BACKGROUND AND PURPOSE—Stroke diagnosis could be challenging in the acute phase. We aimed to develop a blood-based diagnostic tool to differentiate between real strokes and stroke mimics and between ...ischemic and hemorrhagic strokes in the hyperacute phase.
METHODS—The Stroke-Chip was a prospective, observational, multicenter study, conducted at 6 Stroke Centers in Catalonia. Consecutive patients with suspected stroke were enrolled within the first 6 hours after symptom onset, and blood samples were drawn immediately after admission. A 21-biomarker panel selected among previous results and from the literature was measured by immunoassays. Outcomes were differentiation between real strokes and stroke mimics and between ischemic and hemorrhagic strokes. Predictive models were developed by combining biomarkers and clinical variables in logistic regression models. Accuracy was evaluated with receiver operating characteristic curves.
RESULTS—From August 2012 to December 2013, 1308 patients were included (71.9% ischemic, 14.8% stroke mimics, and 13.3% hemorrhagic). For stroke versus stroke mimics comparison, no biomarker resulted included in the logistic regression model, but it was only integrated by clinical variables, with a predictive accuracy of 80.8%. For ischemic versus hemorrhagic strokes comparison, NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) >4.9 (odds ratio, 2.40; 95% confidence interval, 1.55–3.71; P<0.0001) and endostatin >4.7 (odds ratio, 2.02; 95% confidence interval, 1.19–3.45; P=0.010), together with age, sex, blood pressure, stroke severity, atrial fibrillation, and hypertension, were included in the model. Predictive accuracy was 80.6%.
CONCLUSIONS—The studied biomarkers were not sufficient for an accurate differential diagnosis of stroke in the hyperacute setting. Additional discovery of new biomarkers and improvement on laboratory techniques seem necessary for achieving a molecular diagnosis of stroke.
The core pathology of coronavirus disease 2019 (COVID-19) is infection of airway cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in excessive inflammation and ...respiratory disease, with cytokine storm and acute respiratory distress syndrome implicated in the most severe cases. Thrombotic complications are a major cause of morbidity and mortality in patients with COVID-19. Patients with pre-existing cardiovascular disease and/or traditional cardiovascular risk factors, including obesity, diabetes mellitus, hypertension and advanced age, are at the highest risk of death from COVID-19. In this Review, we summarize new lines of evidence that point to both platelet and endothelial dysfunction as essential components of COVID-19 pathology and describe the mechanisms that might account for the contribution of cardiovascular risk factors to the most severe outcomes in COVID-19. We highlight the distinct contributions of coagulopathy, thrombocytopathy and endotheliopathy to the pathogenesis of COVID-19 and discuss potential therapeutic strategies in the management of patients with COVD-19. Harnessing the expertise of the biomedical and clinical communities is imperative to expand the available therapeutics beyond anticoagulants and to target both thrombocytopathy and endotheliopathy. Only with such collaborative efforts can we better prepare for further waves and for future coronavirus-related pandemics.
Exposure to combustion-derived air pollution is associated with an early (1-2 h) and sustained (24 h) rise in cardiovascular morbidity and mortality. We have previously demonstrated that inhalation ...of diesel exhaust causes an immediate (within 2 h) impairment of vascular and endothelial function in humans.
To investigate the vascular and systemic effects of diesel exhaust in humans 24 hours after inhalation.
Fifteen healthy men were exposed to diesel exhaust (particulate concentration, 300 microg/m(3)) or filtered air for 1 hour in a double-blind, randomized, crossover study. Twenty-four hours after exposure, bilateral forearm blood flow, and inflammatory and fibrinolytic markers were measured before and during unilateral intrabrachial bradykinin (100-1,000 pmol/min), acetylcholine (5-20 microg/min), sodium nitroprusside (2-8 microg/min), and verapamil (10-100 microg/min) infusions.
Resting forearm blood flow, blood pressure, and basal fibrinolytic markers were similar 24 hours after either exposure. Diesel exhaust increased plasma cytokine concentrations (tumor necrosis factor-alpha and interleukin-6, p < 0.05 for both) but appeared to reduce acetylcholine (p = 0.01), and bradykinin (p = 0.08) induced forearm vasodilatation. In contrast, there were no differences in either endothelium-independent (sodium nitroprusside and verapamil) vasodilatation or bradykinin-induced acute plasma tissue plasminogen activator release.
Twenty-four hours after diesel exposure, there is a selective and persistent impairment of endothelium-dependent vasodilatation that occurs in the presence of mild systemic inflammation. These findings suggest that combustion-derived air pollution may have important systemic and adverse vascular effects for at least 24 hours after exposure.
Veins of Devotion Copeman, Jacob
2008, 20081118, 2009, 2008-11-30
eBook
According to public health orthodoxy, blood for transfusion is safer when derived from voluntary, nonremunerated donors. As developing nations phase out compensated blood collection efforts to comply ...with this current policy, many struggle to keep their blood stores up.
Veins of Devotion details recent collaborations between guru-led devotional movements and public health campaigns to encourage voluntary blood donation in northern India. Focusing primarily on Delhi, Jacob Copeman carefully situates the practice within the context of religious gift-giving, sacrifice, caste, kinship, and nationalism. The book analyzes the operations of several high-profile religious orders that organize large-scale public blood-giving events and argues that blood donation has become a site not only of frenetic competition between different devotional movements, but also of intense spiritual creativity.
Despite tensions between blood banks and these religious groups, their collaboration is a remarkable success storyùthe nation's blood supply is replenished while blood donors discover new devotional possibilities.
Clinicians are required to assess abnormal liver chemistries on a daily basis. The most common liver chemistries ordered are serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), ...alkaline phosphatase and bilirubin. These tests should be termed liver chemistries or liver tests. Hepatocellular injury is defined as disproportionate elevation of AST and ALT levels compared with alkaline phosphatase levels. Cholestatic injury is defined as disproportionate elevation of alkaline phosphatase level as compared with AST and ALT levels. The majority of bilirubin circulates as unconjugated bilirubin and an elevated conjugated bilirubin implies hepatocellular disease or cholestasis. Multiple studies have demonstrated that the presence of an elevated ALT has been associated with increased liver-related mortality. A true healthy normal ALT level ranges from 29 to 33 IU/l for males, 19 to 25 IU/l for females and levels above this should be assessed. The degree of elevation of ALT and or AST in the clinical setting helps guide the evaluation. The evaluation of hepatocellular injury includes testing for viral hepatitis A, B, and C, assessment for nonalcoholic fatty liver disease and alcoholic liver disease, screening for hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency. In addition, a history of prescribed and over-the-counter medicines should be sought. For the evaluation of an alkaline phosphatase elevation determined to be of hepatic origin, testing for primary biliary cholangitis and primary sclerosing cholangitis should be undertaken. Total bilirubin elevation can occur in either cholestatic or hepatocellular diseases. Elevated total serum bilirubin levels should be fractionated to direct and indirect bilirubin fractions and an elevated serum conjugated bilirubin implies hepatocellular disease or biliary obstruction in most settings. A liver biopsy may be considered when serologic testing and imaging fails to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible.
Organotypic vasculature Augustin, Hellmut G.; Koh, Gou Young
Science (American Association for the Advancement of Science),
08/2017, Letnik:
357, Številka:
6353
Journal Article
Recenzirano
Odprti dostop
Blood vessels form one of the body's largest surfaces, serving as a critical interface between the circulation and the different organ environments. They thereby exert gatekeeper functions on tissue ...homeostasis and adaptation to pathologic challenge. Vascular control of the tissue microenvironment is indispensable in development, hemostasis, inflammation, and metabolism, as well as in cancer and metastasis. This multitude of vascular functions is mediated by organ-specifically differentiated endothelial cells (ECs), whose cellular and molecular heterogeneity has long been recognized. Yet distinct organotypic functional attributes and the molecular mechanisms controlling EC differentiation and vascular bed-specific functions have only become known in recent years. Considering the involvement of vascular dysfunction in numerous chronic and life-threatening diseases, a better molecular understanding of organotypic vasculatures may pave the way toward novel angiotargeted treatments to cure hitherto intractable diseases. This Review summarizes recent progress in the understanding of organotypic vascular differentiation and function.
How best to manage risk involving multi-valued human biological materials is the overarching theme of this book, which draws on the sourcing and supply of blood as a case study. Blood has ethical, ...social, scientific and commercial value. This multi-valuing process presents challenges in terms of managing risk, therefore making it ultimately a matter for political responsibility. This is highlighted through an examination of the circumstances that led to HIV blood contamination episodes in the US, England and France, as well as their consequences. The roles of scientific expertise and innovation in managing risks to the blood system are also analysed, as is the increased use of precautionary and legal strategies in the post-HIV blood contamination era. Finally, consideration is given to a range of policy and legal strategies that should underpin effective risk governance involving multi-valued human biological materials.
Alzheimer's disease causes a progressive dementia that currently affects over 35 million individuals worldwide and is expected to affect 115 million by 2050 (ref. 1). There are no cures or ...disease-modifying therapies, and this may be due to our inability to detect the disease before it has progressed to produce evident memory loss and functional decline. Biomarkers of preclinical disease will be critical to the development of disease-modifying or even preventative therapies. Unfortunately, current biomarkers for early disease, including cerebrospinal fluid tau and amyloid-β levels, structural and functional magnetic resonance imaging and the recent use of brain amyloid imaging or inflammaging, are limited because they are either invasive, time-consuming or expensive. Blood-based biomarkers may be a more attractive option, but none can currently detect preclinical Alzheimer's disease with the required sensitivity and specificity. Herein, we describe our lipidomic approach to detecting preclinical Alzheimer's disease in a group of cognitively normal older adults. We discovered and validated a set of ten lipids from peripheral blood that predicted phenoconversion to either amnestic mild cognitive impairment or Alzheimer's disease within a 2-3 year timeframe with over 90% accuracy. This biomarker panel, reflecting cell membrane integrity, may be sensitive to early neurodegeneration of preclinical Alzheimer's disease.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
BACKGROUND:The aim of the study was to document cardiovascular clinical findings, cardiac imaging and laboratory markers in children presenting with the novel multisystem inflammatory syndrome ...(MIS-C) associated with COVID-19 infection.
METHODS:A real-time internet-based survey endorsed by the Association for European Paediatric and Congenital Cardiologists (AEPC) Working Groups for Cardiac Imaging and Cardiovascular Intensive Care. Inclusion criteria was children 0-18 years admitted to hospital between February 1 and June 6, 2020 with diagnosis of an inflammatory syndrome and acute cardiovascular complications.
RESULTS:A total of 286 children from 55 centers in 17 European countries were included. The median age was 8.4 years (IQR 3.8-12.4 years) and 67% were males. The most common cardiovascular complications were shock, cardiac arrhythmias, pericardial effusion and coronary artery dilatation. Reduced left ventricular ejection fraction was present in over half of the patients and a vast majority of children had raised cardiac troponin (cTnT) when checked. The biochemical markers of inflammation were raised in majority of patients on admissionelevated CRP, serum ferritin, procalcitonin, NT-proBNP, IL-6 level and D-dimers. There was a statistically significant correlation between degree of elevation in cardiac and biochemical parameters and need for intensive care support (p <0.05). Polymerase chain reaction (PCR) for SARS-CoV-2 was positive in 33.6% while IgM and IgG antibodies were positive in 15.7% and IgG 43.6% cases, respectively when checked. One child died in the study cohort.
CONCLUSIONS:Cardiac involvement is common in children with multisystem inflammatory syndrome associated with Covid-19 pandemic. A majority of children have significantly raised levels of NT pro-BNP, ferritin, D-dimers and cardiac troponin in addition to high CRP and procalcitonin levels. Compared to adults with Covid-19, mortality in children with MIS-C is uncommon despite multi-system involvement, very elevated inflammatory markers and need for intensive care support.
Microparticles and cardiovascular diseases Voukalis, Christos; Shantsila, Eduard; Lip, Gregory Y. H.
Annals of medicine (Helsinki),
05/2019, Letnik:
51, Številka:
3-4
Journal Article
Recenzirano
Odprti dostop
Microparticles are a distinctive group of small vesicles, without nucleus, which are involved as significant modulators in several physiological and pathophysiological mechanisms.
Plasma ...microparticles from various cellular lines have been subject of research. Data suggest that they are key players in development and manifestation of cardiovascular diseases and their presence, in high levels, is associated with chronic inflammation, endothelial damage and thrombosis. The strong correlation of microparticle levels with several outcomes in cardiovascular diseases has led to their utilization as biomarkers. Despite the limited clinical application at present, their significance emerges, mainly because their detection and enumeration methods are improving.
This review article summarizes the evidence derived from research, related with the genesis and the function of microparticles in the presence of various cardiovascular risk factors and conditions. The current data provide a substrate for several theories of how microparticles influence various cellular mechanisms by transferring biological information.
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