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  • Predictors of 2-year reoperation in Medicare patients undergoing primary thoracolumbar deformity surgery. Journal of neurosurgery. Spine Varshneya, K., Jokhai, R. T., Fatemi, P., Stienen, M. N., Medress, Z. A., Ho, A. L., Ratliff, J. K., Veeravagu, A. 2020: 1–5

    Abstract

    OBJECTIVE: This was a retrospective cohort study in which the authors used a nationally representative administrative database. Their goal was to identify the risk factors for reoperation in Medicare patients undergoing primary thoracolumbar adult spinal deformity (ASD) surgery. Previous literature reports estimate that 20% of patients undergoing thoracolumbar ASD correction undergo revision surgery within 2 years. Most published data discuss risk factors for revision surgery in the general population, but these have not been explored specifically in the Medicare population.METHODS: Using the MarketScan Medicare Supplemental database, the authors identified patients who were diagnosed with a spinal deformity and underwent ASD surgery between 2007 and 2015. The interactions of patient demographics, surgical factors, and medical factors with revision surgery were investigated during the 2 years following primary ASD surgery. The authors excluded patients without Medicare insurance and those with any prior history of trauma or tumor.RESULTS: Included in the data set were 2564 patients enrolled in Medicare who underwent ASD surgery between 2007 and 2015. The mean age at diagnosis with spinal deformity was 71.5 years. A majority of patients (68.5%) were female. Within 2 years of follow-up, 661 (25.8%) patients underwent reoperation. Preoperative osteoporosis (OR 1.58, p < 0.0001), congestive heart failure (OR 1.35, p = 0.0161), and paraplegia (OR 2.41, p < 0.0001) independently increased odds of revision surgery. The use of intraoperative bone morphogenetic protein was protective against reoperation (OR 0.71, p = 0.0371). Among 90-day postoperative complications, a wound complication was the strongest predictor of undergoing repeat surgery (OR 2.85, p = 0.0061). The development of a pulmonary embolism also increased the odds of repeat surgery (OR 1.84, p = 0.0435).CONCLUSIONS: Approximately one-quarter of Medicare patients with ASD who underwent surgery required an additional spinal surgery within 2 years. Baseline comorbidities such as osteoporosis, congestive heart failure, and paraplegia, as well as short-term complications such as pulmonary embolism and wound complications significantly increased the odds of repeat surgery.

    View details for DOI 10.3171/2020.5.SPINE191425

    View details for PubMedID 32707541

  • A Comparative Analysis of Patients Undergoing Fusion for Adult Cervical Deformity by Approach Type GLOBAL SPINE JOURNAL Varshneya, K., Medress, Z. A., Stienen, M. N., Nathan, J., Ho, A., Pendharkar, A. V., Loo, S., Aikin, J., Li, G., Desai, A., Ratliff, J. K., Veeravagu, A. 2020
  • Designer, injectable gels to prevent transplanted Schwann cell loss during spinal cord injury therapy. Science advances Marquardt, L. M., Doulames, V. M., Wang, A. T., Dubbin, K., Suhar, R. A., Kratochvil, M. J., Medress, Z. A., Plant, G. W., Heilshorn, S. C. 2020; 6 (14): eaaz1039

    Abstract

    Transplantation of patient-derived Schwann cells is a promising regenerative medicine therapy for spinal cord injuries; however, therapeutic efficacy is compromised by inefficient cell delivery. We present a materials-based strategy that addresses three common causes of transplanted cell death: (i) membrane damage during injection, (ii) cell leakage from the injection site, and (iii) apoptosis due to loss of endogenous matrix. Using protein engineering and peptide-based assembly, we designed injectable hydrogels with modular cell-adhesive and mechanical properties. In a cervical contusion model, our hydrogel matrix resulted in a greater than 700% improvement in successful Schwann cell transplantation. The combination therapy of cells and gel significantly improved the spatial distribution of transplanted cells within the endogenous tissue. A reduction in cystic cavitation and neuronal loss were also observed with substantial increases in forelimb strength and coordination. Using an injectable hydrogel matrix, therefore, can markedly improve the outcomes of cellular transplantation therapies.

    View details for DOI 10.1126/sciadv.aaz1039

    View details for PubMedID 32270042

  • Postoperative Complication Burden, Revision Risk, and Health Care Use in Obese Patients Undergoing Primary Adult Thoracolumbar Deformity Surgery GLOBAL SPINE JOURNAL Varshneya, K., Pangal, D. J., Stienen, M. N., Ho, A. L., Fatemi, P., Medress, Z. A., Herrick, D. B., Desai, A., Ratliff, J. K., Veeravagu, A. 2020
  • Single- versus dual-attending strategy for spinal deformity surgery: 2-year experience and systematic review of the literature. Journal of neurosurgery. Spine Cheng, I., Stienen, M. N., Medress, Z. A., Varshneya, K., Ho, A. L., Ratliff, J. K., Veeravagu, A. 2020: 1–12

    Abstract

    Adult spinal deformity (ASD) surgery is complex and associated with high morbidity and complication rates. There is growing evidence in the literature for the beneficial effects of an approach to surgery in which two attending physicians rather than a single attending physician perform surgery for and oversee the surgical care of a single patient in a dual-attending care model. The authors developed a dual-attending care collaboration in August 2017 in which a neurosurgeon and an orthopedic surgeon mutually operated on patients with ASD.The authors recorded data for 2 years of experience with ASD patients operated on by dual attending surgeons. Analyses included estimated blood loss (EBL), transfusions, length of stay (LOS), discharge disposition, complication rates, emergency room visits and readmissions, subjective health status improvement, and disability (Oswestry Disability Index [ODI] score) and pain (visual analog scale [VAS] score) at last follow-up. In addition, the pertinent literature for dual-attending spinal deformity correction was systematically reviewed.The study group comprised 19 of 254 (7.5%) consecutively operated patients who underwent thoracolumbar fusion during the period from January 2017 to June 2019 (68.4% female; mean patient age 65.1 years, ODI score 44.5, VAS pain score 6.8). The study patients were matched by age, sex, anesthesia risk, BMI, smoking status, ODI score, VAS pain score, prior spine surgeries, and basic operative characteristics (type of interbody implants, instrumented segments, pelvic fixation) to 19 control patients (all p > 0.05). There was a trend toward less EBL (mean 763 vs 1524 ml, p = 0.059), fewer intraoperative red blood cell transfusions (mean 0.5 vs 2.3, p = 0.079), and fewer 90-day readmissions (0% vs 15.8%, p = 0.071) in the dual-attending group. LOS and discharge disposition were similar, as were the rates of any < 30-day postsurgery complications, < 90-day postsurgery emergency room visits, and reoperations, and ODI and VAS pain scores at last follow-up (all p > 0.05). At last follow-up, 94.7% vs 68.4% of patients in the dual- versus single-attending group stated their health status had improved (p = 0.036). In the authors' literature search of prior articles on spinal deformity correction, 5 of 8 (62.5%) articles reported lower EBL and 6 of 8 (75%) articles reported significantly lower operation duration in dual-attending cases. The literature contained differing results with regard to complication- or reoperation-sparing effects associated with dual-attending cases. Similar clinical outcomes of dual- versus single-attending cases were reported.Establishing a dual-attending care management platform for ASD correction was feasible at the authors' institution. Results of the use of a dual-attending strategy at the authors' institution were favorable. Positive safety and outcome profiles were found in articles on this topic identified by a systematic literature review.

    View details for DOI 10.3171/2020.3.SPINE2016

    View details for PubMedID 32650315

  • Commentary: Predictors of the Best Outcomes Following Minimally Invasive Surgery for Grade 1 Degenerative Lumbar Spondylolisthesis. Neurosurgery Medress, Z. A., Veeravagu, A. 2020

    View details for DOI 10.1093/neuros/nyaa288

    View details for PubMedID 32687591

  • A Predictive-Modeling Based Screening Tool for Prolonged Opioid Use after Surgical Management of Low Back and Lower Extremity Pain. The spine journal : official journal of the North American Spine Society Zhang, Y., Fatemi, P., Medress, Z., Azad, T. D., Veeravagu, A., Desai, A., Ratliff, J. K. 2020

    Abstract

    Outpatient postoperative pain management in spine patients, specifically involving the use of opioids, demonstrates significant variability.Using preoperative risk factors and 30-day postoperative opioid prescribing patterns, we developed models for predicting long-term opioid use in patients after elective spine surgery.This retrospective cohort study utilizes inpatient, outpatient, and pharmaceutical data from MarketScan databases (Truven Health).In all, 19,317 patients who were newly diagnosed with low back or lower extremity pain (LBP or LEP) between 2008 and 2015 and underwent thoracic or lumbar surgery within one year after diagnosis were enrolled. Some patients initiated opioids after diagnosis but all patients were opioid-naïve prior to the diagnosis.Long-term opioid use was defined as filling ≥180 days of opioids within one year after surgery.Using demographic variables, medical and psychiatric comorbidities, preoperative opioid use, and 30-day postoperative opioid use, we generated seven models on 80% of the dataset and tested the models on the remaining 20%. We used three regression-based models (full logistic regression, stepwise logistic regression, least absolute shrinkage and selection operator [LASSO]), support vector machine, two tree-based models (random forest, stochastic gradient boosting), and time-varying convolutional neural network. Area under the curve (AUC), Brier index, sensitivity, and calibration curves were used to assess the discrimination and calibration of the models.We identified 903 (4.6%) of patients who met criteria for long-term opioid use. The regression-based models demonstrated the highest AUC, ranging from 0.835 to 0.847, and relatively high sensitivities, predicting between 74.9-76.5% of the long-term opioid use patients in the test dataset. The three strongest positive predictors of long-term opioid use were high preoperative opioid use (OR 2.70; 95% CI 2.27-3.22), number of days with active opioid prescription between postoperative days 15-30 (OR 1.10; 95% CI 1.07-1.12), and number of dosage increases between postoperative day 15-30 (OR 1.71, 95% CI 1.41-2.08). The strongest negative predictors were number of dosage decreases in the 30-day postoperative period.We evaluated several predictive models for postoperative long-term opioid use in a large cohort of patients with LBP or LEP who underwent surgery. A regression-based model with high sensitivity and AUC is provided online to screen patients for high risk of long-term opioid use based on preoperative risk factors and opioid prescription patterns in the first 30 days after surgery. It is hoped that this work will improve identification of patients at high risk of prolonged opioid use and enable early intervention and counseling.

    View details for DOI 10.1016/j.spinee.2020.05.098

    View details for PubMedID 32445803

  • Complications, Costs, and Quality Outcomes of Patients Undergoing Cervical Deformity Surgery with Intraoperative BMP Use. Spine Varshneya, K., Wadhwa, H., Pendharkar, A. V., Medress, Z. A., Stienen, M. N., Ratliff, J. K., Veeravagu, A. 2020

    Abstract

    An epidemiological study using national administrative data from the MarketScan database.To identify the impact of bone morphogenetic protein (BMP) on postoperative outcomes in patients undergoing adult cervical deformity (ACD) surgery.BMP has been shown to stimulate bone growth and improve fusion rates in spine surgery. However, the impact of BMP on reoperation rates and postoperative complication rate is controversial.We queried the MarketScan database to identify patients who underwent ACD surgery from 2007-2015. Patients were stratified by BMP use in the index operation. Patients under 18 and those with any history of tumor or trauma were excluded. Baseline demographics and comorbidities, postoperative complication rates and reoperation rates were analyzed.A total of 13,549 patients underwent primary ACD surgery, of which 1155 (8.5%) had intraoperative BMP use. The overall 90-day complication rate was 27.6% in the non-BMP cohort and 31.1% in the BMP cohort (p < 0.05). Patients in the BMP cohort had longer average length of stay (4.0 days vs 3.7 days, p < 0.05) but lower revision surgery rates at 90-days (14.5% vs 28.3%, p < 0.05), 6 months (14.9% vs 28.6%, p < 0.05), 1 year (15.7% vs 29.2%, p < 0.05), and 2 years (16.5% vs 29.9%, p < 0.05) postoperatively. BMP use was associated with higher payments throughout the 2-year follow-up period ($107,975 vs $97,620, p < 0.05). When controlling for baseline group differences, BMP use independently increased the odds of postoperative complication (OR 1.22, 95% CI 1.1 - 1.4) and reduced the odds of reoperation throughout 2-years of follow-up (OR 0.49, 95% CI 0.4 - 0.6).Intraoperative BMP use has benefits for fusion integrity in ACD surgery but is associated with increased postoperative complication rate. Spine surgeons should weigh these benefits and drawbacks to identify optimal candidates for BMP use in ACD surgery.3.

    View details for DOI 10.1097/BRS.0000000000003629

    View details for PubMedID 32756275

  • Postoperative Complication Burden, Revision Risk, and Health Care Use in Obese Patients Undergoing Primary Adult Thoracolumbar Deformity Surgery. Global spine journal Varshneya, K., Pangal, D. J., Stienen, M. N., Ho, A. L., Fatemi, P., Medress, Z. A., Herrick, D. B., Desai, A., Ratliff, J. K., Veeravagu, A. 2020: 2192568220904341

    Abstract

    This is a retrospective cohort study using a nationally representative administrative database.To identify the impact of obesity on postoperative outcomes in patients undergoing thoracolumbar adult spinal deformity (ASD) surgery.The obesity rate in the United States remains staggering, with approximately one-third of all Americans being overweight or obese. However, the impact of elevated body mass index on spine surgery outcomes remains unclear.We queried the MarketScan database to identify patients who were diagnosed with a spinal deformity and underwent ASD surgery from 2007 to 2016. Patients were then stratified by whether or not they were diagnosed as obese at index surgical admission. Propensity score matching (PSM) was then utilized to mitigate intergroup differences between obese and nonobese patients. Patients <18 years and those with any prior history of trauma or tumor were excluded from this study. Baseline demographics and comorbidities, postoperative complication rates, and short- and long-term reoperation rates were determined.A total of 7423 patients met the inclusion criteria of this study, of whom 597 (8.0%) were obese. Initially, patients with obesity had a higher 90-day postoperative complication rate than nonobese patients (46.1% vs 40.8%, P < .05); however, this difference did not remain after PSM. Revision surgery rates after 2 years were similar across the 2 groups following primary surgery (obese, 21.4%, vs nonobese, 22.0%; P = .7588). Health care use occurred at a higher rate among obese patients through 2 years of long-term follow-up (obese, $152 930, vs nonobese, $140 550; P < .05).Patients diagnosed with obesity who underwent ASD surgery did not demonstrate increased rates of complications, reoperations, or readmissions. However, overall health care use through 2 years of follow-up after index surgery was higher in the obesity cohort.

    View details for DOI 10.1177/2192568220904341

    View details for PubMedID 32875891

  • A Comparative Analysis of Patients Undergoing Fusion for Adult Cervical Deformity by Approach Type. Global spine journal Varshneya, K., Medress, Z. A., Stienen, M. N., Nathan, J., Ho, A., Pendharkar, A. V., Loo, S., Aikin, J., Li, G., Desai, A., Ratliff, J. K., Veeravagu, A. 2020: 2192568220915717

    Abstract

    Retrospective cohort study.To provide insight into postoperative complications, short-term quality outcomes, and costs of the surgical approaches of adult cervical deformity (ACD).A national database was queried from 2007 to 2016 to identify patients who underwent cervical fusion for ACD. Patients were stratified by approach type-anterior, posterior, or circumferential. Patients undergoing anterior and posterior approach surgeries were additionally compared using propensity score matching.A total of 6575 patients underwent multilevel cervical fusion for ACD correction. Circumferential fusion had the highest postoperative complication rate (46.9% vs posterior: 36.7% vs anterior: 18.5%, P < .0001). Anterior fusion patients more commonly required reoperation compared with posterior fusion patients (P < .0001), and 90-day readmission rate was highest for patients undergoing circumferential fusion (P < .0001). After propensity score matching, the complication rate remained higher in the posterior, as compared to the anterior fusion group (P < .0001). Readmission rate also remained higher in the posterior fusion group; however, anterior fusion patients were more likely to require reoperation. At index hospitalization, posterior fusion led to 1.5× higher costs, and total payments at 90 days were 1.6× higher than their anterior fusion counterparts.Patients who undergo posterior fusion for ACD have higher complication rates, readmission rates, and higher cost burden than patients who undergo anterior fusion; however, posterior correction of ACD is associated with a lower rate of reoperation.

    View details for DOI 10.1177/2192568220915717

    View details for PubMedID 32875897

  • 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. 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

  • 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

  • Simulating Episode-Based Bundled Payments for Cranial Neurosurgical Procedures. Neurosurgery Medress, Z., Ugiliweneza, B., Parker, J., Wang, D., Burton, E., Boakye, M., Skirboll, S. 2019

    Abstract

    BACKGROUND: Episode-based bundled payments were introduced by Medicare in 2013 as the Bundled Payments for Care Improvement (BPCI) in order to improve care coordination and cost efficiency. BPCI has not yet been applied to cranial neurosurgical procedures.OBJECTIVE: To determine projected values of episode-based bundled payments when applied to common cranial neurosurgical procedures using retrospective data from a large database.METHODS: We performed a large retrospective observational study using the MarketScan administrative database to project bundled payment payments for 4 groups of common cranial neurosurgical procedures.RESULTS: We identified 15 276 procedures that met our inclusion criteria. We observed significant variability between groups, with 90-d bundle projected payments ranging from $58,200 for craniotomy for meningioma to $102,073 for craniotomy for malignant glioma. We also found significant variability in projected bundled payments within each class of operation. On average, payment for the index hospitalization accounted for 85% of projected payments for a 30-d bundle and 70.5% of projected payments for a 90-d bundle. Multivariable analysis showed that hospital readmission, discharge to postacute care facilities, venous-thrombo-embolism, medical comorbidities, adjuvant therapies, and payer status significantly contributed to projected cranial bundle payments.CONCLUSION: For the first time, to our knowledge, we project the values of episode-based bundled payments for common vascular and tumor cranial operations. As previously identified in orthopedic procedures, there is significant variability in total bundle payments within each cranial procedure. Compared to spine and orthopedic procedures, postdischarge care significantly impacts total bundle payments in cranial neurosurgery.

    View details for DOI 10.1093/neuros/nyz353

    View details for PubMedID 31515558

  • Grade II Spondylolisthesis: Reverse Bohlman Procedure with Trans-Discal S1-L5 and S2Ai Screws Placed with Robotic Guidance. World neurosurgery Ho, A. L., Varshneya, K., Medress, Z. A., Pendharkar, A. V., Sussman, E. S., Cheng, I., Veeravagu, A. 2019

    Abstract

    STUDY DESIGN: Technical Report with two illustrative cases.OBJECTIVE: Grade II spondylolisthesis remains a complex surgical pathology for which there is no consensus regarding optimal surgical strategies. Surgical strategies vary regarding extent of reduction, utilization of instrumentation/interbody support, and anterior versus posterior approaches with or without decompression. The objective of this study is to provide the first report on the efficacy of robotic spinal surgery systems in supporting the treatment of grade II spondylolisthesis.METHODS: Utilizing two illustrative cases, we provide a technical report of how a robotic spinal surgery platform can be utilized to treatment grade II spondylolisthesis with a novel instrumentation strategy.RESULTS: We describe how utilization of the "Reverse Bohlman" technique to achieve a large anterior fusion construct spanning the pathologic level and buttressed by the adjacent level above, coupled with a novel, high fidelity posterior fixation scheme with transdiscal S1-L5 and S2Ai screws placed in a minimally invasive fashion with robot guidance allows for the best chance of fusion in situ.CONCLUSIONS: The "Reverse Bohlman" technique coupled with transdiscal S1-L5 and S2Ai screw fixation accomplishes the surgical goals of creating a solid fusion construct, avoiding neurologic injury with aggressive reduction, and halting the progression of anterolisthesis. Utilization of robot guidance allows for efficient placement of these difficult screw trajectories in a minimally invasive fashion.

    View details for DOI 10.1016/j.wneu.2019.07.229

    View details for PubMedID 31398524

  • Stem cell therapies for acute spinal cord injury in humans: a review NEUROSURGICAL FOCUS Jin, M. C., Medress, Z. A., Azad, T. D., Doulames, V. M., Veeravagu, A. 2019; 46 (3): E10

    Abstract

    Recent advances in stem cell biology present significant opportunities to advance clinical applications of stem cell-based therapies for spinal cord injury (SCI). In this review, the authors critically analyze the basic science and translational evidence that supports the use of various stem cell sources, including induced pluripotent stem cells, oligodendrocyte precursor cells, and mesenchymal stem cells. They subsequently explore recent advances in stem cell biology and discuss ongoing clinical translation efforts, including combinatorial strategies utilizing scaffolds, biogels, and growth factors to augment stem cell survival, function, and engraftment. Finally, the authors discuss the evolution of stem cell therapies for SCI by providing an overview of completed (n = 18) and ongoing (n = 9) clinical trials.

    View details for DOI 10.3171/2018.12.FOCUS18602

    View details for Web of Science ID 000460130200010

    View details for PubMedID 30835679

  • Children with epilepsy demonstrate macro- and microstructural changes in the thalamus, putamen, and amygdala. Neuroradiology MacEachern, S. J., Santoro, J. D., Hahn, K. J., Medress, Z. A., Stecher, X., Li, M. D., Hahn, J. S., Yeom, K. W., Forkert, N. D. 2019

    Abstract

    Despite evidence for macrostructural alteration in epilepsy patients later in life, little is known about the underlying pathological or compensatory mechanisms at younger ages causing these alterations. The aim of this work was to investigate the impact of pediatric epilepsy on the central nervous system, including gray matter volume, cerebral blood flow, and water diffusion, compared with neurologically normal children.Inter-ictal magnetic resonance imaging data was obtained from 30 children with epilepsy ages 1-16 (73% F, 27% M). An atlas-based approach was used to determine values for volume, cerebral blood flow, and apparent diffusion coefficient in the cerebral cortex, hippocampus, thalamus, caudate, putamen, globus pallidus, amygdala, and nucleus accumbens. These values were then compared with previously published values from 100 neurologically normal children using a MANCOVA analysis.Most brain volumes of children with epilepsy followed a pattern similar to typically developing children, except for significantly larger putamen and amygdala. Cerebral blood flow was also comparable between the groups, except for the putamen, which demonstrated decreased blood flow in children with epilepsy. Diffusion (apparent diffusion coefficient) showed a trend towards higher values in children with epilepsy, with significantly elevated diffusion within the thalamus in children with epilepsy compared with neurologically normal children.Children with epilepsy show statistically significant differences in volume, diffusion, and cerebral blood flow within their thalamus, putamen, and amygdala, suggesting that epilepsy is associated with structural changes of the central nervous system influencing brain development and potentially leading to poorer neurocognitive outcomes.

    View details for DOI 10.1007/s00234-019-02332-8

    View details for PubMedID 31853588

  • Local axonal protection by WldS as revealed by conditional regulation of protein stability PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Wang, J. T., Medress, Z. A., Vargas, M. E., Barres, B. A. 2015; 112 (33): 10093-10100

    Abstract

    The expression of the mutant Wallerian degeneration slow (WldS) protein significantly delays axonal degeneration from various nerve injuries and in multiple species; however, the mechanism for its axonal protective property remains unclear. Although WldS is localized predominantly in the nucleus, it also is present in a smaller axonal pool, leading to conflicting models to account for the WldS fraction necessary for axonal protection. To identify where WldS activity is required to delay axonal degeneration, we adopted a method to alter the temporal expression of WldS protein in neurons by chemically regulating its protein stability. We demonstrate that continuous WldS activity in the axonal compartment is both necessary and sufficient to delay axonal degeneration. Furthermore, by specifically increasing axonal WldS expression postaxotomy, we reveal a critical period of 4-5 h postinjury during which the course of Wallerian axonal degeneration can be halted. Finally, we show that NAD(+), the metabolite of WldS/nicotinamide mononucleotide adenylyltransferase enzymatic activity, is sufficient and specific to confer WldS-like axon protection and is a likely molecular mediator of WldS axon protection. The results delineate a therapeutic window in which the course of Wallerian degeneration can be delayed even after injures have occurred and help narrow the molecular targets of WldS activity to events within the axonal compartment.

    View details for DOI 10.1073/pnas.1508337112

    View details for Web of Science ID 000359738300028

    View details for PubMedCentralID PMC4547231

  • Local axonal protection by WldS as revealed by conditional regulation of protein stability. Proceedings of the National Academy of Sciences of the United States of America Wang, J. T., Medress, Z. A., Vargas, M. E., Barres, B. A. 2015; 112 (33): 10093-10100

    Abstract

    The expression of the mutant Wallerian degeneration slow (WldS) protein significantly delays axonal degeneration from various nerve injuries and in multiple species; however, the mechanism for its axonal protective property remains unclear. Although WldS is localized predominantly in the nucleus, it also is present in a smaller axonal pool, leading to conflicting models to account for the WldS fraction necessary for axonal protection. To identify where WldS activity is required to delay axonal degeneration, we adopted a method to alter the temporal expression of WldS protein in neurons by chemically regulating its protein stability. We demonstrate that continuous WldS activity in the axonal compartment is both necessary and sufficient to delay axonal degeneration. Furthermore, by specifically increasing axonal WldS expression postaxotomy, we reveal a critical period of 4-5 h postinjury during which the course of Wallerian axonal degeneration can be halted. Finally, we show that NAD(+), the metabolite of WldS/nicotinamide mononucleotide adenylyltransferase enzymatic activity, is sufficient and specific to confer WldS-like axon protection and is a likely molecular mediator of WldS axon protection. The results delineate a therapeutic window in which the course of Wallerian degeneration can be delayed even after injures have occurred and help narrow the molecular targets of WldS activity to events within the axonal compartment.

    View details for DOI 10.1073/pnas.1508337112

    View details for PubMedID 26209654

    View details for PubMedCentralID PMC4547231

  • The role of automatic computer-aided surgical trajectory planning in improving the expected safety of stereotactic neurosurgery INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY Trope, M., Shamir, R. R., Joskowicz, L., Medress, Z., Rosenthal, G., Mayer, A., Levin, N., Bick, A., Shoshan, Y. 2015; 10 (7): 1127-1140

    Abstract

    Minimal invasion computer-assisted neurosurgical procedures with various tool insertions into the brain may carry hemorrhagic risks and neurological deficits. The goal of this study is to investigate the role of computer-based surgical trajectory planning tools in improving the potential safety of image-based stereotactic neurosurgery.Multi-sequence MRI studies of eight patients who underwent image-guided neurosurgery were retrospectively processed to extract anatomical structures-head surface, ventricles, blood vessels, white matter fibers tractography, and fMRI data of motor, sensory, speech, and visual areas. An experienced neurosurgeon selected one target for each patient. Five neurosurgeons planned a surgical trajectory for each patient using three planning methods: (1) conventional; (2) visualization, in which scans are augmented with overlays of anatomical structures and functional areas; and (3) automatic, in which three surgical trajectories with the lowest expected risk score are automatically computed. For each surgeon, target, and method, we recorded the entry point and its surgical trajectory and computed its expected risk score and its minimum distance from the key structures.A total of 120 surgical trajectories were collected (5 surgeons, 8 targets, 3 methods). The surgical trajectories expected risk scores improved by 76 % ([Formula: see text], two-sample student's t test); the average distance of a trajectory from nearby blood vessels increased by 1.6 mm ([Formula: see text]) from 0.6 to 2.2 mm (243 %). The initial surgical trajectories were changed in 85 % of the cases based on the expected risk score and the trajectory distance from blood vessels.Computer-based patient-specific preoperative planning of surgical trajectories that minimize the expected risk of vascular and neurological damage due to incorrect tool placement is a promising technique that yields consistent improvements.

    View details for DOI 10.1007/s11548-014-1126-5

    View details for Web of Science ID 000357278000012

    View details for PubMedID 25408305

  • Molecular and Genetic Predictors of Breast-to-Brain Metastasis: Review and Case Presentation. Cureus Medress, Z., Hayden Gephart, M. 2015; 7 (1)

    Abstract

    Brain metastases are the most common intracranial malignancy, and breast cancer is the second most common cancer to metastasize to the brain. Intracranial disease is a late manifestation of breast cancer with few effective treatment options, affecting 15-50% of breast cancer patients, depending upon molecular subtype. In this review article, we describe the genetic, molecular, and metabolic changes in breast cancer cells that facilitate breast to brain metastasis. We believe that advances in the understanding of breast to brain metastasis pathogenesis will lead to targeted molecular therapies and to improvements in the ability to prospectively identify patients at increased risk for developing intracranial disease.

    View details for DOI 10.7759/cureus.246

    View details for PubMedID 26180670

    View details for PubMedCentralID PMC4494590

  • Cervical Fracture Stabilization within 72 Hours of Injury is Associated with Decreased Hospitalization Costs with Comparable Perioperative Outcomes in a Propensity Score-Matched Cohort. Cureus Medress, Z., Arrigo, R. T., Hayden Gephart, M., Zygourakis, C. C., Boakye, M. 2015; 7 (1)

    Abstract

    Prior studies have indicated that early decompression of traumatic cervical fractures can be performed safely and is associated with improved outcomes, though the economic impact of the timing of surgery in the American population has not been studied. After adjusting for patient, hospital, and injury confounders, we performed propensity score modeling (PSM) on a large clinical administrative database to determine associated costs depending upon timing of surgery for acute cervical fracture.A total of 3,348 patients with surgically treated, traumatic, cervical fractures were identified. Patients were sorted into early (within 72 hours of admission) and late (beyond 72 hours) surgery groups. PSM was able to match 2,132 early and late surgery patients on age, comorbidity, expected payer, trauma severity, hospital type, urgent admission, and surgical approach. Perioperative complications, mortality, and resource utilization were assessed.Late surgery was more frequently associated with increased age, more comorbidities, higher ICISS score, and non-private insurance. Following PSM matching, there were no significant, preoperative differences between early and late surgery groups. Surgery performed after 72 hours was associated with an increase in in-hospital complications (OR=1.3). The early surgery group was associated with decreased length of stay (11 days vs. 16 days, p <0.0001) and hospital charges ($237,786 v. $282,727, p <0.0001).After controlling for potential confounding differences through PSM matching and multivariate analyses, we found late surgery independently associated with increased in-hospital complications, length of stay, and hospital resource utilization. These data suggest surgery within 72 hours may decrease resource utilization without a corresponding increase in postoperative morbidity.

    View details for DOI 10.7759/cureus.244

    View details for PubMedID 26180668

    View details for PubMedCentralID PMC4494543

  • Pilocytic astrocytoma with IDH1 mutation in the cerebellum of an elderly patient. Clinical neuropathology Medress, Z. A., Xu, L. W., Ziskin, J. L., Lefterova, M., Vogel, H., Li, G. 2014

    View details for DOI 10.5414/NP300810

    View details for PubMedID 25295857

  • Axon degeneration: Molecular mechanisms of a self-destruction pathway JOURNAL OF CELL BIOLOGY Wang, J. T., Medress, Z. A., Barres, B. A. 2012; 196 (1): 7-18

    Abstract

    Axon degeneration is a characteristic event in many neurodegenerative conditions including stroke, glaucoma, and motor neuropathies. However, the molecular pathways that regulate this process remain unclear. Axon loss in chronic neurodegenerative diseases share many morphological features with those in acute injuries, and expression of the Wallerian degeneration slow (WldS) transgene delays nerve degeneration in both events, indicating a common mechanism of axonal self-destruction in traumatic injuries and degenerative diseases. A proposed model of axon degeneration is that nerve insults lead to impaired delivery or expression of a local axonal survival factor, which results in increased intra-axonal calcium levels and calcium-dependent cytoskeletal breakdown.

    View details for DOI 10.1083/jcb.201108111

    View details for Web of Science ID 000299269000003

    View details for PubMedID 22232700

    View details for PubMedCentralID PMC3255986

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