Honors & Awards

  • Berg Scholar, Stanford University School of Medicine (2020-2024)
  • Committee Member, AANS Young Neurosurgeon's Committee (2020)
  • Abstract Achievement Award, American Society of Hematology (2017, 2018)

Professional Affiliations and Activities

  • President, American Association of Neurological Surgeons - Medical Student Chapter (2021 - Present)
  • Member, American Association of Neurological Surgeons (2019 - Present)
  • Member, Congress of Neurological Surgeons (2019 - Present)
  • Co-Chair, Otolaryngology Interest Group (2019 - 2020)
  • Member, American Society of Hematology (2017 - Present)
  • Member, American Society of Clinical Oncology (2016 - Present)

Membership Organizations

  • Neurosurgery Interest Group, Co-Chair

Education & Certifications

  • Bachelor of Science, Stanford University, BIO-BSH (2016)
  • Bachelor of Science, Stanford University, STATS-MIN (2016)

All Publications

  • 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


    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

  • Modifiers of and Disparities in Palliative and Supportive Care Timing and Utilization among Neurosurgical Patients with Malignant Central Nervous System Tumors. Cancers Jin, M. C., Hsin, G., Ratliff, J., Thomas, R., Zygourakis, C. C., Li, G., Wu, A. 2022; 14 (10)


    Patients with primary or secondary central nervous system (CNS) malignancies benefit from utilization of palliative care (PC) in addition to other supportive services, such as home health and social work. Guidelines propose early initiation of PC for patients with advanced cancers. We analyzed a cohort of privately insured patients with malignant brain or spinal tumors derived from the Optum Clinformatics Datamart Database to investigate health disparities in access to and utilization of supportive services. We introduce a novel construct, "provider patient racial diversity index" (provider pRDI), which is a measure of the proportion of non-white minority patients a provider encounters to approximate a provider's patient demographics and suggest a provider's cultural sensitivity and exposure to diversity. Our analysis demonstrates low rates of PC, home health, and social work services among racial minority patients. Notably, Hispanic patients had low likelihood of engaging with all three categories of supportive services. However, patients who saw providers categorized into high provider pRDI (categories II and III) were increasingly more likely to interface with supportive care services and at an earlier point in their disease courses. This study suggests that prospective studies that examine potential interventions at the provider level, including diversity training, are needed.

    View details for DOI 10.3390/cancers14102567

    View details for PubMedID 35626171

  • An integrated risk model stratifying seizure risk following brain tumor resection among seizure-naive patients without antiepileptic prophylaxis. Neurosurgical focus Jin, M. C., Parker, J. J., Prolo, L. M., Wu, A., Halpern, C. H., Li, G., Ratliff, J. K., Han, S. S., Skirboll, S. L., Grant, G. A. 2022; 52 (4): E3


    The natural history of seizure risk after brain tumor resection is not well understood. Identifying seizure-naive patients at highest risk for postoperative seizure events remains a clinical need. In this study, the authors sought to develop a predictive modeling strategy for anticipating postcraniotomy seizures after brain tumor resection.The IBM Watson Health MarketScan Claims Database was canvassed for antiepileptic drug (AED)- and seizure-naive patients who underwent brain tumor resection (2007-2016). The primary event of interest was short-term seizure risk (within 90 days postdischarge). The secondary event of interest was long-term seizure risk during the follow-up period. To model early-onset and long-term postdischarge seizure risk, a penalized logistic regression classifier and multivariable Cox regression model, respectively, were built, which integrated patient-, tumor-, and hospitalization-specific features. To compare empirical seizure rates, equally sized cohort tertiles were created and labeled as low risk, medium risk, and high risk.Of 5470 patients, 983 (18.0%) had a postdischarge-coded seizure event. The integrated binary classification approach for predicting early-onset seizures outperformed models using feature subsets (area under the curve [AUC] = 0.751, hospitalization features only AUC = 0.667, patient features only AUC = 0.603, and tumor features only AUC = 0.694). Held-out validation patient cases that were predicted by the integrated model to have elevated short-term risk more frequently developed seizures within 90 days of discharge (24.1% high risk vs 3.8% low risk, p < 0.001). Compared with those in the low-risk tertile by the long-term seizure risk model, patients in the medium-risk and high-risk tertiles had 2.13 (95% CI 1.45-3.11) and 6.24 (95% CI 4.40-8.84) times higher long-term risk for postdischarge seizures. Only patients predicted as high risk developed status epilepticus within 90 days of discharge (1.7% high risk vs 0% low risk, p = 0.003).The authors have presented a risk-stratified model that accurately predicted short- and long-term seizure risk in patients who underwent brain tumor resection, which may be used to stratify future study of postoperative AED prophylaxis in highest-risk patient subpopulations.

    View details for DOI 10.3171/2022.1.FOCUS21751

    View details for PubMedID 35364580

  • Risk of Second Primary Malignancies After External Beam Radiotherapy for Thyroid Cancer. Anticancer research Jin, M. C., Qian, Z. J., Megwalu, U. C. 2022; 42 (3): 1359-1365


    AIM: To investigate the association between external beam radiotherapy (EBRT) and the incidence of second primary tumors in patients with thyroid cancer.MATERIALS AND METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results 9 database. The study cohort included patients diagnosed with thyroid cancer between 1973 and 2017. Risk factors for second primary malignancies were identified with Cox proportional hazards models. Propensity score-matched analyses were used to assess the association between EBRT and second primary malignancies.RESULTS: Out of 72,392 patients with thyroid cancer, 7,684 (10.6%) developed a subsequent primary malignancy. Propensity score-matched analysis demonstrated patients receiving EBRT were more likely to develop second primary malignancies [30-year cumulative incidence=35.3% (95% confidence interval (CI)=30.4-39.8% vs. 28.1% (95% CI=27.0-29.2%); hazard ratio=1.17 (95% CI=1.03-1.33)].CONCLUSION: In patients with thyroid cancer, EBRT is associated with an increased incidence of second primary malignancies.

    View details for DOI 10.21873/anticanres.15605

    View details for PubMedID 35220228

  • Prediction of Discharge Status and Readmissions after Resection of Intradural Spinal Tumors. Neurospine Jin, M. C., Ho, A. L., Feng, A. Y., Medress, Z. A., Pendharkar, A. V., Rezaii, P., Ratliff, J. K., Desai, A. M. 2022; 19 (1): 133-145


    OBJECTIVE: Intradural spinal tumors are uncommon and while associations between clinical characteristics and surgical outcomes have been explored, there remains a paucity of literature unifying diverse predictors into an integrated risk model. To predict postresection outcomes for patients with spinal tumors.METHODS: IBM MarketScan Claims Database was queried for adult patients receiving surgery for intradural tumors between 2007 and 2016. Primary outcomes-of-interest were nonhome discharge and 90-day postdischarge readmissions. Secondary outcomes included hospitalization duration and postoperative complications. Risk modeling was developed using a regularized logistic regression framework (LASSO, least absolute shrinkage and selection operator) and validated in a withheld subset.RESULTS: A total of 5,060 adult patients were included. Most surgeries utilized a posterior approach (n = 5,023, 99.3%) and tumors were most commonly found in the thoracic region (n = 1,941, 38.4%), followed by the lumbar (n = 1,781, 35.2%) and cervical (n = 1,294, 25.6%) regions. Compared to models using only tumor-specific or patient-specific features, our integrated models demonstrated better discrimination (area under the curve [AUC] [nonhome discharge] = 0.786; AUC [90-day readmissions] = 0.693) and accuracy (Brier score [nonhome discharge] = 0.155; Brier score [90-day readmissions] = 0.093). Compared to those predicted to be lowest risk, patients predicted to be highest-risk for nonhome discharge required continued care 16.3 times more frequently (64.5% vs. 3.9%). Similarly, patients predicted to be at highest risk for postdischarge readmissions were readmitted 7.3 times as often as those predicted to be at lowest risk (32.6% vs. 4.4%).CONCLUSION: Using a diverse set of clinical characteristics spanning tumor-, patient-, and hospitalization-derived data, we developed and validated risk models integrating diverse clinical data for predicting nonhome discharge and postdischarge readmissions.

    View details for DOI 10.14245/ns.2143244.622

    View details for PubMedID 35378587

  • 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


    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

  • 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


    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

  • Hemorrhage risk of direct oral anticoagulants in real-world venous thromboembolism patients. Thrombosis research Jin, M. C., Sussman, E. S., Feng, A. Y., Han, S. S., Skirboll, S. L., Berube, C., Ratliff, J. K. 2021; 204: 126-133


    INTRODUCTION: Venous thromboembolism (VTE) management increasingly involves anticoagulation with direct oral anticoagulants (DOACs). Few studies have used competing-risks analyses to ascertain the mortality-adjusted hemorrhage and recurrent VTE (rVTE) risk of individual DOACs. Furthermore, hemorrhage risk factors in patients treated with apixaban remain underexplored.MATERIALS AND METHODS: Patients diagnosed with VTE receiving anticoagulation were identified from the Optum Clinformatics Data Mart (2003-2019). Study endpoints included readmissions for intracranial hemorrhage (ICH), non-intracranial hemorrhage (non-ICH hemorrhage), and rVTE. Coarsened exact matching was used to balance baseline clinical characteristics. Complication incidence was evaluated using a competing-risks framework. We additionally modeled hemorrhage risk in apixaban-treated patients.RESULTS: Overall, 225,559 patients were included, of whom 34,201 received apixaban and 46,007 received rivaroxaban. Compared to rivaroxaban, apixaban was associated with decreased non-ICH hemorrhage (sHR=0.560, 95%CI=0.423-0.741), but not ICH, and rVTE (sHR=0.802, 95%CI=0.651-0.988) risk. This was primarily in emergent readmissions (sHR[emergent hemorrhage]=0.515, 95%CI=0.372-0.711; sHR[emergent rVTE]=0.636, 95%CI=0.488-0.830). Contributors to emergent hemorrhage in apixaban-treated patients include older age (sHR=1.025, 95%CI=1.011-1.039), female sex (sHR=1.662, 95%CI=1.252-2.207), prior prescription antiplatelet therapy (sHR=1.591, 95%CI=1.130-2.241), and complicated hypertension (sHR=1.936, 95%CI=1.134-3.307). Patients anticipated to be "high-risk" experienced elevated ICH (sHR=3.396, 95%CI=1.375-8.388) and non-ICH hemorrhage (sHR=3.683, 95%CI=2.957-4.588) incidence.CONCLUSIONS: In patients with VTE receiving anticoagulation, apixaban was associated with reduced non-ICH hemorrhage and rVTE risk, compared to rivaroxaban. Risk reduction was restricted to emergent readmissions. We present a risk-stratification approach to predict hemorrhage in patients receiving apixaban, potentially guiding future clinical decision-making.

    View details for DOI 10.1016/j.thromres.2021.06.015

    View details for PubMedID 34198049

  • Status epilepticus after intracranial neurosurgery: incidence and risk stratification by perioperative clinical features. Journal of neurosurgery Jin, M. C., Parker, J. J., Zhang, M. n., Medress, Z. A., Halpern, C. H., Li, G. n., Ratliff, J. K., Grant, G. A., Fisher, R. S., Skirboll, S. n. 2021: 1–13


    Status epilepticus (SE) is associated with significant mortality, cost, and risk of future seizures. In one of the first studies of SE after neurosurgery, the authors assess the incidence, risk factors, and outcome of postneurosurgical SE (PNSE).Neurosurgical admissions from the MarketScan Claims and Encounters database (2007 through 2015) were assessed in a longitudinal cross-sectional sample of privately insured patients who underwent qualifying cranial procedures in the US and were older than 18 years of age. The incidence of early (in-hospital) and late (postdischarge readmission) SE and associated mortality was assessed. Procedural, pathological, demographic, and anatomical covariates parameterized multivariable logistic regression and Cox models. Multivariable logistic regression and Cox proportional hazards models were used to study the incidence of early and late PNSE. A risk-stratification simulation was performed, combining individual predictors into singular risk estimates.A total of 197,218 admissions (218,217 procedures) were identified. Early PNSE occurred during 637 (0.32%) of 197,218 admissions for cranial neurosurgical procedures. A total of 1045 (0.56%) cases of late PNSE were identified after 187,771 procedure admissions with nonhospice postdischarge follow-up. After correction for comorbidities, craniotomy for trauma, hematoma, or elevated intracranial pressure was associated with increased risk of early PNSE (adjusted OR [aOR] 1.538, 95% CI 1.183-1.999). Craniotomy for meningioma resection was associated with an increased risk of early PNSE compared with resection of metastases and parenchymal primary brain tumors (aOR 2.701, 95% CI 1.388-5.255). Craniotomies for infection or abscess (aHR 1.447, 95% CI 1.016-2.061) and CSF diversion (aHR 1.307, 95% CI 1.076-1.587) were associated with highest risk of late PNSE. Use of continuous electroencephalography in patients with early (p < 0.005) and late (p < 0.001) PNSE rose significantly over the study time period. The simulation regression model predicted that patients at high risk for early PNSE experienced a 1.10% event rate compared with those at low risk (0.07%). Similarly, patients predicted to be at highest risk for late PNSE were significantly more likely to eventually develop late PNSE than those at lowest risk (HR 54.16, 95% CI 24.99-104.80).Occurrence of early and late PNSE was associated with discrete neurosurgical pathologies and increased mortality. These data provide a framework for prospective validation of clinical and perioperative risk factors and indicate patients for heightened diagnostic suspicion of PNSE.

    View details for DOI 10.3171/2020.10.JNS202895

    View details for PubMedID 33990087

  • Defining and Describing Treatment Heterogeneity in New-Onset Idiopathic Lower Back and Extremity Pain Through Reconstruction of Longitudinal Care Sequences. The spine journal : official journal of the North American Spine Society Jin, M. C., Azad, T. D., Fatemi, P., Ho, A. L., Vail, D., Zhang, Y., Feng, A. Y., Kim, L. H., Bentley, J. P., Stienen, M. N., Li, G., Desai, A. M., Veeravagu, A., Ratliff, J. K. 2021


    Despite established guidelines, long-term management of surgically-treated low back pain (LBP) and lower extremity pain (LEP) remains heterogeneous. Understanding care heterogeneity could inform future approaches for standardization of practices.To describe treatment heterogeneity in surgically-managed LBP and LEP.Retrospective study of a nationwide commercial database spanning inpatient and outpatient encounters for enrollees of eligible employer-supplied healthcare plans (2007-2016).A population-based sample of opioid-naïve adult patients with newly-diagnosed LBP or LEP were identified. Inclusion required at least 12-months of pre-diagnosis and post-diagnosis continuous follow-up.Included treatments/evaluations include conservative management (chiropractic manipulative therapy, physical therapy, epidural steroid injections), imaging (x-ray, MRI, CT), pharmaceuticals (opioids, benzodiazepines), and spine surgery (decompression, fusion).Primary outcomes-of-interest were 12-month net healthcare expenditures (inpatient and outpatient) and 12-month opioid usage.Analyses include interrogation of care sequence heterogeneity and temporal trends in sequence-initiating services. Comparisons were conducted in the framework of sequence-specific treatment sequences, which reflect the personalized order of healthcare services pursued by each patient. Outlier sequences characterized by high opioid use and costs were identified from frequently observed surgical treatment sequences using Mahalanobis distance.A total of 2,496,908 opioid-naïve adult patients with newly-diagnosed LBP or LEP were included (29,519 surgical). In the matched setting, increased care sequence heterogeneity was observed in surgical patients (0.51 vs 0.12 previously-unused interventions/studies pursued per month). Early opioid and MRI use has decreased between 2008 and 2015 but is matched by increases in early benzodiazepine and x-ray use. Outlier sequences, characterized by increased opioid use and costs, were found in 5.8% of surgical patients. Use of imaging prior to conservative management was common in patients pursuing outlier sequences compared to non-outlier sequences (96.5% vs 63.8%, p<0.001). Non-outlier sequences were more frequently characterized by early conservative interventions (31.9% vs 7.4%, p<0.001).Surgically-managed LBP and LEP care sequences demonstrate high heterogeneity despite established practice guidelines. Outlier sequences associated with high opioid usage and costs can be identified and are characterized by increased early imaging and decreased early conservative management. Elements that may portend suboptimal longitudinal management could provide opportunities for standardization of patient care.

    View details for DOI 10.1016/j.spinee.2021.05.019

    View details for PubMedID 34033933

  • Trends in Use and Timing of Intratympanic Corticosteroid Injections for Sudden Sensorineural Hearing Loss. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Jin, M. C., Qian, Z. J., Cooperman, S. P., Alyono, J. C. 2020: 194599820976177


    OBJECTIVE: Oral corticosteroids are treatment mainstays for idiopathic sudden sensorineural hearing loss (SSNHL). Recent studies suggest that intratympanic (IT) steroid injections may be effective as an alternate or adjunctive therapy. We sought to investigate nationwide trends in treatment patterns for SSNHL.STUDY DESIGN: Retrospective cross-sectional study.SETTING: A large nationwide health care claims database spanning 2007 to 2016.METHODS: Patients with SSNHL were identified from the IBM Watson Health MarketScan Database. Multivariable logistic, linear, and Cox regression were used for demographic- and comorbidity-adjusted analyses.RESULTS: Overall, 19,670 patients were included. Between 2007 and 2016, use of oral corticosteroids alone decreased (83.6% to 64.6%, P < .001), while use of IT corticosteroids alone and combination IT-oral corticosteroids increased (IT only, 7.9% to 15.1%, P = .002; IT-oral, 8.5% to 20.4%, P < .001). During the study period, time to treatment initiation decreased for both administration modalities, though more dramatically for IT corticosteroids (IT, 124.0 to 10.6 days, P < .001; oral, 42.6 to 12.7 days, P < .001). In patients receiving both IT and oral corticosteroids, concurrent first-line use increased (25.2% to 52.8%, P < .001). Repeat injections have also become more common but may raise risk of persistent tympanic membrane perforations (vs no injection; hazard ratio [first injection] = 7.95, 95% CI = 5.54-11.42; hazard ratio [fifth or higher injection] = 17.47, 95% CI = 6.93-44.05).CONCLUSION: SSNHL management increasingly involves early IT steroids as an alternative or adjunctive option to oral steroids. Use of repeat IT corticosteroid injections has also increased but may raise risk of persistent tympanic membrane perforations and subsequent tympanoplasty. Future decision analysis and cost-effectiveness studies are necessary to identify an optimal care pattern for SSNHL.

    View details for DOI 10.1177/0194599820976177

    View details for PubMedID 33287664

  • Predictive Modeling of Long-Term Opioid and Benzodiazepine Use after Intradural Tumor Resection. The spine journal : official journal of the North American Spine Society Jin, M. C., Ho, A. L., Feng, A. Y., Zhang, Y., Staartjes, V. E., Stienen, M. N., Han, S. S., Veeravagu, A., Ratliff, J. K., Desai, A. M. 2020


    INTRODUCTION: Despite increased awareness of the ongoing opioid epidemic, opioid and benzodiazepine use remain high after spine surgery. In particular, long-term co-prescription of opioids and benzodiazepines have been linked to high risk of overdose-associated death. Tumor patients represent a unique subset of spine surgery patients and few studies have attempted to develop predictive models to anticipate long-term opioid and benzodiazepine use after spinal tumor resection.METHODS: The IBM Watson Health MarketScan Database and Medicare Supplement were assessed to identify admissions for intradural tumor resection between 2007 and 2015. Adult patients were required to have at least 6-months of continuous pre-admission baseline data and 12-months of continuous post-discharge follow-up. Primary outcomes were long-term opioid and benzodiazepine use, defined as at least 6 prescriptions within 12 months. Secondary outcomes were durations of opioid and benzodiazepine prescribing. Logistic regression models, with and without regularization, were trained on an 80% training sample and validated on the withheld 20%.RESULTS: A total of 1,942 patients were identified. The majority of tumors were extramedullary (74.8%) and benign (62.5%). A minority of patients received arthrodesis (9.2%) and most patients were discharged to home (79.1%). Factors associated with post-discharge opioid use duration include tumor malignancy (vs benign, B=19.8 prescribed-days/year, 95% CI 1.1 to 38.5) and intramedullary compartment (vs extramedullary, B=18.1 prescribed-days/year, 95% CI 3.3 to 32.9). Pre- and peri-operative use of prescribed NSAIDs and gabapentin/pregabalin were associated with shorter and longer duration opioid use, respectively. History of opioid and history of benzodiazepine use were both associated with increased post-discharge opioid and benzodiazepine use. Intramedullary location was associated with longer duration post-discharge benzodiazepine use (B=10.3 prescribed-days/year, 95% CI 1.5 to 19.1). Among assessed models, elastic net regularization demonstrated best predictive performance in the withheld validation cohort when assessing both long-term opioid use (AUC=0.748) and long-term benzodiazepine use (AUC=0.704). Applying our model to the validation set, patients scored as low-risk demonstrated a 4.8% and 2.4% risk of long-term opioid and benzodiazepine use, respectively, compared to 35.2% and 11.1% of high-risk patients.CONCLUSIONS: We developed and validated a parsimonious, predictive model to anticipate long-term opioid and benzodiazepine use early after intradural tumor resection, providing physicians opportunities to consider alternative pain management strategies.

    View details for DOI 10.1016/j.spinee.2020.10.010

    View details for PubMedID 33065272

  • External Beam Radiotherapy for Medullary Thyroid Cancer Following Total or Near-Total Thyroidectomy. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Jin, M., Megwalu, U. C., Noel, J. E. 2020: 194599820947696


    OBJECTIVES: Medullary thyroid carcinoma (MTC) often presents with advanced disease and takes an aggressive course as compared with more well-differentiated thyroid cancers. The role of adjuvant therapy, specifically external beam radiotherapy (EBRT), remains disputed. This study investigated the impact of EBRT on survival in MTC.STUDY DESIGN: Cross-sectional analysis of a national database.SETTING: Patients with MTC were identified from the SEER program (Surveillance, Epidemiology, and End Results).METHODS: Collected variables included age, sex, race, T and N stages, lymph node yield, and use of EBRT. Propensity score matching was performed to determine the association of EBRT with overall and disease-specific survival.RESULTS: A total of 2046 patients with locoregional MTC were identified. Of these, 152 received EBRT. Patients receiving EBRT were older and had more advanced disease. EBRT was not associated with differences in overall survival (hazard ratio, 1.12; 95% CI, 0.76-1.65) or disease-specific survival (1.66; 0.93-2.95), as well as in subset analysis of age and disease extent. Long-term overall survival was similar, with 77.3% (95% CI, 70.1%-85.3%) and 58.3% (48.2%-70.5%) of patients without EBRT alive at 5 and 10 years, respectively (vs 70.7% [63.2%-79.1%] and 52.3% [43.3%-63.2%] of patients with EBRT). There were no differences in 5- and 10-year disease-specific survival.CONCLUSION: EBRT was not associated with improved overall or disease-specific survival in patients with MTC. Decisions regarding EBRT must be made with consideration of morbidity relative to benefit for individual patients.

    View details for DOI 10.1177/0194599820947696

    View details for PubMedID 32746731

  • Integrating genomic features for non-invasive early lung cancer detection NATURE Chabon, J. J., Hamilton, E. G., Kurtz, D. M., Esfahani, M. S., Moding, E. J., Stehr, H., Schroers-Martin, J., Nabet, B. Y., Chen, B., Chaudhuri, A. A., Liu, C., Hui, A. B., Jin, M. C., Azad, T. D., Almanza, D., Jeon, Y., Nesselbush, M. C., Keh, L., Bonilla, R. F., Yoo, C. H., Ko, R. B., Chen, E. L., Merriott, D. J., Massion, P. P., Mansfield, A. S., Jen, J., Ren, H. Z., Lin, S. H., Costantino, C. L., Burr, R., Tibshirani, R., Gambhir, S. S., Berry, G. J., Jensen, K. C., West, R. B., Neal, J. W., Wakelee, H. A., Loo, B. W., Kunder, C. A., Leung, A. N., Lui, N. S., Berry, M. F., Shrager, J. B., Nair, V. S., Haber, D. A., Sequist, L. V., Alizadeh, A. A., Diehn, M. 2020
  • Evaluating Shunt Survival Following Ventriculoperitoneal Shunting with and without Stereotactic Navigation in Previously Shunt-Naïve Patients. World neurosurgery Jin, M. C., Wu, A. n., Azad, T. D., Feng, A. n., Prolo, L. M., Veeravagu, A. n., Grant, G. A., Ratliff, J. n., Li, G. n. 2020

    View details for DOI 10.1016/j.wneu.2020.01.138

    View details for PubMedID 31996335

  • 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


    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

  • Adverse Events and Bundled Costs after Cranial Neurosurgical Procedures: Validation of the LACE Index Across 40,431 Admissions and Development of the LACE-Cranial Index. World neurosurgery Jin, M. C., Wu, A. n., Medress, Z. A., Parker, J. J., Desai, A. n., Veeravagu, A. n., Grant, G. A., Li, G. n., Ratliff, J. K. 2020


    Anticipating post-discharge complications following neurosurgery remains difficult. The LACE index, based on four hospitalization descriptors, stratifies patients by risk of 30-day post-discharge adverse events but has not been validated in a procedure-specific manner in neurosurgery. Our study sought to explore the utility of the LACE index in cranial neurosurgery population and to develop an enhanced model, LACE-Cranial.The Optum Clinformatics Database was used to identify cranial neurosurgery admissions (2004-2017). Procedures were grouped as trauma/hematoma/ICP, open vascular, functional/pain, skull base, tumor, or endovascular. Adverse events were defined as post-discharge death/readmission. LACE-Cranial was developed using a logistic regression framework incorporating an expanded feature set in addition to the original LACE components.A total of 40,431 admissions were included. Predictions of 30-day readmissions was best for skull-base (AUC=0.636) and tumor (AUC=0.63) admissions but was generally poor. Predictive ability of 30-day mortality was best for functional/pain admissions (AUC=0.957) and poorest for trauma/hematoma/ICP admissions (AUC=0.613). Across procedure types except for functional/pain, a high-risk LACE score was associated with higher post-discharge bundled payment costs. Incorporating features identified to contribute independent predictive value, the LACE-Cranial model achieved procedure-specific 30-day mortality AUCs ranging from 0.904 to 0.98. Prediction of 30-day and 90-day readmissions was also improved, with tumor and skull base cases achieving 90-day readmission AUCs of 0.718 and 0.717, respectively.While the unmodified LACE index demonstrates inconsistent classification performance, the enhanced LACE-Cranial model offers excellent prediction of short-term post-discharge mortality across procedure groups and significantly improved anticipation of short-term post-discharge readmissions.

    View details for DOI 10.1016/j.wneu.2020.10.103

    View details for PubMedID 33127572

  • Impact of Proton Radiotherapy on Treatment Timing in Pediatric and Adult Patients with Central Nervous System Tumors Neuro-Oncology Practice Jin, M. C., Shi, S., Wu, A., Sandhu, N., Xiang, M., Soltys, S. G., Hiniker, S., Li, G., Pollom, E. L. 2020

    View details for DOI 10.1093/nop/npaa034

  • Evaluating Surgical Resection Extent and Adjuvant Therapy in the Management of Gliosarcoma. Frontiers in oncology Jin, M. C., Liu, E. K., Shi, S. n., Gibbs, I. C., Thomas, R. n., Recht, L. n., Soltys, S. G., Pollom, E. L., Chang, S. D., Hayden Gephart, M. n., Nagpal, S. n., Li, G. n. 2020; 10: 337


    Introduction: Gliosarcomas are clinically aggressive tumors, histologically distinct from glioblastoma. Data regarding the impact of extent of resection and post-operative adjuvant therapy on gliosarcoma outcomes are limited. Methods: Patients with histologically confirmed gliosarcoma diagnosed between 1999 and 2019 were identified. Clinical, molecular, and radiographic data were assembled based on historical records. Comparisons of categorical variables used Pearson's Chi-square and Fisher's exact test while continuous values were compared using the Wilcoxon signed-rank test. Survival comparisons were assessed using Kaplan-Meier statistics and Cox regressions. Results: Seventy-one gliosarcoma patients were identified. Secondary gliosarcoma was not associated with worse survival when compared to recurrent primary gliosarcoma (median survival 9.8 [3.8 to 21.0] months vs. 7.6 [1.0 to 35.7], p = 0.7493). On multivariable analysis, receipt of temozolomide (HR = 0.02, 95% CI 0.001-0.21) and achievement of gross total resection (GTR; HR = 0.13, 95% CI 0.02-0.77) were independently prognostic for improved progression-free survival (PFS) while only receipt of temozolomide was independently associated with extended overall survival (OS) (HR = 0.03, 95% CI 0.001-0.89). In patients receiving surgical resection followed by radiotherapy and concomitant temozolomide, achievement of GTR was significantly associated with improved PFS (median 32.97 [7.1-79.6] months vs. 5.45 [1.8-26.3], p = 0.0092) and OS (median 56.73 months [7.8-104.5] vs. 14.83 [3.8 to 29.1], p = 0.0252). Conclusion: Multimodal therapy is associated with improved survival in gliosarcoma. Even in patients receiving aggressive post-operative multimodal management, total surgical removal of macroscopic disease remains important for optimal outcomes.

    View details for DOI 10.3389/fonc.2020.00337

    View details for PubMedID 32219069

    View details for PubMedCentralID PMC7078164

  • Long-term follow-up of neurosurgical outcomes for adult patients in Uganda with traumatic brain injury. Journal of neurosurgery Jin, M. C., Kakusa, B. n., Ku, S. n., Vaca, S. D., Xu, L. W., Nalwanga, J. n., Kiryabwire, J. n., Ssenyonjo, H. n., Mukasa, J. n., Muhumuza, M. n., Fuller, A. T., Haglund, M. M., Grant, G. A. 2020: 1–11


    Traumatic brain injury (TBI) is a major cause of mortality and morbidity in Uganda and other low- and middle-income countries (LMICs). Due to the difficulty of long-term in-person follow-up, there is a paucity of literature on longitudinal outcomes of TBI in LMICs. Using a scalable phone-centered survey, this study attempted to investigate factors associated with both mortality and quality of life in Ugandan patients with TBI.A prospective registry of adult patients with TBI admitted to the neurosurgical ward at Mulago National Referral Hospital was assembled. Long-term follow-up was conducted between 10.4 and 30.5 months after discharge (median 18.6 months). Statistical analyses included univariable and multivariable logistic regression and Cox proportional hazards regression to elucidate factors associated with mortality and long-term recovery.A total of 1274 adult patients with TBI were included, of whom 302 (23.7%) died as inpatients. Patients who died as inpatients received surgery less frequently (p < 0.001), had more severe TBI at presentation (p < 0.001), were older (p < 0.001), and were more likely to be female (p < 0.0001). Patients presenting with TBI resulting from assault were at reduced risk of inpatient death compared with those presenting with TBI caused by road traffic accidents (OR 0.362, 95% CI 0.128-0.933). Inpatient mortality and postdischarge mortality prior to follow-up were 23.7% and 9%, respectively. Of those discharged, 60.8% were reached through phone interviews. Higher Glasgow Coma Scale score at discharge (continuous HR 0.71, 95% CI 0.53-0.94) was associated with improved long-term survival. Tracheostomy (HR 4.38, 95% CI 1.05-16.7) and older age (continuous HR 1.03, 95% CI 1.009-1.05) were associated with poor long-term outcomes. More than 15% of patients continued to suffer from TBI sequelae years after the initial injury, including seizures (6.1%) and depression (10.0%). Despite more than 60% of patients seeking follow-up healthcare visits, mortality was still 9% among discharged patients, suggesting a need for improved longitudinal care to monitor recovery progress.Inpatient and postdischarge mortality remain high following admission to Uganda's main tertiary hospital with the diagnosis of TBI. Furthermore, posttraumatic sequelae, including seizures and depression, continue to burden patients years after discharge. Effective scalable solutions, including phone interviews, are needed to elucidate and address factors limiting in-hospital capacity and access to follow-up healthcare.

    View details for DOI 10.3171/2020.4.JNS193092

    View details for PubMedID 32619973

  • Noninvasive Early Identification of Therapeutic Benefit from Immune Checkpoint Inhibition. Cell Nabet, B. Y., Esfahani, M. S., Moding, E. J., Hamilton, E. G., Chabon, J. J., Rizvi, H. n., Steen, C. B., Chaudhuri, A. A., Liu, C. L., Hui, A. B., Almanza, D. n., Stehr, H. n., Gojenola, L. n., Bonilla, R. F., Jin, M. C., Jeon, Y. J., Tseng, D. n., Liu, C. n., Merghoub, T. n., Neal, J. W., Wakelee, H. A., Padda, S. K., Ramchandran, K. J., Das, M. n., Plodkowski, A. J., Yoo, C. n., Chen, E. L., Ko, R. B., Newman, A. M., Hellmann, M. D., Alizadeh, A. A., Diehn, M. n. 2020


    Although treatment of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs) can produce remarkably durable responses, most patients develop early disease progression. Furthermore, initial response assessment by conventional imaging is often unable to identify which patients will achieve durable clinical benefit (DCB). Here, we demonstrate that pre-treatment circulating tumor DNA (ctDNA) and peripheral CD8 T cell levels are independently associated with DCB. We further show that ctDNA dynamics after a single infusion can aid in identification of patients who will achieve DCB. Integrating these determinants, we developed and validated an entirely noninvasive multiparameter assay (DIREct-On, Durable Immunotherapy Response Estimation by immune profiling and ctDNA-On-treatment) that robustly predicts which patients will achieve DCB with higher accuracy than any individual feature. Taken together, these results demonstrate that integrated ctDNA and circulating immune cell profiling can provide accurate, noninvasive, and early forecasting of ultimate outcomes for NSCLC patients receiving ICIs.

    View details for DOI 10.1016/j.cell.2020.09.001

    View details for PubMedID 33007267

  • Proton radiotherapy and treatment delay in head and neck squamous cell carcinoma. The Laryngoscope Jin, M. C., Harris, J. P., Sabolch, A. N., Gensheimer, M., Le, Q., Beadle, B. M., Pollom, E. L. 2019


    OBJECTIVE: For patients with head and neck squamous cell carcinoma (HNSCC), delays in the initiation of radiotherapy (RT) have been closely associated with worse outcomes. We sought to investigate whether RT modality (proton vs. photon) is associated with differences in the time to initiation of RT.METHODS: The National Cancer Database was queried for patients diagnosed with nonmetastatic HNSCC between 2004 and 2015 who received either proton or photon RT as part of their initial treatment. Wilcoxon rank-sum and chi-square tests were used to compare continuous and categorical variables, respectively. Multivariable logistic regression was used to determine the association between use of proton RT and delayed RT initiation.RESULTS: A total of 175,088 patients with HNSCC receiving either photon or proton RT were identified. Patients receiving proton RT were more likely to be white, reside in higher income areas, and have private insurance. Proton RT was associated with delayed RT initiation compared to photon RT (median 59days vs. 45, P <0.001). Receipt of proton therapy was independently associated with RT initiation beyond 6weeks after diagnosis (adjusted OR [aOR, definitive RT] = 1.69; 95% confidence interval [CI] 1.26-2.30) or surgery (aOR [adjuvant RT] = 4.08; 95% CI 2.64-6.62). In the context of adjuvant proton RT, increases in treatment delay were associated with worse overall survival (weeks, adjusted hazard ratio =1.099, 95% CI 1.011-1.194).CONCLUSION: Use of proton therapy is associated with delayed RT in both the definitive and adjuvant settings for patients with HNSCC and could be associated with poorer outcomes.LEVEL OF EVIDENCE: 2b Laryngoscope, 122:0000-0000, 2019 Laryngoscope, 2019.

    View details for DOI 10.1002/lary.28458

    View details for PubMedID 31837165

  • Prognostic Factors and Treatment Patterns in the Management of Giant Cell Glioblastoma WORLD NEUROSURGERY Jin, M. C., Wu, A., Xiang, M., Azad, T. D., Soltys, S. G., Li, G., Pollom, E. L. 2019; 128: E217–E224
  • Dynamic Risk Profiling Using Serial Tumor Biomarkers for Personalized Outcome Prediction. Cell Kurtz, D. M., Esfahani, M. S., Scherer, F., Soo, J., Jin, M. C., Liu, C. L., Newman, A. M., Duhrsen, U., Huttmann, A., Casasnovas, O., Westin, J. R., Ritgen, M., Bottcher, S., Langerak, A. W., Roschewski, M., Wilson, W. H., Gaidano, G., Rossi, D., Bahlo, J., Hallek, M., Tibshirani, R., Diehn, M., Alizadeh, A. A. 2019


    Accurate prediction of long-term outcomes remains a challenge in the care of cancer patients. Due to the difficulty of serial tumor sampling, previous prediction tools have focused on pretreatment factors. However, emerging non-invasive diagnostics have increased opportunities for serial tumor assessments. We describe the Continuous Individualized Risk Index (CIRI), a method to dynamically determine outcome probabilities for individual patients utilizing risk predictors acquired over time. Similar to "win probability" models in other fields, CIRI provides a real-time probability by integrating risk assessments throughout a patient's course. Applying CIRI to patients with diffuse large B cell lymphoma, we demonstrate improved outcome prediction compared to conventional risk models. We demonstrate CIRI's broader utility in analogous models of chronic lymphocytic leukemia and breast adenocarcinoma and perform a proof-of-concept analysis demonstrating how CIRI could be used to develop predictive biomarkers for therapy selection. We envision thatdynamic risk assessment will facilitate personalized medicine and enable innovative therapeutic paradigms.

    View details for DOI 10.1016/j.cell.2019.06.011

    View details for PubMedID 31280963

  • 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


    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

  • Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma JOURNAL OF CLINICAL ONCOLOGY Kurtz, D. M., Scherer, F., Jin, M. C., Soo, J., Craig, A. M., Esfahani, M., Chabon, J. J., Stehr, H., Liu, C., Tibshirani, R., Maeda, L. S., Gupta, N. K., Khodadoust, M. S., Advani, R. H., Levy, R., Newman, A. M., Duehrsen, U., Huettmann, A., Meignan, M., Casasnovas, R., Westin, J. R., Roschewski, M., Wilson, W. H., Gaidano, G., Rossi, D., Diehn, M., Alizadeh, A. A. 2018; 36 (28): 2845-+
  • Distinct Hodgkin lymphoma subtypes defined by noninvasive genomic profiling. Nature Alig, S. K., Esfahani, M. S., Garofalo, A., Li, M. Y., Rossi, C., Flerlage, T., Flerlage, J. E., Adams, R., Binkley, M. S., Shukla, N., Jin, M. C., Olsen, M., Telenius, A., Mutter, J. A., Schroers-Martin, J. G., Sworder, B. J., Rai, S., King, D. A., Schultz, A., Bögeholz, J., Su, S., Kathuria, K. R., Liu, C. L., Kang, X., Strohband, M. J., Langfitt, D., Pobre-Piza, K. F., Surman, S., Tian, F., Spina, V., Tousseyn, T., Buedts, L., Hoppe, R., Natkunam, Y., Fornecker, L. M., Castellino, S. M., Advani, R., Rossi, D., Lynch, R., Ghesquières, H., Casasnovas, O., Kurtz, D. M., Marks, L. J., Link, M. P., André, M., Vandenberghe, P., Steidl, C., Diehn, M., Alizadeh, A. A. 2023


    The scarcity of malignant Hodgkin and Reed-Sternberg (HRS) cells hamper tissue-based comprehensive genomic profiling of classic Hodgkin lymphoma (cHL). Liquid biopsies, in contrast, show promise for molecular profiling of cHL due to relatively high circulating tumor DNA (ctDNA) levels1-4. Here, we show that the plasma representation of mutations exceeds the bulk tumor representation in most cases, making cHL particularly amenable to noninvasive profiling. Leveraging single-cell transcriptional profiles of cHL tumors, we demonstrate HRS ctDNA shedding to be shaped by DNASE1L3, whose increased tumor microenvironment-derived expression drives high ctDNA concentrations. Using this insight, we comprehensively profile 366 patients, revealing two distinct cHL genomic subtypes with characteristic clinical and prognostic correlates, as well as distinct transcriptional and immunological profiles. Furthermore, we identify a novel class of truncating IL4R-mutations that are dependent on IL13 signaling and therapeutically targetable with IL4R blocking antibodies. Finally, using PhasED-Seq5 we demonstrate the clinical value of pre- and on-treatment ctDNA levels for longitudinally refining cHL risk prediction, and for detection of radiographically occult minimal residual disease. Collectively, these results support the utility of noninvasive strategies for genotyping and dynamic monitoring of cHL as well as capturing molecularly distinct subtypes with diagnostic, prognostic, and therapeutic potential.

    View details for DOI 10.1038/s41586-023-06903-x

    View details for PubMedID 38081297

  • Treatment Course and Outcomes of Intracranial Teratomas in Pediatric Patients: A Retrospective 15-Year Case Series Study. Pediatric neurosurgery Wu, A., Jin, M. C., Vogel, H., Hiniker, S., Campen, C., Prolo, L. M., Grant, G. A. 2023; 58 (6): 429-438


    There is no standard treatment paradigm for intracranial teratomas, a rare subset of primary intracranial non-germinomatous germ cell tumors (NGGCT), which comprise less than 1% of pediatric brain tumors. This case series retrospectively analyzes treatment and outcomes of pediatric intracranial teratomas from a single institution.Authors reviewed a comprehensive pathology database at Stanford's Lucile Packard Children's Hospital for intracranial teratomas in pediatric patients treated from 2006 to 2021; their demographics, treatment, and clinical course were analyzed.Among 14 patients, median follow-up time was 4.6 years and mean age at diagnosis was 10.5 years. Ten had elevated tumor markers and underwent chemotherapy as initial treatment for NGGCT. Ultimately, these patients all required surgery for progressive or residual disease. Two patients did not undergo radiation. After biopsy or resection, 8 patients had pure mature teratoma, five had mixed germ cell tumor with teratoma component, and one had immature teratoma. The patient with immature teratoma died during chemotherapy from septic shock. No patients experienced recurrence. Common sequelae were endocrine (42.8%) and eye movement (50.0%) abnormalities.We highlight the variable treatment course and outcome for pediatric patients with intracranial teratomas. Elevated tumor markers at presentation, along with imaging findings, favor chemotherapy initiation for presumed NGGCT. Resection of residual tumor is recommended even if tumor markers return to normal. Prognosis remains excellent; no patients had recurrence with a median follow-up of 4.6 years.

    View details for DOI 10.1159/000534721

    View details for PubMedID 37879310

  • Tracing founder mutations in circulating and tissue-resident follicular lymphoma precursors. Cancer discovery Schroers-Martin, J. G., Soo, J., Brisou, G., Scherer, F., Kurtz, D. M., Sworder, B. J., Khodadoust, M. S., Jin, M. C., Bru, A., Liu, C. L., Stehr, H., Vineis, P., Natkunam, Y., Teras, L. R., Song, J. Y., Nadel, B., Diehn, M., Roulland, S., Alizadeh, A. A. 2023


    Follicular lymphomas (FL) are characterized by BCL2 translocations, often detectable in blood years before FL diagnosis, but also observed in aging healthy individuals suggesting additional lesions are required for lymphomagenesis. We directly characterized early cooperating mutations by ultra-deep sequencing of pre-diagnostic blood and tissue specimens from 48 subjects who ultimately developed FL. Strikingly, CREBBP lysine acetyltransferase (KAT) domain mutations were the most commonly observed precursor lesions, and largely distinguished patients developing FL (14/48, 29%) from healthy adults with or without detected BCL2 rearrangements (0/13, p=0.03 and 0/20, p=0.007, respectively). CREBBP variants were detectable a median of 5.8 years before FL diagnosis, were clonally selected in FL tumors, and appeared restricted to the committed B-cell lineage. These results suggest that mutations affecting the CREBBP KAT domain are common lesions in FL cancer precursor cells (CPC), with potential for discriminating subjects at risk of developing FL or monitoring residual disease.

    View details for DOI 10.1158/2159-8290.CD-23-0111

    View details for PubMedID 36939219

  • Opioid usage in lumbar disc herniation patients with nonsurgical, early, and late surgical treatments. World neurosurgery Zhou, Z., Jin, M. C., Jensen, M. R., Barros Guinle, M. I., Ren, A., Agarwal, A. A., Leaston, J., Ratliff, J. K. 2023


    Assess opioid usage in surgical and non-surgical patients with lumbar disc herniation receiving different treatment approaches and timing.Individuals with newly diagnosed lumbar intervertebral disc without myelopathy were queried from Optum Clinformatics DataMart. Patients were categorized into 3 cohorts: nonsurgical, early surgery, and late surgery. Early surgery cohort patients had surgery within 30-days post-diagnosis; late surgery cohort patients had surgery after 30 days but before 1-year post-diagnosis. The index date was defined as the diagnosis date for nonsurgical patients, and the initial surgery date for surgical patients. The primary outcome was the average daily opioid morphine milligram equivalent (MME) prescribed. Additional outcomes included the percentage of opioid-using patients and cumulative opioid burden.A total of 573,082 patients met inclusion criteria: 533,226 patients received nonsurgical treatments, 22,312 patients received early surgery, and 17,544 patients received late surgery. Both surgical cohorts experienced a "post-surgical hump" of opioid usage, which then sharply declined and gradually plateaued, with daily opioid MME consistently lower in the early as opposed to late surgery cohort. The early surgery cohort also consistently had a lower prevalence of opioid-using patients than the late surgery cohort. Patients receiving nonsurgical demonstrated the highest one-year post-index cumulative opioid burden, and the early surgery cohort consistently had lower cumulative opioid MME than the late surgery cohort.Early surgery in lumbar disc herniation patients is associated with lower long-term average daily MME, incidence of opioid use, and one-year cumulative MME burden compared to nonsurgical and late surgery treatment approaches.

    View details for DOI 10.1016/j.wneu.2023.02.029

    View details for PubMedID 36775237

  • Determinants of resistance to engineered T cell therapies targeting CD19 in large B cell lymphomas. Cancer cell Sworder, B. J., Kurtz, D. M., Alig, S. K., Frank, M. J., Shukla, N., Garofalo, A., Macaulay, C. W., Shahrokh Esfahani, M., Olsen, M. N., Hamilton, J., Hosoya, H., Hamilton, M., Spiegel, J. Y., Baird, J. H., Sugio, T., Carleton, M., Craig, A. F., Younes, S. F., Sahaf, B., Sheybani, N. D., Schroers-Martin, J. G., Liu, C. L., Oak, J. S., Jin, M. C., Beygi, S., Hüttmann, A., Hanoun, C., Dührsen, U., Westin, J. R., Khodadoust, M. S., Natkunam, Y., Majzner, R. G., Mackall, C. L., Diehn, M., Miklos, D. B., Alizadeh, A. A. 2022


    Most relapsed/refractory large B cell lymphoma (r/rLBCL) patients receiving anti-CD19 chimeric antigen receptor (CAR19) T cells relapse. To characterize determinants of resistance, we profiled over 700 longitudinal specimens from two independent cohorts (n = 65 and n = 73) of r/rLBCL patients treated with axicabtagene ciloleucel. A method for simultaneous profiling of circulating tumor DNA (ctDNA), cell-free CAR19 (cfCAR19) retroviral fragments, and cell-free T cell receptor rearrangements (cfTCR) enabled integration of tumor and both engineered and non-engineered T cell effector-mediated factors for assessing treatment failure and predicting outcomes. Alterations in multiple classes of genes are associated with resistance, including B cell identity (PAX5 and IRF8), immune checkpoints (CD274), and those affecting the microenvironment (TMEM30A). Somatic tumor alterations affect CAR19 therapy at multiple levels, including CAR19 T cell expansion, persistence, and tumor microenvironment. Further, CAR19 T cells play a reciprocal role in shaping tumor genotype and phenotype. We envision these findings will facilitate improved chimeric antigen receptor (CAR) T cells and personalized therapeutic approaches.

    View details for DOI 10.1016/j.ccell.2022.12.005

    View details for PubMedID 36584673

  • Circulating Tumor DNA Profiling for Detection, Risk Stratification, and Classification of Brain Lymphomas. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Mutter, J. A., Alig, S. K., Esfahani, M. S., Lauer, E. M., Mitschke, J., Kurtz, D. M., Kühn, J., Bleul, S., Olsen, M., Liu, C. L., Jin, M. C., Macaulay, C. W., Neidert, N., Volk, T., Eisenblaetter, M., Rauer, S., Heiland, D. H., Finke, J., Duyster, J., Wehrle, J., Prinz, M., Illerhaus, G., Reinacher, P. C., Schorb, E., Diehn, M., Alizadeh, A. A., Scherer, F. 2022: JCO2200826


    Clinical outcomes of patients with CNS lymphomas (CNSLs) are remarkably heterogeneous, yet identification of patients at high risk for treatment failure is challenging. Furthermore, CNSL diagnosis often remains unconfirmed because of contraindications for invasive stereotactic biopsies. Therefore, improved biomarkers are needed to better stratify patients into risk groups, predict treatment response, and noninvasively identify CNSL.We explored the value of circulating tumor DNA (ctDNA) for early outcome prediction, measurable residual disease monitoring, and surgery-free CNSL identification by applying ultrasensitive targeted next-generation sequencing to a total of 306 tumor, plasma, and CSF specimens from 136 patients with brain cancers, including 92 patients with CNSL.Before therapy, ctDNA was detectable in 78% of plasma and 100% of CSF samples. Patients with positive ctDNA in pretreatment plasma had significantly shorter progression-free survival (PFS, P < .0001, log-rank test) and overall survival (OS, P = .0001, log-rank test). In multivariate analyses including established clinical and radiographic risk factors, pretreatment plasma ctDNA concentrations were independently prognostic of clinical outcomes (PFS HR, 1.4; 95% CI, 1.0 to 1.9; P = .03; OS HR, 1.6; 95% CI, 1.1 to 2.2; P = .006). Moreover, measurable residual disease detection by plasma ctDNA monitoring during treatment identified patients with particularly poor prognosis following curative-intent immunochemotherapy (PFS, P = .0002; OS, P = .004, log-rank test). Finally, we developed a proof-of-principle machine learning approach for biopsy-free CNSL identification from ctDNA, showing sensitivities of 59% (CSF) and 25% (plasma) with high positive predictive value.We demonstrate robust and ultrasensitive detection of ctDNA at various disease milestones in CNSL. Our findings highlight the role of ctDNA as a noninvasive biomarker and its potential value for personalized risk stratification and treatment guidance in patients with CNSL.

    View details for DOI 10.1200/JCO.22.00826

    View details for PubMedID 36542815

  • Determinants of Resistance to Engineered T-Cell Therapies Targeting CD19 in Large B-Cell Lymphomas Sworder, B., Kurtz, D. M., Alig, S. K., Frank, M. J., Shukla, N. D., Garofalo, A., Macaulay, C., Esfahani, M., Olsen, M., Hamilton, J., Hosoya, H., Hamilton, M. P., Spiegel, J. Y., Baird, J. H., Carleton, M., Craig, A. M., Younes, S. F., Sahaf, B., Sheybani, N., Schroers-Martin, J., Liu, C., Oak, J. S., Jin, M. C., Beygi, S., Huttmann, A., Hanoun, C., Duhrsen, U., Westin, J., Khodadoust, M. S., Natkunam, Y., Majzner, R. G., Mackall, C. L., Diehn, M., Miklos, D. B., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2022: 1301-1303
  • Accurate Detection of Clinically Actionable Copy Number Variants in Diverse Hematological Neoplasms By Routine Targeted Sequencing: A Comparative Performance Study Mosquera, A., Hosoya, H., Jin, M. C., Esfahani, M., Schroers-Martin, J., Sworder, B., Liu, C., Spiteri, E., Natkunam, Y., Zehnder, J. L., Stehr, H., Kurtz, D. M., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2022: 10712-10713
  • Distinct Molecular Subtypes of Classic Hodgkin Lymphoma Identified By Comprehensive Noninvasive Profiling Alig, S. K., Esfahani, M., Li, M. Y., Adams, R., Garofalo, A., Jin, M. C., Olsen, M., Telenius, A., Sworder, B., Schroers-Martin, J., King, D. A., Rossi, C., Schultz, A., Kathuria, K. R., Liu, C., Spina, V., Buedts, L., Flerlage, J. E., Castellino, S. M., Advani, R. H., Rossi, D., Lynch, R. C., Casasnovas, O., Kurtz, D. M., Marks, L. J., Link, M. P., Andre, M., Vandenberghe, P., Steidl, C., Diehn, M., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2022: 1295-1296
  • 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


    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

  • Increased utilization of healthcare services in children with craniosynostosis. Journal of neurosurgery. Pediatrics Ruiz Colón, G. D., Jin, M. C., Grant, G. A., Prolo, L. M. 2022: 1-8


    Craniosynostosis is characterized by the premature fusion of at least one cranial suture. Although evidence suggests that patients with both syndromic and nonsyndromic craniosynostosis may benefit from developmental, behavioral, and mental health support, data on utilization of healthcare services are lacking. In this study the authors compared utilization of mental health care, rehabilitation therapies, and other specialty medical services among children with craniosynostosis, children with plagiocephaly, and healthy controls.The Optum Clinformatics Data Mart database was queried to identify 1340 patients with craniosynostosis, of whom 200 had syndromic craniosynostosis. Long-term utilization of mental health care, rehabilitation therapies, and other medical services up to the age of 6 years was calculated. Rates of utilization were compared to healthy controls (n = 1577) and children with plagiocephaly (n = 1249).Patients with syndromic and nonsyndromic craniosynostosis used mental health care, occupational therapy, speech-language pathology, and other medical services at similar rates (p = 0.1198, p > 0.9999, p = 0.1097, and p = 0.8119, respectively). Mental health services were used more frequently by patients with craniosynostosis (11.0% in patients with syndromic craniosynostosis and 7.5% in those with nonsyndromic craniosynostosis) compared to patients in the plagiocephaly (5.0%, p = 0.0020) and healthy control (2.9%, p < 0.0001) cohorts. Rehabilitation therapies were more frequently used by patients with syndromic craniosynostosis and plagiocephaly (16.0% and 14.1%, respectively), which was significantly higher than use by healthy controls (p < 0.0001). Other medical subspecialty services (developmental pediatrics, ophthalmology, optometry, and audiology) were used by 37.0% of patients with craniosynostosis, compared with 20.9% (p < 0.0001) and 15.1% (p < 0.0001) of patients with plagiocephaly and healthy controls, respectively. Among patients with craniosynostosis, utilization did not differ by race or household income, but it was not uniform by age. Whereas ophthalmology utilization did not differ by age (p = 0.1003), mental health care was most commonly used among older children (p = 0.0107).In this study, the authors demonstrate that rates of utilization of mental health care, rehabilitation therapies, and other medical subspecialty services are similar between patients with syndromic and those with nonsyndromic craniosynostosis, but higher than in healthy controls. Although surgical correction may be considered an isolated event, providers and parents need to monitor all children with craniosynostosis-syndromic and nonsyndromic-for developmental and mental health support longitudinally. Future work should explore risk factors driving utilization, including suture involvement, repair type, and comorbidities.

    View details for DOI 10.3171/2022.2.PEDS2253

    View details for PubMedID 35426826

  • Development of an Integrated Risk Scale for Prediction of Shunt Placement After Neonatal Intraventricular Hemorrhage Jin, M. C., Parker, J. J., Rodrigues, A., Colon, G. R., Garcia, C. A., Mahaney, K. B., Grant, G. A., Prolo, L. M. OXFORD UNIV PRESS INC. 2022: 37-38
  • Circulating tumor DNA in head and neck cancer: Early successes and future promise. Cancer Soo, J., Jin, M. C., Beadle, B. M., Holsinger, F. C., Finegersh, A. 2022


    LAY SUMMARY: The genetic components (DNA) of human papillomavirus-related throat cancer (in the oropharynx) might be measured after surgery to help to predict whether treatment has been successful.

    View details for DOI 10.1002/cncr.34189

    View details for PubMedID 35298053

  • Use of Polysomnography and CPAP in Children Who Received Adenotonsillectomy, US 2004 to 2018. The Laryngoscope Qian, Z. J., Howard, J. M., Cohen, S. M., Jin, M. C., Bhargava, S., Cheng, A. G., Valdez, T. A. 2022


    OBJECTIVES: 1) To determine the prevalence polysomnogram (PSG) and continuous positive airway pressure (CPAP) therapy use in children who received adenotonsillectomy (AT) for sleep symptoms. 2) To identify health care disparities in these regards.STUDY DESIGN: Retrospective database analysis.METHODS: This study used data from Optum (Health Services Innovation Company) to identify 92,490 children who received AT for sleep symptoms between 2004 and 2018. Prevalence of preoperative PSG and postoperative PSG and CPAP were described. Clinical and demographic characteristics were compared between children who had preoperative PSG and those who did not. Characteristics of children with trisomy 21 (T21) were compared to assess PSG and CPAP use in a high-risk cohort. Predictive modeling was used to identify patient characteristics associated with postoperative PSG and CPAP use.RESULTS: Preoperative PSG was obtained in 5.5% of children overall and 33.2% of children with T21. Male sex, obesity, other medical comorbidities, non-White race/ethnicity, and higher parent education were associated with preoperative PSG. Fewer than 3% of children received postoperative PSGs and approximately 3% went on to receive CPAP therapy postoperatively. Multiple logistic regression showed that age at surgery, male sex, obesity, other medical comorbidities, non-White race/ethnicity, and higher parent education were associated with postoperative PSG and CPAP use.CONCLUSIONS AND RELEVANCE: This study described the prevalence pre-AT PSG use and post-AT PSG and CPAP use for persistent symptoms and identified sleep health care disparities in these regards. These results show that increased, equitable access to PSG is needed in children, particularly in the workup and treatment persistent symptoms after AT.LEVEL OF EVIDENCE: 4 Laryngoscope, 2022.

    View details for DOI 10.1002/lary.30103

    View details for PubMedID 35285524

  • Racial Disparities in Surgical Treatment of Obstructive Sleep Apnea. OTO open Cohen, S. M., Howard, J. J., Jin, M. C., Qian, J., Capasso, R. 2022; 6 (1): 2473974X221088870


    Objective: Determine risk factors for failure to receive surgical treatment among patients with obstructive sleep apnea.Study Design: Population-based observational longitudinal cohort study.Setting: Population-based database.Methods: Multivariate analysis of 500,792 individuals with obstructive sleep apnea from Optum's deidentified Clinformatics Data Mart database (2004-2018).Results: Black race, increased age, diabetes, atrial fibrillation, obesity, and congestive heart failure were independently associated with a decreased rate of surgery for obstructive sleep apnea. Asian race, hypertension, arrhythmias other than atrial fibrillation, pulmonary disease, and liver disease were independently associated with an increased rate of surgery for obstructive sleep apnea.Conclusion: Racial disparities in health outcomes related to health care access and in economic resources have an enormous impact on public health and social equity. We found differences in rates of surgery for obstructive sleep apnea based on race. These data are consistent with others demonstrating disparities in medical treatment of sleep apnea with positive pressure and underline a need for a change in awareness and treatment in these populations.

    View details for DOI 10.1177/2473974X221088870

    View details for PubMedID 35321423

  • 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


    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

  • Incorporating patient-centered quality-of-life measures for outcome assessment after Chiari malformation type I decompression in a pediatric population: a pilot study. Journal of neurosurgery. Pediatrics Savchuk, S., Jin, M. C., Choi, S., Kim, L. H., Quon, J. L., Bet, A., Prolo, L. M., Hong, D. S., Mahaney, K. B., Grant, G. A. 2021: 1-8


    OBJECTIVE: Optimal management of pediatric Chiari malformation type I (CM-I) is much debated, chiefly due to the lack of validated tools for outcome assessment, with very few tools incorporating patient-centered measures of health-related quality of life (HRQOL). Although posterior fossa decompression (PFD) benefits a subset of patients, prediction of its impact across patients is challenging. The primary aim of this study was to investigate the role of patient-centered HRQOL measures in the assessment and prediction of outcomes after PFD.METHODS: The authors collected HRQOL data from a cohort of 20 pediatric CM-I patients before and after PFD. The surveys included assessments of selected Patient-Reported Outcomes Measurement Information System (PROMIS) health domains and were used to generate the PROMIS preference (PROPr) score, which is a measure of HRQOL. PROMIS is a reliable standardized measure of HRQOL domains such as pain, fatigue, depression, and physical function, which are all relevant to CM-I. The authors then compared the PROPr scores with Chicago Chiari Outcome Scale (CCOS) scores derived from time-matched clinical documentation. Finally, the authors used the PROPr scores as an outcome measure to predict postsurgical HRQOL improvement at 1 year on the basis of patient demographic characteristics, comorbidities, and radiological and physical findings. The Wilcoxon signed-rank test, Mann-Whitney U-test, and Kendall's correlation were used for statistical analysis.RESULTS: Aggregate analysis revealed improvement of pain severity after PFD (p = 0.007) in anatomical patterns characteristic of CM-I. Most PROMIS domain scores trended toward improvement after surgery, with anxiety and pain interference reaching statistical significance (p < 0.002 and p < 0.03, respectively). PROPr scores also significantly improved after PFD (p < 0.008). Of the baseline patient characteristics, preexisting scoliosis was the most accurate negative predictor of HRQOL improvement after PFD (median -0.095 vs 0.106, p < 0.001). A correlation with modest magnitude (Kendall's tau range 0.19-0.47) was detected between the patient-centered measures and CCOS score.CONCLUSIONS: The authors observed moderate improvement of HRQOL, when measured using a modified panel of PROMIS question banks, in this pilot cohort of pediatric CM-I patients after PFD. Further investigations are necessary to validate this tool for children with CM-I and to determine whether these scores correlate with clinical and radiographic findings.

    View details for DOI 10.3171/2021.8.PEDS21228

    View details for PubMedID 34715646

  • Circulating tumor DNA profiling for noninvasive detection, classification, and risk stratification of patients with CNS lymphomas Mutter, J. A., Alig, S., Lauer, E. M., Esfahani, M. S., Mitschke, J., Kurtz, D. M., Olsen, M., Liu, C. L., Jin, M. C., Bleul, S., Macaulay, C. W., Neidert, N. N., Heiland, D. H., Finke, J., Duyster, J., Wehrle, J., Prinz, M., Illerhaus, G., Reinacher, P. C., Schorb, E., Diehn, M., Alizadeh, A. A., Scherer, F. KARGER. 2021: 90
  • Enhanced detection of minimal residual disease by targeted sequencing of phased variants in circulating tumor DNA. Nature biotechnology Kurtz, D. M., Soo, J., Co Ting Keh, L., Alig, S., Chabon, J. J., Sworder, B. J., Schultz, A., Jin, M. C., Scherer, F., Garofalo, A., Macaulay, C. W., Hamilton, E. G., Chen, B., Olsen, M., Schroers-Martin, J. G., Craig, A. F., Moding, E. J., Esfahani, M. S., Liu, C. L., Duhrsen, U., Huttmann, A., Casasnovas, R., Westin, J. R., Roschewski, M., Wilson, W. H., Gaidano, G., Rossi, D., Diehn, M., Alizadeh, A. A. 2021


    Circulating tumor-derived DNA (ctDNA) is an emerging biomarker for many cancers, but the limited sensitivity of current detection methods reduces its utility for diagnosing minimal residual disease. Here we describe phased variant enrichment and detection sequencing (PhasED-seq), a method that uses multiple somatic mutations in individual DNA fragments to improve the sensitivity of ctDNA detection. Leveraging whole-genome sequences from 2,538 tumors, we identify phased variants and their associations with mutational signatures. We show that even without molecular barcodes, the limits of detection of PhasED-seq outperform prior methods, including duplex barcoding, allowing ctDNA detection in the ppm range in participant samples. We profiled 678 specimens from 213 participants with B cell lymphomas, including serial cell-free DNA samples before and during therapy for diffuse large B cell lymphoma. In participants with undetectable ctDNA after two cycles of therapy using a next-generation sequencing-based approach termed cancer personalized profiling by deep sequencing, an additional 25% have ctDNA detectable by PhasED-seq and have worse outcomes. Finally, we demonstrate the application of PhasED-seq to solid tumors.

    View details for DOI 10.1038/s41587-021-00981-w

    View details for PubMedID 34294911

  • 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


    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

  • Phased variants improve DLBCL minimal residual disease detection at the end of therapy. Kurtz, D., Chabon, J. J., Soo, J., Keh, L., Alig, S., Schultz, A., Jin, M. C., Scherer, F., Craig, A. M., Liu, C., Duehrsen, U., Huettmann, A., Casasnovas, R., Westin, J., Roschewski, M. J., Wilson, W., Gaidano, G., Rossi, D., Diehn, M., Alizadeh, A. A. LIPPINCOTT WILLIAMS & WILKINS. 2021
  • National Trends in Opioid Prescriptions Following Outpatient Otologic Surgery, 2005-2017. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Cooperman, S. P., Jin, M. C., Qian, Z. J., Alyono, J. C. 2021: 194599821994755


    OBJECTIVE: To describe opioid stewardship in ambulatory otologic surgery from 2005 to 2017.STUDY DESIGN: Descriptive study of US private insurance claims.SETTING: Nationwide deidentified private insurance claims database (Clinformatics DataMart; Optum).METHODS: A total of 17,431 adult opioid-naive outpatients were included in the study. Patients were identified from CPT-4 codes (Current Procedural Terminology, Fourth Edition) as having undergone middle ear or mastoid surgery. Multiple regression was used to determine sociodemographic and geographic predictors of postoperative morphine milligram equivalents (MMEs) prescribed, including procedure type, year of procedure, age, sex, education, income level, and geographic region of the United States.RESULTS: The mean prescribed perioperative dose over the examined period was 203.03 MMEs (95% CI, 200.27-205.79; 5-mg hydrocodone pill equivalents, 40.61). In multivariate analysis, patients undergoing mastoid surgery were prescribed more opioids than those undergoing middle ear surgery (mean difference, 39.89 MME [95% CI, 34.37-45.41], P < .01; 5-mg hydrocodone pill equivalents, 8.0). Men were prescribed higher doses than women (mean difference, 15.39 [95% CI, 9.87-20.90], P < .01; 5-mg hydrocodone pill equivalents, 3.1). Overall MMEs prescribed by year demonstrates a sharp drop in MMEs from 2015 to 2017.CONCLUSION: While the amount of opioids prescribed perioperatively has declined in recent years, otologists should continue to be cognizant of potential overprescribing in light of previous studies of patients' relatively low opioid intake.

    View details for DOI 10.1177/0194599821994755

    View details for PubMedID 33618561

  • Stage I-II diffuse large B-cell lymphoma treated with rituximab and chemotherapy with or without radiotherapy. Leukemia & lymphoma Binkley, M. S., Hiniker, S. M., Younes, S., Yoo, C., Wignarajah, A., Jin, M., Guo, H. H., Gupta, N. K., Natkunam, Y., Advani, R. H., Hoppe, R. T. 2021: 1–15


    We set to identify prognostic factors in a retrospective cohort of consecutive patients with stage I-II diffuse large B-cell lymphoma treated with rituximab-chemotherapy with or without radiotherapy from 2001 through 2017 at our institution. We identified 143 patients with median follow-up of 7.7years. The majority were male (59.4%), had stage II (53.1%), had stage-modified IPI 0-1 (smIPI, 58.1%), and had non-bulky disease (<7cm, 68.5%). 99 patients (69.2%) received rituximab-chemotherapy followed by radiotherapy, and 44 patients (30.8%) received rituximab-chemotherapy alone. The 5-year progression-free survival (PFS) and overall survival (OS) were 81.2% and 88.9%, respectively. The 5-year PFS for those with smIPI 0-1 versus 2-4 was 89.5% versus 69.7%, respectively (P=0.005). Bulky disease (≥7cm) was associated with worse PFS and OS on univariable and multivariable analyses (P<0.05). Patients with smIPI 0-1 without bulky disease have excellent outcomes. However, patients with smIPI 2-4 or bulky disease have a high risk of progression.

    View details for DOI 10.1080/10428194.2021.1876859

    View details for PubMedID 33622155

  • Intraoperative Neuromonitoring for Cerebral Arteriovenous Malformation Embolization: A Propensity-Score Matched Retrospective Database Study. Cureus Feng, A. Y., Sussman, E. S., Jin, M. C., Wong, S., Lopez, J., Pulli, B., Heit, J. J., Telischak, N. 2021; 13 (1): e12946


    Introduction The treatment of cerebral arteriovenous malformations (AVMs) may result in neurologic morbidity, particularly when an AVM is located in or adjacent to eloquent brain regions. Intraoperative neurophysiologic monitoring (IONM) may be utilized to reduce the risk of iatrogenic injury during endovascular AVM embolization; however, IONM for endovascular AVM embolization is not ubiquitously the standard of care. Methods Admissions for AVM embolization were assessed from the IBM MarketScan Commercial and Medicare Supplemental databases (IBM Watson Health, Somers, NY). Inclusion criterion for patients was continuous enrollment six months before and after the index encounter. The use of IONM and presence of intracranial hemorrhage (ICH) were noted. Propensity-score matched cohorts with and without IONM were generated to minimize bias between treatment groups (adjusting for age, sex, and comorbidities). Results From 2007 to 2016, there were 16,279 patients diagnosed with cerebral AVM in the MarketScan database. Embolized patients were stratified into IONM and non-IONM cohorts; there were 357 patients in the IONM cohort and 1775 patients in the non-IONM cohort. Provider types were significantly different between cohorts (p<0.005). Unruptured AVMs were significantly more likely to be embolized with adjunctive IONM (17.7%) compared to ruptured AVMs (7.9%) (p<0.005). After balancing for baseline comorbidities, there were 266 patients in the IONM cohort, and 1347 patients in the non-IONM cohort. Among unruptured AVM patients, IONM was linked to a significantly shorter length of stay (2.72 versus 4.92 days; p<0.005), significantly lower rates of complications within 30 days of discharge (0.00% versus 1.88%; p=0.038), and significantly lower total payment ($40,179 versus $50,844; p<0.0001). Conclusion Endovascular embolization for unruptured AVMs performed with adjunctive IONM was associated with shorter length of stay, lower complication rates, and hospitalization costs.

    View details for DOI 10.7759/cureus.12946

    View details for PubMedID 33654622

  • CSF Otorrhea: A Rare Presentation of Spinal Myxopapillary Ependymoma. Neuro-Chirurgie Feng, A. Y., Jin, M. C., Wong, S., Pendharkar, A. V., Ho, A. L., Efron, A. D. 2021

    View details for DOI 10.1016/j.neuchi.2021.01.006

    View details for PubMedID 33485885

  • An Analysis of Public Interest in Elective Neurosurgical Procedures during the COVID-19 Pandemic through Online Search Engine Trends. World neurosurgery Feng, A. Y., Garcia, C. A., Jin, M. C., Ho, A. L., Li, G. n., Grant, G. n., Ratliff, J. n., Skirboll, S. L. 2021


    In the wake of the COVID-19 pandemic, the Centers for Medicare & Medicaid Services (CMS) has recommended the temporary cessation of all elective surgeries. The effects on patients' interest of elective neurosurgical procedures are currently unexplored.Using Google Trends (GT), search terms of seven different neurosurgical procedure categories (Trauma, Spine, Tumor, Movement Disorder, Epilepsy, Endovascular, and Miscellaneous) were assessed in terms of relative search volume (RSV) between January 2015 and September 2020. Analyses of search terms were performed for over the short-term (Feb 18th, 2020-Apr 18th, 2020), intermediate-term (Jan 1st, 2020-May 31st, 2020) and long-term (Jan 2015-Sept 2020). State-level interest during phase I re-opening (Apr 28th, 2020-May 31st, 2020) was also evaluated.In the short-term, RSV of four categories (epilepsy, movement disorder, spine, and tumor) were significantly lower in the post-CMS announcement period. In the intermediate-term, RSV of five categories (miscellaneous, epilepsy, movement disorder, spine, and tumor) were significantly lower in the post-CMS announcement period. In the long-term, RSV of nearly all categories (endovascular, epilepsy, miscellaneous, movement disorder, spine, and tumor) were significantly lower in the post-CMS announcement period. Only the movement disorder procedure category had significantly higher RSV in states that reopened early.With the recommendation for cessation of elective surgeries, patient interest in overall elective neurosurgical procedures have dropped significantly. With gradual reopening, there has been a resurgence in some procedure types. GT has proven to be a useful tracker of patient interest and may be utilized by neurosurgical departments to facilitate outreach strategies.

    View details for DOI 10.1016/j.wneu.2020.12.143

    View details for PubMedID 33412316

  • Acetazolamide-Challenged Arterial Spin Labeling Detects Augmented Cerebrovascular Reserve After Surgery for Moyamoya Stroke Rao, V. L., et al 2021
  • 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


    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

  • 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


    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

  • Management of brain tumors presenting in pregnancy: a case series and systematic review Management of brain tumors presenting in pregnancy: a case series and systematic review Rodrigues, A. 2021; 3 (1)
  • 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
  • Short Diagnosis-to-Treatment Interval Is Associated With Higher Circulating Tumor DNA Levels in Diffuse Large B-Cell Lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Alig, S. n., Macaulay, C. W., Kurtz, D. M., Dührsen, U. n., Hüttmann, A. n., Schmitz, C. n., Jin, M. C., Sworder, B. J., Garofalo, A. n., Shahrokh Esfahani, M. n., Nabet, B. Y., Soo, J. n., Scherer, F. n., Craig, A. F., Casasnovas, O. n., Westin, J. R., Gaidano, G. n., Rossi, D. n., Roschewski, M. n., Wilson, W. H., Meignan, M. n., Diehn, M. n., Alizadeh, A. A. 2021: JCO2002573


    Patients with Diffuse Large B-cell Lymphoma (DLBCL) in need of immediate therapy are largely under-represented in clinical trials. The diagnosis-to-treatment interval (DTI) has recently been described as a metric to quantify such patient selection bias, with short DTI being associated with adverse risk factors and inferior outcomes. Here, we characterized the relationships between DTI, circulating tumor DNA (ctDNA), conventional risk factors, and clinical outcomes, with the goal of defining objective disease metrics contributing to selection bias.We evaluated pretreatment ctDNA levels in 267 patients with DLBCL treated across multiple centers in Europe and the United States using Cancer Personalized Profiling by Deep Sequencing. Pretreatment ctDNA levels were correlated with DTI, total metabolic tumor volumes (TMTVs), the International Prognostic Index (IPI), and outcome.Short DTI was associated with advanced-stage disease (P < .001) and higher IPI (P < .001). We also found an inverse correlation between DTI and TMTV (RS= -0.37; P < .001). Similarly, pretreatment ctDNA levels were significantly associated with stage, IPI, and TMTV (all P < .001), demonstrating that both DTI and ctDNA reflect disease burden. Notably, patients with shorter DTI had higher pretreatment ctDNA levels (P < .001). Pretreatment ctDNA levels predicted short DTI independent of the IPI (P < .001). Although each risk factor was significantly associated with event-free survival in univariable analysis, ctDNA level was prognostic of event-free survival independent of DTI and IPI in multivariable Cox regression (ctDNA: hazard ratio, 1.5; 95% CI [1.2 to 2.0]; IPI: 1.1 [0.9 to 1.3]; -DTI: 1.1 [1.0 to 1.2]).Short DTI largely reflects baseline tumor burden, which can be objectively measured using pretreatment ctDNA levels. Pretreatment ctDNA levels therefore have utility for quantifying and guarding against selection biases in prospective DLBCL clinical trials.

    View details for DOI 10.1200/JCO.20.02573

    View details for PubMedID 33909455

  • Facial Nerve Paralysis Following Endovascular Embolization: A Case Report and Review of the Literature. The Annals of otology, rhinology, and laryngology Feng, A. Y., Jin, M. C., Wong, S., Pepper, J., Jackler, R., Vaisbuch, Y. 2020: 3489420966611


    OBJECTIVE: We report a case of facial nerve paralysis post-endovascular embolization of a sigmoid sinus dural arterio-venous fistula from initial presentation to current management and discuss the merits of observation versus decompression through a systematic review of relevant literature.PATIENT: 61 F with right facial palsy.INTERVENTION: Following a single intravenous dexamethasone injection with oral steroids over 2months, patient was observed with no additional treatment other than Botox chemodenervation and facial rehabilitation.OUTCOME AND RESULTS: The patient initially presented with complete right facial palsy (HB 6/6). Post-op CT imaging indicated Onyx (ev3, Irvine, California, USA) particles present at the geniculate segment of the facial nerve. Observation was chosen over surgical intervention. At the most current follow up of 8months, facial function has improved substantially (HB 2/6).CONCLUSION: Facial palsy is a serious, though rare, complication of transarterial endovascular embolization. With our case report and literature review, we highlight not only how conservative observation is the recommended treatment, but also that facial nerve recovery should be expected to reach near complete recovery, but not sooner than in 3months.

    View details for DOI 10.1177/0003489420966611

    View details for PubMedID 33135423

  • Long-Term Outcomes For Stage I-II Diffuse Large B-Cell Lymphoma Treated With Rituximab And Chemotherapy With Or Without Radiotherapy Binkley, M. S., Hiniker, S. M., Younes, S., Yoo, C., Wignarajah, K., Jin, M., Guo, H. H., Natkunam, Y., Advani, R. H., Hoppe, R. T. ELSEVIER SCIENCE INC. 2020: E758
  • Medical malpractice in spine surgery: a review NEUROSURGICAL FOCUS Medress, Z. A., Jin, M. C., Feng, A., Varshneya, K., Veeravagu, A. 2020; 49 (5): E16


    Medical malpractice is an important but often underappreciated topic within neurosurgery, particularly for surgeons in the early phases of practice. The practice of spinal neurosurgery involves substantial risk for litigation, as both the natural history of the conditions being treated and the operations being performed almost always carry the risk of permanent damage to the spinal cord or nerve roots, a cardiopulmonary event, death, or other dire outcomes. In this review, the authors discuss important topics related to medical malpractice in spine surgery, including tort reform, trends and frequency of litigation claims in spine surgery, wrong-level and wrong-site surgery, catastrophic outcomes including spinal cord injury and death, and ethical considerations.

    View details for DOI 10.3171/2020.8.FOCUS20602

    View details for Web of Science ID 000585759900016

    View details for PubMedID 33130625

  • Resection of Olfactory Groove Meningiomas Through Unilateral vs. Bilateral Approaches: A Systematic Review and Meta-Analysis FRONTIERS IN ONCOLOGY Feng, A. Y., Wong, S., Saluja, S., Jin, M. C., Thai, A., Pendharkar, A. V., Ho, A. L., Reddy, P., Efron, A. D. 2020; 10: 560706


    Introduction: Consensus is limited regarding optimal transcranial approaches (TCAs) for the surgical resection of olfactory groove meningiomas (OGMs). This systematic review and meta-analysis aims to examine operative and peri-operative outcomes of unilateral compared to bilateral TCAs for OGMs. Methods: Electronic databases were searched from inception until December 2019 for studies delineating TCAs for OGM patients. Patient demographics, pre-operative symptoms, surgical outcomes, and complications were evaluated and analyzed with a meta-analysis of proportions. Results: A total of 27 observational case series comparing 554 unilateral vs. 451 bilateral TCA patients were eligible for review. The weighted pooled incidence of gross total resection is 94.6% (95% CI, 90.7-97.5%; I2 = 59.0%; p = 0.001) for unilateral and 90.9% (95% CI, 85.6-95.4%; I2 = 58.1%; p = 0.003) for bilateral cohorts. Similarly, the incidence of OGM recurrence is 2.6% (95% CI, 0.4-6.0%; I2 = 53.1%; p = 0.012) and 4.7% (95% CI, 1.4-9.2%; I2 = 55.3%; p = 0.006), respectively. Differences in oncologic outcomes were not found to be statistically significant (p = 0.21 and 0.35, respectively). Statistically significant differences in complication rates in bilateral vs. unilateral TCA cohorts include meningitis (1.0 vs. 0.0%; p = 0.022) and mortality (3.2 vs. 0.2%; p = 0.007). Conclusions: While both cohorts have similar oncologic outcomes, bilateral TCA patients exhibit higher post-operative complication rates. This may be explained by underlying tumor characteristics necessitating more radical resection but may also indicate increased morbidity with bilateral approaches. However, evidence from more controlled, comparative studies is warranted to further support these findings.

    View details for DOI 10.3389/fonc.2020.560706

    View details for Web of Science ID 000585195900001

    View details for PubMedID 33194626

    View details for PubMedCentralID PMC7642686

  • Opioid Prescribing Patterns Following Pediatric Tonsillectomy in the United States, 2009-2017. The Laryngoscope Qian, Z. J., Alyono, J. C., Jin, M. C., Cooperman, S. P., Cheng, A. G., Balakrishnan, K. 2020


    OBJECTIVES: Assess national trends in opioid prescription following pediatric tonsillectomy: 1) overall percentage receiving opioids and mean quantity, 2) changes during 2009-2017, and 3) determinants of prescription patterns.METHODS: Cross-sectional analysis using 2009-2017 Optum claims data to identify opioid-naive children aged 1-18 with claims codes for tonsillectomy (n = 82,842). Quantities of opioids filled in outpatient pharmacies during the perioperative period were extracted and converted into milligram morphine equivalents (MMEs) for statistical comparison. Demographic, clinical, and socioeconomic predictors of opioid fill rate and quantity were determined using regression analyses.RESULTS: In 2009, 83.3% of children received opioids, decreasing to 58.3% by 2017. Rates of all-cause readmissions and post-tonsillectomy hemorrhages were similar over time. Mean quantity received was 153.47MME (95% confidence intervals [95%CI]: 151.19, 155.76) and did not significantly change during 2009-2017. Opioids were more likely in older children and those with higher household income, but less likely in children with obstructive sleep apnea, other comorbidities, and Hispanic race. Higher quantities of opioids were more likely in older children, while lower quantities were associated with female sex, Hispanic race, and higher household income. Outpatient steroids were prescribed to 8.04% of patients, who were less likely to receive opioids.CONCLUSION: While the percentage of children receiving post-tonsillectomy opioids decreased during 2009-2017, prescribed quantities remain high and have not decreased over time. Prescription practices were also influenced by clinical and sociodemographic factors. These results highlight the need for guidance, particularly with regard to opioid quantity, in children after tonsillectomy.LEVEL OF EVIDENCE: N/A Laryngoscope, 2020.

    View details for DOI 10.1002/lary.29159

    View details for PubMedID 33026683

  • Comparison of Parotidectomy With Observation for Treatment of Pleomorphic Adenoma in Adults. JAMA otolaryngology-- head & neck surgery Kligerman, M. P., Jin, M., Ayoub, N., Megwalu, U. C. 2020


    Importance: There is no consensus regarding optimal management of pleomorphic adenoma in adults.Objectives: To compare parotidectomy with observation for the management of pleomorphic adenoma in patients 50 years or older by age.Design and Setting: This decision analytical model was performed from November 21, 2019, to June 15, 2020, using a Markov model. Model variables and ranges were selected based on a literature review. A 1-way sensitivity analysis was performed to evaluate the age threshold at which each algorithm, either upfront elective parotidectomy or observation, would be favored. A Monte Carlo probabilistic sensitivity analysis using variable ranges was then performed 5 times with patients in the model assigned a starting age of 50, 60, 70, 80, and 90 years to assess how age at diagnosis would be associated with the model results.Main Outcomes and Measures: Model outcomes were measured with quality-adjusted life-years (QALYs).Results: In the study models, the age thresholds at which observation became more beneficial than parotidectomy were 88.5 years for patients with superficial lobe tumors (5.37 QALYs in favor of parotidectomy below this age, and 5.37 QALYs in favor of observation above this age) and 83.4 years for patients with deep lobe tumors (7.51 QALYs in favor of surgery below this age, and 7.51 QALYs in favor of observation above this age). There was no significant difference in outcomes between parotidectomy and observation among patients aged 70 to 80 years.Conclusions and Relevance: This study suggests that the outcomes associated with parotidectomy and observation are similar at 70 years or older among patients with pleomorphic adenoma and that observation may be the favorable treatment in that age group.

    View details for DOI 10.1001/jamaoto.2020.2944

    View details for PubMedID 32970111

  • A noninvasive approach for early prediction of therapeutic benefit from immune checkpoint inhibition for lung cancer Nabet, B. Y., Esfahani, M. S., Hamilton, E. G., Chabon, J. J., Moding, E. J., Rizvi, H., Steen, C. B., Chaudhuri, A. A., Liu, C., Hui, A. B., Stehr, H., Goljenola, L., Jin, M. C., Jeon, Y., Tseng, D., Merghoub, T., Neal, J. W., Wakelee, H. A., Padda, S. K., Ramchandran, K. J., Das, M., Bonilla, R. F., Yoo, C., Chen, E. L., Ko, R. B., Newman, A. M., Hellmann, M. D., Alizadeh, A. A., Diehn, M. AMER ASSOC CANCER RESEARCH. 2020
  • Chromatin accessibility patterns in cell-free DNA reveal tumor heterogeneity Esfahani, M., Mehrmohamadi, M., Steen, C. B., Hamilton, E. G., King, D. A., Soo, J., Macaulay, C., Jin, M., Kurtz, D. M., Nabet, B., Moding, E., Chabon, J., Newman, A., Diehn, M., Alizadeh, A. A. AMER ASSOC CANCER RESEARCH. 2020
  • Neurological adverse effects due to programmed death 1 (PD-1) inhibitors. Journal of neuro-oncology Shi, S., Jaoube, J. A., Kanwar, R., Jin, M. C., Amorin, A., Varanasi, V., Eisinger, E., Thomas, R., Moore, J. M. 2020


    PURPOSE: PD-1 Immunotherapy is integral in treating multiple cancers, but has been associated with neurological adverse events (nAEs). Our study was aimed at identifying the clinical spectrum of nAEs associated with pembrolizumab and nivolumab.METHODS: We performed an IRB approved single-center retrospective cohort study on patients receiving either pembrolizumab or nivolumab. Patients that developed nAEs within 12months of treatment were identified. Descriptive statistics were conducted, and differences between groups were analyzed by the Chi-square or t test method.RESULTS: In total, 649 patients were identified. Seventeen patients (2.6%) developed nAEs. Eight of those were on pembrolizumab and nine were on nivolumab. Average age was 62.1years. Ten were males and 7 were females. Most patients had melanoma (6, 35.3%). Patients who developed nAEs more frequently had intracranial lesions at initiation of anti PD-1 therapy compared to those who did not develop nAEs (76.5% vs 27.8%; p-value<0.001). Fifteen patients (88.2%) permanently stopped PD-1 therapy. In 8 patients, treatment termination resolved symptoms attributed to immune checkpoint blockade. The majority of patients developed grade 3 or 4 nAEs (10 patients, 58.8%), and required hospitalization (11 patients, 64.7%). Eight patients died for nAEs referable causes.CONCLUSION: Pembrolizumab and nivolumab are associated with the development of nAEs associated with increased risk of permanent discontinuation of treatment, hospitalization, and death. Melanoma patients might be at a particularly high risk of such side effects. Future studies are still required to better assess which patients benefit most from such therapies, while minimizing the risk of complications.

    View details for DOI 10.1007/s11060-020-03514-8

    View details for PubMedID 32350779

  • Boda Bodas and Road Traffic Injuries in Uganda: An Overview of Traffic Safety Trends from 2009 to 2017. International journal of environmental research and public health Vaca, S. D., Feng, A. Y., Ku, S., Jin, M. C., Kakusa, B. W., Ho, A. L., Zhang, M., Fuller, A., Haglund, M. M., Grant, G. 2020; 17 (6)


    INTRODUCTION: Road traffic injuries (RTIs) are an important contributor to the morbidity and mortality of developing countries. In Uganda, motorcycle taxis, known as boda bodas, are responsible for a growing proportion of RTIs. This study seeks to evaluate and comment on traffic safety trends from the past decade.METHODS: Traffic reports from the Ugandan police force (2009 to 2017) were analyzed for RTI characteristics. Furthermore, one month of casualty ward data in 2015 and 2018 was collected from the Mulago National Referral Hospital and reviewed for casualty demographics and trauma type.RESULTS: RTI motorcycle contribution rose steadily from 2009 to 2017 (24.5% to 33.9%). While the total number of crashes dropped from 22,461 to 13,244 between 2010 and 2017, the proportion of fatal RTIs increased from 14.7% to 22.2%. In the casualty ward, RTIs accounted for a greater proportion of patients and traumas in 2018 compared to 2015 (10%/41% and 36%/64%, respectively).CONCLUSIONS: Although RTIs have seen a gross reduction in Uganda, they have become more deadly, with greater motorcycle involvement. Hospital data demonstrate a rising need for trauma and neurosurgical care to manage greater RTI patient burden. Combining RTI prevention and care pathway improvements may mitigate current RTI trends.

    View details for DOI 10.3390/ijerph17062110

    View details for PubMedID 32235768

  • Circulating tumor DNA in Genetic Profiling and Monitoring of Pediatric Hodgkin Lymphoma Shyam, R., Kurtz, D., Alig, S., Jin, M., Link, M., Marks, L., Alizadeh, A. GEORG THIEME VERLAG KG. 2020: 81
  • Elucidating Incidence and Outcomes of Perioperative Status Epilepticus after Neurosurgical Procedures American Association of Neurological Surgeons Jin, M. C., Zhang, M., Parker, J. J., Ratliff, J. K., Skirboll, S. 2020
  • Stereotactic Radiosurgery for Resected Brain Metastases - Does the Surgical Corridor Need to be Targeted? Practical radiation oncology Shi, S. n., Sandhu, N. n., Jin, M. n., Wang, E. n., Liu, E. n., Jaoude, J. A., Schofield, K. n., Zhang, C. n., Gibbs, I. C., Hancock, S. L., Chang, S. D., Li, G. n., Gephart, M. H., Pollom, E. L., Soltys, S. G. 2020


    Although consensus guidelines for post-resection stereotactic radiosurgery (SRS) for brain metastases recommend the surgical corridor leading to the resection cavity be included in the SRS plan, no study has reported patterns of tumor recurrence based on inclusion or exclusion of the corridor as a target. We reviewed tumor control and toxicity outcomes of post-resection SRS for deep brain metastases based on whether or not the surgical corridor was targeted.We retrospectively reviewed patients who had resected brain metastases treated with SRS between 2007 and 2018 and included only 'deep' tumors (defined as located ≥1.0 cm from the pial surface prior to resection).In 66 deep brain metastases in 64 patients, the surgical corridor was targeted in 43 (65%). There were no statistical differences in the cumulative incidences of progression at 12-months for targeting vs. not targeting the corridor, respectively, for: overall local failure 2% (95% Confidence Interval [CI],0-11%) vs. 9% (95% CI,1-25%; p=0.25), corridor failure 0% (95% CI,0-0%) vs. 9% (95% CI,1-25%; p=0.06), cavity failure 2% (95% CI,0-11%) vs. 0% (95% CI,0-0%; p=0.91), adverse radiation effect 5% (95% CI,1-15%) vs. 13% (95% CI,3-30%; p=0.22). Leptomeningeal disease (7% (95% CI,2-18%) vs. 26% (95% CI,10-45%; p=0.03)) was higher in those without the corridor targeted.Omitting the surgical corridor in post-operative SRS for resected brain metastases was not associated with statistically significant differences in corridor or cavity recurrence or adverse radiation effect. As seen in recent prospective trials of post-resection SRS, the dominant pattern of progression is within the resection cavity; omission of the corridor would yield a smaller SRS volume that could allow for dose escalation to potentially improve local cavity control.

    View details for DOI 10.1016/j.prro.2020.04.009

    View details for PubMedID 32428766

  • Dual antiplatelet therapy after carotid artery stenting: trends and outcomes in a large national database. Journal of neurointerventional surgery Sussman, E. S., Jin, M. n., Pendharkar, A. V., Pulli, B. n., Feng, A. n., Heit, J. J., Telischak, N. A. 2020


    While dual antiplatelet therapy (dAPT) is standard of care following carotid artery stenting (CAS), the optimal dAPT regimen and duration has not been established.We canvassed a large national database (IBM MarketScan) to identify patients receiving carotid endarterectomy (CEA) or CAS for treatment of ischemic stroke or carotid artery stenosis from 2007 to 2016. We performed univariable and multivariable regression methods to evaluate the impact of covariates on post-CAS stroke-free survival, including post-discharge antiplatelet therapy.A total of 79 084 patients diagnosed with ischemic stroke or carotid stenosis received CEA (71 178; 90.0%) or CAS (7906; 10.0%). After adjusting for covariates, <180 days prescribed post-CAS P2Y12-inhibition was associated with increased risk for stroke (<90 prescribed days HR=1.421, 95% CI 1.038 to 1.946; 90-179 prescribed days HR=1.484, 95% CI 1.045 to 2.106). The incidence of hemorrhagic complications was higher during the period of prescribed P2Y12-inhibition (1.16% per person-month vs 0.49% per person-month after discontinuation, P<0.001). The rate of extracranial hemorrhage was nearly six-fold higher while on dAPT (6.50% per patient-month vs 1.16% per patient-month, P<0.001), and there was a trend towards higher rate of intracranial hemorrhage that did not reach statistical significance (5.09% per patient-month vs 3.69% per patient-month, P=0.0556). Later hemorrhagic events beyond 30 days post-CAS were significantly more likely to be extracranial (P=0.028).Increased duration of post-CAS dAPT is associated with lower rates of readmissions for stroke, and with increased risk of hemorrhagic complications, particularly extracranial hemorrhage. The potential benefit of prolonging dAPT with regard to ischemic complications must be balanced with the corresponding increased risk of predominantly extracranial hemorrhagic complications.

    View details for DOI 10.1136/neurintsurg-2020-016008

    View details for PubMedID 32414894

  • Liquid biopsy for pediatric diffuse midline glioma: a review of circulating tumor DNA and cerebrospinal fluid tumor DNA. Neurosurgical focus Azad, T. D., Jin, M. C., Bernhardt, L. J., Bettegowda, C. 2020; 48 (1): E9


    Diffuse midline glioma (DMG) is a highly malignant childhood tumor with an exceedingly poor prognosis and limited treatment options. The majority of these tumors harbor somatic mutations in genes encoding histone variants. These recurrent mutations correlate with treatment response and are forming the basis for molecularly guided clinical trials. The ability to detect these mutations, either in circulating tumor DNA (ctDNA) or cerebrospinal fluid tumor DNA (CSF-tDNA), may enable noninvasive molecular profiling and earlier prediction of treatment response. Here, the authors review ctDNA and CSF-tDNA detection methods, detail recent studies that have explored detection of ctDNA and CSF-tDNA in patients with DMG, and discuss the implications of liquid biopsies for patients with DMG.

    View details for DOI 10.3171/2019.9.FOCUS19699

    View details for PubMedID 31896079

  • Opioid Use in Adults with Low Back or Lower Extremity Pain who Undergo Spine Surgical Treatment within One Year of Diagnosis. Spine Fatemi, P. n., Zhang, Y. n., Ho, A. n., Lama, R. n., Jin, M. n., Veeravagu, A. n., Desai, A. n., Ratliff, J. K. 2020


    Retrospective longitudinal cohort.We investigated opioid prescribing patterns amongst adults in the United States diagnosed with low back or lower extremity pain (LBP/LEP) who underwent spine surgery.Opioid-based treatment of LBP/LEP and postsurgical pain have separately been associated with chronic opioid use, but a combined and large-scale cohort study is missing.This study utilizes commercial inpatient, outpatient, and pharmaceutical insurance claims. Between 2008 and 2015, patients without prior prescription opioids with a new diagnosis of LBP/LEP who underwent surgery within one year after diagnosis were enrolled. Opioid prescribing patterns after LBP/LEP diagnosis and after surgery were evaluated. All patients had one-year postoperative follow-up. Low and high frequency (≥6 refills in 12 months) opioid prescription groups were identified.25,506 patients without prior prescription opioids were diagnosed with LBP/LEP and underwent surgery within one year of diagnosis. After LBP/LEP diagnosis, 18,219 (71.4%) were prescribed opioids while 7,287 (28.6%) were not. After surgery, 2,952 (11.6%) were prescribed opioids with high frequency and 22,554 (88.4%) with low frequency. Among patients prescribed opioids prior to surgery, those with high frequency prescriptions were more likely to continue this pattern postoperatively than those with low frequency prescriptions preoperatively (OR:2.15, 95% CI:1.97-2.34). For those prescribed opioids preoperatively, average daily morphine milligram equivalent (MME) decreased after surgery (by 2.62 in decompression alone cohort and 0.25 in arthrodesis cohort, p < 0.001). Postoperative low-frequency patients were more likely than high-frequency patients to discontinue opioids one-year after surgery (OR:3.78, 95% CI:3.59-3.99). Postoperative high-frequency patients incurred higher cost than low-frequency patients. Postoperative high-frequency prescribing varied widely across states (4.3%-20%).A stepwise association exists between opioid use after LEP or LBP diagnosis and frequency and duration of opioid prescriptions after surgery. Simultaneously, the strength of prescriptions as measured by MME decreased following surgery.3.

    View details for DOI 10.1097/BRS.0000000000003663

    View details for PubMedID 32833930

  • Next Generation Sequencing of Cerebrospinal Fluid to Improve Diagnostic Sensitivity, Detect Spatial Heterogeneity, and Predict Outcomes for Advanced Lung Cancer Patients with Leptomeningeal Carcinomatosis American Association of Neurological Surgeons Azad, T. D., Nanjo, S., Chabon, J., Jin, M. C., Connolly, I., Ko, R., Yoo, C., Iv, M., Nagpal, S., Gephart, M., Alizadeh, A. A., Diehn, M. 2020
  • Assessing the Incidence and Burden of Post-Neurosurgical Antidepressant Use in Children Undergoing Surgery for Refractory Seizures American Association of Neurological Surgeons Jin, M. C., Prolo, L. M., Parker, J. J., Gallentine, W., Grant, G. A. 2020
  • Evaluating Surgical Resection Extent and Adjuvant Therapy in the Management of Gliosarcoma American Association of Neurological Surgeons Liu, E. K., Jin, M. C., Shi, S., Gibbs, I., Thomas, R., Recht, L., Soltys, S. G., Pollom, E. L., Chang, S., Gephart, M., Nagpal, S., Li, G. 2020
  • Recurrence of cavernous malformations after surgery in childhood. Journal of neurosurgery. Pediatrics Prolo, L. M., Jin, M. C., Loven, T. n., Vogel, H. n., Edwards, M. S., Steinberg, G. K., Grant, G. A. 2020: 1–10


    Cavernous malformations (CMs) are commonly treated cerebrovascular anomalies in the pediatric population; however, the data on radiographic recurrence of pediatric CMs after surgery are limited. The authors aimed to study the clinical presentation, outcomes, and recurrence rate following surgery for a large cohort of CMs in children.Pediatric patients (≤ 18 years old) who had a CM resected at a single institution were identified and retrospectively reviewed. Fisher's exact test of independence was used to assess differences in categorical variables. Survival curves were evaluated using the Mantel-Cox method.Fifty-three patients aged 3 months to 18 years underwent resection of 74 symptomatic CMs between 1996 and 2018 at a single institution. The median length of follow-up was 5.65 years. Patients most commonly presented with seizures (45.3%, n = 24) and the majority of CMs were cortical (58.0%, n = 43). Acute radiographic hemorrhage was common at presentation (64.2%, n = 34). Forty-two percent (n = 22) of patients presented with multiple CMs, and they were more likely to develop de novo lesions (71%) compared to patients presenting with a single CM (3.4%). Both radiographic hemorrhage and multiple CMs were independently prognostic for a higher risk of the patient requiring subsequent surgery. Fifty percent (n = 6) of the 12 patients with both risk factors required additional surgery within 2.5 years of initial surgery compared to none of the patients with neither risk factor (n = 9).Patients with either acute radiographic hemorrhage or multiple CMs are at higher risk for subsequent surgery and require long-term MRI surveillance. In contrast, patients with a single CM are unlikely to require additional surgery and may require less frequent routine imaging.

    View details for DOI 10.3171/2020.2.PEDS19543

    View details for PubMedID 32357336

  • Patterns of Opioid and Benzodiazepine Use in Opioid-Naive Patients with Newly Diagnosed Low Back and Lower Extremity Pain. Journal of general internal medicine Azad, T. D., Zhang, Y., Stienen, M. N., Vail, D., Bentley, J. P., Ho, A. L., Fatemi, P., Herrick, D., Kim, L. H., Feng, A., Varshneya, K., Jin, M., Veeravagu, A., Bhattacharya, J., Desai, M., Lembke, A., Ratliff, J. K. 2019


    BACKGROUND: The morbidity and mortality associated with opioid and benzodiazepine co-prescription is a pressing national concern. Little is known about patterns of opioid and benzodiazepine use in patients with acute low back pain or lower extremity pain.OBJECTIVE: To characterize patterns of opioid and benzodiazepine prescribing among opioid-naive, newly diagnosed low back pain (LBP) or lower extremity pain (LEP) patients and to investigate the relationship between benzodiazepine prescribing and long-term opioid use.DESIGN/SETTING: We performed a retrospective analysis of a commercial database containing claims for more than 75 million enrollees in the USA.PARTICIPANTS: Participants were adult patients newly diagnosed with LBP or LEP between 2008 and 2015 who did not have a red flag diagnosis, had not received an opioid prescription in the 6months prior to diagnosis, and had 12months of continuous enrollment after diagnosis.MAIN OUTCOMES AND MEASURES: Among patients receiving at least one opioid prescription within 12months of diagnosis, we defined discrete patterns of benzodiazepine prescribing-continued use, new use, stopped use, and never use. We tested the association of these prescription patterns with long-term opioid use, defined as six or more fills within 12months.RESULTS: We identified 2,497,653 opioid-naive patients with newly diagnosed LBP or LEP. Between 2008 and 2015, 31.9% and 11.5% of these patients received opioid and benzodiazepine prescriptions, respectively, within 12months of diagnosis. Rates of opioid prescription decreased from 34.8% in 2008 to 27.0% in 2015 (P<0.001); however, prescribing of benzodiazepines only decreased from 11.6% in 2008 to 10.8% in 2015. Patients with continued or new benzodiazepine use consistently used more opioids than patients who never used or stopped using benzodiazepines during the study period (one-way ANOVA, P<0.001). For patients with continued and new benzodiazepine use, the odds ratio of long-term opioid use compared with those never prescribed a benzodiazepine was 2.99 (95% CI, 2.89-3.08) and 2.68 (95% CI, 2.62-2.75), respectively.LIMITATIONS: This study used administrative claims analyses, which rely on accuracy and completeness of diagnostic, procedural, and prescription codes.CONCLUSION: Overall opioid prescribing for low back pain or lower extremity pain decreased substantially during the study period, indicating a shift in management within the medical community. Rates of benzodiazepine prescribing, however, remained at approximately 11%. Concurrent prescriptions of benzodiazepines and opioids after LBP or LEP diagnosis were associated with increased risk of long-term opioid use.

    View details for DOI 10.1007/s11606-019-05549-8

    View details for PubMedID 31720966

  • Stereotactic Radiosurgery for Resected Brain Metastases: Single-Institutional Experience of over 500 Cavities Shi, S., Sandhu, N., Wang, E. H., Liu, E., Jaoude, J., Jin, M., Schofield, K., Zhang, C., Gibbs, I. C., Hancock, S. L., Chang, S. D., Li, G., Hayden, M., Soltys, S. G., Pollom, E. ELSEVIER SCIENCE INC. 2019: E90
  • Factors Associated with Treatment Failure and Radiation Necrosis Following Cavity Radiosurgery for Resected Brain Metastases Wang, E. H., Shi, S., Sandhu, N., Liu, E., Jin, M., Schofield, K., Zhang, C., Jaoude, J., Gibbs, I. C., Hancock, S. L., Chang, S. D., Li, G., Hayden, M., Soltys, S. G., Pollom, E. ELSEVIER SCIENCE INC. 2019: E92
  • Efficacy and toxicity of particle radiotherapy in WHO grade II and grade III meningiomas: a systematic review. Neurosurgical focus Wu, A., Jin, M. C., Meola, A., Wong, H., Chang, S. D. 2019; 46 (6): E12


    OBJECTIVEAdjuvant radiotherapy has become a common addition to the management of high-grade meningiomas, as immediate treatment with radiation following resection has been associated with significantly improved outcomes. Recent investigations into particle therapy have expanded into the management of high-risk meningiomas. Here, the authors systematically review studies on the efficacy and utility of particle-based radiotherapy in the management of high-grade meningioma.METHODSA literature search was developed by first defining the population, intervention, comparison, outcomes, and study design (PICOS). A search strategy was designed for each of three electronic databases: PubMed, Embase, and Scopus. Data extraction was conducted in accordance with the PRISMA guidelines. Outcomes of interest included local disease control, overall survival, and toxicity, which were compared with historical data on photon-based therapies.RESULTSEleven retrospective studies including 240 patients with atypical (WHO grade II) and anaplastic (WHO grade III) meningioma undergoing particle radiation therapy were identified. Five of the 11 studies included in this systematic review focused specifically on WHO grade II and III meningiomas; the others also included WHO grade I meningioma. Across all of the studies, the median follow-up ranged from 6 to 145 months. Local control rates for high-grade meningiomas ranged from 46.7% to 86% by the last follow-up or at 5 years. Overall survival rates ranged from 0% to 100% with better prognoses for atypical than for malignant meningiomas. Radiation necrosis was the most common adverse effect of treatment, occurring in 3.9% of specified cases.CONCLUSIONSDespite the lack of randomized prospective trials, this review of existing retrospective studies suggests that particle therapy, whether an adjuvant or a stand-alone treatment, confers survival benefit with a relatively low risk for severe treatment-derived toxicity compared to standard photon-based therapy. However, additional controlled studies are needed.

    View details for DOI 10.3171/2019.3.FOCUS1967

    View details for PubMedID 31153145

  • Stereotactic radiosurgery for resected brain metastases: Does the surgical corridor need to be treated? Shi, S., Jaoude, J., Sandhu, N., Wang, E., Schofield, K., Jin, M. C., Zhang, C., Liu, E., Pollom, E. L., Soltys, S. G. AMER SOC CLINICAL ONCOLOGY. 2019
  • Prognostic Value of Circulating Tumor DNA in Diffuse Large B-Cell Lymphoma Reply JOURNAL OF CLINICAL ONCOLOGY Kurtz, D. M., Scherer, F., Jin, M. C., Soo, J., Craig, A. M., Esfahani, M. S., Chabon, J. J., Stehr, H., Liu, C., Tibshirani, R., Maeda, L. S., Gupta, N. K., Khodadoust, M. S., Advani, R. H., Newman, A. M., Duehrsen, U., Huettmann, A., Meignan, M., Casasnovas, O., Westin, J. R., Roschewski, M., Wilson, W. H., Gaidano, G., Rossi, D., Diehn, M., Alizadeh, A. A. 2019; 37 (9): 755-+
  • Reply to J. Wang et al. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Kurtz, D. M., Scherer, F., Jin, M. C., Soo, J., Craig, A. F., Esfahani, M. S., Chabon, J. J., Stehr, H., Liu, C. L., Tibshirani, R., Maeda, L. S., Gupta, N. K., Khodadoust, M. S., Advani, R. H., Newman, A. M., Duhrsen, U., Huttmann, A., Meignan, M., Casasnovas, O., Westin, J. R., Roschewski, M., Wilson, W. H., Gaidano, G., Rossi, D., Diehn, M., Alizadeh, A. A. 2019: JCO1801907

    View details for PubMedID 30753108

  • Short Diagnosis-to-Treatment Interval Is Associated with Higher Levels of Circulating Tumor DNA in Aggressive B-Cell Non-Hodgkin Lymphoma American Society of Hematology Alig, S., Macaulay, C., Kurtz, D. M., Ulrich, D., Andreas, H., Jin, M. C., Sworder, B., Garofalo, A., Esfahani, M. S., Soo, J., Scherer, F., Craig, A., Casasnovas, O., Westin, J. R., Gaidano, G., Rossi, D., Diehn, M., Alizadeh, A. A. 2019
  • Stereotactic radiosurgery for resected brain metastases: single-institutional experience of over 500 cavities. International journal of radiation oncology, biology, physics Shi, S. n., Sandhu, N. n., Jin, M. C., Wang, E. n., Jaoude, J. A., Schofield, K. n., Zhang, C. n., Liu, E. n., Gibbs, I. C., Hancock, S. L., Chang, S. D., Li, G. n., Hayden-Gephart, M. n., Adler, J. R., Soltys, S. G., Pollom, E. L. 2019


    Post-operative stereotactic radiosurgery (SRS) has less detrimental impact on cognition and quality of life compared to whole brain radiotherapy (WBRT) and is increasingly used for resected brain metastases (BMs). Post-operative SRS techniques are not standardized, and there is a concern for a different pattern of failure following post-operative SRS compared to WBRT. We aim to study the efficacy, toxicity, and failure pattern of post-operative SRS.We retrospectively reviewed outcomes of patients with resected BMs treated with post-operative SRS between 2007 and 2018. Overall survival (OS) and cumulative incidences of local failure (LF), overall distant intracranial failure [distant parenchymal failure (DPF), nodular leptomeningeal disease (nLMD), classical leptomeningeal disease (cLMD)], and adverse radiation effect (ARE) were reported. Neurological death was determined for patients with leptomeningeal disease (LMD).A total of 442 patients with 501 resected BMs were treated over 475 total SRS courses. Median clinical follow-up and OS after SRS were 10.1 months [interquartile range (IQR) 3.6-20.7 months] and 13.9 months [95% confidence interval (CI) 11.8-15.2 months], respectively. At 12 months, event rates were 7% (95% CI 5%-10%) for LF, 9% (95% CI 7%-12%) for ARE, 44% (95% CI 40%-49%) for overall distant intracranial failure, 37% (95% CI 33%-42%) for DPF and 13% (95% CI 10%-17%) for LMD. The overall incidence of LMD was 15.8% (53% cLMD, 46% nLMD). cLMD was associated with shorter survival than nLMD (2.0 versus 11.2 months, p<0.01) and a higher proportion of neurological death (67% versus 41%, p=0.02). A total of 15% of patients ultimately received WBRT.We report the largest clinical experience of post-operative SRS for resected BMs, showing excellent local control and low toxicity. Intracranial failure was predominantly distant, with a rising incidence of LMD.

    View details for DOI 10.1016/j.ijrobp.2019.11.022

    View details for PubMedID 31785338

  • Stereotactic Radiosurgery for Pediatric and Adult Intracranial and Spinal Ependymomas. Stereotactic and functional neurosurgery Shi, S. n., Jin, M. C., Koenig, J. n., Gibbs, I. C., Soltys, S. G., Chang, S. D., Li, G. n., Hayden Gephart, M. n., Hiniker, S. M., Pollom, E. L. 2019: 1–6


    We report efficacy and toxicity outcomes with stereotactic radiosurgery (SRS) for intracranial and spinal ependymoma.We analyzed adult and pediatric patients with newly diagnosed or recurrent intracranial or spinal ependymoma lesions treated with SRS at our institution. Following SRS, local failure (LF) was defined as failure within or adjacent to the SRS target volume, while distant failure (DF) was defined as failure outside of the SRS target volume. Time to LF and DF was analyzed using competing risk analysis with death as a competing risk.Overall survival (OS) was calculated from the date of first SRS to the date of death or censored at the date of last follow-up using the Kaplan-Meier method.Twenty-one patients underwent SRS to 40 intracranial (n = 30) or spinal (n = 10) ependymoma lesions between 2007 and 2018, most commonly with 18 or 20 Gy in 1 fraction. Median follow-up for all patients after first SRS treatment was 54 months (range 2-157). The 1-year, 2-year, and 5-year rates of survival among patients with initial intracranial ependymoma were 86, 74, and 52%, respectively. The 2-year cumulative incidences of LF and DF after SRS among intracranial ependymoma patients were 25% (95% CI 11-43) and 42% (95% CI 22-60), respectively. No spinal ependymoma patient experienced LF, DF, or death within 2 years of SRS. Three patients had adverse radiation effects.SRS is a viable treatment option for intracranial and spinal ependymoma with excellent local control and acceptable toxicity.

    View details for DOI 10.1159/000502653

    View details for PubMedID 31590165

  • Circulating tumor DNA analysis for detection of minimal residual disease after chemoradiotherapy for localized esophageal cancer. Gastroenterology Azad, T. D., Chaudhuri, A. A., Fang, P. n., Qiao, Y. n., Esfahani, M. S., Chabon, J. J., Hamilton, E. G., Yang, Y. D., Lovejoy, A. n., Newman, A. M., Kurtz, D. M., Jin, M. n., Schroers-Martin, J. n., Stehr, H. n., Liu, C. L., Bik-Yu Hui, A. n., Patel, V. n., Maru, D. n., Lin, S. H., Alizadeh, A. A., Diehn, M. n. 2019


    Biomarkers are needed to identify patients at risk of tumor progression following chemoradiotherapy for localized esophageal cancer. These could improve identification of patients at risk for cancer progression and selection of therapy.We performed deep sequencing (CAPP-Seq) analyses of plasma cell-free DNA collected from 45 patients before and after chemoradiotherapy for esophageal cancer, as well as DNA from leukocytes, and fixed esophageal tumor biopsies collected during esophagogastroduodenoscopy. Patients were treated from May 2010 through October 2015; 23 patients subsequently underwent esophagectomy and 22 did not undergo surgery. We also sequenced DNA from blood samples from 40 healthy individuals (controls). We analyzed 802 regions of 607 genes for single-nucleotide variants previously associated with esophageal adenocarcinoma or squamous cell carcinoma. Patients underwent imaging analyses 6-8 weeks after chemoradiotherapy and were followed for 5 years. Our primary aim was to determine whether detection of circulating tumor DNA (ctDNA) following chemoradiotherapy is associated with risk of tumor progression (growth of local, regional, or distant tumors, detected by imaging or biopsy).The median proportion of tumor-derived DNA in total cell-free DNA before treatment was 0.07%, indicating that ultrasensitive assays are needed for quantification and analysis of ctDNA from localized esophageal tumors. Detection of ctDNA following chemoradiotherapy was associated with tumor progression (hazard ratio, 18.7; P<.0001), formation of distant metastases (hazard ratio, 32.1; P<.0001), and shorter disease-specific survival times (hazard ratio, 23.1; P<.0001). A higher proportion of patients with tumor progression had new mutations detected in plasma samples collected after chemoradiotherapy than patients without progression (P=.03). Detection of ctDNA after chemoradiotherapy preceded radiographic evidence of tumor progression by an average of 2.8 months. Among patients who received chemoradiotherapy without surgery, combined ctDNA and metabolic imaging analysis predicted progression in 100% of patients with tumor progression, compared with 71% for only ctDNA detection and 57% for only metabolic imaging analysis (P<.001 for comparison of either technique to combined analysis).In an analysis of cell-free DNA in blood samples from patients who underwent chemoradiotherapy for esophageal cancer, detection of ctDNA was associated with tumor progression, metastasis, and disease-specific survival. Analysis of ctDNA might be used to identify patients at highest risk for tumor progression.

    View details for DOI 10.1053/j.gastro.2019.10.039

    View details for PubMedID 31711920

  • Risk of Subsequent Primary Cancers After External Beam Radiotherapy Treatment of Pediatric Low Grade Gliomas: A Surveillance, Epidemiology, and End Results Analysis 1973 to 2015 Congress of Neurological Surgeons Rodrigues, A., Jin, M. C., Wu, A., Li, G., Grant, G. A. 2019
  • Patterns of Care and Age Specific Impact of Resection Extent and Adjuvant Radiotherapy in Pediatric Pineoblastoma Congress of Neurological Surgeons Jin, M. C., Prolo, L. M., Wu, A., Azad, T. D., Shi, S., Rodrigues, A., Soltys, S. G., Pollom, E., Li, G., Hiniker, S., Grant, G. A. 2019
  • Phased Variant Enrichment for Enhanced Minimal Residual Disease Detection from Cell-Free DNA American Society of Hematology Kurtz, D. M., Soo, J., Alig, S., Keh, L. C., Macaulay, C., Jin, M. C., Scherer, F., Hamilton, E. G., Liu, C., Chen, B., Craig, A., Diehn, M., Alizadeh, A. A. 2019
  • Towards Non-Invasive Classification of DLBCL Genetic Subtypes By Ctdna Profiling American Society of Hematology Esfahani, M. S., Alig, S., Kurtz, D. M., Soo, J., Jin, M. C., Macaulay, C., Craig, A., Garofalo, A., Steen, C. B., Scherer, F., Sworder, B., Diehn, M., Alizadeh, A. A. 2019
  • Circulating DNA for Molecular Response Prediction, Characterization of Resistance Mechanisms and Quantification of CAR T-Cells during Axicabtagene Ciloleucel Therapy American Society of Hematology Sworder, B., Kurtz, D. M., Macaulay, C., Frank, M. J., Alig, S., Garofalo, A., Sahaf, B., Esfahani, M. S., Spiegel, J. Y., Oak, J., Beygi, S., Jin, M. C., Chabon, J. J., Khodadoust, M. S., Majzner, R. G., Mackall, C. L., Diehn, M., Miklos, D. B., Alizadeh, A. A. 2019
  • Interim Circulating Tumor DNA As a Prognostic Biomarker in the Setting of Interim PET-Based Adaptive Therapy for DLBCL American Society of Hematology Macaulay, C., Alig, S., Kurtz, D. M., Jin, M. C., Opat, S., Soo, J., Sworder, B., Hertzberg, M. S., Gandhi, M. K., Diehn, M., Alizadeh, A. A. 2019
  • Intracranial Response of Brain Metastases to Osimertinib With or Without Upfront Stereotactic Radiosurgery in TKI-Naïve Nonsmall Cell Lung Cancer Patients Congress of Neurological Surgeons Jin, M. C., Liu, E. K., Macaulay, C. W., Gian, A., Shi, S., Koenig, J., Li, G., Soltys, S. G., Pollom, E. L. 2019
  • Pediatric Thyroid Cancer Incidence and Mortality Trends in the United States, 1973-2013. JAMA otolaryngology-- head & neck surgery Qian, Z. J., Jin, M. C., Meister, K. D., Megwalu, U. C. 2019


    The incidence of thyroid cancer is increasing by 3% annually. This increase is often thought to be attributable to overdiagnosis in adults. A previous study reported a 1.1% annual increase in the incidence of pediatric thyroid cancer. However, the analysis was limited to the period from 1973 to 2004 and was performed in a linear fashion, which does not account for changes in incidence trends over time.To analyze trends in pediatric thyroid cancer incidence based on demographic and tumor characteristics at diagnosis.This cross-sectional study included individuals younger than 20 years who had a diagnosis of thyroid cancer in the Surveillance, Epidemiology, and End Results (SEER) 9 database from 1973 to 2013. Cases of thyroid cancer were identified using the International Classification of Diseases for Oncology, Third Edition and were categorized by histologic type, stage, and tumor size.Annual percent change (APC) in the incidence rates was calculated using joinpoint regression analysis.Among 1806 patients included in the analysis, 1454 (80.5%) were female and 1503 (83.2%) were white; most patients were aged 15 to 19 years. The overall incidence rates of thyroid cancer increased annually from 0.48 per 100 000 person-years in 1973 to 1.14 per 100 000 person-years in 2013. Incidence rates gradually increased from 1973 to 2006 (APC, 1.11%; 95% CI, 0.56%-1.67%) and then markedly increased from 2006 to 2013 (APC, 9.56%; 95% CI, 5.09%-14.22%). The incidence rates of large tumors (>20 mm) gradually increased from 1983 to 2006 (APC, 2.23%; 95% CI, 0.93%-3.54%) and then markedly increased from 2006 to 2013 (APC, 8.84%; 95% CI, 3.20%-14.79%); these rates were not significantly different from incidence rates of small (1-20 mm) tumors. The incidence rates of regionally extended thyroid cancer gradually increased from 1973 to 2006 (APC, 1.44%; 95% CI, 0.68%-2.21%) and then markedly increased from 2006 to 2013 (APC, 11.16%; 95% CI, 5.26%-17.40%); these rates were not significantly different from the incidence rates of localized disease.The incidence rates of pediatric thyroid cancer increased more rapidly from 2006 to 2013 than from 1973 to 2006. The findings suggest that there may be a co-occurring increase in thyroid cancer in the pediatric population in addition to enhanced detection.

    View details for DOI 10.1001/jamaoto.2019.0898

    View details for PubMedID 31120475

  • Lymphoma Virome Dynamics Revealed By Cell-Free DNA Sequencing Schroers-Martin, J. G., Garofalo, A., Soo, J., Jin, M. C., Kurtz, D. M., Buedts, L., Duehrsen, U., Huettmann, A., Cottereau, A., Meignan, M., Casasnovas, O., Westin, J. R., Gaidano, G., Rossi, D., Roschewski, M., Wilson, W. H., Advani, R. H., Vandenberghe, P., Diehn, M., Khush, K., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2018
  • Noninvasive Genotyping and Monitoring of Classical Hodgkin Lymphoma Jin, M. C., Schroers-Martin, J. G., Kurtz, D. M., Buedts, L., Esfahani, M. S., Macaulay, C., Sworder, B., Soo, J., Glover, C., Roschewski, M., Wilson, W. H., Duhrsen, U., Huettmann, A., Rossi, D., Gaidano, G., Westin, J. R., Maeda, L. S., Advani, R. H., Vandenberghe, P., Diehn, M., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2018
  • Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Kurtz, D. M., Scherer, F., Jin, M. C., Soo, J., Craig, A. F., Esfahani, M. S., Chabon, J. J., Stehr, H., Liu, C. L., Tibshirani, R., Maeda, L. S., Gupta, N. K., Khodadoust, M. S., Advani, R. H., Levy, R., Newman, A. M., Duhrsen, U., Huttmann, A., Meignan, M., Casasnovas, R., Westin, J. R., Roschewski, M., Wilson, W. H., Gaidano, G., Rossi, D., Diehn, M., Alizadeh, A. A. 2018: JCO2018785246


    Purpose Outcomes for patients with diffuse large B-cell lymphoma remain heterogeneous, with existing methods failing to consistently predict treatment failure. We examined the additional prognostic value of circulating tumor DNA (ctDNA) before and during therapy for predicting patient outcomes. Patients and Methods We studied the dynamics of ctDNA from 217 patients treated at six centers, using a training and validation framework. We densely characterized early ctDNA dynamics during therapy using cancer personalized profiling by deep sequencing to define response-associated thresholds within a discovery set. These thresholds were assessed in two independent validation sets. Finally, we assessed the prognostic value of ctDNA in the context of established risk factors, including the International Prognostic Index and interim positron emission tomography/computed tomography scans. Results Before therapy, ctDNA was detectable in 98% of patients; pretreatment levels were prognostic in both front-line and salvage settings. In the discovery set, ctDNA levels changed rapidly, with a 2-log decrease after one cycle (early molecular response [EMR]) and a 2.5-log decrease after two cycles (major molecular response [MMR]) stratifying outcomes. In the first validation set, patients receiving front-line therapy achieving EMR or MMR had superior outcomes at 24 months (EMR: EFS, 83% v 50%; P = .0015; MMR: EFS, 82% v 46%; P < .001). EMR also predicted superior 24-month outcomes in patients receiving salvage therapy in the first validation set (EFS, 100% v 13%; P = .011). The prognostic value of EMR and MMR was further confirmed in the second validation set. In multivariable analyses including International Prognostic Index and interim positron emission tomography/computed tomography scans across both cohorts, molecular response was independently prognostic of outcomes, including event-free and overall survival. Conclusion Pretreatment ctDNA levels and molecular responses are independently prognostic of outcomes in aggressive lymphomas. These risk factors could potentially guide future personalized risk-directed approaches.

    View details for PubMedID 30125215

  • Circulating Tumor DNA Quantitation for Early Response Assessment of Immune Checkpoint Inhibitors for Metastatic Non-Small Cell Lung Cancer Chaudhuri, A. A., Nabet, B. Y., Merriott, D. J., Jin, M., Chen, E. L., Chabon, J. J., Newman, A. M., Stehr, H., Say, C., Carter, J. N., Walters, S., Becker, H., Das, M., Padda, S. K., Loo, B. W., Wakelee, H. A., Neal, J. W., Alizadeh, A. A., Diehn, M. ELSEVIER SCIENCE INC. 2018: E1–E2
  • Circulating Tumor DNA Quantitation for Early Response Assessment of Immune Checkpoint Inhibitors for Lung Cancer Merriott, D. J., Chaudhuri, A. A., Jin, M., Chabon, J. J., Newman, A., Stehr, H., Say, C., Carter, J. N., Walters, S., Becker, H. R., Das, M., Padda, S., Loo, B. W., Wakelee, H. A., Neal, J. W., Alizadeh, A. A., Diehn, M. ELSEVIER SCIENCE INC. 2017: S20–S21
  • Elucidation of distinct mutational patterns between diffuse large B cell lymphoma subtypes utilizing circulating tumor DNA. Soo, J., Kurtz, D., Scherer, F., Craig, A. M., Jin, M. C., Westin, J. R., Rossi, D., Gaidano, G., Advani, R. H., Diehn, M., Alizadeh, A. A. AMER SOC CLINICAL ONCOLOGY. 2017
  • Noninvasive detection of clinically relevant copy number alterations in diffuse large B-cell lymphoma. Jin, M. C., Kurtz, D., Esfahani, M., Scherer, F., Craig, A. M., Soo, J., Khodadoust, M., Saganty, R., Chabon, J. J., Schroers-Martin, J., Stehr, H., Advani, R. H., Rossi, D., Gaidano, G., Westin, J. R., Diehn, M., Alizadeh, A. A. AMER SOC CLINICAL ONCOLOGY. 2017
  • Noninvasive Detection of BCL2, BCL6, and MYC Translocations in Diffuse Large B-Cell Lymphoma Kurtz, D. M., Scherer, F., Newman, A. M., Craig, A., Jin, M., Stehr, H., Chabon, J. J., Esfahani, M., Liu, C., Zhou, L., Glover, C., Visser, B. C., Poultsides, G., Advani, R. H., Maeda, L. S., Gupta, N. K., Levy, R., Ohgami, R. S., Davis, R., Kunder, C. A., Westin, J. R., Diehn, M., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2016