Daipayan Guha

Low-grade chronic inflammation in regions of the normal mouse arterial intima predisposed to atherosclerosis

Atherosclerotic lesions develop in regions of arterial curvature and branch points, which are exposed to disturbed blood flow and have unique gene expression patterns. The cellular and molecular basis for atherosclerosis susceptibility in these regions is not completely understood. In the intima of atherosclerosis-predisposed regions of the wild-type C57BL/6 mouse aorta, we quantified increased expression of several proinflammatory genes that have been implicated in atherogenesis, including vascular cell adhesion molecule–1 (VCAM-1) and a relative abundance of dendritic cells, but only occasional T cells. In contrast, very few intimal leukocytes were detected in regions resistant to atherosclerosis; however, abundant macrophages, including T cells, were found throughout the adventitia (Adv). Considerably lower numbers of intimal CD68+ leukocytes were found in inbred atherosclerosis-resistant C3H and BALB/c mouse strains relative to C57BL/6 and 129; however, leukocyte distribution throughout the Adv of all strains was similar. The predominant mechanism for the accumulation of intimal CD68+ cells was continued recruitment of bone marrow–derived blood monocytes, suggestive of low-grade chronic inflammation. Local proliferation of intimal leukocytes was low. Intimal CD68+ leukocytes were reduced in VCAM-1–deficient mice, suggesting that mechanisms of leukocyte accumulation in the intima of normal aorta are analogous to those in atherosclerosis.

Iatrogenic spondylolisthesis following laminectomy for degenerative lumbar stenosis: systematic review and current concepts

OBJECT Decompression without fusion for degenerative lumbar stenosis is an effective treatment for both the pain and disability of neurogenic claudication. Iatrogenic instability following decompression may require further intervention to stabilize the spine. The authors review the incidence of postsurgical instability following lumbar decompression, and assess the impact of surgical technique as well as study design on the incidence of instability. METHODS A comprehensive literature search was performed to identify surgical cohorts of patients with degenerative lumbar stenosis, with and without preexisting spondylolisthesis, who were treated with laminectomy or minimally invasive decompression without fusion. Data on patient characteristics, surgical indications and techniques, clinical and radiographic outcomes, and reoperation rates were collected and analyzed. RESULTS A systematic review of 24 studies involving 2496 patients was performed, assessing both open laminectomy and minimally invasive bilateral canal enlargement. Postoperative pain and functional outcomes were similar across the various studies, and postoperative radiographie instability was seen in 5.5% of patients. Instability was seen more frequently in patients with preexisting spondylolisthesis (12.6%) and in those treated with open laminectomy (12%). Reoperation for instability was required in 1.8% of all patients, and was higher for patients with preoperative spondylolisthesis (9.3%) and for those treated with open laminectomy (4.1%). CONCLUSIONS Instability following lumbar decompression is a common occurrence. This is particularly true if decompression alone is selected as a surgical approach in patients with established spondylolisthesis. This complication may occur less commonly with the use of minimally invasive techniques; however, larger prospective cohort studies are necessary to more thoroughly explore these findings.

Stereotactic radiosurgery for intracranial meningiomas: current concepts and future perspectives.

Meningiomas are among the most common adult brain tumors. Although the optimal management of meningiomas would provide complete elimination of the lesion, this cannot always be accomplished safely through resection. Therefore, other therapeutic modalities, such as stereotactic radiosurgery (as primary or adjunctive therapy), have emerged. In the current review, we have provided an overview of the historical outcomes of various radiosurgical modalities applied in the management of meningiomas. Furthermore, we provide a discussion on key factors (eg World Health Organization grade, lesion size, and lesion location) that affect tumor control and adverse event rates. We discuss recent changes in our understanding of meningiomas, based on molecular and genetic markers, and how these will change our perspective on the management of meningiomas. We conclude by outlining the areas in which knowledge gaps persist and provide suggestions as to how these can be addressed.

Augmented Reality in Neurosurgery: A Review of Current Concepts and Emerging Applications

Augmented reality (AR) superimposes computer-generated virtual objects onto the users view of the real world. Among medical disciplines, neurosurgery has long been at the forefront of image-guided surgery, and it continues to push the frontiers of AR technology in the operating room. In this systematic review, we explore the history of AR in neurosurgery and examine the literature on current neurosurgical applications of AR. Significant challenges to surgical AR exist, including compounded sources of registration error, impaired depth perception, visual and tactile temporal asynchrony, and operator inattentional blindness. Nevertheless, the ability to accurately display multiple three-dimensional datasets congruently over the area where they are most useful, coupled with future advances in imaging, registration, display technology, and robotic actuation, portend a promising role for AR in the neurosurgical operating room.

National socioeconomic indicators are associated with outcomes after aneurysmal subarachnoid hemorrhage: a hierarchical mixed-effects analysis

OBJECT Although heterogeneity exists in patient outcomes following subarachnoid hemorrhage (SAH) across different centers and countries, it is unclear which factors contribute to such disparities. In this study, the authors performed a post hoc analysis of a large international database to evaluate the association between a countrys socioeconomic indicators and patient outcome following aneurysmal SAH. METHODS An analysis was performed on a database of 3552 patients enrolled in studies of tirilazad mesylate for aneurysmal SAH from 1991 to 1997, which included 162 neurosurgical centers in North and Central America, Australia, Europe, and Africa. Two primary outcomes were assessed at 3 months after SAH: mortality and Glasgow Outcome Scale (GOS) score. The association between these outcomes, nation-level socioeconomic indicators (percapita gross domestic product [GDP], population-to-neurosurgeon ratio, and health care funding model), and patientlevel covariates were assessed using a hierarchical mixed-effects logistic regression analysis. RESULTS Multiple previously identified patient-level covariates were significantly associated with increased mortality and worse neurological outcome, including age, intraventricular hemorrhage, and initial neurological grade. Among national-level covariates, higher per-capita GDP (p < 0.05) was associated with both reduced mortality and improved neurological outcome. A higher population-to-neurosurgeon ratio (p < 0.01), as well as fewer neurosurgical centers per population (p < 0.001), was also associated with better neurological outcome (p < 0.01). Health care funding model was not a significant predictor of either primary outcome. CONCLUSIONS Higher per-capita gross GDP and population-to-neurosurgeon ratio were associated with improved outcome after aneurysmal SAH. The former result may speak to the availability of resources, while the latter may be a reflection of better outcomes with centralized care. Although patient clinical and radiographic phenotypes remain the primary predictors of outcome, this study shows that national socioeconomic disparities also explain heterogeneity in outcomes following SAH.

Spinal intraoperative three-dimensional navigation: correlation between clinical and absolute engineering accuracy

BACKGROUND CONTEXT Spinal intraoperative computer-assisted navigation (CAN) may guide pedicle screw placement. Computer-assisted navigation techniques have been reported to reduce pedicle screw breach rates across all spinal levels. However, definitions of screw breach vary widely across studies, if reported at all. The absolute quantitative error of spinal navigation systems is theoretically a more precise and generalizable metric of navigation accuracy. It has also been computed variably and reported in less than a quarter of clinical studies of CAN-guided pedicle screw accuracy. PURPOSE This study aimed to characterize the correlation between clinical pedicle screw accuracy, based on postoperative imaging, and absolute quantitative navigation accuracy. DESIGN/SETTING This is a retrospective review of a prospectively collected cohort. PATIENT SAMPLE We recruited 30 patients undergoing first-time posterior cervical-thoracic-lumbar-sacral instrumented fusion±decompression, guided by intraoperative three-dimensional CAN. OUTCOME MEASURES Clinical or radiographic screw accuracy (Heary and 2 mm classifications) and absolute quantitative navigation accuracy (translational and angular error in axial and sagittal planes). METHODS We reviewed a prospectively collected series of 209 pedicle screws placed with CAN guidance. Each screw was graded clinically by multiple independent raters using the Heary and 2 mm classifications. Clinical grades were dichotomized per convention. The absolute accuracy of each screw was quantified by the translational and angular error in each of the axial and sagittal planes. RESULTS Acceptable screw accuracy was achieved for significantly fewer screws based on 2 mm grade versus Heary grade (92.6% vs. 95.1%, p=.036), particularly in the lumbar spine. Inter-rater agreement was good for the Heary classification and moderate for the 2 mm grade, significantly greater among radiologists than surgeon raters. Mean absolute translational-angular accuracies were 1.75 mm-3.13° and 1.20 mm-3.64° in the axial and sagittal planes, respectively. There was no correlation between clinical and absolute navigation accuracy. CONCLUSIONS Radiographic classifications of pedicle screw accuracy vary in sensitivity across spinal levels, as well as in inter-rater reliability. Correlation between clinical screw grade and absolute navigation accuracy is poor, as surgeons appear to compensate for navigation registration error. Future studies of navigation accuracy should report absolute translational and angular errors. Clinical screw grades based on postoperative imaging may be more reliable if performed in multiple by radiologist raters.

Outcome Evaluation of Acute Ischemic Stroke Patients Treated with Endovascular Thrombectomy: A Single-Institution Experience in the Era of Randomized Controlled Trials

BACKGROUND Endovascular thrombectomy is an effective procedure to treat selected ischemic strokes, as shown in recent randomized controlled trials (RCTs). The generalizability of these trial data to real-world settings, however, is unknown. The aim of this study was to examine our single-center experience with endovascular thrombectomy for acute ischemic strokes and perform a comparative outcome analysis to the most recent RCTs. METHODS We performed a 5-year retrospective analysis, from April 2011 to March 2016, on 66 consecutive patients with acute ischemic stroke who received endovascular thrombectomy at our institution. The Alberta Stroke Program Early CT Score (ASPECTS) and the National Institutes of Health Stroke Scale were used to assess preoperative status. Our primary outcomes were the modified Rankin Score (mRS) at 90 days and recanalization grade measured by the 6-point thrombolysis in cerebral infarction (TICI) grading system. RESULTS Sixty-six patients received endovascular treatment during the study period. Among the patients examined, 35 (53%) had a favorable outcome (mRS 0-2 at 90 days), 23 (35%) a poor outcome (mRS 3-5), and 8 (12%) died. Successful recanalization (TICI score 3-5) was achieved in 68% of cases. In univariate analysis, patients with good outcome at 90 days had significantly greater ASPECTS, lower National Institutes of Health Stroke Scale, and higher TICI scores. In a multiple logistic regression model, higher ASPECTS and TICI scores were significantly and independently associated with favorable outcome. CONCLUSIONS Excellent outcomes, as demonstrated by the recent RCTs, can be achieved in clinical practice and reproduced in dedicated tertiary centers.

Effects of decompressive craniectomy on functional outcomes and death in poor-grade aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis

OBJECTIVE Patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) (World Federation of Neurosurgical Societies Grade IV or V) are often considered for decompressive craniectomy (DC) as a rescue therapy for refractory intracranial hypertension. The authors performed a systematic review and meta-analysis to assess the impact of DC on functional outcome and death in patients after poor-grade aSAH. METHODS A systematic review and meta-analysis were performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles were identified through the Ovid Medline, Embase, Web of Science, and Cochrane Library databases from inception to October 2015. Only studies dedicated to patients with poor-grade aSAH were included. Primary outcomes were death and functional outcome assessed at any time period. Patients were grouped as having a favorable outcome (modified Rankin Scale [mRS] Scores 1-3, Glasgow Outcome Scale [GOS] Scores 4 and 5, extended Glasgow Outcome Scale [GOSE] Scores 5-8) or unfavorable outcome (mRS Scores 4-6, GOS Scores 1-3, GOSE Scores 1-4). Pooled estimates of event rates and odds ratios with 95% confidence intervals were calculated using the random-effects model. RESULTS Fifteen studies encompassing 407 patients were included in the meta-analysis (all observational cohorts). The pooled event rate for poor outcome across all studies was 61.2% (95% CI 52%-69%) and for death was 27.8% (95% CI 21%-35%) at a median of 12 months after aSAH. Primary (or early) DC resulted in a lower overall event rate for unfavorable outcome than secondary (or delayed) DC (47.5% [95% CI 31%-64%] vs 74.4% [95% CI 43%-91%], respectively). Among studies with comparison groups, there was a trend toward a reduced mortality rate 1-3 months after discharge among patients who did not undergo DC (OR 0.58 [95% CI 0.27-1.25]; p = 0.168). However, this trend was not sustained at the 1-year follow-up (OR 1.09 [95% CI 0.55-2.13]; p = 0.79). CONCLUSIONS Results of this study summarize the best evidence available in the literature for DC in patients with poor-grade aSAH. DC is associated with high rates of unfavorable outcome and death. Because of the lack of robust control groups in a majority of the studies, the effect of DC on functional outcomes versus that of other interventions for refractory intracranial hypertension is still unknown. A randomized trial is needed.

Neurosurgeon academic impact is associated with clinical outcomes after clipping of ruptured intracranial aneurysms

Background Surgeon-dependent factors such as experience and volume are associated with patient outcomes. However, it is unknown whether a surgeon’s research productivity could be related to outcomes. The main aim of this study is to investigate the association between the surgeon’s academic productivity and clinical outcomes following neurosurgical clipping of ruptured aneurysms. Methods We performed a post-hoc analysis of 3567 patients who underwent clipping of ruptured intracranial aneurysms in the randomized trials of tirilazad mesylate from 1990 to 1997. These trials included 162 centers and 156 surgeons from 21 countries. Primary and secondary outcomes were: Glasgow outcome scale score and mortality, respectively. Total publications, H-index, and graduate degrees were used as academic indicators for each surgeon. The association between outcomes and academic factors were assessed using a hierarchical logistic regression analysis, adjusting for patient covariates. Results Academic profiles were available for 147 surgeons, treating a total of 3307 patients. Most surgeons were from the USA (62, 42%), Canada (18, 12%), and Germany (15, 10%). On univariate analysis, the H-index correlated with better functional outcomes and lower mortality rates. In the multivariate model, patients under the care of surgeons with higher H-indices demonstrated improved neurological outcomes (p = 0.01) compared to surgeons with lower H-indices, without any significant difference in mortality. None of the other academic indicators were significantly associated with outcomes. Conclusion Although prognostication following surgery for ruptured intracranial aneurysms primarily depends on clinical and radiological factors, the academic impact of the operating neurosurgeon may explain some heterogeneity in surgical outcomes.

Management of raised intracranial pressure in aneurysmal subarachnoid hemorrhage: time for a consensus?

Elevated intracranial pressure (ICP) is a well-recognized phenomenon in aneurysmal subarachnoid hemorrhage (aSAH) that has been demonstrated to lead to poor outcomes. Despite significant advances in clinical research into aSAH, there are no consensus guidelines devoted specifically to the management of elevated ICP in the setting of aSAH. To treat high ICP in aSAH, most centers extrapolate their treatment algorithms from studies and published guidelines for traumatic brain injury. Herein, the authors review the current management strategies for treating raised ICP within the aSAH population, emphasize key differences from the traumatic brain injury population, and highlight potential directions for future research in this controversial topic.