Citations

AbstractBackground: Stroke is a devastating condition encompassing a wide range of pathophysiological entities that include thrombosis, hemorrhage, and embolism. Current diagnosis of stroke relies on physician clinical examination and is further supplemented with various neuroimaging techniques. A single set or multiple sets of blood biomarkers that could be used in an acute setting to diagnosis stroke, differentiate between stroke types, or even predict an initial/reoccurring stroke would be extremely valuable.Content: We discuss the current classification, diagnosis, and treatment of stroke, focusing on use of novel biomarkers (either solitary markers or multiple markers within a panel) that have been studied in a variety of clinical settings.Summary: The current diagnosis of stroke remains hampered and delayed due to lack of a suitable mechanism for rapid (ideally point-of-care), accurate, and analytically sensitive biomarker-based testing. There is a clear need for further development and translational research in this area. Potential biomarkers identified need to be transitioned quickly into clinical validation testing for further evaluation in an acute stroke setting; to do so would impact and improve patient outcomes and quality of life.

Background and Purpose— We performed a meta-analysis of published studies on the endovascular treatment of very small intracranial aneurysms, including 71 patients treated at our institution. Methods— We conducted a computerized MEDLINE search of the literature for reports on the treatment of intracranial aneurysms with a maximum dimension of ≤3 mm by using the search terms “small,” “tiny,” “intracranial aneurysm,” “endovascular,” and “coil.” A total of 7 studies, including our institution’s consecutive case series of 71 intracranial aneurysms, were included in this study. We extracted information regarding intraoperative complications, procedural mortality and morbidity, immediate- and long-term angiographic outcomes, and retreatment rate. The meta-analysis was performed with the statistical package Comprehensive Meta-Analysis. Results— Approximately 61% of the aneurysms in this meta-analysis presented as ruptured, whereas 39% of the aneurysms were unruptured. Procedural rupture rates for very small aneurysms was 8.3% (95% CI, 6.0% to 11.4%). The mortality rate due to procedural rupture was 2.4% (95% CI, 1.2% to 4.7%). The morbidity rate due to thromboembolic complications was 1.9% (95% CI, 0.9% to 3.9%). Subarachnoid hemorrhage within 1 month of treatment occurred in 1.6% (95% CI, 0.6% to 3.7%) of cases. There was no statistically significant difference between unruptured and ruptured aneurysms for any of these outcomes. Conclusion— Our meta-analysis suggests that treatment of very small aneurysms is feasible and effective in >90% of treated aneurysms. However, the risk of periprocedural rupture is higher than that reported for larger aneurysms. Similarly, the combined rate of periprocedural mortality and morbidity is not negligible (7.3%) and should be considered when considering the best therapeutic option for these aneurysms.

Abstract We compared the clinical concordance of estimated glomerular filtration rate (eGFR) based on 3 whole blood creatinine assays with the eGFR calculated from a reference plasma creatinine assay. Whole blood creatinine on the Radiometer ABL800 FLEX (Radiometer A/S, Bronshoj, Denmark) demonstrated the best correlation and concordance to plasma creatinine/eGFR compared with the i-STAT (i-STAT, East Windsor, NJ) and StatSensor (Nova Biomedical, Waltham, MA). The i-STAT had better sensitivity (compared with Radiometer) but poorer specificity for prediction of plasma eGFR less than 60 mL/min/1.73 m2. The StatSensor demonstrated lower concordance of whole blood to plasma eGFR but offered a slope and an intercept offset feature that partially compensates for this effect. The optimal device for use in rapid determination of eGFR from whole blood creatinine may depend on whether it is more important in a given practice to optimize sensitivity, specificity, or overall concordance for determining plasma eGFR less than 60 mL/min/1.73 m2.

Hacs1, a SH3 and SAM domain‐containing adaptor protein, is up‐regulated by IL‐4 in activated B cells and strongly expressed in dendritic cells. To elucidate the function of Hacs1 in immune regulation, we generated Hacs1 − / − mice by deletion of the SH3 and SAM domains. Hacs1 − / − mice were viable and fertile and had normal bone marrow B‐cell development and normal splenic T‐ and B‐cell populations. However, adult Hacs1 − / − mice had increased peritoneal Bla cells (IgM + CD5 + ). On immunization with T‐cell‐independent antigen TNP‐Ficoll, Hacs1 − / − mice had increased production of anti‐TNP IgM and IgG3. Purified splenic B cells from Hacs1 − / − mice showed increased cell proliferation on BCR (B‐cell receptor) stimulation. We further demonstrate that the Hacs1 − / − B cells had increased global tyrosine phosphorylation, including tyrosine kinases Lyn and Akt. Both T‐helper type 1 (T h 1) and T‐helper type 2 (T h 2) humoral responses were enhanced in Hacs1 − / − mice. In vitro bone marrow‐derived Hacs1 − / − dendritic cells showed increased IL‐12 production on stimulation with ovalbumin (OVA). This study suggests that Hacs1 is an immunoinhibitory adaptor that might be a useful target for immune suppression therapy.—Wang, D., Stewart, A. K., Zhuang, L., Zhu, Y., Wang, Y., Shi, C., Keating, A., Slutsky, A., Zhang, H., Wen, X.‐Y. Enhanced adaptive immunity in mice lacking the immunoinhibitory adaptor Hacs1. FASEBJ. 24, 947–956 (20l0). www.fasebj.org

AbstractCertain malignant B cells rely on B-cell receptor (BCR)–mediated survival signals. Spleen tyrosine kinase (Syk) initiates and amplifies the BCR signal. In in vivo analyses of B-cell lymphoma cell lines and primary tumors, Syk inhibition induces apoptosis. These data prompted a phase 1/2 clinical trial of fostamatinib disodium, the first clinically available oral Syk inhibitor, in patients with recurrent B-cell non-Hodgkin lymphoma (B-NHL). Dose-limiting toxicity in the phase 1 portion was neutropenia, diarrhea, and thrombocytopenia, and 200 mg twice daily was chosen for phase 2 testing. Sixty-eight patients with recurrent B-NHL were then enrolled in 3 cohorts: (1) diffuse large B-cell lymphoma (DLBCL), (2) follicular lymphoma (FL), and (3) other NHL, including mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), mucosa-associated lymphoid tissue lymphoma, lymphoplasmacytic lymphomas, and small lymphocytic leukemia/chronic lymphocytic leukemia (SLL/CLL). Common toxicities included diarrhea, fatigue, cytopenias, hypertension, and nausea. Objective response rates were 22% (5 of 23) for DLBCL, 10% (2 of 21) for FL, 55% (6 of 11) for SLL/CLL, and 11% (1/9) for MCL. Median progression-free survival was 4.2 months. Disrupting BCR-induced signaling by inhibiting Syk represents a novel and active therapeutic approach for NHL and SLL/CLL. This trial was registered at www.clinicaltrials.gov as #NCT00446095.