Objectives The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene ( LPA ) on vascular diseases with different atherosclerotic and thrombotic components. ...Background It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with lipoprotein(a) levels and coronary artery disease (CAD), confer susceptibility predominantly via atherosclerosis or thrombosis. Methods The 2 LPA variants were combined and examined as LPA scores for the association with ischemic stroke (and TOAST Trial of Org 10172 in Acute Stroke Treatment subtypes) (effective sample size ne = 9,396); peripheral arterial disease ( ne = 5,215); abdominal aortic aneurysm ( ne = 4,572); venous thromboembolism ( ne = 4,607); intracranial aneurysm ( ne = 1,328); CAD ( ne = 12,716), carotid intima-media thickness (n = 3,714), and angiographic CAD severity (n = 5,588). Results LPA score was associated with ischemic stroke subtype large artery atherosclerosis (odds ratio OR: 1.27; p = 6.7 × 10–4 ), peripheral artery disease (OR: 1.47; p = 2.9 × 10–14 ), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 × 10–5 ), but not with the ischemic stroke subtypes cardioembolism (OR: 1.03; p = 0.69) or small vessel disease (OR: 1.06; p = 0.52). Although the LPA variants were not associated with carotid intima-media thickness, they were associated with the number of obstructed coronary vessels (p = 4.8 × 10–12 ). Furthermore, CAD cases carrying LPA risk variants had increased susceptibility to atherosclerotic manifestations outside of the coronary tree (OR: 1.26; p = 0.0010) and had earlier onset of CAD (–1.58 years/allele; p = 8.2 × 10–8 ) than CAD cases not carrying the risk variants. There was no association of LPA score with venous thromboembolism (OR: 0.97; p = 0.63) or intracranial aneurysm (OR: 0.85; p = 0.15). Conclusions LPA sequence variants were associated with atherosclerotic burden, but not with primarily thrombotic phenotypes.
Abstract Introduction Obesity is associated with increased all-cause mortality, but weight loss may not decrease cardiovascular events. In fact, very low calorie diets have been linked to arrhythmias ...and sudden death. The QT interval is the standard marker for cardiac repolarization, but T-wave morphology analysis has been suggested as a more sensitive method to identify changes in cardiac repolarization. We examined the effect of a major and rapid weight loss on T-wave morphology. Methods and Results Twenty-six individuals had electrocardiograms (ECG) taken before and after eight weeks of weight loss intervention along with plasma measurements of fasting glucose, HbA1c, and potassium. For assessment of cardiac repolarization changes, T-wave Morphology Combination Score (MCS) and ECG intervals: RR, PR, QT, QTcF (Fridericia-corrected QT-interval), and QRS duration were derived. The participants lost on average 13.4 % of their bodyweight. MCS, QRS, and RR intervals increased at week 8 (p<0.01), while QTcF and PR intervals were unaffected. Fasting plasma glucose (p<0.001) and HbA1c both decreased at week 8 (p<10 - 5 ), while plasma potassium was unchanged. MCS but not QTcF was negatively correlated with HbA1c (p<0.001) and fasting plasma glucose (p<0.01). Conclusion Rapid weight loss induces changes in cardiac repolarization. Monitoring of MCS during calorie restriction makes it possible to detect repolarization changes with higher discriminative power than the QT-interval during major rapid weight loss interventions. MCS was correlated with decreased HbA1c. Thus, sustained low blood glucose levels may contribute to repolarization changes.
Abstract Background The European study MetaCardis aims to investigate the role of the gut microbiota in health and cardiometabolic diseases in France, Germany, and Denmark. To evaluate long-term ...diet–disease relationships, a food frequency questionnaire (FFQ) was found to be the most relevant dietary assessment method for the MetaCardis study. Objective The objectives of this study were to describe the development of three semiquantitative online FFQs used in the MetaCardis study—one FFQ per country—and to assess the relative validity of the French MetaCardis FFQ. Design The layout and format of the MetaCardis FFQ was based on the European Prospective Investigation of Cancer (EPIC)-Norfolk FFQ and the content was based on relevant European FFQs. Portion size and nutrient composition were derived from national food consumption surveys and food composition databases. To assess the validity of the French MetaCardis FFQ, a cross-sectional study design was utilized. Participants/setting The validation study included 324 adults recruited between September 2013 and June 2015 from different hospitals in Paris, France. Main outcome measures Food intakes were measured with both the French MetaCardis FFQ and 3 consecutive self-administered web-based 24-hour dietary recalls (DRs). Statistical analyses performed Several measures of validity of the French MetaCardis FFQ were evaluated: estimations of food groups, energy, and nutrient intakes from the DRs and the FFQ, Spearman and Pearson correlations, cross-classification, and Bland-Altman analyses. Results The French MetaCardis FFQ tended to report higher food, energy, and nutrient intakes compared with the DRs. Mean correlation coefficient was 0.429 for food, 0.460 for energy, 0.544 for macronutrients, 0.640 for alcohol, and 0.503 for micronutrient intakes. Almost half of participants (44.4%) were correctly classified within tertiles of consumption, whereas 12.9% were misclassified in the opposite tertile. Performance of the FFQ was relatively similar after stratification by sex. Conclusions The French MetaCardis FFQ was found to have an acceptable level of validity and may be a useful instrument to rank individuals based on their food and nutrient intakes.
Both hypoglycemia and severe hyperglycemia constitute known risk factors for cardiac repolarization changes potentially leading to malignant arrhythmias. Patients with loss of function mutations in ...KCNQ1 are characterized by long QT syndrome (LQTS) and may be at increased risk for glucose-induced repolarization disturbances.
The purpose of this study was to test the hypothesis that KCNQ1 LQTS patients are at particular risk for cardiac repolarization changes during the relative hyperglycemia that occurs after an oral glucose load.
Fourteen KCNQ1 LQTS patients and 28 control participants matched for gender, body mass index, and age underwent a 3-hour oral 75-g glucose tolerance test with ECGs obtained at 7 time points. Fridericia corrected QT interval (QTcF), Bazett corrected QT interval (QTcB), and the Morphology Combination Score (MCS) were calculated.
QTc and MCS increased in both groups. MCS remained elevated until 150 minutes after glucose ingestion, and the maximal change from baseline was larger among KCNQ1 LQTS patients compared with control subjects (0.28 ± 0.27 vs 0.15 ± 0.13; P <.05).
Relative hyperglycemia induced by ingestion of 75-g glucose caused cardiac repolarization disturbances that were more severe in KCNQ1 LQTS patients compared with control subjects.
Summary The MART1-verified Ki-67 proliferation index is a valuable aid to distinguish melanomas from nevi. Because such indices are quantifiable by image analysis, they may provide a novel automated ...diagnostic aid. This study aimed to validate the diagnostic performance of automated dermal Ki-67 indices and to explore the diagnostic capability of epidermal Ki-67 in lesions both with and without a dermal component. In addition, we investigated the automated indices' ability to predict sentinel lymph node (SLN) status. Paraffin-embedded tissues from 84 primary cutaneous melanomas (35 with SLN biopsy), 22 melanoma in situ, and 270 nevi were included consecutively. Whole slide images were captured from Ki-67/MART1 double stains, and image analysis computed Ki-67 indices for epidermis and dermis. In lesions with a dermal component, the area under the receiver operating characteristic (ROC) curve was 0.79 (95% confidence interval CI, 0.72-0.86) for dermal indices. By excluding lesions with few melanocytic cells, this area increased to 0.93 (95% CI, 0.88-0.98). A simultaneous analysis of epidermis and dermis yielded an ROC area of 0.94 (95% CI, 0.91-0.96) for lesions with a dermal component and 0.98 (95% CI, 0.97-1.0) for lesions with a considerable dermal component. For all lesions, the ROC area of the simultaneous analysis was 0.89 (95% CI, 0.85-0.92). SLN-positive patients generally had a higher index than SLN-negative patients ( P ≤ .003). Conclusively, an automated diagnostic aid seems feasible in melanocytic pathology. The dermal Ki-67 index was inferior to a combined epidermal and dermal index in diagnosis but valuable for predicting the SLN status of our melanoma patients.
ECTR is an elegant minimally invasive operative treatment of CTS, providing a rapid rehabilitation without increasing the risk of complications. However, there is a significant learning curve and the ...cost of the operation is significantly higher than with conventional open technique. However, the faster rehabilitation and the probability of reducing sick leave may lead to ECTR being overall more cost-effective than open CTR.
Background Because the hospitals in Norway are mostly rural community hospitals that see life-threatening trauma only infrequently, we developed a course in damage control surgery based on a live ...porcine model in 1999. The course also focuses on teamwork and leadership training based on crew resource management principles. The aim of this study was to evaluate the direct educational benefit from the course and whether participants had used the damage control techniques in their subsequent daily practice. Study Design A total of 103 participants completed 2 questionnaires about the self-efficacy for damage control surgery, the first at completion of the course and the second at least 6 months after the course. Results There was a significant increase in the number of trauma team members who felt comfortable performing damage control surgery (from 17% before the course to 62% at followup; p < 0.001). Almost half the surgeons and operating room nurses reported using damage control techniques in their subsequent practice. Participants considered the focus on team-oriented training important. Four of every five participants thought this course had improved their ability to handle severely injured patients. Conclusions This study shows that a team-oriented operative trauma course is not only beneficial in the short term, but the principles and techniques learned are subsequently applied by the graduates in their daily practice. Course content and structure, particularly the emphasis on integral operating room teams working together, is especially suitable for the rural setting.
Accurate monitoring of changes in dietary patterns in response to food policy implementation is challenging. Metabolic profiling allows simultaneous measurement of hundreds of metabolites in urine, ...the concentrations of which can be affected by food intake. We hypothesised that metabolic profiles of urine samples developed under controlled feeding conditions reflect dietary intake and can be used to model and classify dietary patterns of free-living populations.
In this randomised, controlled, crossover trial, we recruited healthy volunteers (aged 21–65 years, BMI 20–35 kg/m2) from a database of a clinical research unit in the UK. We developed four dietary interventions with a stepwise variance in concordance with the WHO healthy eating guidelines that aim to prevent non-communicable diseases (increase fruits, vegetables, whole grains, and dietary fibre; decrease fats, sugars, and salt). Participants attended four inpatient stays (72 h each, separated by at least 5 days), during which they were given one dietary intervention. The order of diets was randomly assigned across study visits. Randomisation was done by an independent investigator, with the use of opaque, sealed, sequentially numbered envelopes that each contained one of the four dietary interventions in a random order. Participants and investigators were not masked from the dietary intervention, but investigators analysing the data were masked from the randomisation order. During each inpatient period, urine was collected daily over three timed periods: morning (0900–1300 h), afternoon (1300–1800 h), and evening and overnight (1800–0900 h); 24 h urine samples were obtained by pooling these samples. Urine samples were assessed by proton nuclear magnetic resonance (1H-NMR) spectroscopy, and diet-discriminatory metabolites were identified. We developed urinary metabolite models for each diet and identified the associated metabolic profiles, and then validated the models using data and samples from the INTERMAP UK cohort (n=225) and a healthy-eating Danish cohort (n=66). This study is registered with ISRCTN, number ISRCTN43087333.
Between Aug 13, 2013, and May 18, 2014, we contacted 300 people with a letter of invitation. 78 responded, of whom 26 were eligible and invited to attend a health screening. Of 20 eligible participants who were randomised, 19 completed all four 72 h study stays between Oct 2, 2013, and July 29, 2014, and consumed all the food provided. Analysis of 1H-NMR spectroscopy data indicated that urinary metabolic profiles of the four diets were distinct. Significant stepwise differences in metabolite concentrations were seen between diets with the lowest and highest metabolic risks. Application of the derived metabolite models to the validation datasets confirmed the association between urinary metabolic and dietary profiles in the INTERMAP UK cohort (p<0·0001) and the Danish cohort (p<0·0001).
Urinary metabolite models developed in a highly controlled environment can classify groups of free-living people into consumers of diets associated with lower or higher non-communicable disease risk on the basis of multivariate metabolite patterns. This approach enables objective monitoring of dietary patterns in population settings and enhances the validity of dietary reporting.
UK National Institute for Health Research and UK Medical Research Council.
Dilatation of aortic prosthetic grafts is commonly reported, but most reports are anecdotal, with little objective data in the literature. We performed a prospective trial of 303 patients who ...underwent prosthetic graft repair for aortic aneurysm or occlusive disease, randomizing patients between insertion of a woven polyester or expanded polytetrafluoroethylene (ePTFE) graft. Patients were followed with computed tomography and ultrasonography for up to 5 years in order to assess the frequency and magnitude of postoperative dilatation. Graft dilatation was documented in patients with polyester grafts at 12 months. Thereafter and up to 60 months, polyester grafts did not dilate further. After 5 years, polyester prostheses had dilated by 25% and ePTFE by 12.5%, as determined by computed tomography imaging. These observations suggest that dilatation of prosthetic grafts is more frequent with knitted polyester grafts compared with ePTFE. Dilatation occurs within the first year after implantation and can be, in part, explained by a discrepancy between the initial nominal graft diameter and its diameter after clamp release, probably due to an in vivo adaptation of the textile structure. Interestingly, graft dilatation did not appear to be associated with an increased frequency of graft-related complications.
Abstract Retroviral infections e.g. HIV still represent a unique burden in the field of vaccine research. A common challenge in vaccine design is to find formulations that create appropriate immune ...responses to protect against and/or control the given pathogen. Nanoparticles have been considered to be ideal vaccination vehicles that mimic invading pathogens. In this study, we present biodegradable calcium phosphate (CaP) nanoparticles, functionalized with CpG and retroviral T cell epitopes of Friend virus (FV) as excellent vaccine delivery system. CaP nanoparticles strongly increased antigen delivery to antigen-presenting cells to elicit a highly efficient T cell-mediated immune response against retroviral FV infection. Moreover, single-shot immunization of chronically FV-infected mice with functionalized CaP nanoparticles efficiently reactivated effector T cells which led to a significant decrease in viral loads. Thus, our findings clearly indicate that a nanoparticle-based peptide immunization is a promising approach to improve antiretroviral vaccination. From the Clinical Editor In this study, biodegradable calcium phosphate nanoparticles were used as a vaccine delivery system after functionalization with CpG and Friend virus-derived T-cell epitopes. This vaccination strategy resulted in increased T-cell mediated immune response even in chronically infected mice, providing a promising approach to the development of clinically useful antiretroviral vaccination strategies.
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