Flow cytometer for a dilution-free measurement approach with sample recollection.

Blood testing using flow cytometry is a common and rapid method for the initial screening and diagnosis of patients. Measurements are often combined with other scientific techniques, and analyzed samples are commonly diluted and discarded afterward. When the sample is recollected instead, sample dilution is a challenge when the sample is intended or needed for additional measurements. Therefore, it is advantageous to recollect the undiluted sample. In order to enable measurements of the same undiluted sample aliquot, we designed and constructed a purpose-built flow cytometer. Our instrument employs syringes, acoustic focusing, and an open fluidics system to recollect and reuse the unadulterated sample. The cytometer is compact, which reduces sample consumption. It acquires forward, sideward, and fluorescence signals, offering opportunities for diverse measurement approaches. In particular, our cytometer has been designed to be ready for additional downstream analysis of cells, e.g., applying mass spectrometry, magnetic resonance spectroscopy, or other analytical tools. This study presents results on instrument performance, a comparison with a cytometer that uses standard hydrodynamic focusing, and a proof of concept for multiple measurements.

Pharmacological Prevention of Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Causes of morbidity and mortality following aneurysmal subarachnoid hemorrhage (aSAH) include early brain injury and delayed neurologic deterioration, which may result from delayed cerebral ischemia (DCI). Complex pathophysiological mechanisms underlie DCI, which often includes angiographic vasospasm (aVSP) of cerebral arteries. METHODS: Despite the study of many pharmacological therapies for the prevention of DCI in aSAH, nimodipine-a dihydropyridine calcium channel blocker-remains the only drug recommended universally in this patient population. A common theme in the research of preventative therapies is the use of promising drugs that have been shown to reduce the occurrence of aVSP but ultimately did not improve functional outcomes in large, randomized studies. An example of this is the endothelin antagonist clazosentan, although this agent was recently approved in Japan. RESULTS: The use of the only approved drug, nimodipine, is limited in practice by hypotension. The administration of nimodipine and its counterpart nicardipine by alternative routes, such as intrathecally or formulated as prolonged release implants, continues to be a rational area of study. Additional agents approved in other parts of the world include fasudil and tirilazad. CONCLUSIONS: We provide a brief overview of agents currently being studied for prevention of aVSP and DCI after aSAH. Future studies may need to identify subpopulations of patients who can benefit from these drugs and perhaps redefine acceptable outcomes to demonstrate impact.

Static couch non-coplanar arc selection optimization for lung SBRT treatment planning.

Objective. Non-coplanar arc geometry optimizations that take advantage of beam's eye view (BEV) geometric overlap information have been proven to reduce dose to healthy organs-at-risk (OARs). Recently, a metric called mean arc distance (MAD) has been developed that quantifies the arc geometry sampling of 4πspace. The purpose of this research is to combine improved BEV overlap information with MAD to generate static couch lung stereotactic body radiotherapy (SBRT) treatment plans deliverable on a C-arm linear accelerator.Approach. An algorithm utilizing the Moller-Trumbore ray-triangle intersection method was employed to compute a cost surrogate for dose to overlapping OARs using distances interpolated onto a PDD. Cost was combined with MAD for 100 000 random combinations of arc trajectories. A pathfinding algorithm for arc selection was created, balancing the contributions of MAD and 4πcost for the final trajectory. This methodology was evaluated for 18 lung SBRT patients. Cases were also planned with arcs from a clinical treatment template protocol for dosimetric and plan quality comparison. Results were evaluated using dose constraints in the context of RTOG0915.Main results. Five of six OARs had maximum dose reductions when planned with the arc trajectory optimization algorithm. Significant maximum dose reductions were found for esophagus (7.41 ± 0.91 Gy,p= 0.00019), trachea (5.56 ± 1.55 Gy,p= 0.0025), spinal cord (2.87 ± 1.13 Gy,p= 0.039), large bronchus (3.47 ± 1.49 Gy,p= 0.0075), and aorta (3.13 ± 0.99 Gy,p= 0.012). Mean dose to contralateral lung was also significantly reduced (0.50 ± 0.06 Gy,p= 0.00019). There were two significant increases in OAR doses: mean dose to ipsilateral lung (0.40 ± 0.09,p= 0.00086) and V5Gyto ipsilateral lung (1.95 ± 0.70%,p= 0.011). Paddick conformity index increased by 0.03 ± 0.02 (p= 0.14), remaining below a limit of 1.2 for both techniques.Significance. Static couch non-coplanar optimization yielded maximum dose reductions to OARs while maintaining target conformity for lung SBRT.

Skin/mucosa avoidance radiotherapy (SMART) versus conventional volumetric arc-based radiotherapy (VMAT) for the treatment of head and neck cancer: Dosimetric feasibility study.

BACKGROUND: Intensity modulated radiotherapy (IMRT) for head and neck cancer has led to a reduction in radiotherapy doses to normal tissues, like the salivary glands, while maintaining high rates of local control. Oral mucosal and skin toxicity is still a major source of treatment-related morbidity, occurring in most patients. PURPOSE: We conducted a dosimetric feasibility study with the goal of creating a methodology that could theoretically reduce the dose of radiation to skin and oral mucosa, while maintaining comparable avoidance of other organs at risk, and planning target volume (PTV) coverage. METHODS: The clinical plans of patients treated previously were replanned using coplanar VMAT arcs on a TrueBeam STx using the photon optimizer (PO) version 15.6 and the Acuros XB dose calculation algorithm. Comparisons were made between three methodologies: "Conventional," "Skin Sparing" and a skin/mucosa avoiding ("SMART") technique, with dose metrics being compared using analysis of variance, with a Bonferroni correction to account for multiple pairwise comparisons. The maximum grade of mucositis and radiation dermatitis during treatment was correlated to different dose-volume metrics to predict what could be clinically meaningful. RESULTS: Sixteen patients met the study criteria and were replanned using the skin sparing and SMART techniques. Maximum doses to the skin sparing structure were reduced from 64.2 Gy to 56.6 and 55.9 Gy, in the skin sparing and SMART plans (p < 0.0001), and mean doses reduced from 26.7 Gy to 20.0 and 20.2 Gy, respectively (p < 0.0001). Maximum doses to the oral cavity structure were not reduced by either technique, however mean dose to the oral cavity structure was reduced from 39.03 Gy to 33.5 Gy by the SMART technique (p < 0.0001). There was a slight reduction in PTV_High coverage by the V95% in the SMART plans (99.52% vs. 98.79%, p = 0.0073), and a similar slight reduction in PTV_Low coverage by the V95% by both the skin sparing and SMART plans (99.74% vs. 97.89% vs. 97.42%, p < 0.0001). Maximum doses to organs at risk were not statistically different between techniques. Dose to oral cavity and maximum grade experienced during radiotherapy correlated. The Spearman correlation coefficient for dose to 20%, 50%, and 80% of the volume of oral cavity was 0.5 (p = 0.048), 0.64 (p = 0.007), and 0.62 (p = 0.010), respectively. Skin toxicity grade was only found to be correlated with the D20% of the skin sparing structure (Spearman correlation coefficient of 0.58, p = 0.0177). CONCLUSION: The SMART technique appears to be able to reduce maximum and mean skin dose, as well as mean oral cavity doses, while only slightly reducing PTV coverage, with acceptable OAR doses. We feel the improvements warrant investigation in a clinical trial.

Evaluation of plan quality and treatment efficiency in cranial stereotactic radiosurgery treatment plans with a variable source-to-axis distance.

INTRODUCTION: Radiotherapy deliveries with dynamic couch motions that shorten the source-to-axis distance (SAD) on a C-arm linac have the potential to increase treatment efficiency through the increase of the effective dose rate. In this investigation, we convert clinically deliverable volumetric modulated arc therapy (VMAT) and dynamic conformal arc (DCA) plans for cranial radiosurgery into virtual isocenter plans through implementation of couch trajectories that maintain the target at a shortened but variable SAD throughout treatment. MATERIALS AND METHODS: A randomly sampled population of patients treated with cranial radiosurgery from within the last three years were separated into groups with one, two, and three lesions. All plans had a single isocenter (regardless of number of targets), and a single prescription dose. Patient treatment plans were converted from their original delivery at a standard isocenter to a dynamic virtual isocenter in MATLAB. The virtual isocenter plan featured a variable isocenter position based upon the closest achievable source-to-target distance (referred to herein as a virtual source-to-axis distance [vSAD]) which avoided collision zones on a TrueBeam STx platform. Apertures were magnified according to the vSAD and monitor units at a given control point were scaled based on the inverse square law. Doses were calculated for the plans with a virtual isocenter in the Eclipse (v13.6.23) treatment planning system (TPS) and were compared with the clinical plans. Plan metrics (MU, Paddick conformity index, gradient index, and the volume receiving 12 Gy or more), normal brain dose-volume differences, as well as maximum doses received by organs at risk (OARs) were assessed. The values were compared between standard and virtual isocenter plans with Wilcoxon Sign Ranked tests to determine significance. A subset of the plans were mapped to the MAX-HD anthropomorphic phantom which contained an insert housing EBT3 GafChromic film and a PTW 31010 microion chamber for dose verification on a linac. RESULTS: Delivering plans at a virtual isocenter resulted in an average reduction of 20.9% (p = 3×10-6 ) and 20.6% (p = 3.0×10-6 ) of MUs across all VMAT and all DCA plans, respectively. There was no significant change in OAR max doses received by plans delivered at a virtual isocenter. The low dose wash (1.0-2.0 Gy or 5-11% of the prescription dose) was increased (by approximately 20 cc) for plans with three lesions. This was equivalent to a 2.7%-3.8% volumetric increase in normal tissue receiving the respective dose level when comparing the plan with a virtual isocenter to a plan with a standard isocenter. Gamma pass rates with a 5%/1mm analysis criteria were 96.40% ± 2.90% and 95.07% ± 3.10% for deliveries at standard and virtual isocenter, respectively. Absolute point dose agreements were within -0.36% ± 3.45% and -0.55% ± 3.39% for deliveries at a standard and virtual isocenter, respectively. Potential time savings per arc were found to have linear relationship with the monitor units delivered per arc (savings of 0.009 s/MU with an r2 = 0.866 when fit to plans with a single lesion). CONCLUSIONS: Converting clinical plans at standard isocenter to a virtual isocenter design did not show any losses to plan quality while simultaneously improving treatment efficiency through MU reductions.

Early Release Science of the exoplanet WASP-39b with JWST NIRSpec PRISM.

Transmission spectroscopy1-3 of exoplanets has revealed signatures of water vapour, aerosols and alkali metals in a few dozen exoplanet atmospheres4,5. However, these previous inferences with the Hubble and Spitzer Space Telescopes were hindered by the observations' relatively narrow wavelength range and spectral resolving power, which precluded the unambiguous identification of other chemical species-in particular the primary carbon-bearing molecules6,7. Here we report a broad-wavelength 0.5-5.5 µm atmospheric transmission spectrum of WASP-39b8, a 1,200 K, roughly Saturn-mass, Jupiter-radius exoplanet, measured with the JWST NIRSpec's PRISM mode9 as part of the JWST Transiting Exoplanet Community Early Release Science Team Program10-12. We robustly detect several chemical species at high significance, including Na (19σ), H2O (33σ), CO2 (28σ) and CO (7σ). The non-detection of CH4, combined with a strong CO2 feature, favours atmospheric models with a super-solar atmospheric metallicity. An unanticipated absorption feature at 4 µm is best explained by SO2 (2.7σ), which could be a tracer of atmospheric photochemistry. These observations demonstrate JWST's sensitivity to a rich diversity of exoplanet compositions and chemical processes.

Clinical Burden of Angiographic Vasospasm and Its Complications After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review.

INTRODUCTION: Angiographic vasospasm (VSP), the narrowing of intracranial arteries, is a complication of aneurysmal subarachnoid hemorrhage (aSAH) and often results in delayed cerebral ischemia (DCI) and cerebral infarction. The objective of this systematic review was to summarize the clinical burden of angiographic VSP and its related complications (DCI and cerebral infarction) after aSAH. METHODS: Systematic searches of MEDLINE, Embase, and the Cochrane Library were conducted (in January 2021) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify studies reporting clinical outcomes of angiographic VSP and its related complications after aSAH. Study outcomes included measures of functional status (modified Rankin Scale [mRS], Glasgow Outcome Scale [GOS], extended Glasgow Outcome Scale [GOS-E], modified Barthel Index, or the modified National Institutes of Health Stroke Scale), cognitive status (Montreal Cognitive Assessment or the Mini Mental State Exam), clinical events (rebleeding), and mortality. Study selection, data extraction, and qualitative analyses were conducted. RESULTS: Of 5704 abstracts reviewed, 110 studies were selected: 20 comparative and 39 regression-based studies were included in the qualitative synthesis, 51 descriptive studies were excluded. Most studies (51) were observational and conducted in a single country (53). The occurrence of angiographic VSP and its related complications after aSAH resulted in significantly poorer functional outcomes in three of nine comparative and 11 of 13 regression-based studies, measured by the mRS, and in five of six comparative and eight of nine regression-based studies, measured by the GOS and GOS-E. Angiographic VSP and its related complications were significantly associated with poor cognitive status in all five regression-based studies. Numerically or significantly higher mortality rates in patients with versus those without angiographic VSP and its related complications were reported in five of ten comparative studies and in eight of nine regression-based studies. Six studies looked at specific VSP populations (e.g., by severity or timing of VSP). CONCLUSION: Patients with angiographic VSP and its related complications often had poor functional, neurological, and cognitive outcomes and reduced odds of survival both in hospital and at follow-up. We estimate that angiographic VSP and its related complications, DCI and cerebral infarction, lead to an approximately threefold higher odds of poor functional and cognitive outcomes, and about a twofold increase in the odds of death.

Aneurysmal subarachnoid hemorrhage is a medical emergency in which an aneurysm, a weakened outpouching of a cerebral blood vessel, ruptures causing bleeding in the subarachnoid space. Components from the bleeding can trigger a process leading to the constriction of cerebral arteries, called angiographic vasospasm. Angiographic vasospasm is a frequent occurrence after aneurysmal subarachnoid hemorrhage and can also result in delayed cerebral ischemia and cerebral infarction, which can severely impact patients' health. This study summarizes the published literature to describe the clinical burden that patients may experience due to angiographic vasospasm, delayed cerebral ischemia, and cerebral infarction after aneurysmal subarachnoid hemorrhage. The evidence from these studies emphasizes numerous clinical consequences that patients may experience. These patients may suffer from diminished neurological and intellectual activity, leading to disability and a loss of functional independence in everyday activities. Angiographic vasospasm and its related complications also reduce the chances of survival, both in the hospital and at follow-up. The considerable clinical burden associated with angiographic vasospasm, delayed cerebral ischemia, and cerebral infarction highlights the importance of their prevention.

Rethinking the initial changes in subarachnoid haemorrhage: Focusing on real-time metabolism during early brain injury.

Over the last two decades, neurological researchers have uncovered many pathophysiological mechanisms associated with subarachnoid haemorrhage (SAH), with early brain injury and delayed cerebral ischaemia both contributing to morbidity and mortality. The current dilemma in SAH management inspired us to rethink the nature of the insult in SAH: sudden bleeding into the subarachnoid space and hypoxia due to disturbed cerebral circulation and increased intracranial pressure, generating exogenous stimuli and subsequent pathophysiological processes. Exogenous stimuli are defined as factors which the brain tissue is not normally exposed to when in the healthy state. Intersections of these initial pathogenic factors lead to secondary brain injury with related metabolic changes after SAH. Herein, we summarized the current understanding of efforts to monitor and analyse SAH-related metabolic changes to identify those precise pathophysiological processes and potential therapeutic strategies; in particular, we highlight the restoration of normal cerebrospinal fluid circulation and the normalization of brain-blood interface physiology to alleviate early brain injury and delayed neurological deterioration after SAH.

Mean Arc Distance (MAD): a quantity to compare trajectory 4πsampling in single target cranial stereotactic radiotherapy.

Purpose.C-arm linac-based radiotherapy has seen a recent interest in 4πmethods of delivery using simultaneous rotations of couch and gantry to reduce doses to organs-at-risk (OARs) and increase dose compactness. While many methods use heuristics to generate trajectories that avoid OARs, combined with arbitrary trajectory restrictions to prevent oversampling, a quantity has not yet been developed to succinctly compare sampling of the 4πspace for candidate trajectories as a surrogate for dosimetric compactness.Methods.Evenly spaced sampling points were distributed across a 4πsphere centred on isocentre. A metric, mean arc distance (MAD), was defined that quantifies the average arc distance between all sampling points and their nearest field in a radiotherapy trajectory. The relationship between isodose volume and MAD was examined in 2,047 plans: 900 unique trajectories of fixed port DCA plans, 900 unique trajectories of contiguous field DCA plans, 192 VMAT plans (eight volumes in four locations, each with six trajectories) in matRad with 5 VMAT plans repeated for validation in a clinical planning system, and 10 clinical VMAT cases replanned with five trajectories in a clinical treatment planning system.Results.All isodose volumes greater than 10% of the prescription dose decreased with decreasing MAD in all comparisons. In the range of 10% to 100% of the prescription dose, the rate of isodose volume decrease was exponential as a function of MAD in all comparisons. Reduction of absolute isodose volume is seen with increased 4πsampling, with larger target volumes exhibiting larger absolute reductions. Very low isodoses (0% to 10% of prescription) increased with decreasing MAD.Conclusions.MAD is a 4πsampling quantity useful in quantifying the decrease of isodose volume, relevant for sparing normal tissues. By quantifying this feature, candidate dynamic trajectories can be efficiently compared for 4πsampling. This quantity is explored here for single target cranial radiotherapy but may have applications to other radiotherapy treatment sites.

Intra-arc binary collimation with dynamic axes trajectory optimization for the SRS treatment of multiple metastases with multiple prescriptions.

PURPOSE: This work generates multi-metastases cranial stereotactic radiosurgery/radiotherapy (SRS/SRT) plans using a novel treatment planning technique in which dynamic couch, collimator, and gantry trajectories are used with periodic binary target collimation. The performance of this planning technique is evaluated against conventional volumetric arc therapy (VMAT) planning in terms of various dose and plan quality metrics. METHODS: A 3D cost space (referred to herein as the combined optimization of dynamic axes or CODA cube) was calculated based on an overlap between targets and organs-at-risk (OARs) and uncollimated areas between targets (island blocking) for all combinations of couch, gantry, and collimator angles. Gradient descent through the cube was applied to determine dynamic trajectories. At each control point (CP), each target can either be conformally treated or blocked by the multi-leaf collimator (referred to as intra-arc binary collimation, iABC). Simulated annealing was used to optimize the collimation patterns throughout the arcs as well as the monitor units (MUs) delivered at each CP. Seven previously treated VMAT plans were selected for comparison against the CODA-iABC planning technique. Two CODA-iABC plans were developed: a single gantry arc plan and a plan with one gantry arc and two couch arcs. Plan quality comparison metrics included maximum and mean dose to OARs (brainstem, chiasm, optic nerves, eyes, and lenses), the volume of normal brain receiving 12 Gy (V12Gy), total MUs, target conformity, and dose-gradient index. RESULTS: Treatment plans generated with 1-arc CODA-iABC plans delivered an average of 21% and 30% higher maximum and mean doses to brainstem, respectively, when compared to VMAT plans. Treatment plans generated with 3-arc CODA-iABC used an average of 24% fewer MUs and resulted in an average reduction of 48% maximum dose and 50% mean dose to the OARs, when compared to VMAT. Target conformity values were worse in both CODA-iABC plans than VMAT by an average of 35% and 15%, respectively. There are no significant differences in V12Gy for all three planning techniques; however, 3-arc CODA-iABC is more effective at reducing dose to normal brain in the low-dose region (<12 Gy). CONCLUSION: CODA-iABC is a novel planning technique that has been developed to automatically generate patient-specific multi-axis trajectories for multiple metastases cranial SRS/SRT. This work has demonstrated the feasibility of planning with this novel method. The 1-arc CODA-iABC planning technique is slightly dosimetric inferior to VMAT. With an increased sampling of a three-dimensional CODA cube by using a 3-arc CODA-iABC technique, there was improved total dose sparing to all the OARs and increased MU efficiency, but with a cost in target conformity, when compared to VMAT.

Classical Regression and Predictive Modeling.

BACKGROUND: With the advent of personalized and stratified medicine, there has been much discussion about predictive modeling and the role of classical regression in modern medical research. We describe and distinguish the goals in these 2 frameworks for analysis. METHODS: The assumptions underlying and utility of classical regression are reviewed for continuous and binary outcomes. The tenets of predictive modeling are then discussed and contrasted. Principles are illustrated by simulation and through application of methods to a neurosurgical study. RESULTS: Classical regression can be used for insights into causal mechanisms if careful thought is given to the role of variables of interest and potential confounders. In predictive modeling, interest lies more in accuracy of predictions and so alternative metrics are used to judge adequacy of models and methods; methods which average predictions over several contending models can improve predictive performance but these do not admit a single risk score. CONCLUSIONS: Both classical regression and predictive modeling have important roles in modern medical research. Understanding the distinction between the 2 frameworks for analysis is important to place them in their appropriate context and interpreting findings from published studies appropriately.

Editor's Choice - Peri-Operative Outcomes of Carotid Endarterectomy are Not Improved on Dual Antiplatelet Therapy vs. Aspirin Monotherapy: A Systematic Review and Meta-Analysis.

OBJECTIVE: A systematic review and meta-analysis of the peri-operative outcomes of carotid endarterectomy (CEA) on dual antiplatelet therapy (DAPT) vs. aspirin monotherapy was carried out, to determine optimal peri-operative management with these antiplatelet agents. DATA SOURCES: The Web of Science, Pubmed, and Embase databases were searched from inception to July 2021. The corresponding authors of excluded articles were contacted to obtain additional data for possible inclusion. REVIEW METHODS: The main outcomes included ischaemic complications (stroke, transient ischaemic attack [TIA], and transcranial Doppler [TCD] measured micro-emboli), haemorrhagic complications (haemorrhagic stroke, neck haematoma, and re-operation for bleeding), and composite outcomes. Pooled estimates using odds ratios (ORs) were combined using a random or fixed effects model based on the results of the chi square test and calculation of I2. RESULTS: In total, 47 411 patients were included in 11 studies, with 14 345 (30.2%) receiving DAPT and 33 066 (69.7%) receiving aspirin only. There was no significant difference in the rates of peri-operative stroke (OR 0.87, 95% confidence interval [CI] 0.72 - 1.05) and TIA (OR 0.78, 95% CI 0.52 - 1.17) despite a significant reduction in TCD measured micro-emboli (OR 0.19, 95% CI 0.10 - 0.35) in the DAPT compared with the aspirin monotherapy group. Subgroup analysis did not reveal any significant difference in ischaemic stroke risk between patients with asymptomatic and symptomatic carotid artery stenosis. DAPT was associated with an increased risk of neck haematoma (OR 2.79, 95% CI 1.87 - 4.18) and re-operation for bleeding (OR 1.98, 95% CI 1.77 - 2.23) vs. aspirin. Haemorrhagic stroke was an under reported outcome in the literature. CONCLUSION: This meta-analysis found that CEA while on DAPT increased the risk of haemorrhagic complications, with similar rates of ischaemic complications, vs. aspirin monotherapy. This suggests that the risks of performing CEA on DAPT outweigh the benefits, even in patients with symptomatic carotid stenosis. The overall quality of studies was low, and improved reporting of CEA outcomes in the literature is necessary.

Body Mass Index and the Risk of Poor Outcome in Surgically Treated Patients With Good-Grade Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Heterogeneity among study populations and treatment procedures has led to conflicting results on outcome predictors for patients with aneurysmal subarachnoid hemorrhage (aSAH). One such conflicting predictor is body mass index (BMI). OBJECTIVE: To clarify whether high BMI values protect patients from poor outcome after aSAH, as previously suggested. METHODS: We surveyed 6 prospective studies conducted in 14 different countries (93 healthcare units) between 1985 and 2016 and pooled the data on surgically treated patients with good-grade (Glasgow Coma Scale 13-15 on admission) aSAH. We calculated BMI for each patient and created 4 balanced categories based on the BMI quartiles of each cohort. We calculated adjusted odds ratios (ORs) with 95% CIs for the 3-month poor outcome (Glasgow Outcome Scale 1-3) by BMI. RESULTS: The pooled study cohort included 1692 patients with good-grade aSAH (mean age 51 years; 64% female). At 3 months, 288 (17%) had poor outcomes. The risk for poor outcomes increased with increasing BMI values (OR = 1.15 [1.02-1.31] per each standard deviation increase of BMI). The risk for poor outcome was over 1.6 times higher (OR = 1.66 [1.13-2.43]) in the highest BMI category (range 27.1-69.2) compared with the lowest BMI category (range 14.4-23.8). These associations were found in each of the 6 study cohorts in both men and women, regardless of age. CONCLUSION: Because higher BMI values seem to associate with poor outcomes in surgically treated patients with good-grade aSAH, it seems unlikely that obesity protects patients with aSAH from poor outcomes.

Optimal Glucose Target After Aneurysmal Subarachnoid Hemorrhage: A Matched Cohort Study.

BACKGROUND: Hyperglycemia has been associated with poor outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, there remains debate as to what optimal glucose targets should be in this patient population. OBJECTIVE: To assess whether we could identify an optimal glucose target for patients with aSAH. METHODS: We performed a post hoc analysis of the "clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage" trial data set. Patients had laboratory results drawn daily for the entirety of their intensive care unit stay. Maximum blood glucose levels were assessed for a relationship with unfavorable outcomes using multiple logistic regression analysis. Maximum blood glucose levels were dichotomized based on the Youden index, which identified a maximum level of <9.2 mmol/L as the optimal cut point for prediction of unfavorable outcomes. Nearest neighbor matching was used to assess the relationship between maintaining glucose levels below the cut point and unfavorable functional outcomes (defined as a modified Rankin score of >2 at 3 mo post-aSAH). The matching was performed after calculation of a propensity score based on identified predictors of outcome and glucose levels. RESULTS: Three hundred eighty-nine patients were included in the matched analysis. Propensity scores were balanced on both the covariates and outcomes of interest. There was a significant average treatment effect (-0.143: 95% confidence interval -0.267 to -0.019) for patients who maintained glucose levels <9.2 mmol/L. CONCLUSION: Maintaining glucose levels below the identified cut point was associated with a decreased risk for unfavorable outcomes in this retrospective matched study.

Simulating the cumulative effects of potential open-pit mining and climate change on streamflow and water quality in a mountainous watershed.

Land use and climate change effects on water quality and water quantity are well documented globally. Most studies evaluate individual factors and effects, without considering the interrelationships between land use, climate, water quality, and water quantity. This study provides an integrated assessment of the cumulative effects of climate change and potential open-pit coal mining on streamflow and water quality in the Oldman River Basin, Alberta, Canada. A hydrological model was developed that incorporates estimates of future selenium loading, water use, and projected changes in air temperature and precipitation to evaluate changes in water quantity and quality. Model results indicate that estimated selenium concentrations, absent any attenuation, are likely to be substantially above most water quality guidelines and strong reliance on mitigation technologies would be required to maintain adequate water quality in the watershed if mine development were to take place. Streamflow is sensitive to changes in climatic conditions, and modelling results suggest there are likely to be increases in winter flow, earlier peak flow, and reductions in flow during the summer and fall months under the climate change scenarios. These changes can have direct impacts on the degree of selenium dilution and more generally on aquatic habitat, ecosystem health, and socioeconomic needs. This study highlights that water management decisions may mis-evaluate the risks and tradeoffs of future mine development if they fail to adequately consider climate change and changing streamflow regimes and their indirect effects on water quality.

Surgical treatment of brainstem cavernous malformations: an international Delphi consensus.

OBJECTIVE: Indication for surgery in brainstem cavernous malformations (BSCMs) is based on many case series, few comparative studies, and no randomized controlled trials. The objective of this study was to seek consensus about surgical management aspects of BSCM. METHODS: A total of 29 experts were invited to participate in a multistep Delphi consensus process on the surgical treatment of BSCM. RESULTS: Twenty-two (76%) of 29 experts participated in the consensus. Qualitative analysis (content analysis) of an initial open-ended question survey resulted in 99 statements regarding surgical treatment of BSCM. By using a multistep survey with 100% participation in each round, consensus was reached on 52 (53%) of 99 statements. These were grouped into 4 categories: 1) definitions and reporting standards (7/14, 50%); 2) general and patient-related aspects (11/16, 69%); 3) anatomical-, timing of surgery-, and BSCM-related aspects (22/37, 59%); and 4) clinical situation-based decision-making (12/32, 38%). Among other things, a consensus was reached for surgical timing, handling of associated developmental venous anomalies, handling of postoperative BSCM remnants, assessment of specific anatomical BSCM localizations, and treatment decisions in typical clinical BSCM scenarios. CONCLUSIONS: A summary of typical clinical scenarios and a catalog of various BSCM- and patient-related aspects that influence the surgical treatment decision have been defined, rated, and interpreted.