Animal Models for Studying Protein-Bound Uremic Toxin Removal-A Systematic Review.

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.

Mesoscale oceanographic meanders influence protist community function and structure in the southern Indian Ocean.

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.

Portable, wearable and implantable artificial kidney systems: needs, opportunities and challenges.

Haemodialysis is life sustaining but expensive, provides limited removal of uraemic solutes, is associated with poor patient quality of life and has a large carbon footprint. Innovative dialysis technologies such as portable, wearable and implantable artificial kidney systems are being developed with the aim of addressing these issues and improving patient care. An important challenge for these technologies is the need for continuous regeneration of a small volume of dialysate. Dialysate recycling systems based on sorbents have great potential for such regeneration. Novel dialysis membranes composed of polymeric or inorganic materials are being developed to improve the removal of a broad range of uraemic toxins, with low levels of membrane fouling compared with currently available synthetic membranes. To achieve more complete therapy and provide important biological functions, these novel membranes could be combined with bioartificial kidneys, which consist of artificial membranes combined with kidney cells. Implementation of these systems will require robust cell sourcing; cell culture facilities annexed to dialysis centres; large-scale, low-cost production; and quality control measures. These challenges are not trivial, and global initiatives involving all relevant stakeholders, including academics, industrialists, medical professionals and patients with kidney disease, are required to achieve important technological breakthroughs.

A systematic review of the Woven EndoBridge device-do findings in pre-clinical animal models compare to clinical results?

BACKGROUND: The Woven Endobridge (WEB) is designed to treat intracranial wide-neck bifurcation aneurysms, preventing subarachnoid hemorrhage. The translational value of animal models used for WEB device testing is unknown. With this systematic review, we aim to identify the existing animal models used in testing the WEB device and compare the efficacy and safety outcomes to those of prospective clinical studies. METHODS: This study was funded by ZonMw: project number 114024133. A comprehensive search was performed in PubMed and in EMBASE via the Ovid interface. The following exclusion criteria were used: 1) not an original full-length research paper, 2) not an in vivo animal study or a human study, 3) no WEB implantation, 4) if in humans: not a prospective study. The SYRCLE risk of bias tool (animal studies) and the Newcastle-Ottawa quality assessment scale for cohort studies (clinical studies) were used to assess risks of bias. A narrative synthesis was performed. RESULTS: Six animal studies and 17 clinical studies met the inclusion criteria. The rabbit elastase aneurysm model was the only animal model used to assess WEB device performance. Safety outcomes were never reported in animal studies. Efficacy outcomes were more heterogeneous in animal studies than in clinical studies, which could be due to limited external validity of the animal models in terms of aneurysm induction and dimensions. Both animal and clinical studies were predominantly single-arm studies, and were at unclear risk of several types of bias. CONCLUSIONS: The rabbit elastase aneurysm model was the only pre-clinical animal model used to assess WEB device performance. Safety outcomes were not evaluated in animal studies and could therefore not be compared to clinical outcomes. Efficacy outcomes were more heterogeneous in animal studies than in clinical studies. Future research should focus on improving methodology and reporting in order to draw accurate conclusions on the performance of the WEB device.

Surpass Intracranial Aneurysm Embolization System Pivotal Trial to Treat Large or Giant Wide-Neck Aneurysms - SCENT: 3-year outcomes.

BACKGROUND: To report the 3-year safety and effectiveness of the Surpass Streamline flow diverter in the SCENT trial (Surpass Intracranial Aneurysm Embolization System Pivotal Trial to Treat Large or Giant Wide-Neck Aneurysms). METHODS: The Surpass Streamline flow diverter device was evaluated in a multicenter, prospective, single-arm, non-randomized interventional trial including patients with uncoilable or previously treated but failed aneurysms of the intracranial internal carotid artery. 3-year outcomes were tabulated with descriptive statistics and compared with 1-year outcomes. RESULTS: Of 180 patients in the modified intent-to-treat (mITT) cohort, 36-month clinical and angiographic follow-up was available in 134 and 117 cases, respectively. Effectiveness endpoint of complete aneurysm occlusion without clinically significant stenosis or retreatment was met in 71.8% (79/110, 95% CI 62.4% to 80.0%) of cases. Safety composite endpoint was 12.2% (22/180) over the 3-year period, with two major safety events (ipsilateral ischemic strokes) occurring between 12-36 months. Complete aneurysm occlusion was noted in 77.8% (91/117), and 99.1% (116/117) of the patients demonstrated adequate aneurysm occlusion (complete occlusion or neck residual). There were four cases (2.2%) of aneurysm rupture, all occurring within the first month of the index procedure. Target aneurysm retreatment rate was 2.8% (5/180). CONCLUSION: The present findings support the long-term safety and effectiveness of the Surpass Streamline flow diverter device. TRIAL REGISTRATION: NCT01716117.

European Stroke Organisation (ESO) - European Society for Minimally Invasive Neurological Therapy (ESMINT) Guidelines on Mechanical Thrombectomy in Acute Ischemic Stroke.

BACKGROUND: Mechanical thrombectomy (MT) has become the cornerstone of acute ischemic stroke management in patients with large vessel occlusion (LVO). OBJECTIVE: To assist physicians in their clinical decisions with regard toMT. METHODS: These guidelines were developed based on the standard operating procedure of the European Stroke Organisation and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. An interdisciplinary working group identified 15 relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote evidence-based recommendations. Expert opinion was provided if not enough evidence was available to provide recommendations based on the GRADE approach. RESULTS: We found high-quality evidence to recommend MT plus best medical management (BMM, including intravenous thrombolysis whenever indicated) to improve functional outcome in patients with LVO-related acute ischemic stroke within 6 hours after symptom onset. We found moderate quality of evidence to recommend MT plus BMM in the 6-24h time window in patients meeting the eligibility criteria of published randomized trials. These guidelinesdetails aspects of prehospital management, patient selection based on clinical and imaging characteristics, and treatment modalities. CONCLUSIONS: MT is the standard of care in patients with LVO-related acute stroke. Appropriate patient selection and timely reperfusion are crucial. Further randomized trials are needed to inform clinical decision-making with regard tothe mothership and drip-and-ship approaches, anesthaesia modalities during MT, and to determine whether MT is beneficial in patients with low stroke severity or large infarct volume.

Safety and efficacy of the eCLIPs bifurcation remodelling system for the treatment of wide necked bifurcation aneurysms: 1 year results from the European eCLIPs Safety, Feasibility, and Efficacy Study (EESIS).

BACKGROUND: The eCLIPs bifurcation remodelling system is a non-circumferential implant that bridges the neck from outside of a bifurcation aneurysm. The goal of the multicenter, post-marketing European eCLIPs Safety, FeasIbility, and Efficacy Study (EESIS), was to present the efficacy and safety results of the eCLIPs device after 365 days of follow-up. METHODS: All patients were to receive an eCLIPs in conjunction with coils. The study was conducted according to good clinical practices and included independent adjudication of safety and efficacy outcomes. RESULTS: Twenty patients were enrolled at four European centers. Mean age was 60 years (range 41-74) and aneurysms were located at the basilar tip (n=19) and carotid tip (n=1). Average aneurysm dome height was 6.0 mm (range 2.0-15.0). Mean neck length was 5.1 mm (range 2.6-8.5). The technical success rate was 90% (18 of 20). No major territorial strokes or deaths occurred between the index procedure and after 365 days of follow-up. Complete occlusion was achieved in 60% of patients (12 of 20 patients) and 67% of patients with an eCLIPs device (12 of 18) after 365 days of follow-up. Adequate occlusion (complete occlusion and neck remnant) was achieved in 80% of patients (16 of 20 patients) and 89% of patients with an eCLIPs device (16 of 18 patients) after 365 days of follow-up. CONCLUSION: In this small series, treatment with eCLIPs was feasible, safe, and efficacious, considering the challenging nature of the aneurysms. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02607501.

Treatment of large and giant posterior communicating artery aneurysms with the Surpass streamline flow diverter: results from the SCENT trial.

BACKGROUND: The Surpass flow diverter was developed to treat intracranial aneurysms not amenable to standard treatment. Indications for use allow placement in the internal carotid artery to the terminus, including the communicating artery segment. METHODS: The Surpass Intracranial Aneurysm Embolization System Pivotal Trial to Treat Large or Giant Wide Neck Aneurysms (SCENT) trial is an international, multicenter, prospective, non-randomized trial comparing the outcomes of Surpass flow diverter treatment with historic control designed to evaluate the effectiveness and safety of Surpass for the treatment of wide neck (≥4 mm) large or giant intracranial aneurysms ≥10 mm. The primary effectiveness endpoint is the percentage of subjects with 100% aneurysm occlusion without significant stenosis of the parent artery and without retreatment of the target aneurysm at 12 months. The primary safety endpoint is the percentage of subjects experiencing neurologic death or major ipsilateral stroke at 12 months. We report the effectiveness and safety of flow diversion in the subgroup of posterior communicating artery (PComA) aneurysms. RESULTS: Of the 180 patients treated, 38 harbored a PComA aneurysm. Mean aneurysm size was 12.2 mm and mean neck width was 4.8 mm. The mean number of Surpass devices used was 1.1 per procedure, with 94.7% of aneurysms treated with one flow diverter. The 12 month primary effectiveness rate was 73.7% (28/38). At 36 months, 68.4% (26/38) of aneurysms remained completely occluded. The 12 month major ipsilateral stroke or neurological death rate was 10.5%. No patients with PComA occlusion after flow diverter placement (54.5%) had clinical sequelae. CONCLUSIONS: SCENT demonstrated acceptable 12 month effectiveness of flow diversion in PComA aneurysms. Despite associated PComA occlusions in many cases, arterial occlusions were clinically silent. TRIAL REGISTRATION NUMBER: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT01716117.

A Uremic Pig Model for Peritoneal Dialysis.

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.

Evidence on continuous flow peritoneal dialysis: A review.

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.

Outcomes after Flow Diverter Treatment in Subarachnoid Hemorrhage: A Meta-Analysis and Development of a Clinical Prediction Model (OUTFLOW).

BACKGROUND: patients with a subarachnoid hemorrhage (SAH) might need a flow diverter (FD) placement for complex acutely ruptured intracranial aneurysms (IAs). We conducted a meta-analysis and developed a prediction model to estimate the favorable clinical outcome after the FD treatment in acutely ruptured IAs. METHODS: a systematic literature search was performed from 2010 to January 2021 in PubMed and Embase databases. Studies with more than five patients treated with FDs within fifteen days were included. In total, 1157 studies were identified. The primary outcome measure was the favorable clinical outcome (mRS 0-2). Secondary outcome measures were complete occlusion rates, aneurysm rebleeding, permanent neurologic deficit caused by procedure-related complications, and all-cause mortality. A prediction model was constructed using individual patient-level data. RESULTS: 26 retrospective studies with 357 patients and 368 aneurysms were included. The pooled rates of the favorable clinical outcome, mortality, and complete aneurysm occlusion were 73.7% (95% CI 64.7-81.0), 17.1% (95% CI 13.3-21.8), and 85.6% (95% CI 80.4-89.6), respectively. Rebleeding occurred in 3% of aneurysms (11/368). The c-statistic of the final model was 0.83 (95% CI 0.76-0.89). All the studies provided a very low quality of evidence. CONCLUSIONS: FD treatment can be considered for complex ruptured IAs. Despite high complication rates, the pooled clinical outcomes seem favorable. The prediction model needs to be validated by larger prospective studies before clinical application.

Time trends in the risk of delayed cerebral ischemia after subarachnoid hemorrhage: a meta-analysis of randomized controlled trials.

OBJECTIVE: Delayed cerebral ischemia (DCI) contributes to morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). Continuous improvement in the management of these patients, such as neurocritical care and aneurysm repair, may decrease the prevalence of DCI. In this study, the authors aimed to investigate potential time trends in the prevalence of DCI in clinical studies of DCI within the last 20 years. METHODS: PubMed, Embase, and the Cochrane library were searched from 2000 to 2020. Randomized controlled trials that reported clinical (and radiological) DCI in patients with aSAH who were randomized to a control group receiving standard care were included. DCI prevalence was estimated by means of random-effects meta-analysis, and subgroup analyses were performed for the DCI sum score, Fisher grade, clinical grade on admission, and aneurysm treatment method. Time trends were evaluated by meta-regression. RESULTS: The search strategy yielded 5931 records, of which 58 randomized controlled trials were included. A total of 4424 patients in the control arm were included. The overall prevalence of DCI was 0.29 (95% CI 0.26-0.32). The event rate for prevalence of DCI among the high-quality studies was 0.30 (95% CI 0.25-0.34) and did not decrease over time (0.25% decline per year; 95% CI -2.49% to 1.99%, p = 0.819). DCI prevalence was higher in studies that included only higher clinical or Fisher grades, and in studies that included only clipping as the treatment modality. CONCLUSIONS: Overall DCI prevalence in patients with aSAH was 0.29 (95% CI 0.26-0.32) and did not decrease over time in the control groups of the included randomized controlled trials.

Factors Associated with Subsequent Subarachnoid Hemorrhages in Patients with Multiple Intracranial Aneurysms.

BACKGROUND: Detection of multiple intracranial aneurysms (MIAs) in patients with aneurysmal subarachnoid hemorrhage (aSAH) is common and the optimal management of the additional unruptured intracranial aneurysms (UIA) is often a matter of debate. We calculate the incidence and the factors associated with subsequent aSAHs from untreated additional aneurysms in a single-center group of patients with aSAH and MIAs. METHODS: Charts of patients with MIAs admitted to our neurosurgery department for aSAH between January 2000 and March 2020 were retrospectively reviewed. Incidence rate and factors associated with subsequent aSAHs were calculated with univariable and multivariable analyses. RESULTS: Of the unruptured aneurysms, 50% were preventively treated. During a median follow-up of 3 years, 20 of 174 patients (11.5%) presented with a second aSAH. Incidence of rupture of an additional untreated aneurysm was 18.05 per 1000 person/years (confidence interval, 10.69-30.47). Rupture incidence of an additional aneurysm located in the anterior circulation was 32.70 per 1000 person/years and 40.73 per 1000 person/years in the posterior circulation. Presence of untreated mirror and de novo aneurysms increased the risk of overall subsequent aSAHs by 16.9-fold and 7.6-fold, respectively. Most untreated additional aneurysms causing a subsequent aSAH were smaller than 7 mm (73.3%), with middle cerebral artery being the most frequent location (40.0%). CONCLUSIONS: Incidence of subsequent aSAHs is high in patients with aSAH-MIA. Untreated mirror and de novo aneurysms are associated with higher rupture risk. Longer follow-up and prophylactic treatment of asymptomatic aneurysms at higher rupture risk are recommended to prevent the significant poor outcome of subsequent aSAHs.

A Uremic Goat Model Created by Subtotal Renal Artery Embolization and Gentamicin.

A large animal model of (end-stage) kidney disease (ESKD) is needed for the preclinical testing of novel renal replacement therapies. This study aimed to create stable uremia via subtotal renal artery embolization in goats and induce a temporary further decline in kidney function by administration of gentamicin. Renal artery embolization was performed in five Dutch white goats by infusing polyvinyl alcohol particles in branches of the renal artery, aiming for the embolization of ~80% of one kidney and complete embolization of the contralateral kidney. Gentamicin was administered to temporarily further increase the plasma concentrations of uremic toxins. After initial acute kidney injury, urea and creatinine plasma concentrations stabilized 1.5 ± 0.7 months post-embolization and remained elevated (12 ± 1.4 vs. 5.6 ± 0.8 mmol/L and 174 ± 45 vs. 65 ± 5.6 µmol/L, resp.) during follow-up (16 ± 6 months). Gentamicin induced temporary acute-on-chronic kidney injury with a variable increase in plasma concentrations of small solutes (urea 29 ± 15 mmol/L, creatinine 841 ± 584 µmol/L, phosphate 2.2 ± 0.3 mmol/L and potassium 5.0 ± 0.6 mmol/L) and protein-bound uremic toxins representative of patients with ESKD. A uremic goat model characterized by stable moderate uremia was established via subtotal renal artery embolization with the induction of temporary severe acute-on-chronic kidney injury by the administration of gentamicin, allowing preclinical in vivo validation of novel renal replacement technologies.

Limitations of Flow Diverters in Posterior Communicating Artery Aneurysms.

BACKGROUND: Treatment of intracranial aneurysms with flow diverters (FDs) showed promising results. However, a subset of patients treated for posterior communicating artery (PComA) aneurysms has variable occlusion rates. Especially the fetal type-associated PComA aneurysms seemed to respond differently to treatment. We analyze our series of fetal type PComA aneurysms treated with a FD. The literature on this subject is reviewed. METHODS: Data from patients treated with FD for all PComA aneurysms at the RadboudUMC Nijmegen were retrospectively analysed. Primary end-point was complete aneurysm occlusion at six months. Secondary end-points were clinical outcome, treatment safety, and results of secondary treatment after non-closure. The results for the fetal PComA aneurysms were compared to the literature. RESULTS: Nineteen consecutive patients harboring 21 PComA aneurysms were treated. Three aneurysms had ipsilateral fetal type PCA (14.3%). Overall, none of the fetal type PcomA aneurysm showed complete occlusion versus 77.8% of the others (p = 0.03). Mortality and permanent morbidity rates were respectively 5.3% and 0%. CONCLUSIONS: FD treatment for PComA aneurysm with fetal type circulation seemed to be less effective compared to other types of PComA aneurysms. Flow characteristics at the PComA bifurcation are thought to be causative Alternative strategies should be considered as first line treatment.

eCLIPs bifurcation remodeling system for treatment of wide neck bifurcation aneurysms with extremely low dome-to-neck and aspect ratios: a multicenter experience.

BACKGROUND: Wide necked bifurcation aneurysms (WNBA) are among the most difficult aneurysms to treat. Very low dome-to-neck (DTN) and aspect ratios provide an even greater challenge in the management of WNBAs. We present the safety and efficacy profile for endovascular clip system (eCLIPs) device in the treatment of this subset of WNBAs with very unfavorable morphologies. METHODS: In our case series, 24 patients treated at 12 international centers were taken from a larger prospective voluntary post-marketing registry of 65 patients treated with the eCLIPs device and coiling. Those who had WNBAs at either the carotid or basilar terminus with a DTN ratio <1.6 and aspect ratio <1.2 were included. Radiologic and clinical outcomes were assessed immediately after the procedure and at the latest follow-up. RESULTS: The eCLIPs device was successfully deployed in 23 cases (96%). One patient (4.2%) died due to guidewire perforation distal to the implant site. No other complications were documented. After a mean follow-up of 15.8 months (range 3-40 months), good radiologic outcomes (modified Raymond-Roy classification (MRRC) scores of 1 or 2) were documented in 20 of 21 patients (95%) with follow-up data. The lone patient with an MRRC score of 3 showed coiled compaction after incomplete neck coverage with the device. CONCLUSION: Our series of patients with aneurysms having adverse DTN and aspect ratios demonstrated that the eCLIPs device has a safety and efficacy profile comparable with currently available devices in the treatment of WNBAs.

(No) escape from reality? Cigarette craving in virtual smoking environments.

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.

Evaluation of a system for sorbent-assisted peritoneal dialysis in a uremic pig model.

A system for sorbent-assisted peritoneal dialysis (SAPD) has been developed that continuously recirculates dialysate via a tidal mode using a single-lumen peritoneal catheter with the regeneration of spent dialysate by means of sorbents. SAPD treatment may improve plasma clearance by the maintenance of a high plasma-to-dialysate concentration gradient and by increasing the mass transfer area coefficient (MTAC) of solutes. The system is designed for daily 8-hr treatment (12 kg, nighttime system). A wearable system (2.3 kg, daytime system) may further enhance the clearance of phosphate and organic waste solutes during the day. Uremic pigs (n = 3) were treated with the day- (n = 3) and nighttime system (n = 15) for 4-8 hr per treatment. Plasma clearance (Cl), MTAC, and total mass transport (MT) of urea, creatinine, phosphate, and potassium were compared with a static dwell (n = 28). Cl, MTAC, and MT of urea, creatinine, phosphate, and potassium were low in the pig as compared to humans due to the pig's low peritoneal transport status and could be enhanced only to a limited extent by SAPD treatment compared with a static dwell (nighttime system: Cl urea: ×1.5 (p = .029), Cl creatinine: ×1.7 (p = .054), Cl phosphate: ×1.5 (p = .158), Cl potassium: ×1.6 (p = .011); daytime system: Cl creatinine: ×2.7 (p = .040), Cl phosphate: ×2.2 (p = .039)). Sorbent-assisted peritoneal dialysis treatment in a uremic pig model is safe and enhances small solute clearance as compared to a static dwell. Future studies in humans or animal species with higher peritoneal transport should elucidate whether our SAPD system enhances clearance to a clinically relevant extent as compared to conventional PD.

The Comaneci Device for Entering an Acute-Angled Small Feeder during Cerebral Arteriovenous Malformation Embolization: A Novel Technique to Support Microcatheterization.

In this report, we describe the use of the Comaneci device to support microcatheterization in a small branch arising from a parent artery during embolization. In 2 cases, arteriovenous malformations presented with intracranial hemorrhage. A microcatheter was navigated into a small feeder while the Comaneci device was deployed just distal to the feeder with an acute angle from the parent artery. Our technical note represents an alternative option of catheterization in cases with difficult access to small feeders originating from higher flow arteries at a sharp angle while maintaining continuous flow in the parent artery.

Elevation of inflammatory S100A8/S100A9 complexes in intracranial aneurysms.

BACKGROUND: Inflammation-related factors might give further insight into the pathophysiology of vessel wall inflammation and intracranial aneurysm (IA) rupture. One of these factors is the protein complex S100A8/A9, which is released by neutrophils, monocytes, and activated macrophages and is known for its role in cardiovascular disease. OBJECTIVE: To determine if venous S100A8/A9 levels in patients with a ruptured IA (rIA) or unruptured IA (uIA) are elevated compared with a control group. Second, to assess differences between venous and intra-aneurysmal S100A8/A9 levels of rIA and uIA patients. METHODS: A prospective case study was performed between June 2016 and May 2017 in patients harboring a ruptured or unruptured saccular IA. Primary outcome measures were individual S100A8/A9 serum concentrations as measured in venous and intra-aneurysmal blood samples during endovascular treatment. Venous serum S100A8/A9 concentrations from a healthy control group served as a reference. RESULTS: We included 16 patients with either a rIA or uIA and 47 healthy controls. Venous S100A8/A9 concentrations were higher in aneurysm patients (rIA and uIA) than those of healthy controls (P≤0.001). S100A8/A9 concentrations were higher in intra-aneurysmal samples than in venous samples of rIA patients (P=0.011). This difference was not found in uIA patients (P=0.054). Intra-aneurysmal S100A8/A9 levels were higher in rIAs than in uIAs (P=0.04). CONCLUSIONS: Venous S100A8/A9 levels are elevated in patients with both rIAs and uIAs compared with healthy controls and likely represents aneurysm wall inflammation. S100A8/A9 causes macrophage-induced inflammation and degeneration of the vessel wall which might explain higher intra-aneurysmal S100A8/A9 levels found in rIAs than in uIAs.