Showing papers by "Cameron G. McDougall published in 2021"

Monocyte-based inflammatory indices predict outcomes following aneurysmal subarachnoid hemorrhage

Abstract: The contribution of specific immune cell populations to the post-hemorrhagic inflammatory response in aneurysmal subarachnoid hemorrhage (aSAH) and correlations with clinical outcomes, such as vasospasm and functional status, remains unclear. We aimed to compare the predictive value of leukocyte ratios that include monocytes as compared to the neutrophil-to-lymphocyte ratio (NLR) in aSAH. A prospectively accrued database of consecutive patients presenting to our institution with aSAH between January 2013 and December 2018 was used. Patients with signs and symptoms of infection (day 1–3) were excluded. Admission values of the NLR, monocyte-neutrophil-to-lymphocyte ratio (M-NLR), and lymphocyte-to-monocyte ratio (LMR) were calculated. Associations with functional status, the primary outcome, and vasospasm were evaluated using univariable and multivariable logistic regression analyses. In the cohort of 234 patients with aSAH, the M-NLR and LMR, but not the NLR, were significantly associated with poor functional status (modified Rankin scale > 2) at 12–18 months following discharge (p = 0.001, p = 0.023, p = 0.161, respectively). The area under the curve for predicting poor functional status was significantly lower for the NLR (0.543) compared with the M-NLR (0.603, p = 0.024) and LMR (0.608, p = 0.040). The M-NLR (OR = 1.01 [1.01–1.02]) and LMR (OR = 0.88 [0.78–0.99]) were independently associated with poor functional status while controlling for age, hypertension, Fisher grade, and baseline clinical status. The LMR was significantly associated with vasospasm (OR = 0.84 [0.70–0.99]) while adjusting for age, hypertension, Fisher grade, aneurysm size, and current smoking. Inflammatory indices that incorporate monocytes (e.g., M-NLR and LMR), but not those that include only neutrophils, predict outcomes after aSAH.

Management of unruptured intracranial aneurysms: correlation of UIATS, ELAPSS, and PHASES with referral center practice

Abstract: Concordance between the Unruptured Intracranial Aneurysm Treatment Score (UIATS), Earlier Subarachnoid Hemorrhage, Location, Age, Population, Size, Shape (ELAPSS) score, and Population, Hypertension, Age, Size, Earlier Subarachnoid Hemorrhage, Site (PHASES) score with real-world management decisions in unruptured intracranial aneurysms (UIAs) remains unclear, especially in current practice. This study aimed to investigate this concordance, while developing an optimal model predictive of recent decision practices at a quaternary referral center. A prospective database of patients presenting with UIAs to our institution from January 1 to December 31, 2018, was used. Concordance between the scores and real-world management decisions on every UIA was assessed. Complications and length of stay (LOS) were compared between aneurysms in the UIATS-recommended treatment and observation groups. A subgroup analysis of concordance was also conducted among junior and senior surgeons. An optimal logistic regression model predictive of real-world decisions was also derived. The cohort consisted of 198 patients with 271 UIAs, of which 42% were treated. The UIATS demonstrated good concordance with an AUC of 0.765. Of the aneurysms in the UIATS-recommended “observation” group, 22% were discordantly treated. The ELAPSS score demonstrated good discrimination (AUC = 0.793), unlike the PHASES score (AUC = 0.579). Endovascular treatment rates, complications, and LOS were similar between aneurysms in the UIATS-recommended treatment and observation groups. Similar concordance was obtained among junior and senior surgeons. The optimal predictive model consisted of several significantly associated variables and had an AUC of 0.942. Cerebrovascular specialists may be treating aneurysms slightly more than these scores would recommend, independently of years in practice. Wide variation still exists in management practices of UIAs.

Five-year results of randomized bioactive versus bare metal coils in the treatment of intracranial aneurysms: the Matrix and Platinum Science (MAPS) Trial.

Abstract: Background No randomized trial of intracranial aneurysm coiling has compared long-term efficacy of polymer-modified coils to bare metal coils (BMCs). We report 5-year results comparing Matrix2 coils to BMCs. The primary objective was to compare the rates of target aneurysm recurrence (TAR) at 12 months. Secondary objectives included angiographic outcomes at TAR or 12 months and TAR at 5 years. Methods A total of 626 patients were randomized to BMCs or Matrix2 coils. Detailed methods and 1-year results have been published previously. Results Of 580 patients eligible for 5-year follow-up, 431 (74.3%) completed follow-up or reached TAR. Matrix2 coils were non-inferior to BMCs (P=0.8) but did not confer any benefit. Core lab reported post-treatment residual aneurysm filling (Raymond III) correlated with TAR (P Conclusions After 5 years Matrix2 coils were non-inferior to BMCs but no benefit was demonstrated. Post-treatment residual angiographic aneurysm filling (Raymond III) is strongly associated with TAR (P

Application of unruptured aneurysm scoring systems to a cohort of ruptured aneurysms: are we underestimating rupture risk?

Abstract: The predictive values of current risk stratification scales such as the Unruptured Intracranial Aneurysm Treatment Score (UIATS) and the PHASES score are debatable. We evaluated these scores using a cohort of ruptured intracranial aneurysms to simulate their management recommendations had the exact same patients presented prior to rupture. A prospectively maintained database of ruptured saccular aneurysm patients presenting to our institution was used. The PHASES score was calculated for 992 consecutive patients presenting between January 2002 and December 2018, and the UIATS was calculated for 266 consecutive patients presenting between January 2013 and December 2018. A shorter period was selected for the UIATS cohort given the larger number of variables required for calculation. Clinical outcomes were compared between UIATS-recommended "observation" aneurysms and all other aneurysms. Out of 992 ruptured aneurysms, 54% had a low PHASES score (≤5). Out of the 266 ruptured aneurysms, UIATS recommendations were as follows: 68 (26%) "observation," 97 (36%) "treatment," and 101 (38%) "non-definitive." The UIATS conservative group of patients developed more SAH-related complications (78% vs. 65%, p=0.043), had a higher rate of non-home discharge (74% vs. 46%, p 2) after 12-18 months (68% vs. 51%, p=0.014). Current predictive scoring systems for unruptured aneurysms may underestimate future rupture risk and lead to more conservative management strategies in some patients. Patients that would have been recommended for conservative therapy were more likely to have a worse outcome after rupture.

PD-1+ Monocytes Mediate Cerebral Vasospasm Following Subarachnoid Hemorrhage.

Abstract: Background Cerebral vasospasm is a major source of morbidity and mortality following aneurysm rupture and has limited treatment options. Objective To evaluate the role of programmed death-1 (PD-1) in cerebral vasospasm. Methods Endovascular internal carotid artery perforation (ICAp) was used to induce cerebral vasospasm in mice. To evaluate the therapeutic potential of targeting PD-1, programmed death ligand-1 (PD-L1) was administered 1 h after ICAp and vasospasm was measured histologically at the level of the ICA bifurcation bilaterally. PD-1 expressing immune cell populations were evaluated by flow cytometry. To correlate these findings to patients and evaluate the potential of PD-1 as a biomarker, monocytes were isolated from the peripheral blood and analyzed by flow cytometry in a cohort of patients with ruptured cerebral aneurysms. The daily frequency of PD-1+ monocytes in the peripheral blood was correlated to transcranial Doppler velocities as well as clinical and radiographic vasospasm. Results We found that PD-L1 administration prevented cerebral vasospasm by inhibiting ingress of activated Ly6c+ and CCR2+ monocytes into the brain. Human correlative studies confirmed the presence of PD-1+ monocytes in the peripheral blood of patients with ruptured aneurysms and the frequency of these cells corresponded with cerebral blood flow velocities and clinical vasospasm. Conclusion Our results identify PD-1+ monocytes as mediators of cerebral vasospasm and support PD-1 agonism as a novel therapeutic strategy.

Predictors of an academic career among fellowship-trained open vascular and endovascular neurosurgeons

Abstract: Objective Although previous studies have explored factors that predict an academic career among neurosurgery residents in general, such predictors have yet to be determined within specific neurosurgical subspecialties. The authors report on predictors they identified as correlating with academic placement among fellowship-trained vascular neurosurgeons. Methods A database was created that included all physicians who graduated from ACGME (Accreditation Council for Graduate Medical Education)-accredited neurosurgery residency programs between 1960 and 2018 using publicly available online data. Neurosurgeons who completed either open vascular or endovascular fellowships were identified. Subsequent employment of vascular or endovascular neurosurgeons in academic centers was determined. A position was considered academic if the hospital of employment was affiliated with a neurosurgery residency program; all other positions were considered non-academic. Bivariate analyses were conducted using Fisher's exact test or the Mann-Whitney U-test, and multivariate analysis was performed using a logistic regression model. Results A total of 83 open vascular neurosurgeons and 115 endovascular neurosurgeons were identified. In both cohorts, the majority of neurosurgeons were employed in academic positions after training. In bivariate analysis, only 2 factors were significantly associated with a career in academic neurosurgery for open vascular neurosurgeons: 1) an h-index of ≥ 2 during residency (OR 3.71, p = 0.016), and 2) attending a top 10 residency program based on U.S. News and World Report rankings (OR 4.35, p = 0.030). In bivariate analysis, among endovascular neurosurgeons, having an h-index of ≥ 2 during residency (OR 4.35, p = 0.0085) and attending a residency program affiliated with a top 10 U.S. News and World Report medical school (OR 2.97, p = 0.029) were significantly associated with an academic career. In multivariate analysis, for both open vascular and endovascular neurosurgeons, an h-index of ≥ 2 during residency was independently predictive of an academic career. Attending a residency program affiliated with a top 10 U.S. News and World Report medical school independently predicted an academic career among endovascular neurosurgeons only. Conclusions The authors report that an h-index of ≥ 2 during residency predicts pursuit of an academic career among vascular and endovascular neurosurgeons. Additionally, attendance of a residency program affiliated with a top research medical school independently predicts an academic career trajectory among endovascular neurosurgeons. This result may be useful to identify and mentor residents interested in academic vascular neurosurgery.

Aging Patient Population With Ruptured Aneurysms: Trend Over 28 Years.

Abstract: BACKGROUND Given increasing life expectancy in the United States and worldwide, the proportion of elderly patients affected by aneurysmal subarachnoid hemorrhage (aSAH) would be expected to increase. OBJECTIVE To determine whether an aging trend exists in the population of aSAH patients presenting to our institution over a 28-yr period. METHODS A prospectively maintained database of consecutive patients presenting to our institution with subarachnoid hemorrhage between January 1991 and December 2018 was utilized. The 28-yr period was categorized into 4 successive 7-yr quarter intervals. The age of patients was compared among these intervals, and yearly trends were derived using linear regression. RESULTS The cohort consisted of 1671 ruptured aneurysm patients with a mean age of 52.8 yr (standard deviation = 15.0 yr). Over the progressive 7-yr time intervals during the 28-yr period, there was an approximately 4-fold increase in the proportion of patients aged 80 yr or above (P < .001) and an increase in mean patient age from 51.2 to 54.6 yr (P = .002). Independent of this trend but along the same lines, there was a 29% decrease in the proportion of younger patients (<50 yr) from 49% to 35%. On linear regression, there was 1-yr increase in mean patient age per 5 calendar years (P < .001). CONCLUSION Analyses of aSAH patients demonstrate an increase in patient age over time with a considerable rise in the proportion of octogenarian patients and a decrease in patients younger than 50 yr. This aging phenomenon presents a challenge to the continued improvement in outcomes of aSAH patients.

Safety and efficacy results of the Flow Redirection Endoluminal Device (FRED) stent system in the treatment of intracranial aneurysms: US pivotal trial.

Abstract: Objective To evaluate the safety and effectiveness of the Flow Redirection Endoluminal Device (FRED) flow diverter in support of an application for Food and Drug Administration approval in the USA. Methods 145 patients were enrolled in a prospective, single-arm multicenter trial. Patients with aneurysms of unfavorable morphology for traditional endovascular therapies (large, wide-necked, fusiform, etc) were included. The trial was designed to demonstrate non-inferiority in both safety and effectiveness, comparing trial results with performance goals (PGs) established from peer-reviewed published literature. The primary safety endpoint was death or major stroke (National Institutes of Health Stroke Scale score ≥4 points) within 30 days of the procedure, or any major ipsilateral stroke or neurological death within the first year. The primary effectiveness endpoint was complete occlusion of the target aneurysm with ≤50% stenosis of the parent artery at 12 months after treatment, and in which an alternative treatment of the target intracranial aneurysm had not been performed. Results 145 patients underwent attempted placement of a FRED device, and one or more devices were placed in all 145 patients. 135/145 (93%) had a single device placed. Core laboratory adjudication deemed 106 (73.1%) of the aneurysms large or giant. A safety endpoint was experienced by 9/145 (6.2%) patients, successfully achieving the safety PG of 46% aneurysm occlusion was also achieved, with the effectiveness endpoint being met in 80/139 (57.6%) Conclusion As compared with historically derived performance benchmarks, the FRED flow diverter is both safe and effective for the treatment of appropriately selected intracranial aneurysms. Clinical registration number NCT01801007

Neuroprotective Role of Acidosis in Ischemia: Review of the Preclinical Evidence

Abstract: Efforts to develop effective neuroprotective therapies for ischemic stroke have had little success to date. One promising approach to neuroprotection is ischemic postconditioning, which utilizes brief bouts of ischemia after acute ischemic stroke to elicit neuroprotection, although the mechanism is largely unknown. As the primary components of transient ischemia are local hypoxia and acidosis, and hypoxic postconditioning has had little success, it is possible that the acidosis component may be the primary driver. To address the evidence behind this, we performed a systematic review of preclinical studies focused on the neuroprotective role of transient acidosis after ischemia. Animal studies demonstrated that mild-to-moderate acidosis after ischemic events led to better functional neurologic outcomes with reduced infarct volumes, while severe acidosis often led to cerebral edema and worse functional outcomes. In vitro studies demonstrated that mild-to-moderate acidosis improves neuronal survival largely through two means: (1) inhibition of harmful superoxide formation in the excitotoxic pathway and (2) remodeling neuronal mitochondria to allow for efficient ATP production (i.e., oxidative phosphorylation), even in the absence of oxygen. Similar to the animal studies, acidotic postconditioning in humans would entail short cycles of carbon dioxide inhalation, which has already been demonstrated to be safe as part of a hypercapnic challenge when measuring cerebrovascular reactivity. Due to the preclinical efficacy of acidotic postconditioning, its relatively straightforward translation into humans, and the growing need for neuroprotective therapies, future preclinical studies should focus on filling the current knowledge gaps that are currently restricting the development of phase I/II clinical trials.

Spinal Arteriovenous Metameric Syndrome and Spinal Cord Arteriovenous Malformations

Abstract: Spinal arteriovenous metameric syndrome (SAMS) is defined by the presence of at least 2 vascular malformations along an embryonic metamere. The associated spinal vascular malformation most commonly develops as an extradural–intradural arteriovenous malformation (AVM); however, associated extradural arteriovenous fistulas (AVFs) or intradural AVMs or AVFs have also been described. Patients with SAMS may be more likely to develop associated spinal aneurysms. The natural history of vascular malformations in SAMS must incorporate the risk of hemorrhage and deficits resulting from venous hypertension or lesion mass effect. Purely extradural or intradural vascular malformations may be managed similarly to how they are managed in nonmetameric disease. The management of extradural–intradural AVMs requires individualized approaches aimed at alleviating symptomatic mass effect, venous hypertension, or decreasing the hemorrhage risk by embolizing associated aneurysms. The overall prognosis for extradural–intradural lesions is worse than for other spinal vascular malformations.

Transvenous embolization of cerebral dural arteriovenous fistulas

Abstract: Indications and procedural techniques for successful transvenous embolization of cerebral dural arteriovenous fistulas (dAVFs) are reviewed. A brief historic context for transvenous embolization is presented. We discuss important anatomical considerations and present illustrative cases for ideal scenarios and more challenging transvenous approaches.