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Introduction: Neurologic disorders with autoimmune dysregulation are commonly encountered in the critical care setting. Frequently encountered diseases include Guillain-Barré syndrome (GBS), myasthenia gravis, multiple sclerosis, acute demyelinating encephalomyelitis, and encephalitides. Immunomodulatory therapies, including high-dose corticosteroids, plasmapheresis, and intravenous immunoglobulins, are the cornerstone of the treatment of these diseases. Here we review the efficacy and side effects of immunomodulatory therapies commonly utilized in critically ill neurologic patients in the intensive care setting.Methods: Search of Medline, Cochrane databases, and manual review of article bibliographies.Results: The efficacy of high-dose corticosteroids, plasmapheresis, and intravenous immunoglobulins have been studied extensively in GBS, myasthenia gravis, and demyelinating disorders such as multiple sclerosis and acute demyelinating encephalomyelitis. For these diseases, however, the duration of treatment, dosing regimens, and choices among different therapeutic modalities remain controversial. For many of the other diseases (e.g., encephalitis and status epilepticus of autoimmune etiology) discussed in this review, evidence is limited to small case series.Conclusions: There is good evidence for the efficacy and tolerability of immunomodulatory therapies in GBS, myasthenia gravis, and acute central nervous system demyelination, though data to establish superiority of one therapeutic regimen over another remains lacking. For most other conditions, the data for immunomodulatory therapies are limited, and further research is required. [ABSTRACT FROM AUTHOR]

Purpose: Telemedicine care dramatically expanded during the COVID-19 pandemic. We characterized facilitators and barriers to telemedicine implementation among safety-net primary care clinics serving patients with limited English proficiency (LEP)., Methods: We collected data on telemedicine volume and patient demographics among safety-net clinics participating in a telemedicine learning collaborative. Data on various metrics were reported to the collaborative from February 2019 through August 2021. We conducted semi-structured interviews with clinical and quality leaders, purposively sampling clinics serving high proportions of patients with LEP. We analyzed interviews with a mixed inductive-deductive approach applying the Consolidated Framework for Implementation Research., Results: By September 2020, the 23 sites served 121,589 unique patients with in-person and 120,338 with telephone visits; 47% of these patients had LEP. Of 10,897 unique patients served by video visits, 38% had LEP. As a proportion of total visits, telemedicine (telephone and video) visits increased from 0-17% in October 2019-March 2020 to 10-98% in March-August 2020. We conducted 14 interviews at 11 sites. Themes included (1) existing telemedicine platforms and interpreter services were not optimized to support patients with LEP; (2) clinics invested significant labor iterating workflows; (3) sites with technological infrastructure and language-concordant staff were best suited to serve patients; (4) patients speaking less-represented languages or experiencing intersecting literacy barriers were underserved with telemedicine. Interviewees recommended innovations in telemedicine platforms and community-based access., Conclusions: Safety-net sites relied on existing resources to accommodate patients with LEP, but struggled providing access for the most marginalized. Proactive, data-driven strategies to address patient and community barriers as well as optimize clinical workflows with high-quality, certified medical interpreters are needed to ensure equitable access., (© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Addressing social determinants of health (SDoH) is associated with improved clinical outcomes for patients with chronic diseases in safety-net settings. This qualitative study supplemented by descriptive quantitative analysis investigates the degree of alignment between patient and clinicians’ perceptions of SDoH resources and referrals in clinics within the public healthcare delivery system in San Francisco. We conducted a qualitative analysis of in-depth interviews, patient-led neighborhood tours, and in-person clinic visit observations with 10 patients and 7 primary care clinicians. Using a convergent parallel mixed methodology, we also completed a descriptive quantitative analysis comparing the categories of neighborhood health resources mentioned by patients or community leaders to the resources integrated into the electronic health record. We found that patients held a wealth of knowledge about neighborhood resources relevant to SDoH that were highly localized and specific to their communities. In addition, multiple stakeholders were involved in conducting SDoH screenings and referrals, including clinicians, system navigators such as case workers, and community-based organizations. Yet, the information flow between these stakeholders and patients lacked systematization, and the prioritization of social needs by patients and clinicians was misaligned, as represented by qualitative themes as well as quantitative differences in resource category distribution analysis (p < 0.001). Our results shed light upon opportunities for strengthening social care delivery in safety-net healthcare settings by improving patient engagement, clinic workflow, EHR engagement, and resource dissemination.

In the wake of the racial injustices laid bare in 2020, on top of centuries of systemic racism, it is clear we need actionable strategies to fundamentally restructure health care systems to achieve racial/ethnic health equity. This paper outlines the pillars of a health equity framework from the Institute for Healthcare Improvement, overlaying a concrete example of telemedicine equity. Telemedicine is a particularly relevant and important topic, given the growing evidence of disparities in uptake by racial/ethnic, linguistic, and socioeconomic groups in the United States during the COVID-19 pandemic, as well as the new standard of care that telemedicine represents post-pandemic. We present approaches for telemedicine equity across the domains of: (1) strategic priorities of a health care organization, (2) structures and processes to advance equity, (3) strategies to address multiple determinants of health, (4) elimination of institutional racism and oppression, and (5) meaningful partnerships with patients and communities., (© 2022 Annals of Family Medicine, Inc.)

Objective: Vulnerable populations face numerous barriers in managing chronic disease(s). As healthcare systems work toward integrating social risk factors into electronic health records and healthcare delivery, we need better understanding of the interrelated nature of social needs within patients' everyday lives to inform effective informatics interventions to advance health equity., Materials and Methods: We conducted in-depth interviews, participant-led neighborhood tours, and clinic visit observations involving 10 patients with diabetes in underserved San Francisco neighborhoods and 10 community leaders serving those neighborhoods. We coded health barriers and facilitators using a socioecological framework. We also linked these qualitative data with early persona development, focusing on patients' experiences in these communities and within the healthcare system, as a starting place for our future informatics design., Results: We identified social risk and protective factors across almost every socioecological domain and level-from physical disability to household context to neighborhood environment. We then detailed the complex interplay across domains and levels within two critical aspects of patients' lives: housing and food. Finally, from these data we generated 3 personas that capture the intersectional nature of these determinants., Conclusion: Drawing from different disciplines, our study provides a socioecological approach to understanding health promotion for patients with chronic disease in a safety-net healthcare system, using multiple methodologies. Future digital health research should center the lived experiences of marginalized patients to effectively design and implement informatics solutions for this audience., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Characteristics of the neighborhood built environment influence health and health behavior. Google Street View (GSV) images may facilitate measures of the neighborhood environment that are meaningful, practical, and adaptable to any geographic boundary. We used GSV images and computer vision to characterize neighborhood environments (green streets, visible utility wires, and dilapidated buildings) and examined cross-sectional associations with chronic health outcomes among patients from the University of California, San Francisco Health system with outpatient visits from 2015 to 2017. Logistic regression models were adjusted for patient age, sex, marital status, race/ethnicity, insurance status, English as preferred language, assignment of a primary care provider, and neighborhood socioeconomic status of the census tract in which the patient resided. Among 214,163 patients residing in California, those living in communities in the highest tertile of green streets had 16-29% lower prevalence of coronary artery disease, hypertension, and diabetes compared to those living in communities in the lowest tertile. Conversely, a higher presence of visible utility wires overhead was associated with 10-26% more coronary artery disease and hypertension, and a higher presence of dilapidated buildings was associated with 12-20% greater prevalence of coronary artery disease, hypertension, and diabetes. GSV images and computer vision models can be used to understand contextual factors influencing patient health outcomes and inform structural and place-based interventions to promote population health.

Introduction: Social determinants of health (SDoH) influence health outcomes and contribute to disparities in chronic disease in vulnerable populations. To inform health system strategies to address SDoH, we conducted a multi-stakeholder qualitative study to capture the multi-level influences on health for those living in socio-economically deprived contexts., Methods: Varied qualitative inquiry methods - in-depth interviews, participant-led neighborhood tours, and clinic visit observations - involving a total of 23 participants (10 patients with chronic illnesses in San Francisco neighborhoods with high chronic disease rates, 10 community leaders serving the same neighborhoods, and 3 providers from San Francisco's public health care delivery system). Qualitative analyses were guided by the Chronic Care Model (CCM)., Results: Several key themes emerged from this study. First, we enumerated a large array, neighborhood resources such as food pantries, parks/green spaces, and financial assistance services that interact with patients' self-management. Health service providers leveraged these resources to address patients' social needs but suggested a clear need for expanding this work. Second, analyses uncovered multiple essential mechanisms by which community-based organizations (CBOs) provided and navigated among many neighborhood health resources, including social support and culturally aligned knowledge. Finally, many examples of how structural issues such as institutional racism, transportation, and housing inequities are intertwined with health and social service delivery were elucidated., Conclusion: The results contribute new evidence toward the community domain of the CCM. Health care systems must intentionally partner with CBOs to address SDoH and improve community resources for chronic care management, and directly address structural issues to make progress., Competing Interests: Conflict of interest: None., (© Copyright 2021 by the American Board of Family Medicine.)

Objectives: We sought to determine the prevalence of phosphodiesterase type 5 inhibitor (PDE-5) mediated drug-drug interactions (DDIs) in males with HIV infection receiving antiretroviral therapy (ART) and identify factors associated with PDE-5-mediated DDIs., Methods: Male US Military HIV Natural History Study participants diagnosed with erectile dysfunction (ED) and having a PDE-5 inhibitor and potentially-interacting ART co-dispensed within 30 days were included. DDIs were defined according to criteria found in published guidelines and drug information resources. The primary outcome of interest was overall PDE-5 inhibitor-mediated DDI prevalence and episode duration. A secondary logistic regression analysis was performed on those with and without DDIs to identify factors associated with initial DDI episode., Results: A total of 235 male participants with ED met inclusion criteria. The majority were White (50.6%) or African American (40.4%). Median age at medication co-dispensing (45 years), duration of HIV infection (14 years), and duration of ED (1 year) did not differ between the two groups (p>0.05 for all). PDE-5 inhibitors included sildenafil (n = 124), vardenafil (n = 99), and tadalafil (n = 14). ART regimens included RTV-boosted protease inhibitors (PIs) atazanavir (n = 83) or darunavir (n = 34), and COBI-boosted elvitegravir (n = 43). Potential DDIs occurred in 181 (77.0%) participants, of whom 122 (67.4%) had multiple DDI episodes. The median DDI duration was 8 (IQR 1-12) months. In multivariate analyses, non-statistically significant higher odds of DDIs were observed with RTV-boosted PIs or PI-based ART (OR 2.13, 95% CI 0.85-5.37) and in those with a diagnosis of major depressive disorder (OR 1.74, 95% CI 0.83-3.64)., Conclusions: PDE-5-mediated DDIs were observed in the majority of males with HIV infection on RTV- or COBI-boosted ART in our cohort. This study highlights the importance of assessing for DDIs among individuals on ART, especially those on boosted regimens., Competing Interests: The authors have declared that no competing interests exist.

Screen-printing provides an economically attractive means for making Ag electrical contacts to Si solar cells, but the use of Ag substantiates a significant manufacturing cost, and the glass frit used in the paste to enable contact formation contains Pb. To achieve optimal electrical performance and to develop pastes with alternative, abundant and non-toxic materials, a better understanding the contact formation process during firing is required. Here, we use in situ X-ray diffraction during firing to reveal the reaction sequence. The findings suggest that between 500 and 650 °C PbO in the frit etches the SiNx antireflective-coating on the solar cell, exposing the Si surface. Then, above 650 °C, Ag(+) dissolves into the molten glass frit - key for enabling deposition of metallic Ag on the emitter surface and precipitation of Ag nanocrystals within the glass. Ultimately, this work clarifies contact formation mechanisms and suggests approaches for development of inexpensive, nontoxic solar cell contacting pastes.

Rapid thermal processing (RTP) is widely used for processing a variety of materials, including electronics and photovoltaics. Presently, optimization of RTP is done primarily based on ex-situ studies. As a consequence, the precise reaction pathways and phase progression during the RTP remain unclear. More awareness of the reaction pathways would better enable process optimization and foster increased adoption of RTP, which offers numerous advantages for synthesis of a broad range of materials systems. To achieve this, we have designed and developed a RTP instrument that enables real-time collection of X-ray diffraction data with intervals as short as 100 ms, while heating with ramp rates up to 100 °Cs(-1), and with a maximum operating temperature of 1200 °C. The system is portable and can be installed on a synchrotron beamline. The unique capabilities of this instrument are demonstrated with in-situ characterization of a Bi2O3-SiO2 glass frit obtained during heating with ramp rates 5 °C s(-1) and 100 °C s(-1), revealing numerous phase changes.

Background: General anesthesia (GA) for acute stroke interventions may be associated with inferior functional outcomes. Our goal was to identify physiologic parameters that mediate this association., Methods: Consecutive patients treated at our institution between August 2007 and December 2010 were identified from a prospective database. Clinical data were then extracted by retrospective chart review. Variables significantly associated with outcome in univariate analysis were also examined in multivariate analysis, controlling for well-established prespecified predictors of functional outcome., Results: Of the 106 patients identified, 20 were excluded (17 due to the absence of 90-day mRS and 3 due to insufficient anesthetic records). Blood pressure (BP) decreased significantly after induction of GA, but there was no association between BP and outcome. End tidal carbon dioxide values (ETCO2) at 60 and 90 min, however, were significantly associated with outcomes in both univariate and multivariate analyses. Mean ETCO2 in patients with favorable outcomes (modified Rankin Scale (mRS) 0-3) was higher than in those with unfavorable outcomes (mRS 4-6): 35.2 mmHg versus 32.2 (p = 0.03) at 60 min and 34.9 versus 31.9 (p = 0.04) at 90 min. The adjusted odds ratios for poor outcomes for each 1 mmHg decrease in ETCO2 were the same: 0.76 (95 % CI 0.65-0.92; p = 0.004) at 60 min and 0.76 (95 % CI 0.61-0.93; p = 0.01) at 90 min., Conclusions: While BP decreased significantly in patients undergoing GA for acute stroke intervention, it did not correlate with patient outcome. Decreases in ETCO2 at 30 and 60 min, however, were associated with 90-day mRS.

Background and Purpose: Treatment of patients with ischemic stroke after endovascular treatment requires in-depth knowledge of complications. The goal of this study was to make endovascular treatment for acute ischemic stroke safer through an in-depth review of the major periprocedural complications observed in the Solitaire FR With Intention for Thrombectomy (SWIFT) trial., Materials and Methods: The SWIFT data base was searched for major peri-procedural complications defined as symptomatic intracranial hemorrhage within 36 hours, SAH, air emboli, vessel dissection, major groin complications, and emboli to new vascular territories., Results: Major peri-procedural complications occurred in 18 of 144 patients (12.5%) as follows: symptomatic intracranial hemorrhage, 4.9%; air emboli, 1.4%; vessel dissection, 4.2%; major groin complications, 2.8%; and emboli to new vascular territories, 0.7%. Rates of symptomatic intracranial bleeding by subtype were PH1, 0.7%; PH2, 0.7% (PH1 indicates hematoma within ischemic field with some mild space-occupying effect but involving ≤ 30% of the infarcted area; PH2, hematoma within ischemic field with space-occupying effect involving >30% of the infarcted area); intracranial hemorrhage remote from ischemic zone, 0%; intraventricular hemorrhage, 0.7%; and SAH, 3.5%. We did not observe any statistically significant associations of peri-procedural complications with age; type of treatment center; duration of stroke symptoms; NIHSS score, IV thrombolytics, atrial fibrillation, site of vessel occlusion; rescue therapy administered after endovascular treatment; or device. Comparing the Merci with the Solitaire FR retrieval device, we observed symptomatic cerebral hemorrhage (10.9% versus 1.1%; P = .013); symptomatic SAH (7.3% versus 1.1%; P = .07), air emboli (1.8% versus 1.1%; P = 1.0), emboli to new vascular territories (1.8% versus 0%; P = .38), vessel dissection (1.8% versus 4.5%; P = .65), and major groin complications (3.6% versus 7.9%; P = .48). Angiographic vasospasm was common but without clinical sequelae., Conclusions: Understanding of procedural complications is important for treatment of patients with stroke after endovascular treatment. We observed fewer endovascular complications with the Solitaire FR device treatment compared with Merci device treatment, particularly symptomatic cerebral hemorrhage.

Background: Due to anatomic features, including wide necks and incorporation of important branches, endovascular coiling of middle cerebral artery (MCA) aneurysms has proved challenging. Stent assisted embolization may increase the likelihood of successful treatment., Methods: Consecutive patients undergoing stent assisted coil embolization utilizing the Neuroform stent from 2004 to 2009 were identified by hospital billing records. Procedural and clinical information-including procedure related mortality and morbidity and long term outcomes-were then obtained by retrospective chart review., Results: Treatment was successful in 22/23 (96%) patients. Median age was 61 years and 16/22 (73%) were women. Aneurysm size was: <5 mm in 5/22 (23%); 5-9 mm in 14/22 (64%); and ≥10 mm in 3/22 (14%) patients. There were four periprocedural complications (including one stroke and one intraprocedural rupture), none associated with neurological dysfunction. Angiographic follow-up was available in 18/22 (82%) and clinical follow-up in 19/22 (86%) patients, both at a median of 1 year (mean 1.2 years) after coiling. Aneurysm occlusion was complete in 12/18 (67%), a neck remnant was present in 3/18 (17%) and persistent aneurysmal filling was present in 3/18 (17%) patients, requiring retreatment in 1/18 (6%) patient. In-stent stenosis of 50%, which was asymptomatic, occurred in 1/18 (6%) patient. No subarachnoid hemorrhages and no ischemic events related to the procedure were observed during follow-up., Conclusion: In this small series, the technical success rate was 96%, there were no transient or permanent neurological complications and complete aneurysmal occlusion was achieved in two-thirds of treated aneurysms on follow-up angiography. These results suggest that in appropriately selected patients, stent assisted coil embolization of MCA aneurysms can be performed with a high degree of safety and acceptable durability.

Background: Lumboperitoneal shunt (LPS), ventriculoperitoneal shunt (VPS) and optic nerve sheath fenestration (ONSF) are accepted surgical therapies for medically refractory idiopathic intracranial hypertension (IIH). In the subset of patients with IIH and venous sinus stenosis, dural venous sinus stenting has emerged as an alternative surgical approach., Methods: All cases of dural stents for IIH at our institution were retrospectively reviewed. Eligibility criteria included medically refractory IIH with documented papilledema and dural venous sinus stenosis of the dominant venous outflow system (gradient ≥10 mm Hg)., Results: Fifteen cases (all women) of mean age 34 years were identified. All had failed medical therapy and six had failed surgical intervention. Technical success was achieved in all patients without major periprocedural complications. The mean preprocedural gradient across the venous stenosis was reduced from 24 mm Hg before the procedure to 4 mm Hg after the procedure. Headache resolved or improved in 10 patients. Papilledema resolved in all patients and visual acuity stabilized or improved in 14 patients. There were no instances of restenosis among the 14 patients with follow-up imaging., Conclusion: In this small case series, dural sinus stenting for IIH was performed safely with a high degree of technical success and with excellent clinical outcomes. These results suggest that angioplasty and stenting for the treatment of medically refractory IIH in patients with dural sinus stenosis warrants further investigation as an alternative to LPS, VPS and ONSF.

Arterial dissections account for 2% of strokes in all age groups, and up to 25% in patients aged 45 years or younger. The safety of endovascular intervention in this patient population is not well characterized. We identified all patients in the Merci registry - a prospective, multi-center post-market database enrolling patients treated with the Merci Retriever thrombectomy device - with arterial dissection as the most likely stroke etiology. Stroke presentation and procedural details were obtained prospectively; data regarding procedural complications, intracerebral hemorrhage (ICH), and the use of stenting of the dissected artery were obtained retrospectively. Of 980 patients in the registry, ten were identified with arterial dissection (8/10 ICA; 2/10 vertebrobasilar). The median age was 48 years with a baseline NIH stroke scale score of 16 and median time to treatment of 4.9 h. The procedure resulted in thrombolysis in cerebral ischemia (TICI) scores of 2a or better in eight out of ten and TICI 2b or better in six out of ten patients. Stenting of the dissection was performed in four of nine (44%). The single complication (1/9; 11%) - extension of a dissected carotid artery - was treated effectively with stenting. No symptomatic ICH or stroke in a previously unaffected territory occurred. A favorable functional outcome was observed in eight out of ten patients. Despite severe strokes on presentation, high rates of recanalization (8/10) and favorable functional outcomes (8/10) were observed. These results suggest that mechanical thrombectomy in patients with acute stroke resulting from arterial dissection is feasible, safe, and may be associated with favorable functional outcomes.

Background and Purpose: Although the combined end point of partial and complete recanalization is a well-established predictor of good outcome following acute stroke intervention, few investigations have evaluated the effect of the degree of recanalization. We hypothesized that greater degrees of recanalization would be associated with a higher likelihood of favorable functional outcomes., Materials and Methods: Data from MERCI and Multi MERCI-prospective single-arm trials of endovascular mechanical thrombectomy for acute stroke-were pooled. The TIMI score was used to define the degree of recanalization, and a favorable outcome was defined as an mRS score of 0-2 at 90 days., Results: A total of 305 patients were included. Age, stroke severity, and site of arterial occlusion did not differ among groups stratified by the TIMI score. The unadjusted OR for a favorable outcome increased significantly as the TIMI score increased from 0 to 1 (OR, 5.9; 95% CI, 1.7-20.0; P = .007) and from 2 to 3 (OR. 2.3; 95% CI, 1.2-4.5; P = .01) and the likelihood of death decreased significantly as the TIMI score increased from 2 to 3 (OR, 2.2; 95% CI, 1.1-4.3; P = .05). In multivariate analysis, each increase in TIMI grade increased the odds of a good outcome 2.6-fold (95% CI, 1.9-3.4, P < .0001)., Conclusions: Increases in the TIMI score were highly associated with improved outcomes. This finding not only provides additional evidence that restoration of blood flow improves clinical outcomes in ischemic stroke but also suggests that interventionalists should strive for complete revascularization when they provide endovascular treatment for acute ischemic stroke.

Background: Elevated levels of B-type natriuretic peptide (BNP) have been associated with cardiac dysfunction and adverse neurological outcomes after subarachnoid hemorrhage (SAH). We sought to determine whether elevated levels of BNP are independently associated with radiographic cerebral infarction after SAH., Methods: Plasma BNP levels were measured after admission, a mean of 5.5 ± 3.0 days after SAH onset. Cerebral infarction was determined by retrospective review of computerized tomography (CT) scans. Cerebral vasospasm was confirmed by the presence of vascular narrowing on cerebral angiogram. The association between BNP and cerebral infarction was quantified using multivariable logistic regression and reverse stepwise elimination of clinical covariates. A stratified analysis was performed to quantify the association between BNP levels and infarction in patients with and without angiographic vasospasm., Results: BNP levels were measured from 119 subjects. The median BNP level was 105 pg/ml (interquartile range 37-275 pg/ml). In our multivariable model, the top quartile of BNP levels (≥ 276 pg/ml) were associated with an increased odds of cerebral infarction (OR 4.2, P = 0.009). The stratified analysis showed that the association between BNP and infarction was strongest in patients without angiographic vasospasm (OR 7.8, P = 0.006)., Conclusions: Elevated levels of BNP are strongly and independently associated with cerebral infarction, and the association is most pronounced in patients without angiographic vasospasm. These results provide further evidence that other mechanisms can contribute to infarction, and BNP may be a useful biomarker in detecting patients at risk for adverse outcomes without large vessel vasospasm.

Background: Randomized clinical trials supporting the use of intra-arterial administration of thrombolytics (IAT) for the treatment of stroke due to middle cerebral artery (MCA) occlusion have been positive on some, but not all, endpoints. A meta-analysis was performed to estimate with more precision the effect of IAT on several key clinical endpoints., Methods: All randomized trials of IAT in the treatment of MCA stroke were identified by PUBMED search and by hand search of potentially relevant references. Trial methodologies were assessed for compatibility in study protocols and statistical analysis. A meta-analysis was performed evaluating the effect of IAT on functional outcome at 90 days and symptomatic intracranial hemorrhage (SICH) within 24 h., Results: Three trials met the criteria for the meta-analysis. IAT treated patients were significantly more likely to have a modified Rankin scale (mRS) ≤ 1 (31% vs 20%, OR 2.0, 95% CI 1.2 to 3.4, p=0.01); mRS ≤ 2 (43% vs 31%, OR 1.9, 95% CI 1.2 to 3.0, p=0.01); and NIH Stroke Scale score 0 or 1 (23% vs 12%, OR 2.4, 95% CI 1.3 to 4.4, p=0.007) at the 90 day follow-up. There was no effect on mortality at 90 days (20% vs 19%, OR 0.84, 95% CI 0.5 to 1.5). The risk of SICH was significantly increased in the active treatment arms (11% vs 2%, OR 4.6, 95% CI 1.3 to 16, p=0.02)., Conclusions: Our meta-analysis demonstrates that all standard functional endpoints for stroke trials were substantially improved in the active treatment arms. Despite an increased risk of SICH, there was no effect on mortality. These results support endovascular treatment of acute ischemic stroke due to MCA occlusion with intra-arterial thrombolytics.

The use of bare metal stents (BMS) to prevent recurrent stroke due to stenosis of the cerebral vasculature is associated with high rates of restenosis. Drug-eluting stents (DES) may decrease this risk. We evaluated the performance of DES in a cohort of patients treated at our institution.Consecutive patients treated with DES were identified by a case log and billing records; data regarding procedural details, clinical outcome and angiographic follow-up was obtained by retrospective chart review.Twenty-six patients (27 vessels; 14 vertebral origin (VO); 13 intracranial) were treated. Stenosis was reduced from mean 81% to 8% at the VO and 80% to 2% intracranially. No strokes occurred in the first 24 hours after stenting or at any time point in the VO group during a mean follow-up period of nine months. Among patients with intracranial stents, stroke with permanent disability occurred within 30 days in 1/12 (8%) and after 30 days in 1/11 (9%) with clinical follow-up (mean follow-up, 14 months). Follow-up catheter angiography was obtained in 14/14 (100%) in the VO group at mean eight months and in 8/11 surviving patients (73%) at a mean of ten months after stenting in the intracranial group. The restenosis rate was 21% at the VO (3/14) and 38% (3/8) for intracranial stents. Restenosis at the VO was less frequent than might have been expected from reports utilizing BMS, however, overall restenosis rates appeared higher than previously reported for patients with intracranial DES and comparable with restenosis rates for intracranial BMS.

Background: Levodopa-responsive Parkinsonism is a rare complication of subarachnoid hemorrhage and no cases have been reported to occur in the absence of hydrocephalus., Methods: Case report., Results: We describe a 42-year-old woman who developed progressive severe Parkinsonism in the second week after aneurysmal subarachnoid hemorrhage. No hydrocephalus was present. Neuroimaging revealed striking abnormalities of the midbrain in the region of the substantia nigra. She was ultimately treated with high dose levodopa/carbidopa with a dramatic response., Conclusions: This case suggests that Parkinsonism may occur as a delayed complication of subarachnoid hemorrhage, and that in these patients, a trial of levodopa-carbidopa may be warranted.

Background and Purpose: Devices to close a femoral arteriotomy are frequently used after catheterization for interventional radiology and cardiac procedures to decrease the time to hemostasis and ambulation and, potentially, to decrease local complications. The Mynx vascular closure device uses a sealant designed to occlude the access tract, resulting in hemostasis., Materials and Methods: We retrospectively reviewed all cases in which the Mynx device was used and for which follow-up angiography was available. A total of 146 devices were deployed in 135 patients. A follow-up vascular study visualizing the femoral artery was performed in 26 patients (27 studies)., Results: There were 5 (5/27, 18%) cases of intravascular Mynx sealant on follow-up vascular imaging. Three pseudoaneurysms (3/27, 11%) were identified., Conclusions: In this small study, intravascular sealant and pseudoaneurysms were found frequently after femoral arterial closure with the Mynx vascular closure device.

Venous thrombo-embolism (VTE) is frequently encountered in critically ill neurological and neurosurgical patients admitted to intensive care units. This patient population includes those with brain neoplasm, intracranial hemorrhage, ischemic stroke, subarachnoid hemorrhage, pre- and post-operative patients undergoing neurosurgical procedures and those with traumatic brain injury, and acute spinal cord injury (SCI). There is a wide variability in clinical practice for thromboprophylaxis in these patients, in part due to paucity of data based on randomized clinical trials. Here, we review the current literature on the incidence of VTE in the critically ill neurological and neurosurgical patients as well as appraise available data to support particular practice paradigms for specific subsets of these patients. Data synthesis was conducted via search of Medline, Cochrane databases, and manual review of article bibliographies. Critically ill neurological and neurosurgical patients have higher susceptibility to VTE. Intermittent compression devices with or without anti-thrombotics is generally the method of choice for thromboprophylaxis. Low molecular weight heparin is the method of choice in certain patient subgroups such as those with SCI and ischemic stroke. Inferior vena cava filters may play a role in thromboprophylaxis in selected cases. Without clear guidelines that can be universally applied to this diverse group of patients, prophylaxis for VTE should be tailored to the individual patient with cautious assessment of benefits versus risks. There is a need for higher level evidence to guide VTE prophylaxis in certain subgroups of this patient population.

Acute ischemic stroke is the leading cause of severe disability and the third leading cause of death in the USA. Intravenous tissue plasminogen activator (IV tPA) remains the most widely advocated treatment, but this therapy is limited by a narrow time window (<4.5 h after stroke onset), exclusion of patients with coagulopathy and recanalization rates of less than 50%. As a result, only 5% of acute stroke patients are treated with IV tPA. Endovascular mechanical thrombectomy may be employed, either as a standalone therapy or as an adjunct to IV tPA, and has several potential advantages, including a wider time window (up to 8 h), the capacity for use in coagulopathic patients and higher recanalization rates (up to 82%). Nonetheless, mechanical thrombectomy has engendered controversy because no randomized trials have yet been performed to support its use. In this article, we review the clinical applications of mechanical thrombectomy for the treatment of acute ischemic stroke. Ultimately, the results of ongoing trials are necessary to delineate the patient populations most likely to benefit from this therapy.

Intracranial stenosis accounts for 8-10% of all ischemic strokes in North America, a frequency slightly less than that of extracranial carotid stenosis. Among patients presenting with transient ischemic attack or stroke due to intracranial stenosis, the risk of recurrent stroke in the first year after initial symptoms is about 14%. Those with high-risk features (recent stroke and severe stenosis) have up to a 23% rate of recurrent stroke in the year after their initial event. Angioplasty with stenting has emerged as a potential treatment strategy, particularly in high-risk patients, although evidence is currently limited to uncontrolled prospective trials and retrospective case series. In this article, we critically review the clinical results supporting the use of stenting and highlight some key considerations in the application of this technology, including patient selection, procedural management, technical issues, and risk factors for complications and in-stent restenosis.

Background: Despite recent advances, the clinical features of cerebral venous thrombosis (CVT) remain incompletely characterized. To our knowledge, no case series have been reported from North American centers with detailed long-term outcome data, and few studies have evaluated recanalization rates., Methods: All cases of CVT at a single tertiary care hospital between 1995 and 2004 were retrospectively reviewed. Follow-up information was obtained from direct patient interviews., Results: Follow-up data were available for 58 of 61 CVT patients (median 50 months). Average age was 40, and 66% were women. Headache and focal neurological deficits were noted in 82% and 72%, respectively. Intracranial hemorrhage was seen in 44%. Hypercoagulable risk factors were identified in 84%. Anticoagulation was initiated acutely in 84%, including in all patients with intraparenchymal hemorrhage (IPH). The percentage of patients with a modified Rankin Score (mRS) of 0 to 2 at admission, hospital discharge and last follow-up were 41%, 67%, 90%, respectively; the rate of favorable long-term outcome did not differ significantly between patients with and without IPH. In the subset of 21 patients with follow-up imaging available for direct review, 90% had partial or complete recanalization., Conclusions: The demographics, clinical presentation, imaging findings, and risk factors in this large North American cohort of CVT patients strongly support the observations of previous European case series. In addition, the favorable long-term outcome and recanalization rates observed lend further support to the safety and efficacy of acute heparin therapy for the treatment of symptomatic CVT (irrespective of the presence of ICH).

Background: The efficacy of intravenous thrombolytics in acute stroke is limited by low rates of recanalization of occluded arteries. Treatment with intravenous thrombolytics followed by mechanical thrombectomy is a novel approach that may increase recanalization rates without compromising time to initiation of treatment., Objectives: To report our experience with 2 patients who received this combination therapy and outline plans for a prospective pilot study., Design and Setting: Case studies at a university hospital., Interventions: Patients treated with intravenous thrombolytics within 3 hours of symptom onset subsequently underwent computed tomographic angiography. If an occlusion of a proximal cerebral vessel was shown by a computed tomographic angiogram, mechanical thrombectomy was performed. Patients were observed for 1 month after treatment., Main Outcome Measures: National Institutes of Health Stroke Scale (NIHSS) score., Results: The computed tomographic angiography of 2 patients showed complete occlusion of the M1 branch of the middle cerebral artery following administration of intravenous thrombolytics. The NIHSS scores were 21 and 13. In both cases, blood flow through the occluded artery was restored with mechanical thrombectomy and dramatic neurologic improvement occurred. There were no complications. The NIHSS scores were 0 and 2 at 1-month follow-up., Conclusion: Treatment with intravenous thrombolytics followed by mechanical thrombectomy may improve outcomes in acute stroke patients and a pilot safety trial is warranted.

Recently discovered sexual dimorphism within developing brain structures such as the amygdala and hippocampus suggests that biological factors may account for many of the sex differences in stress reactivity. In this study, we have relied on studies of naturally occurring anomalous processes, such as congenital adrenal hyperplasia (CAH) and Klinefelter's syndrome (XXY), to observe the effects of hormones and sex chromosomes on brain structures thought to influence an individual's vulnerability to stress. Brain magnetic resonance imaging (MRI) scans were obtained both from 16 boys with classic CAH and 34 age- and sex-matched controls and from 20 XXY children and 40 age-matched controls. Smaller amygdala volumes were observed in boys with CAH than in matched controls, and in XXY patients than in matched controls. XXY patients were also found to have smaller hippocampus volumes when compared with matched controls. Acknowledging that hormone and sex chromosome effects upon the developing human brain are widespread and complex, it is difficult to conclude, with any certainty, the etiology of the differences found in this study. Future studies that examine longitudinal data and/or other diagnostic groups, however, may help to better elucidate specific hormone and sex chromosome effects upon stress-related structures in the brain.

Children with classic congenital adrenal hyperplasia (CAH) have multiple endocrine imbalances, including prenatal glucocorticoid and adrenomedullary deficiency and androgen excess, with possible postnatal iatrogenic glucocorticoid excess, hyperandrogenism, and adrenomedullary hypofunction. Prenatal masculinization of the brain has been suggested in girls with classic CAH. Hormones of the hypothalamic-pituitary-adrenal axis and sex hormones interact with extrahypothalamic regulatory centers of the brain, including the amygdala and hippocampus. The amygdala is important in the processing of emotion and generation of fear, whereas the hippocampus plays an important role in memory. Chronic hypercortisolemia has been shown to be associated with hippocampal damage, while glucocorticoids and corticotropin-releasing factor play a major role in the regulation of amygdala function. We performed magnetic resonance imaging of the brain on 27 children with classic CAH and 47 sex- and age-matched controls. Volumes of the cerebrum, ventricles, temporal lobe, amygdala, and hippocampus were quantified. Females with CAH did not have brains with male-specific characteristics. In contrast, a significant decrease in amygdala volume was observed in both males and females with CAH (males, P = 0.01; females, P = 0.002). Iatrogenic effects on the hippocampus due to glucocorticoid therapy were not observed in children with CAH. These results suggest that prenatal glucocorticoid deficiency with resulting alterations in hypothalamic-pituitary-adrenal axis regulation, sex steroid excess, or some combination of these preferentially affect the growth and development of the amygdala, a structure with major functional implications that warrant further exploration.

OXONE over silica gel or, in some cases, alumina has been found to oxidize the primary and secondary amines 3 selectively to the corresponding hydroxylamines 4, in either the presence or absence of a solvent. Treatment of Boc-protected L-lysine (6) under the latter conditions afforded hydroxylamine 7 in excellent yield. The trialkylamine 1a and pyridine (1b), in which selectivity is not an issue, were readily oxidized to the corresponding oxides 2 by OXONE over silica gel or alumina, as well as by (CH(3))(3)COOH over silica gel. Solvent-free oxidation assisted by microwave irradiation was more forcing, while still affording the hydroxylamines 4 selectively, and is the synthetic method of choice. The mechanistic aspects of these reactions are discussed.

The overall affinity of the bacteriophage lambda Cro repressor for its operator DNA site is limited by dimer dissociation at submicromolar concentrations. Since Cro dimer-operator complexes form at nanomolar concentrations of Cro subunits where free dimers are rare, these dimers must bind with compensating high affinities. Previous studies of the covalent dimer Cro V55C suggest little change in DNA binding affinity even though the dimeric species is quantitatively populated; this is an apparent contradiction to the expectation of high intrinsic dimer-DNA affinity. In contrast to the disulfide linkage at the center of the dimer interface in Cro V55C, polypeptide linkers that join the two subunits allow single-chain Cro repressors to bind operator DNA with picomolar affinities. A series of five single-chain Cro repressors have been expressed from fused tandem cro genes. Each contains a peptide linker of 8-16 hydrophilic residues that connects the C-terminus of one subunit to the N-terminus of the next. All bind to operator DNA with at least 100-fold higher affinity than Cro V55C. Proteins containing the longest and shortest linkers have been purified and characterized in detail. Both exhibit similar CD spectra to wild-type Cro and enhanced thermal stability. Sedimentation equilibrium experiments show that single-chain Cro repressors do not associate at concentrations up to 30 microM. The rate of dissociation of Cro-DNA complexes is almost unchanged by covalent linkage. Biophysical characterization of Cro variants such as these, where DNA binding is uncoupled from subunit assembly, is necessary for a quantitative understanding of the structural and energetic determinants of DNA recognition in this simple model system.