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Abstract Increasing recognition of germline DDX41 variants in patients with hematological malignancies prompted us to provide DDX41‐specific recommendations for diagnosis, surveillance, and treatment. Causative germline variants in the DDX41 predispose to the development of myeloid neoplasms (MNs), especially myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Almost 3%–5% of all patients with MDS or AML carry a pathogenic or likely pathogenic germline DDX41 variant, while half of them acquire a somatic second hit in the other allele. DDX41‐associated MNs exhibit unique clinical characteristics compared to other hematological malignancies with germline predisposition: MNs occur mostly at advanced age and follow an indolent clinical course. Male carriers are more prone to develop MDS or AML than females. DDX41‐associated MN is often hypoplastic, and the malignancy may be preceded by cytopenias.

Abstract Background Anticoagulants (AC) were introduced in March 2020 as standard of care in nursing home (NH) residents affected with COVID‐19 in the Stockholm region, Sweden. ACs are proven to reduce the risk of complications and mortality from COVID‐19 among patients of other ages and settings, but there is limited scientific evidence underpinning this practice in the NH setting. Methods This matched cohort study included 182 NH residents in the Stockholm Region diagnosed with COVID‐19 in March–May 2020. The main exposure was any AC treatment. Exposed (n = 91), 49% prevalent (pre‐COVID‐19 diagnosis) AC and 51% incident AC were compared with unexposed controls (n = 91). The outcome was 28‐days all‐cause mortality after COVID‐19 infection. The mortality odds ratios (OR) were assessed using logistic regression, adjusted for age, sex, multimorbidity, and mobility, also stratified by incident or prevalent AC‐type, age group, and sex. Results Of the 182 individuals diagnosed with COVID‐19 (median age 88 years, 68% women), 39% died within 28 days after diagnosis. Use of either incident or prevalent AC was associated with a reduced, adjusted 28‐day mortality (OR[95% CI]: 0.31[0.16–0.62]). In stratified analyses, the association was significant in both age groups: 70–89 (OR: 0.37 [0.15–0.89]) and 90–99 years of age (OR: 0.22 [0.07–0.65]. In sex‐stratified analysis, the AC‐lowering effect was significant in women only (OR: 0.28[0.11–0.67]). In the analyses stratified by AC type, the mortality‐lowering effect was observed for both prevalent AC (OR: 0.35[0.12–0.99]) and incident AC (OR: 0.29[0.11–0.76]). Conclusions Both prevalent and incident use of ACs in prophylactic dosing was associated with reduced 28‐day mortality among older individuals with COVID‐19 in a NH setting. The effect was seen across age‐strata and in women. The findings present new insight in best practice for individuals diagnosed with COVID‐19 in the NH setting.

Abstract Objective To study if treatment with triheptanoin, a 7‐carbon triglyceride, improves exercise tolerance in patients with McArdle disease. McArdle patients have a complete block in glycogenolysis and glycogen‐dependent expansion of tricarboxylic acid cycle (TCA), which may restrict fat oxidation. We hypothesized that triheptanoin metabolism generates substrates for the TCA, which potentially boosts fat oxidation and improves exercise tolerance in McArdle disease. Methods Double‐blind, placebo‐controlled, crossover study in patients with McArdle disease completing two treatment periods of 14 days each with a triheptanoin or placebo diet (1 g/kg/day). Primary outcome was change in mean heart rate during 20 min submaximal exercise on a cycle ergometer. Secondary outcomes were change in peak workload and oxygen uptake along with changes in blood metabolites and respiratory quotients. Results Nineteen of 22 patients completed the trial. Malate levels rose on triheptanoin treatment versus placebo (8.0 ± SD2.3 vs. 5.5 ± SD1.8 µmol/L, P

Abstract. Myeloid neoplasms (MNs) with germline predisposition have recently been recognized as novel entities in the latest World Health Organization (WHO) classification for MNs. Individuals with MNs due to germline predisposition exhibit increased risk for the development of MNs, mainly acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Setting the diagnosis of MN with germline predisposition is of crucial clinical significance since it may tailor therapy, dictate the selection of donor for allogeneic hematopoietic stem cell transplantation (allo-HSCT), determine the conditioning regimen, enable relevant prophylactic measures and early intervention or contribute to avoid unnecessary or even harmful medication. Finally, it allows for genetic counseling and follow-up of at-risk family members. Identification of these patients in the clinical setting is challenging, as there is no consensus due to lack of evidence regarding the criteria defining the patients who should be tested for these conditions. In addition, even in cases with a strong suspicion of a MN with germline predisposition, no standard diagnostic algorithm is available. We present the first version of the Nordic recommendations for diagnostics, surveillance and management including considerations for allo-HSCT for patients and carriers of a germline mutation predisposing to the development of MNs.

Background Physical activity enhances the uptake of air pollutants, possibly reducing its beneficial effects. We examined the effects of leisure‐time and transport‐related physical activities on the risk of myocardial infarction (MI), and whether potential benefits on MI are reduced by exposure to traffic‐related air pollution. Methods and Results A group of 57 053 participants (50–65 years of age) from the Danish Diet, Cancer, and Health cohort reported physical activity at baseline (1993–1997) and were linked to registry data on hospital contacts and out‐of‐hospital deaths caused by MI, until December 2015. Nitrogen dioxide levels were estimated at participants’ baseline residences. We used Cox regressions to associate participation in sports, cycling, walking, and gardening with incident and recurrent MI, and tested for interaction by nitrogen dioxide. Of 50 635 participants without MI at baseline, 2936 developed incident MI, and of 1233 participants with MI before baseline, 324 had recurring MI during follow‐up. Mean nitrogen dioxide concentration was 18.7 μg/m3 at baseline (1993–1997). We found inverse statistically significant associations between participation in sports (hazard ratio; 95% confidence interval: 0.85; 0.79–0.92), cycling (0.91; 0.84–0.98), gardening (0.87; 0.80–0.95), and incident MI, while the association with walking was statistically nonsignificant (0.95; 0.83–1.08). Recurrent MI was statistically nonsignificantly inversely associated with cycling (0.80; 0.63–1.02), walking (0.82, 0.57–1.16), and gardening (0.91; 0.71–1.18), and positively with sports (1.06; 0.83–1.35). There was no effect modification of the associations between physical activity and MI by nitrogen dioxide. Conclusions Benefits of physical activity on both the incidence and the recurrence of MI are not reduced by exposure to high levels of air pollution.

Introduction: Oral moist snuff is widely used in Sweden including during pregnancy. Maternal snuff use has been associated with increased risks of adverse pregnancy outcomes in epidemiological studies. Self-reported maternal snuff use has not been validated previously. The main objective of this study was to validate self-reported snuff use in pregnancy in a prospective cohort study and in the Medical Birth Register., Material and Methods: A prospective Swedish cohort study, 2005-2011, in which 572 women were asked to participate. Of 474 recruited women, 381 non-smokers (263 snuff users and 118 non-tobacco users) were included in the main analyses. Participants prospectively reported snuff use through questionnaires. Medical Birth Register data on the participants was obtained. Maternal urine cotinine was collected in late pregnancy and was used as a biomarker., Results: Cotinine levels in maternal urine confirmed a high validity of self-reported snuff use through questionnaires in late pregnancy; sensitivity and specificity values were 98% and 96%, respectively. In the Medical Birth Register, 45% of the snuff users were misclassified as nonusers in late pregnancy. There were significant differences in median cotinine levels between users of mini pouches and users of standard pouches, but there was a great difference of cotinine levels among users with similar number of pouches used daily., Conclusions: Self-reported snuff use through questionnaires has high validity. In the Medical Birth Register, in late pregnancy, many snuff users were misclassified as nonusers. As a consequence, there is a risk of underestimating the harmful effects of snuff use when using late pregnancy Medical Birth Register data., (© 2018 Nordic Federation of Societies of Obstetrics and Gynecology.)