Low-Dose Eptifibatide for Tandem Occlusion in Stroke: Safety and Carotid Artery Patency

BACKGROUND AND PURPOSE:Maintaining carotid patency and avoiding symptomatic intracranial hemorrhage are competing concerns in tandem occlusions. This study provides data regarding the safety and efficacy of eptifibatide in stroke from tandem occlusion of the extracranial carotid artery and the intracranial carotid or middle cerebral artery.MATERIALS AND METHODS:This is a retrospective analysis of 58 consecutive patients who received low-dose eptifibatide (135-mcg/kg bolus, 1-mcg/kg/min infusion) during treatment of tandem occlusions. Brain imaging and carotid sonography were performed at 24–36 hours. mRS was documented at 90 days, and carotid sonography, at 30–60 days.RESULTS:The median age and NIHSS score were 64 years and 15, respectively. Twenty-five patients (43%) received tPA. ASPECTSs were 8–10 in 47 (81%) and 5–7 in 11 (19%) patients. Thirty-eight patients had angioplasty/stent placement acutely; 20 had angioplasty alone. Symptomatic intracranial hemorrhage occurred in 1 patient (2%). TICI 2b or higher was achieved in 56 patients (96%). Fifty-seven of 58 patients had clinical follow-up at 90 days (1 lost to follow up). The 90-day mRS was 0–2 in 42 patients (72%). There were 4/58 (7%) re-occlusions within 24–36 hours, all originally treated with stent placement. Forty-nine of 53 surviving patients had carotid sonography at 30–60 days, with 3 delayed re-occlusions, 2 with stents and 1 with angioplasty alone. The overall carotid patency at 30–60 days was 42/49 (86%). Carotid re-occlusion was not associated with clinical decline.CONCLUSIONS:Low-dose eptifibatide seemed to be safe in tandem occlusions (symptomatic intracranial hemorrhage, 2%), although asymptomatic cervical carotid artery re-occlusions still occurred in 14% of patients.

Tandem occlusion presents the simultaneous problem of an intracranial embolic large-vessel occlusion and an acute plaque rupture/thrombotic event in the cervical carotid artery. Tandem occlusion is common, representing between 13% and 32% of patients with large-vessel occlusion.^1-3 Outcomes in the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial were similar between patients with and without tandem occlusions.⁴ The goal of tandem occlusion treatment is to remove the intracranial embolus and re-establish normal flow in the cervical carotid artery without causing hemorrhage. Optimal conditions for elective carotid stent placement include therapeutic dual-antiplatelet therapy, statin loading, and intraprocedural anticoagulation. Unfortunately, such a strategy, and particularly the use of heparin, increases the risk of intracranial hemorrhage in the setting of acute stroke and particularly tandem occlusion.⁵ In general, following a successful intracranial embolectomy, extracranial carotid re-occlusion is not always associated with neurologic deterioration and poor neurologic outcome, whereas symptomatic intracranial hemorrhage (SICH) almost always is.^5-7 Avoiding SICH must be the primary consideration. However, re-occlusion of the internal carotid artery may be associated with repeat embolization. Also, direct carotid inflow to support pial collaterals may be beneficial when less-than-perfect results were achieved with intracranial thrombectomy (eg, modified TICI [mTICI] <3). At least 1 retrospective study suggested that re-occlusion is associated with worse clinical outcomes in the tandem occlusion population.⁸ Judicious medical therapy to preserve the patency of the internal carotid artery following angioplasty or stent placement is therefore reasonable, providing this can be accomplished without increasing the risk of SICH. This report aims to provide evidence regarding the safety of a specific low-dose eptifibatide antiplatelet strategy in the tandem occlusion population applied uniformly to both patients who were treated with stents and those treated with angioplasty alone and also to provide data regarding carotid artery patency in both the acute phase and the postoperative period.     

Intracranial circulation: pulse-sequence considerations in three- dimensional (volume) MR angiography

The technique and feasibility of magnetic resonance (MR) angiography of intracranial vessels were studied in 35 healthy volunteers. Variations in image orientation, repetition time (TR), and flip angle were evaluated to determine their effects on flow-related enhancement. Gradient modifications--including echo time (TE), motion compensation, bandwidth, and field of view--were also studied in an effort to reduce motion-induced phase shifts. Results indicated that a FISP (fast imaging with steady precession) sequence with a TR of 50 msec, TE of 15 msec, velocity compensation in the read and section-select directions, acceleration compensation in the read direction, anisotropic volume, and a 1.25-mm partition thickness produced three-dimensional angiographic MR images that were accurate and reproducible in the depiction of the major intracranial vessels. Difficulties with field of view, persistent signal void secondary to higher-order motion, and spatial resolution remain major problems requiring additional study.     

FM sonography in diffuse liver disease: prospective assessment and blinded analysis

FM sonography - a signal-processing technique that uses frequency and phase information as well as amplitude data - shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsy-proved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalities. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease.     

Pancreas divisum: thin-section CT

Twelve patients with known pancreas divisum underwent thin-section computed tomography (CT) to determine the capability of CT to depict this pancreatic anomaly. Focal pancreatic enlargement was present in five patients. Two distinct pancreatic moieties separated by a fat cleft were noted in three patients; a fourth patient had focal atrophy in the distribution of the dorsal pancreas. The two pancreatic moieties were identified at the same craniocaudal level in all four of these patients. The dorsal duct was depicted in all 12 patients, while the short ventral duct was seen in only five of the 12 patients. Failure of the ventral and dorsal pancreatic ducts to fuse was identified in all five patients in whom both ducts were seen. CT may not enable specific diagnosis of pancreas divisum in the majority of patients. If, however, distinct pancreatic moieties or unfused ductal systems are evident, the diagnosis may be confidently suggested.     

Specific cleavage of human type III and IV collagens by Pseudomonas aeruginosa elastase.

Purified Pseudomonas aeruginosa elastase cleaved human type III and IV collagens with the formation of specific cleavage products. Furthermore, type I collagen appeared to be slowly cleaved by both P. aeruginosa elastase and alkaline protease. These cleavage fragments from type III and IV collagens were separated from the intact collagen chains by SDS polyacrylamide gradient gel electrophoresis run under reducing conditions, and they were detected by their characteristic Coomassie blue staining pattern. The results of these studies suggest that the pathogenesis of tissue invasion and hemorrhagic tissue necrosis observed in P. aeruginosa infections may be related to the degradation of these collagen types by bacterial extracellular proteases.     

Degradation of soluble laminin and depletion of tissue-associated basement membrane laminin by Pseudomonas aeruginosa elastase and alkaline protease.

Purified Pseudomonas aeruginosa elastase and alkaline protease rapidly cleaved soluble laminin, with each enzyme yielding different cleavage products. These cleavage fragments were separated from the intact laminin A and B polypeptide chains by sodium dodecyl sulfate-polyacrylamide gradient gel electrophoresis and detected by their characteristic Coomassie blue staining patterns. Pseudomonas elastase produced rapid and extensive degradation of both A and B chains, including the disulfide-rich regions. Apparently complete degradation to limit digests was obtained after 30 min with a substrate/enzyme ratio of 30:0.5. Under similar conditions, alkaline protease rapidly degraded the A chain while slowly degrading the B chain. In addition, immunoreactive laminin was released from authentic basement membranes after incubation with either enzyme as detected by an enzyme-linked immunoabsorption assay and by immunofluorescence. The results from these studies suggest a direct role for elastase and alkaline protease in both tissue invasion and hemorrhagic tissue necrosis in P. aeruginosa infections.     

Active surveillance is superior to radical nephrectomy and equivalent to partial nephrectomy for preserving renal function in patients with small renal masses: Results from the DISSRM registry

Purpose

We compared renal function outcomes among patients in the surveillance and intervention arms of the DISSRM registry.

Efficacy,Predictive Factors,and Prediction Nomograms for 68Ga-labeled Prostate-specific Membrane Antigen–ligand Positron-emission Tomography/Computed Tomography in Early Biochemical Recurrent Prostate Cancer After Radical Prostatectomy

Recently, ⁶⁸Ga-labeled prostate-specific membrane antigen (PSMA)–ligand positron-emission tomography (PET) imaging has been shown to improve detection rates in recurrent prostate cancer (PC). However, published studies include only small patient numbers at low prostate-specific antigen (PSA) values. For this study, 272 consecutive patients with biochemical recurrence after radical prostatectomy and PSA value between 0.2 and 1 ng/ml were included. The ⁶⁸Ga-PSMA-ligand PET/computed tomography (CT) was evaluated, and detection rates were determined and correlated to various clinical variables using univariate and multivariable analyses. Subgroups of patients with very low (0.2–0.5 ng/ml) and low (>0.5–1.0 ng/ml) PSA values were analyzed. In total, lesions indicative of PC recurrence were detected in 55% (74/134) and 74% (102/138) with very low and low PSA values, respectively. Main sites of recurrence were pelvic or retroperitoneal lymph nodes metastases, followed by local recurrence and bone metastases with higher probability in the low versus very low PSA subgroup. Detection rates significantly increased with higher PSA values, primary pT ≥ 3a, primary pN+ disease, grade group ≥4, previous radiation therapy, and concurrent androgen deprivation therapy (ADT) in univariate analysis. In a multivariable logistic regression model, concurrent ADT and PSA values were identified as most relevant predictors of positive ⁶⁸Ga-PSMA-ligand PET/CT. Further, prediction nomograms were established, which may help in estimating pretest PSMA-ligand PET positivity in clinical practice.