Ethan Schonfeld

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

• 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

• Vertebrae segmentation in reduced radiation CT imaging for augmented reality applications. International journal of computer assisted radiology and surgery Schonfeld, E., de Lotbiniere-Bassett, M., Jansen, T., Anthony, D., Veeravagu, A. 1800

  Abstract

  PURPOSE: There is growing evidence for the use of augmented reality (AR) navigation in spinal surgery to increase surgical accuracy and improve clinical outcomes. Recent research has employed AR techniques to create accurate auto-segmentations, the basis of patient registration, using reduced radiation dose intraoperative computed tomography images. In this study, we aimed to determine if spinal surgery AR applications can employ reduced radiation dose preoperative computed tomography (pCT) images.METHODS: We methodically decreased the imaging dose, with the addition of Gaussian noise, that was introduced into pCT images to determine the image quality threshold that was required for auto-segmentation. The Gaussian distribution's standard deviation determined noise level, such that a scalar multiplier (L: [0.00, 0.45], with steps of 0.03) simulated lower doses as L increased. We then enhanced the images with denoising algorithms to evaluate the effect on the segmentation.RESULTS: The pCT radiation dose was decreased to below the current lowest clinical threshold and the resulting images produced segmentations that were appropriate for input into AR applications. This held true at simulated dose L=0.06 (estimated 144 mAs) but not at L=0.09 (estimated 136 mAs). The application of denoising algorithms to the images resulted in increased artifacts and decreased bone density.CONCLUSIONS: The pCT image quality that is required for AR auto-segmentation is lower than that which is currently employed in spinal surgery. We recommend a reduced radiation dose protocol of approximately 140 mAs. This has the potential to reduce the radiation experienced by patients in comparison to procedures without AR support. Future research is required to identify the specific, clinically relevant radiation dose thresholds required for surgical navigation.

  View details for DOI 10.1007/s11548-022-02561-y

  View details for PubMedID 35025073

• Autocatalytic-protection for an unknown locus CRISPR-Cas countermeasure for undesired mutagenic chain reactions. Journal of theoretical biology Schonfeld, E., Schonfeld, E., Schonfeld, D. 2021; 528: 110831

  Abstract

  The mutagenic chain reaction (MCR) is a genetic tool to use a CRISPR-Cas construct to introduce a homing endonuclease, allowing gene drive to influence whole populations in a minimal number of generations (Esvelt et al., 2014; Gantz and Bier, 2015; Gantz and Bier, 2016). The question arises: if an active genetic terror event is released into a population, could we prevent the total spread of the undesired allele (Gantz, et al., 2015; Webber et al., 2015)? Thus far, effective protection methods require knowledge of the terror locus (Grunwald et al., 2019). Here we introduce a novel approach, an autocatalytic-Protection for an Unknown Locus (a-PUL), whose aim is to spread through a population and arrest and decrease an active terror event's spread without any prior knowledge of the terror-modified locus, thus allowing later natural selection and ERACR drives to restore the normal locus (Hammond et al., 2017). a-PUL, using a mutagenic chain reaction, includes (i) a segment encoding a non-Cas9 endonuclease capable of homology-directed repair suggested as Type II endonuclease Cpf1 (Cas12a), (ii) a ubiquitously-expressed gene encoding a gRNA (gRNA1) with a U4AU4 3'-overhang specific to Cpf1 and with crRNA specific to some desired genomic sequence of non-coding DNA, (iii) a ubiquitously-expressed gene encoding two gRNAs (gRNA2/gRNA3) both with tracrRNA specific to Cas9 and crRNA specific to two distinct sites of the Cas9 locus, and (iv) homology arms flanking the Cpf1/gRNA1/gRNA2/gRNA3 cassette that are identical to the region surrounding the target cut directed by gRNA1 (Khan, 2016; Zetsche et al., 2015). We demonstrate the proof-of-concept and efficacy of our protection construct through a Graphical Markov model and computer simulation.

  View details for DOI 10.1016/j.jtbi.2021.110831

  View details for PubMedID 34274311

• On the relation of gene essentiality to intron structure: a computational and deep learning approach LIFE SCIENCE ALLIANCE Schonfeld, E., Vendrow, E., Vendrow, J., Schonfeld, E. 2021; 4 (6)

  Abstract

  Essential genes have been studied by copy number variants and deletions, both associated with introns. The premise of our work is that introns of essential genes have distinct characteristic properties. We provide support for this by training a deep learning model and demonstrating that introns alone can be used to classify essentiality. The model, limited to first introns, performs at an increased level, implicating first introns in essentiality. We identify unique properties of introns of essential genes, finding that their structure protects against deletion and intron-loss events, especially centered on the first intron. We show that GC density is increased in the first introns of essential genes, allowing for increased enhancer activity, protection against deletions, and improved splice site recognition. We find that first introns of essential genes are of remarkably smaller size than their nonessential counterparts, and to protect against common 3' end deletion events, essential genes carry an increased number of (smaller) introns. To demonstrate the importance of the seven features we identified, we train a feature-based model using only these features and achieve high performance.

  View details for DOI 10.26508/lsa.202000951

  View details for Web of Science ID 000654748200008

  View details for PubMedID 33906938

  View details for PubMedCentralID PMC8127325

• Lateralized Deficits in Motor, Sensory, and Olfactory Domains in Dementia JOURNAL OF ALZHEIMERS DISEASE Schonfeld, E., Schonfeld, E., Aman, C., Gill, N., Kim, D., Rabin, S., Shamshuddin, B., Sealey, L., Senno, R. 2021; 79 (3): 1033-1040

  Abstract

  There exist functional deficits in motor, sensory, and olfactory abilities in dementias. Measures of these deficits have been discussed as potential clinical markers.We measured the deficit of motor, sensory, and olfactory functions on both the left and right body side, to study potential body lateralizations.This IRB-approved study (N = 84) performed left/right clinical tests of gross motor (dynamometer test), sensory (Von Frey test), and olfactory (peppermint oil test) ability. The Mini-Mental Status Exam was administered to determine level of dementia; medical and laboratory data were collected.Sensory and olfactory deficits lateralized to the left side of the body, while motor deficits lateralized to the right side. We found clinical correlates of motor lateralization: female, depression, MMSE <15, and diabetes. While clinical correlates of sensory lateralization: use of psychotherapeutic agent, age ≥85, MMSE <15, and male. Lastly, clinical correlates of olfactory lateralization: age <85, number of medications >10, and male.These lateralized deficits in body function can act as early clinical markers for improved diagnosis and treatment. Future research should identify correlates and corresponding therapies to strengthen at-risk areas.

  View details for DOI 10.3233/JAD-201216

  View details for Web of Science ID 000618072600010

  View details for PubMedID 33459707

• OnabotulinumtoxinA injections: treatment of reversible cerebral vasoconstriction syndrome chronic daily headaches BMJ CASE REPORTS Senno, R., Schonfeld, E., Nagar, C. 2019; 12 (5)

  Abstract

  Reversible cerebral vasoconstriction syndrome (RCVS) is a rare condition characterised by repetitive, multifocal, vasofluctuations of cerebral arteries. A key symptom is chronic, disabling 'thunderclap' headaches, which are extremely difficult to treat as established medications may exacerbate the pathophysiology of RCVS. OnabotulinumtoxinA (OBT-A) injections are used for the prophylaxis of chronic daily headaches (CDH). The mechanism of action of OBT-A significantly differs from oral headache treatments. Thus, OBT-A may be an effective, safe treatment of RCVS-CDH. A 51-year-old woman with RCVS-CDH presented to outpatient clinic. This case report describes the first, believed, documented treatment of RCVS-CDH by OBT-A injections. In 2018, the consented patient received a total of 200 units of OBT-A, 155 units to the 31 approved U.S. Food and Drug Administration (FDA) sites and 45 units injected into the bilateral occipital belly of occipitofrontalis muscles. The patient reported 3 months of excellent pain relief (60% reduction). Three rounds of OBT-A injection, each 3 months apart, resulted in 80% reduction. OBT-A injections may prove a successful, novel treatment for RCVS-CDH.

  View details for DOI 10.1136/bcr-2018-228562

  View details for Web of Science ID 000661395200086

  View details for PubMedID 31151973

  View details for PubMedCentralID PMC6557340