Abstract
BACKGROUND
Stent-assisted coiling (SAC) is increasingly being performed as intervention for wide-neck intracranial aneurysms. The NeuroForm Atlas Stent (CE-marked; Stryker, Kalamazoo, ...Michigan) is relatively new.
OBJECTIVE
To evaluate the effectiveness and safety of NeuroForm Atlas SAC for intracranial aneurysms in the first such study.
METHODS
We retrospectively analyzed data from all patients treated with the NeuroForm Atlas SAC of an intracranial aneurysm, both ruptured and unruptured, between June 2015 and December 2016. Primary end-points were favorable clinical outcomes (modified Rankin scale score 0-2) and successful aneurysm occlusion (Raymond-Roy class I/II), both at 6-mo follow-up. Secondary end-points were the occurrence of intervention-related complications leading to permanent neurological deficit, the occurrence of intervention-related stroke and neurological death, immediate aneurysm occlusion, rupture (or rerupture) of the aneurysm, and recanalization.
RESULTS
Twenty-seven consecutive patients, 10 with ruptured saccular wide-neck aneurysms, were treated with NeuroForm Atlas SAC. At 6-mo follow-up, 18/26 (69.2%) survivors had successful aneurysm occlusion and 22/26 (84.6%) had favorable clinical outcome. One patient had died of a cause unrelated to treatment. No intervention-related complications leading to permanent neurological deficit occurred. However, intraprocedural thromboembolic complications occurred in 4/27 patients (14.8%), and ischemic stroke related to treatment occurred in 4/26 (15.4%). No hemorrhagic complications were observed.
CONCLUSION
NeuroForm Atlas SAC is a feasible way to treat ruptured and unruptured wide-neck aneurysms that are not amenable to conventional coiling or clipping. Aneurysm occlusion and favorable clinical outcome are consistent with previously reported rates for SAC of wide-neck aneurysms with other devices.
The interface between the nutrient‐rich Southern Ocean and oligotrophic Indian Ocean creates unique environmental conditions that can strongly influence biological processes. We investigated protist ...communities across a mesoscale meander of the Subtropical Front within the Southern Indian Ocean. 18S V9 rDNA metabarcoding suggests a diverse protist community in which the dinoflagellates and parasitic Syndiniales were abundant. Diversity was highest in frontal waters of the mesoscale meander, with differences in community structure inside and outside the meander. While the overall community was dominated by mixotrophic taxa, the frontal boundary of the meander had increased abundances of heterotrophic taxa, with potential implications for net atmospheric CO2 drawdown. Pulse amplitude modulated (PAM) fluorimetry revealed significant differences in the photophysiology of phytoplankton communities inside and outside the meander. By using single‐cell PAM microscopy, we identified physiological differences between dinoflagellate and coccolithophore taxa, which may have contributed to changes in photophysiology observed at community level. Overall, our results demonstrate that frontal areas have a strong impact on the composition of protist communities in the Southern Ocean with important implications for understanding biological processes in this region.
We studied species composition and photo physiological properties of protist communities across a meander region in the Southern Indian Ocean. Metabarcoding revealed varying community composition in different meander regions corresponding to environmental gradients. Taxon‐specific photo physiological properties indicate that overall community physiology is determined by both community composition and species‐specific physiology.
FRET-based caspase activity probes have become important tools to monitor apoptotic cell signaling. However, their dependence on external illumination is incompatible with light sensitive cells and ...hampers applications that suffer from autofluorescence and light scattering. Here we report the development of three caspase sensor proteins based on Bioluminescence Resonance Energy Transfer (BRET) that retain the advantages of genetically encoded, ratiometric optical probes but do not require external illumination. These sensors consist of the bright and stable luciferase NanoLuc and the fluorescent protein mNeonGreen, fused together via a linker containing a recognition site for caspase-3, -8, or -9. In vitro characterization showed that each caspase sensor displayed a robust 10-fold decrease in BRET ratio upon linker cleavage, with modest caspase specificity. Importantly, whereas scattering and background fluorescence precluded FRET-based detection of intracellular caspase activity in plate-reader assays, such measurements could be easily performed using our caspase BRET sensors in a high throughput format. The brightness of the BRET sensors also enabled long-term single-cell imaging, allowing BRET-based recording of cell heterogeneity in caspase activity in a heterogenic cell population.
Clinical application of continuous flow peritoneal dialysis (CFPD) has been explored since the 1960s, but despite anticipated clinical benefits, CFPD has failed to gain a foothold in clinical ...practice, among others due to the typical use of two catheters (or a dual‐lumen catheter) and large dialysate volumes required per treatment. Novel systems applying CFPD via the existing single‐lumen catheter using rapid dialysate cycling may solve one of these hurdles. Novel on‐demand peritoneal dialysate generation systems and sorbent‐based peritoneal dialysate regeneration systems may considerably reduce the storage space for peritoneal dialysate and/or the required dialysate volume. This review provides an overview of current evidence on CFPD in vivo. The available (pre)clinical evidence on CFPD is limited to case reports/series with inherently nonuniform study procedures, or studies with a small sample size, short follow‐up, and no hard endpoints. Small solute clearance appears to be higher in CFPD compared to conventional PD, in particular at dialysate flows ≥100 mL/min using two single‐lumen catheters or a double‐lumen catheter. Results of CFPD using rapid cycling via a single‐lumen catheter are too preliminary to draw any conclusions. Continuous addition of glucose to dialysate with CFPD appears to be effective in reducing the maximum intraperitoneal glucose concentration while increasing ultrafiltration efficiency (mL/g absorbed glucose). Patient tolerance may be an issue since abdominal discomfort and sterile peritonitis were reported with continuous circulation of the peritoneal dialysate. Thus, well‐designed clinical trials of longer duration and larger sample size, in particular applying CFPD via the existing catheter, are urgently required.
Cue-Exposure Therapy (CET) is considered an effective strategy to combat cigarette cravings and smoking relapses, but evidence is mixed. In this lab-based experimental study, we manipulated levels of ...realism for smoking scenarios in Virtual Environments (VE) and randomly exposed smokers and recent-quitters to one of two versions (low versus high realism) of these scenarios. Prior and after scenario exposure, valid measures of cigarette craving were obtained. Prior to exposure, we assessed nicotine dependence and smoking status (current smokers versus recent-quitter). Within-subject repeated measures analysis of covariance showed that there was an interaction of experimental condition with smoking status on cigarette craving. Amongst recent-quitters, high realistic scenarios produced stronger increases in craving than low realistic scenarios, but this effect was reversed in current smokers. It is concluded that VE technologies are a potentially relevant tool for smoking CET that warrant further exploration.
Protein-bound uremic toxins (PBUTs) are associated with the progression of chronic kidney disease (CKD) and its associated morbidity and mortality. The conventional dialysis techniques are unable to ...efficiently remove PBUTs due to their plasma protein binding. Therefore, novel approaches are being developed, but these require validation in animals before clinical trials can begin. We conducted a systematic review to document PBUT concentrations in various models and species. The search strategy returned 1163 results for which abstracts were screened, resulting in 65 full-text papers for data extraction (rats (n = 41), mice (n = 17), dogs (n = 3), cats (n = 4), goats (n = 1), and pigs (n = 1)). We performed descriptive and comparative analyses on indoxyl sulfate (IS) concentrations in rats and mice. The data on large animals and on other PBUTs were too heterogeneous for pooled analysis. Most rodent studies reported mean uremic concentrations of plasma IS close to or within the range of those during kidney failure in humans, with the highest in tubular injury models in rats. Compared to nephron loss models in rats, a greater rise in plasma IS compared to creatinine was found in tubular injury models, suggesting tubular secretion was more affected than glomerular filtration. In summary, tubular injury rat models may be most relevant for the in vivo validation of novel PBUT-lowering strategies for kidney failure in humans.
Heparin is a widely used anticoagulant which inhibits factor Xa and thrombin through potentiation of antithrombin. We recently identified that the nucleic acid stain SYTOX reacts with platelet ...polyphosphate due to molecular similarities, some of which are shared by heparin. We attempted to study heparin in flowing blood by live-cell fluorescence microscopy, using SYTOX for heparin visualisation. Immunostaining was performed with monoclonal antibodies directed against various heparin-binding proteins. In addition, we studied modulation of heparin activity in coagulation assays, as well its effects on fibrin formation under flow in recalcified whole blood. We found that SYTOX-positive polymers appear in heparinised blood under flow. These polymers typically associate with platelet aggregates and their length (reversibly) increases with shear rate. Immunostaining revealed that of the heparin-binding proteins assessed, they only contain histones. In coagulation assays and flow studies on fibrin formation, we found that addition of exogenous histones reverses the anticoagulant effects of heparin. Furthermore, the polymers do not appear in the presence of DNase I, heparinase I/III, or the heparin antidote protamine. These findings suggest that heparin forms polymeric complexes with cell-free DNA in whole blood through a currently unidentified mechanism.
With increasing interest in home dialysis, there is a need for a translational uremic large animal model to evaluate technical innovations in peritoneal dialysis (PD). To this end, we developed a ...porcine model with kidney failure. Stable chronic kidney injury was induced by bilateral subtotal renal artery embolization. Before applying PD, temporary aggravation of uremia was induced by administration of gentamicin (10 mg/kg i.v. twice daily for 7 days), to obtain uremic solute levels within the range of those of dialysis patients. Peritoneal transport was assessed using a standard peritoneal permeability assessment (SPA). After embolization, urea and creatinine concentrations transiently increased from 1.6 ± 0.3 to 7.5 ± 1.2 mM and from 103 ± 14 to 338 ± 67 µM, respectively, followed by stabilization within 1–2 weeks to 2.5 ± 1.1 mM and 174 ± 28 µM, respectively. Gentamicin induced temporary acute-on-chronic kidney injury with peak urea and creatinine concentrations of 16.7 ± 5.3 mM and 932 ± 470 µM respectively. PD was successfully applied, although frequently complicated by peritonitis. SPA showed a low transport status (D/P creatinine at 4 h of 0.41 (0.36–0.53)) with a mass transfer area coefficient of 9.6 ± 3.1, 4.6 ± 2.6, 3.4 ± 2.3 mL/min for urea, creatinine, and phosphate respectively. In conclusion, this porcine model with on-demand aggravation of uremia is suitable for PD albeit with peritoneal transport characterized by a low transport status.
OBJECTIVE Treatment of wide-necked intracranial aneurysms is associated with higher recanalization and complication rates; however, the most commonly used methods are not specifically designed to ...work in bifurcation lesions. To address these issues, the authors describe the evolution in the design and use of the eCLIPs (Endovascular Clip System) device, a novel hybrid stent-like assist device with flow diverter properties that was first described in 2008. METHODS A registry was established covering 13 international centers at which patients were treated with the second-generation eCLIPs device. Aneurysm morphology and rupture status, device neck coverage, coil retention, and procedural and late morbidity and mortality were recorded. For those patients who had undergone successful implantation more than 6 months earlier, the final imaging and clinical follow-up results and need for re-treatment were recorded. RESULTS Thirty-three patients were treated between June 2013 and September 2015. Twenty-five (76%) patients had successful placement of an eCLIPs device; 23 (92%) of these 25 patients had complete data. Eight cases of nondeployment occurred during the 1st year of use, consistent with a learning curve; no failures of deployment occurred thereafter. Two periprocedural transient ischemic attacks and 2 asymptomatic thrombotic events occurred. Twenty-one (91%) of 23 patients underwent follow-up at an average of 8 months (range 3-18 months); 9 (42.9%) of these 21 patients demonstrated an improvement in Raymond grade at follow-up; no cases of worsening Raymond grade were recorded, and 17 (81.0%) patients sustained a modified Raymond-Roy Classification class of I or II angiographic result at follow-up. Two delayed ruptures were recorded, both in previously coiled, symptomatic giant aneurysms where the device was used as a part of a salvage strategy. CONCLUSIONS The second-generation eCLIPs device is a viable treatment option for bifurcation aneurysms. The aneurysm occlusion rates in this initial clinical series are comparable to the initial experience with other bifurcation support devices.
PDF
