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Background: Rapid and accurate acute ischemic stroke (AIS) diagnosis is needed to expedite emergent thrombolytic and mechanical thrombectomy treatment. Changes in blood-based protein biomarkers during the first 24 h of AIS, the time window for treatment, could complement imaging techniques and facilitate rapid diagnosis and treatment., Methods: We performed a systematic review according to PRISMA guidelines. MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were searched for eligible studies comparing levels of blood-based protein biomarkers in AIS patients with levels in healthy controls and stroke mimics. Protein biomarkers from the following pathophysiological categories were included: neurovascular inflammation (MMP-9, TNF-alpha), endothelial integrity (VCAM-1, ICAM-1), cell migration (E-Selectin, P-Selectin, L-Selectin), markers of glial and neuronal origin (GFAP, S100, S100B, NSE), and cardiac dysfunction (BNP, NT-proBNP). The literature search was limited to English-language publications before November 7th, 2023., Results: A total of 61 studies from 20 different countries were identified, which included in total, 4,644 AIS patients, 2,242 stroke mimics, and 2,777 controls. Studies investigating TNF-alpha, MMP-9, VCAM-1, ICAM-1, E-Selectin, L-Selectin, GFAP, NSE, and S100B showed pronounced methodological heterogeneity, making between-study comparisons difficult. However, in 80% of NT-proBNP and BNP studies, and all P-selectin studies, higher biomarker levels were observed in AIS patients compared to healthy controls and/or patients with stroke mimics., Conclusion: None of the biomarkers included showed sufficient evidence for additional diagnostic benefit for AIS. Comprehensive standardized global multicenter studies are needed to (1) permit comparability, (2) enable valid statements about protein-based biomarkers, and (3) reflect real-world scenarios., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Rahmig, Chanpura, Schultz, Barone, Gustafson and Baird.)

The most prevalent symptoms of post-COVID-19 condition are pulmonary dysfunction, fatigue and muscle weakness, anxiety, anosmia, dysgeusia, headaches, difficulty in concentrating, sexual dysfunction, and digestive disturbances. Hence, neurological dysfunction and autonomic impairments predominate in post-COVID-19 condition. Tachykinins including the most studied substance P are neuropeptides expressed throughout the nervous and immune systems, and contribute to many physiopathological processes in the nervous, immune, gastrointestinal, respiratory, urogenital, and dermal systems and participate in inflammation, nociception, and cell proliferation. Substance P is a key molecule in neuroimmune crosstalk; immune cells near the peripheral nerve endings can send signals to the brain with cytokines, which highlights the important role of tachykinins in neuroimmune communication. We reviewed the evidence that relates the symptoms of post-COVID-19 condition to the functions of tachykinins and propose a putative pathogenic mechanism. The antagonism of tachykinins receptors can be a potential treatment target., Competing Interests: Declaration of interests EPD holds an advisory and consultant role with Abbott Diagnostics and Imaware Diagnostics. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Aim(s) We tested the following hypotheses: would better oral hygiene self-care (OHS) influence cardiovascular (CVD) mortality? Will using mouthwash in addition to OHS affect CVD mortality? How does mouthwash usage impact the oral microbes?Design and methods Among 354 dentate subjects from the Kuopio Oral Health and Heart study, the association of OHS with CVD mortality was assessed using Cox regression analyses, adjusting for age, sex, smoking, dyslipidemia, diabetes, hypertension and education. Additionally, whether using mouthwash would affect this relationship was evaluated.Results In the multivariable-adjusted models, OHS was associated with a 51% reduction in the risk of CVD mortality (hazard ratio [HR] 0.49 [0.28-0.85]; p = 0.01). Even those who had coronary artery disease at baseline showed a marginally significant benefit (0.50 [0.24-1.06]; p = 0.07). However, mouthwash usage did not change OHS effects (HR = 0.49 [0.27-0.87]; p = 0.01), indicating no additional benefits nor detriments. All tested microbes trended to decrease with mouthwash usage in the short term, but none were statistically significant.Conclusion Good OHS significantly lowered the risk of CVD mortality relative to poor OHS. Mouthwash usage did not show any long-term harm or benefit on CVD mortality beyond the benefits rendered by brushing and flossing., (© 2023. The Author(s), under exclusive licence to the British Dental Association.)

The introduction of thrombolytic therapy in the 1990s has transformed acute ischemic stroke treatment. Thus far, intravenous recombinant tissue plasminogen activator (rt-PA) also known as alteplase is the only thrombolytic proven to be efficacious and approved by the United States Food and Drug Administration. But the thrombolytic agent tenecteplase (TNK) is emerging as a potential replacement for rt-PA. TNK has greater fibrin specificity, slower clearance, and higher resistance to plasminogen activator inhibitor-1 than rt-PA. Hence, TNK has the potential to provide superior lysis with fewer hemorrhagic complications. Also, easier bolus-only administration makes TNK a very practical rt-PA alternative. In several clinical trials, TNK has shown similar efficacy and safety to rt-PA, and the potential to be at least noninferior to rt-PA in some settings. TNK may be superior to rt-PA for reperfusing large vessel occlusions in patients with salvageable penumbra, although this has not yet translated to improved clinical outcomes. Further phase 3 studies are in progress comparing rt-PA with TNK for acute ischemic stroke during the first 4.5 hours. Studies are also in progress to evaluate the use of TNK for extended applications, such as wake-up stroke., Competing Interests: None., (Thieme. All rights reserved.)

Currently there is no in vitro diagnostic test for acute ischemic stroke (AIS), yet rapid diagnosis is crucial for effective thrombolytic treatment. We previously demonstrated the utility of CD8(+) T-cells' mRNA expression for AIS detection; however extracellular vesicles (EVs) were not evaluated as a source of mRNA for AIS testing. We now report a microfluidic device for the rapid and efficient affinity-enrichment of CD8(+) EVs and subsequent EV's mRNA analysis using droplet digital PCR (ddPCR). The microfluidic device contains a dense array of micropillars modified with anti-CD8α monoclonal antibodies that enriched 158 ± 10 nm sized EVs at 4.3 ± 2.1 × 10 9 particles/100 µL of plasma. Analysis of mRNA from CD8(+) EVs and their parental T-cells revealed correlation in the expression for AIS-specific genes in both cell lines and healthy donors. In a blinded study, 80% test positivity for AIS patients and controls was revealed with a total analysis time of 3.7 h.

Introduction: There is a short time window (4.5 h) for the effective treatment of acute ischemic stroke (AIS), which uses recombinant tissue plasminogen activator (rt-PA). Unfortunately, this short therapeutic timeframe is a contributing factor to the relatively small number of patients (~7%) that receive rt-PA. While neuroimaging is the major diagnostic for AIS, more timely decisions could be made using a molecular diagnostic., Areas Covered: In this review, we survey neuroimaging techniques used to diagnose stroke and their limitations. We also highlight the potential of various molecular/cellular biomarkers, especially peripheral blood-based ( i.e . liquid biopsy) biomarkers, for diagnosing stroke to allow for precision decisions on managing stroke in a timely manner. Both protein and nucleic acid molecular biomarkers are reviewed. In particular, mRNA markers are discussed for AIS and hemorrhagic stroke diagnosis sourced from both cells and extracellular vesicles., Expert Opinion: While there are a plethora of molecular markers for stroke diagnosis that have been reported, they have yet to be FDA-cleared. Possible reasons include the inability for these markers to appear in sufficient quantities for highly sensitive clinical decisions within the rt-PA therapeutic time.

Background: Oral menopausal hormone therapy causes venous thrombosis but whether biomarkers of thrombosis risk can identify women at risk is unknown., Methods: We completed a nested case control study in the two Women's Health Initiative hormone trials; 27 347 women aged 50-79 were randomized to hormone therapy (conjugated equine estrogen with or without medroxyprogesterone acetate) or placebo. With 4 years follow-up, biomarkers were measured using stored baseline samples prior to starting treatment, and one-year later, in 215 women who developed thrombosis and 867 controls., Results: Overall, lower protein C and free protein S, and higher D-dimer, prothrombin fragment 1.2 and plasmin-antiplasmin complex were associated with risk of future thrombosis with odds ratios ranging from 1.9 to 3.2. Compared to women with normal biomarkers assigned to placebo, the risk of thrombosis with hormone therapy was increased among women with abnormal biomarkers, especially elevated D-dimer, elevated plasmin-antiplasmin, and low free protein S; the largest association was for D-dimer: odds ratio 6.0 (95% CI 3.6-9.8). Differences in associations by hormone use were not significant on the multiplicative scale. Considering a multi-marker score of eight biomarkers, women with three or more abnormal biomarkers had 15.5-fold increased odds of VT (95% CI 6.8-35.1). One-year changes in biomarkers were not robustly associated with subsequent thrombosis risk., Conclusion: Abnormal levels of biomarkers of thrombosis risk identified women at increased risk of future venous thrombosis with oral menopausal hormone therapy. Findings support the potential for clinical use of D-dimer testing in advance of hormone therapy prescription.

Objective: The fractal dimension of retinal arteries and veins is a measure of the complexity of the vascular tree. We hypothesized that retinal fractal dimension would be associated with brain volume and white matter integrity in HIV-infected women., Design: Nested case-control within longitudinal cohort study., Methods: Women were recruited from the Brooklyn site of the Women's Interagency HIV study (WIHS); 34 HIV-infected and 21 HIV-uninfected women with analyzable MRIs and retinal photographs were included. Fractal dimension was determined using the SIVA software program on skeletonized retinal images. The relationship between predictors (retinal vascular measures) and outcomes (quantitative MRI measures) were analyzed with linear regression models. All models included age, intracranial volume, and both arterial and venous fractal dimension. Some models were adjusted for blood pressure, race/ethnicity, and HIV-infection., Results: The women were 45.6 ± 7.3 years of age. Higher arterial dimension was associated with larger cortical volumes, but higher venous dimension was associated with smaller cortical volumes. In fully adjusted models, venous dimension was significantly associated with fractional anisotropy (standardized β = -0.41, p = 0.009) and total gray matter volume (β = -0.24, p = 0.03), and arterial dimension with mean diffusivity (β = -0.33,.p = 0.04) and fractional anisotropy (β = 0.34, p = 0.03). HIV-infection was not associated with any retinal or MRI measure., Conclusions: Higher venous fractal dimension was associated with smaller cortical volumes and lower fractional anisotropy, whereas higher arterial fractal dimension was associated with the opposite patterns. Longitudinal studies are needed to validate this finding.

Advances in genomic and transcriptome sequencing are revealing the massive scale of previously unrecognised alterations occurring during neoplastic transformation. Breast cancers are genetically and phenotypically heterogeneous. Each of the three major subtypes [ERBB2 amplified, estrogen receptor (ESR)-positive and triple-negative] poses diagnostic and therapeutic challenges. Here we show, using high-resolution next-generation transcriptome sequencing, that in all three breast cancer subtypes, but not matched controls, there was significant overexpression of transcripts from intronic and untranslated regions in addition to exons from specific genes, particularly amplified oncogenes and hormone receptors. For key genes ERBB2 and ESR1, we demonstrate that overexpression is linked to the production of highly modified and truncated splice variants in tumours, but not controls, correlated with tumour subtype. Translation of these tumour-specific splice variants generates truncated proteins with altered subcellular locations and functions, modifying the phenotype, affecting tumour biology, and targeted antitumour therapies. In contrast, tumour suppressors TP53, BRCA1/2 and NF1 did not show intronic overexpression or truncated splice variants in cancers. These findings emphasize the detection of intronic as well as exonic changes in the transcriptional landscapes of cancers have profound therapeutic implications.

Stroke is a leading cause of death and disability in adults, but at present, treatment for ischemic stroke reaches only a small percentage of patients. This is because of the very short time window for treatment and the time-consuming evaluation involved. Intense efforts are underway to find novel approaches to expedite stroke diagnosis and treatment. In this review, we provide the rationale for the use of blood-based nucleic acid biomarkers to advance stroke diagnosis. We describe mRNA markers identified in genomic profiling of circulating leukocytes and then outline technological issues involved in the application of these results. We then describe the novel point-of-care technology that is in development for the rapid detection of multiple mRNA molecules in circulating leukocytes.

Efforts are underway to develop novel platforms for stroke diagnosis to meet the criteria for effective treatment within the narrow time window mandated by the FDA-approved therapeutic (<3 h). Blood-based biomarkers could be used for rapid stroke diagnosis and coupled with new analytical tools, could serve as an attractive platform for managing stroke-related diseases. In this review, we will discuss the physiological processes associated with stroke and current diagnostic tools as well as their associated shortcomings. We will then review information on blood-based biomarkers and various detection technologies. In particular, point of care testing that permits small blood volumes required for the analysis and rapid turn-around time measurements of multiple markers will be presented.

In microarray studies alterations in gene expression in circulating leukocytes have shown utility for ischemic stroke diagnosis. We studied forty candidate markers identified in three gene expression profiles to (1) quantitate individual transcript expression, (2) identify transcript clusters and (3) assess the clinical diagnostic utility of the clusters identified for ischemic stroke detection. Using high throughput next generation qPCR 16 of the 40 transcripts were significantly up-regulated in stroke patients relative to control subjects (p<0.05). Six clusters of between 5 and 7 transcripts were identified that discriminated between stroke and control (p values between 1.01e-9 and 0.03). A 7 transcript cluster containing PLBD1, PYGL, BST1, DUSP1, FOS, VCAN and FCGR1A showed high accuracy for stroke classification (AUC=0.854). These results validate and improve upon the diagnostic value of transcripts identified in microarray studies for ischemic stroke. The clusters identified show promise for acute ischemic stroke detection., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Over the past decade rapid advances have occurred in the understanding of RNA expression and its regulation. Quantitative polymerase chain reactions (qPCR) have become the gold standard for quantifying gene expression. Microfluidic next generation, high throughput qPCR now permits the detection of transcript copy number in thousands of reactions simultaneously, dramatically increasing the sensitivity over standard qPCR. Here we present a gene expression analysis method applicable to both standard polymerase chain reactions (qPCR) and high throughput qPCR. This technique is adjusted to the input sample quantity (e.g., the number of cells) and is independent of control gene expression. It is efficiency-corrected and with the use of a universal reference sample (commercial complementary DNA (cDNA)) permits the normalization of results between different batches and between different instruments--regardless of potential differences in transcript amplification efficiency. Modifications of the input quantity method include (1) the achievement of absolute quantification and (2) a non-efficiency corrected analysis. When compared to other commonly used algorithms the input quantity method proved to be valid. This method is of particular value for clinical studies of whole blood and circulating leukocytes where cell counts are readily available.

T lymphocytes may play an important role in the evolution of ischemic stroke. Depletion of γδT cells has been found to abrogate ischemia reperfusion injury in murine stroke. However, the role of γδT cells in human ischemic stroke is unknown. We aimed to determine γδT cell counts and γδT cell interleukin 17A (IL-17A) production in the clinical setting of ischemic stroke. We also aimed to determine the associations of γδT cell counts with ischemic lesion volume, measures of clinical severity and with major stroke risk factors. Peripheral blood samples from 43 acute ischemic stroke patients and 26 control subjects matched on race and gender were used for flow cytometry and complete blood count analyses. Subsequently, cytokine levels and gene expression were measured in γδT cells. The number of circulating γδT cells was decreased by almost 50% (p = 0.005) in the stroke patients. γδT cell counts did not correlate with lesion volume on magnetic resonance diffusion-weighted imaging or with clinical severity in the stroke patients, but γδT cells showed elevated levels of IL-17A (p = 0.048). Decreased γδT cell counts were also associated with older age (p = 0.004), pre-existing hypertension (p = 0.0005) and prevalent coronary artery disease (p = 0.03), with pre-existing hypertension being the most significant predictor of γδT cell counts in a multivariable analysis. γδT cells in human ischemic stroke are reduced in number and show elevated levels of IL-17A. A major reduction in γδT lymphocytes also occurs in hypertension and may contribute to the development of hypertension-mediated stroke and vascular disease.

We report the design and performance of a polymer microfluidic device that can affinity select multiple types of biological cells simultaneously with sufficient recovery and purity to allow for the expression profiling of mRNA isolated from these cells. The microfluidic device consisted of four independent selection beds with curvilinear channels that were 25 μm wide and 80 μm deep and were modified with antibodies targeting antigens specifically expressed by two different cell types. Bifurcated and Z-configured device geometries were evaluated for cell selection. As an example of the performance of these devices, CD4+ T-cells and neutrophils were selected from whole blood as these cells are known to express genes found in stroke-related expression profiles that can be used for the diagnosis of this disease. CD4+ T-cells and neutrophils were simultaneously isolated with purities >90% using affinity-based capture in cyclic olefin copolymer (COC) devices with a processing time of ∼3 min. In addition, sufficient quantities of the cells could be recovered from a 50 μL whole blood input to allow for reverse transcription-polymerase chain reaction (RT-PCR) following cell lysis. The expression of genes from isolated T-cells and neutrophils, such as S100A9, TCRB, and FPR1, was evaluated using RT-PCR. The modification and isolation procedures demonstrated here can also be used to analyze other cell types as well where multiple subsets must be interrogated.

Aim: To test whether the number of teeth, an inverse proxy for composite oral infection scores is associated with better survival., Materials and Methods: The Kuopio Oral Health and Heart study initiated a case-control study in 1995-1996 consisting of 256 consecutive coronary artery disease patients and 250 age and gender-matched controls. We appended the mortality data and formulated a longitudinal study. By May 31st, 2011, 124 mortalities had occurred and 80 of which were of cardiovascular origin. Using Cox proportional hazards models, we assessed the association of the teeth group (Teethgrp) - consisting of 10 teeth - with cardiovascular and all-cause mortality after 15.8 years of median follow-up., Results: In multivariate models, with the edentulous state as reference, one level increase in Teethgrp was associated with significantly increased survival from cardiovascular disease (CVD) mortality with a Hazard Ratio (HR) 0.73, p-value = 0.02 but not with all-cause mortality (HR = 0.87, p = 0.13). The findings were not mediated by C-reactive protein (CRP) levels ≥3 mg/L or by median fibrinogen levels, but were mediated by CRP levels >5 mg/L., Conclusion: Each increment of 10 teeth from the edentulous state was associated with a 27% improved CVD survival, independent of low-grade systemic inflammation., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Associations between the angiotensin II type 1 receptor (AGTR1) gene A1166C polymorphism and hypertension, aortic abdominal aneurysms (as a risk factor) as well as cardiovascular disorders (as a risk factor and an outcome predictor) have been demonstrated. We aimed to investigate the role of this polymorphism as risk factors and outcome predictors in primary intracerebral hemorrhage (PICH) and aneurysmal subarachnoid hemorrhage (aSAH). We have prospectively recruited 1078 Polish participants to the study: 261 PICH patients, 392 aSAH patients, and 425 unrelated control subjects. The A1166C AGTR1 gene polymorphism was studied using the tetra-primer ARMS-PCR method. Allele and genotype frequencies were compared with other ethnically different populations. The A1166C polymorphism was not associated with the risk of PICH or aSAH. Among the aSAH patients the AA genotype was associated with a good outcome, defined by a Glasgow Outcome Scale of 4 or 5 (p<0.02). The distribution of A1166C genotypes in our cohort did not differ from other white or other populations of European descent. In conclusion, we found an association between the A1166C AGTR1 polymorphism and outcome of aSAH patients, but not with the risk of PICH or aSAH., (Copyright © 2014 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Clinical studies of gene expression are increasingly using the whole blood, peripheral blood mononuclear cells, and leukocyte subsets involved in the innate and adaptive immune responses. However, the small amount of RNA available in the clinical setting is a limitation for commonly used methods such as quantitative polymerase chain reactions (qPCR) and microarrays. Our aim was to design 96 gene assays to simultaneously measure gene expression in the whole blood and seven leukocyte subsets using a new-generation qPCR method--high-throughput nanofluidic reverse transcription qPCR (HT RT-qPCR). The leukocyte subset purity was 94% to 98% for seven subsets and was less for the γδ T-cell receptor subset (80%). The HT RT-qPCR replicate sample measurements were highly reproducible (r = 0.997, p < 2.2 × 10(-16)), and the ΔΔCt values from HT RT-qPCR correlated significantly with those from qPCR. The control genes were differentially expressed across the eight leukocyte subsets in the control subjects (p = 1.3 × 10(-5), analysis of variance). Two analytical methods, absolute and relative, gave concordant results and were significantly correlated (p = 1.9 × 10(-9)). HT RT-qPCR permits the rapid, reproducible, and quantitative measurement of multiple transcripts using minimal sample amounts. The protocol described yielded leukocyte subsets of high purity and identified two analytic methods for use.

Expression analysis of mRNAs transcribed from certain genes can be used as important sources of biomarkers for in vitro diagnostics. While the use of reverse transcription quantitative PCR (RT-qPCR) can provide excellent analytical sensitivity for monitoring transcript numbers, more sensitive approaches for expression analysis that can report results in near real-time are needed for many critical applications. We report a novel assay that can provide exquisite limits-of-quantitation and consists of reverse transcription (RT) followed by a ligase detection reaction (LDR) with single-pair fluorescence resonance energy transfer (spFRET) to provide digital readout through molecular counting. For this assay, no PCR was employed, which enabled short assay turnaround times. To facilitate implementation of the assay, a cyclic olefin copolymer (COC) microchip, which was fabricated using hot embossing, was employed to carry out the LDR in a continuous flow format with online single-molecule detection following the LDR. As demonstrators of the assay's utility, MMP-7 mRNA was expression profiled from several colorectal cancer cell lines. It was found that the RT-LDR/spFRET assay produced highly linear calibration plots even in the low copy number regime. Comparison to RT-qPCR indicated a better linearity over the low copy number range investigated (10-10,000 copies) with an R(2) = 0.9995 for RT-LDR/spFRET and R(2) = 0.98 for RT-qPCR. In addition, differentiating between copy numbers of 10 and 50 could be performed with higher confidence using RT-LDR/spFRET. To demonstrate the short assay turnaround times obtainable using the RT-LDR/spFRET assay, a two thermal cycle LDR was carried out on amphiphysin gene transcripts that can serve as important diagnostic markers for ischemic stroke. The ability to supply diagnostic information on possible stroke events in short turnaround times using RT-LDR/spFRET will enable clinicians to treat patients effectively with appropriate time-sensitive therapeutics.

Objectives: Recent developments of new direct oral anticoagulants that target specific clotting factors necessitate understanding of coagulation biology. The objective of this tutorial is to offer dental professionals a review of coagulation mechanisms and the pharmacodynamics of the conventional and new oral anticoagulants. Also, we summarized the dental implications of the conventional and new anticoagulants., Method: We searched Medline using search terms "antithrombotic", "antihemostasis" or "anticoagulation" and combined them with the search results of "dental", "oral surgery" or "periodontal". We restricted the results to "human" and "English"., Results: The early coagulation cascade, the new cell-based coagulation model, the pharmacokinetics and pharmacodynamics of conventional antithrombotics, and new oral anticoagulants were reviewed. The new direct factor Xa inhibitors and the direct thrombin inhibitor (s), called direct oral anticoagulants (DOAs) have rapid onset of action, fast elimination on cessation, and fewer drug-drug or drug-food interactions than warfarin. However, the lack of antidotes raises concerns that some dental procedures may trigger serious hemorrhagic events. Additionally, careful perioperative withdrawal and resumption protocols for the DOAs are reviewed, because DOAs' blood levels are dependent on renal function. Also, various reversal strategies in the event of excessive bleedings are summarized. Perioperative management of dental patients taking new DOAs and conventional oral anticoagulants are also discussed. However, the perioperative strategies for DOAs are yet to be validated in randomized trials.

We report a case of probable contrast-induced neurotoxicity that followed a technically challenging cardiac catheterization in a 69-year-old woman. The procedure had involved the administration of a large cumulative dose of an iodinated, nonionic contrast medium into the innominate artery: twelve hours following the catheterization, the patient developed a seizure followed by a left hemiplegia, and an initial computed tomography (CT) scan showed sulcal effacement in the right cerebral hemisphere due to cerebral swelling. The patient's clinical symptoms resolved within 24 hours, and magnetic resonance imaging at 32 hours showed resolution of swelling. Contrast-induced neurotoxicity should be found in the differential diagnosis of acute neurological deficits occurring after radiological procedures involving iodinated contrast media, whether ionic or nonionic.

Introduction: Salivary lysozyme (SLZ) is a proteolytic enzyme secreted by oral leucocytes and contains a domain that has an affinity to advanced glycation end products (AGE). Thus, we hypothesized that SLZ would be associated with metabolic syndrome (metS), a pro-inflammatory state., Methods: Utilizing cross-sectional data from 250 coronary artery disease (CAD) and 250 non-CAD patients, the association of SLZ with metS was tested by logistic regression analyses controlling for age, sex, smoking, total cholesterol and C-reactive protein (CRP) levels. The analyses were stratified by CAD status to control for the possible effects of CAD., Results: MetS was found in 122 persons. The adjusted odds ratio (OR) for metS associated with the highest quartile of SLZ was 1.95 with 95% confidence interval (CI) 1.20-3.12, p-value=0.007, compared with the lower three quartiles combined. Among the 40 subjects with metS but without CAD, the OR was 1.63 (CI: 0.64-4.15, p=0.31), whereas in the CAD group, SLZ was significantly associated with metS [OR=1.96 (1.09-3.52), p=0.02]. In both subgroups, CRP was not significantly associated with metS., Conclusion: SLZ was significantly associated with metS (OR=1.95) independent of CRP level. Future longitudinal research is warranted.

Evidence for a genetic basis for stroke comes from twin and family studies and from the occurrence of a number of uncommon monogenic disorders, but the contribution of genetic factors identified for stroke so far is small. Advances in genetics and genomics may permit new insights. In recent genome-wide association studies, a number of single-nucleotide polymorphisms have been associated with specific stroke subtypes and major stroke risk factors such as diabetes and atrial fibrillation. These await replication. Studies of messenger ribonucleic acid expression have also shown promise for the development of genomic signatures for stroke classification. Stroke and coronary heart disease share some features of pathophysiology, risk, and treatment, and their genetic and genomic bases also appear to overlap., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Although low levels of adiponectin are associated with coronary heart disease and cardiovascular disease risk factors, it is unclear whether adiponectin levels are related to the risk of developing ischemic stroke., Methods: We examined the relationship between baseline high-molecular-weight (HMW) adiponectin levels and incident ischemic stroke in postmenopausal women using data and specimens from the Hormones and Biomarkers Predicting Stroke Study, a case-control study nested within the Women's Health Initiative Observational Study. Included were 855 incident ischemic stroke cases and 855 control subjects matched for age, race-ethnicity, date of entry into the cohort, and follow-up time. ORs of incident ischemic stroke associated with baseline HMW adiponectin levels were calculated using conditional logistic regression modeling adjusting for body mass index, type 2 diabetes, hypertension, smoking, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, physical activity, C-reactive protein, and aspirin use., Results: Lower levels of HMW adiponectin were significantly associated with type 2 diabetes, hypertension, higher body mass index, waist circumference, glucose, and insulin levels and lower high-density lipoprotein cholesterol levels. The distribution of incident stroke cases by HMW adiponectin quartiles was 49.9%, 50.5%, 50.7%, and 48.9%, respectively (P=0.96). Multivariable-adjusted ORs of stroke associated with the top 3 quartiles of HMW adiponectin versus the first quartile were 0.99 (95% CI, 0.71 to 1.37), 1.37 (0.99 to 1.91), and 1.25 (0.88 to 1.79), respectively (P trend=0.14)., Conclusions: Despite moderate associations between HMW adiponectin and cardiovascular disease risk factors, we found no evidence of an association between HMW adiponectin levels and incident ischemic stroke in these postmenopausal women.

Stroke remains the third most important cause of mortality in industrialized countries; this has prompted research for improvements in both diagnostic and therapeutic strategies for patients with signs of acute cerebral ischemia. Over the last decade, there has been a parallel in progress in techniques in both diagnostic and therapeutic options. While previously only used for excluding hemorrhage, imaging now has the possibility to detect ischemia, vascular occlusion, as well as detect tissue at risk in one setting. It should also allow to monitor treatment and predict/exclude therapeutic complications. Parallel to advances in magnetic resonance imaging of stroke, computed tomography has improved immensely over the last decade due to the development of CT scanners that are faster and that allow to acquire studies such as CT perfusion or CT angiography in a reliable way. CT can detect many signs that might help us detect impending signs of massive infarction, but we still lack the experience to use these alone to prevent a patient from benefitting from possible therapy.

Background: Inflammatory and hemostasis-related biomarkers may identify women at risk of stroke., Methods: Hormones and Biomarkers Predicting Stroke is a study of ischemic stroke among postmenopausal women participating in the Women's Health Initiative observational study (n = 972 case-control pairs). A Biomarker Risk Score (BRS) was derived from levels of 7 inflammatory and hemostasis-related biomarkers that appeared individually to predict risk of ischemic stroke: C-reactive protein (CRP), interleukin-6, tissue plasminogen activator, D-dimer, white blood cell count, neopterin, and homocysteine. The c index was used to evaluate discrimination., Results: Of all the individual biomarkers examined, CRP emerged as the only independent single predictor of ischemic stroke (adjusted odds ratio comparing Quartile(4)v Quartile(1) = 1.64, 95% confidence interval: 1.15-2.32, P = .01) after adjustment for other biomarkers and standard stroke risk factors. The BRS identified a gradient of increasing stroke risk with a greater number of elevated inflammatory/hemostasis biomarkers, and improved the c index significantly compared with standard stroke risk factors (P = .02). Among the subset of individuals who met current criteria for high-risk levels of CRP (>3.0 mg/L), the BRS defined an approximately 2-fold gradient of risk. We found no evidence for a relationship between stroke and levels of E-selectin, fibrinogen, tumor necrosis factor-alpha, vascular cell adhesion molecule-1, prothrombin fragment 1+2, Factor VIIC, or plasminogen activator inhibitor-1 antigen (P > .15)., Discussion: The findings support the further exploration of multiple biomarker panels to develop approaches for stratifying an individual's risk of stroke.

Background and Purpose: Accurate diagnosis of the degree of internal carotid artery (ICA) stenosis is needed for decisions regarding optimal stroke prevention. Noninvasive magnetic resonance angiography (MRA) is being proposed and used as a replacement for the gold standard, intra-arterial angiography. Our purpose was to perform a systematic review and diagnostic meta-analysis to determine the sensitivity and specificity of time-of-flight (TOF) MRA and contrast-enhanced (CE) MRA for the detection of (1) high-grade (> or = 70% to 99%) ICA stenoses; (2) ICA occlusions; (3) moderately severe (50% to 69%) ICA stenoses; and (4) compare the overall accuracy of the 2 MRA techniques., Methods: The medical literature on MRA and the diagnosis of ICA steno-occlusive disease was reviewed through the PubMed, EMBASE, and SCOPUS databases. All publication years were included through to November 2006. Studies were eligible for inclusion if they compared the accuracy of TOF or CE MRA for the detection of ICA disease against intra-arterial angiography and reported sufficient data., Results: The overall sensitivity of TOF MRA for the detection of > or = 70% to 99% ICA stenoses was 91.2% (95% CI: 88.9% to 93.1%) with a specificity of 88.3% (86.7% to 89.7%), whereas the sensitivity of CE MRA was 94.6% (92.4% to 96.4%) with a specificity of 91.9% (90.3% to 93.4%). For the detection of ICA occlusions, the sensitivity of TOF MRA was 94.5% (91.2% to 96.8%) and the specificity was 99.3% (98.9% to 99.6%), whereas the sensitivity and specificity values for CE MRA were 99.4% (96.8% to 100%) and 99.6% (99.2% to 99.9%), respectively. For moderately severe (50% to 69%) stenoses, TOF MRA had a sensitivity of only 37.9% (29.3% to 47.1%) and a specificity of 92.1% (89.6% to 94.1%); for CE MRA, the pooled sensitivity value was somewhat better at 65.9% (57.0% to 74.0%), whereas the specificity was 93.5% (91.3% to 95.3%)., Conclusions: TOF MRA and CE MRA showed high accuracy for the detection of high-grade ICA stenoses and occlusions with CE MRA having the edge over TOF MRA, but had only poor (TOF MRA) to fair (CE MRA) sensitivity for the detection of moderately severe stenoses.

Background: Strokes are a leading cause of morbidity and the first cause of adult disability in the United States. Currently, no biomarkers are being used clinically to diagnose acute ischemic stroke. A diagnostic test using a blood sample from a patient would potentially be beneficial in treating the disease., Results: A classification approach is described for differentiating between proteomic samples of stroke patients and controls, and a second novel predictive model is developed for predicting the severity of stroke as measured by the National Institutes of Health Stroke Scale (NIHSS). The models were constructed by applying the Logical Analysis of Data (LAD) methodology to the mass peak profiles of 48 stroke patients and 32 controls. The classification model was shown to have an accuracy of 75% when tested on an independent validation set of 35 stroke patients and 25 controls, while the predictive model exhibited superior performance when compared to alternative algorithms. In spite of their high accuracy, both models are extremely simple and were developed using a common set consisting of only 3 peaks., Conclusion: We have successfully identified 3 biomarkers that can detect ischemic stroke with an accuracy of 75%. The performance of the classification model on the validation set and on cross-validation does not deteriorate significantly when compared to that on the training set, indicating the robustness of the model. As in the case of the LAD classification model, the results of the predictive model validate the function constructed on our support-set for approximating the severity scores of stroke patients. The correlation and root mean absolute error of the LAD predictive model are consistently superior to those of the other algorithms used (Support vector machines, C4.5 decision trees, Logistic regression and Multilayer perceptron).

Few studies have investigated the role of elevated lipoprotein-associated phospholipase A2 (Lp-PLA(2)) with stroke risk, and those that have are based on small numbers of strokes. No study has evaluated the effect of hormone therapy use on the association of Lp-PLA(2) and stroke. We assessed the relationship between Lp-PLA(2) and the risk of incident ischemic stroke in 929 stroke patients and 935 control subjects in the Hormones and Biomarkers Predicting Stroke Study, a nested case-control study from the Women's Health Initiative Observational Study. Mean (SD) levels of Lp-PLA(2) were significantly higher among case subjects (309.0 [97.1]) than control subjects (296.3 [87.3]; P<0.01). Odds ratio for ischemic stroke for the highest quartile of Lp-PLA(2), compared with lowest, controlling for multiple covariates, was 1.08 (95% CI: 0.75 to 1.55). However, among 1137 nonusers of hormone therapy at baseline, the corresponding odds ratio was 1.55 (95% CI: 1.05 to 2.28),whereas there was no significant association among 737 hormone users (odds ratio: 0.70; 95% CI: 0.42 to 1.17; P for interaction=0.055). Moreover, among nonhormone users, women with high C-reactive protein and high Lp-PLA2 had more than twice the risk of stroke (odds ratio: 2.26; 95% CI: 1.55 to 3.35) compared with women low levels in both biomarkers. Furthermore, different stroke cases were identified as high risk by Lp-PLA(2) rather than by C-reactive protein. Lp-PLA(2) was associated with incident ischemic stroke independently of C-reactive protein and traditional cardiovascular risk factors among nonusers of hormone therapy with highest risk in those who had both high C-reactive protein and high Lp-PLA(2).

Background and Purpose: Walking speed is a simple, reliable, and valid measure of functional status that has been shown to be strongly correlated with age-related outcomes and may be an indicator of subclinical cerebrovascular disease. However, few studies have investigated the association of walking speed with risk of incident ischemic stroke., Methods: The present analyses included 13,048 postmenopausal women (mean age 65 years) from the Women's Health Initiative free of stroke at baseline, 264 of whom had incident ischemic strokes on follow-up. Cox proportional hazards regression was used to obtain hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the relationship between performance on a timed walk and risk of incident ischemic stroke. Multivariate adjustment included age, race/ethnicity, body mass index, waist-hip ratio, depression, arthritis, hypertension, smoking, systolic blood pressure, treated diabetes, hormone use, NSAID use, aspirin use, self-reported general health, and history of coronary heart disease., Results: Slower walking speed was a significant predictor of incident ischemic stroke. After multivariate adjustment, the hazard for incident ischemic stroke was increased for the slowest walking speed tertile compared to the fastest walking speed tertile (HR=1.69, 95% CI: 1.21, 2.36). Additional adjustment for other physical function variables (grip strength and chair stands) did not change the association significantly., Conclusions: Slow walking speed was found to be a strong predictor of increased risk of incident ischemic stroke among postmenopausal women independent of other established risk factors for stroke.

Metabolic syndrome and type 2 diabetes (T2DM) resulting from sustained hyperglycemia are considered as risk factors for cardiovascular disease (CVD) but the mechanism for their contribution to cardiopathogenesis is not well understood. Hyperglycemia induces nonenzymatic glycation of protein-yielding advanced glycation end products (AGE), which are postulated to stimulate interleukin-6 (IL-6) expression, triggering the liver to secrete tissue necrosis factor alpha (TNF-alpha) and C-reactive protein (CRP) that contribute to CVD pathogenesis. Although the high prevalence of periodontitis among individuals with diabetes is well known by dental researchers, it is relatively unrecognized in the medical community. The expression of the same proinflammatory mediators implicated in hyperglycemia (i.e., IL-6, TNF-alpha, and CRP) have been reported to be associated with periodontal disease and increased risk for CVD. We will review published evidence related to these 2 pathways and offer a consensus.

Objective: The Women's Health Initiative hormone trials identified a 44% increase in ischemic stroke risk with combination estrogen plus progestin and a 39% increase with estrogen alone. We undertook a case-control biomarker study to elucidate underlying mechanisms, and to potentially identify women who would be at lower or higher risk for stroke with postmenopausal hormone therapy (HT)., Design: The hormone trials were randomized, double-blind, and placebo controlled., Setting: The Women's Health Initiative trials were conducted at 40 clinical centers in the United States., Participants: The trials enrolled 27,347 postmenopausal women, aged 50-79 y., Interventions: We randomized 16,608 women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or placebo, and 10,739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo., Outcome Measures: Stroke was ascertained during 5.6 y of follow-up in the estrogen plus progestin trial and 6.8 y of follow-up in the estrogen alone trial., Results: No baseline clinical characteristics, including gene polymorphisms, identified women for whom the stroke risk from HT was higher. Paradoxically, women with higher baseline levels of some stroke-associated biomarkers had a lower risk of stroke when assigned to estrogen plus progestin compared to placebo. For example, those with higher IL-6 were not at increased stroke risk when assigned to estrogen plus progestin (odds ratio 1.28) but were when assigned to placebo (odds ratio 3.47; p for difference = 0.02). Similar findings occurred for high baseline PAP, leukocyte count, and D-dimer. However, only an interaction of D-dimer during follow-up interaction with HT and stroke was marginally significant (p = 0.03)., Conclusions: Biomarkers did not identify women at higher stroke risk with postmenopausal HT. Some biomarkers appeared to identify women at lower stroke risk with estrogen plus progestin, but these findings may be due to chance.

Atherosclerotic cardiovascular disease (CVD) is a major health problem in the United States and around the world. Evidence accumulated over decades convincingly demonstrates that family history in a parent or a sibling is associated with atherosclerotic CVD, manifested as coronary heart disease, stroke, and/or peripheral arterial disease. Although there are several mendelian disorders that contribute to CVD, most common forms of CVD are believed to be multifactorial and to result from many genes, each with a relatively small effect working alone or in combination with modifier genes and/or environmental factors. The identification and the characterization of these genes and their modifiers would enhance prediction of CVD risk and improve prevention, treatment, and quality of care. This scientific statement describes the approaches researchers are using to advance understanding of the genetic basis of CVD and details the current state of knowledge regarding the genetics of myocardial infarction, atherosclerotic CVD, hypercholesterolemia, and hypertension. Current areas of interest and investigation--including gene-environment interaction, pharmacogenetics, and genetic counseling--are also discussed. The statement concludes with a list of specific recommendations intended to help incorporate usable knowledge into current clinical and public health practice, foster and guide future research, and prepare both researchers and practitioners for the changes likely to occur as molecular genetics moves from the laboratory to clinic.

Advances in microarray technology and the sequencing of the human genome are opening up new possibilities for applying genomic information in clinical medicine, using information about structural polymorphisms in DNA and changes in gene expression as measured by mRNA. Gene expression profiling studies in cancer samples have led to the identification of clinical signatures that are already being applied in some centers. In stroke, it may be possible to use peripheral blood as a source of mRNA to study gene expression. After stroke, there is a selective recruitment and migration of white blood cells to the ischemic focus in the brain. This appears to involve all white cell types and is believed to impact significantly on tissue and clinical outcome through the exacerbation of ischemic injury, particularly after reperfusion, on the one hand, and conversely contributing to tissue remodeling and repair days to weeks after stroke. The first results from clinical studies in ischemic stroke suggest that a gene expression signature can be demonstrated from peripheral white blood cells and that this represents at least a partial adaptation to the altered cerebral microenvironment. Further studies are indicated to see whether these methods may lead to new management approaches for stroke.

Identifying blood biomarkers may be of particular value in neurologic disorders such as stroke because of the difficulty in directly studying the brain and its blood vessels. Markers of brain injury, inflammation, excitotoxicity, and oxidative damage have been evaluated for their value in stroke diagnosis, treatment, and management, but none have proved to be sensitive or specific enough for routine clinical use. However, new cellular and molecular profiling approaches using the peripheral blood offer the potential for identifying panels of genes and proteins by increasing specificity while maintaining sensitivity. Furthermore, the first biomarker for predicting stroke risk associated with atherosclerosis (lipoprotein-associated phospholipase A2) was recently approved by the United States Food and Drug Administration. The ultimate aim for stroke biomarkers is to develop rapid, easy to use, widely available, and inexpensive diagnostic tests that can be used in the clinic and in clinical trials.

Since acute stroke is now considered a potentially treatable medical emergency, a rapid and correct diagnosis must be made. The first step is to exclude hemorrhage, then to visualize any early ischemic changes, demonstrate the presence of hypoperfusion and locate the presence of a vascular underlying pathology as well as elucidate the presence of a potential penumbra (tissue at risk). Thanks to improvements and advances in both MR and CT technology, this can now be done in a number of ways. At the moment, CT is the most widely available and fast method for obtaining imaging of the brain and neck vessels of patients presenting with acute stroke. MRI can provide more precise information, although it remains slightly more time-consuming, but is, however, the method of choice for follow-up imaging. The main point is to take the one-stop-shopping approach where imaging of the vessels and brain is done from the aortic arch to the circle of Willis in one single session in order to have all the necessary information in the acute phase.

Background: The Women's Health Initiative (WHI) Estrogen Alone trial assessed the balance of benefits and risks of hormone use in healthy postmenopausal women. The trial was stopped prematurely because there was no benefit for coronary heart disease and an increased risk of stroke. This report provides a thorough analysis of the stroke finding using the final results from the completed trial database., Methods and Results: The WHI Estrogen Alone hormone trial is a multicenter, double-blind, placebo-controlled, randomized clinical trial in 10,739 women aged 50 to 79 years who were given daily conjugated equine estrogen (CEE; 0.625 mg; n=5310) or placebo (n=5429). During an average follow-up of 7.1 years, there were 168 strokes in the CEE group and 127 in the placebo group; 80.3% of strokes were ischemic. For all stroke the intention-to-treat hazard ratio [HR] (95% CI) for CEE versus placebo was 1.37 (1.09 to 1.73). The HR (95% CI) was 1.55 (1.19 to 2.01) for ischemic stroke and 0.64 (0.35, 1.18) for hemorrhagic stroke. The HRs indicate excess risk of ischemic stroke was apparent in all categories of baseline stroke risk, including younger and more recently menopausal women and in women with prior or current use of statins or aspirin., Conclusions: CEE increases the risk of ischemic stroke in generally healthy postmenopausal women. The excess risk appeared to be present in all subgroups of women examined, including younger and more recently menopausal women. There was no convincing evidence to suggest that CEE had an effect on the risk of hemorrhagic stroke.

Our understanding of the mechanisms underlying cerebrovascular atherosclerosis has improved in recent years, but significant gaps remain. New insights into the vascular biological processes that result in ischemic stroke may come from cellular and molecular profiling studies of the peripheral blood. In recent cellular profiling studies, increased levels of a proinflammatory T-cell subset (CD4 (+)CD28 (-)) have been associated with stroke recurrence and death. Expansion of this T-cell subset may occur after ischemic stroke and be a pathogenic mechanism leading to recurrent stroke and death. Increases in certain phenotypes of endothelial cell microparticles have been found in stroke patients relative to controls, possibly indicating a state of increased vascular risk. Molecular profiling approaches include gene expression profiling and proteomic methods that permit large-scale analyses of the transcriptome and the proteome, respectively. Ultimately panels of genes and proteins may be identified that are predictive of stroke risk. Cellular and molecular profiling studies of the peripheral blood and of atherosclerotic plaques may also pave the way for the development of therapeutic agents for primary and secondary stroke prevention.

Background: Direct brain biopsy is rarely indicated during acute stroke. This study uses peripheral blood mononuclear cells (PBMCs) to determine whether a systemic gene expression profile could be demonstrated in patients with acute ischemic stroke., Methods and Results: Using oligonucleotide microarrays, we compared the gene expression profile of an index cohort of 20 patients with confirmed ischemic stroke on neuroimaging studies with that of 20 referent subjects. Validation studies used quantitative real-time polymerase chain reaction to measure the levels of 9 upregulated genes in the index cohort, and an independent cohort of 9 patients and 10 referent subjects was prospectively studied to determine the accuracy of the Prediction Analysis for Microarrays list to classify stroke. After correction for multiple comparisons with the Bonferroni technique, 190 genes were significantly different between the stroke and referent groups. Broad classes of genes included white blood cell activation and differentiation (approximately 60%), genes associated with hypoxia and vascular repair, and genes potentially associated with an altered cerebral microenvironment. Real-time polymerase chain reaction confirmed increased mRNA expression in 9 of 9 upregulated stroke-associated genes in the index cohort. A panel of 22 genes derived from the Prediction Analysis for Microarrays algorithm in the index cohort classified stroke in the validation cohort with a sensitivity of 78% and a specificity of 80%. Control for the Framingham stroke risk score revealed only a partial dependence of the stroke gene expression profile in PBMCs on vascular risk., Conclusions: This study demonstrated an altered gene expression profile in PBMCs during acute ischemic stroke. Some genes with altered expression were consistent with an adaptive response to central nervous system ischemia.

Context: Noncontrast computed tomography (CT) is the standard brain imaging study for the initial evaluation of patients with acute stroke symptoms. Multimodal magnetic resonance imaging (MRI) has been proposed as an alternative to CT in the emergency stroke setting. However, the accuracy of MRI relative to CT for the detection of hyperacute intracerebral hemorrhage has not been demonstrated., Objective: To compare the accuracy of MRI and CT for detection of acute intracerebral hemorrhage in patients presenting with acute focal stroke symptoms., Design, Setting, and Patients: A prospective, multicenter study was performed at 2 stroke centers (UCLA Medical Center and Suburban Hospital, Bethesda, Md), between October 2000 and February 2003. Patients presenting with focal stroke symptoms within 6 hours of onset underwent brain MRI followed by noncontrast CT., Main Outcome Measures: Acute intracerebral hemorrhage and any intracerebral hemorrhage diagnosed on gradient recalled echo (GRE) MRI and CT scans by a consensus of 4 blinded readers., Results: The study was stopped early, after 200 patients were enrolled, when it became apparent at the time of an unplanned interim analysis that MRI was detecting cases of hemorrhagic transformation not detected by CT. For the diagnosis of any hemorrhage, MRI was positive in 71 patients with CT positive in 29 (P<.001). For the diagnosis of acute hemorrhage, MRI and CT were equivalent (96% concordance). Acute hemorrhage was diagnosed in 25 patients on both MRI and CT. In 4 other patients, acute hemorrhage was present on MRI but not on the corresponding CT--each of these 4 cases was interpreted as hemorrhagic transformation of an ischemic infarct. In 3 patients, regions interpreted as acute hemorrhage on CT were interpreted as chronic hemorrhage on MRI. In 1 patient, subarachnoid hemorrhage was diagnosed on CT but not on MRI. In 49 patients, chronic hemorrhage, most often microbleeds, was visualized on MRI but not on CT., Conclusion: MRI may be as accurate as CT for the detection of acute hemorrhage in patients presenting with acute focal stroke symptoms and is more accurate than CT for the detection of chronic intracerebral hemorrhage.

Background: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have neuroprotective effects in experimental stroke models and are commonly prescribed in clinical practice. The aim of this study was to determine if patients taking statins before hospital admission for stroke had an improved clinical outcome., Methods: This was an observational study of 436 patients admitted to the National Institutes of Health Suburban Hospital Stroke Program between July 2000 and December 2002. Self-reported risk factors for stroke were obtained on admission. Stroke severity was determined by the admission National Institutes of Health Stroke Scale score. Good outcome was defined as a Rankin score < 2 at discharge. Statistical analyses used univariate and multivariate logistic regression models., Results: There were 436 patients with a final diagnosis of ischemic stroke; statin data were available for 433 of them. A total of 95/433 (22%) of patients were taking a statin when they were admitted, rising from 16% in 2000 to 26% in 2002. Fifty-one percent of patients taking statins had a good outcome compared to 38% of patients not taking statins (p = 0.03). After adjustment for confounding factors, statin pretreatment was associated with a 2.9 odds (95% CI: 1.2-6.7) of a good outcome at the time of hospital discharge., Conclusions: The proportion of patients taking statins when they are admitted with stroke is rising rapidly. Statin pretreatment was significantly associated with an improved functional outcome at discharge. This finding could support the early initiation of statin therapy after stroke.

Background: Oral infections have been postulated to produce cytokines that may contribute to the pathogenesis of coronary heart disease (CHD). We hypothesized that by estimating the combined production of inflammatory mediators attributable to several oral pathologies, we might be able to explain CHD with better precision., Methods and Results: A total of 256 consecutive Finnish cardiac patients from Kuopio University Hospital with angiographically confirmed CHD and 250 age-, gender-, and residence-matched noncardiac patients (controls) were recruited. All dental factors expected to generate inflammatory mediators, including pericoronitis, dental caries, dentate status, root remnants, and gingivitis, were examined, and an asymptotic dental score (ADS) was developed by logistic regression analyses with an appropriate weighting scheme according to the likelihood ratio. We validated the explanatory ability of ADS by comparing it to that of the Total Dental Index and examining whether the ADS was associated with known predictors of CHD. A model that included ADS, C-reactive protein, HDL, and fibrinogen offered an explanatory ability that equaled or exceeded that of the Framingham heart score (C statistic=0.82 versus 0.80). When ADS was removed from this model, the C-statistic decreased to 0.77, which indicates that the ADS was a significant contributor to the explanatory ability of a logistic model., Conclusions: ADS may be useful as a prescreening tool to promote proactive cardiac evaluation among individuals without overt symptoms of CHD. However, additional prospective study is needed to validate the use of an oral health score as a predictor of incident CHD.