Transradial versus transfemoral access for mechanical thrombectomy in acute ischemic stroke: A retrospective cohort study.

BACKGROUND: The objective of this study was to compare procedural and clinical outcomes in patients with acute ischemic stroke (AIS) treated via transradial access (TRA) mechanical thrombectomy (MT) versus conventional transfemoral access (TFA). METHODS: We performed a retrospective analysis of consecutive patients with AIS treated with TRA versus TFA MT at our tertiary comprehensive stroke center. Access choice was individualized based on occlusion site, aortic and arch anatomy. Outcomes were extracted from our institutional stroke registry and included procedural time, Thrombolysis in Cerebral Infarction (TICI) reperfusion score, NIHSS, 90-day mRS and 90-day mortality. Comparisons were performed using Student t-Test and Fischer's exact test as appropriate. RESULTS: 175 mechanical thrombectomies were performed during the study interval; 39 (22%) were performed via TRA and 136 (79%) TFA. Access to reperfusion time was 36.3 ± 24.5 minutes in the TRA group and 21.9 ± 17.6 in the TFA group (p<0.001). The proportion of patients with a TICI reperfusion score of 2b or 3 was similar in both groups (TRA: 34 (87%) vs. TFA: 121 (89%) p=0.559. The median 90-day mRS was similar between both groups (p=0.170), as was the 90-day mortality (p = 0.509). CONCLUSIONS: While TFA is faster in our cohort, TFA and TRA are both safe and effective for MT in acute ischemic stroke. While TFA remains mainstay, TRA can be valuable in variant anatomy despite its technical limitations. Individualizing access based on advanced imaging and patient factors may improve practice; however, updates in catheter and access technology are necessary to optimize outcomes with TRA.

Further Validation of the Female Sexual Function Index: Specificity and Associations With Clinical Interview Data.

Female sexual function is a multi-faceted psychophysiological construct. The Female Sexual Function Index (FSFI) is considered a "gold standard" self-report instrument that assesses the various aspects of sexual function. However, researchers have recently proposed potential limitations of the FSFI, highlighting the need for continued validation research. The aims of the current analyses were (a) to assess the correlations between FSFI scores and information regarding specific rates of functional impairment gained via clinical interview; and (b) to assess the specificity of FSFI subscale scores in reflecting corresponding aspects of sexual function (e.g., whether the Sexual Desire subscale reflects sexual desire specifically rather than sexual arousal, orgasm, etc.). The participants were 97 sexually active women who reported impairments in sexual function. Clinical interview data exhibited moderate-to-strong correlations with FSFI scores. Additionally, FSFI subscales generally exhibited adequate specificity in terms of reflecting their corresponding aspects of sexual function more strongly than other aspects. The results generally supported the validity of the FSFI. Implications for the measurement and conceptualization of female sexual function are discussed.

Immune Thrombocytopenic Purpura Presenting with Pituitary Apoplexy: A Case Report and Literature Review.

Background Pituitary apoplexy is a rare condition that usually occurs in the setting of a pituitary adenoma. It can present with symptoms of visual disturbances, vertigo, headache, and neurological impairments. Computed tomography (CT) scans can aid in identifying pituitary apoplexy and ruling out other diseases. We present a unique case of pituitary apoplexy in the setting of immune thrombocytopenic purpura (ITP). Case Description A 61-year-old man with a past medical history significant for myocardial infarction presented to the emergency department with symptoms of diplopia and headache 36 hours after onset. The patient was found to have severe thrombocytopenia with a platelet count below 20,000. A CT of the head revealed a possible pituitary adenoma with compression of the optic chiasm. The patient's platelet count continued to decrease throughout his admission and dropped below 7,000 on day 2 of admission. The patient was given platelet transfusion along with intravenous immunoglobulins. The patient underwent endoscopic transsphenoidal resection of the pituitary mass. Pathology of the mass revealed immature platelets characteristic of immune ITP in the setting of pituitary apoplexy. Conclusion While ITP in the setting of pituitary apoplexy is a rare entity, we believe that clinicians should have pituitary apoplexy on their differential diagnosis in patients with ITP.

Radial Access Intervention.

Leveraging from the interventional cardiology experience, the transradial access (TRA) for neurointervention has also started to become more used for both diagnostic and therapeutic procedures. A growing body of evidence is showing a superiority of the TRA compared with the conventional transfemoral access (TFA) in terms of access site complications (ACSs), patient satisfaction and preference, hospital length of stay, and cost. Outcomes via the transradial are noninferior, and at times superior, in select neuroendovascular procedures. Future advancements in technology with radial-specific catheters and further operator experience will aid in the full adoption of the TRA for endovascular procedures.

Combined Decompressive Hemicraniectomy and Port-Based Minimally Invasive Parafascicular Surgery for the Treatment of Subcortical Intracerebral Hemorrhage: Case Series, Technical Note, and Review of Literature.

BACKGROUND: Intracerebral hemorrhage (ICH) is a neurosurgical emergency. Combined decompressive hemicraniectomy (DHC) and minimally invasive parafascicular surgery (MIPS) may provide a practical method of managing subcortical ICH. OBJECTIVE: 1) To present a case series of combined DHC-MIPS for the treatment of subcortical-based ICH; 2) to describe technical nuances of DHC-MIPS; and 3) to provide a literature overview of MIPS for ICH. METHODS: The following inclusion criteria were used: 1) Glasgow Coma Scale (GCS) score <3-4; 2) admission within 6 hours of onset; 3) increased intracranial pressure caused by hemorrhage; 4) patient unresponsive to medical management; 5) hemorrhage >30 cm3; 6) subcortical location; and 7) midline shift (mm). Before DHC, sulcal cannulation used the following coordinates: intersection of tragus-frontal bone and midpoint of midpupillary line and midline; coronal suture: 3-4 cm posterior to this point). RESULTS: Three patients were selected: a 62-year old woman, a 45-year old woman, and a 36-year-old man. GCS and ICH scores on admission were 7 and 3, 3 and 4, and 3 and 4, respectively. ICH was located in left basal ganglia in patients 1 and 3 and right basal ganglia in patient 2, all with intraventricular extension. ICH volume was 81.7, 68.2, and 42.3 cm3, respectively. The postoperative GCS score was 11, 10, and 6, respectively. There were no intraoperative complications or mortalities. Evacuation was within 15 minutes in all patients. The modified Rankin Scale score was 3, 4, and 5, respectively, with semi-independence in case 1. CONCLUSIONS: Combined DHC-MIPS, with the use of craniometric points, can provide a unique and simple surgical option for the management of subcortical ICH.

Minimally Invasive Parafascicular Surgical Approach for the Management of a Pediatric Third Ventricular Ependymoma: Case Report and Review of Literature.

BACKGROUND: Minimally invasive parafascicular surgery (MIPS) has evolved into a safe alternative to access deep-seated subcortical and intraventricular pathologies. We present a case of a port-mediated resection of a pediatric third ventricular tumor. CASE DESCRIPTION: The patient is a 7-year-old boy who presented with worsening headache, nausea, vomiting, dizziness, unsteady gait, photophobia, and blind spots with positional changes. Magnetic resonance imaging (MRI) scan revealed a large isointense mass, with areas of hyperintensities suggestive of intratumoral hemorrhage, centered in the posterior segment of the third ventricle with extension into the aqueduct of Sylvius. The superior frontal sulcus was used as an access corridor for the port to the frontal horn of the lateral ventricle en route to the third ventricle. Intraoperative visualization was aided with a 3-dimensional exoscopic system. After cannulation, the tumor was seen within the foramen of Monro and tethered to the thalamostriate vein. The tumor was removed completely, with the exception of small residual attached to the thalamostriate vein, which was left intentionally. A flexible endoscope was placed through the port to verify the absence of residual along the superior wall of the third ventricle. Intraoperative MRI scan confirmed presence of residual, along with normal postoperative changes, including pneumocephalus. Postoperative MRI scan revealed cortical recovery along the sulcal path and resolution of ventriculomegaly. CONCLUSIONS: The patient improved from baseline, with no remaining visual deficits, headaches, or balance issues. Pathology reported a World Health Organization grade II tanycytic ependymoma. To our knowledge, few cases have reported the utilization of port-based MIPS in pediatric patients.

Ligand-independent activation of androgen receptors by Rho GTPase signaling in prostate cancer.

Prostate cancer invariably recurs after androgen deprivation therapy. Growth of this recurrent/androgen-independent form of prostate cancer may be due to increased androgen receptor (AR) transcriptional activity in the absence of androgen. This ligand-independent AR activation is promoted by some growth factors but the mechanism is not well understood. Vav3, a Rho guanosine triphosphatase guanine nucleotide exchange factor, which is activated by growth factors, is up-regulated in human prostate cancer. We show here that Vav3 levels increase during in vivo progression of prostate cancer to androgen independence. Vav3 strikingly enhanced growth factor activation of AR in the absence of androgen. Because Vav3 may be chronically activated in prostate cancer by growth factor receptors, we examined the effects of a constitutively active (Ca) form of Vav3 on AR transcriptional activity. Ca Vav3 caused nuclear localization and ligand-independent activation of AR via the Rho guanosine triphosphatase, Rac1. Ca Rac1 activation of AR occurred, in part, through MAPK/ERK signaling. Expression of active Rac1 conferred androgen-independent growth of prostate cancer cells in culture, soft agar, and mice. These findings suggest that Vav3/Rac 1 signaling is an important modulator of ligand-independent AR transcriptional activity in prostate cancer progression.

Vav3, a Rho GTPase guanine nucleotide exchange factor, increases during progression to androgen independence in prostate cancer cells and potentiates androgen receptor transcriptional activity.

The progression of prostate cancer from androgen dependence to androgen independence is often accompanied by enhanced androgen receptor (AR) transcriptional activity. We observed a marked increase in the expression of Vav3, a Rho GTPase guanine nucleotide exchange factor (GEF), during the progression of human prostate cancer LNCaP cells to the androgen-independent derivative, LNCaP-R1. GEFs activate Rho family GTPases by promoting the exchange of GDP for GTP. Reporter gene assays showed that Vav3 potentiated AR transcriptional activity, and knock down of Vav3 resulted in decreased AR transactivation. Vav3 also increased androgen-induced levels of prostate-specific antigen mRNA. Furthermore, Vav3 enhanced AR activity at subnanomolar concentrations of androgen. This finding is particularly relevant because low androgen levels may be present in prostate tissue of patients undergoing androgen deprivation therapy. Enhancement of AR activity by Vav3 required amino terminal activation function 1 (AF1) of AR; however, Vav3 did not interact with AR or increase AR levels. Neither GEF function nor the C-terminal domains of Vav3 were required for Vav3-mediated enhancement of AR activity; however, the pleckstrin homology domain was obligatory. These data show that Vav3 levels rise during progression to androgen independence and support continued AR signaling (even under conditions of low androgen) by a novel GEF-independent cross-talk mechanism.

Deregulation of the Rho GTPase, Rac1, suppresses cyclin-dependent kinase inhibitor p21(CIP1) levels in androgen-independent human prostate cancer cells.

Abnormally suppressed levels of cyclin-dependent kinase inhibitors (CKIs) are associated with aggressive androgen-independent prostate cancer and contribute to uncontrolled proliferation. The androgen-independent human prostate cancer cell lines, LNCaP-104R1, ALVA31 and PC-3, express low levels of the CKI, p21(CIP1), compared to the less-malignant, androgen-dependent LNCaP cells. We investigated the mechanism underlying this suppression by examining the role of Rho GTPases, signaling proteins that play important roles in cell cycle progression, at least in part through regulation of CKIs. Inhibition of Rac1 induced p21 expression in androgen-independent lines but had no effect on the higher p21 levels characteristic of LNCaP cells. This induction of p21 was functionally significant as evidenced by inhibition of cyclin-dependent kinase 2 activity and decreased cell proliferation. Conversely, overexpression of constitutively active Rac1 suppressed the higher p21 levels seen in LNCaP cells. Thus, Rac1 activity is both necessary and sufficient for suppression of p21 in prostate cancer cells. Furthermore, Rac1 activity was significantly higher in all three androgen-independent cell lines compared to LNCaP cells. Thus in three models of aggressive human prostate cancer, hyperactivity of Rac1 corresponds to suppressed levels of p21. These results are unique in describing a role for Rac1 in p21 regulation and may implicate the Rac1 signaling pathway as a potential therapeutic target for controlling prostate cancer cell growth following progression to androgen independence.

Inhibition of the Rho GTPase, Rac1, decreases estrogen receptor levels and is a novel therapeutic strategy in breast cancer.

Rac1, a Rho GTPase, modulates diverse cellular processes and is hyperactive in some cancers. Estrogen receptor-alpha (ERα) in concert with intracellular signaling pathways regulates genes associated with cell proliferation, tumor development, and breast cancer cell survival. Therefore, we examined the possibility of Rac1 and ERα crosstalk in breast cancer cells. We found that Rac1 enhanced ERα transcriptional activity in breast cancer cells. Vav3, a Rho guanine nucleotide exchange factor that activates Rac1, was an upstream mediator, and P21/Cdc42/Rac1 activating kinase-1 (Pak-1) was a downstream effector of Rac1 enhancement of ERα activity. These results suggest that Rac1 may prove to be a therapeutic target. To test this hypothesis, we used a small molecule Rac inhibitor, EHT 1864, and found that EHT 1864 inhibited ERα transcriptional activity. Furthermore, EHT 1864 inhibited estrogen-induced cell proliferation in breast cancer cells and decreased tamoxifen-resistant breast cancer cell growth. EHT 1864 decreased activity of the promoter of the ERα gene resulting in down-regulation of ERα mRNA and protein levels. Therefore, ERα down-regulation by EHT 1864 is the likely mechanism of EHT 1864-mediated inhibition of ERα activity and estrogen-stimulated breast cancer cell proliferation. Since ERα plays a critical role in the pathogenesis of breast cancer and the Rac inhibitor EHT 1864 down-regulates ERα expression and breast cancer cell proliferation, further investigation of the therapeutic potential of Rac1 targeting in the treatment of breast cancer is warranted.