Clinical significance of post-interventional cerebral hyperdensities after endovascular mechanical thrombectomy in acute ischaemic stroke

Introduction

This study aims to investigate the clinical significance of post-interventional cerebral hyperdensities (PCHD) after endovascular mechanical thrombectomy in acute ischaemic stroke.

Methods

Data of 102 consecutive patients who received post-interventional CT scans within 4.5 h after mechanical thrombectomy were analysed retrospectively.

Results

Sixty-two of 102 patients (60.8 %) had PCHD on their post-interventional CT scans. The most common site of PCHD was the basal ganglia. PCHD were persisting in 13 of 62 patients (21.0 %), and transient in the remaining 49 patients (79.0 %) within 24 h. Four patients with PCHD and four patients without PCHD suffered from parenchymal haemorrhage. Neither ASA nor Clopidogrel, Tirofiban or rtPA were risk factors for PCHD. Final infarction size was congruent with or bigger than areas of PCHD in 93.3 % of cases in our series.

Conclusion

PCHD was not a risk factor for parenchymal haemorrhage in our series. The occurrence of PCHD was strongly related to the prior presence of infarction. PCHD was also a strong predictor for final infarction size.     

Phase I–IIa study of BMS-690514, an EGFR,HER-2 and -4 and VEGFR-1 to -3 oral tyrosine kinase inhibitor,in patients with advanced or metastatic solid tumours

PurposeBMS-690514 is a potent, reversible oral inhibitor of epidermal growth factor receptor (EGFR/HER-1), HER-2 and -4, and vascular endothelial growth factor receptors (VEGFRs)-1 to -3 offering targeted inhibition of tumour growth and vascularisation in a single agent. This phase I–IIa study was designed to identify the maximum tolerated dose (MTD) and assess safety, antitumour activity, pharmacokinetics and pharmacodynamics of BMS-690514.Patients and methodsIn phase I, patients with advanced solid tumours received escalating doses of once-daily BMS-690514. In phase IIa, erlotinib-naïve (cohort A) or erlotinib-resistant (cohort B) patients with advanced non-small-cell lung cancer (NSCLC) received BMS-690514 once-daily at the MTD.ResultsIn phase I (n = 28), the MTD was determined to be 200 mg daily. BMS-690514 was rapidly absorbed and highly metabolised after repeated oral administration with minimum drug accumulation. In phase IIa (n = 62), the most frequent treatment-related adverse events were diarrhoea and acneiform rash. Adverse events that led to >1 discontinuation were diarrhoea (n = 4; 4%) and rash (n = 2; 2%). Disease control (?4 months) and objective response rates, respectively, were 43.3% and 3.3% (cohort A) and 22.6% and 3.2% (cohort B). Six of 21 (29%) NSCLC patients with wild-type EGFR achieved disease control versus seven of 10 (70%) patients with EGFR mutations (including T790M). At MTD, BMS-690514 modulated pharmacodynamic biomarkers associated with inhibition of VEGFR- and EGFR-signalling pathways.ConclusionThis phase I–IIa study suggests that BMS-690514 has manageable safety profile and antitumour activity in patients with NSCLC at 200 mg/d, including those with EGFR mutations conferring resistance to erlotinib.     

Copy number variation in patients with cervical artery dissection

Cervical artery dissection (CeAD) occurs in healthy young individuals and often entails ischemic stroke. Skin biopsies from most CeAD-patients show minor connective tissue alterations. We search for rare genetic deletions and duplication that may predispose to CeAD. Forty-nine non-traumatic CeAD-patients with electron microscopic (EM) alterations of their dermal connective tissue (EM+ patients) and 21 patients with normal connective tissue in skin biopsies (EM− patients) were analyzed. Affymetrix 6.0 microarrays (Affymetrix) from all patients were screened for copy number variants (CNVs). CNVs absent from 403 control subjects and from 2402 published disease-free individuals were considered as CeAD-associated. The genetic content of undentified CNVs was analyzed by means of the Gene Ontology (GO) Term Mapper to detect associations with biological processes. In 49 EM+ patients we identified 13 CeAD-associated CNVs harboring 83 protein-coding genes. In 21 EM− patients we found five CeAD-associated CNVs containing only nine genes (comparison of CNV gene density between the groups: Mann–Whitney P=0.039). Patients'' CNVs were enriched for genes involved in extracellular matrix organization (COL5A2, COL3A1, SNTA1, P=0.035), collagen fibril organization COL5A2, COL3A1, (P=0.0001) and possibly for genes involved in transforming growth factor beta (TGF)-beta receptor signaling pathway (COL3A1, DUPS22, P=0.068). We conclude that rare genetic variants may contribute to the pathogenesis of CeAD, in particular in patients with a microscopic connective tissue phenotype.     

Application of Electrochemical Biosensors in Clinical Diagnosis

Analyses in the clinical area need quick and reliable analytical methods and devices. For this purpose, biosensors can be a suitable option, whereas they are constructed to be simple for use, specific for the target analyte, capable of continuous monitoring and giving quick results, potentially low‐costing and portable. In this article, we describe electrochemical biosensors developed for clinical diagnosis, namely for glucose, lactate, cholesterol, urea, creatinine, DNA, antigens, antibodies, and cancer markers assays. Chosen biosensors showed desirable sensitivity, selectivity, and potential for application on real samples. They are often designed to avoid interference with undesired components present in the monitored systems.     

Vertebrectomy and its possible use in repair of spinal cord injuries by neural transplantation

Spinal cord (SC) injury followed by autodestruction and resection of damaged tissue necessarily leads to the formation of a gap between the disconnected cord stumps. For any attempts to reconstruct the transected cord it may accordingly be useful to narrow or close this gap. Physically this can be achieved by vertebral resection with shortening of the spinal column. In cats and rabbits the dynamics of SC autodestruction was examined, and a technique for removal of autodestructed tissue developed, together with a surgical technique for resection of the second lumbar vertebra. By means of these techniques the volume of the gap between the SC stumps in rabbits was reduced from 200 mm3 to almost zero. In future research this should allow use of neural grafts of a reasonably small volume.     

Projections from auditory structures to the superior colliculus in the rat

Arginine-vasopressin (AVP) and related peptides were administered by microinjection into the nucleus tractus solitarius of the rat. AVP produced a rise both in mean arterial pressure and in heart rate. This effect was abolished by pretreatment with a specific antagonist of V1 receptors and was not seen either after injections of oxytocin or of the V2 agonist deamino-D-arginine-vasopressin. This study provides evidence for a specific action of vasopressin on the cardiovascular system in the nucleus of the tractus solitarius, which is mediated neither by V2 nor oxytocin receptors.     

Deoxyribonuclease activity in plasma of pregnant women and experimental animals

Clinical observations and animal experiments have shown that higher fetal DNA in maternal plasma could participate on the pathogenesis of preeclampsia. The understudied factor that could participate in interindividual variability in cell-free DNA is enzymatic activity of deoxyribonuclease (DNase). We have found that healthy pregnant animals have higher plasma DNase activity than healthy pregnant women. Injection of cell-free fetal DNA into pregnant animals had no effect on DNase activity. Interspecies differences in DNase activity should be considered in animal experiments focusing on the role of fetal DNA in preeclampsia and cell-free DNA in other disease models.