Assessment of Patients' Willingness to Participate in a Randomized Trial of Spinal versus General Anesthesia for Lumbar Spine Surgery.

BACKGROUND: Prospective nonrandomized studies have found less postoperative fatigue and improved quality of life in patients undergoing awake spine surgery under spinal anesthesia compared with general anesthesia. Randomized trials are needed to validate these findings. OBJECTIVE: To prospectively investigate patients' willingness to enroll in randomized trials of lumbar spine surgery under spinal versus general anesthesia and identify any potential barriers. METHODS: We recruited patients undergoing lumbar spine surgery for degenerative disease. We described a randomized trial of spine surgery under spinal versus general anesthesia and assessed patients' willingness to participate in such trial. We elicited preferences for treatment along with demographics. The association between these factors and willingness to participate in the trial was examined. RESULTS: Fifty patients completed interviews; 58% were female, mean age of 60.9 ± 12.5 years. A total of 52% patients stated that they were definitely willing to participate in the hypothetical randomized trial, and 8% probably willing. Only 16% of patients were aware of spinal anesthesia as an option for low back surgery, and 60% indicated no strong preference for the anesthesia techniques. Patients without strong preferences stated a greater willingness to participate than those with strong preferences (80% vs. 10% definitely willing, P < 0.0001). Age, sex, education, work status, and race were not significantly associated with willingness to participate. CONCLUSION: Sixty percent of patients stated that they were either definitely or probably willing to participate in the randomized trial. Subjects lacking strong preferences for the anesthesia technique stated a greater willingness to enroll than those with strong preference.

Bifrontal Osteoplastic Flap: An Option to Decrease Infection in Bifrontal Craniotomies with Skull Base Osteotomies.

Infection can be a common complication following bifrontal craniotomy with skull base osteotomies given the potential violation of sinuses and entry into the nasal structures. Our objective was to examine our series of patients who underwent a bifrontal craniotomy with skull base osteotomies and describe the infection rate. We propose the bifrontal osteoplastic flap as an adjunct to infection prevention. A retrospective single-center study of a patient database was performed. Twenty patients were identified. Fifty-five percent were male. The mean age was 55.7 ± 13.9 years. The most common indications for surgery were esthesioneuroblastomas (35%) and anterior skull base meningiomas (30%). Six patients (30%) developed an infection, 1 patient (5%) developed a CSF leak, and no patients developed a mucocele. All 6 infected cases had nasal pathology with intracranial extension, they all received chemoradiation post-operatively and were all combined cases with otorhinolaryngology. Eighty-three percent of these patients required a craniectomy and all of them required long-term IV antibiotics. Infection is not uncommon after a bifrontal craniotomy with skull base osteotomies and the use of the bifrontal osteoplastic flap in cases where the risk of infection is high, i.e., esthesioneuroblastomas surgery, may help reduce said risk and lead to better patient outcomes.

Modern Approaches to Evacuating Intracerebral Hemorrhage.

PURPOSE OF REVIEW: The present review aims to discuss the recent advances in surgical management of spontaneous intracerebral hemorrhage (ICH), safety and efficacy of minimally invasive surgical techniques, and the existing evidence supporting their use. RECENT FINDINGS: Newer surgical techniques, collectively referred to as minimally invasive surgery (MIS), have been evaluated and studied in management of ICH. Stereotactic evacuation of intracerebral hemorrhage using aspiration-irrigation technique has showed significant reductions in the hematoma volume with minimal intra-operative bleeding. Catheter-based evacuation in combination with use of recombinant tissue plasminogen activator (rt-PA) produces lysis and drainage of spontaneous ICH and intraventricular hemorrhage (IVH) rapidly with minimal major adverse events. Recent advances in the management of spontaneous ICH highlights potential advantages including safety and efficacy in clot lysis and reduction in hematoma volume especially with image-guided catheter-based drainage and concurrent use of rt-PA. Controlled trials are required to conclusively establish standard surgical techniques and rt-PA dosage, before incorporating minimally invasive surgery plus rt-PA, as a standard of care in patients with spontaneous ICH.

Characteristics of Accredited Transcranial Doppler Ultrasound Laboratories in the United States.

PURPOSE: The aim of this study was to describe in detail the characteristics and accreditation compliance of laboratories in the United States applying for Intersocietal Accreditation Commission (IAC) transcranial Doppler (TCD) accreditation. METHODS: This was a retrospective study of all applicant laboratories from 2012 to 2015. We used the IAC database to extract laboratory characteristics and guideline compliance metrics. RESULTS: Evaluation of 97 laboratories demonstrated that 67% were hospital-based and located in the South (43.3%), corresponding to the location of "Stroke Belt" states. Cases from 186 interpreting physicians, of which 110 (59%) were neurologists, were evaluated during the accreditation process. Established practice was the most common training pathway (54.8%), and a majority had not obtained an additional vascular interpretation credential (72.6%). From 318 case studies, the most frequent indications were subarachnoid hemorrhage (31.0%), stroke (17.0%), and carotid stenosis (14.3%). Although most laboratories had been previously accredited, accreditation was delayed for 77.3% due to incomplete studies (33.0%), discrepant findings between the report and the laboratory's diagnostic criteria (23.7%), and discrepant findings between the report and the waveforms/images (17.5%). CONCLUSIONS: The results suggest that there are significant differences between IAC applicant laboratories and laboratories represented by Centers for Medicaid and Medicare Services (CMS) claims data. In addition, accurate study reporting, physician training, and ongoing quality improvement activities may not be optimized in laboratories applying for accreditation. With the information learned from this study, educational strategies by professional organizations, including the IAC, can be tailored to help improve TCD practice.

A Series of Cerebral Venous Sinus Thromboses Treated with Intra-Arterial tPA infused over Ten Hours with a 0.027-inch Catheter and Literature Review.

Cerebral venous sinus thrombosis (CVST) can have devastating results, with mortality reported in 44% of cases. No randomized trials exist in order to define what qualifies as failure of conservative therapy, and there is no specific intervention to date which is considered safe and effective. Case series suggest that thrombolysis infusion is safer than thrombectomy, but methods of administration, dose, and duration of therapy tend to vary widely. We present three consecutive CVST patients treated with heparin who suffered both clinical and radiographic deterioration, and went on to have endovascular therapy. Each patient was successfully recanalized by placing a 0.027-inch microcatheter at the proximal portion of the thrombus and infusing 20 mg of alteplase dissolved in 1 liter of normal saline infused at 100 ml per hour for an infusion of 2 mg of alteplase per hour for ten hours.

Effect of serotonin on platelet function in cocaine exposed blood.

5-hydroxytryptamine (5-HT) reuptake inhibitors counteract the pro-thrombotic effect of elevated plasma 5-HT by down-regulating the 5-HT uptake rates of platelets. Cocaine also down-regulates the platelet 5-HT uptake rates but in contrast, the platelets of cocaine-injected mice show a much higher aggregation rate than the platelets of control mice. To examine the involvement of plasma 5-HT in cocaine-mediated platelet aggregation, we studied the function of platelets isolated from wild-type and transgenic, peripheral 5-HT knock-out (TPH1-KO) mice, and cocaine-insensitive dopamine transporter knock in (DAT-KI) mice. In cocaine-injected mice compared to the control mice, the plasma 5-HT level as well as the surface level of P-selectin was elevated; in vitro platelet aggregation in the presence of type I fibrillar collagen was enhanced. However, cocaine injection lowered the 5-HT uptake rates of platelets and increased the plasma 5-HT levels of the DAT-KI mice but did not change their platelets aggregation rates further which are already hyper-reactive. Furthermore, the in vitro studies supporting these in vivo findings suggest that cocaine mimics the effect of elevated plasma 5-HT level on platelets and in 5-HT receptor- and transporter-dependent pathways in a two-step process propagates platelet aggregation by an additive effect of 5-HT and nonserotonergic catecholamine.

Impact of elevated plasma serotonin on global gene expression of murine megakaryocytes.

BACKGROUND: Serotonin (5-HT) is a biogenic amine that also acts as a mitogen and a developmental signal early in rodent embryogenesis. Genetic and pharmacological disruption of 5-HT signaling causes various diseases and disorders via mediating central nervous system, cardiovascular system, and serious abnormalities on a growing embryo. Today, neither the effective modulators on 5-HT signaling pathways nor the genes affected by 5-HT signal are well known yet. METHODOLOGY/PRINCIPAL FINDINGS: In an attempt to identify the genes altered by 5-HT signaling pathways, we analyzed the global gene expression via the Illumina array platform using the mouse WG-6 v2.0 Expression BeadChip containing 45,281 probe sets representing 30,854 genes in megakaryocytes isolated from mice infused with 5-HT or saline. We identified 723 differentially expressed genes of which 706 were induced and 17 were repressed by elevated plasma 5-HT. CONCLUSIONS/SIGNIFICANCE: Hierarchical gene clustering analysis was utilized to represent relations between groups and clusters. Using gene ontology mining tools and canonical pathway analyses, we identified multiple biological pathways that are regulated by 5-HT: (i) cytoskeletal remodeling, (ii) G-protein signaling, (iii) vesicular transport, and (iv) apoptosis and survival. Our data encompass the first extensive genome-wide based profiling in the progenitors of platelets in response to 5-HT elevation in vivo.

Down-regulation of the serotonin transporter in hyperreactive platelets counteracts the pro-thrombotic effect of serotonin.

An elevated plasma concentration of serotonin ([5-HT]) is a common feature of cardiovascular disease often associated with enhanced platelet activation and thrombosis. Whether elevated in vivo plasma 5-HT per se represents an independent risk factor for platelet hyperreactivity or only is an epiphenomenon of cardiovascular disease is poorly understood. We examined in vitro and in vivo platelet function following a 24h elevation of plasma [5-HT] in mice. In vivo administration of 5-HT using osmotic minipumps increased plasma [5-HT] in treated mice compared to control mice instrumented with saline loaded pumps. 5-HT infusion did not increase systolic blood pressure, but markers of platelet activation including P-selectin and (PE)Jon/A staining were increased and these findings coincided with the enhanced aggregation of isolated platelets in response to type I fibrillar collagen. Tail bleeding times and the time to occlusion following chemical damage to the carotid artery were shortened in 5-HT-infused mice. 5-HT-infused mice were treated with paroxetine (Prx) to block 5-HT uptake via the serotonin transporter (SERT). Prx lowered platelet [5-HT] and attenuated platelet activation and aggregation. These results and our biochemical indices of enhanced 5-HT intracellular signaling in the platelets of 5-HT-infused mice reveal a mechanistic link between elevated plasma [5-HT], abnormal intracellular 5-HT signaling and accentuated platelet aggregation. Although a down-regulation of the serotonin transporter (SERT) on the platelet surface may counteract the pro-thrombotic influence of elevated plasma [5HT], this compensatory mechanism may fail to prevent the increased thrombotic risk caused by elevated plasma [5-HT].

Communication between 5-HT and small GTPases.

Advances over the past decade have improved our understanding of the serotonin (5-HT) biology outside the central nervous system specifically the molecular mechanisms of serotonergic signaling in association with small GTPases. It is now recognized that the communication between 5-HT and GTPases plays important roles in peripheral tissues, vascular cells and are involved in coagulation, hypertension, inflammation, healing and protection. Furthermore, 5-HT receptors as heterotrimeric GTP-binding protein-coupled receptors act as effector protein on the small GTPases. Therefore, the antagonists or agonists of the effector proteins of small GTPases could be useful therapeutic agents for the treatment of several diseases and disorders.

The cellular distribution of serotonin transporter is impeded on serotonin-altered vimentin network.

BACKGROUND: The C-terminus of the serotonin transporter (SERT) contains binding domains for different proteins and is critical for its functional expression. In endogenous and heterologous expression systems, our proteomic and biochemical analysis demonstrated that an intermediate filament, vimentin, binds to the C-terminus of SERT. It has been reported that 5HT-stimulation of cells leads to disassembly and spatial reorientation of vimentin filaments. METHODOLOGY/PRINCIPAL FINDINGS: We tested the impact of 5HT-stimulation on vimentin-SERT association and found that 5HT-stimulation accelerates the translocation of SERT from the plasma membrane via enhancing the level of association between phosphovimentin and SERT. Furthermore a progressive truncation of the C-terminus of SERT was performed to map the vimentin-SERT association domain. Deletion of up to 20, but not 14 amino acids arrested the transporters at intracellular locations. Although, truncation of the last 14 amino acids, did not alter 5HT uptake rates of transporter but abolished its association with vimentin. To understand the involvement of 5HT in phosphovimentin-SERT association from the plasma membrane, we further investigated the six amino acids between Delta14 and Delta20, i.e., the SITPET sequence of SERT. While the triple mutation on the possible kinase action sites, S(611), T(613), and T(616) arrested the transporter at intracellular locations, replacing the residues with aspartic acid one at a time altered neither the 5HT uptake rates nor the vimentin association of these mutants. However, replacing the three target sites with alanine, either simultaneously or one at a time, had no significant effect on 5HT uptake rates or the vimentin association with transporter. CONCLUSIONS/SIGNIFICANCE: Based on our findings, we propose that phosphate modification of the SITPET sequence differentially, one at a time exposes the vimentin binding domain on the C-terminus of SERT. Conversely, following 5HT stimulation, the association between vimentin-SERT is enhanced which changes the cellular distribution of SERT on an altered vimentin network.