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Leucine-rich glioma-inactivated protein 1 antibody encephalitis: A case report

Wed, 05/27/2015 - 3:51pm

OBJECTIVE: To describe a case of leucine-rich glioma-inactivated protein 1 (LGI1) antibody-associated encephalitis.

METHODS: The clinical and ancillary data and brain MRIs were gathered retrospectively by chart review. Relevant literature on similar cases was also reviewed.

RESULTS: The diagnosis of LGI1 antibody-associated autoimmune encephalitis was based on the typical clinical presentation of seizures, psychiatric symptoms, and memory loss as well as negative diagnostic testing for cancer; the diagnosis was confirmed by positive LGI1 antibody. The patient responded favorably to treatment with IV immunoglobulin and continues to do well.

CONCLUSION: LGI1 antibody-associated encephalitis has increasingly been recognized as a primary autoimmune disorder with good prognosis and response to treatment.

Flow artifact in the anterior communicating artery resembling aneurysm on the time of flight MR angiogram

Wed, 05/27/2015 - 3:51pm

BACKGROUND: Magnetic resonance angiogram (MRA) of the brain is a widely employed non-invasive test to diagnose aneurysms. However, its overall accuracy is less than digital subtraction angiography and is prone to give false-positive or false-negative results. False-negative results can be seen with hemorrhage, lipoma, dermoid, posterior lobe of the pituitary gland, and the flow artifacts.

PURPOSE: To describe the findings associated with false aneurysms in the anterior communicating artery on the time of flight MRA and review the physical principles behind this artifact.

MATERIAL AND METHODS: This short series comprises of four patients whose MRA showed suspicious aneurysms in the region of the anterior communicating artery (ACOM) on time of flight MRA.

RESULTS: Two patients underwent catheter angiogram and the other two patients had computed tomography angiogram. None of these cases proved to have aneurysms and normal anterior communicating arteries were seen in all the patients. The findings on the MR angiograms were considered artifacts. All of the pseudoaneurysm had tapered appearance.

CONCLUSION: MR angiogram can result in artifacts at ACOM which may be mistaken for aneurysm. Such pseudoaneurysms have characteristic appearance and should be followed up with non-invasive tests.

Risk of distal embolization with stent retriever thrombectomy and ADAPT

Wed, 05/27/2015 - 3:51pm

BACKGROUND: There is a discrepancy in clinical outcomes and the achieved recanalization rates with stent retrievers in the endovascular treatment of ischemic stroke. It is our hypothesis that procedural release of embolic particulate may be one contributor to poor outcomes and is a modifiable risk. The goal of this study is to assess various treatment strategies that reduce the risk of distal emboli.

METHODS: Mechanical thrombectomy was simulated in a vascular phantom with collateral circulation. Hard fragment-prone clots (HFC) and soft elastic clots (SECs) were used to generate middle cerebral artery (MCA) occlusions that were retrieved by the Solitaire FR devices through (1) an 8 Fr balloon guide catheter (BGC), (2) a 5 Fr distal access catheter at the proximal aspect of the clot in the MCA (Solumbra), or (3) a 6 Fr guide catheter with the tip at the cervical internal carotid artery (guide catheter, GC). Results from mechanical thrombectomy were compared with those from direct aspiration using the Penumbra 5MAX catheter. The primary endpoint was the size distribution of emboli to the distribution of the middle and anterior cerebral arteries.

RESULTS: Solumbra was the most efficient method for reducing HFC fragments (p 1000 microm) was significantly increased using GC. A non-statistically significant benefit of direct aspiration was observed in several subgroups of emboli with size 50-1000 microm. However, compared with the stent-retriever mechanical thrombectomy techniques, direct aspiration significantly increased the risk of SEC fragmentation ( < 50 microm) by at least twofold.

CONCLUSIONS: The risk of distal embolization is affected by the catheterization technique and clot mechanics. already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Targeted drug delivery to flow-obstructed blood vessels using mechanically activated nanotherapeutics

Wed, 05/27/2015 - 3:51pm

Obstruction of normal blood flow, which occurs in a variety of diseases, including thromboembolism in stroke and atherosclerosis, is a leading cause of death and long-term adult disability in the Western world. This review focuses on a novel nanotherapeutic drug-delivery platform that is mechanically activated within blood vessels by high-fluid shear stresses to selectively target drugs to sites of vascular obstruction. In vitro and in vivo studies have shown that this approach can be used to efficiently lyse clots using a significantly lower amount of thrombolytic drug than is required when administered in a soluble formulation. This nanotherapeutic strategy can potentially improve both the efficacy and safety of thrombolytic drugs, particularly in patients who are at high risk for brain hemorrhage, and thus provide a new approach for the treatment of many life-threatening and debilitating vascular disorders.

Quantitative analysis of high-resolution, contrast-enhanced, cone-beam CT for the detection of intracranial in-stent hyperplasia

Wed, 05/27/2015 - 3:51pm

BACKGROUND: Intracranial in-stent hyperplasia is a stroke-associated complication that requires routine surveillance. OBJECTIVE: To compare the results of in vivo experiments to determine the accuracy and precision of in-stent hyperplasia measurements obtained with modified C-arm contrast-enhanced, cone-beam CT (CE-CBCT) imaging with those obtained by 'gold standard' histomorphometry. Additionally, to carry out clinical analyses comparing this CE-CBCT protocol with digital subtraction angiography (DSA). METHODS: A non-binned CE-CBCT protocol (VasoCT) was used that acquires x-ray images with a small field-of-view and applies a full-scale reconstruction algorithm providing high-resolution three-dimensional (3D) imaging with 100 microm isotropic voxels. In an vivo porcine model, VasoCT cross-sectional area measurements were compared with gold standard vessel histology. VasoCT and DSA were used to calculate in-stent stenosis in 23 imaging studies. RESULTS: Porcine VasoCT cross-sectional stent, lumen, and in-stent hyperplasia areas strongly correlated with histological measurements (r(2)=0.97, 0.93, 0.90; slope=1.14, 1.07, and 0.76, respectively; p<0.0001). Clinical VasoCT percentage stenosis correlated well with DSA percentage stenosis (r(2)=0.84; slope=0.76), and the two techniques were free of consistent bias (Bland-Altman, bias=3.29%; 95% CI -14.75% to 21.33%). An illustrative clinical case demonstrated the advantages of VasoCT, including 3D capability and non-invasive IV contrast administration, for detection of in-stent hyperplasia. CONCLUSIONS: C-arm VasoCT is a high-resolution 3D capable imaging technique that has been validated in an animal model for measurement of in-stent tissue growth. Successful clinical implementation of the protocol was performed in a small case series. already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Skull fractures in pediatric patients on computerized tomogram: comparison between routing bone window images and 3D volume-rendered images

Wed, 05/27/2015 - 3:51pm

Skull fracture is a common finding following head trauma. It has a prognostic significance and its presence points to severe trauma. Additionally, there is a greater possibility of detecting associated small underlying extra-axial hematomas and subtle injuries to the brain parenchyma. In pediatric patients, the presence of multiple open sutures often makes fracture evaluation challenging. In our experience, 3D volume (3DV)-rendered CT images complement routine axial bone window (RBW) images in detection and characterization of fractures. This is a multi-reader, multi-case, paired retrospective study to compare the sensitivity and specificity of RBW and 3DV images in detection of calvarial fractures in pediatric patients. A total of 60 cases (22 with fractures and 38 without) were analyzed. Two experienced neuroradiologists and a radiology trainee were the readers of the study. For all readers, the sensitivity was not statistically different between the RBW and the 3DV interpretations. For each reader, there was a statistically significant difference in the interpretation times between the RBW and the 3DV viewing formats. A greater number of sutural diastasis was identified on 3DV. We propose that 3DV images should be part of routine head trauma imaging, especially in the pediatric age group. It requires minimal post-processing time and no additional radiation. Furthermore, 3DV images help in reducing the interpretation time and also enhance the ability of the radiologist to characterize the calvarial fractures.

Endovascular treatment of tandem vascular occlusions in acute ischemic stroke

Wed, 05/27/2015 - 3:51pm

BACKGROUND AND PURPOSE:

Tandem vascular occlusions are an important cause of acute ischemic stroke (AIS) and present unique treatment challenges. We report our experience of managing a subset of AIS patients with extracranial vascular stenting/angioplasty and intracranial revascularization.

METHODS: Consecutive patients who presented at three centers with AIS from tandem vascular occlusions confirmed by brain and neck CT imaging were included in the study. We retrospectively analyzed the patient demographics, National Institute of Health Stroke Scale (NIHSS) score and modified Rankin Scale (mRS) score at the time of admission, treatment strategy, angiographic results using the Thrombolysis In Cerebral Infarction (TICI) score, and clinical and imaging follow-up.

RESULTS: Twenty-eight patients were included. The mean NIHSS score at admission was 18. Extracranial carotid occlusions with a concomitant middle cerebral artery occlusion were seen in 89.3% of patients (n = 25) and vertebral artery combined with basilar artery lesions in 10.7% (n = 3). An antegrade approach (ie, treatment of the extracranial lesion first) was used in 24 patients (85.7%). Proximal occlusion recanalization was achieved usually with a stent (n = 27; 96.4%). Pursuant to intracranial revascularization techniques, greater than or equal to TICI 2A recanalization was seen in 96.4% of patients. An mRS score of less than or equal to 2 at 90 days was achieved in 56.5% of patients.

CONCLUSIONS: Our study shows preliminary data from three centers on recanalization of tandem occlusions in patients presenting with AIS. There was a preference to revascularize the proximal occlusion using a stent followed by distal recanalization with mechanical thrombectomy, intra-arterial thrombolysis or a combination of these. This approach has low periprocedural complications and can achieve an excellent angiographic and clinical outcome.

Late Consequences of Acute Coronary Syndromes: Global Registry of Acute Coronary Events (GRACE) Follow-up.

Wed, 05/27/2015 - 11:58am

PURPOSE: Short-term outcomes have been well characterized in acute coronary syndromes; however, longer-term follow-up for the entire spectrum of these patients, including ST-segment-elevation myocardial infarction, non-ST-segment-elevation myocardial infarction, and unstable angina, is more limited. Therefore, we describe the longer-term outcomes, procedures, and medication use in Global Registry of Acute Coronary Events (GRACE) hospital survivors undergoing 6-month and 2-year follow-up, and the performance of the discharge GRACE risk score in predicting 2-year mortality.

METHODS: Between 1999 and 2007, 70,395 patients with a suspected acute coronary syndrome were enrolled. In 2004, 2-year prospective follow-up was undertaken in those with a discharge acute coronary syndrome diagnosis in 57 sites.

RESULTS: From 2004 to 2007, 19,122 (87.2%) patients underwent follow-up; by 2 years postdischarge, 14.3% underwent angiography, 8.7% percutaneous coronary intervention, 2.0% coronary bypass surgery, and 24.2% were re-hospitalized. In patients with 2-year follow-up, acetylsalicylic acid (88.7%), beta-blocker (80.4%), renin-angiotensin system inhibitor (69.8%), and statin (80.2%) therapy was used. Heart failure occurred in 6.3%, (re)infarction in 4.4%, and death in 7.1%. Discharge-to-6-month GRACE risk score was highly predictive of all-cause mortality at 2 years (c-statistic 0.80).

CONCLUSION: In this large multinational cohort of acute coronary syndrome patients, there were important later adverse consequences, including frequent morbidity and mortality. These findings were seen in the context of additional coronary procedures and despite continued use of evidence-based therapies in a high proportion of patients. The discriminative accuracy of the GRACE risk score in hospital survivors for predicting longer-term mortality was maintained.

A comparative study of zwitterionic ligands-mediated mineralization and the potential of mineralized zwitterionic matrices for bone tissue engineering.

Wed, 05/27/2015 - 11:58am

Cationic and anionic residues of the extracellular matrices (ECM) of bone play synergistic roles in recruiting precursor ions and templating the nucleation, growth and crystalline transformations of calcium apatite in natural biomineralization. We previously reported that zwitterionic sulfobetaine ligands can template extensive 3-dimensional (3-D) hydroxyapaptite (HA)-mineralization of photo-crosslinked polymethacrylatehydrogels. Here, we compared the potency of two other major zwitterionic ligands, phosphobetaine and carboxybetaine, with that of the sulfobetaine in mediating 3-D mineralization using the crosslinked polymethacrylate hydrogel platform. We confirmed that all three zwitterionic hydrogels were able to effectively template 3-D mineralization, supporting the general ability of zwitterions to mediate templated mineralization. Among them, however, sulfobetaine and phosphobetaine hydrogels templated denser 3-D mineralizationthan the carboxybetaine hydrogel, likely due to their higher free water fractions and better maintenance of zwitterionic nature throughout the pH-changes during the in vitro mineralization process. We further demonstrated that the extensively mineralized zwitterionic hydrogels could be exploited for efficient retention (e.g. 99% retention after 24-h incubation in PBS) of osteogenic growth factor recombinant bone morphogenetic protein-2 (rhBMP-2) and subsequent sustained local release with retained bioactivity. Combined with the excellent cytocompatibility of all three zwitterionic hydrogels and the significantly improved cell adhesive properties of their mineralized matrices, these materials could find promising applications in bone tissue engineering.

Academic-Correctional Health Partnerships: Preparing the Correctional Health Workforce for the Changing Landscape-Focus Group Research Results

Wed, 05/27/2015 - 11:58am

Providing health care in corrections is challenging. Attracting clinicians can be equally challenging. The future holds a shortage of nurses and primary care physicians. We have a unique opportunity, now, to develop and stabilize our workforce, create a positive image, and enhance quality before the health care landscape changes even more dramatically. Focus groups were conducted with 22 correctional health care professionals divided into three groups: physicians (6), nurses (4), and nurse practitioners/physician assistants (12). Content focused on curricular themes, but additional themes emerged related to recruitment and retention. This article describes recruitment challenges, strategic themes identified, and the proposed initiatives to support a stable, high-quality correctional health workforce.

Understanding smoking after acute illness: An application of the sentinel event method

Wed, 05/27/2015 - 11:58am

The sentinel event theory provides a stepwise approach for building models to understand how negative events can spark health behaviour change. This study tested a preliminary model using the sentinel events method in a sample (N = 300) of smokers who sought care for acute cardiac symptoms. Patients completed measures on: smoking-related causal attribution, perceived severity of the acute illness event, illness-related fear and intentions to quit smoking. Patients were followed up one week after the health event and a seven-day timeline follow back was completed to determine abstinence from tobacco. Structural equation models were performed using average predictor scale scores at baseline, as well as three different time anchors for ratings of illness severity and illness-related fear. Quit intentions, actual illness severity and age were the consistent, positive and independent predictors of seven-day point prevalence abstinence. Additional research on the influences of perceptions and emotional reactions is warranted.

Developing a complex endovascular fenestrated and branched aortic program

Wed, 05/27/2015 - 11:58am

In 2008, the top priority in our division's 5-year strategic plan was "to become an internationally recognized center of excellence for the endovascular treatment of complex aortic pathology extending from the aortic valve to the external iliac artery." Five components were identified as "most critical" to achieve this strategic priority: (1) training at centers of excellence in complex endovascular repair; (2) industry partnership to improve access to developing technologies; (3) a fully integrated team approach with one leader involved in all steps of all cases; (4) prospective data collection; and (5) development and implementation of a physician-sponsored investigational device exemption for juxtarenal, pararenal, and thoracoabdominal aneurysms. We have now performed 49 repairs (16 commercially manufactured devices, 33 physician-modified devices) for 3 common iliac, 20 juxtarenal, 9 pararenal, and 17 thoracoabdominal aneurysms, using 142 fenestrations, branches, and scallops. All patients had complete 30-day follow-up for calculation of 30-day events. Kaplan-Meier analysis was used to calculate 1-year events. In 5 years, we developed a successful complex endovascular aortic program that uses fenestrated/branched repair techniques. A focused team strategic planning approach to program development is an effective way for vascular surgery divisions to gain experience and expertise with new complex technologies while ensuring acceptable patient outcomes.

"Look who's talking!" Gaze Patterns for Implicit and Explicit Audio-Visual Speech Synchrony Detection in Children With High-Functioning Autism

Wed, 05/27/2015 - 11:58am

Conversation requires integration of information from faces and voices to fully understand the speaker's message. To detect auditory-visual asynchrony of speech, listeners must integrate visual movements of the face, particularly the mouth, with auditory speech information. Individuals with autism spectrum disorder may be less successful at such multisensory integration, despite their demonstrated preference for looking at the mouth region of a speaker. We showed participants (individuals with and without high-functioning autism (HFA) aged 8-19) a split-screen video of two identical individuals speaking side by side. Only one of the speakers was in synchrony with the corresponding audio track and synchrony switched between the two speakers every few seconds. Participants were asked to watch the video without further instructions (implicit condition) or to specifically watch the in-synch speaker (explicit condition). We recorded which part of the screen and face their eyes targeted. Both groups looked at the in-synch video significantly more with explicit instructions. However, participants with HFA looked at the in-synch video less than typically developing (TD) peers and did not increase their gaze time as much as TD participants in the explicit task. Importantly, the HFA group looked significantly less at the mouth than their TD peers, and significantly more at non-face regions of the image. There were no between-group differences for eye-directed gaze. Overall, individuals with HFA spend less time looking at the crucially important mouth region of the face during auditory-visual speech integration, which is maladaptive gaze behavior for this type of task.

Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.

MicroRNAs in alcoholic liver disease

Wed, 05/27/2015 - 11:58am

Alcoholic liver disease (ALD) is characterized by hepatocyte damage, inflammatory cell activation and increased intestinal permeability leading to the clinical manifestations of alcoholic hepatitis. Selected members of the family of microRNAs are affected by alcohol, resulting in an abnormal miRNA profile in the liver and circulation in ALD. Increasing evidence suggests that mRNAs that regulate inflammation, lipid metabolism and promote cancer are affected by excessive alcohol administration in mouse models of ALD. This communication highlights recent findings in miRNA expression and functions as they relate to the pathogenesis of ALD. The cell-specific distribution of miRNAs, as well as the significance of circulating extracellular miRNAs, is discussed as potential biomarkers. Finally, the prospects of miRNA-based therapies are evaluated in ALD.

Time-to-infection by Plasmodium falciparum is largely determined by random factors

Wed, 05/27/2015 - 11:58am

BACKGROUND: The identification of protective immune responses to P. falciparum infection is an important goal for the development of a vaccine for malaria. This requires the identification of susceptible and resistant individuals, so that their immune responses may be studied. Time-to-infection studies are one method for identifying putative susceptible individuals (infected early) versus resistant individuals (infected late). However, the timing of infection is dependent on random factors, such as whether the subject was bitten by an infected mosquito, as well as individual factors, such as their level of immunity. It is important to understand how much of the observed variation in infection is simply due to chance.

METHODS: We analyse previously published data from a treatment-time-to-infection study of 201 individuals aged 0.5 to 78 years living in Western Kenya. We use a mathematical modelling approach to investigate the role of immunity versus random factors in determining time-to-infection in this cohort. We extend this analysis using a modelling approach to understand what factors might increase or decrease the utility of these studies for identifying susceptible and resistant individuals.

RESULTS: We find that, under most circumstances, the observed distribution of time-to-infection is consistent with this simply being a random process. We find that age, method for detection of infection (PCR versus microscopy), and underlying force of infection are all factors in determining whether time-to-infection is a useful correlate of immunity.

CONCLUSIONS: Many epidemiological studies of P. falciparum infection assume that the observed variation in infection outcomes, such as time-to-infection or presence or absence of infection, is determined by host resistance or susceptibility. However, under most circumstances, this distribution appears largely due to the random timing of infection, particularly in children. More direct measurements, such as parasite growth rate, may be more useful than time-to-infection in segregating patients based on their level of immunity.

Structure-Guided Design of a High Affinity Inhibitor to Human CtBP

Wed, 05/27/2015 - 11:58am

Oncogenic transcriptional coregulators C-terminal Binding Protein (CtBP) 1 and 2 possess regulatory d-isomer specific 2-hydroxyacid dehydrogenase (D2-HDH) domains that provide an attractive target for small molecule intervention. Findings that the CtBP substrate 4-methylthio 2-oxobutyric acid (MTOB) can interfere with CtBP oncogenic activity in cell culture and in mice confirm that such inhibitors could have therapeutic benefit. Recent crystal structures of CtBP 1 and 2 revealed that MTOB binds in an active site containing a dominant tryptophan and a hydrophilic cavity, neither of which are present in other D2-HDH family members. Here, we demonstrate the effectiveness of exploiting these active site features for the design of high affinity inhibitors. Crystal structures of two such compounds, phenylpyruvate (PPy) and 2-hydroxyimino-3-phenylpropanoic acid (HIPP), show binding with favorable ring stacking against the CtBP active site tryptophan and alternate modes of stabilizing the carboxylic acid moiety. Moreover, ITC experiments show that HIPP binds to CtBP with an affinity greater than 1000-fold over that of MTOB, and enzymatic assays confirm that HIPP substantially inhibits CtBP catalysis. These results, thus, provide an important step, and additional insights, for the development of highly selective antineoplastic CtBP inhibitors.

Society for Vascular Surgery practice guidelines for atherosclerotic occlusive disease of the lower extremities: management of asymptomatic disease and claudication

Wed, 05/27/2015 - 11:58am

Peripheral arterial disease (PAD) continues to grow in global prevalence and consumes an increasing amount of resources in the United States health care system. Overall rates of intervention for PAD have been rising steadily in recent years. Changing demographics, evolution of technologies, and an expanding database of outcomes studies are primary forces influencing clinical decision making in PAD. The management of PAD is multidisciplinary, involving primary care physicians and vascular specialists with varying expertise in diagnostic and treatment modalities. PAD represents a broad spectrum of disease from asymptomatic through severe limb ischemia. The Society for Vascular Surgery Lower Extremity Practice Guidelines committee reviewed the evidence supporting clinical care in the treatment of asymptomatic PAD and intermittent claudication (IC). The committee made specific practice recommendations using the GRADE (Grades of Recommendation Assessment, Development and Evaluation) system. There are limited Level I data available for many of the critical questions in the field, demonstrating the urgent need for comparative effectiveness research in PAD. Emphasis is placed on risk factor modification, medical therapies, and broader use of exercise programs to improve cardiovascular health and functional performance. Screening for PAD appears of unproven benefit at present. Revascularization for IC is an appropriate therapy for selected patients with disabling symptoms, after a careful risk-benefit analysis. Treatment should be individualized based on comorbid conditions, degree of functional impairment, and anatomic factors. Invasive treatments for IC should provide predictable functional improvements with reasonable durability. A minimum threshold of a > 50% likelihood of sustained efficacy for at least 2 years is suggested as a benchmark. Anatomic patency (freedom from restenosis) is considered a prerequisite for sustained efficacy of revascularization in IC. Endovascular approaches are favored for most candidates with aortoiliac disease and for selected patients with femoropopliteal disease in whom anatomic durability is expected to meet this minimum threshold. Conversely, caution is warranted in the use of interventions for IC in anatomic settings where durability is limited (extensive calcification, small-caliber arteries, diffuse infrainguinal disease, poor runoff). Surgical bypass may be a preferred strategy in good-risk patients with these disease patterns or in those with prior endovascular failures. Common femoral artery disease should be treated surgically, and saphenous vein is the preferred conduit for infrainguinal bypass grafting. Patients who undergo invasive treatments for IC should be monitored regularly in a surveillance program to record subjective improvements, assess risk factors, optimize compliance with cardioprotective medications, and monitor hemodynamic and patency status.

Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

A piece of my mind. Should C be a passing grade for the USPSTF?

Wed, 05/27/2015 - 11:58am

I trust the US Preventive Services Task Force to be unbiased and to base its recommendations on the best science available at the time (though this group clearly needs a catchier name). Despite that, I have been forced to conclude that C should, frequently, be a failing grade for the USPSTF. I am referring to issuing recommendations with a C grade...