Patel, Naresh P.

Introduction Endovascular procedures have become increasingly popular in recent years due to preference of minimally invasive approaches and technological advancement.This study aims to characterize the trends in procedural rates of common neuro‐endovascular procedures performed by neurologists, neurosurgeons, and radiologists. Methods The Medicare Provider Utilization Database was queried from 2013 to 2019 for all primary Current Procedural Terminology codes identified by the American Medical Association as pertaining to endovascular procedures of the nervous system (61623, 61624, 61630, 61635, 61626, 61645, and 61650). Statistical analyses, including data aggregation, exploratory analysis, and propensity adjustment, were performed using R, version 4.0.1 (The R Foundation, Vienna, Austria). The two‐sided Mann‐Kendall trend test, a non‐parametric statistical test that assesses for monotonic trends in either an upward or downward trend, was utilized to assess for trends over time. A significance level of 0.05 was used. Results Between 2013 to 2019 a total of 40,730 endovascular procedures were performed by neurosurgeons, neurologists and radiologists treating Medicare patients. When all codes were combined, there was a significant increase in the number of procedures done by all specialists: Radiology (2013:1080; 2019:4938; p:0.02), Neurosurgery (2013:1230; 2019:4508; p< 0.01), and Neurology (2013:205; 2019:2397; p:0.04). Significant increases in mechanical thrombectomy (CPT61645) were observed in all fields: Radiology (2016:1287, 2019:3542; p< 0.01), Neurosurgery (2016:610; 2019:2326; p< 0.01), Neurology (2016:569; 2019:1951; p< 0.01). Increases in transcatheter permanent occlusion (CPT61624) were observed in neurosurgery (2013:1230; 2019:2049; p:0.04). Increases in temporary balloon artery occlusion (CPT61623) were noted in neurology (2013:21; 2019:27; p:0.04). Conclusions Endovascular procedures have seen a dramatic rise in utilization over a short amount of time, particularly mechanical thrombectomy. Future investigation should include more inclusive datasets beyond the Medicare population.

Abstract High grade glioma (HGG) represents a group of devastating diseases with dismal prognosis. Surgical resection of the contrast enhancing (CE) region of HGG remains the mainstay of treatment, but recurrence inevitably arises from the unresected non-contrast enhancing (NE) region, surgically inaccessible due to cancer cell invasion into healthy brain tissue. Due to its critical role in recurrence, understanding of the NE region is central to the improvement of clinical outcomes. We reveal the biological characteristics of this region through image localized multi-regional sampling. We linked microenvironmental characteristics measured by multi-parametric MRI to genomic mutations and transcriptional phenotypes using mixed effect modeling which allowed us to control for individualized patient effects. We first confirmed that T2 is a significant indicator of IDH mutation status in the NE region, being the first description of such a relationship in a HGG cohort. We found the combination of EGFR amplification and CDKN2A homozygous loss was associated with a significantly lower mean diffusivity (MD) compared to double wild type tumors in the NE region, indicating the presence of greater cellular packing and proliferation in EGFR amplification/CDKN2A loss regions. Finally, using single cell pathway based tumor classifications, we showed that nK2, a DSC-MRI metric representing cell size heterogeneity, correlated positively with neuronal signature and negatively with glycolytic/plurimetabolic signature within the NE tumor, indicating that glycolytic/plurimetobolic tumors possessed a high amount of cell size heterogeneity compared to neuronal samples. This hypothesis was supported using digital reference object (DRO) modeling which confirmed that cell size and heterogeneity drove the differential nK2 signal between neuronal and glycolytic/plurimetabolic samples. We identified immune cell infiltrate as one possible mechanism of increased cell size heterogeneity using transcriptomic signature analysis which found more immune cell signatures within glycolytic/plurimetobolic tumors compared to neuronal. Collectively this study demonstrates the central role of multi-parametric MRI as a non-invasive measure of tumor biology and a tool for understanding the clinically critical NE region which can then inform new therapies targeting this region of HGG recurrence. Citation Format: Matthew Flick, Taylor Weiskittel, Kevin Meng-Lin, Fulvio D'Angelo, Francesca Caruso, Shannon Ensign, Mylan Blomquist, Luija Wang, Christopher Sereduk, Gustavo De Leon, Ashley Nespodzany, Javier Urcuyo, Ashlynn Gonzalez, Lee Curtin, Kyle Singleton, Aliya Anil, Natenael Simmineh, Erika Lewis, Teresa Noviello, Reyna Patel, Panwen Wang, Junwen Wang, Jennifer Eschbacher, Andrea Hawkins-Daarud, Pamela Jackson, Kris Smith, Peter Nakaji, Bernard Bendok, Richard Zimmerman, Chandan Krishna, Devi Patra, Naresh Patel, Mark Lyons, Matthew Neal, Kliment Donev, Maciej Mrugala, Alyx Porter, Scott Beeman, Yuxiang Zhou, Leslie Baxter, Christopher Plaisier, Jing Li, Hu Li, Anna Lasorella, Chad Quarles, Kristin Swanson, Michele Ceccarelli, Antonio Iavarone, Nhan Tran, Leland Hu. Multi-parametric MRI maps regional heterogeneity of high grade glioma phenotypes. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5621.

Abstract High grade gliomas (HGG) are aggressive primary brain malignancies typified by diffuse invasion, genetic heterogeneity, and a universally fatal outcome. MRI-defined contrast-enhancing (CE) tumor burden serves as the clinical standard that guides maximal surgical resection and post-therapy response assessment. However, HGGs also comprise an invasive non-enhancing (NE) tumor margin that extends beyond the CE core and harbors the cells that contribute to recurrence. Sampling restrictions have hindered the comprehensive study of these NE HGG cell populations driving tumor progression. Herein, we present an integrated multi-omic analysis of 313 spatially matched multi-regional CE and NE tumor biopsies from 68 HGG patients, performing whole exome and RNA sequencing of both IDH wild-type and IDH mutant HGGs. We report spatially restricted molecular profiles in IDH-mutant HGG, highlighting a concern for sampling bias given the importance of molecular diagnosis and prognostication in IDH-mutant HGG. Regardless of IDH status, we found that NE tumor regions harbored the highest proportion of private mutations, which reflects an increased development of regional genomic complexity in infiltrative tumor. The multiregional genomic profiling of our IDH wild-type HGG cohort reveals that EGFR and NF1 somatic alterations occur as mutually exclusive events in 98.7% of tumors. However, we resolved rare low allele frequency co-alterations of EGFR and NF1 within the NE region. We find this co-occurrence enriched in recurrent tumors, pointing to the early emergence of NF1 inactivation in the NE regions. We constructed genomic models predictive of recurrent disease from both NE and CE regions, which highlight the occurrence of clonal EGFR copy number alterations and NF1 loss as clonal or subclonal events, respectively, emphasizing the regional and temporal complexity of well-studied canonical driver alterations. We detailed the spatially unique acquisition of multiple distinct EGFR alterations giving rise to intra-tumoral EGFR mosaicism, a challenge in the implementation of EGFR directed therapies. Our study also identified two transcriptomic clusters delineated by the significant overrepresentation of neuronal (NEU) and glycolytic/plurimetabolic (GPM) pathway-based functional states in the NE region. NE regions of the NEU subtype harbor the greatest proportion of private mutations, suggesting these infiltrative tumor cells accumulate alterations without clonal expansion. GPM populations conversely displayed a less branched phylogeny and were transcriptionally enriched in immune cell signatures. This phenotypic dichotomy between GPM and NEU populations supports the growing body of evidence that invasive GBM cells either take on a neuronal phenotype for active invasion or a more metabolic phenotype involving interaction with astrocytes, other glial cells, and infiltrating immune cells. Citation Format: Mylan R. Blomquist, Leland S. Hu, Fulvio D'Angelo, Taylor M. Weiskittel, Francesca P. Caruso, Shannon P. Fortin Ensign, Christopher Sereduk, Gustavo De Leon, Lee Curtin, Javier Urcuyo, Ashlynn Gonzalez, Ashley Nespodzany, Teresa Noviello, Jennifer M. Eschbacher, Kris A. Smith, Peter Nakaji, Bernard R. Bendok, Richard S. Zimmerman, Chandan Krishna, Devi Patra, Naresh Patel, Mark Lyons, Kliment Donev, Maciej Mrugala, Alyx Porter, Anna Lasorella, Kristin R. Swanson, Michele Ceccarelli, Antonio Iavarone, Nhan L. Tran. Multiregional sampling of high grade glioma identifies regional biologic signatures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1507.

Background: Radiation necrosis (RN) is a clinically relevant complication of stereotactic radiosurgery (SRS) for intracranial metastasis (ICM) treatments. Radiation necrosis development is variable following SRS. It remains unclear if risk factors for and clinical outcomes following RN may be different for melanoma patients. We reviewed patients with ICM from metastatic melanoma to understand the potential impact of RN in this patient population. Methods: Patients who received SRS for ICM from melanoma at Mayo Clinic Arizona between 2013 and 2018 were retrospectively reviewed. Data collected included demographics, tumor characteristics, radiation parameters, prior surgical and systemic treatments, and patient outcomes. Radiation necrosis was diagnosed by clinical evaluation including brain magnetic resonance imaging (MRI) and, in some cases, tissue evaluation. Results: Radiation necrosis was diagnosed in 7 (27%) of 26 patients at 1.6 to 38 months following initial SRS. Almost 92% of all patients received systemic therapy and 35% had surgical resection prior to SRS. Patients with RN trended toward having larger ICM and a prior history of surgical resection, although statistical significance was not reached. Among patients with resection, those who developed RN had a longer period between surgery and SRS start (mean 44 vs 33 days). Clinical improvement following treatment for RN was noted in 2 (29%) patients. Conclusions: Radiation necrosis is relatively common following SRS for treatment of ICM from metastatic melanoma and clinical outcomes are poor. Further studies aimed at mitigating RN development and identifying novel approaches for treatment are warranted.

OBJECTIVE This analysis evaluated if spinal cord stimulation (SCS) at 10 kHz plus conventional medical management (CMM) is cost-effective compared with CMM alone for the treatment of nonsurgical refractory back pain (NSRBP). METHODS NSRBP subjects were randomized 1:1 into the 10-kHz SCS (n = 83) or CMM (n = 76) group. Outcomes assessed at 6 months included EQ-5D 5-level (EQ-5D-5L), medication usage, and healthcare utilization (HCU). There was an optional crossover at 6 months and follow-up to 12 months. The incremental cost-effectiveness ratio (ICER) was calculated with cost including all HCU and medications except for the initial device and implant procedure, and cost-effectiveness was analyzed based on a willingness-to-pay threshold of < $50,000 per quality-adjusted life-year. RESULTS Treatment with 10-kHz SCS resulted in a significant improvement in quality of life (QOL) over CMM (EQ-5D-5L index score change of 0.201 vs −0.042, p < 0.001) at a lower cost, based on reduced frequency of HCU resulting in an ICER of −$4964 at 12 months. The ICER was −$8620 comparing the 6 months on CMM with postcrossover on 10-kHz SCS. CONCLUSIONS Treatment with 10-kHz SCS provides higher QOL at a lower average cost per patient compared with CMM. Assuming an average reimbursement for device and procedure, 10-kHz SCS therapy is predicted to be cost-effective for the treatment of NSRBP compared with CMM within 2.1 years.

Background: The first instance of a robotic-assisted surgery occurred in neurosurgery; however, it is now more common in other fields such as urology and gynecology. This study aims to characterize the prevalence of robotic surgery among current neurosurgery programs as well as identify trends in clinical trials pertaining to robotic neurosurgery. Methods: Each institution’s website was analyzed for the mention of a robotic neurosurgery program and procedures. The future potential of robotics in neurosurgery was assessed by searching for current clinical trials pertaining to neurosurgical robotic surgery. Results: Of the top 100 programs, 30 offer robotic cranial and 40 offer robotic spinal surgery. No significant differences were observed with robotic surgical offerings between geographic regions in the US. Larger programs (faculty size 16 or over) had 20 of the 30 robotic cranial programs (66.6%), whereas 21 of the 40 robotic spinal programs (52.5%) were at larger programs. An initial search of clinical trials revealed 223 studies, of which only 13 pertained to robotic neurosurgery. Spinal fixation was the most common intervention (six studies), followed by Deep Brain Stimulation (DBS, two studies), Cochlear implants (two studies), laser ablation (LITT, one study), and endovascular embolization (one study). Most studies had industry sponsors (9/13 studies), while only five studies had hospital sponsors. Conclusion: Robotic neurosurgery is still in its infancy with less than half of the top programs offering robotic procedures. Future directions for robotics in neurosurgery appear to be focused on increased automation of stereotactic procedures such as DBS and LITT and robot-assisted spinal surgery.

Background: Ankylosing spondylitis (AS) is a chronic, progressive, inflammatory disease of the spine and SI joints. Diagnostic criteria and treatments have continued to evolve, necessitating a historical compendium of AS and its management. This paper aims to review the historical context underlying the discovery of AS, as well as the major diagnostic and therapeutic discoveries in the last two centuries. Methods: A scoping review of the literature pertaining to AS was performed via the Pubmed, Scopus, and Web of Science databases. Future directions of AS treatments were assessed by querying the clinicaltrials.gov website. Results: The history of AS can be traced as far back as ancient Egypt (as evidenced by the discovery of its presence in ancient Egyptian mummies) to the late 20th century, when the inherited nature of AS was linked to a genetic factor, HLA-B27. Each discovery made throughout the years led to further investigations into the pathophysiology, diagnosis, and treatment of AS. The criteria to differentiate AS from rheumatoid arthritis were first reported in 1893. Since then, diagnostic criteria for AS have undergone a series of changes before the present-day diagnostic criteria for AS were ultimately determined in 2009 by the Assessment of Spondyloarthritis International Society. Conclusion: As the pathophysiology of AS is better understood, healthcare providers are able to diagnose and treat the condition more effectively. In particular, earlier diagnosis and multiple treatment options have facilitated efficient and more effective treatment.

OBJECTIVE Procedural reimbursement for spine surgery has changed drastically over the past 20 years. A comprehensive understanding of these trends is important as major changes in reimbursement models of spine surgery continue to evolve within various spine specialties as well as broader national healthcare policy. In this study the authors evaluated the monetary trends in Medicare reimbursement rates for the 15 most common spinal surgery procedures from 2000 to 2021. METHODS The National Surgery Quality Improvement Project database (2019) was queried to determine the 15 most commonly performed spine surgery procedures. The Current Procedural Terminology (CPT) codes for each of these procedures were obtained from the Physician Fee Schedule Look-Up Tool from the Centers for Medicare and Medicaid Services, and comprehensive reimbursement data for each code were extracted. Changes in Medicare reimbursement rates were calculated and averaged for each procedure as both raw percent changes and percent changes adjusted for inflation to 2021 US dollars (USD) based on the consumer price index (CPI). The adjusted R2 value, the compound annual growth rate (CAGR), and both the average annual and the total percent change in reimbursement were calculated based on these adjusted trends for all included procedures. RESULTS After adjustment for inflation, average reimbursement for all procedures decreased by 33.8% from 2000 to 2021. The greatest mean decrease was seen in anterior cervical arthrodesis (−38.7%), while the smallest mean decrease was in vertebral body excision (−17.1%). From 2000 to 2021, the adjusted reimbursement rate for all included procedures decreased by an average of 1.9% each year, with an average R2 value of 0.69. CONCLUSIONS This is the first study to evaluate monetary trends in Medicare reimbursement for spine surgery procedures. After adjusting for inflation, Medicare reimbursement for the 15 most commonly performed spine procedures has steadily decreased from 2000 to 2021. Increased awareness of these trends and the forces driving them will be critical in the coming years as negotiations regarding reimbursement models continue to unfold. Greater understanding of spine surgery reimbursement among policy makers, hospitals, and surgeons will be important to ensure continued access to quality surgical spine care in the United States.