Impact of maternal diabetes exposure on soluble adhesion molecules in the offspring.

BACKGROUND AND AIMS: Soluble adhesion molecules are associated with cardiovascular disease and increased in individuals with diabetes. This study assesses the impact of diabetes exposure in utero on the abundance of circulating adhesion molecules in cord serum and soluble adhesion molecules released from human umbilical vein endothelial cells (HUVEC) exposed to high glucose concentrations. METHODS AND RESULTS: Women with and without diabetes were recruited. DM was diagnosed based on the American Diabetes Association criteria. Primary cultures of HUVEC were cultured in 5 mM and 25 mM glucose with 25 mM mannitol osmotic control. The soluble adhesion molecules, intracellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM) and E-selectin were measured by ELISA in the cord blood serum and conditioned HUVEC media. The mothers with DM were older with higher BMI (p = 0.027 and 0.008, respectively). In a fully adjusted model, VCAM was significantly increased in the cord serum of infants born to mothers with diabetes (p = 0.046), but ICAM and E-selectin were not different. ICAM was also significantly correlated with maternal HbA1c (r2 = 0.16, p = 0.004) and cord serum non-esterified fatty acids (r2 = 0.08, p = 0.013). From the HUVEC media, the abundance of adhesion molecules was not different based on DM or high glucose exposure; however, VCAM abundance in the HUVEC supernatant was significantly correlated with ICAM (r2 = 0.27, p = 0.010) and cord serum c-peptide (R2 = 0.19, p = 0.043). CONCLUSIONS: Alterations in soluble adhesion molecule abundance in infants exposed to the diabetic milieu of pregnancy may reflect early alterations in vascular function predicting future cardiovascular disease.

A DELPHI consensus statement on antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of mechanical thrombectomy.

PURPOSE: There is little data and lack of consensus regarding antiplatelet management for intracranial stenting due to underlying intracranial atherosclerosis in the setting of endovascular treatment (EVT). In this DELPHI study, we aimed to assess whether consensus on antiplatelet management in this situation among experienced experts can be achieved, and what this consensus would be. METHODS: We used a modified DELPHI approach to address unanswered questions in antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of EVT. An expert-panel (19 neurointerventionalists from 8 countries) answered structured, anonymized on-line questionnaires with iterative feedback-loops. Panel-consensus was defined as agreement ≥ 70% for binary closed-ended questions/≥ 50% for closed-ended questions with > 2 response options. RESULTS: Panel members answered a total of 5 survey rounds. They acknowledged that there is insufficient data for evidence-based recommendations in many aspects of antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of EVT. They believed that antiplatelet management should follow a standardized regimen, irrespective of imaging findings and reperfusion quality. There was no consensus on the timing of antiplatelet-therapy initiation. Aspirin was the preferred antiplatelet agent for the peri-procedural period, and oral Aspirin in combination with a P2Y12 inhibitor was the favored postprocedural regimen. CONCLUSION: Data on antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of EVT are limited. Panel-members in this study achieved consensus on postprocedural antiplatelet management but did not agree upon a preprocedural and intraprocedural antiplatelet regimen. Further prospective studies to optimize antiplatelet regimens are needed.

Comparison of Three Risk Scores to Predict Outcomes of Severe Lower Gastrointestinal Bleeding.

BACKGROUND AND AIMS: Improved medical decisions by using a score at the initial patient triage level may lead to improvements in patient management, outcomes, and resource utilization. There is no validated score for management of lower gastrointestinal bleeding (LGIB) unlike for upper gastrointestinal bleeding. The aim of our study was to compare the accuracies of 3 different prognostic scores [Center for Ulcer Research and Education Hemostasis prognosis score, Charlson index, and American Society of Anesthesiologists (ASA) score] for the prediction of 30-day rebleeding, surgery, and death in severe LGIB. METHODS: Data on consecutive patients hospitalized with severe gastrointestinal bleeding from January 2006 to October 2011 in our 2 tertiary academic referral centers were prospectively collected. Sensitivities, specificities, accuracies, and area under the receiver operator characteristic curve were computed for 3 scores for predictions of rebleeding, surgery, and mortality at 30 days. RESULTS: Two hundred thirty-five consecutive patients with LGIB were included between 2006 and 2011. Twenty-three percent of patients rebled, 6% had surgery, and 7.7% of patients died. The accuracies of each score never reached 70% for predicting rebleeding or surgery in either. The ASA score had a highest accuracy for predicting mortality within 30 days (83.5%), whereas the Center for Ulcer Research and Education Hemostasis prognosis score and the Charlson index both had accuracies <75% for the prediction of death within 30 days. CONCLUSIONS: ASA score could be useful to predict death within 30 days. However, a new score is still warranted to predict all 30 days outcomes (rebleeding, surgery, and death) in LGIB.

Formation and function of acute stroke-ready hospitals within a stroke system of care recommendations from the brain attack coalition.

BACKGROUND AND PURPOSE: Many patients with an acute stroke live in areas without ready access to a Primary or Comprehensive Stroke Center. The formation of care facilities that meet the needs of these patients might improve their care and outcomes and guide them and emergency responders to such centers within a stroke system of care. METHODS: The Brain Attack Coalition conducted an electronic search of the English medical literature from January 2000 to December 2012 to identify care elements and processes shown to be beneficial for acute stroke care. We used evidence grading and consensus paradigms to synthesize recommendations for Acute Stroke-Ready Hospitals (ASRHs). RESULTS: Several key elements for an ASRH were identified, including acute stroke teams, written care protocols, involvement of emergency medical services and emergency department, and rapid laboratory and neuroimaging testing. Unique aspects include the use of telemedicine, hospital transfer protocols, and drip and ship therapies. Emergent therapies include the use of intravenous tissue-type plasminogen activator and the reversal of coagulopathies. Although many of the care elements are similar to those of a Primary Stroke Center, compliance rates of ≥67% are suggested in recognition of the staffing, logistical, and financial challenges faced by rural facilities. CONCLUSIONS: ASRHs will form the foundation for acute stroke care in many settings. Recommended elements of an ASRH build on those proven to improve care and outcomes at Primary Stroke Centers. The ASRH will be a key component for patient care within an evolving stroke system of care.

Championing person-first language: a call to psychiatric mental health nurses.

At the heart of recovery-oriented psychiatric mental health care are the dignity and respect of each person and the ways in which helping professionals convey a person's uniqueness, strengths, abilities, and needs. "Person-first language" is a form of linguistic expression relying on words that reflect awareness, a sense of dignity, and positive attitudes about people with disabilities. As such, person-first language places emphasis on the person first rather than the disability (e.g., "person with schizophrenia" rather than "a schizophrenic"). This article champions the use of person-first language as a foundation for recovery-oriented practice and enhanced collaborative treatment environments that foster respect, human dignity, and hope.

Revised and updated recommendations for the establishment of primary stroke centers: a summary statement from the brain attack coalition.

BACKGROUND AND PURPOSE: The formation and certification of Primary Stroke Centers has progressed rapidly since the Brain Attack Coalition's original recommendations in 2000. The purpose of this article is to revise and update our recommendations for Primary Stroke Centers to reflect the latest data and experience. METHODS: We conducted a literature review using MEDLINE and PubMed from March 2000 to January 2011. The review focused on studies that were relevant for acute stroke diagnosis, treatment, and care. Original references as well as meta-analyses and other care guidelines were also reviewed and included if found to be valid and relevant. Levels of evidence were added to reflect current guideline development practices. RESULTS: Based on the literature review and experience at Primary Stroke Centers, the importance of some elements has been further strengthened, and several new areas have been added. These include (1) the importance of acute stroke teams; (2) the importance of Stroke Units with telemetry monitoring; (3) performance of brain imaging with MRI and diffusion-weighted sequences; (4) assessment of cerebral vasculature with MR angiography or CT angiography; (5) cardiac imaging; (6) early initiation of rehabilitation therapies; and (7) certification by an independent body, including a site visit and disease performance measures. CONCLUSIONS: Based on the evidence, several elements of Primary Stroke Centers are particularly important for improving the care of patients with an acute stroke. Additional elements focus on imaging of the brain, the cerebral vasculature, and the heart. These new elements may improve the care and outcomes for patients with stroke cared for at a Primary Stroke Center.

Telehealth stroke education for rural elderly Virginians.

OBJECTIVE: Stroke is a prevalent condition found in elderly, rural populations. However, stroke education, which can be effective in addressing the risks, is often difficult to provide in these remote regions. The objective of this study is to evaluate the effectiveness of delivering stroke education to elderly individuals through telehealth versus in-person stroke prevention education methods. MATERIALS AND METHODS: A quasi-experimental nonequivalent control group design was used in this study. A convenience sample of 11 elderly adults (36% men, 64% women) with a mean age of 70 was selected from an Appalachian Program for All Inclusive Care for the Elderly (day care) facility. Subjects completed preintervention surveys, received a 20-min group in-person or telehealth delivered education session, and then completed the postintervention surveys. RESULTS: Satisfaction with delivery method and post-education knowledge was equivalent between the two groups. Knowledge increased in both groups after the educational programs. Likelihood of reducing risk factors showed no differences pre-posttest. However, there were significant improvements in the pre-post likelihood scores of the telehealth group in contrast to the in-person group. CONCLUSIONS: This project provided a rural, high-risk population access to telehealth stroke education, thus enabling these individuals to receive education at a distance from experts in the field. The telehealth program was found to be equivalent to in-person stroke education in regards to satisfaction, knowledge, and likelihood of making changes to decrease vascular risk factors. The study demonstrated feasibility in providing effective stroke education through telehealth, thus suggesting an often overlooked route for providing patient education at a distance.

Role of metformin in epigenetic regulation of placental mitochondrial biogenesis in maternal diabetes.

Adverse maternal environments, such as diabetes and obesity, impair placental mitochondrial function, which affects fetal development and offspring long-term health. The underlying mechanisms and effective interventions to abrogate such effect remain unclear. Our previous studies demonstrated impaired mitochondrial biogenesis in male human placenta of diabetic mothers. In the present studies, epigenetic marks possibly related to mitochondrial biogenesis in placentae of women with diabetes (n = 23) and controls (n = 23) were analyzed. Effects of metformin were examined in human placental explants from a subgroup of diabetic women and in a mouse model of maternal high fat diet feeding. We found that maternal diabetes was associated with epigenetic regulation of mitochondrial biogenesis in human placenta in a fetal sex-dependent manner, including decreased histone acetylation (H3K27 acetylation) and increased promoter methylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). In male placenta, the levels of H3K27 acetylation and PGC-1α promoter methylation correlated significantly with the activity of AMP-activated protein kinase (AMPK). Metformin treatment on male diabetic placental explant activated AMPK and stimulated PGC-1α expression, concomitant with increased H3K27 acetylation and decreased PGC-1α promoter methylation. In vivo, we show that maternal metformin treatment along with maternal high fat diet significantly increased mouse placental abundance of PGC-1α expression and downstream mitochondrial transcription factor A (TFAM) and inhibited maternal high fat diet-impaired placental efficiency and glucose tolerance in offspring. Together, these findings suggest the capability of metformin to stimulate placental mitochondrial biogenesis and inhibit the aberrant epigenetic alterations occurring in maternal diabetes during pregnancy, conferring protective effects on offspring.

Performance and training standards for endovascular ischemic stroke treatment.

Stroke is the third-leading cause of death in the United States, Canada, Europe, and Japan. According to the American Heart Association and the American Stroke Association, 750,000 new strokes occur each year, resulting in 200,000 deaths (or 1 of every 16 deaths) per year in the United States alone. Endovascular therapy for patients with acute ischemic stroke is an area of intense investigation. The American Stroke Association has given a qualified endorsement of intra-arterial (IA) thrombolysis in selected patients. IA thrombolysis has been studied in 2 randomized trials and numerous case series. Although 2 devices have been granted FDA 3 approval with an indication for mechanical stroke thrombectomy, none of these devices has demonstrated efficacy in improving patient outcomes. This report defines what constitutes adequate training to perform neuroendovascular procedures in patients with acute ischemic stroke and identifies the performance standards that should be adopted to assess outcomes. These guidelines have been written and approved by multiple neuroscience societies that historically have been directly involved in the medical, surgical, and endovascular care of patients with acute stroke, including the Neurovascular Coalition and its participating societies: the Society of NeuroInterventional Surgery; American Academy of Neurology; American Association of Neurological Surgeons, Cerebrovascular Section; and Society of Vascular & Interventional Neurology.

Posterior circulation perforator aneurysms: a proposed management algorithm.

INTRODUCTION: Subarachnoid hemorrhage (SAH) from posterior circulation perforator aneurysms (PCPAs) is rare and its natural history is unknown. Diagnosis may be difficult, acute management is poorly defined, and long-term recurrent SAH rates and clinical outcome data are lacking. METHODS: We searched our institution's records for cases of PCPA rupture and analyzed patient demographics, Hunt and Hess (HH) grades, diagnostic imaging, management, and clinical outcomes. We conducted telephone interviews to calculate modified Rankin Scale (mRS) scores. RESULTS: We identified 9 patients (6 male, 3 female) with a ruptured PCPA who presented to the University of Virginia Health System (Charlottesville, VA, USA) between 2010 and 2016. Median and mean ages were 62 and 63 years, respectively. Median HH grade was 3. Seven of nine (78%) PCPAs were angiographically occult on initial imaging and median time to diagnosis was 5 days. Three conservatively managed patients had a mean mRS score of 0.67 (range 0-1) at mean follow-up of 35.3 months. Antifibrinolytic therapy was administered to all conservatively managed patients without thrombotic complication. Six patients receiving endovascular treatment had a mean mRS score of 2.67 (range 0-6) at mean follow-up of 49.2 months. No cases of recurrent SAH were seen in the study. CONCLUSIONS: The rarity of PCPA has precluded long-term clinical follow-up until now. Our experience suggests low recurrent SAH rates. Until further studies are performed, conservative management, possibly combined with antifibrinolytic therapy, may be a viable treatment with acceptable long-term outcome.

Subarachnoid hemorrhage and diffuse vasculopathy in an adult infected with HIV. Case report.

This 34-year-old man with a 10-year history of HIV infection presented with an acute onset of severe headache, fever, nausea, vomiting, and left-sided weakness. Computed tomography (CT) scanning demonstrated diffuse subarachnoid hemorrhage (SAH), and subsequent CT angiography revealed multiple large and giant intracranial aneurysms with diffuse vasculopathy. The patient's CD4-positive cell count was low, although he had been receiving combination antiretroviral therapy and his viral load was undetectable. The preponderance of the literature on HIV-infected patients with intracranial vascular involvement has concerned children in whom there is a high viral load. In such children, appropriate antiretroviral therapy may result in the complete resolution of these vascular abnormalities. In the present study, the authors report on the unique case of an HIV-infected adult patient who presented with SAH, diffuse intracranial vasculopathy, and multiple giant and fusiform aneurysms, despite having received adequate antiretroviral treatment and demonstrating an undetectable viral load. Intracranial vascular involvement in these patients may become increasingly common as the management of HIV infection continues to improve and afflicted patients survive for longer periods.

Transorbital Approach for Endovascular Occlusion of Carotid-Cavernous Fistulas: Technical Note and Review of the Literature.

Carotid-cavernous fistulas (CCFs) pose an anatomically and physiologically challenging problem for clinicians. The most common method of treatment for these lesions is transvenous endovascular embolization via the inferior petrosal sinus or the facial vein. When transvenous access is not possible, an alternate approach must be devised. We describe a case example with bilateral Barrow Type B CCFs, which were inaccessible using the traditional transvenous approach. Hence, a direct transorbital approach, performed under fluoroscopic guidance, was employed to successfully obliterate the CCF. At five months follow-up, the patient was recovering without complications. This case delineates the technical aspects of transorbital CCF embolization and demonstrates that this approach is a viable alternative to conventional transvenous methods for appropriately selected CCF cases. We supplement our case example and technical note with a literature review of this approach.

An overview of antithrombotics in ischemic stroke.

The use of antithrombotic medications is an important component of ischemic stroke treatment and prevention. This article reviews the evidence for best practices for antithrombotic use in stroke with focused discussion on the specific agents used to treat and prevent stroke.

Preoperative Embolization of Cerebral Arteriovenous Malformations with Silk Suture and Particles: Technical Considerations and Outcomes.

OBJECTIVE: Embolization of cerebral arteriovenous malformations (AVMs) is commonly performed prior to surgical resection in order to reduce intraoperative bleeding and improve the safety of resection. Although most modern embolization procedures utilize permanent embolic agents, silk suture and polyvinyl alcohol (PVA) particles may offer unique advantages for preoperative devascularization. The aims of this retrospective cohort study are to describe the technical considerations and determine the outcomes for preoperative silk suture and PVA particle embolization (SPE) of AVMs. MATERIALS AND METHODS: We performed a retrospective review of our AVM embolization database. AVM patients who underwent preoperative SPE and subsequent surgical resection were included for analysis. Baseline patient demographics, AVM characteristics, embolization and operative records, and post-treatment outcomes were reviewed. RESULTS: A total of 11 patients who underwent 12 preoperative SPE procedures were included for analysis. Five AVMs were ruptured (45%), and the median nidus volume was 3.0 cm3 (range: 1.3-42.9 cm3). The Spetzler-Martin grade was I-II in seven patients (64%) and III-IV in four patients (36%). The degree of nidal obliteration was less than 25% in two procedures (17%), 25-50% in one procedure (8%), 50-75% in eight procedures (67%), and greater than 75% in one procedure (8%). The rates of post-embolization AVM hemorrhage and mortality were 8% and 0%, respectively. The postoperative angiographic obliteration rate was 100%, and the modified Rankin Scale score improved or stable in 91% of patients (median follow-up duration 2 months). CONCLUSION: Preoperative AVM SPE affords a reasonable risk to benefit profile for appropriately selected patients.

Prevalence of dural venous sinus stenosis and hypoplasia in a generalized population.

BACKGROUND AND PURPOSE: While recent literature has described the prevalence of transverse sinus stenosis in patients with idiopathic intracranial hypertension, tinnitus, and refractory headaches, it is unclear what the prevalence is in the general population. This study evaluates the prevalence of venous sinus stenosis and hypoplasia in the general patient population. MATERIALS AND METHODS: 355 of 600 consecutive patients who underwent CT angiography of the head met the inclusion criteria. The diameters of the dural venous sinuses were recorded. Each study was evaluated by a neuroradiologist for the presence of stenoses. Univariate and multivariate statistical analyses were performed by a statistician. RESULTS: The prevalence of unilateral transverse sinus stenosis or hypoplasia in a sample of patients representing the general population was 33%, the prevalence of bilateral transverse sinus stenosis was 5%, and the prevalence of unilateral stenosis with contralateral hypoplasia was 1%. A multivariate analysis identified arachnoid granulations as a predictor of stenosis (p<0.001). Gender trended toward significance (p=0.094). Race was not a significant predictor of stenosis (p=0.745). CONCLUSIONS: The prevalence of bilateral transverse sinus stenosis in the general population is not trivial. These data may be used as a reference for understanding the mechanistic role of stenoses in idiopathic intracranial hypertension, tinnitus, and refractory headaches.

Endovascular treatment of ophthalmic artery aneurysms: ophthalmic artery patency following flow diversion versus coil embolization.

BACKGROUND AND PURPOSE: The Pipeline Embolization Device (PED) has been shown to effectively treat complex internal carotid artery aneurysms while maintaining patency of covered side branches. The purpose of this retrospective matched cohort study is to evaluate the effect of flow diversion on the patency of the ophthalmic artery when treating ophthalmic artery aneurysms. METHODS: A retrospective review of our prospectively collected institutional database identified 19 ophthalmic artery aneurysms treated with a PED. These were matched according to aneurysm diameter in a 1:2 fashion to ophthalmic artery aneurysms treated via coil embolization, although it is important to note that there was a statistically significance difference in the neck diameter between the two groups (p=0.045). Clinical and angiographic outcomes were recorded and analyzed. RESULTS: On follow-up angiography, decreased flow through the ophthalmic artery was observed in 26% of the PED cohort and 0% of the coil embolization cohort (p=0.003). No ophthalmologic complications were noted in either cohort. Complete occlusion at 12 months was more common following PED treatment than coil embolization (74% vs 47%; p=0.089), although lower than reported in previous trials. This may be due to inflow into the ophthalmic artery keeping the aneurysm patent. Retreatments were more common following coil embolization than PED (24% vs 11%), but this was not significant (p=0.304). Permanent morbidity rates were not significantly different between the PED (11%) and coil embolization (3%) cohorts (p=0.255). CONCLUSIONS: Our results suggest that ophthalmic artery aneurysms may be adequately and safely treated with either the PED or coil embolization. However, treatment with the PED carries a higher risk of impeding flow to the ophthalmic artery, although this did not result in clinical sequelae in the current study.