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Operative volume and outcomes of cerebrovascular neurosurgery in children

Kimon Bekelis, Ian D. Connolly, Huy M. Do, and Omar Choudhri

OBJECTIVE

The impact of procedural volume on the outcomes of cerebrovascular surgery in children has not been determined. In this study, the authors investigated the association of operative volume on the outcomes of cerebrovascular neurosurgery in pediatric patients.

METHODS

The authors performed a cohort study of all pediatric patients who underwent a cerebrovascular procedure between 2003 and 2012 and were registered in the Kids' Inpatient Database (KID). To control for confounding, the authors used multivariable regression models, propensity-score conditioning, and mixed-effects analysis to account for clustering at the hospital level.

RESULTS

During the study period, 1875 pediatric patients in the KID underwent cerebrovascular neurosurgery and met the inclusion criteria for the study; 204 patients (10.9%) underwent aneurysm clipping, 446 (23.8%) underwent coil insertion for an aneurysm, 827 (44.1%) underwent craniotomy for arteriovenous malformation resection, and 398 (21.2%) underwent bypass surgery for moyamoya disease. Mixed-effects multivariable regression analysis revealed that higher procedural volume was associated with fewer inpatient deaths (OR 0.58; 95% CI 0.40–0.85), a lower rate of discharges to a facility (OR 0.87; 95% CI 0.82–0.92), and shorter length of stay (adjusted difference −0.22; 95% CI −0.32 to −0.12). The results in propensity-adjusted multivariable models were robust.

CONCLUSIONS

In a national all-payer cohort of pediatric patients who underwent a cerebrovascular procedure, the authors found that higher procedural volume was associated with fewer deaths, a lower rate of discharges to a facility, and decreased lengths of stay. Regionalization initiatives should include directing children with such rare pathologies to a center of excellence.

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Surgical outcomes of cervical spondylotic myelopathy: an analysis of a national, administrative, longitudinal database

Anand Veeravagu, Ian D. Connolly, Layton Lamsam, Amy Li, Christian Swinney, Tej D. Azad, Atman Desai, and John K. Ratliff

OBJECTIVE

The authors performed a population-based analysis of national trends, costs, and outcomes associated with cervical spondylotic myelopathy (CSM) in the United States. They assessed postoperative complications, resource utilization, and predictors of costs, in this surgically treated CSM population.

METHODS

MarketScan data (2006–2010) were used to retrospectively analyze the complications and costs of different spine surgeries for CSM. The authors determined outcomes following anterior cervical discectomy and fusion (ACDF), posterior fusion, combined anterior/posterior fusion, and laminoplasty procedures.

RESULTS

The authors identified 35,962 CSM patients, comprising 5154 elderly (age ≥ 65 years) patients (mean 72.2 years, 54.9% male) and 30,808 nonelderly patients (mean 51.1 years, 49.3% male). They found an overall complication rate of 15.6% after ACDF, 29.2% after posterior fusion, 41.1% after combined anterior and posterior fusion, and 22.4% after laminoplasty. Following ACDF and posterior fusion, a significantly higher risk of complication was seen in the elderly compared with the nonelderly (reference group). The fusion level and comorbidity-adjusted ORs with 95% CIs for these groups were 1.54 (1.40–1.68) and 1.25 (1.06–1.46), respectively. In contrast, the elderly population had lower 30-day readmission rates in all 4 surgical cohorts (ACDF, 2.6%; posterior fusion, 5.3%; anterior/posterior fusion, 3.4%; and laminoplasty, 3.6%). The fusion level and comorbidity-adjusted odds ratios for 30-day readmissions for ACDF, posterior fusion, combined anterior and posterior fusion, and laminoplasty were 0.54 (0.44–0.68), 0.32 (0.24–0.44), 0.17 (0.08–0.38), and 0.39 (0.18–0.85), respectively.

CONCLUSIONS

The authors' analysis of the MarketScan database suggests a higher complication rate in the surgical treatment of CSM than previous national estimates. They found that elderly age (≥ 65 years) significantly increased complication risk following ACDF and posterior fusion. Elderly patients were less likely to experience a readmission within 30 days of surgery. Postoperative complication occurrence, and 30-day readmission were significant drivers of total cost within 90 days of the index surgical procedure.

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Therapeutic strategies to improve drug delivery across the blood-brain barrier

Tej D. Azad, James Pan, Ian D. Connolly, Austin Remington, Christy M. Wilson, and Gerald A. Grant

Resection of brain tumors is followed by chemotherapy and radiation to ablate remaining malignant cell populations. Targeting these populations stands to reduce tumor recurrence and offer the promise of more complete therapy. Thus, improving access to the tumor, while leaving normal brain tissue unscathed, is a critical pursuit. A central challenge in this endeavor lies in the limited delivery of therapeutics to the tumor itself. The blood-brain barrier (BBB) is responsible for much of this difficulty but also provides an essential separation from systemic circulation. Due to the BBB's physical and chemical constraints, many current therapies, from cytotoxic drugs to antibody-based proteins, cannot gain access to the tumor. This review describes the characteristics of the BBB and associated changes wrought by the presence of a tumor. Current strategies for enhancing the delivery of therapies across the BBB to the tumor will be discussed, with a distinction made between strategies that seek to disrupt the BBB and those that aim to circumvent it.

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The strokes that killed Churchill, Roosevelt, and Stalin

Rohaid Ali, Ian D. Connolly, Amy Li, Omar A. Choudhri, Arjun V. Pendharkar, and Gary K. Steinberg

From February 4 to 11, 1945, President Franklin D. Roosevelt of the United States, Soviet Union Premier Joseph Stalin, and British Prime Minister Winston Churchill met near Yalta in Crimea to discuss how post–World War II (WWII) Europe should be organized. Within 2 decades of this conference, all 3 men had died. President Roosevelt died 2 months after the Yalta Conference due to a hemorrhagic stroke. Premier Stalin died 8 years later, also due to a hemorrhagic stroke. Finally, Prime Minister Churchill died 20 years after the conference because of complications due to stroke. At the time of Yalta, these 3 men were the leaders of the most powerful countries in the world. The subsequent deterioration of their health and eventual death had varying degrees of historical significance. Churchill's illness forced him to resign as British prime minister, and the events that unfolded immediately after his resignation included Britain's mismanagement of the Egyptian Suez Crisis and also a period of mistrust with the United States. Furthermore, Roosevelt was still president and Stalin was still premier at their times of passing, so their deaths carried huge political ramifications not only for their respective countries but also for international relations. The early death of Roosevelt, in particular, may have exacerbated post-WWII miscommunication between America and the Soviet Union—miscommunication that may have helped precipitate the Cold War.

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Sports-related brain injuries: connecting pathology to diagnosis

James Pan, Ian D. Connolly, Sean Dangelmajer, James Kintzing, Allen L. Ho, and Gerald Grant

Brain injuries are becoming increasingly common in athletes and represent an important diagnostic challenge. Early detection and management of brain injuries in sports are of utmost importance in preventing chronic neurological and psychiatric decline. These types of injuries incurred during sports are referred to as mild traumatic brain injuries, which represent a heterogeneous spectrum of disease. The most dramatic manifestation of chronic mild traumatic brain injuries is termed chronic traumatic encephalopathy, which is associated with profound neuropsychiatric deficits. Because chronic traumatic encephalopathy can only be diagnosed by postmortem examination, new diagnostic methodologies are needed for early detection and amelioration of disease burden. This review examines the pathology driving changes in athletes participating in high-impact sports and how this understanding can lead to innovations in neuroimaging and biomarker discovery.

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A review of potential applications of MR-guided focused ultrasound for targeting brain tumor therapy

Layton Lamsam, Eli Johnson, Ian D. Connolly, Max Wintermark, and Melanie Hayden Gephart

Magnetic resonance–guided focused ultrasound (MRgFUS) has been used extensively to ablate brain tissue in movement disorders, such as essential tremor. At a lower energy, MRgFUS can disrupt the blood-brain barrier (BBB) to allow passage of drugs. This focal disruption of the BBB can target systemic medications to specific portions of the brain, such as for brain tumors. Current methods to bypass the BBB are invasive, as the BBB is relatively impermeable to systemically delivered antineoplastic agents. Multiple healthy and brain tumor animal models have suggested that MRgFUS disrupts the BBB and focally increases the concentration of systemically delivered antitumor chemotherapy, immunotherapy, and gene therapy. In animal tumor models, combining MRgFUS with systemic drug delivery increases median survival times and delays tumor progression. Liposomes, modified microbubbles, and magnetic nanoparticles, combined with MRgFUS, more effectively deliver chemotherapy to brain tumors. MRgFUS has great potential to enhance brain tumor drug delivery, while limiting treatment toxicity to the healthy brain.

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Effects of rod diameter on kinematics of posterior cervical spine instrumented constructs: an ex vivo study

Ali Kiapour, Ashutosh Khandha, Elie Massaad, Ian D. Connolly, Muhamed Hadzipasic, Ganesh M. Shankar, Vijay Goel, and John H. Shin

OBJECTIVE

Posterior cervical spine fixation is a robust strategy for stabilizing the spine for a wide range of spinal disorders. With the evolution of spinal implant technology, posterior fixation with lateral mass screws in the subaxial spine is now common. Despite interest in variable rod diameters to meet a wide range of clinical needs such as trauma, revision, and deformity surgery, indications for use of posterior cervical spine fixation are not clear. This laboratory investigation evaluates the mechanical stability and kinematic properties of lateral mass fixation with various commercially available rod diameters.

METHODS

The authors conducted an ex vivo experiment using 13 fresh-frozen human cervical spine specimens, instrumented from C3 to C6 with lateral mass screws, to evaluate the effects of titanium rod diameter on kinematic stability. Each intact spine was tested using a kinematic profiling machine with an optoelectrical camera and infrared sensors applying 1.5-Nm bending moments to the cranial vertebra (C2) simulating flexion-extension, lateral bending, and axial rotation anatomical motions. A compressive follower preload of 150 N was applied in flexion-extension prior to application of a bending moment. Instrumented spines were then tested with rod diameters of 3.5, 4.0, and 4.5 mm. The kinematic data between intact and surgical cases were studied using a nonparametric Wilcoxon signed-rank test. A multivariable, multilevel linear regression model was built to identify the relationship between segmental motion and rod diameter.

RESULTS

Instrumentation resulted in significant reduction in range of motion in all three rod constructs versus intact specimens in flexion-extension, lateral bending, and axial rotation (p < 0.05). The maximum reductions in segmental ROM versus intact spines in 3.5-, 4.0-, and 4.5-mm rod constructs were 61%, 71%, and 81% in flexion-extension; 70%, 76%, and 81% in lateral bending; and 50%, 60%, and 75% in axial rotation, respectively. Segmental motion at the adjacent segments (C2–3 and C6–7) increased significantly (p < 0.05) with increasing rod diameter. The 4.5-mm rod construct had the greatest increase in motion compared to the intact spine.

CONCLUSIONS

With increasing rod diameters from 3.5 to 4.0 mm, flexion-extension, lateral bending, and axial rotation across C3–6 were significantly reduced (p < 0.05). Similar trends were observed with a statistically significant reduction in motion in all anatomical planes when the rod diameter was increased to 4.5 mm. Although the increase in rod diameter resulted in a more rigid construct, it also created an increase (p < 0.05) in the kinematics of the adjacent segments (C2–3 and C6–7). Whether this increase translates into adverse long-term clinical effects in vivo requires further investigation and clinical assessment.

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Surgical outcomes of pediatric spinal cord astrocytomas: systematic review and meta-analysis

Tej D. Azad, Arjun V. Pendharkar, James Pan, Yuhao Huang, Amy Li, Rogelio Esparza, Swapnil Mehta, Ian D. Connolly, Anand Veeravagu, Cynthia J. Campen, Samuel H. Cheshier, Michael S. B. Edwards, Paul G. Fisher, and Gerald A. Grant

OBJECTIVE

Pediatric spinal astrocytomas are rare spinal lesions that pose unique management challenges. Therapeutic options include gross-total resection (GTR), subtotal resection (STR), and adjuvant chemotherapy or radiation therapy. With no randomized controlled trials, the optimal management approach for children with spinal astrocytomas remains unclear. The aim of this study was to conduct a systematic review and meta-analysis on pediatric spinal astrocytomas.

METHODS

The authors performed a systematic review of the PubMed/MEDLINE electronic database to investigate the impact of histological grade and extent of resection on overall survival among patients with spinal cord astrocytomas. They retained publications in which the majority of reported cases included astrocytoma histology.

RESULTS

Twenty-nine previously published studies met the eligibility criteria, totaling 578 patients with spinal cord astrocytomas. The spinal level of intramedullary spinal cord tumors was predominantly cervical (53.8%), followed by thoracic (40.8%). Overall, resection was more common than biopsy, and GTR was slightly more commonly achieved than STR (39.7% vs 37.0%). The reported rates of GTR and STR rose markedly from 1984 to 2015. Patients with high-grade astrocytomas had markedly worse 5-year overall survival than patients with low-grade tumors. Patients receiving GTR may have better 5-year overall survival than those receiving STR.

CONCLUSIONS

The authors describe trends in the management of pediatric spinal cord astrocytomas and suggest a benefit of GTR over STR for 5-year overall survival.

Open access

Evaluating frailty, mortality, and complications associated with metastatic spine tumor surgery using machine learning–derived body composition analysis

Elie Massaad, Christopher P. Bridge, Ali Kiapour, Mitchell S. Fourman, Julia B. Duvall, Ian D. Connolly, Muhamed Hadzipasic, Ganesh M. Shankar, Katherine P. Andriole, Michael Rosenthal, Andrew J. Schoenfeld, Mark H. Bilsky, and John H. Shin

OBJECTIVE

Cancer patients with spinal metastases may undergo surgery without clear assessments of prognosis, thereby impacting the optimal palliative strategy. Because the morbidity of surgery may adversely impact recovery and initiation of adjuvant therapies, evaluation of risk factors associated with mortality risk and complications is critical. Evaluation of body composition of cancer patients as a surrogate for frailty is an emerging area of study for improving preoperative risk stratification.

METHODS

To examine the associations of muscle characteristics and adiposity with postoperative complications, length of stay, and mortality in patients with spinal metastases, the authors designed an observational study of 484 cancer patients who received surgical treatment for spinal metastases between 2010 and 2019. Sarcopenia, muscle radiodensity, visceral adiposity, and subcutaneous adiposity were assessed on routinely available 3-month preoperative CT images by using a validated deep learning methodology. The authors used k-means clustering analysis to identify patients with similar body composition characteristics. Regression models were used to examine the associations of sarcopenia, frailty, and clusters with the outcomes of interest.

RESULTS

Of 484 patients enrolled, 303 had evaluable CT data on muscle and adiposity (mean age 62.00 ± 11.91 years; 57.8% male). The authors identified 2 clusters with significantly different body composition characteristics and mortality risks after spine metastases surgery. Patients in cluster 2 (high-risk cluster) had lower muscle mass index (mean ± SD 41.16 ± 7.99 vs 50.13 ± 10.45 cm2/m2), lower subcutaneous fat area (147.62 ± 57.80 vs 289.83 ± 109.31 cm2), lower visceral fat area (82.28 ± 48.96 vs 239.26 ± 98.40 cm2), higher muscle radiodensity (35.67 ± 9.94 vs 31.13 ± 9.07 Hounsfield units [HU]), and significantly higher risk of 1-year mortality (adjusted HR 1.45, 95% CI 1.05–2.01, p = 0.02) than individuals in cluster 1 (low-risk cluster). Decreased muscle mass, muscle radiodensity, and adiposity were not associated with a higher rate of complications after surgery. Prolonged length of stay (> 7 days) was associated with low muscle radiodensity (mean 30.87 vs 35.23 HU, 95% CI 1.98–6.73, p < 0.001).

CONCLUSIONS

Body composition analysis shows promise for better risk stratification of patients with spinal metastases under consideration for surgery. Those with lower muscle mass and subcutaneous and visceral adiposity are at greater risk for inferior outcomes.

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Abstracts of the 2014 Annual Meeting of the Lumbar Spine Research Society Chicago, Illinois • May 1–2, 2014