Factors associated with intracerebral hemorrhage after thrombolytic therapy for ischemic stroke pooled analysis of placebo data from the Stroke-Acute Ischemic NXY Treatment (SAINT) I and SAINT II trials

<p><b>Background and Purpose:</b> A number of factors have been associated with postthrombolysis intracerebral hemorrhage, but these have varied across studies.</p> <p><b>Methods:</b> We examined patients with acute ischemic stroke treated with intravenous tissue plasminogen activator within 3 hours of symptom onset who were enrolled in the placebo arms of 2 trials (Stroke-Acute Ischemic NXY Treatment [SAINT] I and II Trials) of a putative neuroprotectant. Early CT changes were graded using the Alberta Stroke Program Early CT Score (ASPECTS). Post–tissue plasminogen activator symptomatic intracerebral hemorrhage was defined as a worsening in National Institutes of Health Stroke Scale of ≥4 points within 36 hours with evidence of hemorrhage on follow-up neuroimaging. Good clinical outcome was defined as a modified Rankin scale of 0 to 2 at 90 days.</p> <p><b>Results:</b> Symptomatic intracerebral hemorrhage occurred in 5.6% of 965 patients treated with tissue plasminogen activator. In multivariable analysis, symptomatic intracerebral hemorrhage was increased with baseline antiplatelet use (single antiplatelet: OR, 2.04, 95% CI, 1.07 to 3.87, P=0.03; double antiplatelet: OR, 9.29, 3.28 to 26.32, P<0.001), higher National Institutes of Health Stroke Scale score (OR, 1.09 per point, 1.03 to 1.15, P=0.002), and CT changes defined by ASPECTS (ASPECTS 8 to 9: OR, 2.26, 0.63 to 8.10, P=0.21; ASPECTS ≤7: OR, 5.63, 1.66 to 19.10, P=0.006). Higher National Institutes of Health Stroke Scale was associated with decreased odds of good clinical outcome (OR, 0.82 per point, 0.79 to 0.85, P<0.001). There was no relationship between baseline antiplatelet use or CT changes and clinical outcome.</p> <p><b>Conclusions:</b> Along with higher National Institutes of Health Stroke Scale and extensive early CT changes, baseline antiplatelet use (particularly double antiplatelet therapy) was associated with an increased risk of post–tissue plasminogen activator symptomatic intracerebral hemorrhage. Of these factors, only National Institutes of Health Stroke Scale was associated with clinical outcome.</p&gt

Sentinel Case of Candida auris in the Western United States Following Prolonged Occult Colonization in a Returned Traveler from India.

Candida auris is an emerging multidrug-resistant yeast with high mortality. We report the sentinel C. auris case on the United States West Coast in a patient who relocated from India. We identified close phylogenetic relatedness to the South Asia clade and ERG11 Y132F and FKS1 S639Y mutations potentially explaining antifungal resistance

Pan-viral serology implicates enteroviruses in acute flaccid myelitis.

Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)1-6. Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)2. CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM

Measuring Coupling of Rhythmical Time Series Using Cross Sample Entropy and Cross Recurrence Quantification Analysis

The aim of this investigation was to compare and contrast the use of cross sample entropy (xSE) and cross recurrence quantification analysis (cRQA) measures for the assessment of coupling of rhythmical patterns. Measures were assessed using simulated signals with regular, chaotic, and random fluctuations in frequency, amplitude, and a combination of both. Biological data were studied as models of normal and abnormal locomotor-respiratory coupling. Nine signal types were generated for seven frequency ratios. Fifteen patients with COPD (abnormal coupling) and twenty-one healthy controls (normal coupling) walked on a treadmill at three speeds while breathing and walking were recorded. xSE and the cRQA measures of percent determinism,maximum line,mean line, and entropy were quantified for both the simulated and experimental data. In the simulated data, xSE, percent determinism, and entropy were influenced by the frequency manipulation. The 1 : 1 frequency ratio was different than other frequency ratios for almost all measures and/or manipulations. The patients with COPD used a 2 : 3 ratio more often and xSE, percent determinism,maximum line, mean line, and cRQA entropy were able to discriminate between the groups. Analysis of the effects of walking speed indicated that all measures were able to discriminate between speeds

Driving vascular endothelial cell fate of human multipotent Isl1+ heart progenitors with VEGF modified mRNA

Distinct families of multipotent heart progenitors play a central role in the generation of diverse cardiac, smooth muscle and endothelial cell lineages during mammalian cardiogenesis. The identification of precise paracrine signals that drive the cell-fate decision of these multipotent progenitors, and the development of novel approaches to deliver these signals in vivo, are critical steps towards unlocking their regenerative therapeutic potential. Herein, we have identified a family of human cardiac endothelial intermediates located in outflow tract of the early human fetal hearts (OFT-ECs), characterized by coexpression of Isl1 and CD144/vWF. By comparing angiocrine factors expressed by the human OFT-ECs and non-cardiac ECs, vascular endothelial growth factor (VEGF)-A was identified as the most abundantly expressed factor, and clonal assays documented its ability to drive endothelial specification of human embryonic stem cell (ESC)-derived Isl1+ progenitors in a VEGF receptor-dependent manner. Human Isl1-ECs (endothelial cells differentiated from hESC-derived ISL1+ progenitors) resemble OFT-ECs in terms of expression of the cardiac endothelial progenitor- and endocardial cell-specific genes, confirming their organ specificity. To determine whether VEGF-A might serve as an in vivo cell-fate switch for human ESC-derived Isl1-ECs, we established a novel approach using chemically modified mRNA as a platform for transient, yet highly efficient expression of paracrine factors in cardiovascular progenitors. Overexpression of VEGF-A promotes not only the endothelial specification but also engraftment, proliferation and survival (reduced apoptosis) of the human Isl1+ progenitors in vivo. The large-scale derivation of cardiac-specific human Isl1-ECs from human pluripotent stem cells, coupled with the ability to drive endothelial specification, engraftment, and survival following transplantation, suggest a novel strategy for vascular regeneration in the heart

Development of the Italian Version of the National Institutes of Health Stroke Scale It-NIHSS

Background and Purpose-The National Institutes of Health Stroke Scale (NIHSS) is a basic component of the assessment of patients with acute stroke. To foster and standardize the use of the NIHSS among Italian health professionals, we translated the scale, dubbed into Italian the training and test videotapes devised by the National Institutes of Health researchers, and conducted a series of certification courses using the translated videos. Methods-Translation, text adaptation, video dubbing, and editing of the Italian NIHSS videotapes relied on a team of bilingual stroke neurologists. Three waves of training courses were organized for mixed classes of medical and nonmedical health professionals. The certification test was based on the usual set of 5 videotaped patients. Scoring rules were those provided by the National Institutes of Neurological Disorders and Stroke. Reliability of the Italian NIHSS was assessed using kappa statistics and compared with that of the original NIHSS. Results-During 3 years, 850 nurses, 460 nonneurologist physicians, and 246 neurologists were trained. Pass rates were respectively 44%, 75%, and 87%, respectively. Overall, 80% of scale items showed moderate to excellent reliability. Independent significant predictors of test failure at multivariate logistic regression were nurse profession (OR, 5.41; 95% CI, 4.07 to 7.20), older age (OR, 1.03; 95% CI, 1.02 to 1.05), and first edition of the course (OR, 3.13; 95% CI, 2.43 to 4.05). The agreement across all items between NIHSS and the Italian NIHSS was 80% (kappa = 0.70 +/- 0.18, z < 0.001). Conclusions-The Italian translation, supervised by experienced vascular neurologists, did not influence the clinimetric characteristics of the NIHSS. Our findings support the implementation of NIHSS video training in languages other than English. (Stroke. 2009; 40: 2557-2559.

Evolution of the Thrombolytic Treatment Window for Acute Ischemic Stroke

Ischemic stroke is a major cause of morbidity and mortality for which the only approved treatment in the acute setting is intravenous thrombolysis. The efficacy and safety of recombinant tissue plasminogen activator (rt-PA) have been firmly established within 3 h of symptom onset; however, few patients are eligible for treatment in this time window. Expanding the time for treatment has been challenging, but new evidence has demonstrated a modest statistical improvement in selected patients when rt-PA is administered within 4.5 h. This important finding hopefully will enable more patients to receive treatment and simultaneously provides an opportunity to reaffirm that the benefits of rt-PA diminish with time

Correlation of adrenomedullin gene expression in peripheral blood leukocytes with severity of ischemic stroke

Human adrenomedullin (ADM), a 52-amino acid peptide, belongs to the calcitonin/calcitonin gene-related peptide (CGRP)/amylin peptide family. ADM acts as a multifunctional regulatory peptide and is upregulated in response to hypoxia. Previous microarray studies have found increased ADM gene (ADM) expression in peripheral blood cells of patients with stroke, however, it is unknown if an increased ADM level is correlated with severity of human ischemic stroke. This study investigated ADM expression in peripheral blood leukocytes (PBL) of healthy controls and subjects at day 1, week 1 and week 3 postacute ischemic stroke using rtPCR methodology. We found that ADM expression was significantly upregulated on the first day of stroke compared to the healthy subjects and the disease controls; the levels remained elevated for up to week 3. Further, ADM expression at day 1 was correlated with stroke severity measured by the National Institute of Healthy Stroke Scale (NIHSS), the modified Barthel Index (mBI) and the modified Rankin Scale (mRS). This could indicate that ADM expression level is related to the severity of tissue damage. We suggest that increased ADM expression in PBL after acute ischemic stroke is most likely to indicate that these cells have been subjected to hypoxia and that the magnitude of expression is likely to be related to the volume of hypoxic tissue. Hypoxia can affect lymphocytes function and could affect the immune response to stroke. The correlation of ADM expression level with the measures of stroke severity implicates ADM - a potential blood bio-marker in studies of ischemic stroke