Despite the central role of quantitative PCR (qPCR) in the quantification of mRNA transcripts, most analyses of qPCR data are still delegated to the software that comes with the qPCR apparatus. This ...is especially true for the handling of the fluorescence baseline. This article shows that baseline estimation errors are directly reflected in the observed PCR efficiency values and are thus propagated exponentially in the estimated starting concentrations as well as 'fold-difference' results. Because of the unknown origin and kinetics of the baseline fluorescence, the fluorescence values monitored in the initial cycles of the PCR reaction cannot be used to estimate a useful baseline value. An algorithm that estimates the baseline by reconstructing the log-linear phase downward from the early plateau phase of the PCR reaction was developed and shown to lead to very reproducible PCR efficiency values. PCR efficiency values were determined per sample by fitting a regression line to a subset of data points in the log-linear phase. The variability, as well as the bias, in qPCR results was significantly reduced when the mean of these PCR efficiencies per amplicon was used in the calculation of an estimate of the starting concentration per sample.
Diastolic dysfunction of the left ventricle (LVDD) is equally common in elderly women and men. LVDD is a condition that can remain latent for a long time but is also held responsible for elevated ...left ventricular filling pressures and high pulmonary pressures that may result in (exercise-induced) shortness of breath. This symptom is the hallmark of heart failure with preserved ejection fraction (HFpEF) which is predominantly found in women as compared to men within the HF spectrum. Given the mechanistic role of LVDD in the development of HFpEF, we review risk factors and mechanisms that may be responsible for this sex-specific progression of LVDD towards HFpEF from an epidemiological point-of-view and propose future research directions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To assess the trend in age- and sex-stratified mortality after hospitalization for heart failure (HF) in the Netherlands.
Two nationwide cohorts of patients, hospitalized for new onset heart failure ...between 01.01.2000-31.12.2002 and between 01.01.2008-31.12.2010, were constructed by linkage of the Dutch Hospital Discharge Registry and the National Cause of Death registry. 30-day, 1-year and 5 -year overall and cause-specific mortality rates stratified by age and sex were assessed and compared over time.
We identified 40,230 men and 41,582 women. In both cohorts, men were on average younger than women (74-75 and 78-79 years, respectively) and more often had comorbid conditions (37 and 30%, respectively). In the 2008-10 cohort, mortality rates for men were 13, 32 and 64% for respectively 30-day, 1-year and 5-year mortality and 14, 33 and 66% for women. Mortality rates increased considerably with age similarly in men and women (e.g. from 10.5% in women aged 25-54 to 46.1% in those aged 85 and older after 1 year). Between the two time periods, mortality rates dropped across all ages, equally strong in women as in men. The 1-year absolute risk of death declined by 4.0% (from 36.1 to 32.1%) in men and 3.2% (from 36.2 to 33.0%) in women.
Mortality after hospitalization for new onset HF remains high, however, both short-term and long-term survival is improving over time. This improvement was similar across all ages and equally strong in women as in men.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To provide evidence that early electroencephalography (EEG) allows for reliable prediction of poor or good outcome after cardiac arrest.
Methods
In a 5‐center prospective cohort study, we ...included consecutive, comatose survivors of cardiac arrest. Continuous EEG recordings were started as soon as possible and continued up to 5 days. Five‐minute EEG epochs were assessed by 2 reviewers, independently, at 8 predefined time points from 6 hours to 5 days after cardiac arrest, blinded for patients’ actual condition, treatment, and outcome. EEG patterns were categorized as generalized suppression (<10 μV), synchronous patterns with ≥50% suppression, continuous, or other. Outcome at 6 months was categorized as good (Cerebral Performance Category CPC = 1–2) or poor (CPC = 3–5).
Results
We included 850 patients, of whom 46% had a good outcome. Generalized suppression and synchronous patterns with ≥50% suppression predicted poor outcome without false positives at ≥6 hours after cardiac arrest. Their summed sensitivity was 0.47 (95% confidence interval CI = 0.42–0.51) at 12 hours and 0.30 (95% CI = 0.26–0.33) at 24 hours after cardiac arrest, with specificity of 1.00 (95% CI = 0.99–1.00) at both time points. At 36 hours or later, sensitivity for poor outcome was ≤0.22. Continuous EEG patterns at 12 hours predicted good outcome, with sensitivity of 0.50 (95% CI = 0.46–0.55) and specificity of 0.91 (95% CI = 0.88–0.93); at 24 hours or later, specificity for the prediction of good outcome was <0.90.
Interpretation
EEG allows for reliable prediction of poor outcome after cardiac arrest, with maximum sensitivity in the first 24 hours. Continuous EEG patterns at 12 hours after cardiac arrest are associated with good recovery. ANN NEUROL 2019;86:203–214
A trial involving comatose survivors of cardiac arrest tested whether aggressively treating rhythmic and periodic EEG activity would improve neurologic outcomes. Despite suppression of abnormal EEG ...activity, the incidence of a poor neurologic outcome did not differ significantly from that with standard care, and mortality was high.
Abstract
Background
Microvascular dysfunction plays a crucial role in complications of type 2 diabetes and might contribute to heart failure with preserved ejection fraction (HFpEF), a disease that ...disproportionally affects women. We aimed to investigate if presence and degree of microvascular dysfunction (MVD) in skin relates to markers of left ventricular diastolic dysfunction (LVDD) and HFpEF risk in adults with type 2 diabetes, and whether sex modifies this association.
Methods
We recruited 154 participants (50% women) from the Hoorn Diabetes Care System Cohort, a prospective cohort study, for in vivo evaluation of skin MVD, echocardiography and blood sampling. MVD was assessed by laser speckle contrast analysis combined with iontophoresis of insulin, acetylcholine and sodium nitroprusside (SNP). We performed a cross-sectional analysis of the association between perfusion responses and echocardiographic and clinical markers of LVDD and the H2FPEF score by multivariable linear regression analysis adjusted for confounders. Sex was evaluated as a potential effect modifier and the analysis was stratified.
Results
Mean age was 67 ± 6y, mean HbA1c 7.6 ± 1.3%. Women were more frequently obese (54.5 vs. 35.1%), had higher NT-proBNP plasma levels (80, IQR:34–165 vs. 46, 27–117 pg/ml) and E/E’(13.3 ± 4.3 vs. 11.4 ± 3.0) than men. Eleven women and three men were diagnosed with HFpEF, and showed lower perfusion response to insulin than those without HFpEF. A lower perfusion response to insulin and acetylcholine was associated with higher HFpEF risk in women, but not men (10% decreased perfusion response was associated with 5.8% 95%CI: 2.3;9.4% and 5.9% 1.7;10.1% increase of the H2FPEF score, respectively). A lower perfusion response to SNP was associated with higher pulmonary arterial systolic pressure in men while a lower perfusion response to acetylcholine associated with higher LV mass index in women and with worse LV longitudinal strain in the total population. No significant associations were found between perfusion responses and conventional LVDD markers.
Conclusions
Impaired microvascular responses to insulin and acetylcholine in skin confers a higher risk of HFpEF in women with type 2 diabetes. In vivo measures of systemic MVD could represent novel risk markers for HFpEF, opening new avenues for the prevention of HFpEF in type 2 diabetes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
8.
Management of Extracranial Carotid Artery Aneurysm Welleweerd, J.C; den Ruijter, H.M; Nelissen, B.G.L ...
European journal of vascular and endovascular surgery,
08/2015, Letnik:
50, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Introduction Aneurysms of the extracranial carotid artery (ECAA) are rare. Several treatments have been developed over the last 20 years, yet the preferred method to treat ECAA remains unknown. This ...paper is a review of all available literature on the risk of complications and long-term outcome after conservative or invasive treatment of patients with ECAA. Methods Reports on ECAA treatment until July 2014 were searched in PubMed and Embase using the key words aneurysm, carotid, extracranial, and therapy. Results A total of 281 articles were identified. Selected articles were case reports ( n = 179) or case series ( n = 102). Papers with fewer than 10 patients were excluded, resulting in the final selection of 39 articles covering a total of 1,239 patients. Treatment consisted of either conservative treatment in 11% of the cases or invasive treatment in 89% of the cases. Invasive treatment comprised surgery in 94%, endovascular approach in 5%, and a hybrid approach in 1% of the patients. The most common complication described after invasive therapy was cranial nerve damage, which occurred in 11.8% of patients after surgery. The 30 day mortality rate and stroke rate in conservatively treated patients was 4.67% and 6.67%, after surgery 1.91% and 5.16%. Information on confounders in the present study was incomplete. Therefore, adjustments to correct for confounding by indication could not be done. Conclusions This review summarizes the largest available series in the literature on ECAA management. The number of ECAAs reported in current literature is scarce. The early and long-term outcome of invasive treatment in ECAA is favorable; however, cranial nerve damage after surgery occurs frequently. Unfortunately, due to limitations in reporting of results and confounding by indication in the available literature, it was not possible to determine the optimal treatment strategy. There is a need for a multicenter international registry to reveal the optimal treatment for ECAA.
RATIONALE:Atherosclerotic lesions are known for their cellular heterogeneity, yet the molecular complexity within the cells of human plaques has not been fully assessed.
OBJECTIVE:Using single-cell ...transcriptomics and chromatin accessibility, we gained a better understanding of the pathophysiology underlying human atherosclerosis.
METHODS AND RESULTS:We performed single-cell RNA and single-cell ATAC sequencing on human carotid atherosclerotic plaques to define the cells at play and determine their transcriptomic and epigenomic characteristics. We identified 14 distinct cell populations including endothelial cells, smooth muscle cells, mast cells, B cells, myeloid cells, and T cells and identified multiple cellular activation states and suggested cellular interconversions. Within the endothelial cell population, we defined subsets with angiogenic capacity plus clear signs of endothelial to mesenchymal transition. CD4 and CD8 T cells showed activation-based subclasses, each with a gradual decline from a cytotoxic to a more quiescent phenotype. Myeloid cells included 2 populations of proinflammatory macrophages showing IL (interleukin) 1B or TNF (tumor necrosis factor) expression as well as a foam cell-like population expressing TREM2 (triggering receptor expressed on myeloid cells 2) and displaying a fibrosis-promoting phenotype. ATACseq data identified specific transcription factors associated with the myeloid subpopulation and T cell cytokine profiles underlying mutual activation between both cell types. Finally, cardiovascular disease susceptibility genes identified using public genome-wide association studies data were particularly enriched in lesional macrophages, endothelial, and smooth muscle cells.
CONCLUSIONS:This study provides a transcriptome-based cellular landscape of human atherosclerotic plaques and highlights cellular plasticity and intercellular communication at the site of disease. This detailed definition of cell communities at play in atherosclerosis will facilitate cell-based mapping of novel interventional targets with direct functional relevance for the treatment of human disease.
Background
Guidelines recommend treating patients with an internal carotid artery near occlusion (ICANO) with best medical therapy (BMT) based on weak evidence. Consequently, patients with ICANO were ...excluded from randomized trials. The aim of this individual‐patient data (IPD) meta‐analysis was to determine the optimal treatment approach.
Methods
A systematic search was performed in MEDLINE, EMBASE and the Cochrane Library databases in January 2018. The primary outcome was the occurrence of any stroke or death within the first 30 days of treatment, analysed by multivariable mixed‐effect logistic regression. The secondary outcome was the occurrence of any stroke or death beyond 30 days up to 1 year after treatment, evaluated by Kaplan–Meier survival analysis.
Results
The search yielded 1526 articles, of which 61 were retrieved for full‐text review. Some 32 studies met the inclusion criteria and pooled IPD were available from 11 studies, including some 703 patients with ICANO. Within 30 days, any stroke or death was reported in six patients (1·8 per cent) in the carotid endarterectomy (CEA) group, five (2·2 per cent) in the carotid artery stenting (CAS) group and seven (4·9 per cent) in the BMT group. This resulted in a higher 30‐day stroke or death rate after BMT than after CEA (odds ratio 5·63, 95 per cent c.i. 1·30 to 24·45; P = 0·021). No differences were found between CEA and CAS. The 1‐year any stroke‐ or death‐free survival rate was 96·1 per cent for CEA, 94·4 per cent for CAS and 81·2 per cent for BMT.
Conclusion
These data suggest that BMT alone is not superior to CEA or CAS with respect to 30‐day or 1‐year stroke or death prevention in patients with ICANO. These patients do not appear to constitute a high‐risk group for surgery, and consideration should made to including them in future RCTs of internal carotid artery interventions.
Best medical therapy is not superior to carotid endartectomy or carotid artery stenting with respect to 30‐day or 1‐year stroke/death prevention in patients with an internal carotid artery near occlusion. These patients do not constitute a high‐risk subgroup for surgery and should not be excluded from future RCTs.
Surgery and stenting less risky than previously thought
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