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.

Racial/ethnic disparities in hospital utilization in intracerebral hemorrhage.

BACKGROUND AND PURPOSE: There is evidence that racial and ethnic differences among intracerebral hemorrhage (ICH) patients exist. We sought to establish the occurrence of disparities in hospital utilization in the United States. METHODS: We identified ICH patients from United States Nationwide Inpatient Sample database for years 2006-2014 using codes (DX1 = 431, 432.0) from the International Classification of Diseases, 9th edition. We compared five race/ethnic categories: White, Black, Hispanic, Asian or Pacific Islander, and Others ( Native American and other) with regard to demographics, comorbidities, disease severity, in-hospital complications, in-hospital procedures, length of stay (LOS), total hospital charges, in-hospital mortality, palliative care, (PC) and do not resuscitate (DNR). We categorized procedures as lifesaving (i.e. ventriculostomy, craniotomy, craniectomy, and ventriculoperitoneal (VP) shunt), life sustaining (i.e. mechanical ventilation, tracheostomy, transfusions, and gastrostomy). White race/ethnicity was set as the reference group. RESULTS: Out of 710,293 hospitalized patients with ICH 470,539 (66.2%), 114,821 (16.2%), 66,451 (9.3%), 30,297 (4.3%) and 28,185 (3.9%) were White, Black, Hispanic, Asian or Pacific Islander, and Others, respectively. Minorities (Black, Hispanic, Asian or Pacific Islander, and Others) had a higher rate of in-hospital complications, in-hospital procedures, mean LOS, and hospital charges compared to Whites. In contrast, Whites had a higher rate of in-hospital mortality, PC, and DNR. In multivariable analysis, all minorities had higher rate of MV, tracheostomy, transfusions, and gastrostomy compared to Whites, while Hispanics had higher rate of craniectomy and VP shunt; and Asian or Pacific Islander and Others had higher rate of craniectomy. Whites had a higher rate of in-hospital mortality, palliative care, and DNR compared to minorities. In mediation analysis, in-hospital mortality for whites remained high after adjusting with PC and DNR. CONCLUSION: Minorities had greater utilization of lifesaving and life sustaining procedures, and longer LOS. Whites had greater utilization of palliative care, hospice, and higher in-hospital mortality. These results may reflect differences in culture or access to care and deserve further study.

Cervical Arterial Fibromuscular Dysplasia in a Biethnic Population: A Retrospective Study in the U.S.-Mexican Border.

Background There have been studies trying to characterize Fibromuscular Dysplasia (FMD); however, most of them are based in mainly non-Hispanic sample. The objective of this study is to better understand the epidemiology and clinical characteristics of craniocervical FMD in the Hispanic population. Methods We retrospectively reviewed the cerebral angiograms performed in our center in a period of 3.5 years under any indication looking for angiographic patterns of FMD. Exclusion criteria consisted of cases in which the first angiogram was done when the patients were younger than 18 years. Patients were subdivided based on those with FMD and those without it for baseline characteristics and were looked for any associations. We further compared the same baseline characteristics among Hispanic FMD and non-Hispanic FMD population. A chart review was conducted looking for clinical features and vascular events. Results We analyzed 448 angiograms among patients younger than 18 years. We identified 47 patients with evidence of FMD involving the cervical arteries and 401 patients without FMD. Of the 47 patients with FMD in our neuroendovascular registry, we found that 76.6% were women and 57.4% were Hispanics. There was no statistical significant difference when comparing the variables across ethnicities, except history of cigarette smoking and dyslipidemia. The most common associated supra-aortic arterial lesions seen in the FMD group were intracranial aneurysm and arterial dissections. We then used same variables to compare Hispanic FMD with non-Hispanic FMD. We have found that there has been a positive association of cigarette smoking and dyslipidemia with FMD ( p ≤ 0.05). Conclusion Our study suggests that FMD affecting the carotid and vertebral arteries has similar demographic pattern across ethnicities in the United States. In Hispanics, the disease appears to have a predilection for women and history of cigarette smoking. Intracranial aneurysm and arterial dissection were the most commonly associated arterial lesions.

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.

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.

Topsy-turvy by the Belly Dancer.

In our patient presenting with abdominal myoclonus, it is important to understand its pathophysiology. Various etiologies need to be taken into consideration before coming to a conclusion. The finding on Magnetic resonance imaging (MRI)-Spine disclosing cervical lesion may just be an incidental finding.

Combined surgical and endovascular treatment of complex high-flow conus medullaris arteriovenous fistula associated with Parkes Weber syndrome: case report.

Parkes Weber syndrome (PWS) is a congenital overgrowth disorder characterized by unilateral limb and axial hypertrophy, capillary malformations of the skin, and high-flow arteriovenous fistulas (AVFs). Spinal AVFs in the setting of PWS are challenging vascular lesions that often contain multiple arteriovenous (AV) shunts. The present case report highlights an adolescent girl with PWS who presented with a ruptured complex high-flow conus medullaris AVF. She was successfully treated with endovascular embolization and microsurgery. At the 2-year follow-up, the patient remained free of neurological symptoms and had no recurrence of the vascular malformation.

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.

Trans-arterial Onyx Embolization of a Functional Thoracic Paraganglioma.

Paragangliomas are rare tumors of the endocrine system. They are highly vascular and in some cases hormonally active, making their management challenging. Although there is strong evidence of the safety and effectiveness of preoperative embolization in the management of spinal tumors, only five cases have been reported in the setting of thoracic paragangliomas. We present the case of a 19-year-old man with a large, primary, functional, malignant paraganglioma of the thoracic spine causing a vertebral fracture and spinal cord compression. To our knowledge this is the first report of preoperative trans-arterial balloon augmented Onyx embolization of a thoracic paraganglioma.

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.

Vessel occlusion using a single long oversized coil in vertebral artery dissection: a technical note.

Vertebral artery dissection may lead to stroke. Medical therapy is usually the first line of treatment. The endovascular approach of medically refractory vertebral artery dissection may include numerous techniques, including coil occlusion of the parent vessel. Two cases are presented of medically refractory symptomatic vertebral artery dissections in which vessel coil occlusion was successfully achieved with a single long oversized coil. There were no periprocedural complications and both patients had excellent clinical and angiographic outcome and remained asymptomatic on follow-up. The use of a single long oversized coil in vessel sacrifice has not been described previously. It represents a safe, rapid and cost effective alternative to the current existing techniques for vessel sacrifice.

Safety and effectiveness of endovascular treatment after 6 hours of symptom onset in patients with anterior circulation ischemic stroke: a matched case control study.

BACKGROUND: Endovascular treatment within 6 hours of symptom onset appears to be beneficial in carefully selected patients with ischemic stroke. It is unclear whether endovascular treatment beyond 6 hours of symptom onset is safe and efficacious. METHODS: Over a 6-year period, 52 patients with acute ischemic stroke in the anterior circulation underwent emergent endovascular thrombolytic infusion and mechanical thrombectomy after 6 hours of symptom onset at 3 institutions. Their outcomes were compared to 52 placebo-treated patients matched by baseline National Institutes of Health Stroke Scale (NIHSS) score and nonlacunar anterior circulation location from the Trial of Org 10172 in Acute Stroke Treatment trial using a 1:1 ratio. Univariate and multivariate analyses were performed comparing the rates of symptomatic intracerebral hemorrhage, early neurologic improvement, favorable outcome at 7 days or discharge, and in-hospital mortality between the 2 groups. RESULTS: After adjustment for gender, time interval between symptom onset to treatment, hypertension, hyperlipidemia, and history of cigarette smoking, rates of neurologic improvement at 24 hours (odds ratio [OR] 1.15; 95% confidence interval [CI] 0.43-3.1) and favorable outcome at 7 days or discharge (OR 1.39; 95% CI 0.47-4.05) were similar in the 2 groups. No differences in the rates of symptomatic intracerebral hemorrhage or death were found after adjusting for potential confounders. In an analysis limited to only those patients who underwent computed tomographic perfusion or magnetic resonance imaging before receiving endovascular treatment, the rate of favorable outcome at 7 days or discharge was similar between patients who underwent endovascular treatment and control patients (35.7% v 32.1%; P = .77). CONCLUSIONS: We did not observe any evidence of benefit in halting neurologic worsening or improving outcomes among patients undergoing endovascular treatment for treatment of an anterior circulation ischemic stroke after 6 hours of symptom onset. Strong evidence of both the safety and efficacy of emergent endovascular treatment when administered to patients with stroke in the anterior circulation is needed.

Comparison of single versus multiple spontaneous extra- and/or intracranial arterial dissection.

BACKGROUND: Anecdotal data suggest that approximately 20% of patients with a spontaneous extra- and/or intracranial arterial dissection have multiple arterial involvement. Limited data exist regarding the clinical and angiographic characteristics of patients with multiple arterial dissections. We compared the clinical and angiographic features of patients with spontaneous multiple extra- and/or intracranial arterial dissections with those who have a single arterial dissection. METHODS: A retrospective chart review of the consecutive ischemic stroke database over a 7-year period, maintained at 2 institutions, was conducted to identify patients with spontaneous extra- and/or intracranial arterial dissection. The patients' clinical characteristics and angiographic features (including the artery affected, presence of pseudoaneurysm, fibromuscular dysplasia, and degree of stenosis) were analyzed. RESULTS: A total of 76 patients were admitted with spontaneous extra- and/or intracranial arterial dissection; 46 dissections were confirmed with 4-vessel cerebral angiography. Multiple arterial dissections were found in a total of 10 (22%) patients. Involvement of multiple arteries was more prevalent in the young, when compared to a single spontaneous arterial dissection (7 [70%] in patients <45 years of age v 11 [31%]; P = .03). Patients with multiple arterial dissections had a higher proportion of pseudoaneurysms (9 [90%] v 11 [31%]; P = .001), a higher prevalence of underlying fibromuscular dysplasia (3 [30%] v 3 [8%]; P = .11), and were more likely to involve the posterior circulation (P < .0001). CONCLUSIONS: The presence of multiple, simultaneous spontaneous extra- and/or intracranial arterial dissections must be considered when a single spontaneous arterial dissection is identified.

A comparison of outcomes associated with carotid artery stent placement performed within and outside clinical trials in the United States.

BACKGROUND: A discrepancy between characteristics of patients treated with carotid angioplasty and stent placement (CAS) within and outside clinical trials, particularly characteristics with direct impact on clinical outcome, may limit generalization of clinical trial results. The objective of this study was to identify differences in demographic and clinical characteristics and outcomes related to CAS in patients treated within clinical trials and those treated outside clinical trials in a large national cohort. METHODS: We determined the frequency of CAS performed within and outside clinical trials and associated in-hospital outcomes using data from the Nationwide Inpatient Survey data files from 2005 to 2009. All the in-hospital outcomes were analyzed after adjusting for potential confounders using multivariate analysis. RESULTS: Of the 81,638 patients who underwent CAS, 16,078 (19.6%) underwent the procedure as part of a clinical trial. The mean age of the patients was significantly lower in patients treated with CAS as part of a clinical trial than those treated with CAS outside a clinical trial. The proportion of women and nonwhites was lower among patients treated with CAS as part of a clinical trial. The in-hospital mortality was two-fold higher among patients treated with CAS outside clinical trials (1.12% vs 0.53%; P = .0005). The rate of composite endpoint of stroke, cardiac events, and death was significantly higher among patients treated with CAS outside clinical trials (P = .02). After adjusting for age, gender, presence of renal failure, and hospital bed size, CAS performed as part of a clinical trial was associated with lower rates of in-hospital mortality (odds ratio, 0.467; 95% confidence interval, 0.290-0.751; P = .0017) and composite endpoint of stroke, cardiac events, and death (odds ratio, 0.752; 95% confidence interval, 0.594-0.952; P = .0180). CONCLUSIONS: Our results suggest that CAS procedures performed as part of clinical trials was associated with lower rates of in-hospital mortality and composite endpoint of stroke, cardiac events, and death in United States. These findings highlight the need for strategies that ensure appropriate adoption of CAS to ensure that the benefits observed in clinical trials can be replicated in general practice.

Potential synergy between advanced primary stroke centers and level I or II trauma centers in the United States.

OBJECTIVE: The objective of this study is to determine the number of primary stroke centers (PSCs) that exist concurrently (synergic relationship) with designated higher level trauma centers (level I or level II trauma centers) and associated characteristics. METHODS: We identified all PSCs certified by the Joint Commission or local state authorities in 2010. Concurrently, all the higher level trauma centers (designated level I or level II) were identified using data collected from the trauma information exchange program. Additional data was collected from the Accreditation Council for Graduate Medical Education and the American hospital directory. RESULTS: A total of 788 existing designated PSCs were identified in 2010; coexisting PSC-trauma centers were found in 252 centers (32%) with PSCs coexisting with level I trauma centers in 138 hospitals (17.5%). The remaining 536 PSCs (68%) are based in hospitals without trauma centers. There was a higher proportion of residency training programs including neurology, neurosurgery, and general surgery in coexisting PSC-trauma centers (P < .001). In a proof-of-concept analysis in 1 state, PSCs with level I trauma facilities were found to have the highest rates of thrombolytic administration as compared with PSCs with level II trauma centers and PSCs without trauma facilities (12.8% vs 3.8% vs 4.9%)(P < .0001). Primary stroke centers with level I trauma facilities were also more likely to follow the drip-and-ship paradigm (5.7% vs 1.8% vs 0.9%) (P < .0001). CONCLUSIONS: Despite evidence of higher capability among institutions with coexisting PSC-trauma centers, two thirds of PSCs are in hospitals without advanced trauma systems. These findings have implications for establishing stroke systems in the United States.

Age differential between outcomes of carotid angioplasty and stent placement and carotid endarterectomy in general practice.

BACKGROUND: Data derived from prospective randomized clinical trials suggest differential comparative benefit between carotid angioplasty and stent (CAS) placement and carotid endarterectomy (CEA) in various age strata. We sought to investigate the impact of age on outcomes of CAS and CEA in general practice. METHODS: We analyzed the data from the Nationwide Inpatient Sample (NIS), which is representative of all admissions in the United States from 2005 to 2008. The primary end point was occurrence of stroke, cardiac complications, or death during the postprocedural period. Outcomes of interest were compared between patients aged ≥70 years and <70 years, undergoing CEA and CAS. Multivariate logistic regression was performed to determine the effect of age on occurrence of postoperative stroke, cardiac complications, or death. Covariates included in the logistic regression were patient's age, gender, comorbid conditions, including hypertension, diabetes mellitus (DM), chronic lung disease, coronary artery disease (CAD), congestive heart failure (CHF), and renal failure; symptom status (symptomatic vs asymptomatic status), and hospital characteristics. RESULTS: Of the total 495,331 estimated patients who received treatment for CAD during the study period, 88% underwent CEA and the remaining 12% underwent CAS. Of the total procedures, 41% of the procedures were performed in patients aged <70 years compared to the remaining 59% that were performed among patients aged ≥70 years. For patients undergoing CAS, age ≥70 years was an important predictor of postoperative stroke (P = .0025; odds ratio [OR], 1.7; 95% confidence interval [CI], 1.2-2.5) and cardiac complications postprocedure (P = .045; OR, 1.3; 95% CI, 1.0-1.6). For patients undergoing CEA, age ≥70 years was associated with higher cardiac complications (P < .001; OR, 1.5; 95% CI, 1.3-1.7) and higher postoperative mortality risk (P = .0008; OR, 1.4; 95% CI, 1.1-1.8) compared to patients aged <70 years. The increased risk of composite end point (postoperative stroke/cardiac complications/mortality) among patients aged ≥70 years was a significant factor for patients undergoing either CAS or CEA (OR of 1.3 for both procedures). CONCLUSION: Our analysis suggests that most CAS and CEAs are performed in patients aged ≥70 years in general practice, and higher rates of postoperative complications are observed among these patients regardless of procedure choice.

Conformational flexibility of transmembrane helix VII of the human serotonin transporter impacts ion dependence and transport.

The serotonin transporter (SERT) regulates the serotonin concentration in the synapse and is a target of several antidepressant and psychostimulant drugs. Previous work suggested that the middle transmembrane helices (TMHs) of the biogenic amine transporters (TMHs) play a role in substrate and ion recognition. We focused our present studies on exploring the role of TMH VII in transporter function and ion recognition. Residues divergent between human SERT and Drosophila SERT (hSERT and dSERT, respectively) were identified and mutated in hSERT to the corresponding identity in dSERT. hSERT mutants V366S, M370L, S375A, and T381S exhibited a decrease in transport capacity. To further explore the role of these residues in the transport process, we generated cysteine mutants at multiple positions. Pretreatment with [2-(trimethylammonium)ethyl] methanethiosulfonate (MTSET) caused a decrease in transport of [(3)H]5-HT in the V366C and M370C mutants. The hSERT V366S, M370L, and M370C mutations also altered the sodium and chloride dependence for substrate transport. Interpretation of our results in the context of a homology model of SERT based on the crystal structure of the Aquifex aeolicus leucine transporter suggests flexibility in the conformation of TMH VII that impacts ion dependence and substrate transport.

Helix XI contributes to the entrance of the serotonin transporter permeation pathway.

The sodium-dependent transporters for dopamine, norepinephrine, and serotonin that regulate neurotransmission, also translocate the neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)). Previous studies implicated residues in transmembrane helix (TMH) XI of DAT as important sites for MPP(+) transport. We examined the importance of TMH XI residues F551 and F556 for MPP(+) translocation by human SERT. Mutations at hSERT F556, but not F551, reduced both 5-HT and MPP(+) transport compared to wild type. However, F556S/hSERT showed a reduction in surface expression explaining the decrease of transport activity for 5-HT, but did not account for the decrease in MPP(+) transport observed. Cysteine mutants at those positions confirmed the accessibility of hSERT/F556 to different methanethiosulfonate (MTS) reagents, suggesting its presence in a hydrophilic environment of the protein. In the presence of MTSET, current induced by 5-HT and MPP(+) was inhibited at the F556C mutant. In agreement with our homology model of SERT, based on the leucine transporter (LeuT(Aa)) from Aquifex aeolicus structure, these results are consistent with the hypothesis that a portion of TMH XI lines the entrance into the substrate permeation pathway.