthy individuals.

Background: The prevalence of acquired angioedema (AAE) is hitherto unknown and, to date, less than 200 patients have been reported worldwide. AAE is associated with lymphoproliferative conditions and autoantibodies against C1 inhibitor (C1INH). Rituximab (RTX) is increasingly used in the treatment of AAE patients. Methods: A nationwide study of AAE patients was performed in Denmark. Clinical features, associated disorders, treatments and outcomes were registered. Results: Eight AAE patients were identified. The diagnostic delay was on average 1 year and 8 months. Patients were treated with C1INH concentrate or icatibant on demand. Six patients were diagnosed with a clonal B-cell disorder during follow-up, on average 2.5 years after the first swelling. Two patients had monoclonal B-cell lymphocytosis (MBL). Two patients received RTX. Conclusions: AAE is a rare condition occurring in less than 10% of patients with C1INH deficiency in Denmark. AAE is highly associated with haematologic disorders, and we recommend yearly follow-up visits with clinical examination and blood tests including flow cytometry to diagnose B-cell conditions at an early stage. We report 2 patients with AAE and associated MBL, which is a benign expansion of clonal B lymphocytes. MBL can be the precursor of chronic lymphocytic leukaemia or is associated with non-Hodgkin's lymphoma. If angioedema is poorly controlled with standard treatment regimens, we suggest treatment of the associated haematologic disorder. Based on a review of the literature and our own data, we recommend therapy with RTX, especially in patients with anti-C1INH autoantibodies.

Introduction Mastocytosis is a group of rare heterogeneous diseases with a prevalence previously found to be 10–23 per 100,000 persons. More awareness and improvements in the diagnostic methods in later years have led to more patients being diagnosed. Here, we set out to present the prevalence and incidence rate of mastocytosis among the adult Danish population. By merging data from the Danish National Patient Register, the Danish Pathology Register and the Danish Cancer Register we included all adult patients (≥ 18 years) diagnosed with mastocytosis in Denmark prior to 2022. A cohort of 1,594 patients with mastocytosis was identified. The prevalence of mastocytosis was 27.43 per 100,000 persons (95% confidence interval [CI]: 25.95–28.96) as of January 1, 2022, and the 25-year average incidence rate between 1997 and 2021 was 1.21 per 100,000 persons (95%CI: 1.02–1.40) with an increasing incidence rate since 2002. We found a higher prevalence of mastocytosis among adults in the Danish population than previously reported, and an increasing incidence rate during the last 20 years. Increased awareness of the disease and better diagnostic methods most likely contributed to this.

Limited data is available on the health-related quality of life (HRQoL) and symptoms of patients with chronic myeloid leukemia (CML) who are in treatment-free remission (TFR). We herein report HRQoL results from the EURO-SKI trial. Patients who had been on tyrosine kinase inhibitors (TKIs) therapy for at least 3 years and achieved MR4 for at least 1 year were enrolled from 11 European countries, and the EORTC QLQ-C30 and the FACIT-Fatigue questionnaires were used to assess HRQoL and fatigue respectively. Patients were categorized into the following age groups: 18–39, 40–59, 60–69 and ≥70 years. Of 728 patients evaluated at baseline, 686 (94%) completed HRQoL assessments. The median age at TKI discontinuation was 60 years. Our findings indicate that HRQoL and symptom trajectories may vary depending on specific age groups, with younger patients benefiting the most. Improvements in patients aged 60 years or older were marginal across several HRQoL and symptom domains. At the time of considering TKI discontinuation, physicians could inform younger patients that they may expect valuable HRQoL benefits. Considering the marginal improvements observed in patients aged 60 years or above, it may be important to further investigate the value of TFR compared to a lowest effective dose approach in this older group of patients.

In Denmark, the acceptance of the HPV vaccination program has been threatened by reports of suspected adverse events. Epstein Barr Virus (EBV) infection is associated with symptoms of long-lasting tiredness and may be misinterpreted as HPV vaccine adverse events. The main aim of this study was to examine if EBV infection around time of HPV vaccination was a risk factor for later suspected vaccine adverse events. The study was a nationwide register-based matched case-control study. Cases were females vaccinated against HPV in the period 2011 throughout 2017 with suspected adverse events. For each case, five HPV vaccinated females without suspected adverse events were selected. Information about EBV infection was obtained from the Danish Microbiology Database and assessed for three time periods: (1) before first HPV vaccination, (2) around time of HPV vaccination, and (3) any time during the study period 2010–2017. Multiple logistic regression was used to estimate the association between EBV and suspected adverse events. We identified 1217 cases, matched to 6085 controls. A higher proportion of cases (38; 3.1%) than controls (31; 0.5%) were tested for EBV around time of HPV vaccination and cases had elevated odds for testing both EBV positive (OR 4.52, 95% CI 2.68–7.63) and EBV negative (OR 20.99, 95% CI 5.81–75.79). Only five females were classified with acute/recent EVB infection in this period. Misinterpretation of EBV infection late symptoms is not a leading explanation for Danish females experiencing suspected adverse events after HPV vaccination. Although EBV cannot be excluded as an explanatory factor for a very small proportion of suspected adverse events, the findings are more likely explained by protopathic bias, i.e. the fact that a larger proportion of females suspecting adverse events are tested for EBV.