Adipose Tissue Fatty Acid Patterns and Changes in Anthropometry: A Cohort Study

INTRODUCTION: Diets rich in n-3 long chain polyunsaturated fatty acids (LC-PUFA), but low in n-6 LC-PUFA and 18:1 trans-fatty acids (TFA), may lower the risk of overweight and obesity. These fatty acids have often been investigated individually. We explored associations between global patterns in adipose tissue fatty acids and changes in anthropometry. METHODS: 34 fatty acid species from adipose tissue biopsies were determined in a random sample of 1100 men and women from a Danish cohort study. We used sex-specific principal component analysis and multiple linear regression to investigate the associations of adipose tissue fatty acid patterns with changes in weight, waist circumference (WC), and WC controlled for changes in body mass index (WC(BMI)), adjusting for confounders. RESULTS: 7 principal components were extracted for each sex, explaining 77.6% and 78.3% of fatty acid variation in men and women, respectively. Fatty acid patterns with high levels of TFA tended to be positively associated with changes in weight and WC for both sexes. Patterns with high levels of n-6 LC-PUFA tended to be negatively associated with changes in weight and WC in men, and positively associated in women. Associations with patterns with high levels of n-3 LC-PUFA were dependent on the context of the rest of the fatty acid pattern. CONCLUSIONS: Adipose tissue fatty acid patterns with high levels of TFA may be linked to weight gain, but patterns with high n-3 LC-PUFA did not appear to be linked to weight loss. Associations depended on characteristics of the rest of the pattern

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

Cancer and Thrombosis: New Treatments, New Challenges

The direct-acting oral anticoagulant (DOAC) has become an alternative to low-molecular-weight heparin (LMWH) for treatment and prophylaxis of venous thromboembolism (VTE) in cancer patients. The clinicians are, however, faced with difficult decisions regarding DOAC treatment: Which patients cannot use DOACs? Should incidental VTE be treated similar to symptomatic VTE? Is it safe to give DOACs to patients with gastrointestinal or urogenital cancers? How about drug–drug interactions? Should all cancer patients receive thromboprophylaxis? Is arterial thrombosis a problem? The current article reviews the available literature regarding these questions and aims to provide practical solutions based on data from the clinical trials and new guidelines

Bias in animal studies of estrogen effects on cardiovascular disease: A systematic review and meta-analysis

Background: Randomized controlled trials on menopausal hormone therapy in humans have not confirmed the benefit of estrogens on cardiovascular disease found in animal studies. Flawed methodology or publication bias in animal studies may explain the dicrepancy. Objectives: The aim of this study was to investigate whether publication of the randomized controlled trials Heart and Estrogen/Progestin Replacement Study and Women's Health Initiative influenced study authors' assessment of research findings (confirmation bias) as well as to investigate publication bias and small-study effects in animal studies of estrogen effects on atherosclerosis. Methods: The data source for this study was PubMed from inception to 2018. We selected animal studies with cardiovascular outcomes comparing 17-β-estradiol, its natural metabolites, or conjugated equine estrogen with control. Qualitative data were extracted on authors' conclusions about estrogen effects on cardiovascular disease, as well as quantitative data for atherosclerosis outcomes. Fixed- and random-effects meta-analyses were used. Publication bias/small-study effects were assessed using funnel plots and Egger's regression. Trim-and-fill plots and extrapolation from Egger's regression were used to adjust for publication bias. The main outcomes and measures were the primary study authors' interpretation of their own results, and estrogen effects on cardiovascular disease in general before and after publication of the Women's health Initiative study (2003). The effects of estrogens on atherosclerosis were measured as standardized mean difference between intervention and control. Results: Of 1925 studies retrieved, 360 were eligible for analyses. Study-specific statements concluded that estrogens were protective against cardiovascular disease in 75% of studies before 2003 and 78% after, but the percentage of general statements about estrogens being cardioprotective changed from 70% to 40%. Meta-analyses showed less atherosclerosis in estrogen-treated animals. Extremely skewed funnel plots and P < .01 in Egger's regression suggested publication bias and/or exaggerated effects in small studies, which was more pronounced after 2002. There was substantial heterogeneity of effects (I 2 = 68%-86%) overall and in all subgroups except cynomolgus monkeys (I 2 = 9%), the only animal subgroup without clear bias. Adjusting for publication bias, overall estimates of estrogen effects on atherosclerosis were close to null effect. Conclusions: We found substantial evidence of publication bias but not of confirmation bias. Publication bias and flawed small studies may partly explain why findings differ between animal studies and clinical trials on the effect of estrogens on cardiovascular disease. Keywords: animals; cardiovascular disease; estrogens; publication bias; systematic review. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH

Low diagnostic accuracy and inter-observer agreement on CT and MRI in diagnosis of spinal fractures in multiple myeloma

Skeletal disease is common in multiple myeloma. We investigated the inter-observer agreement and diagnostic accuracy of spinal fractures diagnosed by computer tomography (CT) and magnetic resonance imaging (MRI) from 12 myeloma patients. Two radiologists independently assessed the images. CT, MRI, and other images were combined to a gold standard. The inter-observer agreement was assessed with Cohen’s kappa. Radiologist 1 diagnosed 20 malignant spinal fractures on CT and 26 on MRI, while radiologist 2 diagnosed 12 malignant spinal fractures on CT and 22 on MRI. In comparison the gold standard diagnosed 10 malignant spinal fractures. The sensitivity for malignant fractures varied from 0.5 to 1 for CT and MRI, and the specificity varied from 0.17 to 0.67. On MRI, the specificity for malignant spinal fractures was 0.17 for both radiologists. The inter-observer agreement for malignant spinal fractures on CT was −0.42 (Cohen’s kappa) and −0.13 for MRI, while for osteoporotic fractures it was −0.24 for CT and 0.53 for MRI. We conclude that malignant spinal fractures were over-diagnosed on CT and MRI. The inter-observer agreement was extremely poor

Safety of D-dimer testing as a stand-alone test for the exclusion of deep vein thrombosis as compared with other strategies

Background: Several strategies for safely excluding deep vein thrombosis (DVT) while limiting the number of imaging tests have been explored. Objectives: To determine whether D-dimer testing could safely and efficiently exclude DVT as a stand-alone test, and evalu- ate its performance as compared with strategies that incorporate the Wells score and age-adjusted D-dimer. Patients/Methods: We included consecutive outpatients referred with suspected DVT to the Emergency Depart- ment at Østfold Hospital, Norway. STA-Liatest D-Di PLUS D-dimer was analyzed for all patients. Patients with a D-dimer level of ≥ 0.5 lgmL 1 were referred for compression ultrasonography (CUS). In patients with a D-dimer level of < 0.5 lgmL 1 , no further testing was performed and anticoagulation was withheld. Patients were followed for 3 months for venous thromboembolism (VTE). Results: Of the 913 included patients, 298 (33%) had a negative D-dimer result. One hundred and seventy- three patients (18.9%) were diagnosed with DVT at baseline. One of 298 patients had DVT despite having a negative D-dimer result, resulting in a failure rate of 0.3% (95% confidence interval [CI] 0.1–1.9%). Adding the modified Wells score would have yielded a failure rate of 0.0% (95% CI 0.0–1.8%) while necessitating 87 more CUS examinations. Age-adjusted D-dimer as a stand- alone test would have necessitated 80 fewer CUS exami- nations than fixed D-dimer as a stand-alone test, at the cost of a failure rate of 1.6% (95% CI 0.7– 3.4%). Con- clusions: This outcome study shows that a negative high-sensitivity D-dimer result safely excludes DVT in an outpatient population, and necessitates fewer CUS than if used in combination with Wells score. The safety of stand-alone age-adjusted D-dimer needs further assess- ment in prospective outcome studies

Elevated complement C3 and C4 levels are associated with postnatal pregnancy-related venous thrombosis

High levels of complement C3 are associated with venous thrombosis (VT) in the general population. We investigated if high C3 and C4 levels were associated with pregnancy-related VT. We undertook the Norwegian VIP study, a case–control study of VT in pregnancy or within 3 months postpartum (cases, n = 313) and women without pregnancy-related VT (controls, n = 353). Determinants of C3 and C4 in the control women were investigated with linear regression and the odds ratio (OR) for pregnancy-related VT was calculated with logistic regression. We found that levels of C3 and C4 were associated with body mass index (BMI), C-reactive protein (CRP); with the coagulation factors (F) fibrinogen, FVIII, and FIX; and with the coagulation inhibitors antithrombin, protein C, protein S, and tissue factor pathway inhibitor. These associations were influenced by CRP levels. The crude OR for pregnancy-related VT was 1.8 (95% confidence interval [CI], 1.1–3.0) for C3 above the 90th percentile and 2.0 (95% CI, 1.2–3.2) for C4 above the 90th percentile. Stratification in antenatal and postnatal VT showed that C3 and C4 were only associated with postnatal VT with an OR for high C3 of 3.0 (95% CI, 1.8–5.0), and for high C4 of 2.6 (95% CI, 1.5–4.6). Adjustment for high FIX and BMI reduced the ORs. We conclude that the association between postnatal VT and C3 and C4 suggests that there is clinically relevant crosstalk between the complement and the coagulation system

Circadian rhythms of hemostatic factors in tetraplegia: a double-blind, randomized, placebo-controlled cross-over study of melatonin

Study design: This is a double-blind, randomized, placebo-controlled cross-over study of melatonin in complete tetraplegia. Objectives: Tetraplegic patients have an increased risk of venous thrombosis despite prophylaxis, blunted variations in melatonin and altered circadian variation of several hemostatic markers. To examine whether melatonin could modify the regulation of hemostasis, we measured plasma melatonin and several markers of hemostasis in tetraplegic subjects with or without melatonin supplement. Setting: The study was conducted in the Section for Spinal Cord Injury, Sunnaas Hospital, Nesoddtangen, Norway. Methods: Six subjects with long-standing complete tetraplegia were included in this cross-over study with 2 mg of melatonin or placebo given 4 days before sampling. We also included six able-bodied men without any intervention. Plasma samples were then collected frequently during a 24-h awake/sleep cycle. The plasma concentrations of melatonin and the various markers were analyzed using linear mixed models. Results: The 24-h profiles of prothrombin fragment 1+2 and von Willebrand factor, but not D-dimer, activated FVII, tissue factor pathway inhibitor and plasminogen activator inhibitor type 1, differed (Po0.05) between tetraplegic patients and able-bodied subjects. The absolute plasma concentration of activated FVII was higher (Po0.05) among the able-bodied compared with the tetraplegic groups. Supplementation of melatonin had no impact on these findings. Conclusions: We found differences in circadian variation of several hemostatic markers between able-bodied and tetraplegics. These differences were apparently unrelated to fluctuations in the melatonin concentrations, suggesting little or no role of melatonin in the regulation of hemostasis in tetraplegia