Light to moderate long-term grazing enhances ecosystem carbon across a broad climatic gradient in northern temperate grasslands.

Grasslands are globally abundant and provide many ecosystem services, including carbon (C) storage. While grasslands are widely subject to livestock grazing, the influence of grazing on grassland ecosystem C remains unclear. We studied the effect of long-term livestock grazing on C densities of different ecosystem components in 110 northern temperate grasslands across a broad agroclimatic gradient in Alberta, Canada. These grasslands stored 50 to 180 t ha-1C in live and dead vegetation, as well as soil C to 30 cm depth, with the majority as soil organic C (SOC). The mulch layer comprised a large amount of C (~18 t ha-1C) especially within humid grasslands. Although grazing reduced C densities in litter mass, total ecosystem C was 8.5 % greater under grazing (127.8 t ha-1) compared to those non-grazed (117.8 t ha-1), primarily due to increases in SOC and roots. Increases in SOC were consistently observed in the 0-15 cm layer across all climatic conditions, with changes in SOC of the 15-30 cm layer inversely related to aridity. A structural equation model revealed that increased SOC under grazing was indirectly attributed to increases in eudicot rather than graminoid biomass. In addition, SOC increased with graminoid quality (i.e., a reduced carbon to nitrogen ratio), which together with elevated eudicots, increased litter and mulch C, and ultimately enhanced SOC densities. When applied to spatial maps of habitat type and land use (livestock grazing) activity across the region, an area of ~3.8 M ha of grassland was projected to contain an additional 17.1 M t of C under grazing, primarily in mesic grasslands, worth an estimated $3.1 B (Cdn.) under current C valuation guidelines in Canada. Overall, these results highlight the importance of grasslands for C storage and establishing policies that maintain and promote their sustainable use, including light to moderate grazing.

Intracranial atherosclerosis update for neurointerventionalists.

The management of intracranial atherosclerotic disease (ICAD) has been evolving with advanced imaging, refinements of best medical treatment, and the development of endovascular options. There has been a significant increase in the use of endovascular therapy for symptomatic ICAD in the USA over the past 6 years. The rationale for this review is to update neurointerventionalists in these areas so that evidence-based decisions can be considered when counseling potential patients regarding their risks, benefits, and potential complications. The landmark SAMMPRIS trial demonstrated superiority of aggressive medical management (AMM) over intracranial stenting as an initial treatment. However, the risk of disabling or fatal stroke remains high in patients presenting with stroke treated with AMM. Recent studies showed a significantly lower rate of periprocedural complications from intracranial stenting. Patients who have failed medical treatment may therefore benefit from intracranial stenting, particularly in those with hemodynamic compromise and large vessel embolic stroke. Drug coated angioplasty balloons and drug eluting stents may potentially reduce the risk of in-stent re-stenosis. Large vessel occlusion (LVO) due to underlying ICAD is seen in a subset of thrombectomy-eligible patients. The use of stenting as a rescue therapy in LVO thrombectomy has also shown promising early results.

Pivotal trial of the Neuroform Atlas stent for treatment of posterior circulation aneurysms: one-year outcomes.

BACKGROUND: Stent-assisted coiling of wide-necked intracranial aneurysms (IAs) using the Neuroform Atlas Stent System (Atlas) has shown promising results. OBJECTIVE: To present the primary efficacy and safety results of the ATLAS Investigational Device Exemption (IDE) trial in a cohort of patients with posterior circulation IAs. METHODS: The ATLAS trial is a prospective, multicenter, single-arm, open-label study of unruptured, wide-necked, IAs treated with the Atlas stent and adjunctive coiling. This study reports the results of patients with posterior circulation IAs. The primary efficacy endpoint was complete aneurysm occlusion (Raymond-Roy (RR) class I) on 12-month angiography, in the absence of re-treatment or parent artery stenosis >50%. The primary safety endpoint was any major ipsilateral stroke or neurological death within 12 months. Adjudication of the primary endpoints was performed by an imaging core laboratory and a Clinical Events Committee. RESULTS: The ATLAS trial enrolled and treated 116 patients at 25 medical centers with unruptured, wide-necked, posterior circulation IAs (mean age 60.2±10.5 years, 81.0% (94/116) female). Stents were placed in all patients with 100% technical success rate. A total of 95/116 (81.9%) patients had complete angiographic follow-up at 12 months, of whom 81 (85.3%) had complete aneurysm occlusion (RR class I). The primary effectiveness outcome was achieved in 76.7% (95% CI 67.0% to 86.5%) of patients. Overall, major ipsilateral stroke and secondary persistent neurological deficit occurred in 4.3% (5/116) and 1.7% (2/116) of patients, respectively. CONCLUSIONS: In the ATLAS IDE posterior circulation cohort, the Neuroform Atlas Stent System with adjunctive coiling demonstrated high rates of technical and safety performance. Trial registration number https://clinicaltrials.gov/ct2/show/NCT02340585.

POSITIVE: Perfusion imaging selection of ischemic stroke patients for endovascular therapy.

BACKGROUND: The PerfusiOn imaging Selection of Ischemic sTroke patIents for endoVascular thErapy (POSITIVE) trial was designed to evaluate functional outcome in patients with emergent large vessel occlusion (ELVO) presenting within 0-12 hours with pre-specified bifurcated arms of early and late window presentation, who were selected for endovascular thrombectomy with non-vendor specific commercially available perfusion imaging software. Recent trials demonstrating the benefit of thrombectomy up to 16-24 hours following ELVO removed equipoise to randomize late window ELVO patients and therefore the trial was halted. METHODS: Up to 200 patients were to be enrolled in this FDA-cleared, prospective, randomized, multicenter international trial to compare thrombectomy and best medical management in patients with ELVO ineligible for or refractory to treatment with IV tissue plasminogen activator (IV-tPA) selected with perfusion imaging and presenting within 0-12 hours of last seen normal. The primary outcome was 90-day clinical outcome as measured by the raw modified Rankin Scale (mRS) with scores 5 and 6 collapsed (mRS shift analysis). RESULTS: The POSITIVE trial suspended enrollment with the release of results from the DAWN trial and was stopped after the release of the DEFUSE 3 trial results. Thirty-three patients were enrolled (21 for medical management and 12 for thrombectomy). Twelve of the 33 patients were enrolled in the 6-12 hour cohort. Despite the early cessation, the primary outcome demonstrated statistically significant superior clinical outcomes for patients treated with thrombectomy (P=0.0060). The overall proportion of patients achieving an mRS score of 0-2 was 75% in the thrombectomy cohort and 43% in the medical management cohort (OR 4.00, 95% CI 0.84 to 19.2). CONCLUSION: POSITIVE supports the already established practice of delayed thrombectomy for appropriately selected patients presenting within 0-12 hours selected by perfusion imaging from any vendor. The results of the POSITIVE trial are consistent with other thrombectomy trials. The statistically significant effect on functional improvement, despite the small number of patients, reinforces the robust benefits of thrombectomy. CLINICAL TRIAL REGISTRATION: NCT01852201.

Encephaloduroarteriosynangiosis (EDAS) revascularization for symptomatic intracranial atherosclerotic steno-occlusive (ERSIAS) Phase-II objective performance criterion trial.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is one of the most challenging stroke etiologies, with frequent recurrences despite optimized medical management. Encephaloduroarteriosynangiosis (EDAS) is an indirect revascularization method that produces extra-cranial collaterals to intracranial vessels. We present the results of a phase-II trial of EDAS in intracranial atherosclerotic disease patients. AIMS: To evaluate the feasibility, safety, and preliminary efficacy of EDAS in intracranial atherosclerotic disease patients. METHODS: ERSIAS was a prospective objective-performance-criterion trial of EDAS plus intensive medical management (IMM) in intracranial atherosclerotic disease (ICAD) patients failing medical treatment. Primary endpoint was any stroke/death within 30-days post-surgery or stroke in the territory of the qualifying artery beyond 30 days. The primary analysis compared event rates through one year with an objective-performance-criterion based on a 10% reduction from the 20% rate in the intensive medical management arm of the stenting versus aggressive medical management for preventing recurrent stroke in intracranial stenosis trial (SAMMPRIS) in patients with poor collaterals. Event rates through two years were compared with propensity-score-matched (PSM) medically treated patients from SAMMPRIS and the carotid occlusion surgery study (COSS). RESULTS: During a median follow-up of 24.5 months, 5 (9.6%) of 52 patients had a primary endpoint event. The primary endpoint rate at one year met the threshold for nonfutility and advancement to phase III (<10%). In the sensitivity analysis, primary endpoint event rate at two years was lower than in PSM controls, 9.6% versus 21.2% (p < 0.07). Overall, 86% of EDAS-plus-intensive medical management patients were functionally independent at last follow-up and 89% demonstrated neovascularization. There were two (3.8%) surgical complications and no intracranial hemorrhages. CONCLUSION: ERSIAS phase II provides evidence of safety and strong signals of efficacy of EDAS-plus-intensive medical management, supporting advancement to a seamless phase-IIb/III trial. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov.NCT01819597.

The WOVEN trial: Wingspan One-year Vascular Events and Neurologic Outcomes.

BACKGROUND: Prior studies evaluating the Wingspan stent for treatment of symptomatic intracranial atherosclerotic disease have included patients with a spectrum of both on-label and off-label indications for the stent. The WEAVE trial assessed 152 patients stented with the Wingspan stent strictly by its current on-label indication and found a 2.6% periprocedural stroke and death rate. OBJECTIVE: This WOVEN study assesses the 1-year follow-up from this cohort. METHODS: Twelve of the original 24 sites enrolling patients in the WEAVE trial performed follow-up chart review and imaging analysis up to 1 year after stenting. Assessment of delayed stroke and death was made in 129 patients, as well as vascular imaging follow-up to assess for in-stent re-stenosis. RESULTS: In the 1-year follow-up period, seven patients had a stroke (six minor, one major). Subsequent to the periprocedural period, no deaths were recorded in the cohort. Including the four patients who had periprocedural events in the WEAVE study, there were 11 strokes or deaths of the 129 patients (8.5%) at the 1-year follow-up. CONCLUSIONS: The WOVEN study provides the 1-year follow-up on a cohort of 129 patients who were stented according to the current on-label use. It provides a more homogeneous patient group for analysis than prior studies, and demonstrates a relatively low 8.5% 1-year stroke and death rate in stented patients.

Breathing fresh air into respiratory research with single-cell RNA sequencing.

The complex cellular heterogeneity of the lung poses a unique challenge to researchers in the field. While the use of bulk RNA sequencing has become a ubiquitous technology in systems biology, the technique necessarily averages out individual contributions to the overall transcriptional landscape of a tissue. Single-cell RNA sequencing (scRNA-seq) provides a robust, unbiased survey of the transcriptome comparable to bulk RNA sequencing while preserving information on cellular heterogeneity. In just a few years since this technology was developed, scRNA-seq has already been adopted widely in respiratory research and has contributed to impressive advancements such as the discoveries of the pulmonary ionocyte and of a profibrotic macrophage population in pulmonary fibrosis. In this review, we discuss general technical considerations when considering the use of scRNA-seq and examine how leading investigators have applied the technology to gain novel insights into respiratory biology, from development to disease. In addition, we discuss the evolution of single-cell technologies with a focus on spatial and multi-omics approaches that promise to drive continued innovation in respiratory research.

Update in the treatment of intracranial atherosclerotic disease.

This review highlights the recent evolution of the imaging, medical management, surgical options and endovascular therapies for symptomatic intracranial atherosclerotic disease (ICAD). Recent imaging developments including optical coherence tomography and other modalities to assess the intracranial arteries for symptomatic ICAD are reviewed, not only to diagnose ICAD but to determine if ICAD plaques have any high-risk features for treatment. Potential future developments in the treatment of ICAD are discussed, including the development of trackable drug-coated balloons for the cerebral circulation to treat primary or restenotic arteries, new iterations of self-expanding intracranial stents with easier delivery systems, and the re-examination of indirect surgical bypass techniques for revascularisation. In addition to these important technological developments, however, is the evolving evidence regarding the best treatment window for these techniques and additional factors in medical management which can improve patient outcomes in this devastating pathology.

Device profile of the Wingspan Stent System for the treatment of intracranial atherosclerotic disease: overview of its safety and efficacy.

Introduction: This Wingspan Stent is a self-expanding, laser-cut, nitinol stent designed for the treatment of severe symptomatic intracranial artery stenosis to be used in conjunction with the Gateway angioplasty balloon. This review will describe the technical features of the stent, its composition, design, and functional characteristics, as well as an overview of its safety and efficacy.Areas covered: The engineering and manufacturing specifications are described for the stent. A systematic review of the literature from 2005 to 2019 is performed to define the safety profile of the stent as an implant for cerebral artery revascularization, stroke prophylaxis, and acute stroke treatment. These reports are compared to the published reports of patients with similar characteristics treated with medical therapy alone.Expert opinion: Although prior off-label studies have shown variable results, recent on-label studies have shown that the Wingspan stent itself is very safe, with low complication rates, and that it may confer long-term benefits in stroke prevention compared to medical therapy alone. Provided that established guidelines are followed, the Wingspan stent is effective in cerebral artery revascularization, and improves clinical outcomes in acute large vessel occlusive stroke with underlying intracranial atherosclerotic stenosis.

Flow-Diverter Stenting of Intracavernous Internal Carotid Artery Mycotic Aneurysm.

This is the first reported case in which a mycotic aneurysm refractory to the first medical treatment was treated with a Pipeline embolization device (PED), and the first case of a mycotic aneurysm from Brucella treated by endovascular therapy. A 35-year-old man presented with left eye pain and ptosis, and fever for 2 weeks. Before symptom onset, he visited Vietnam where he developed a flu-like illness; however, antibiotics were ineffective. We suspected Brucella as the most likely infectious etiology for the patient's intracavernous aneurysm. Since the aneurysm did not reduce in size following 2 weeks of antibiotic therapy, we placed a PED in the left internal carotid artery. Follow-up angiogram 4 months later showed no residual aneurysm, and cranial nerve palsies had completely resolved. From the results of this case, it appears that flow diverter stenting may be a safe and effective treatment of mycotic aneurysms of the cavernous segment of ICA.

WEAVE Trial: Final Results in 152 On-Label Patients.

Background and Purpose- The WEAVE trial (Wingspan Stent System Post Market Surveillance) is a postmarket surveillance trial mandated by the Food and Drug Administration to assess the periprocedural safety of the Wingspan Stent system in the treatment of symptomatic intracranial atherosclerotic disease. Methods- A total of 152 consecutive patients who met the Food and Drug Administration on-label usage criteria were enrolled at 24 hospitals and underwent angioplasty and stenting with the Wingspan stent. On-label criteria included age 22 to 80 years, symptomatic intracranial atherosclerotic stenosis of 70% to 99%, baseline modified Rankin Scale score ≤3, ≥2 strokes in the vascular territory of the stenotic lesion with at least 1 stroke while on medical therapy, and stenting of the lesion ≥8 days after the last stroke. The primary analysis assessed the periprocedural stroke, bleed, and death rate within 72 hours of the procedure with adjudication by a core study Stroke Neurologist. Results- The trial was stopped early after interim analysis of 152 consecutive patients demonstrated a lower than expected 2.6% (4/152 patients) periprocedural stroke, bleed, and death rate. This was lower than the 4% periprocedural primary event safety benchmark set for the interim analysis in the study. A total of 97.4% (148/152) patients were event-free at 72 hours, 1.3% (2/152) had nonfatal strokes, and 1.3% (2/152) of patients died. Conclusions- With experienced interventionalists, and proper patient selection following the on-label usage guidelines, the use of the Wingspan stent for intracranial atherosclerotic disease demonstrated a low periprocedural complication rate and excellent safety profile. This is the largest on-label, multicenter, prospective trial of the Wingspan stent system to date with the lowest reported complication rate. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02034058.

Optimizing Outcomes for Mechanically Ventilated Patients in an Era of Endovascular Acute Ischemic Stroke Therapy.

Endovascular mechanical thrombectomy is a new standard of care for acute ischemic stroke (AIS). The majority of these patients receive mechanical ventilation (MV), which has been associated with poor outcomes. The implication of this is significant, as most neurointerventionalists prefer general compared to local anesthesia during the procedure. Consequences of hemodynamic and respiratory perturbations during general anesthesia and MV are thought to contribute significantly to the poor outcomes that are encountered. In this review, we first describe the unique risks associated with MV in the specific context of AIS and then discuss evidence of brain goal-directed approaches that may mitigate these risks. These strategies include an individualized approach to hemodynamic parameters (eg, adherence to a minimum blood pressure goal and adequate volume resuscitation), respiratory parameters (eg, arterial carbon dioxide optimization), and the use of ventilator settings that optimize neurological outcomes (eg, arterial oxygen optimization).

Safety and outcomes of simultaneous vasospasm and endovascular aneurysm treatment (SVAT) in subarachnoid hemorrhage.

BACKGROUND: Simultaneous vasospasm and endovascular aneurysm treatment (SVAT) has been shown to be effective with good clinical outcomes in small series, but these studies have not examined predictive factors for clinical outcome after treatment. OBJECTIVE: To identify the safety and efficacy of SVAT in a large multicenter patient cohort and evaluate prognostic markers of clinical outcome following SVAT. METHODS: This study retrospectively enrolled 50 consecutive patients undergoing SVAT at 11 different centers. We analyzed Hunt and Hess and Fisher grades, aneurysm location, angiographic vasospasm grade, Glasgow Outcome Scale (GOS) at discharge, and 90-day modified Rankin Scale (mRS) scores. RESULTS: A total of 50 patients undergoing SVAT between the years 2003 and 2009 were identified. Patients presented, on average, 6.48±4.45 days after subarachnoid hemorrhage. Hunt and Hess and Fisher grades were 1 (n=7), 2 (n=12), 3 (n=14), 4 (n=15), 5 (n=2), and 3 and 4 (n=33), respectively. Aneurysm location was distributed as follows: anterior (n=32), posterior (n=16), anterior and posterior (n=2). Patients with good clinical condition (Hunt and Hess score 1-3) had significantly higher odds of surviving (OR=17.5, 95% CI 1.9 to 161.5), favorable GOS (OR=4.2, 95% CI 1.2 to 14.8), and favorable 90-day mRS (OR=4.2, 95% CI 1.2 to 14.8). CONCLUSIONS: SVAT is safe, with the majority of patients achieving good clinical outcome. Patients with lower Hunt and Hess grades have higher odds of surviving and favorable clinical prognosis.