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Background: Elevated serum bile acids (BA) are harmful to the heart and alterations in the BA composition have been suggested to cause cardiovascular disturbances in cirrhosis., Aim: To investigate any associations between specific groups or individual serum BA and structural and functional cardiac abnormalities in patients with cirrhosis., Methods: An explorative study in 86 patients with cirrhosis. All participants underwent extensive cardiac assessment, including cardiac MRI with quantification of myocardial extracellular volume (ECV), which is indicative of diffuse myocardial fibrosis. A panel of 15 individual serum BA and C4, a marker of de novo bile acid synthesis, were assessed., Results: Patients with advanced cirrhosis had higher levels of total BA and conjugated BA, as well as lower C4 levels (p < 0.001). Conjugated BA levels were higher in patients with a high cardiac index (p < 0.001), increased left atrial volume index (LAVI) (p < 0.001), and in those with an abnormal myocardial ECV (p < 0.05). We also found several strong correlations between conjugated BA, both as a group and individually, and parameters of cardiac dysfunction. In a model adjusted for sex, age, BMI and MELD, conjugated BA remained significantly associated with LAVI, septal e', left ventricular volumes and cardiac index. In addition, taurocholic acid correlated closely with hepatic venous pressure gradient (HVPG) (p = 0.01)., Conclusions: Increased serum concentrations of conjugated BA are associated with several cardiac parameters, indicating a potential role in the development of hyperdynamic circulation and cardiac dysfunction in cirrhosis. Moreover, taurine-conjugated BA are associated with portal hypertension., (© 2023 John Wiley & Sons Ltd.)

Objective: Uncertainty exists for the absolute risk of ischemic and hemorrhagic stroke in users of oral contraceptives (OCs). Estimates greatly vary between countries. In Denmark, absolute risk of ischemic stroke (IS) is estimated to be 21 per 100,000 person-years. Risk of cerebral hemorrhage (CH) is unknown. Using the Danish Stroke Registry, we investigated absolute risk of IS and CH in users of OC., Material and Methods: For the Danish female population aged 15-49 years during 2003-2011, we obtained information on hospital admission for IS and CH and current use of OC from Danish nationwide registries. We defined current use of OC as redeeming at least two OC prescriptions within the previous year., Results: The Danish female population years 2003-2011 consisted mean of 1,246,142 women per year. Of these, 29.6% were OC users. In the study period, OC users had 291 IS and 14 CH. Absolute risk of IS in OC users was 8.8 per 100,000 person-years and of CH it was 0.4 per 100,000 person-years., Conclusions: In OC users, absolute risk of IS was 8.8 per 100,000 person-years. This is more than half that of the risk previously assumed in Denmark. Risk of CH in OC users was very low and 0.4 per 100,000 person-years., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: While early treatment of posterior uveal melanoma can save the eye, the effect of early treatment on survival remains unknown. Therefore, we aimed to determine whether the tumour size at diagnosis has changed over time, and if this has affected survival rates of patients with posterior uveal melanoma in Denmark., Methods: Nationwide retrospective cohort study linking data from registry-based resources to data from clinical charts and pathology records. Including all Danish patients diagnosed with posterior uveal melanoma from 1943 to 2017. Incidence rates were estimated as annual percentage change (APC) overall and by American Joint Committee on Cancer (AJCC) tumour sizes. The age-period-cohort model was applied to estimate the relative risk of calendar period. The cox proportional hazards model, relative survival Kaplan-Meier curves and cumulative incidence curves were applied to estimate the effect of calendar period on survival., Results: An overall increase in incidence rate of uveal melanoma was found (APC = 0.25%, 0.08-0.42; 95% CI). This was due to increasing incidence rate of AJCC T1 + T2 tumours (APC = 0.97%, 0.57-1.37; 95% CI), whereas no increase in incidence rates of AJCC T3 + T4 tumours was found (APC = -0.01%, -0.26 to 0.25; 95% CI). The disease-specific survival improved with calendar period for all tumour sizes (HR = 0.988; 0.984-0.993; 95% CI)., Conclusion: Increasing incidence rate and improved survival rate for uveal melanoma was found concordantly with a decrease in tumour size during a 70-year period., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Objectives: Stroke is associated with a higher risk of occult cancer. We studied the types of occult cancer most often associated with stroke., Materials and Methods: All patients with incident stroke in Denmark 2003-2015 were identified through the Danish Stroke Registry (n = 85 893) and matched 1:10 on age and sex to the Danish background population without history of stroke (n = 858 740). Linking data to the Danish Cancer Registry, we determined the prevalence of occult cancer in stroke defined as the event of previously unknown cancer during a one-year follow-up in the stroke and the background population. We stratified cancers into the 15 most common cancers and into cancers related to and not related to smoking., Results: Prevalence (per 1000 person-years; stroke/background population) of smoking-related occult cancers (lung, colon, bladder rectum, pancreas, kidney, stomach, and head and neck) was 13.3/8.1 (P < .01) and of cancers not related to smoking (prostate, breast, melanoma, non-Hodgkin lymphoma, ovary, endometrial) it was 6.6/6.2 (P > .05). Among men with stroke prostate (5.8), lung (5.7), and colon cancers (2.9) were most frequent; among women, it was lung (4.7), breast(3.5), and colon cancer(2.8). Among men in the background population, prostate(5.4), lung (3.0), and colon cancers (2.1) were most frequent. Among women, it was breast (3.7), lung(2.1), and colon cancers (1.9)., Conclusion: Stroke patients' increased risk of occult cancer was predominantly for smoking-related cancers while there was no higher risk for the most frequent cancers unrelated to smoking, that is, prostate and breast cancers. Lung cancer is the dominant type of occult cancer in stroke., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Cancer is associated with higher risk of stroke. Whether this translates into higher risk of cancer in stroke of an extent calling for cancer screening in stroke is unclear. We investigated prevalence and risk of occult cancer in stroke compared to the background population without history of stroke., Materials and Methods: All patients >40 years of age with incident stroke in Denmark 2003-2015 were identified through the Danish Stroke Registry (n = 85 893) and matched 1:10 on age and sex to the Danish background population without history of stroke (n = 858 740). Linking data to the Danish Cancer Registry, we determined prevalence of occult cancer in stroke defined as the event of previously unknown cancer during a 1-year follow-up in the stroke and in the background population. Cox regression models were used to study risk in comparison to the background population., Results: Prevalence (per 1000) of occult cancer in the stroke/background cohorts was 25.0/15.8 in women and 29.8/20.4 in men. Prevalence was dependent on age and sex. Highest among stroke patients aged 70-80 years (35.6 in women, 42.4 in men); lowest in patients aged 40-50 years (8.3 in women, 6.8 in men). Stroke was associated with an overall 54% higher risk of occult cancer but risk increased significantly with smoking, hazard ratio (HR) 1.47, age HR 1.27 per 10 years, male sex HR 1.25, and diabetes HR 1.25., Conclusions: Prevalence and risk of occult cancer in stroke is considerable and calls for attention when designing the stroke investigation program., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Most studies show that marriage conveys a survival advantage. Whether this is valid also for stroke patients is unclear. Results of studies have been inconsistent and conflicting., Material & Methods: We studied 1-week and 1-month stroke case-fatality in relation to marital status (married, unmarried, divorced, and widowed) in all patients admitted to hospital for incident stroke in Denmark during 2003-2012. We used information from Danish registries on stroke merged to information on age, sex, marital status, stroke severity, stroke subtype, socioeconomic status, cardiovascular risk profile, and causes of death. We studied deaths due to the index stroke within the first week and month after stroke. Multivariate Cox regression models were applied to estimate cause-specific hazards and relative risks., Results: We included 60507 patients with an incident stroke of which 51.19% were married, 9.47% were unmarried, 13.29% were divorced, and 26.05% were widowers. Death within the first week and first month was caused by stroke in 2110 (3.5%) and 3423 (5.7%) patients, respectively. Compared to married stroke patients, 1-week/1-month case-fatality (by stroke) was lower for the unmarried (HR (hazard ratio):0.69/0.74), divorced (HR:0.69/0.72), and widowed (HR:0.80/0.74) men and the unmarried (HR:0.84/0.86), divorced (HR:0.82/0.80), and widowed (HR:0.87/0.88) women with stroke., Conclusions: One-week and one-month case-fatality by stroke was lower among the unmarried, divorced, and widowed than among the married stroke patients. Selection by so-called mortality displacement linked to shorter life expectancy among divorced, widowed, and singles may explain our findings., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Most studies report that marriage carries a lower risk of stroke than single living. Whether the marriage advantage is applicable with respect to all other marital status categories (unmarried, divorced, widow) remains unclear. We studied marital status and its association with incident stroke., Material and Methods: We included all patients > 40 years of age admitted to hospital for stroke in Denmark during 2003-2012 and compared marital status to the general Danish population (5.5 millions). Relative risks (RR) for stroke were estimated in log-linear Poisson regression models adjusting for age, sex, calendar year, income, and length of education., Results: A total of 58 847 patients with incident stroke were included. Crude incidence rates of stroke (per 1000 per year) among the four marital status categories were as follows: 1.96 (married), 1.52 (unmarried), 2.36 (divorced), and 5.43 (widowed). Compared to married persons, adjusted risk of stroke was significantly increased for divorced (RR 1.23; CI 1.19-1.27) and unmarried men (RR 1.07; CI 1.03-1.11) but not for widowed men (RR 1.02; CI 0.98-1.06); risk was slightly increased for divorced women (RR 1.10; CI 1.06-1.15) while not for widowed (RR 1.0; CI 0.97-1.03) and unmarried women (RR 0.97; CI 0.97-1.03)., Conclusions: Divorce was associated with higher risk of stroke, especially in men. Living in marriage or as unmarried or widower had only little or no impact on the risk of stroke., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Severe sepsis is defined by organ failure, often of the kidneys, heart, and brain. It has been proposed that inadequate delivery of oxygen, or insufficient extraction of oxygen in tissue, may explain organ failure. Despite adequate maintenance of systemic oxygen delivery in septic patients, their morbidity and mortality remain high. The assumption that tissue oxygenation can be preserved by maintaining its blood supply follows from physiological models that only apply to tissue with uniformly perfused capillaries. In sepsis, the microcirculation is profoundly disturbed, and the blood supply of individual organs may therefore no longer reflect their access to oxygen. We review how capillary flow patterns affect oxygen extraction efficacy in tissue, and how the regulation of tissue blood flow must be adjusted to meet the metabolic needs of the tissue as capillary flows become disturbed as observed in critical illness. Using the brain, heart, and kidney as examples, we discuss whether disturbed capillary flow patterns might explain the apparent mismatch between organ blood flow and organ function in sepsis. Finally, we discuss diagnostic means of detecting capillary flow disturbance in animal models and in critically ill patients, and address therapeutic strategies that might improve tissue oxygenation by modifying capillary flow patterns., (© 2015 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Background: Uncertainty remains about whether stroke affects men and women similarly. We studied differences between men and women with regard to stroke severity and survival., Methods and Results: We used the Danish Stroke Registry, with information on all hospital admissions for stroke in Denmark between 2003 and 2012 (N=79 617), and the Danish Register of Causes of Death. Information was available on age, sex, marital status, stroke severity, stroke subtype, socioeconomic status, and cardiovascular risk profile. We studied only deaths due to the index stroke, with the assumption that death reported on death certificates as due to stroke was related to the index stroke if death occurred within the first week or month after stroke. Multivariate Cox regression analysis and multiple imputation were applied. Stroke was the cause of death for 4373 and 5512 of the 79 617 patients within 1 week (5.5%) or 1 month (6.9%), respectively. After the age of 60 years, women had more severe strokes than men. Up to ages in the mid-60s, no difference in the risk of death from stroke was seen between the 2 sexes. For people aged >65 years, however, the risk gradually became greater in men than in women and significantly so (>15%) from the mid-70s (adjusted for age, marital status, stroke severity, stroke subtype, socioeconomic status, and cardiovascular risk factors). Results were essentially the same when analyzing deaths within 1 week, 1 month and ischemic and hemorrhagic stroke separately., Conclusions: Stroke affects women and men differently. Elderly women were affected more severely than elderly men but were more likely to survive., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: A greater burden of stroke risk factors in general is associated with a higher risk for stroke among people of lower than those of higher socioeconomic position. The relative impact of individual stroke risk factors is still unclear., Methods and Results: We studied the relations between socioeconomic position, measured as household income and length of education, and all hospital admissions for a first ischemic stroke among 54 048 people over the age of 40 years in Denmark in 2003-2012 in comparison with the general Danish population (23.5 million person-years). We also studied the cardiovascular risk factor profile associated with socioeconomic position in stroke patients. Relative risks for stroke were estimated in log-linear Poisson regression models. The risk for hospitalization for a first ischemic stroke was almost doubled for people in the lowest income group, and the risk of those of working age (<65 years) was increased by 36% among people with the shortest education. Diabetes, obesity, smoking, and high alcohol consumption in particular and, to a lesser extent, previous myocardial infarction or intermittent arterial claudication were significantly overrepresented among stroke patients with lower socioeconomic position. Atrial fibrillation and hypertension were not., Conclusions: In Denmark, there is a strong relation between low socioeconomic position and risk for hospitalization for stroke. Lifestyle, as indicated by smoking, obesity, and alcohol consumption, and diabetes appears to increase the risk for stroke in people with lower socioeconomic position., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)