Status Update and Interim Results from the Asymptomatic Carotid Surgery Trial-2 (ACST-2)

Objectives: ACST-2 is currently the largest trial ever conducted to compare carotid artery stenting (CAS) with carotid endarterectomy (CEA) in patients with severe asymptomatic carotid stenosis requiring revascularization. Methods: Patients are entered into ACST-2 when revascularization is felt to be clearly indicated, when CEA and CAS are both possible, but where there is substantial uncertainty as to which is most appropriate. Trial surgeons and interventionalists are expected to use their usual techniques and CE-approved devices. We report baseline characteristics and blinded combined interim results for 30-day mortality and major morbidity for 986 patients in the ongoing trial up to September 2012. Results: A total of 986 patients (687 men, 299 women), mean age 68.7 years (SD ± 8.1) were randomized equally to CEA or CAS. Most (96%) had ipsilateral stenosis of 70-99% (median 80%) with contralateral stenoses of 50-99% in 30% and contralateral occlusion in 8%. Patients were on appropriate medical treatment. For 691 patients undergoing intervention with at least 1-month follow-up and Rankin scoring at 6 months for any stroke, the overall serious cardiovascular event rate of periprocedural (within 30 days) disabling stroke, fatal myocardial infarction, and death at 30 days was 1.0%. Conclusions: Early ACST-2 results suggest contemporary carotid intervention for asymptomatic stenosis has a low risk of serious morbidity and mortality, on par with other recent trials. The trial continues to recruit, to monitor periprocedural events and all types of stroke, aiming to randomize up to 5,000 patients to determine any differential outcomes between interventions. Clinical trial: ISRCTN21144362. © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

Quantification of gastrointestinal liquid volumes and distribution following a 240 mL dose of water in the fasted state

Previous imaging studies offered a snapshot of water distribution in fasted humans and showed that water in the small intestine is distributed in small pockets. This study aimed to quantify the volume and number of water pockets in the upper gut of fasted healthy humans following ingestion of a glass of water (240 mL, as recommended for bioavailability/bioequivalence (BA/BE) studies), using recently validated noninvasive magnetic resonance imaging (MRI) methods. Twelve healthy volunteers underwent upper and lower abdominal MRI scans before drinking 240 mL (8 fluid ounces) of water. After ingesting the water, they were scanned at intervals for 2 h. The drink volume, inclusion criteria, and fasting conditions matched the international standards for BA/BE testing in healthy volunteers. The images were processed for gastric and intestinal total water volumes and for the number and volume of separate intestinal water pockets larger than 0.5 mL. The fasted stomach contained 35 ± 7 mL (mean ± SEM) of resting water. Upon drinking, the gastric fluid rose to 242 ± 9 mL. The gastric water volume declined rapidly after that with a half emptying time (T50%) of 13 ± 1 min. The mean gastric volume returned back to baseline 45 min after the drink. The fasted small bowel contained a total volume of 43 ± 14 mL of resting water. Twelve minutes after ingestion of water, small bowel water content rose to a maximum value of 94 ± 24 mL contained within 15 ± 2 pockets of 6 ± 2 mL each. At 45 min, when the glass of water had emptied completely from the stomach, total intestinal water volume was 77 ± 15 mL distributed into 16 ± 3 pockets of 5 ± 1 mL each. MRI provided unprecedented insights into the time course, number, volume, and location of water pockets in the stomach and small intestine under conditions that represent standard BA/BE studies using validated techniques. These data add to our current understanding of gastrointestinal physiology and will help improve physiological relevance of in vitro testing methods and in silico transport analyses for prediction of bioperformance of oral solid dosage forms, particularly for low solubility Biopharmaceutics Classification System (BCS) Class 2 and Class 4 compounds

High incidence of Kaposi sarcoma-associated herpesvirus infection in HIV-related solid immunoblastic/plasmablastic diffuse large B-cell lymphoma

Kaposi sarcoma-associated herpesvirus ( KSHV) is known to be associated with two distinct lymphoproliferative disorders: primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD)/MCD-associated plasmablastic lymphoma. We here report a high incidence of KSHV infection in solid HIV-associated immunoblastic/plasmablastic non-Hodgkin's lymphomas (NHLs), in patients lacking effusions and without evidence of ( prior) MCD. Within a cohort of 99 HIV-related NHLs, 10 cases were found to be KSHV positive on the basis of immunostaining for KSHV LNA-1 as well as KSHV-specific polymerase chain reaction. All but one of the tumors coexpressed Epstein - Barr virus. Interestingly, all KSHV-positive cases belonged to a distinctive subgroup of 26 diffuse large B-cell lymphomas characterized by the expression of CD138 (syndecan-1) and plasmablastic/immunoblastic morphology. These KSHV-positive lymphomas were preceded by Kaposi sarcoma in 60% of the patients and involved the gastrointestinal tract in 80%. Our results indicate that KSHV infection is not restricted to PEL and MCD; it is also common (38%) in HIV-related solid immunoblastic/plasmablastic lymphoma

The Zilver® PTX® Single Arm Study: 12-month results from the TASC C/D lesion subgroup

AIM:The aim of the present article was to report the 12-month results of the Zilver® PTX® Single Arm StudyTASC C/D de novo lesion subgroup.METHODS:The Zilver PTX Drug-Eluting Peripheral Stent is a self-expanding nitinol stent with a polymer-free paclitaxel coating. This is a prospective, single-arm, multicentre clinical study evaluating the Zilver PTX Drug-Eluting Peripheral Stent for treating patients with symptomatic lesions in the above-the-knee femoropopliteal artery. This study enrolled 787 patients (900 lesions) with Rutherford class 2 or higher treated with the Zilver PTX stent; 135 were long de novo lesions, corresponding to TASC II Class C or D.RESULTS:The 135 long lesions had a mean length of 226.1±43.6 mm. The 12-month Kaplan-Meier estimates included a 77.6% primary patency rate, an 84.7% event-free survival rate, and an 85.4% rate of freedom from target lesion revascularization (TLR). The 12-month stent fracture rate was 2.1%.CONCLUSION:The primary patency rates in the analysis of the TASC C/D de novo lesion subgroup of the Zilver PTX Single Arm Study indicate that endovascular therapy outcomes with a paclitaxel eluting stent may equal those of bypass surgery. Endovascular treatment with DES may play an important role for treatment of patients who present with TASC C or D femoropopliteal lesions