All Publications

  • 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


    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

  • Affinity-matured DLL4 ligands as broad-spectrum modulators of Notch signaling. Nature chemical biology Gonzalez-Perez, D., Das, S., Antfolk, D., Ahsan, H. S., Medina, E., Dundes, C. E., Jokhai, R. T., Egan, E. D., Blacklow, S. C., Loh, K. M., Rodriguez, P. C., Luca, V. C. 2022


    The Notch pathway regulates cell fate decisions and is an emerging target for regenerative and cancer therapies. Recombinant Notch ligands are attractive candidates for modulating Notch signaling; however, their intrinsically low receptor-binding affinity restricts their utility in biomedical applications. To overcome this limitation, we evolved variants of the ligand Delta-like 4 with enhanced affinity and cross-reactivity. A consensus variant with maximized binding affinity, DeltaMAX, binds human and murine Notch receptors with 500- to 1,000-fold increased affinity compared with wild-type human Delta-like 4. DeltaMAX also potently activates Notch in plate-bound, bead-bound and cellular formats. When administered as a soluble decoy, DeltaMAX inhibits Notch in reporter and neuronal differentiation assays, highlighting its dual utility as an agonist or antagonist. Finally, we demonstrate that DeltaMAX stimulates increased proliferation and expression of effector mediators in T cells. Taken together, our data define DeltaMAX as a versatile tool for broad-spectrum activation or inhibition of Notch signaling.

    View details for DOI 10.1038/s41589-022-01113-4

    View details for PubMedID 36050494

  • 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


    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

  • The impact of osteoporosis on adult deformity surgery outcomes in Medicare patients. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society Varshneya, K., Bhattacharjya, A., Jokhai, R. T., Fatemi, P., Medress, Z. A., Stienen, M. N., Ho, A. L., Ratliff, J. K., Veeravagu, A. 2021


    OBJECTIVE: To identify the impact of osteoporosis (OS) on postoperative outcomes in Medicare patients undergoing ASD surgery.BACKGROUND: Patients with OP and advanced age experience higher than average rates of ASD. However, poor bone density could undermine the durability of a deformity correction.METHODS: We queried the MarketScan Medicare Supplemental database to identify patients Medicare patients who underwent ASD surgery from 2007 to 2016.RESULTS: A total of 2564 patients met the inclusion criteria of this study, of whom n=971 (61.0%) were diagnosed with osteoporosis. Patients with OP had a similar 90-day postoperative complication rates (OP: 54.6% vs. non-OP: 49.2%, p=0.0076, not significant after multivariate regression correction). This was primarily driven by posthemorrhagic anemia (37.6% in OP, vs. 33.1% in non-OP). Rates of revision surgery were similar at 90days (non-OP 15.0%, OP 16.8%), but by 2years, OP patients had a significantly higher reoperation rate (30.4% vs. 22.9%, p<0.0001). In multivariate regression analysis, OP increased odds for revision surgery at 1year (OR 1.4) and 2years (OR 1.5) following surgery (all p<0.05). OP was also an independent predictor of readmission at all time points (90days, OR 1.3, p<0.005).CONCLUSION: Medicare patients with OP had elevated rates of complications, reoperations, and outpatient costs after undergoing primary ASD surgery.

    View details for DOI 10.1007/s00586-021-06985-z

    View details for PubMedID 34655336

  • Factors which predict adverse events following surgery in adults with cervical spinal deformity. The bone & joint journal Varshneya, K., Jokhai, R., Medress, Z. A., Stienen, M. N., Ho, A., Fatemi, P., Ratliff, J. K., Veeravagu, A. 2021; 103-B (4): 734–38


    AIMS: The aim of this study was to identify the risk factors for adverse events following the surgical correction of cervical spinal deformities in adults.METHODS: We identified adult patients who underwent corrective cervical spinal surgery between 1 January 2007 and 31 December 2015 from the MarketScan database. The baseline comorbidities and characteristics of the operation were recorded. Adverse events were defined as the development of a complication, an unanticipated deleterious postoperative event, or further surgery. Patients aged < 18 years and those with a previous history of tumour or trauma were excluded from the study.RESULTS: A total of 13,549 adults in the database underwent primary corrective surgery for a cervical spinal deformity during the study period. A total of 3,785 (27.9%) had a complication within 90 days of the procedure, and 3,893 (28.7%) required further surgery within two years. In multivariate analysis, male sex (odds ratio (OR) 0.90 (95% confidence interval (CI) 0.8 to 0.9); p = 0.019) and a posterior approach (compared with a combined surgical approach, OR 0.66 (95% CI 0.5 to 0.8); p < 0.001) significantly decreased the risk of complications. Osteoporosis (OR 1.41 (95% CI 1.3 to 1.6); p < 0.001), dyspnoea (OR 1.48 (95% CI 1.3 to 1.6); p < 0.001), cerebrovascular accident (OR 1.81 (95% CI 1.6 to 2.0); p < 0.001), a posterior approach (compared with an anterior approach, OR 1.23 (95% CI 1.1 to 1.4); p < 0.001), and the use of bone morphogenic protein (BMP) (OR 1.22 (95% CI 1.1 to 1.4); p = 0.003) significantly increased the risks of 90-day complications. In multivariate regression analysis, preoperative dyspnoea (OR 1.50 (95% CI 1.3 to 1.7); p < 0.001), a posterior approach (compared with an anterior approach, OR 2.80 (95% CI 2.4 to 3.2; p < 0.001), and postoperative dysphagia (OR 2.50 (95% CI 1.8 to 3.4); p < 0.001) were associated with a significantly increased risk of further surgery two years postoperatively. A posterior approach (compared with a combined approach, OR 0.32 (95% CI 0.3 to 0.4); p < 0.001), the use of BMP (OR 0.48 (95% CI 0.4 to 0.5); p < 0.001) were associated with a significantly decreased risk of further surgery at this time.CONCLUSION: The surgical approach and intraoperative use of BMP strongly influence the risk of further surgery, whereas the comorbidity burden and the characteristics of the operation influence the rates of early complications in adult patients undergoing corrective cervical spinal surgery. These data may aid surgeons in patient selection and surgical planning. Cite this article: Bone Joint J2021;103-B(4):734-738.

    View details for DOI 10.1302/0301-620X.103B4.BJJ-2020-0845.R2

    View details for PubMedID 33789479

  • 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


    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

  • Fluorofunctionalization of C=C Bonds with Selectfluor: Synthesis of beta-Fluoropiperazines through a Substrate-Guided Reactivity Switch JOURNAL OF ORGANIC CHEMISTRY Capilato, J. N., Bume, D., Lee, W., Hoffenberg, L. S., Jokhai, R., Lectka, T. 2018; 83 (23): 14234-14244


    The halofunctionalization of alkene substrates remains an essential tool for synthetic chemists. Herein, we report regioselective ammoniofluorination of unactivated alkenes through photochemical means. A one-pot transformation of the ammonium fluoride products into pharmaceutically relevant β-fluoropiperazines is highlighted. Furthermore, a substrate-guided reactivity switch is observed: certain alkenes are shown to react with the same fluorinating reagent to instead give the less-substituted fluoride. We hope that the ammoniofluorination reaction will be of utility in the area of medicinal chemistry, where nitrogen and fluorine are among the most important heteroatoms.

    View details for DOI 10.1021/acs.joc.8b02429

    View details for Web of Science ID 000452929900002

    View details for PubMedID 30418026

  • Direct, visible light-sensitized benzylic C-H fluorination of peptides using dibenzosuberenone: selectivity for phenylalanine-like residues TETRAHEDRON Bume, D., Pitts, C., Jokhai, R., Lectka, T. 2016; 72 (40): 6031-6036