Adrian John Rodrigues

All Publications

• Clinical Outcomes and Cost Profiles for Cage and Allograft Anterior Cervical Discectomy and Fusion Procedures in the Adult Population: A Propensity Score-Matched Study. Asian spine journal Rodrigues, A. J., Varshneya, K., Stienen, M. N., Schonfeld, E., Than, K. D., Veeravagu, A. 2023

  Abstract

  Retrospective cohort study.To characterize the postoperative outcomes and economic costs of anterior cervical discectomy and fusion (ACDF) procedures using synthetic biomechanical intervertebral cage (BC) and structural allograft (SA) implants.ACDF is a common spine procedure that typically uses an SA or BC for the cervical fusion. Previous studies that compared the outcomes between the two implants were limited by small sample sizes, short-term postoperative outcomes, and procedures with single-level fusion.Adult patients who underwent an ACDF procedure in 2007-2016 were included. Patient records were extracted from MarketScan, a national registry that captures person-specific clinical utilization, expenditures, and enrollments across millions of inpatient, outpatient, and prescription drug services. Propensity-score matching (PSM) was employed to match the patient cohorts across demographic characteristics, comorbidities, and treatments.Of 110,911 patients, 65,151 (58.7%) received BC implants while 45,760 (41.3%) received SA implants. Patients who underwent BC surgeries had slightly higher reoperation rates within 1 year after the index ACDF procedure (3.3% vs. 3.0%, p=0.004), higher postoperative complication rates (4.9% vs. 4.6%, p=0.022), and higher 90-day readmission rates (4.9% vs. 4.4%, p =0.001). After PSM, the postoperative complication rates did not vary between the two cohorts (4.8% vs. 4.6%, p=0.369), although dysphagia (2.2% vs. 1.8%, p<0.001) and infection (0.3% vs. 0.2%, p=0.007) rates remained higher for the BC group. Other outcome differences, including readmission and reoperation, decreased. Physician's fees remained high for BC implantation procedures.We found marginal differences in clinical outcomes between BC and SA ACDF interventions in the largest published database cohort of adult ACDF surgeries. After adjusting for group-level differences in comorbidity burden and demographic characteristics, BC and SA ACDF surgeries showed similar clinical outcomes. Physician's fees, however, were higher for BC implantation procedures.

  View details for DOI 10.31616/asj.2022-0261

  View details for PubMedID 37226385

• The Impact of Preoperative Myelopathy on Postoperative Outcomes among Anterior Cervical Discectomy and Fusion Procedures in the Nonelderly Adult Population: A Propensity-Score Matched Study. Asian spine journal Rodrigues, A. J., Schonfeld, E., Varshneya, K., Stienen, M. N., Veeravagu, A. 2023

  Abstract

  Retrospective cohort study.Anterior cervical discectomy and fusion (ACDF) is a common surgical intervention for patients diagnosed with cervical degenerative diseases with or without myelopathy. A thorough understanding of outcomes in patients with and without myelopathy undergoing ACDF is required because of the widespread utilization of ACDF for these indications.Non-ACDF approaches achieved inferior outcomes in certain myelopathic cases. Studies have compared patient outcomes across procedures, but few have compared outcomes concerning myelopathic versus nonmyelopathic cohorts.The MarketScan database was queried from 2007 to 2016 to identify adult patients who were ≤65 years old, and underwent ACDF using the international classification of diseases 9th version and current procedural terminology codes. Nearest neighbor propensity-score matching was employed to balance patient demographics and operative characteristics between myelopathic and nonmyelopathic cohorts.Of 107,480 patients who met the inclusion criteria, 29,152 (27.1%) were diagnosed with myelopathy. At baseline, the median age of patients with myelopathy was higher (52 years vs. 50 years, p <0.001), and they had a higher comorbidity burden (mean Charlson comorbidity index, 1.92 vs. 1.58; p <0.001) than patients without myelopathy. Patients with myelopathy were more likely to undergo surgical revision at 2 years (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.54-1.73) or are readmitted within 90 days (OR, 1.27; 95% CI, 1.20-1.34). After patient cohorts were matched, patients with myelopathy remained at elevated risk for reoperation at 2 years (OR, 1.55; 95% CI, 1.44-1.67) and postoperative dysphagia (2.78% vs. 1.68%, p <0.001) compared to patients without myelopathy.We found inferior postoperative outcomes at baseline for patients with myelopathy undergoing ACDF compared to patients without myelopathy. Patients with myelopathy remained at significantly greater risk for reoperation and readmission after balancing potential confounding variables across cohorts, and these differences in outcomes were largely driven by patients with myelopathy undergoing 1-2 level fusions.

  View details for DOI 10.31616/asj.2022.0347

  View details for PubMedID 37226379

• Cytodifferentiation of pituitary tumors influences pathogenesis and cavernous sinus invasion. Journal of neurosurgery Asmaro, K., Zhang, M., Rodrigues, A. J., Mohyeldin, A., Vigo, V., Nernekli, K., Vogel, H., Born, D. E., Katznelson, L., Fernandez-Miranda, J. C. 2023: 1-9

  Abstract

  Pituitary tumors (PTs) continue to present unique challenges given their proximity to the cavernous sinus, whereby invasive behavior can limit the extent of resection and surgical outcome, especially in functional tumors. The aim of this study was to elucidate patterns of cavernoinvasive behavior by PT subtype.A total of 169 consecutive first-time surgeries for PTs were analyzed; 45% of the tumors were functional. There were 64 pituitary transcription factor-1 (PIT-1)-expressing, 62 steroidogenic factor-1 (SF-1)-expressing, 38 T-box transcription factor (TPIT)-expressing, and 5 nonstaining PTs. The gold standard for cavernous sinus invasion (CSI) was based on histopathological examination of the cavernous sinus medial wall and intraoperative exploration.Cavernous sinus disease was present in 33% of patients. Of the Knosp grade 3 and 4 tumors, 12 (19%) expressed PIT-1, 7 (11%) expressed SF-1, 8 (21%) expressed TPIT, and 2 (40%), were nonstaining (p = 0.36). PIT-1 tumors had a significantly higher predilection for CSI: 53% versus 24% and 18% for TPIT and SF-1 tumors, respectively (OR 6.08, 95% CI 2.86-13.55; p < 0.001). Microscopic CSI-defined as Knosp grade 0-2 tumors with confirmed invasion-was present in 44% of PIT-1 tumors compared with 7% and 13% of TPIT and SF-1 tumors, respectively (OR 11.72, 95% CI 4.35-35.50; p < 0.001). Using the transcavernous approach to excise cavernous sinus disease, surgical biochemical remission rates for patients with acromegaly, prolactinoma, and Cushing disease were 88%, 87%, and 100%, respectively. The granule density of PIT-1 tumors and corticotroph functional status did not influence CSI.The likelihood of CSI differed by transcription factor expression; PIT-1-expressing tumors had a higher predilection for invading the cavernous sinus, particularly microscopically, compared with the other tumor subtypes. This elucidates a unique cavernoinvasive behavior absent in cells from other lineages. Innovative surgical techniques, however, can mitigate tumor behavior and achieve robust, reproducible biochemical remission and gross-total resection rates. These findings can have considerable implications on the surgical management and study of PT biology and behavior.

  View details for DOI 10.3171/2023.3.JNS221949

  View details for PubMedID 37119095

• Clinical outcomes and cost differences between patients undergoing primary anterior cervical discectomy and fusion procedures with private or Medicare insurance: a propensity score matched study. World neurosurgery Shah, V., Rodrigues, A. J., Malhotra, S., Johnstone, T., Varshneya, K., Haider, G., Stienen, M. N., Veeravagu, A. 2023

  Abstract

  To assess whether insurance type reflects a patient's quality of care following an ACDF procedure, by comparing differences in post-operative complications, readmission rates, reoperation rates, length of hospital stay, and cost of treatment between patients with Medicare versus private insurance.Propensity score matching (PSM) was employed to match patient cohorts insured by Medicare and private insurance in the MarketScan Commercial Claims and Encounters Database (2007-2016). Age, sex, year of operation, geographic region, comorbidities, and operative factors were used to match cohorts of patients undergoing an ACDF procedure.A total of 110,911 patients met the inclusion criteria, of which 97,543 patients (87.9%) were privately insured and 13,368 patients (12.1%) were insured by Medicare. The PSM algorithm matched 7,026 privately insured patients to 7,026 Medicare patients. After matching, there was no significant difference in 90-day post-operative complication rates, length of stay, or reoperation rates between the Medicare and privately insured cohorts. The Medicare group had lower post-operative readmission rates for all time points: 30 days (1.8% vs. 4.6%; p < 0.001), 60 days (2.5% vs. 6.3%; p < 0.001), and 90 days (4.2% vs. 7.7%; p < 0.001). The median payments to physicians were significantly lower for the Medicare group ($3,885 vs. $5,601; p < 0.001).In this study, propensity score matched patients covered by Medicare and private insurance that underwent an ACDF procedure were found to have similar treatment outcomes.

  View details for DOI 10.1016/j.wneu.2023.02.129

  View details for PubMedID 36871653

• Proof of Principle for Intracarotid Injection of Leukemia As Model for Late Stage Central Nervous System Leukemia Wang, C., Rodrigues, A., Chernikova, S., Davis, K. L., Gephart, M. AMER SOC HEMATOLOGY. 2022: 11522-11523

  View details for DOI 10.1182/blood-2022-158294

  View details for Web of Science ID 000893230304287

• Predictors of spine metastases at initial presentation of pediatric brain tumor patients: a single-institution study. Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery Rodrigues, A. J., Medress, Z. A., Sayadi, J., Bhambhvani, H., Falkson, S. R., Jokhai, R., Han, S. S., Hong, D. S. 2022

  Abstract

  PURPOSE: Given the rarity of disseminated disease at the time of initial evaluation for pediatric brain tumor patients, we sought to identify clinical and radiographic predictors of spinal metastasis (SM) at the time of presentation.METHODS: We performed a single-institution retrospective chart review of pediatric brain tumor patients who first presented between 2004 and 2018. We extracted information regarding patient demographics, radiographic attributes, and presenting symptoms. Univariate and multivariate logistic regression was used to estimate the association between measured variables and SMs.RESULTS: We identified 281 patients who met our inclusion criteria, of whom 19 had SM at initial presentation (6.8%). The most common symptoms at presentation were headache (n=12; 63.2%), nausea/vomiting (n=16; 84.2%), and gait abnormalities (n=8; 41.2%). Multivariate models demonstrated that intraventricular and posterior fossa tumors were more frequently associated with SM (OR: 5.28, 95% CI: 1.79-15.59, p=0.003), with 4th ventricular (OR: 7.42, 95% CI: 1.77-31.11, p=0.006) and cerebellar parenchymal tumor location (OR: 4.79, 95% CI: 1.17-19.63, p=0.030) carrying the highest risk for disseminated disease. In addition, evidence of intracranial leptomeningeal enhancement on magnetic resonance imaging (OR: 46.85, 95% CI: 12.31-178.28, p<0.001) and hydrocephalus (OR: 3.19; 95% CI: 1.06-9.58; p=0.038) were associated with SM.CONCLUSIONS: Intraventricular tumors and the presence of intracranial leptomeningeal disease were most frequently associated with disseminated disease at presentation. These findings are consistent with current clinical expectations and offer empirical evidence that heightened suspicion for SM may be prospectively applied to certain subsets of pediatric brain tumor patients at the time of presentation.

  View details for DOI 10.1007/s00381-022-05702-5

  View details for PubMedID 36266365

• 5-Aminolevulinic Acid Imaging of Malignant Glioma. Surgical oncology clinics of North America Li, G., Rodrigues, A., Kim, L., Garcia, C., Jain, S., Zhang, M., Hayden-Gephart, M. 2022; 31 (4): 581-593

  Abstract

  High-grade glioma is the most common malignant primary brain tumor in adults. Glioma infiltration renders it difficult to treat and likely to recur. Increasing the extent of resection has been associated with improving progression-free survival and overall survival by several months. The introduction of 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery has allowed surgeons to better differentiate between neoplastic tissue and normal tissue, thus achieving greater extent of resection. The development of new intraoperative imaging modalities in combination with 5-ALA may provide additional benefits for glioma patients.

  View details for DOI 10.1016/j.soc.2022.06.002

  View details for PubMedID 36243495

• Comparison of Deep Learning and Classical Machine Learning Algorithms to Predict Post-operative Outcomes for Anterior Cervical Discectomy and Fusion Procedures with State-of-the-art Performance. Spine Rodrigues, A. J., Schonfeld, E., Varshneya, K., Stienen, M. N., Staartjes, V. E., Jin, M. C., Veeravagu, A. 2022

  Abstract

  STUDY DESIGN: Retrospective cohort.OBJECTIVE: Due to Anterior cervical discectomy and fusion (ACDF) popularity, it is important to predict post-operative complications, unfavorable 90-day readmissions, and 2-year re-operations to improve surgical decision making, prognostication and planning.SUMMARY OF BACKGROUND DATA: Machine learning has been applied to predict post-operative complications for ACDF; however, studies were limited by sample size and model type. These studies achieved 0.70 AUC. Further approaches, not limited to ACDF, focused on specific complication types, and resulted in AUC between 0.70-0.76.METHODS: The IBM MarketScan Commercial Claims and Encounters Database and Medicare Supplement were queried from 2007-2016 to identify adult patients who underwent an ACDF procedure (N=176,816). Traditional machine learning algorithms, logistic regression, support vector machines, were compared with deep neural networks to predict: 90-day post-operative complications, 90-day readmission, and 2-year reoperation. We further generated random deep learning model architectures and trained them on the 90-day complication task to approximate an upper bound. Lastly, using deep learning, we investigated the importance of each input variable for the prediction of 90-day post-operative complications in ACDF.RESULTS: For the prediction of 90-day complication, 90-day readmission, and 2-year reoperation, the deep neural network-based models achieved area under the curve (AUC) of 0.832, 0.713, and 0.671. Logistic regression achieved AUCs of 0.820, 0.712, and 0.671. SVM approaches were significantly lower. The upper bound of deep learning performance was approximated as 0.832. Myelopathy, age, HIV, previous myocardial infarctions, obesity, and documentary weakness were found to be the strongest variable to predict 90-day post-operative complications.CONCLUSIONS: The deep neural network may be used to predict complications for clinical applications after multi-center validation. The results suggest limited added knowledge exists in interactions between the input variables used for this task. Future work should identify novel variables to increase predictive power.

  View details for DOI 10.1097/BRS.0000000000004481

  View details for PubMedID 36149852

• Chronic opioid use prior to ACDF surgery is associated with inferior post-operative outcomes: a propensity-matched study of 17,443 chronic opioid users. World neurosurgery Rodrigues, A. J., Varshneya, K., Schonfeld, E., Malhotra, S., Stienen, M. N., Veeravagu, A. 2022

  Abstract

  STUDY DESIGN: Retrospective cohort OBJECTIVE: Candidates for anterior cervical discectomy and fusion (ACDF) have a higher rate of opioid use than does the public, but studies on pre-operative opioid use have not been conducted. We aimed to understand how pre-operative opioid use affects post-ACDF outcomes.METHODS: The MarketScan Database was queried from 2007-2015 to identify adult patients who underwent an ACDF. Patients were classified into separate cohorts based on the number of separate opioid prescriptions in the year before their ACDF. 90-day post-operative complications, post-operative readmission, re-operation, and total inpatient costs were compared between opioid strata. Propensity-score matching (PSM) matched patient cohorts across observed comorbidities.RESULTS: Of 81,671 ACDF patients, 31,312 (38.3%) were non-users, 30,302 (37.1%) were mild users, and 20,057 (24.6%) were chronic users. Chronic opioid users had a higher comorbidity burden, on average, than patients with less frequent opioid use (p<0.001). Chronic opioid users had higher rates of post-operative complications (9.1%) than mild opioid users (6.0%) and non-users (5.3%) (p<0.001), and higher rates of readmission and reoperation. After balancing opioid non-users vs. chronic opioid users along demographic, pre-operative comorbidity, and operative characteristics, post-operative complications remained elevated for chronic opioid users relative to opioid non-users (8.6% vs. 5.7%; p<0.001), as did rates of readmission and reoperation.CONCLUSIONS: Chronic opioid users had more comorbidities than opioid non-users and mild opioid users, longer hospitalizations, and higher rates of post-operative complication, readmission, and reoperation. After balancing patients across covariates, the outcome differences persisted, suggesting a durable association between pre-operative opioid use and negative post-operative outcomes.

  View details for DOI 10.1016/j.wneu.2022.07.002

  View details for PubMedID 35809840

• Is a single-staged endovascular embolization and microsurgical resection approach preferred to a multi-staged approach for the treatment of brain arteriovenous malformations? Annals of translational medicine Novis, H. S., Rodrigues, A. J., Campbell, G. J., Falkson, S. R. 2022; 10 (14): 758

  View details for DOI 10.21037/atm-22-3395

  View details for PubMedID 35965807

• Health Care Resource Utilization in Management of Opioid-Naive Patients With Newly Diagnosed Neck Pain. JAMA network open Jin, M. C., Jensen, M., Zhou, Z., Rodrigues, A., Ren, A., Barros Guinle, M. I., Veeravagu, A., Zygourakis, C. C., Desai, A. M., Ratliff, J. K. 2022; 5 (7): e2222062

  Abstract

  Importance: Research has uncovered heterogeneity and inefficiencies in the management of idiopathic low back pain, but few studies have examined longitudinal care patterns following newly diagnosed neck pain.Objective: To understand health care utilization in patients with new-onset idiopathic neck pain.Design, Setting, and Participants: This cross-sectional study used nationally sourced longitudinal data from the IBM Watson Health MarketScan claims database (2007-2016). Participants included adult patients with newly diagnosed neck pain, no recent opioid use, and at least 1 year of continuous postdiagnosis follow-up. Exclusion criteria included prior or concomitant diagnosis of traumatic cervical disc dislocation, vertebral fractures, myelopathy, and/or cancer. Only patients with at least 1 year of prediagnosis lookback were included. Data analysis was performed from January 2021 to January 2022.Main Outcomes and Measures: The primary outcome of interest was 1-year postdiagnosis health care expenditures, including costs, opioid use, and health care service utilization. Early services were those received within 30 days of diagnosis. Multivariable regression models and regression-adjusted statistics were used.Results: In total, 679 030 patients (310 665 men [45.6%]) met the inclusion criteria, of whom 7858 (1.2%) underwent surgery within 1 year of diagnosis. The mean (SD) age was 44.62 (14.87) years among nonsurgical patients and 49.69 (9.53) years among surgical patients. Adjusting for demographics and comorbidities, 1-year regression-adjusted health care costs were $24 267.55 per surgical patient and $515.69 per nonsurgical patient. Across all health care services, $95 379 949 was accounted for by nonsurgical patients undergoing early imaging who did not receive any additional conservative therapy or epidural steroid injections, for a mean (SD) of $477.53 ($1375.60) per patient and median (IQR) of $120.60 ($20.70-$452.37) per patient. On average, patients not undergoing surgery, physical therapy, chiropractic manipulative therapy, or epidural steroid injection, who underwent either early advanced imaging (magnetic resonance imaging or computed tomography) or both early advanced and radiographic imaging, accumulated significantly elevated health care costs ($850.69 and $1181.67, respectively). Early conservative therapy was independently associated with 24.8% (95% CI, 23.5%-26.2%) lower health care costs.Conclusions and Relevance: In this cross-sectional study, early imaging without subsequent intervention was associated with significantly increased health care spending among patients with newly diagnosed idiopathic neck pain. Early conservative therapy was associated with lower costs, even with increased frequency of therapeutic services, and may have reduced long-term care inefficiency.

  View details for DOI 10.1001/jamanetworkopen.2022.22062

  View details for PubMedID 35816312

• Impact of socio-economic factors on radiation treatment after resection of metastatic brain tumors: trends from a private insurance database. Journal of neuro-oncology Dadey, D. Y., Rodrigues, A., Haider, G., Pollom, E. L., Adler, J. R., Veeravagu, A. 2022

  Abstract

  BACKGROUND: Stereotactic radiosurgery (SRS) to the surgical bed of resected brain metastases is now considered the standard of care due to its advantages over whole brain radiation therapy (WBRT). Despite the upward trend in SRS adoption since the 2000s, disparities have been reported suggesting that socio-economic factors can influence SRS utilization.OBJECTIVE: To analyze recent trends in SRS use and identify factors that influence treatment.METHODS: We conducted a retrospective cohort study with the Optum Commercial Claims and Encounters Database and included all patients from 2004 to 2021 who received SRS or WBRT within 60days after resection of tumors metastatic to the brain.RESULTS: A total of 3495 patients met the inclusion and exclusion criteria. There were 1998 patients in the SRS group and 1497 patients in the WBRT group. SRS use now supersedes WBRT by a wide margin. Lung, breast and colon were the most common sites of primary tumor. Although we found no significant differences based on race among the treatment groups, patients with annual household income greater than $75,000 and those with some college or higher education are significantly more likely to receive SRS (OR 1.44 and 1.30; 95% CI 1.18-1.76 and 1.08-1.56; P=0.001 and 0.005, respective). Patients with Elixhauser Comorbidity Index of three or more were significantly more likely to receive SRS treatment.CONCLUSION: The use of post-surgical SRS for brain metastasis has increased significantly over time, however education and income were associated with differential SRS utilization.

  View details for DOI 10.1007/s11060-022-04031-6

  View details for PubMedID 35596873

• A Retrospective Cohort Study of Implantable Pulse Generator Surgical Site Infections After Deep Brain Stimulation Surgery With an Antibacterial Envelope. Neuromodulation : journal of the International Neuromodulation Society Sayadi, J. J., Rodrigues, A. J., Patel, N. A., Ayer, A., Henderson, J. M. 2022

  Abstract

  INTRODUCTION: Deep brain stimulation (DBS) surgery is an established treatment for many patients with neurologic disease, and a common complication of DBS is surgical site infection (SSI). In 2016, neurosurgeons at our institution began enclosing implantable pulse generators (IPGs) within fully absorbable, antibacterial envelopes in patients who underwent initial DBS implantation. We sought to determine whether the use of antibacterial envelopes reduced IPG-related SSIs.MATERIALS AND METHODS: We performed a retrospective chart review of all adult patients who underwent initial DBS implantation at Stanford Hospital between November 14, 2012, and November 9, 2020. Operative details, perioperative antibiotics, comorbidities, and postoperative complications were extracted for all patients. Univariate and multivariate logistic regression were used to identify factors associated with SSIs within three months of surgery, and interrupted time-series analysis was performed to assess whether the departmental adoption of the antibacterial envelope led to a reduction in IPG SSIs.RESULTS: Of 344 patients who underwent initial IPG implantation with the antibacterial envelope, one developed an SSI within three months of surgery (0.3%), compared with six of 204 patients (2.9%) who underwent the same procedure without the antibacterial envelope (odds ratio: 0.10, 95% CI: 0.01-0.80, p= 0.031). Univariate logistic regression revealed that the antibacterial envelope and 2000-mg intravenous cefazolin perioperatively were associated with reduced SSI risk, whereas no other factors reached statistical significance. After adjusting for comorbidities, no association remained statistically significant. Interrupted time-series analysis showed a reduction in SSIs after 2016, but the effect was not significant.CONCLUSIONS: The adoption of antibacterial envelopes was found to reduce IPG SSIs at the univariate level, but this association did not remain significant after controlling for confounding variables including perioperative antibiotic administration. Although encouraging, this study does not conclusively establish that the use of antibacterial pouches in patients who underwent initial DBS implantation reduces the incidence of IPG SSIs. Future prospective studies that control for confounding variables are necessary to determine the efficacy of antibacterial envelopes in reducing post-DBS infections at the IPG site before clear recommendationscan be made.

  View details for DOI 10.1016/j.neurom.2022.02.227

  View details for PubMedID 35422367

• Factors Which Predict Adverse Outcomes in Anterior Cervical Discectomy and Fusion Procedures in the Nonelderly Adult Population. Clinical spine surgery Rodrigues, A. J., Jokhai, R., Varshneya, K., Stienen, M. N., Veeravagu, A. 2022

  Abstract

  STUDY DESIGN: Retrospective cohort.OBJECTIVE: The largest published cohort of anterior cervical discectomy and fusion (ACDF) patients was queried to better characterize demographic and operative factors that predict 90-day complication and 2-year reoperation risk.SUMMARY OF BACKGROUND DATA: The MarketScan Database was queried from 2007 to 2016 to identify adult patients until 65 years, who underwent an ACDF procedure using International Classification of Diseases 9th Version (ICD-9) and Current Procedural Terminology (CPT) codes. MarketScan is a national insurance claims database that contains millions of patient records across all 50 states.METHODS: Multivariate logistic regression was used to identify factors associated with complications until 90 days and reoperations until 2 years.RESULTS: Of 138,839 ACDF procedures, 8500 patients (6.1%) experienced a complication within 90 days of the ACDF, and 7433 (5.4%) underwent surgical revision by 2 years. While the use of anterior cervical plating did not predict 2-year reoperation, it was associated with dramatically reduced 90-day complication risk (adjusted odds ratio [aOR]: 0.32; 95% confidence interval [CI]: 0.30-0.34;P<0.001). Upon multivariate analysis, female sex (aOR: 0.83; 95% CI: 0.79-0.87;P<0.001) was associated with decreased risk of 2-year reoperation, while depression predicted a 50% increase in reoperation risk (aOR: 1.51; 95% CI: 1.43-1.59;P<0.001). The single largest factor associated with reoperation risk, however, was the presence of a 90-day postoperative complication (aOR: 1.79; 95% CI: 1.66-1.94;P<0.001).CONCLUSION: Increased patient comorbidities and the use of bone morphogenic protein were found to increase the risk for postoperative complications, while cervical plating was associated with a strong decline in this risk. In addition, poor patient mental health outweighed the adverse of impact of other comorbidities on 2-year revision risk. The presence of a postoperative complication was the key modifiable risk factor associated with reoperation risk. Conclusions from this study may help surgeons better identify high-risk ACDF patients for more careful patient selection, counseling, informed consent, and management.

  View details for DOI 10.1097/BSD.0000000000001326

  View details for PubMedID 35385403

• A Discussion of Machine Learning Approaches for Clinical Prediction Modeling. Acta neurochirurgica. Supplement Jin, M. C., Rodrigues, A. J., Jensen, M., Veeravagu, A. 2022; 134: 65-73

  Abstract

  While machine learning has occupied a niche in clinical medicine for decades, continued method development and increased accessibility of medical data have led to broad diversification of approaches. These range from humble regression-based models to more complex artificial neural networks; yet, despite heterogeneity in foundational principles and architecture, the spectrum of machine learning approaches to clinical prediction modeling have invariably led to the development of algorithms advancing our ability to provide optimal care for our patients. In this chapter, we briefly review early machine learning approaches in medicine before delving into common approaches being applied for clinical prediction modeling today. For each, we offer a brief introduction into theory and application with accompanying examples from the medical literature. In doing so, we present a summarized image of the current state of machine learning and some of its many forms in medical predictive modeling.

  View details for DOI 10.1007/978-3-030-85292-4_9

  View details for PubMedID 34862529

• Rapid intraoperative diagnosis of pediatric brain tumors using Raman spectroscopy: A machine learning approach. Neuro-oncology advances Jabarkheel, R., Ho, C., Rodrigues, A. J., Jin, M. C., Parker, J. J., Mensah-Brown, K., Yecies, D., Grant, G. A. 2022; 4 (1): vdac118

  Abstract

  Background: Surgical resection is a mainstay in the treatment of pediatric brain tumors to achieve tissue diagnosis and tumor debulking. While maximal safe resection of tumors is desired, it can be challenging to differentiate normal brain from neoplastic tissue using only microscopic visualization, intraoperative navigation, and tactile feedback. Here, we investigate the potential for Raman spectroscopy (RS) to accurately diagnose pediatric brain tumors intraoperatively.Methods: Using a rapid acquisition RS device, we intraoperatively imaged fresh ex vivo brain tissue samples from 29 pediatric patients at the Lucile Packard Children's Hospital between October 2018 and March 2020 in a prospective fashion. Small tissue samples measuring 2-4 mm per dimension were obtained with each individual tissue sample undergoing multiple unique Raman spectra acquisitions. All tissue samples from which Raman spectra were acquired underwent individual histopathology review. A labeled dataset of 678 unique Raman spectra gathered from 160 samples was then used to develop a machine learning model capable of (1) differentiating normal brain from tumor tissue and (2) normal brain from low-grade glioma (LGG) tissue.Results: Trained logistic regression model classifiers were developed using our labeled dataset. Model performance was evaluated using leave-one-patient-out cross-validation. The area under the curve (AUC) of the receiver-operating characteristic (ROC) curve for our tumor vs normal brain model was 0.94. The AUC of the ROC curve for LGG vs normal brain was 0.91.Conclusions: Our work suggests that RS can be used to develop a machine learning-based classifier to differentiate tumor vs non-tumor tissue during resection of pediatric brain tumors.

  View details for DOI 10.1093/noajnl/vdac118

  View details for PubMedID 35919071

• Development of an integrated risk scale for prediction of shunt placement after neonatal intraventricular hemorrhage. Journal of neurosurgery. Pediatrics Jin, M. C., Parker, J. J., Rodrigues, A. J., Ruiz Colón, G. D., Garcia, C. A., Mahaney, K. B., Grant, G. A., Prolo, L. M. 2022: 1-10

  Abstract

  Neonatal intraventricular hemorrhage (IVH) is a major cause of mortality and morbidity, particularly following premature birth. Even after the acute phase, posthemorrhagic hydrocephalus is a long-term complication, frequently requiring permanent ventriculoperitoneal shunt (VPS) placement. Currently, there are no risk classification methods integrating the constellation of clinical data to predict short- and long-term prognosis in neonatal IVH. To address this need, the authors developed a two-part machine learning approach for predicting short- and long-term outcomes after diagnosis of neonatal IVH. Integrating both maternal and neonatal characteristics, they developed a binary classifier to predict short-term mortality risk and a clinical scale to predict the long-term risk of VPS placement.Neonates with IVH were identified from the Optum Clinformatics Data Mart administrative claims database. Matched maternal and childbirth characteristics were obtained for all patients. The primary endpoints of interest were short-term (30 day) mortality and long-term VPS placement. Classification of short-term mortality risk was evaluated using 5 different machine learning approaches and the best-performing method was validated using a withheld validation subset. Prediction of long-term shunt risk was performed using a multivariable Cox regression model with stepwise variable selection, which was subsequently converted to an easily applied integer risk scale.A total of 5926 neonates with IVH were identified. Most patients were born before 32 weeks' gestation (67.2%) and with low birth weight (81.2%). Empirical 30-day mortality risk was 10.9% across all IVH grades and highest among grade IV IVH (34.3%). Among the neonates who survived > 30 days, actuarial 12-month postdiagnosis risk of shunt placement was 5.4% across all IVH grades and 31.3% for grade IV IVH. The optimal short-term risk classifier was a random forest model achieving an area under the receiver operating characteristic curve of 0.882 with important predictors ranging from gestational age to diverse comorbid medical conditions. Selected features for long-term shunt risk stratification were IVH grade, respiratory distress syndrome, disseminated intravascular coagulation, and maternal preeclampsia or eclampsia. An integer risk scale, termed the Shunt Prediction After IVH in Neonates (SPAIN) scale, was developed from these 4 features, which, evaluated on withheld cases, demonstrated improved risk stratification compared with IVH grade alone (Harrell's concordance index 0.869 vs 0.852).In a large cohort of neonates with IVH, the authors developed a two-pronged, integrated, risk classification approach to anticipate short-term mortality and long-term shunt risk. The application of such approaches may improve the prognostication of outcomes and identification of higher-risk individuals who warrant careful surveillance and early intervention.

  View details for DOI 10.3171/2021.11.PEDS21390

  View details for PubMedID 35090135

• An updated comparison between WHO grade 2 gemistocytic and diffuse astrocytoma survival and treatment patterns. World neurosurgery Rodrigues, A., Zhang, M., Toland, A., Bhambhvani, H., Hayden-Gephart, M. 2021

  Abstract

  BACKGROUND: In 2016, the World Health Organization (WHO) revised its guidelines to retain only gemistocytic astrocytoma (GemA) as a distinct variant of diffuse astrocytoma (DA). In the past, grade 2 GemAs have been linked with a worse prognosis than DA. However, it is unclear how consistently the tumor subtype has been diagnosed over time. We used more recent data to compare outcomes between grade 2 GemA and DA.METHODS: WHO grade 2 DA and GemA patients were extracted from the SEER database between 1973-2016. Kaplan-Meier curves estimated survival differences across different eras, with a focus on patients diagnosed between 2000-2016, and propensity score matching (PSM) was used to balance baseline characteristics between DA and GemA cohorts RESULTS: Of 2,467 grade 2 astrocytoma patients between 2000-2016, 132 (5.35%) were diagnosed with GemA, and 2,335 (94.65%) were diagnosed with DA. At baseline, marked demographic and treatment differences were noted between tumor subtypes, including age of diagnosis and female sex. GemA patients did not have worse survival compared to DA patients at baseline (p=0.349) or after PSM (p=0.497). Multivariate Cox models found that surgical extent of resection was associated with a survival benefit for DA patients, and both DA and GemA patients aged >65 years had dramatically inferior survival.CONCLUSIONS: Our data suggest that the impact of GemA versus DA histopathology depends more upon the decade of queried data rather than patient-specific demographics. Using more recent longitudinal data, we found that grade 2 GemA and DA tumors did not have significant differences in survival. These data may prove useful for clinicians counseling patients diagnosed with grade 2 GemA.

  View details for DOI 10.1016/j.wneu.2021.11.089

  View details for PubMedID 34844008

• Socioeconomic disparities in brain metastasis survival and treatment: a population-based study. World neurosurgery Rodrigues, A., Li, G., Bhambhvani, H., Hayden-Gephart, M. 2021

  Abstract

  INTRODUCTION: In the present study, we utilized a validated socioeconomic status (SES) index and population-based registry to identify and quantify the impact of SES on access to treatment and overall survival for patients diagnosed with synchronous brain metastases (BM).METHODS: The SEER was used to extract all patients between 2010 and 2016 with BM at initial presentation. SES was stratified into tertiles and quintiles using the validated Yost index. Multivariable logistic regressions were used to evaluate the impact of demographic, tumor, and socioeconomic covariates on receipt of radio- and chemotherapy. Kaplan-Meier curves were used to estimate survival.RESULTS: Between 2010-2016, 35,595 patients presented with brain metastases at the time of primary cancer diagnosis. Most patients received radiation and/or chemotherapy as part of the initial course of their treatment; 71.6% (n=25,484) were irradiated while 54.4% (n=19,371) received chemotherapy and 44.9% (n=15,984) received chemoradiation. Patients in the highest Yost tertile and quintile experienced longer overall survival (p < 0.001). Additionally, multivariable logistic regression revealed that the lowest Yost quintile was significantly less likely to receive either radiation (adjusted OR (aOR): 0.82; 95% CI: 0.75-0.89; p<0.001) or chemotherapy (aOR: 0.62; 95% CI: 0.58-0.67; p<0.001).CONCLUSIONS: In a large, population-based analysis of brain metastasis patients, we found significant differences in treatment access and mild survival differences along socioeconomic strata. More specifically, patients in lower SES tiers suffered worse outcomes and received radiation and chemotherapy less frequently than patients in higher tiers, even after accounting for other tumor- and demographic-related information.

  View details for DOI 10.1016/j.wneu.2021.11.036

  View details for PubMedID 34785360

• Risk of secondary neoplasms after external-beam radiation therapy treatment of pediatric low-grade gliomas: a SEER analysis, 1973-2015. Journal of neurosurgery. Pediatrics Rodrigues, A. J., Jin, M. C., Wu, A., Bhambhvani, H. P., Li, G., Grant, G. A. 2021: 1-9

  Abstract

  Although past studies have associated external-beam radiation therapy (EBRT) with higher incidences of secondary neoplasms (SNs), its effect on SN development from pediatric low-grade gliomas (LGGs), defined as WHO grade I and II gliomas of astrocytic or oligodendrocytic origin, is not well understood. Utilizing a national cancer registry, the authors sought to characterize the risk of SN development after EBRT treatment of pediatric LGG.A total of 1245 pediatric patient (aged 0-17 years) records from 1973 to 2015 were assembled from the Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable subdistribution hazard regression models were used to evaluate the prognostic impact of demographic, tumor, and treatment-related covariates. Propensity score matching was used to balance baseline characteristics. Cumulative incidence analyses measured the time to, and rate of, SN development, stratified by receipt of EBRT and controlled for competing mortality risk. The Fine and Gray semiparametric model was used to estimate future SN risk in EBRT- and non-EBRT-treated pediatric patients.In this study, 366 patients received EBRT and 879 did not. Forty-six patients developed SNs after an LGG diagnosis, and 27 of these patients received EBRT (OR 3.61, 95% CI 1.90-6.95; p < 0.001). For patients alive 30 years from the initial LGG diagnosis, the absolute risk of SN development in the EBRT-treated cohort was 12.61% (95% CI 8.31-13.00) compared with 4.99% (95% CI 4.38-12.23) in the non-EBRT-treated cohort (p = 0.013). Cumulative incidence curves that were adjusted for competing events still demonstrated higher rates of SN development in the EBRT-treated patients with LGGs. After matching across available covariates and again adjusting for the competing risk of mortality, a clear association between EBRT and SN development remained (subhazard ratio 2.26, 95% CI 1.21-4.20; p = 0.010).Radiation therapy was associated with an increased risk of future SNs for pediatric patients surviving LGGs. These data suggest that the long-term implications of EBRT should be considered when making treatment decisions for this patient population.

  View details for DOI 10.3171/2021.1.PEDS20859

  View details for PubMedID 34144522

• Differences in treatment patterns and overall survival between grade II and anaplastic pleomorphic xanthoastrocytomas. Journal of neuro-oncology Rodrigues, A., Bhambhvani, H., Medress, Z. A., Malhotra, S., Hayden-Gephart, M. 2021

  Abstract

  INTRODUCTION: Pleomorphic xanthoastrocytomas (PXAs) are classified as a grade II neoplasm, typically occur in children, and have favorable prognoses. However, their anaplastic counterparts remain poorly understood and vaguely characterized. In the present study, a large cohort of grade II PXA patients were compared with primary anaplastic PXA (APXA) patients to characterize patterns in treatment and survival.METHODS: Data were collected from the National Cancer Institute's SEER database. Univariate and multivariate Cox regressions were used to evaluate the prognostic impact of demographic, tumor, and treatment-related covariates. Propensity score matching was used to balance baseline characteristics. Kaplan-Meier curves were used to estimate survival.RESULTS: A total of 346 grade II PXA and 62 APXA patients were identified in the SEER database between 2000 and 2016. Kaplan-Meier analysis revealed substantially inferior survival for APXA patients compared to grade II PXA patients (median survival: 51months vs. not reached) (p<0.0001). After controlling across available covariates, increased age at diagnosis was identified as a negative predictor of survival for both grade II and APXA patients. In multivariate and propensity-matched analyses, extent of resection was not associated with improved outcomes in either cohort.CONCLUSIONS: Using a large national database, we identified the largest published cohort of APXA patients to date and compared them with their grade II counterparts to identify patterns in treatment and survival. Upon multivariate analysis, we found increased age at diagnosis was inversely associated with survival in both grade II and APXA patients. Receipt of chemoradiotherapy or complete surgical resection was not associated with improved outcomes in the APXA cohort.

  View details for DOI 10.1007/s11060-021-03772-0

  View details for PubMedID 33970405

• Patient Experience and Satisfaction with Telemedicine During Coronavirus Disease 2019: A Multi-Institution Experience. Telemedicine journal and e-health : the official journal of the American Telemedicine Association Rodrigues, A., Yu, J. S., Bhambhvani, H., Uppstrom, T., Ricci, W. M., Dines, J. S., Hayden-Gephart, M. 2021

  Abstract

  Introduction: The coronavirus disease 2019 (COVID-19) heralded an unprecedented increase in telemedicine utilization. Our objective was to assess patient satisfaction with telemedicine during the COVID-19 era. Methods: Telemedicine visit data were gathered from Stanford Health Care (Stanford) and the Hospital for Special Surgery (HSS). Patient satisfaction data from HSS were captured from a Press-Ganey questionnaire between April 19, 2020, and December 12, 2020, whereas Stanford data were taken from a novel survey instrument that was distributed to all patients between June 22, 2020, and November 1, 2020. Participants: There were 60,550 telemedicine visits at Stanford, each linked with a postvisit survey. At HSS, there were 66,349 total telemedicine visits with 7,348 randomly linked with a postvisit survey. Main Outcomes and Measures: Two measures of patient satisfaction were used for this study: (1) a patient's "overall visit score" and (2) whether the patient indicated the highest possible "likelihood to recommend" (LTR) score (LTR top box score). Results: The LTR top box percentage at Stanford increased from 69.6% to 74.0% (p=0.0002), and HSS showed no significant change (p=0.7067). In the multivariable model, the use of a cell phone (adjusted odds ratio [aOR]: 1.18; 95% confidence interval [CI]: 1.12-1.23) and tablet (aOR: 1.15; 95% CI: 1.07-1.23) was associated with higher overall scores, whereas visits with interrupted connections (aOR: 0.49; 95% CI: 0.42-0.57) or help required to connect (aOR: 0.49; 95% CI: 0.42-0.56) predicted lower patient satisfaction. Conclusions: We present the largest published description of patient satisfaction with telemedicine, and we identify important telemedicine-specific factors that predict increased overall visit score. These include the use of cell phones or tablets, phone reminders, and connecting before the visit was scheduled to begin. Visits with poor connectivity, extended wait times, or difficulty being seen, examined, or understood by the provider were linked with reduced odds of high scores. Our results suggest that attention to connectivity and audio/visual definition will help optimize patient satisfaction with future telemedicine encounters.

  View details for DOI 10.1089/tmj.2021.0060

  View details for PubMedID 33961522

• Epidemiological and Treatment Trends for Acute Ischemic Stroke Preceding and during the COVID-19 Pandemic. Cerebrovascular diseases (Basel, Switzerland) Rodrigues, A., Jin, M. C., Pendharkar, A. 2021: 1-4

  Abstract

  The coronavirus disease 2019 (COVID-19) pandemic heralded a number of indirect perturbations to patient behavior and disease epidemiology, and mounting evidence suggests that the COVID-19 pandemic may have exacerbated underlying health disparities along racial and socioeconomic (SES) groups for acute ischemic stroke (AIS). We used 1 large national insurance database to identify whether patient demographics, disease severity, or mechanical thrombectomy (MT) rates changed for the treatment and management of AIS during COVID-19.AIS patient records were queried from the Clinformatics® Data Mart Optum SES Database from the following 2 time periods: March 1, 2019-June 30, 2019 (pre-COVID-19), and March 1, 2020-June 30, 2020 (COVID-19). The database contains the longitudinal healthcare claims of approximately 77 million patients covered by a major insurance provider between 2003 and June 30, 2020 across all 50 states. Interrupted time-series analyses were used to assess trend differences before and after the COVID-19 pandemic.During the pre-COVID-19 period (March 1, 2019-June 30, 2019), there were 9,072 patients who presented for AIS, compared to 7,366 during COVID-19 (March 1, 2020-June 30, 2020). In both periods, the majority of patients were white (66.83% pre-COVID-19 and 67.91% during COVID-19). The average hospitalization duration was not different during the 2 time periods (p = 0.632), nor were rates of MT (p = 0.260). Total inpatient costs rose slightly for the COVID-19 period (USD 30,739 vs. USD 29,406; p = 0.015), and the median National Institutes of Health Stroke Scale (NIHSS) score was higher during CO-VID-19 (5 vs. 4; p = 0.023). When longitudinal trends were assessed for rates of MT and average NIHSS score for black and white patients, no differences were noted during the CO-VID-19 pandemic. Patients without any undergraduate experience did not present with AIS in increasing or decreasing incidence during COVID-19 (p = 0.268), but they did undergo declining rates of MT (p = 0.013).In the largest SES analysis of AIS patients during the COVID-19 era, we found that several SES factors, including race and income, did not seem to significantly impact utilization of MT for the treatment of AIS or the severity of the stroke at presentation.

  View details for DOI 10.1159/000518935

  View details for PubMedID 34551413

• Focused ultrasound: growth potential and future directions in neurosurgery. Journal of neuro-oncology Zhang, M., Rodrigues, A., Zhou, Q., Li, G. 2021

  Abstract

  Over the past two decades, vast improvements in focused ultrasound (FUS) technology have made the therapy an exciting addition to the neurosurgical armamentarium. In this time period, FUS has gained US Food and Drug Administration (FDA) approval for the treatment of two neurological disorders, and ongoing efforts seek to expand the lesion profile that is amenable to ultrasonic intervention. In the following review, we highlight future applications for FUS therapy and compare its potential role against established technologies, including deep brain stimulation and stereotactic radiosurgery. Particular attention is paid to tissue ablation, blood-brain-barrier opening, and gene therapy. We also address technical and infrastructural challenges involved with FUS use and summarize the hurdles that must be overcome before FUS becomes widely accepted in the neurosurgical community.

  View details for DOI 10.1007/s11060-021-03820-9

  View details for PubMedID 34410576

• Changes in Orthopaedic diagnoses during the COVID-19 pandemic. Journal of clinical orthopaedics and trauma Yu, J. S., Rodrigues, A. J., Bovonratwet, P., Shen, T., Premkumar, A., Sehgal, R., Carr Ii, J. B., Dines, J. S., Ricci, W. M. 2021; 22: 101603

  Abstract

  The coronavirus disease 2019 (COVID-19) pandemic has been accompanied by significant reductions in patient volumes for non-COVID-19-related conditions ranging from acute coronary syndrome to ischemic strokes to acute trauma. However, the impact of the COVID-19 pandemic on patient volumes for a broad range of orthopedic conditions remains unknown. The purpose of this study was to investigate the association of the COVID-19 pandemic with changes in patient volumes of 35 emergent (e.g. dislocations, open fractures), urgent (e.g. fractures), and nonurgent orthopedic conditions (e.g. osteoarthritis, sprains).A retrospective interrupted time-series analysis of patient volumes was conducted for 35 orthopedic conditions based on ICD-10 diagnosis codes. Patient hospitalizations and new problem visits were aggregated across two institutions in New York state, including one urban tertiary care orthopedic hospital, one urban academic medical center, and all state outpatient facilities affiliated with the orthopedic institution. Patient volumes in the COVID-19 peak period (03/2020-05/2020) and COVID-19 recovery period (06/2020-10/2020) were compared against pre-COVID-19 vol (01/2018-02/2020).Overall, 169,047 cases were included in the analysis across 35 conditions with 3775 emergent cases, 6376 urgent cases, and 158,896 nonurgent cases. During the COVID-19 peak period, patient caseloads for 1 out of 7 emergent conditions (p = 0.02) and 26 out of 28 urgent and nonurgent conditions (p < 0.05) were significantly reduced compared to the pre-COVID-19 period. During the COVID-19 recovery period, patient volumes in 3 out of 13 emergent and urgent conditions (p < 0.03) and 11 out of 22 nonurgent conditions (p < 0.04) were decreased compared to pre-COVID-19 vol.This study found that the pandemic was associated with considerable changes in patient patterns for non-COVID-19 orthopedic conditions. The long-term effects of patient volume reductions on both patient outcomes and orthopedic health systems remain to be seen.Cohort study; level of evidence IV.

  View details for DOI 10.1016/j.jcot.2021.101603

  View details for PubMedID 34580568

  View details for PubMedCentralID PMC8458105

• High-quality neurosurgeon communication and visualization during telemedicine encounters improves patient satisfaction Journal of Clinical Neuroscience Rodrigues, A., Li, G., Zhang, M., Jin, M., Hayden-Gephart, M. 2021; 94: 18-23

  View details for DOI 10.1016/j.jocn.2021.09.013

• Improved survival and disease control following pembrolizumab-induced immune-related adverse events in high PD-L1 expressing non-small cell lung cancer with brain metastases. Journal of neuro-oncology Zhang, M. n., Rodrigues, A. J., Pollom, E. L., Gibbs, I. C., Soltys, S. G., Hancock, S. L., Neal, J. W., Padda, S. K., Ramchandran, K. J., Wakelee, H. A., Chang, S. D., Lim, M. n., Hayden Gephart, M. n., Li, G. n. 2021

  Abstract

  Immune checkpoint inhibitors have become standard of care for many patients with non-small cell lung cancer (NSCLC). These agents often cause immune-related adverse events (IRAEs), which have been associated with increased overall survival (OS). Intracranial disease control and OS for patients experiencing IRAEs with metastatic NSCLC and brain metastases have not yet been described.We performed a single-institution, retrospective review of patients with NSCLC and existing diagnosis of brain metastasis, who underwent pembrolizumab treatment and developed any grade IRAE. The primary outcome of the study was intracranial time to treatment failure (TTF), defined from time of pembrolizumab initiation to new intracranial disease progression or death. Kaplan-Meier and Cox proportional hazard analyses were performed.A total of 63 patients with NSCLC brain metastasis were identified, and 24 developed IRAEs. Patients with any grade IRAEs had longer OS (21 vs. 10 months, p = 0.004), systemic TTF (15 vs. 4 months, p < 0.001) and intracranial TTF (14 vs. 5 months, p = 0.001), relative to patients without IRAEs. Presence of IRAEs and high PD-L1 (≥ 50%), but not absent/moderate PD-L1 (0-49%), had a positive association for OS, systemic TTF, and intracranial TTF. Following multivariable analysis, IRAE experienced on pembrolizumab was an independent predictor of OS, systemic TTF, and intracranial TTF.In our series of patients with NSCLC and brain metastases treated with pembrolizumab, IRAE presence was associated with a significant increase in OS, systemic TTF, and intracranial TTF. Future studies with increased cohorts will clarify how IRAEs should be interpreted among molecular subtypes.

  View details for DOI 10.1007/s11060-020-03686-3

  View details for PubMedID 33415659

• Management of brain tumors presenting in pregnancy: a case series and systematic review. American journal of obstetrics & gynecology MFM Rodrigues, A. J., Waldrop, A. R., Suharwardy, S., Druzin, M. L., Iv, M., Ansari, J. R., Stone, S. A., Jaffe, R. A., Jin, M. C., Li, G., Hayden-Gephart, M. 2021; 3 (1): 100256

  Abstract

  Patients who present with brain tumors during pregnancy require unique imaging and neurosurgical, obstetrical, and anesthetic considerations. Here, we review the literature and discuss the management of patients who present with brain tumors during pregnancy. Between 2009 and 2019, 9 patients were diagnosed at our institution with brain tumors during pregnancy. Clinical information was extracted from the electronic medical records. The median age at presentation was 29 years (range, 25-38 years). The most common symptoms at presentation included headache (n=5), visual changes (n=4), hemiparesis (n=3), and seizures (n=3). The median gestational age at presentation was 20.5 weeks (range, 11-37 weeks). Of note, 8 patients (89%) delivered healthy newborns, and 1 patient terminated her pregnancy. In addition, 5 patients (56%) required neurosurgical procedures during pregnancy (gestational ages, 14-37 weeks) because of disease progression (n=2) or neurologic instability (n=3). There was 1 episode of postneurosurgery morbidity (pulmonary embolism [PE]) and no surgical maternal mortality. The median length of follow-up was 15 months (range, 6-45 months). In cases demonstrating unstable or progressive neurosurgical status past the point of fetal viability, neurosurgical intervention should be considered. The physiological and pharmacodynamic changes of pregnancy substantially affect anesthetic management. Pregnancy termination should be discussed and offered to the patient when aggressive disease necessitates immediate treatment and the fetal gestational age remains previable, although neurologically stable patients may be able to continue the pregnancy to term. Ultimately, pregnant patients with brain tumors require an individualized approach to their care under the guidance of a multidisciplinary team.

  View details for DOI 10.1016/j.ajogmf.2020.100256

  View details for PubMedID 33451609

• Hospital Volumes of 5 Medical Emergencies in the COVID-19 Pandemic in 2 US Medical Centers. JAMA internal medicine Bhambhvani, H. P., Rodrigues, A. J., Yu, J. S., Carr, J. B., Hayden Gephart, M. 2020

  View details for DOI 10.1001/jamainternmed.2020.3982

  View details for PubMedID 33104161

• The primary sites leading to brain metastases: Shifting trends at a tertiary care center. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Bhambhvani, H. P., Granucci, M., Rodrigues, A., Kakusa, B. W., Hayden Gephart, M. 2020; 80: 121–24

  Abstract

  While the majority of brain metastases arise from lung cancer, breast cancer, or melanoma, new treatments and improved prognoses have altered the profile of primary cancers that metastasize to the brain. We sought to determine the proportion of brain metastases from less common primary sites and conduct trend analyses. We reviewed the charts of 3585 patients with brain metastases seen at our institution from 2008 to 2018. We determined the primary site for each of these patients, and the Mann-Kendall test was used to evaluate temporal trends in the yearly proportion of brain metastases originating from each primary cancer. The five most common primary sites were lung (43.0%), breast (19.9%), melanoma (8.2%), renal (5.0%), and colorectal (3.8%). The proportion of yearly brain metastases originating from breast cancer (p=0.029) and melanoma (p=0.013) decreased by 23.8% and 46.7%, respectively, from 2008 (0.21 breast, 0.15 melanoma) to 2018 (0.16 breast, 0.08 melanoma), while no change was found in the proportion of brain metastases from lung, renal, and colorectal cancers. Brain metastases arising from rare primary sites, defined as those comprising at most 2% of all brain metastases, increased by 34.4% (p=0.005). Limited sample size prohibited trend analysis of other individual primary sites. We report a decrease over 11years in the proportion of brain metastases originating from breast cancer and melanoma at our institution, and an increase in brain metastases from rare primary sites. Further work with larger, multi-center databases will enable additional evaluation of brain metastases from rare primary sites.

  View details for DOI 10.1016/j.jocn.2020.08.006

  View details for PubMedID 33099333

• Leptomeningeal Carcinomatosis: Molecular Landscape, Current Management, and Emerging Therapies. Neurosurgery clinics of North America Bhambhvani, H. P., Rodrigues, A. J., Umeh-Garcia, M. C., Hayden Gephart, M. 2020; 31 (4): 613–25

  Abstract

  Leptomeningeal carcinomatosis is a devastating consequence of late-stage cancer, and despite multimodal treatment, remains rapidly fatal. Definitive diagnosis requires identification of malignant cells in the cerebrospinal fluid (CSF), or frank disease on MRI. Therapy is generally palliative and consists primarily of radiotherapy and/or chemotherapy, which is administered intrathecally or systemically. Immunotherapies and novel experimental therapies have emerged as promising options for decreasing patient morbidity and mortality. In this review, the authors discuss a refined view of the molecular pathophysiology of leptomeningeal carcinomatosis, current approaches to disease management, and emerging therapies.

  View details for DOI 10.1016/j.nec.2020.06.010

  View details for PubMedID 32921356

• Racial and socioeconomic correlates of treatment and survival among patients with meningioma: a population-based study. Journal of neuro-oncology Bhambhvani, H. P., Rodrigues, A. J., Medress, Z. A., Hayden Gephart, M. n. 2020

  Abstract

  Though meningioma is the most common primary brain tumor, there is a paucity of epidemiologic studies investigating disparities in treatment and patient outcomes. Therefore, we sought to explore how sociodemographic factors are associated with rates of gross total resection (GTR) and radiotherapy as well as survival.The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database was queried to identify adult patients with meningioma diagnosed between 2005 and 2015. Socioeconomic status (SES) was determined using a validated composite index in which patients were stratified into tertiles and quintiles. Multivariable logistic regression and Cox proportional hazards analyses were used to identify predictors of treatment and survival, respectively.71,098 patients met our inclusion criteria. Low SES quintile was associated with reduced odds of receiving GTR (OR 0.76, 95% CI 0.69-0.83, p < 0.0001) and radiotherapy (OR 0.83, 95% CI 0.76-0.91, p < 0.0001) as well as worse survival (HR 1.48, 95% CI 1.41-1.56) as compared to the highest SES quintile. Black patients had reduced odds of GTR (OR 0.74, 95% CI 0.67-0.71, p < 0.0001) and worse survival (HR 1.23, 95% CI 1.18-1.29, p < 0.0001) as compared to white patients.This national study of patients with meningioma found socioeconomic status and race to be independent inverse correlates of likelihood of GTR, radiotherapy, and survival. Limited access to care may underlie these disparities in part, and future studies are warranted to identify specific causes for these findings.

  View details for DOI 10.1007/s11060-020-03455-2

  View details for PubMedID 32193691

• Intracranial Tumor Control Following Immune-Related Adverse Events and Discontinuation of Immunotherapy for Melanoma. World neurosurgery Zhang, M. n., Rodrigues, A. J., Bhambhvani, H. P., Fatemi, P. n., Pollom, E. L., Gibbs, I. C., Thomas, R. P., Soltys, S. G., Hancock, S. L., Chang, S. D., Reddy, S. A., Gephart, M. H., Li, G. n. 2020

  Abstract

  Immunotherapy for melanoma patients with brain metastasis has significantly improved outcomes; however, they have also been characterized by potentially dangerous immune-related adverse events (IRAEs). Several reports suggest these reactions can precede improved treatment responses. We sought to identify if such association exists for intracranial disease control.We conducted a retrospective chart review of melanoma patients who underwent immunotherapy treatment following diagnosis of brain metastasis. The study cohort was then stratified into two groups based on their history of developing an IRAE that prompted discontinuation of that regimen. The primary outcome variable included intracranial progression-free survival (PFS). Kaplan-Meier and Cox proportional hazard analysis were used to evaluate survival and predictors of outcomes.Fifty-two patients met inclusion criteria, seventeen of whom experienced severe IRAEs that led to discontinuation of immunotherapy. Median intracranial PFS was 19.9 vs 10.5 months (p = 0.053) in patients who did and did not experience severe IRAEs prompting discontinuation, respectively. No additional outcome benefits were identified for systemic PFS or overall survival, mean (33.1 months and 27.6 months, respectively). Multivariable analysis identified BRAF mutation status as a negative prognosticator of brain progression (p = 0.013, HR = 3.90). Initial treatment with BRAF inhibitor was also a negative predictor of all-cause mortality (p = 0.015, HR = 10.73) CONCLUSION: Immune related adverse events may signify an underlying immunogenic response that has intracranial disease control benefits. Despite their associated side effects, immunotherapies continue to demonstrate promising outcomes as a first-line agent for melanoma with brain metastasis.

  View details for DOI 10.1016/j.wneu.2020.08.124

  View details for PubMedID 32853767

• Patterns of Care and Age-Specific Impact of Extent of Resection and Adjuvant Radiotherapy in Pediatric Pineoblastoma. Neurosurgery Jin, M. C., Prolo, L. M., Wu, A. n., Azad, T. D., Shi, S. n., Rodrigues, A. J., Soltys, S. G., Pollom, E. L., Li, G. n., Hiniker, S. M., Grant, G. A. 2020

  Abstract

  Pediatric pineoblastomas are highly aggressive tumors that portend poor outcomes despite multimodal management. Controversy remains regarding optimal disease management.To evaluate patterns of care and optimal clinical management of pediatric pineoblastoma.A total of 211 pediatric (age 0-17 yr) histologically confirmed pineoblastoma patients diagnosed between 2004 and 2015 were queried from the National Cancer Database. Wilcoxon rank-sum statistics and chi-squared analyses were used to compare continuous and categorical variables, respectively. Univariable and multivariable Cox regressions were used to evaluate prognostic impact of covariates. Propensity-score matching was used to balance baseline characteristics.Older patients (age ≥ 4 yr) experienced improved overall survival compared to younger patients (age < 4 yr) (hazard ratio [HR] = 0.41; 95% CI 0.25-0.66). Older patients (adjusted odds ratio [aOR] = 5.21; 95% CI 2.61-10.78) and those residing in high-income regions (aOR = 3.16; 95% CI 1.21-8.61) received radiotherapy more frequently. Radiotherapy was independently associated with improved survival in older (adjusted HR [aHR] = 0.31; 95% CI 0.12-0.87) but not younger (aHR = 0.64; 95% CI 0.20-1.90) patients. The benefits of radiotherapy were more pronounced in patients receiving surgery than in those not receiving surgery (aHR [surgical patients] = 0.23; 95% CI 0.08-0.65; aHR [nonsurgical patients] = 0.46; 95% CI 0.22-0.97). Older patients experienced improved outcomes associated with aggressive resection (P = .041); extent of resection was not associated with survival in younger patients (P = .880).Aggressive tumor resection was associated with improved survival only in older pediatric patients. Radiotherapy was more effective in patients receiving surgery. Age-stratified approaches might allow for improved disease management of pediatric pineoblastoma.

  View details for DOI 10.1093/neuros/nyaa023

  View details for PubMedID 32110805

• Risks, costs, and outcomes of cerebrospinal fluid leaks after pediatric skull fractures: a MarketScan analysis between 2007 and 2015 NEUROSURGICAL FOCUS Varshneya, K., Rodrigues, A. J., Medress, Z. A., Stienen, M. N., Grant, G. A., Ratliff, J. K., Veeravagu, A. 2019; 47 (5): E10

  Abstract

  Skull fractures are common after blunt pediatric head trauma. CSF leaks are a rare but serious complication of skull fractures; however, little evidence exists on the risk of developing a CSF leak following skull fracture in the pediatric population. In this epidemiological study, the authors investigated the risk factors of CSF leaks and their impact on pediatric skull fracture outcomes.The authors queried the MarketScan database (2007-2015), identifying pediatric patients (age < 18 years) with a diagnosis of skull fracture and CSF leak. Skull fractures were disaggregated by location (base, vault, facial) and severity (open, closed, multiple, concomitant cerebral or vascular injury). Descriptive statistics and hypothesis testing were used to compare baseline characteristics, complications, quality metrics, and costs.The authors identified 13,861 pediatric patients admitted with a skull fracture, of whom 1.46% (n = 202) developed a CSF leak. Among patients with a skull fracture and a CSF leak, 118 (58.4%) presented with otorrhea and 84 (41.6%) presented with rhinorrhea. Patients who developed CSF leaks were older (10.4 years vs 8.7 years, p < 0.0001) and more commonly had skull base (n = 183) and multiple (n = 22) skull fractures (p < 0.05). These patients also more frequently underwent a neurosurgical intervention (24.8% vs 9.6%, p < 0.0001). Compared with the non-CSF leak population, patients with a CSF leak had longer average hospitalizations (9.6 days vs 3.7 days, p < 0.0001) and higher rates of neurological deficits (5.0% vs 0.7%, p < 0.0001; OR 7.0; 95% CI 3.6-13.6), meningitis (5.5% vs 0.3%, p < 0.0001; OR 22.4; 95% CI 11.2-44.9), nonroutine discharge (6.9% vs 2.5%, p < 0.0001; OR 2.9; 95% CI 1.7-5.0), and readmission (24.7% vs 8.5%, p < 0.0001; OR 3.4; 95% CI 2.5-4.7). Total costs at 90 days for patients with a CSF leak averaged $81,206, compared with $32,831 for patients without a CSF leak (p < 0.0001).The authors found that CSF leaks occurred in 1.46% of pediatric patients with skull fractures and that skull fractures were associated with significantly increased rates of neurosurgical intervention and risks of meningitis, hospital readmission, and neurological deficits at 90 days. Pediatric patients with skull fractures also experienced longer average hospitalizations and greater healthcare costs at presentation and at 90 days.

  View details for DOI 10.3171/2019.8.FOCUS19543

  View details for Web of Science ID 000493985900010

  View details for PubMedID 31675705

• Trends in Anterior Lumbar Interbody Fusion in the United States: A MarketScan Study From 2007 to 2014. Clinical spine surgery Varshneya, K., Medress, Z. A., Jensen, M., Azad, T. D., Rodrigues, A., Stienen, M. N., Desai, A., Ratliff, J. K., Veeravagu, A. 2019

  Abstract

  BACKGROUND: Although the incidence of spinal fusions has increased significantly in the United States over the last quarter century, national trends of anterior lumbar interbody fusion (ALIF) utilization are not known.PURPOSE: The objective of this study was to characterize trends, clinical characteristics, risk factors associated with, and outcomes of ALIF in the United States.STUDY DESIGN: This was an epidemiological study using national administrative data from the MarketScan database.METHODS: Using a large administrative database, we identified adults who underwent ALIF in the United States from 2007 to 2014. The incidence of ALIF was studied longitudinally over time and across geographic regions in the United States. Data related to postoperative complications, length of stay, readmission, and cost were collected.RESULTS: We identified 49,945 patients that underwent ALIF in the United States between 2007 and 2014. The total number of ALIF procedures increased from 3650 in 2007 to 6151 in 2014, accounting for an average increase of 24.07% annually. The Southern United States performed the highest number of ALIFs. The most common conditions treated were degenerative disc disease and spondylolisthesis. Over one third of patients (34.6%) underwent multilevel fusion. The most common complications were iron deficiency anemia, urinary tract infections, and pulmonary complications. Hospital and physician pay increased significantly during the study period.CONCLUSIONS: For the first time in our knowledge, we identified national trends in ALIF utilization, outcomes, and cost using a large administrative database. Our study reaffirms prior work that has demonstrated low rates of complications, mortality, and readmission following ALIF.LEVEL OF EVIDENCE: Level III.

  View details for DOI 10.1097/BSD.0000000000000904

  View details for PubMedID 31609798