Current Advances in Endovascular Treatment of Intracranial Atherosclerotic Disease and Future Prospective.

OBJECTIVES/BACKGROUND: Medical therapy is the first line of treatment for intracranial atherosclerotic disease (ICAD). Percutaneous transluminal angioplasty and stenting (PTAS) are mainly considered for those patients with severe stenosis and recurrent events despite aggressive medical therapy. In this review, we discuss the application of PTAS as a treatment option for ICAD and its future prospect. MATERIALS AND METHODS: We did the literature review of the key articles and guidelines to elaborate on the role of PTAS in the management of ICAD based on the current data and expert opinion. We searched PubMed, Google Scholar, and Scopus up to August 2020, and included articles published only in the English language. RESULTS: Since the publication of the results from SAMMPRIS and VISSIT trials, stenting is no longer recommended for secondary stroke prevention in patients with symptomatic ICAD. However, recent clinical studies on intracranial stenting for a subgroup of ICAD patients have shown promising results, likely due to better patient selection and continued advancement of endovascular techniques. CONCLUSION: There exists a lack of consensus regarding the best endovascular treatment approach (e.g., angioplasty alone or balloon mounted stent vs. self-expanding stent with or without prior angioplasty) or management of in-stent restenosis. Another area of clinical controversy relates to the ideal use and duration of antiplatelet therapy.

IAT-TiMeS: Intra-Arterial Thrombectomy Transfer Metric Study in Texas.

OBJECTIVE: We aim to report intra-arterial thrombectomy transfer metrics for ischemic stroke patients that were transferred to hub hospitals for possible intra-arterial thrombectomy in multiple geographic regions throughout the state of Texas and to identify potential barriers and delays in the intra-arterial thrombectomy transfer process. METHOD: We prospectively collected data from 8 participating Texas comprehensive stroke/thrombectomy capable centers from 7 major regions in the State of Texas. We collected baseline clinical and imaging data related to the pre-transfer evaluation, transfer metrics, and post-transfer clinical and imaging data. RESULTS: A total of 103 acute ischemic stroke patients suspected/confirmed to have large vessel occlusions between December 2016 to May 2019 that were transferred to hubs as possible intra-arterial thrombectomy candidates were enrolled. A total of 56 (54%) patients were sent from the spoke to the hub via ground ambulance with 47 (46%) patients traveling via air ambulance. The median spoke arrival to hub arrival time was 174 min, median spoke arrival to departure from spoke was 131 min, and median travel time was 39 min. The spoke arrival time to transfer initiation was 68 min. CT-perfusion obtained at the spoke and earlier initiation of transfer were statistically associated with shorter transfer times. CONCLUSION: Transfer of intra-arterial thrombectomy patients in Texas may take over 4 h from spoke arrival to hub arrival. This time may be shortened by earlier transfer initiation and acceptance.

Intramolecular allosteric communication in dopamine D2 receptor revealed by evolutionary amino acid covariation.

The structural basis of allosteric signaling in G protein-coupled receptors (GPCRs) is important in guiding design of therapeutics and understanding phenotypic consequences of genetic variation. The Evolutionary Trace (ET) algorithm previously proved effective in redesigning receptors to mimic the ligand specificities of functionally distinct homologs. We now expand ET to consider mutual information, with validation in GPCR structure and dopamine D2 receptor (D2R) function. The new algorithm, called ET-MIp, identifies evolutionarily relevant patterns of amino acid covariations. The improved predictions of structural proximity and D2R mutagenesis demonstrate that ET-MIp predicts functional interactions between residue pairs, particularly potency and efficacy of activation by dopamine. Remarkably, although most of the residue pairs chosen for mutagenesis are neither in the binding pocket nor in contact with each other, many exhibited functional interactions, implying at-a-distance coupling. The functional interaction between the coupled pairs correlated best with the evolutionary coupling potential derived from dopamine receptor sequences rather than with broader sets of GPCR sequences. These data suggest that the allosteric communication responsible for dopamine responses is resolved by ET-MIp and best discerned within a short evolutionary distance. Most double mutants restored dopamine response to wild-type levels, also suggesting that tight regulation of the response to dopamine drove the coevolution and intramolecular communications between coupled residues. Our approach provides a general tool to identify evolutionary covariation patterns in small sets of close sequence homologs and to translate them into functional linkages between residues.

Comparative Outcomes of Respiratory Failure Associated with Common Neuromuscular Emergencies: Myasthenia Gravis versus Guillain-Barré Syndrome.

Background and objectives: Myasthenia gravis (MG) and Guillain-Barré Syndrome (GBS) are autoimmune neuromuscular disorders that may present as neuromuscular emergencies requiring mechanical ventilation and critical care. Comparative outcomes of these disease processes, once severe enough to require mechanical ventilation, are not known. In this study, we compared the patients requiring mechanical ventilation in terms of in-hospital complications, length of stay, disability, and mortality between these two disease entities at a national level. Materials and Methods: Mechanically ventilated patients with primary diagnosis of MG (n = 6684) and GBS (n = 5834) were identified through retrospective analysis of Nationwide Inpatient Sample (NIS) database for the years 2006 to 2014. Results: Even though mechanically ventilated MG patients were older (61.0 ± 19.1 versus 54.9 ± 20.1 years) and presented with more medical comorbidities, they had lower disease severity on admission, as well as lower in-hospital complications sepsis, pneumonia, and urinary tract infections as compared with GBS patients. In the multivariate analysis, after adjusting for confounders including treatment, GBS patients had significantly higher disability (odds ratio (OR) 15.6, 95% confidence interval (CI) 10.9-22.2) and a longer length of stay (OR 3.48, 95% CI 2.22-5.48). There was no significant difference in mortality between the groups (8.45% MG vs. 10.0% GBS, p = 0.16). Conclusion: Mechanically ventilated GBS patients have higher disease severity at admission along with more in-hospital complications, length of stay, and disability compared with MG patients. Potential explanations for these findings include delay in the diagnosis, poor response to immunotherapy particularly in patients with axonal GBS variant, or longer recovery time after nerve damage.

ß2-Adrenergic receptor activation mobilizes intracellular calcium via a non-canonical cAMP-independent signaling pathway.

Beta adrenergic receptors (ßARs) are G-protein-coupled receptors essential for physiological responses to the hormones/neurotransmitters epinephrine and norepinephrine which are found in the nervous system and throughout the body. They are the targets of numerous widely used drugs, especially in the case of the most extensively studied ßAR, ß2AR, whose ligands are used for asthma and cardiovascular disease. ßARs signal through Gαs G-proteins and via activation of adenylyl cyclase and cAMP-dependent protein kinase, but some alternative downstream pathways have also been proposed that could be important for understanding normal physiological functioning of ßAR signaling and its disruption in disease. Using fluorescence-based Ca2+ flux assays combined with pharmacology and gene knock-out methods, we discovered a previously unrecognized endogenous pathway in HEK-293 cells whereby ß2AR activation leads to robust Ca2+ mobilization from intracellular stores via activation of phospholipase C and opening of inositol trisphosphate (InsP3) receptors. This pathway did not involve cAMP, Gαs, or Gαi or the participation of the other members of the canonical ß2AR signaling cascade and, therefore, constitutes a novel signaling mechanism for this receptor. This newly uncovered mechanism for Ca2+ mobilization by ß2AR has broad implications for adrenergic signaling, cross-talk with other signaling pathways, and the effects of ßAR-directed drugs.

Current Endovascular Approach to the Management of Acute Ischemic Stroke.

PURPOSE OF REVIEW: The review provides an overview of current endovascular management of patients with acute ischemic stroke in the light of recent landmark trials proving unequivocal benefit of the intervention. RECENT FINDINGS: Several randomized trials looking at selective groups of patients presenting after an acute ischemic stroke due to large vessel occlusion in the anterior circulation demonstrated an overwhelming benefit of the endovascular treatment compared to intravenous thrombolysis, leading to expedited changes in the American Heart Association/American Stroke Association guidelines. Nonetheless, there are a relative large number of patients that were not included in those trials that might still benefit from endovascular treatment (acute posterior circulation-related strokes or acute embolic occlusion of middle cerebral artery beyond the main trunk for instances) and in which further studies are needed. We also briefly discuss endovascular techniques, post-procedure care, and endovascular treatment delivery models to expedite stroke patient assessment and rapid transport using updated and improved workflow protocols to provide timely recanalization. Endovascular treatment of acute occlusion of a proximal large artery in the anterior circulation is currently the standard of care. Time and quality of recanalization are the most important variables that determine the outcome. The indication for endovascular therapy in different scenarios (acute embolic occlusion in the posterior circulation or more distal branch occlusions) has to be individualized according to each patient's particular characteristics until new evidence is provided.

Prolonged Microcatheter-Based Local Thrombolytic Infusion as a Salvage Treatment After Failed Endovascular Treatment for Cerebral Venous Thrombosis: A Multicenter Experience.

BACKGROUND AND PURPOSE: To determine the effectiveness of prolonged microcatheter-based local thrombolytic infusion in treatment of patients with cerebral venous thrombosis who achieved no or suboptimal recanalization with transvenous endovascular treatment. METHODS: Data collection: Prospectively registries supplemented by retrospective review. SETTINGS: Three hospitals with tertiary referral base. PATIENTS: Patients who underwent transvenous endovascular treatment for cerebral venous thrombosis. INTERVENTION: Prolonged microcatheter-based local thrombolytic infusion of alteplase at the rate of 0.5-1 mg/h in patients in whom initial angiographic outcome was deemed suboptimal, either due to incomplete or no recanalization. RESULTS: Serial angiograms were performed to assess treatment response as follows: grade I, partial recanalization of one or more occluded dural sinuses with improved flow or visualization of branches; grade II, complete recanalization of one sinus but persistent occlusion of the other sinuses (A-no residual flow, B-nonocclusive flow); grade III, complete recanalization. Clinical outcome was determined at 1-3 months using modified Rankin scale. A total of 14 patients underwent 15 transvenous endovascular treatments. Initial treatment was considered suboptimal in 12/15 procedures due to no recanalization in five (grade 0), partial recanalization (grade I) in four, complete recanalization of one sinus but persistent occlusion of the other sinuses (grade 2A in two and 2B in one). A prolonged microcatheter-based local recombinant tissue plasminogen activator infusion was used following ten of the 15 procedures for a median duration of 18 h (range 13-22 h). Follow-up angiography demonstrated complete recanalization in four procedures and improvement in grades of partial recanalization in six procedures (final grades 2A in three and 2B in three procedures). None of the patients developed new symptomatic intracranial hemorrhage associated with local thrombolytic infusion. At follow-up, patients in five of ten procedures had achieved a modified Rankin scale of 0 and one patient had achieved a score of 1 (no neurological deficits but had residual headaches). CONCLUSION: Prolonged microcatheter-based local thrombolytic infusion appeared to be effective treatment in patients who have suboptimal response to acute transvenous endovascular treatment without any additional adverse events.

Albumin-Induced Neuroprotection in Focal Cerebral Ischemia in the ALIAS Trial: Does Severity, Mechanism, and Time of Infusion Matter?

OBJECTIVE: To determine whether there is any differential benefit of albumin administration within 2 h of onset of ischemia and in settings (severe ischemia with reperfusion in cardioembolic strokes with National Institutes of Health Stroke Scale [NIHSS] ≥15), most representative of experimental models of cerebral ischemia in which albumin was effective in reducing neurological injury. BACKGROUND: High-dose intravenous (IV) albumin treatment for acute ischemic stroke (ALIAS) trial did not show overall clinical benefit in ischemic stroke patients in contrast to preclinical studies; however, models of preclinical studies were not completely followed. METHODS: A total of 1275 patients combined from ALIAS trials I and II were included in our analysis. We analyzed preclinical studies and selected patients with large ischemic stroke (NIHSS ≥15) related to cardioembolic etiology (n = 189). Outcomes were then studied including time from onset to IV albumin administration. RESULTS: The odds of excellent outcome (mRS 0-1) at 3 months was not different with high-dose IV albumin infusion (n = 100) compared with placebo (n = 89) ((odds ratio [OR]) 1.632 [0.719-3.708], p value 0.2419). When we further classified these subjects according to time of IV albumin administration, we observed significantly higher odds of excellent outcome at 3 months when patients received IV albumin within 2 h, OR 9.369 (CI 1.040-84.405), p value 0.0461, after adjusting for age, gender, baseline NIHSS score, and any therapeutic procedure. CONCLUSION: A trend for benefit is noted in ischemic stroke patients with large cardioembolic stroke (NIHSS ≥15) when high-dose albumin was initiated within 2 h, suggesting that certain ischemic stroke subgroups of patients most representative of preclinical settings may benefit from such a treatment. Additional clinical trials maybe needed to stratify subjects and treatment assignments according to NIHSS severity and timely randomization to evaluate this concept further.

Are We Overlooking Stroke Chameleons? A Retrospective Study on the Delayed Recognition of Stroke Patients.

BACKGROUND AND PURPOSE: New effective recanalization therapies are currently available for acute ischemic stroke; yet a vast majority of stroke patients are left untreated. The lack of early recognition may be because often times, stroke patients present with atypical manifestations that resemble other conditions (which are referred to as "stroke chameleons"). We set to study the proportion of patients with delayed stroke recognition in a single center. METHODS: We performed a retrospective analysis of a prospectively collected data over a 9-year period. All adult patients discharged with the diagnosis of ischemic stroke or transient ischemic attack (TIA) were identified and traced for their diagnosis on admission. Those cases with a diagnosis other than ischemic stroke or TIA on admission were identified as possible stroke chameleons and categorized into different groups according to the occurrence of neurological or non-neurological manifestations at presentation. RESULTS: Of 2,303 cases with discharge diagnosis of ischemic stroke or TIA, 919 (39.9%) were found to be possible stroke chameleons. More than half of these patients (58.4%) presented with neurological manifestations including disorders of the somatic sensation (33%), alteration of consciousness (30%), and disorders of speech/language (11%). The remaining possible stroke chameleons had manifestations pertaining to other organ systems such as cardiopulmonary, gastrointestinal, systemic infection, trauma, and thromboembolic events elsewhere. CONCLUSIONS: In our cohort, a surprisingly large percentage of possible stroke chameleons was observed. It is important to confirm our findings, study the impact on clinical outcome, and develop strategies for early stroke patient recognition.

Black Tar Heroin Skin Popping as a Cause of Wound Botulism.

BACKGROUND: Botulism is a rare potentially fatal and treatable disorder caused by a bacteria-produced toxin that affects the presynaptic synaptic membrane resulting in a characteristic neuromuscular dysfunction. It is caused by either the ingestion of the toxin or the bacteria, inhalation, or wound infection. We present our observations with a descriptive case series of wound botulism secondary to black tar heroin (BTH) injection. METHODS: We report a retrospective single-center case series of 15 consecutive cases of wound botulism presenting to University Medical Center of El Paso. Medical records where reviewed to obtain demographic information, clinical presentation, treatment, and outcome. RESULTS: We identified fifteen patients with mean age of 47 years: twelve men, and three women. All had administered BTH through skin popping and had abscesses in the administration areas. By history, the most common symptoms were dysphagia (66%), proximal muscle weakness of upper and lower extremity (60%), neck flexor muscle weakness (33%), ophthalmoplegia (53%), bilateral ptosis (46%), dysarthria (53%), double vision (40%), blurred vision (33%), and dry mouth (20%). During the examination, the most common features noted were: proximal muscle weakness of upper and lower extremities (73%), ophthalmoplegia (53%), ptosis (46%). In patients with documented wound botulism, the pupils were reactive in 46%. All patients required mechanical ventilation and were treated with the trivalent antitoxin. Eleven patients (73.3%) were discharged home, two were transferred to a skill nursing facility, and two were transferred to long-term acute care facility. CONCLUSION: In our patients, BTH injection, involving the action of injecting under the skin acetylated morphine derivatives (mostly 6-monoacetylmorphine and 3-monoacetylmorphine), was associated with the development of botulism. The availability of BTH at the US-Mexican border is not surprising since it is frequently produced in Latin America. Its association with the development of botulism should be recognized early to allow a prompt diagnosis and treatment with the antitoxin. A clinical feature worth noting is the presence of normal pupillary light reflex in nearly half of patients. Therefore, the presence of a normal pupillary response does not exclude the presence of wound botulism.

Incident cancer in a cohort of 3,247 cancer diagnosis free ischemic stroke patients.

BACKGROUND: Subclinical cancer can manifest as a thromboembolic event and may be detected at a later interval in ischemic stroke survivors. We determined the rate of incident cancer and effect on cardiovascular endpoints in a large cohort of ischemic stroke survivors. METHODS: An analysis of 3,680 adults with nondisabling cerebral infarction who were followed for two years within the randomized, double-blinded VISP trial was performed. The primary intervention was best medical/surgical management plus a daily supplementation of vitamin B6, vitamin B12, and folic acid. We calculated age-adjusted rates of incidence of cancer among ischemic stroke survivors and standardized incidence ratios (SIR) with 95% confidence intervals (CI) based on comparison with age-adjusted rates in the general population. The significant variables from univariate analysis were entered in a Cox Proportional Hazards analysis to identify the association between various baseline factors and incident cancer after adjusting age, gender, and race/ethnicity. A logistic regression analysis evaluated the association between incident cancer and various endpoints including stroke, coronary heart disease, myocardial infarction, and death after adjusting age, gender, and race/ethnicity. RESULTS: A total of 3,247 patients (mean age ± SD of 66 ± 11; 2,013 were men) were cancer free at the time of enrollment. The incidence of new cancer was 0.15, 0.80, 1.2, and 2.0 per 100 patients at 1 month, 6 months, 1 year, and 2 years, respectively. The age-adjusted annual rate of cancer in patients with ischemic stroke was higher than in persons in the general population at 1 year (581.8/100,000 persons vs. 486.5/100,000 persons, SIR 1.2, 95% CI 1.16-1.24) and 2 years (1,301.7/100,000 vs. 911.5/100,000, SIR 1.4, 95% CI 1.2-1.6) after recruitment. There was a higher risk for death (odds ratio (OR) 3.1, 95% CI 1.8-5.4), and composite endpoint of stroke, coronary heart disease, and/or death (OR 1.4, 95% CI 1.0-2.2) among participants who developed incident cancer compared with those who were cancer free after adjusting for potential confounders. CONCLUSIONS: The annual rate of age-adjusted cancer incidence was higher among ischemic stroke patients compared with those in the general population. The odds of mortality were three folds higher among stroke survivors who developed incident cancer.

High risk of new episode of symptomatic vasospasm in unaffected arteries in subarachnoid hemorrhage patients receiving targeted endovascular treatment for symptomatic focal vasospasm.

BACKGROUND: There is controversy whether asymptomatic vasospasm in other arteries should be concurrently treated (global treatment) in patients receiving targeted endovascular treatment [percutaneous-transluminal-angioplasty (PTA) and/or intra-arterial (IA) vasodilators] for focal symptomatic vasospasm. OBJECTIVE: To determine the rates of occurrence of new symptomatic vasospasm in previously asymptomatic arterial distributions among patients with aneurysmal subarachnoid hemorrhage (SAH) who underwent targeted endovascular treatment for focal symptomatic vasospasm. METHODS: We identified all patients with SAH who had received targeted endovascular treatment during a 4-year period. We ascertained any new occurrence of symptomatic vasosopasm requiring endovascular treatment in previously unaffected (and untreated) arterial distributions within the same hospitalization. Blinded reviewers quantitatively graded angiographic vasospasm (<25, 26-49, ≥50 %) in all major arteries for each patient at the time of targeted treatment. RESULTS: Of the 41 patients who received targeted endovascular treatment (PTA in 41 % and vasodilators in 59 %), 11 (27 %) developed new symptomatic vasospasm in previously asymptomatic vascular distributions requiring endovascular treatment. Moderate severity of angiographic vasospasm in asymptomatic arteries at the time of targeted treatment tended to predict the occurrence of new symptomatic vasospasm. The rate of death and disability at discharge [modified Rankin scale (mRS) of 3-6] was 82 % (9/11) among those who developed a new episode of symptomatic vasospasm compared with 70 % (21/30) in those who did not (P = 0.58). CONCLUSIONS: High risk of new occurrence of ischemic symptoms in previously asymptomatic (and untreated) arterial distributions among patients receiving targeted treatment should be recognized. Further studies should evaluate the benefit of performing global endovascular treatment during the initial targeted endovascular treatment session.

"No turn back approach" to reduce treatment time for endovascular treatment of acute ischemic stroke.

BACKGROUND: A delay in endovascular treatment is less likely if acute ischemic stroke patients proceed from emergency department (ED) to computed tomographic (CT) scanner and directly to angiographic suite (no turn back approach). We determined the feasibility of the "no turn back approach" and its effect on treatment times and patient outcomes. METHODS: The primary outcomes were procedures performed with a time interval: (1) between ED arrival and microcatheter placement of less than 120 minutes and (2) between CT scan acquisition and microcatheter placement of less than 90 minutes. We determined the effect of the no turn back approach on favorable outcome at discharge. RESULTS: There was a significantly higher rate of CT scan acquisition and microcatheter placement time of less than 90 minutes in patients in whom no turn back approach was used (57.6% versus 31.6%, P = .0007). There was a significantly higher rate of ED arrival to microcatheter placement time of less than 120 minutes in patients in whom no turn back approach was used (31.8% versus 13.7%, P = .004). In the exploratory analysis, there was a trend toward higher rate of favorable outcomes (odds ratio 1.6, 95% confidence interval .9-2.8, P = .07) among those treated with no turn back approach after adjusting for age, admission National Institutes of Health Stroke Scale score strata, congestive heart failure, and diabetes mellitus. CONCLUSIONS: The no turn back approach appeared to be feasible and reduced the time interval between ED arrival and microcatheter placement in acute ischemic stroke patients undergoing endovascular treatment.

Impact of advanced healthcare directives on treatment decisions by physicians in patients with acute stroke.

BACKGROUND: The implementation of advanced healthcare directives, prepared by almost half of the adult population in United States remains relatively under studied. We determined the impact of advanced healthcare directives on treatment decisions by multiple physicians in stroke patients. METHODS: A deidentified summary of clinical and radiological records of 28 patients with stroke was given to six stroke physicians who were not involved in the care of the patients. Each physician independently rated 28 treatment decisions per patient in the presence or absence of advanced healthcare directives 1 month apart to allow memory washout. The percentage agreement to treat/intervene per patient and proportion of treatment withheld as a group were estimated for each of the 28 treatment decision items. We also determined the interobserver reliability between the two raters (attorneys) in interpretation of six items characterizing the adequacy of documentation within the 28 advanced healthcare directives. RESULTS: The percentage agreement among physician raters for treatment decisions in 28 stroke patients was highest for treatment of hyperpyrexia (100%, 100%) and lowest for ICU monitoring duration based on family-physician considerations outside of accepted criteria within institution (68%, 69%) in presence and absence of advanced healthcare directives. The physician rater agreement in choosing "yes" was highest for "routine-complexity" treatment decisions and lowest for "moderate-complexity" treatment decisions. The choice of withholding treatment in "routine-complexity," "moderate-complexity," or "high-complexity" treatment decisions was remarkably similar among raters in presence or absence of advanced healthcare directives. The only treatment decision that showed an impact of advanced healthcare directives was ICU monitoring withheld in 32% of treatment decisions in presence of directives (compared with 8% in the absence of directives). IV medication and defibrillation for cardiac arrest was withheld in 29% (compared with 19%) of the treatment decisions in the presence of advanced healthcare directives. The two attorney raters found the description of acceptable outcome inadequate in 14 and 21 of 28 advanced healthcare directives reviewed, respectively. The overall mean kappa for agreement regarding adequacy of documentation was modest (43%) for "does the advanced healthcare directive specify which treatments the patient would choose, or refuse to receive if they were diagnosed with an acute, terminal condition?" and lowest (3%) for "description of acceptable outcome." CONCLUSIONS: We did not find any prominent differences in most "routine-complexity," "moderate-complexity," or "high-complexity" treatment decisions in patient management in the presence of advanced healthcare directives. Presence of advanced healthcare directives also did not reduce the prominent variance among physicians in treatment decisions.

Rates and factors associated with admission in patients presenting to the ED with TIA in the United States-2006 to 2008.

BACKGROUND: The estimates of patients who present with transient ischemic attacks (TIA) in the emergency departments (EDs) of United States and their disposition and factors that determine hospital admission are not well understood. OBJECTIVE: We used a nationally representative database to determine the rate and predictors of admission in TIA patients presenting to EDs. METHODS: We analyzed data from the National Emergency Department Sample (2006-2008) for all patients presenting with a primary diagnosis of TIA in the United States. Samples were weighted to provide national estimates of TIA hospitalizations and identify factors that increase the odds of hospital admission including age, sex, type of insurance, median household income, and hospital type (urban teaching, urban nonteaching, and nonurban). Multivariate logistic regression analysis was used to identify independent predictors of hospital admission. RESULTS: There were 812908 ED visits for primary diagnosis of TIA; mean age (±SD), 70.3 ± 14.9 years; and 57.9% were women from 2006 to 2008. Of these ED visits, 516837 (63.5%) were admitted to the hospital, whereas 296071 (36.5%) were discharged from the ED to home. In the multivariate logistic regression analysis adjusting age, sex, and medical comorbidities, independent factors associated with hospital admissions were median household income $64000 or higher (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.22-1.44; P = .003), Medicare insurance type (OR, 1.19; 95% CI, 1.14-1.26; P < .0001), and metropolitan teaching hospital ED (OR, 2.17; 95% CI, 1.90-2.48; P < .0001). CONCLUSION: From 2006 to 2008, approximately 64% of all patients presenting with TIAs to the EDs within United States were admitted to the hospital. Factors unrelated to patients' condition such as median household income, insurance status, and ED affiliated hospital type play an important role in the decision to admit TIA patients to the hospitals.

Evolution-guided discovery and recoding of allosteric pathway specificity determinants in psychoactive bioamine receptors.

G protein-coupled receptors for dopamine and serotonin control signaling pathways targeted by many psychoactive drugs. A puzzle is how receptors with similar functions and nearly identical binding site structures, such as D2 dopamine receptors and 5-HT2A serotonin receptors, could evolve a mechanism that discriminates stringently in their cellular responses between endogenous neurotransmitters. We used the Difference Evolutionary Trace (Difference-ET) and residue-swapping to uncover two distinct sets of specificity-determining sequence positions. One at the ligand-binding pocket determines the relative affinities for these two ligands, and a distinct, surprising set of positions outside the binding site determines whether a bound ligand can trigger the conformational rearrangement leading to G protein activation. Thus one site specifies affinity while the other encodes a filter for efficacy. These findings demonstrate that allosteric pathways linking distant interactions via alternate conformational states enforce specificity independently of the ligand-binding site, such that either one may be rationally rekeyed to different ligands. The conversion of a dopamine receptor effectively into a serotonin receptor illustrates the plasticity of GPCR signaling during evolution, or in pathological states, and suggests new approaches to drug discovery, targeting both classes of sites.

Factors associated with favorable response to hyperbaric oxygen therapy among patients presenting with iatrogenic cerebral arterial gas embolism.

BACKGROUND: Iatrogenic cerebral arterial gas embolism (CAGE) is an uncommon but potentially a fatal condition. Hyperbaric oxygen (HBO2) therapy is the only definitive treatment for patients with CAGE presenting with acute neurologic deficits. METHODS: We reviewed medical records and neuroimaging of consecutive CAGE patients treated with HBO2 at a state referral hyperbaric facility over a 22-year period. We analyzed the effect of demographics, source of intra-arterial gas, signs and symptoms, results of imaging studies, time between event and HBO2 treatment, and response to HBO2 treatment in 36 consecutive patients. Favorable outcome was defined by complete resolution or improvement of CAGE signs and symptoms at 24 h after HBO2 treatment. Unfavorable outcome was defined by unchanged or worsened neurologic signs and symptoms or in hospital death. RESULTS: A total of 26 (72%) of the 36 patients had favorable outcome. Patients with favorable outcome were younger compared to those with unfavorable outcome (mean age [years, SD] 44.7 ± 17.8 vs. 58.1 ± 24.1, p = 0.08). Cardiopulmonary symptoms were significantly more common in CAGE related to venous source of gas compared to arterial source (p = 0.024) but did not influence the rate of favorable outcomes. Adjusted multivariate analysis demonstrated that time from event to HBO2 ≤ 6 h (positively) and the presence of infarct/edema on head computerized tomography (CT)/magnetic resonance imaging (MRI) before HBO2 (negatively) were independent predictors of favorable outcome at 24 h after HBO2 treatment [odds ratio (OR) 9.08 confidence interval (CI) (1.13-72.69), p = 0.0376, and (OR) 0.034 (CI) (0.002-0.58), p = 0.0200, respectively]. Two of the 36 patients were treated with thrombolytics because of acute focal deficits and suspected ischemia-one with intravenous and the second with intra-arterial thrombolysis. The latter patient developed fatal intracerebral hemorrhage. CONCLUSIONS: A high proportion of CAGE patients treated with HBO2 had favorable outcomes. Time-to-HBO2 ≤ 6 h increased the odds of favorable outcome, whereas the presence of infarct/edema on CT/MRI scan before HBO2 reduced the odds of a favorable outcome. Timely diagnosis and differentiation from thrombo-embolic ischemic events appears to be an important determinant of successful HBO2 treatment.

Diagnosis of stroke by emergency medical dispatchers and its impact on the prehospital care of patients.

BACKGROUND: Emergency medical dispatchers represent the first line of communication with a patient, and their decision plays an important role in the prehospital care of stroke. We evaluated the rate and accuracy of stroke diagnosis by dispatchers and its influence in the prehospital care of potential stroke patients. METHODS: We analyzed the 2009 National Emergency Medical Services Information System. Study population was based on the diagnosis of stroke made by emergency medical technicians (EMT). This was then divided in those coded as stroke/cerebrovascular accident versus others reported by dispatchers and compared with each other. RESULTS: In all, 67,844 cases were identified as stroke by EMT, but transportation time was available for 52,282 cases that represented the final cohort. Cases identified as stroke by dispatchers were 27,566 (52.7%). When this group compared with stroke cases not identified by dispatchers, we found that the mean age was significantly higher (71.2 versus 68.6 years, P<.0001); advanced life support was dispatched more frequently (84% versus 72.8%, P<.0001), dispatchers offered help and instructions to the caller more frequently, and they arrived at a facility at a shorter time (41.8 versus 49.8 minutes, P<0001). Sensitivity and specificity for the diagnosis of stroke by dispatchers were 34.61 and 99.46, respectively. CONCLUSIONS: Recognition of symptoms and diagnosis of a potential stroke by dispatchers positively affect the care of patients by decreasing the arrival time to a hospital and providing the highest level of prehospital care possible. Education is needed to increase dispatcher's detection of stroke cases.

Adherence to guidelines by emergency medical services during transport of stroke patients receiving intravenous thrombolytic infusion.

BACKGROUND: The "drip and ship" paradigm among acute ischemic stroke (AIS) patients has resulted in expansion of thrombolytic treatment in patients eligible for intravenous (IV) recombinant tissue plasminogen activator (rt-PA). It remains controversial whether the settings within the emergency medical services (EMS) transport are adequate for IV rt-PA infusion. We sought to determine EMS adherence to guidelines during the transport of drip and ship AIS patients treated with IV rt-PA while being transferred to comprehensive stroke centers (CSCs) and the effect of nonadherence on outcome upon discharge. METHODS: A retrospective evaluation of patients transferred to our CSC was conducted to determine the rates of adherence to quality parameters during EMS transport with infusion of IV rt-PA. Favorable outcome was defined as modified Rankin Scale (mRS) score ≤ 1 upon discharge. RESULTS: Among the 40 patients studied (55% men; mean age 71.9 ± 13.9 years), 38 patients received vital sign monitoring at 10- to 20-minute intervals. The mean transit time was 37.7 ± 20.2 minutes. Of the 39 patients with blood pressure (BP) monitoring, 7 patients had at least 1 episode of BP elevation above the recommended parameters (>180/105 mm Hg); only 1 of those was treated with an antihypertensive agent. Five of the 40 patients were considered to have worsened between the outside ED and CSC ED evaluations without IV rt-PA discontinuation during transfer. The rate of favorable outcome of patients who had interim neurologic deterioration without discontinuation of IV rt-PA or BP >180/105 mm Hg without antihypertensive treatment was similar to those who experienced neither event (41.7% and 35.7%; P = .736). CONCLUSIONS: Efforts are required to improve EMS adherence to guidelines in patients receiving IV rt-PA during EMS transport in anticipation of broader use of the "drip and ship" paradigm.