Citations

Introduction: White matter hyperintensities (WMH) is the most prominent neuroimaging feature of small vessel disease (SVD). SVD is thought to be a result of arteriolosclerosis, chronic hypoperfusion of white matter, selective oligodendrocyte death and degeneration of myelinated fibers. The risk of ischemic stroke is significantly increased with the presence of WMH. The presence of intracranial collaterals is a strong predictor of salvageable neurological function in acute stroke; however, the factors affecting the ability to recruit collaterals are poorly understood. We wanted to study if the presence and severity of small vessel white matter disease had an adverse effect on cerebral collateral flow in acute embolic large vessel stroke. Methods: We identified a consecutive series of adult subjects with acute embolic large vessel strokes confirmed on CT angiography (CTA) from a 10-year institutional database. Patients without a brain MRI within six months of CTA were excluded. Collateral scores of the affected hemisphere were calculated on CTA using the modified Tan scale (0-4) by two independent trained reviewers and confirmed by a neuroradiologist. The WMH was quantified using the Fazekas scale (0-3) incorporating both deep and periventricular components. Areas of restricted diffusion on brain MRI in the peri-stroke period were eliminated from the assessment of Fazekas score. Spearman’s correlation tests were performed for the association between collateral scores and WMH. Results: A total of 234 patients (mean age 70±14 years, 47% [110/234] women) satisfied the inclusion criteria. The prevalence of periventricular and deep WMH was 83% and 87% respectively. Aging had a significant impact on periventricular WMH (r=0.48, p <0.001) and deep WMH (r=0.47, p <0.001). However, collateral scores exhibited no statistically significant relationship with the presence or severity of periventricular scores (r=0.08, p=0.17) or deep WMH scores (r=0.01, p=0.77). Conclusions: Our results indicate that the presence of SVD does not affect cerebral collateral flow. The vascular niche and risk factors of SVD appear to be distinct from that of intracranial vessels responsible for collateral reperfusion of ischemic territory in acute large vessel embolic stroke.

Introduction: Poor leptomeningeal collateral flow is related to worse neurological outcome in acute ischemic stroke. The increased release of stress hormones during the first hours of acute stroke leads to inhibition of insulin secretion and increase insulin resistance, thus inducing stress hyperglycemia, which is often evident on blood glucose levels at admission. While admission hyperglycemia, independent of diabetes mellitus (DM) is associated with poor clinical outcome in ischemic stroke, studies on its effect on collateral circulation after acute cerebral embolism are largely inconclusive. Methods: We identified a consecutive series of patients aged 18 years and older from 2008 to 2018 with acute embolic large vessel stroke confirmed on CT angiography (CTA) using an institutional database. Individual CTAs were over-read, and collateral scores of the affected hemisphere were calculated using a modification of the Tan scale (0-4), by two trained readers. We reviewed the electronic medical records for presenting NIHSS, admission glucose and HbA1C levels, and prior history of DM. Spearman’s ρ, odds ratios (OR), and their 95% confidence intervals (CI) were analyzed. All tests were considered significant when P<0.05. Results: Of the 405 patients identified through the database (mean age 70 years [range, 55-85], 45% [183/405] women), 35% (142/405) had a prior history of DM. Mean admission glucose was 134±51 mg/dL, and median NIHSS at presentation was 17. Blood glucose level at admission was negatively correlated with collateral scores (ρ= -0.23, P=0.008). Specifically, glucose levels above 120 mg/dL were significantly associated (OR 1.68 CI 1.13-2.5) with poor collateral scores (≤1). However, collateral scores exhibited no statistically significant relationship with HbA1c (ρ=-0.08, P=0.15) or prior history of DM (P=0.73). Conclusions: Patients with higher admission glucose levels have poor collateral scores, while HbA1c and prior DM do not have a similar effect on collateral flow. Our results suggest that poor collateral flow may explain adverse outcomes associated with hyperglycemia in acute ischemic stroke. Determining if there is a benefit of aggressive glycemic control within the first few hours of embolic stroke warrants further study.

Introduction: Good collateral flow is associated with improved outcomes in acute embolic stroke. There is compelling data linking smoking to all types of stroke, with current smokers at a higher risk than former or never smokers. Smoking has, however, been shown to promote collaterals in coronary vascular bed in humans. It is unknown if there is a similar effect in cerebral collateral flow. We aimed to investigate if cigarette smoking was positively associated with collateral blood flow in a homogenous cohort of patients with acute large vessel occlusive embolic stroke. Methods: We identified all patients aged ≥18 with acute ischemic stroke showing embolic occlusion of ICA terminus/M1 MCA on admission CT angiography (CTA), between 2008 to 2018, through an institutional database. Patients with chronic occlusions and stenotic lesions were excluded. Individual CTAs were independently reviewed by two trained investigators to calculate collateral scores of the affected hemisphere using the modified Tan scale (0-4) as a reference. Details of cigarette smoking history were obtained from the electronic medical records. Patients were grouped into smokers (former and current smokers) and never smokers. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated, and all tests were considered significant when P<0.05. Results: Of the 612 patients identified through the database, 429/612 patients (mean age 71±16 years, 45% [194/429] women) satisfied the inclusion criteria. 64.8% (278/429) had a positive history of smoking with an average of 47±12 pack-years. There was a significant association between good collateral scores (≥2) with smoking history (OR 1.74 CI 1.17-2.61, P=0.006). This trend remained significant even after comparing raw collateral scores (0-4) ( P=0.006, Spearman’s ρ=0.22). However, number of pack-years and collateral scores exhibited no statistically significant relationship (P=0.6). Conclusions: Our study shows that patients who have ever smoked have higher intracranial collateral vessel scores in the event of an acute embolic stroke. Increased impedance and reduced cerebral blood flow resulting from cigarette smoking may stimulate collateral recruitment in cerebral pial circulation, similar to the effect in coronary bed.

ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell‐released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV‐associated functional activities. Finally, a checklist is provided with summaries of key points.

Mucopolysaccharidosis type VI (MPS VI) is a clinically heterogeneous lysosomal disease, which can be divided into 2 main categories on the basis of age of onset and severity of symptoms. The diagnosis of the attenuated form is often delayed given subtle facial features rather than the typical coarse facial features of the classic form. Here, we discuss the difficulties in establishing the diagnosis of MPS VI on the basis of the report of 4 individuals. The most common signs and symptoms in our series were bone abnormalities and hip pain as initial manifestations and cardiac changes detected after follow-up studies. On the basis of our cohort and others worldwide, awareness of attenuated forms of MPS VI should be increased particularly among general practitioners, pediatricians, rheumatologists, orthopedists, ophthalmologists, and cardiologists. Moreover, these health care providers should be aware of the technical aspects involved in the molecular and biochemical diagnosis process so that they are aware how diagnostic errors may occur.

e17580 Background: Cabozantinib is a small molecule multiple-receptor tyrosine kinase inhibitor that primarily targets MET and vascular endothelial growth factor receptor 2 (VEGFR2). We evaluated the effect of cabozantinib on BTM in RAIR DTC. We also assessed the response of BM to cabozantinib using 18F Sodium Fluoride (NaF) PET and radionuclide bone scans. Methods: This prospective analysis was performed as part of a multicenter International Thyroid Oncology Group phase II study of cabozantinibin patients with RAIR DTC who progressed on prior VEGFR-targeted therapy (NCT01811212). BTM [serum C-telopeptide (CTx), osteocalcin, N-telopeptide (NTx), procollagen type 1 (Pc1) and urinary NTx] and NaF PET or Tc-MDP scans were done at baseline and after 8 weeks of therapy. A paired t-test was used between baseline and week 8 BTM. Results: Primary study results were presented elsewhere (Shah, et al. 2015, International Thyroid Congress) showing a response rate of 36% with cabozantinib. Of 25 patients (pts) enrolled, 21 had BM, 10 of whom were on bone-modifying agents (BMA) prior to week 8. Only 2 pts had elevated BTM at baseline. In all pts who had paired BTM, there was a statistically significant decline in all BTM except NTx by week 8 (table). Pts not on BMA also had a significant decline in CTx (p 0.0003), urine NTx (p 0.0300), and Pc1 (p 0.0030) compared to baseline. 19 pts were evaluable for overall response and there was no correlation between BTM and response rate. 6/21 patients underwent paired NaF PET scans and 4/6 had minor reduction in lesion uptake at 8 weeks. Conclusions: Interestingly, most of our patients had normal baseline BTM despite BM. Cabozantinib was associated with a strikingly significant reduction in all BTM (even when BTM were within normal limits at baseline) except NTx by week 8. Minor decreases in bone lesion uptake was noted on NaF PET in 4/6 evaluable patients. Clinical trial information: NCT01811212. [Table: see text]

Introduction Robotic-assisted surgery (RAS) has emerged as an alternative minimally invasive surgical option. Despite its growing applicability, the frequent need for pneumoperitoneum and Trendelenburg position could significantly affect respiratory mechanics during RAS. AVATaR is an international multicenter observational study aiming to assess the incidence of postoperative pulmonary complications (PPC), to characterise current practices of mechanical ventilation (MV) and to evaluate a possible association between ventilatory parameters and PPC in patients undergoing RAS. Methods and analysis AVATaR is an observational study of surgical patients undergoing MV for general anaesthesia for RAS. The primary outcome is the incidence of PPC during the first five postoperative days. Secondary outcomes include practice of MV, effect of surgical positioning on MV, effect of MV on clinical outcome and intraoperative complications. Ethics and dissemination This study was approved by the Institutional Review Board of the Hospital Israelita Albert Einstein. The study results will be published in peer-reviewed journals and disseminated at international conferences. Trial registration number NCT02989415 ; Pre-results.