Publications by authors named "Christopher S Hong"

74 Publications

Independent Association of Obesity and Nonroutine Discharge Disposition After Elective Anterior Cervical Discectomy and Fusion for Cervical Spondylotic Myelopathy.

World Neurosurg 2021 May 18. Epub 2021 May 18.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA.

Objective: The prevalence of obesity continues to rise in the United States at a disparaging rate. Although previous studies have attempted to identify the influence obesity has on short-term outcomes following elective spine surgery, few studies have assessed the impact on discharge disposition following anterior cervical discectomy and fusion (ACDF) for cervical spondylotic myelopathy (CSM). The aim of this study was to determine whether obesity impacts the hospital management, cost, and discharge disposition after elective ACDF for adult CSM.

Methods: The National Inpatient Sample database was queried using the International Classification of Diseases, 10th revision, Clinical Modification, coding system to identify all (≥18 years) patients with a primary diagnosis of CSM undergoing an elective ACDF for the years 2016 and 2017. Discharge weights were used to estimate national demographics, Elixhauser comorbidities, complications, length of stay, total cost of admission, and discharge disposition.

Results: There were 17,385 patients included in the study, of whom 3035 (17.4%) had obesity (no obesity: 14,350; obesity: 3035). The cohort with obesity had a significantly greater proportion of patients with 3 or more comorbidities compared with the cohort with no obesity (no obesity: 28.1% vs. obesity: 43.5%, P < 0.001). The overall complication rates were greater in the cohort with obesity (no obesity: 10.3% vs. obesity: 14.3%, P = 0.003). On average, the cohort with obesity incurred a total cost of admission $1154 greater than the cost of the cohort with no obesity (no obesity: $19,732 ± 11,605 vs. obesity: $20,886 ± 10,883, P = 0.034) and a significantly greater proportion of nonroutine discharges (no obesity: 16.6% vs. obesity: 24.2%, P < 0.001). In multivariate regression analysis, obesity, age, race, health care coverage, hospital bed size, region, comorbidity, and complication rates all were independently associated with nonroutine discharge disposition.

Conclusions: Our study demonstrates that obesity is an independent predictor for nonroutine discharge disposition following elective anterior cervical discectomy and fusion for cervical spondylotic myelopathy.
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http://dx.doi.org/10.1016/j.wneu.2021.05.022DOI Listing
May 2021

Impact of race on outcomes and healthcare utilization following spinal fusion for adolescent idiopathic scoliosis.

Clin Neurol Neurosurg 2021 Jul 4;206:106634. Epub 2021 May 4.

Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA. Electronic address:

Objectives: Racial disparities in spine surgery have been shown to impact surgical management and postoperative complications. However, for adolescent patients with idiopathic scoliosis (AIS) treated by posterior spinal fusion (PSF), the influence of race on postoperative outcomes remains unclear. The aim of the study was to investigate the differences in baseline patient demographics, inpatient management, and postoperative complications for adolescents with AIS undergoing elective, posterior spinal surgery (≥ 4 levels).

Patients And Methods: The Kids' Inpatient Database year 2012 was queried. Adolescent patients (age 10-17 years old) with AIS undergoing elective, PSF (≥ 4 levels) were selected using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. Patients were divided into 4 cohorts: Black, White, Hispanic, and Other. Patient demographics, comorbidities, complications, length of hospital stay (LOS), discharge disposition and total cost were recorded. The primary outcome was the rate of intraoperative and postoperative complications and resource utilization after elective PSF intervention.

Results: Patient demographics significantly differed between the four cohorts. While age was similar (p = 0.288), the White cohort had a greater proportion of female patients (White: 79.0%; Black: 72.1%; Hispanic: 78.2%; Other: 75.9%, p = 0.006), and the Black cohort had the largest proportion of patients in the 0-25th income quartile (White: 16.1%; Black: 43.3%; Hispanic: 28.0%; Other: 15.3%, p < 0.001). There were significant differences in hospital region (p < 0.001) and bed size (p < 0.001) between the cohorts, with more Hispanic adolescents being treated in the West (White: 21.9%; Black: 8.9%; Hispanic: 40.3%; Other: 29.3%) at small hospitals (White: 14.0%; Black: 13.9%; Hispanic: 16.2%; Other: 7.1%). Baseline comorbidities were similar between the cohorts. The use of blood transfusions was significantly greater in the Black cohort compared to the other racial groups (White: 16.7%; Black: 25.0%; Hispanic: 24.5%; Other: 22.7%, p < 0.001). The number of vertebral levels involved differed significantly between the cohorts (p < 0.001), with the majority of patients having 9-levels or greater involved (White: 80.9%; Black: 81.7%; Hispanic: 84.3%; Other: 67.3%). The rate of complications encountered during admission was greatest in the Other cohort (White: 21.9%; Black: 23.6%; Hispanic: 22.2%; Other: 34.9%, p < 0.001). While LOS was similar between the cohorts (p = 0.702), median total cost of admission was highest for Hispanic patients (White: $49,340 [37,908-65,078]; Black: $47,787 [37,718-64,670]; Hispanic: $54,718 [40,689-69,266]; Other: $54,110 [41,292-71,540], p < 0.001).

Conclusions: Our study suggests that race may not have a significant impact on surgical outcomes after elective posterior spine surgery for adolescent idiopathic scoliosis. Further studies are necessary to corroborate our findings.
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http://dx.doi.org/10.1016/j.clineuro.2021.106634DOI Listing
July 2021

Multiple meningiomas arising within the same hemisphere associated with Li-Fraumeni syndrome.

Surg Neurol Int 2021 17;12:99. Epub 2021 Mar 17.

Department of Neurosurgery, Yale University School of Medicine, 20 York Street, LCI 8, New Haven, Connecticut, United States.

Background: While meningiomas are some of the most common intracranial tumors, the presence of multiple ones at the time of presentation is rare and can most commonly be observed in patients with well-described syndromes (i.e., neurofibromatosis type 2) or those with prior cranial radiation history. In others, however, the pathophysiology remains unclear.

Case Description: A 49-year-old female with no significant personal or familial oncologic medical history presented with a generalized seizure and was found to have ten meningiomas arising within the right hemisphere. She underwent a two-staged resection of all tumors, with pathology revealing the World Health Organization Grade I meningioma. Whole-exome sequencing revealed somatic mutations and heterozygous deletion of chromosome 22 overlapping with , and analysis of the germline uncovered mutations of , rendering a diagnosis of Li-Fraumeni Syndrome.

Conclusions: This case represents a novel presentation of multiple meningiomas in a patient with newly diagnosed Li-Fraumeni syndrome, suggesting meningioma may be considered as part of this tumor-predisposed patient population.
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http://dx.doi.org/10.25259/SNI_125_2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053471PMC
March 2021

Somatic NF1 mutations in pituitary adenomas: Report of two cases.

Cancer Genet 2021 Apr 2;256-257:26-30. Epub 2021 Apr 2.

Department of Neurosurgery, Yale School of Medicine, 20 York Street, LCI8, New Haven, CT 06511, United States. Electronic address:

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http://dx.doi.org/10.1016/j.cancergen.2021.03.004DOI Listing
April 2021

The Role of Mismatch Repair in Glioblastoma Multiforme Treatment Response and Resistance.

Neurosurg Clin N Am 2021 Apr 18;32(2):171-180. Epub 2021 Feb 18.

Department of Therapeutic Radiology, Yale School of Medicine, 333 Cedar Street Hunter 2, New Haven, CT 06510, USA. Electronic address:

Mismatch repair (MMR) is a highly conserved DNA repair pathway that is critical for the maintenance of genomic integrity. This pathway targets base substitution and insertion-deletion mismatches, which primarily arise from replication errors that escape DNA polymerase proof-reading function. Here, the authors review key concepts in the molecular mechanisms of MMR in response to alkylation damage, approaches to detect MMR status in the clinic, and the clinical relevance of this pathway in glioblastoma multiforme treatment response and resistance.
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http://dx.doi.org/10.1016/j.nec.2020.12.009DOI Listing
April 2021

Genomic Characterization of Radiation-Induced Intracranial Undifferentiated Pleomorphic Sarcoma.

Case Rep Genet 2021 8;2021:5586072. Epub 2021 Mar 8.

Department of Neurosurgery, Yale School of Medicine, New Haven 06511, CT, USA.

Intracranial undifferentiated pleomorphic sarcoma remains a rare pathology within the sarcoma literature that may arise primarily or secondary after radiation therapy. Despite first-line treatment with maximal surgical resection, followed by nonstandardized adjuvant chemotherapy/radiation regimens, clinical prognosis remains exceedingly poor. Furthermore, there is a lack of genetic or molecular characterization to guide potential for targeted therapies. We present genomic analysis of a radiation-induced intracranial undifferentiated pleomorphic sarcoma in an 83-year-old woman with notable KIT and PDGFRA alterations. Further similar genomic studies of intracranial pleomorphic sarcoma are needed to develop better therapies for this rare but challenging disease entity.
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http://dx.doi.org/10.1155/2021/5586072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960067PMC
March 2021

Hypermutated phenotype in gliosarcoma of the spinal cord.

NPJ Precis Oncol 2021 Feb 12;5(1). Epub 2021 Feb 12.

Department of Neurosurgery, Yale School of Medicine, New Haven, CT, 06511, USA.

Gliosarcoma is a variant of glioblastoma with equally poor prognosis and characterized by mixed glial and mesenchymal pathology. Metastasis is not uncommon but the involvement of the spinal cord is rare, and comprehensive genetic characterization of spinal gliosarcoma is lacking. We describe a patient initially diagnosed with a low-grade brain glioma via biopsy, followed by adjuvant radiation and temozolomide treatment. Nearly 2 years after diagnosis, she developed neurological deficits from an intradural, extramedullary tumor anterior to the spinal cord at T4, which was resected and diagnosed as gliosarcoma. Whole-exome sequencing (WES) of this tumor revealed a hypermutated phenotype, characterized by somatic mutations in key DNA mismatch repair (MMR) pathway genes, an abundance of C>T transitions within the identified somatic single nucleotide variations, and microsatellite stability, together consistent with temozolomide-mediated hypermutagenesis. This is the first report of a hypermutator phenotype in gliosarcoma, which may represent a novel genomic mechanism of progression from lower grade glioma.
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http://dx.doi.org/10.1038/s41698-021-00143-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881101PMC
February 2021

Thirty- and 90-day Readmissions After Spinal Surgery for Spine Metastases: A National Trend Analysis of 4423 Patients.

Spine (Phila Pa 1976) 2021 Jun;46(12):828-835

Department of Neurosurgery, Yale University School of Medicine, New Haven, CT.

Study Design: Retrospective cohort study.

Objective: The aim of this study was to investigate differences in 30- and 90-day readmissions for spine metastases treated with decompression and/or fusion spine surgery in a nationwide readmission database.

Summary Of Background Data: Patients with metastases to the spine represent a particularly vulnerable patient group that may encounter frequent readmissions. However, the 30- and 90-day rates for readmission following surgery for spine metastases have not been well described.

Methods: The Nationwide Readmission Database years 2013 to 2015 was queried. Patients were grouped by no readmission (non-R), readmission within 30 days (30-R), and readmission within 31 to 90 days (90-R). Weighted multivariate analysis assessed impact of treatment approach and clinical factors associated with 30- and 90-day readmissions.

Results: There were a total of 4423 patients with a diagnosis of spine metastases identified who underwent spine surgery, of which 1657 (37.5%) encountered either a 30-or 90-day unplanned readmission (30-R: n = 1068 [24-.1%]; 90-R: n = 589 [13.3%]; non-R: n = 2766). The most prevalent inpatient complications observed were postoperative infection (30-R: 16.3%, 90-R: 14.3%, non-R: 11.5%), acute post-hemorrhagic anemia (30-R: 13.4%, 90-R: 14.2%, non-R: 14.5%), and genitourinary complication (30-R: 5.7%, 90-R: 2.9%, non-R: 6.2%). The most prevalent 30-day and 90-day reasons for admission were sepsis (30-R: 10.2%, 90-R: 10.8%), postoperative infection (30-R: 13.7%, 90-R: 6.5%), and genitourinary complication (30-R: 3.9%, 90-R: 4.1%). On multivariate regression analysis, surgery type, age, hypertension, and renal failure were independently associated with 30-day readmission; rheumatoid arthritis/collagen vascular diseases, and coagulopathy were independently associated with 90-day readmission.

Conclusion: In this study, we demonstrate several patient-level factors independently associated with unplanned hospital readmissions after surgical treatment intervention for spine metastases. Furthermore, we find that the most common reasons for readmission are sepsis, postoperative infection, and genitourinary complications.Level of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003907DOI Listing
June 2021

Case Report: Suprasellar Pituitary Adenoma Presenting With Temporal Lobe Seizures.

Front Surg 2020 1;7:598138. Epub 2020 Dec 1.

Department of Neurosurgery, Yale School of Medicine, New Haven, CT, United States.

Seizures in patients with pituitary pathology are uncommon and typically secondary to electrolyte disturbances. Rarely, seizures have been described from mass effect related to large prolactinomas undergoing medical treatment. We describe a 54 year-old male who presented with a first-time generalized seizure, secondary to a pituitary macroadenoma compressing the left temporal lobe. His seizures abated after endoscopic endonasal debulking of the tumor. This report highlights isolated seizures as a potential sole presenting symptom of pituitary macroadenomas without visual or endocrine dysfunction. Prompt surgical debulking to relieve mass effect on the temporal lobe may effectively prevent further seizure activity.
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http://dx.doi.org/10.3389/fsurg.2020.598138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736041PMC
December 2020

Genetic characterization of an aggressive optic nerve pilocytic glioma.

Brain Tumor Pathol 2021 Jan 24;38(1):59-63. Epub 2020 Oct 24.

Department of Neurosurgery, Yale School of Medicine, 300 Cedar Street, TAC S327, New Haven, CT, 06511, USA.

Optic nerve glioma (ONG) is a rare, typically slow-growing WHO I grade tumor that affects the visual pathways. ONG is most commonly seen in the pediatric population, in association with neurofibromatosis type 1 syndrome. However, sporadic adult cases may also occur and may clinically behave more aggressively, despite benign histopathology. Genetic characterization of these tumors, particularly in the adult population, is lacking. A 39-year-old female presented with 1 month of progressive left-sided visual loss secondary to a enhancing mass along the left optic nerve sheath. Initial empiric management with focal radiotherapy failed to prevent tumor progression, prompting open biopsy which revealed a WHO I pilocytic astrocytoma of the optic nerve. Whole-exome sequencing of the biopsy specimen revealed somatic mutations in NF1,FGFR1 and PTPN11 that may provide actionable targets for molecularly guided therapies. Genetic characterization of ONG is lacking but is needed to guide the management of these rare but complex tumors. The genomic alterations reported in this case contributes to understanding the pathophysiology of adult sporadic ONG and may help guide future clinical prognostication and development of targeted therapies.
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http://dx.doi.org/10.1007/s10014-020-00383-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585354PMC
January 2021

Genetic characterization of a case of sellar metastasis from bronchial carcinoid neuroendocrine tumor.

Surg Neurol Int 2020 25;11:303. Epub 2020 Sep 25.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, United States.

Background: Metastasis to the pituitary gland from neuroendocrine tumors is a rare occurrence that may originate from primary tumors the lung, gastrointestinal tract, thyroid, and pancreas, among others. Patients may present with signs of endocrine dysfunction secondary to pituitary involvement, as well as mass effect-related symptoms including headaches and visual deficits. Despite a small but accumulating body of literature describing the clinical and histopathological correlates for pituitary metastases from neuroendocrine tumors, the genetic basis underlying this presentation remains poorly characterized.

Case Description: We report the case of a 68-year-old with a history of lung carcinoid tumor who developed a suprasellar lesion, causing mild visual deficits but otherwise without clinical or biochemical endocrine abnormalities. She underwent endoscopic endonasal resection of her tumor with final pathology confirming metastasis from her original neuroendocrine tumor. Whole-exome sequencing was performed on the resected sellar tumor and matching blood, revealing increased genomic instability and key mutations in and that have been previously implicated in both systemic neuroendocrine and primary pituitary tumors with potentially actionable therapeutic targets.

Conclusion: This is the first genomic characterization of a metastatic tumor to the sella and reports potential genetic insight, implicating and mutations, into the pathophysiology of sellar metastasis from primary systemic tumors.
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http://dx.doi.org/10.25259/SNI_265_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568119PMC
September 2020

Impact of Preoperative Anemia on Outcomes After Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis.

World Neurosurg 2021 Feb 19;146:e214-e224. Epub 2020 Oct 19.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA. Electronic address:

Objective: The aim of this study was to investigate the relationship of preoperative anemia and outcomes after posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS).

Methods: A retrospective cohort study was performed using the American College of Surgeons National Surgical Quality Improvement Program-Pediatric database from 2016 to 2018. All pediatric patients (age 10-18 years) with AIS undergoing PSF were identified. Two cohorts were categorized into anemic and nonanemic cohorts based on age-based and sex-based criteria for anemia. Thirty-day outcomes and readmission rates were evaluated.

Results: A total of 4929 patients were identified, of whom 592 (12.0%) were found to have preoperative anemia. The anemic cohort had a greater prevalence of comorbidities and longer operative times. Compared with the nonanemic cohort, the anemic cohort experienced significantly higher rates of perioperative bleed/transfusion (nonanemic, 67.4% vs. anemic, 73.5%; P = 0.004) and required a greater total amount of blood transfused (nonanemic, 283.2 ± 265.5 mL vs. anemic, 386.7 ± 342.6 mL; P < 0.001). The anemic cohort experienced significantly longer hospital stays (nonanemic, 3.8 ± 2.2 days vs. anemic, 4.2 ± 3.9 days; P = 0.001), yet discharge disposition (P = 0.58), 30-day complication rates (P = 0.79) and unplanned reoperation rates (P = 0.90) were similar between cohorts. On multivariate analysis, anemia was found to be an independent predictor of perioperative bleed/transfusion (odds ratio, 1.36; 95% confidence interval, 1.12-1.66; P = 0.002) as well as a longer length of hospital stay (relative risk, 0.46; 95% confidence interval, 0.25-0.67; P < 0.001) but was not an independent predictor for postoperative complications (P = 0.85).

Conclusions: Our study suggests that preoperative anemia may be a risk factor for a greater perioperative bleed/transfusion event and slightly longer length of stay; however, it was not associated with greater 30-day complication and readmission rates in patients with AIS undergoing PSF.
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http://dx.doi.org/10.1016/j.wneu.2020.10.074DOI Listing
February 2021

Characteristics of Reported Industry Payments to Neurosurgeons: A 5-Year Open Payments Database Study.

World Neurosurg 2021 01 1;145:e90-e99. Epub 2020 Oct 1.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut.

Objective: The aim of this study was to characterize the payments made by medical industry to neurosurgeons from 2014 to 2018.

Methods: A retrospective study was performed from January 1, 2014 to December 31, 2018 of the Open Payments Database. Collected data included the total number of industry payments, the aggregate value of industry payments, and the mean value of each industry payment made to neurosurgeons per year over the 5-year period.

Results: A total of 105,150 unique surgeons, with 13,668 (12.99%) unique neurosurgeons, were identified to have received an industry payment during 2014-2018. Neurosurgeons were the second highest industry-paid surgical specialty, with a total 421,151 industry payments made to neurosurgeons, totaling $477,451,070. The mean average paid amount per surgeon was $34,932 (±$936,942). The largest proportion of payments were related to food and beverage (75.5%), followed by travel and lodging (14.9%), consulting fees (3.5%), nonconsulting service fees (2.1%), and royalties or licensing (1.9%), totaling 90.4% of all industry payments to neurologic surgeons. Summed across the 5-year period, the largest paid source types were royalties and licensing (64.0%; $305,517,489), consulting fees (11.8%; $56,445,950), nonconsulting service fees (7.3%; $34,629,109), current or prospective investments (6.8%, $32,307,959), and travel and lodging (4.8%, $22,982,165).

Conclusions: Our study shows that over the most recent 5-year period (2014-2018) of the Centers for Medicare and Medicaid Services Open Payments Database, there was a decreasing trend of the total number of payments, but an increasing trend of the total amount paid to neurosurgeons.
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http://dx.doi.org/10.1016/j.wneu.2020.09.137DOI Listing
January 2021

Laser interstitial thermal therapy in neuro-oncology applications.

Surg Neurol Int 2020 8;11:231. Epub 2020 Aug 8.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, United States.

Background: Laser interstitial thermal therapy (LITT) is a minimally invasive surgical treatment for multiple intracranial pathologies that are of growing interest to neurosurgeons and their patients and is emerging as an effective alternative to standard of care open surgery in the neurosurgical armamentarium. This option was initially considered for those patients with medical comorbidities and lesion-specific characteristics that confer excessively high risk for resection through a standard craniotomy approach but indications are changing.

Methods: The PubMed database was searched for studies in the English literature on LITT for the treatment of primary and metastatic brain tumors, meningiomas, as well as for radiation necrosis (RN) in previously irradiated brain tumors.

Results: This review provides an update of the relevant literature regarding application of LITT in neurosurgical oncology for the treatment of and recurrent primary gliomas and brain metastases radiographically regrowing after previous irradiation as recurrent tumor or RN. In addition, this review details the limited experience of LITT with meningiomas and symptomatic peritumoral edema after radiosurgery. The advantages and disadvantages, indications, and comparisons to standard of care treatments such as craniotomy for open surgical resection are discussed for each pathology. Finally, the literature on cost-benefit analyses for LITT are reviewed.

Conclusion: The studies discussed in this review have helped define the role of LITT in neurosurgical oncology and delineate optimal patient selection and tumor characteristics most suitable to this intervention.
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http://dx.doi.org/10.25259/SNI_496_2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451173PMC
August 2020

Laser interstitial thermal therapy for treatment of cerebral radiation necrosis.

Int J Hyperthermia 2020 07;37(2):68-76

Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.

Radiation necrosis is a well described complication after radiosurgical treatment of intracranial pathologies - best recognized after the treatment of patients with arteriovenous malformations and brain metastases but possibly also affecting patients treated with radiosurgery for meningioma. The pathophysiology of radiation necrosis is still not well understood but is most likely a secondary local tissue inflammatory response to brain tissue injured by radiation. Radiation necrosis in brain metastases patients may present radiographically and behave clinically like recurrent tumor. Differentiation between radiation necrosis and recurrent tumor has been difficult based on radiographic changes alone. Biopsy or craniotomy therefore remains the gold standard method of diagnosis. For symptomatic patients, corticosteroids are first-line therapy, but patients may fail medical management due to intolerance of chronic steroids or persistence of symptoms. In these cases, open surgical resection has been shown to be successful in management of surgically amenable lesions but may be suboptimal in patients with deep-seated lesions or extensive prior cranial surgical history, both carrying high risk for peri-operative morbidity. Laser interstitial thermal therapy has emerged as a viable, alternative surgical option. In addition to allowing access to tissue for diagnosis, thermal treatment of the lesion can also be delivered precisely and accurately under real-time imaging guidance. This review highlights the pertinent studies that have shaped the impetus for use of laser interstitial thermal therapy in the treatment of radiation necrosis, reviewing indications, outcomes, and nuances toward successful application of this technology in patients with suspected radiation necrosis.
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http://dx.doi.org/10.1080/02656736.2020.1760362DOI Listing
July 2020

Molecular Diagnosis and Extracranial Extension in Cushing Disease.

JAMA Otolaryngol Head Neck Surg 2020 09;146(9):865-867

Yale School of Medicine, Department of Neurosurgery, New Haven, Connecticut.

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http://dx.doi.org/10.1001/jamaoto.2020.1471DOI Listing
September 2020

Comparison of epidemiology, treatments, and outcomes in pediatric versus adult ependymoma.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa019. Epub 2020 Feb 21.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA.

Background: Mounting evidence supports the presence of heterogeneity in the presentation of ependymoma patients with respect to location, histopathology, and behavior between pediatric and adult patients. However, the influence of age on treatment outcomes in ependymoma remains obscure.

Methods: The SEER database years 1975-2016 were queried. Patients with a diagnosis of ependymoma were identified using the International Classification of Diseases for Oncology, Third Edition, coding system. Patients were classified into one of 4 age groups: children (age 0-12 years), adolescents (age 13-21 years), young adults (age 22-45 years), and older adults (age >45 years). The weighed multivariate analysis assessed the impact of age on survival outcomes following surgical treatment.

Results: There were a total of 6076 patients identified with ependymoma, of which 1111 (18%) were children, 529 (9%) were adolescents, 2039 (34%) were young adults, and 2397 (40%) were older adults. There were statistically significant differences between cohorts with respect to race ( < .001), anatomical location ( < .001), extent of resection ( < .001), radiation use ( < .001), tumor grade ( < .001), histological classification ( < .001), and all-cause mortality ( < .001). There was no significant difference between cohorts with respect to gender ( = .103). On multivariate logistic regression, factors associated with all-cause mortality rates included males (vs females), supratentorial location (vs spinal cord tumors), and radiation treatment (vs no radiation).

Conclusions: Our study using the SEER database demonstrates the various demographic and treatment risk factors that are associated with increased rates of all-cause mortality between the pediatric and adult populations following a diagnosis of ependymoma.
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http://dx.doi.org/10.1093/noajnl/vdaa019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212900PMC
February 2020

Laser interstitial thermal therapy (LITT) vs. bevacizumab for radiation necrosis in previously irradiated brain metastases.

J Neurooncol 2020 Jul 29;148(3):641-649. Epub 2020 Jun 29.

Department of Neurosurgery, Yale University School of Medicine, 333 Cedar St, New Haven, CT, 06520, USA.

Purpose: Both laser interstitial thermal therapy (LITT) and bevacizumab have been used successfully to treat radiation necrosis (RN) after radiation for brain metastases. Our purpose is to compare pre-treatment patient characteristics and outcomes between the two treatment options.

Methods: Single-institution retrospective chart review identified brain metastasis patients who developed RN between 2011 and 2018. Pre-treatment factors and treatment responses were compared between those treated with LITT versus bevacizumab.

Results: Twenty-five patients underwent LITT and 13 patients were treated with bevacizumab. The LITT cohort had a longer overall survival (median 24.8 vs. 15.2 months for bevacizumab, p = 0.003) and trended to have a longer time to local recurrence (median 12.1 months vs. 2.0 for bevacizumab), although the latter failed to achieve statistical significance (p = 0.091). LITT resulted in an initial increase in lesional volume compared to bevacizumab (p < 0.001). However, this trend reversed in the long term follow-up, with LITT resulting in a median volume decrease at 1 year post-treatment of - 64.7% (range - 96.0% to +  > 100%), while bevacizumab patients saw a median volume increase of +  > 100% (range - 63.0% to +  > 100%), p = 0.010.

Conclusions: Our study suggests that patients undergoing LITT for RN have longer overall survival and better long-term lesional volume reduction than those treated with bevacizumab. However, it remains unclear whether our findings are due only to a difference in efficacy of the treatments or the implications of selection bias.
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http://dx.doi.org/10.1007/s11060-020-03570-0DOI Listing
July 2020

Persistent mutation despite multimodal therapy in recurrent pediatric glioblastoma.

NPJ Genom Med 2020 1;5:23. Epub 2020 Jun 1.

Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06511 USA.

Similar to their adult counterparts, the prognosis for pediatric patients with high-grade gliomas remains poor. At time of recurrence, treatment options are limited and remain without consensus. This report describes the genetic findings, obtained from whole-exome sequencing of a pediatric patient with glioblastoma who underwent multiple surgical resections and treatment with standard chemoradiation, as well as a novel recombinant poliovirus vaccine therapy. Strikingly, despite the variety of treatments, there was persistence of a tumor clone, characterized by a deleterious mutation, whose deficiency in preclinical studies can cause aneuploidy and aberrant mitotic progression, but remains understudied in the clinical setting. There was near elimination of an mutated and amplified tumor clone after gross total resection, standard chemoradiation, and poliovirus therapy, followed by the emergence of a persistently mutated clone, with rare mutations in and , the latter composed of a novel deleterious mutation previously not reported in pediatric glioblastoma (p.D594G). This was accompanied by a mutation signature shift towards one characterized by increased DNA damage repair defects, consistent with the known underlying deficiency. As such, this case represents a novel report following the clinical and genetic progression of a mutated glioblastoma, including treatment with a novel and emerging immunotherapy. Although deficiency comprises only a small subset of gliomas, this case adds clinical evidence to existing preclinical data supporting a role for mutations in gliomagenesis and resistance to standard therapies.
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http://dx.doi.org/10.1038/s41525-020-0130-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264170PMC
June 2020

Pre-operative headaches and obstructive hydrocephalus predict an extended length of stay following suboccipital decompression for pediatric Chiari I malformation.

Childs Nerv Syst 2021 Jan 9;37(1):91-99. Epub 2020 Jun 9.

Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA.

Purpose: For young children and adolescents with Chiari malformation type I (CM-I), the determinants of extended length of hospital stay (LOS) after neurosurgical suboccipital decompression are obscure. Here, we investigate the impact of patient- and hospital-level risk factors on extended LOS following surgical decompression for CM-I in young children to adolescents.

Methods: The Kids' Inpatient Database year 2012 was queried. Pediatric CM-I patients (6-18 years) undergoing surgical decompression were identified. Weighted patient demographics, comorbidities, complications, LOS, disposition, and total cost were recorded. A multivariate logistic regression was used to determine the odds ratio for risk-adjusted LOS. The primary outcome was the degree patient comorbidities or post-operative complications correlated with extended LOS.

Results: A total of 1592 pediatric CM-I patients were identified for which 328 (20.6%) patients had extended LOS (normal LOS, 1264; extended LOS, 328). Age, gender, race, median household income quartile, and healthcare coverage distributions were similar between the two cohorts. Patients with extended LOS had significantly greater admission comorbidities including headache symptoms, nausea and vomiting, obstructive hydrocephalus, lack of coordination, deficiency anemias, and fluid and electrolyte disorders. On multivariate logistic regression, several risk factors were associated with extended LOS, including headache symptoms, obstructive hydrocephalus, and fluid and electrolyte disorders.

Conclusions: Our study using the Kids' Inpatient Database demonstrates that presenting symptoms and signs, including headaches and obstructive hydrocephalus, respectively, are significantly associated with extended LOS following decompression for pediatric CM-I.
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http://dx.doi.org/10.1007/s00381-020-04688-2DOI Listing
January 2021

The Patient-Centered Approach: A Review of the Literature and Its Application for Acoustic Neuromas.

J Neurol Surg B Skull Base 2020 Jun 6;81(3):280-286. Epub 2019 Jun 6.

Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut, United States.

Patient-centered care is defined as "care that is consistent with and respects the values, needs, and wishes of patients" and is best achieved when clinicians involve patients and their support system in health care discussions and decisions. While this approach has been well established and supported in more general medical specialties, such as primary care, that may encompass a more holistic approach, it has rarely been described in surgical disciplines. Acoustic neuromas (ANs) can be unique among other skull base and intracranial pathologies, in that the management of these tumors can vary from patient to patient depending on various factors. Moreover, typical options, including observation, radiation, and surgery, may often have equipoise for some patients and their tumors. Therefore, a patient-centered approach, strongly guided by the expertise of experienced skull base surgeons, may likely be the most appropriate type of care for patients with ANs. Herein, we review the documented use of patient-centered care in other aspects of medicine, propose the benefits of this approach for patients with ANs, and provide ways this can be better implemented in practice.
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http://dx.doi.org/10.1055/s-0039-1692396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253312PMC
June 2020

Risk Factors for the Development of Post-Traumatic Hydrocephalus in Children.

World Neurosurg 2020 09 7;141:e105-e111. Epub 2020 May 7.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA. Electronic address:

Objective: The aim of this study was to investigate the national impact of demographic, hospital, and inpatient risk factors on posttraumatic hydrocephalus (PTH) development in pediatric patients who presented to the emergency department after a traumatic brain injury (TBI).

Methods: The Nationwide Emergency Department Sample database 2010-2014 was queried. Patients (<21 years old) with a primary diagnosis of TBI and subsequent secondary diagnosis of PTH were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system.

Results: We identified 1,244,087 patients who sustained TBI, of whom 930 (0.07%) developed PTH. The rates of subdural hemorrhage and subarachnoid hemorrhage were both significantly higher for the PTH cohort. On multivariate regression, age 6-10 years (odds ratio [OR], 0.6; 95% confidence interval [CI], 0.38-0.93; P = 0.022), 11-15 years (OR, 0.32; 95% CI, 0.21-0.48; P < 0.0001), and 16-20 years (OR, 0.24; 95% CI, 0.15-0.37; P < 0.0001) were independently associated with decreased risk of developing hydrocephalus, compared with ages 0-5 years. Extended loss of consciousness with baseline return and extended loss of consciousness without baseline return were independently associated with increased risk of developing hydrocephalus. Respiratory complication (OR, 28.35; 95% CI, 15.75-51.05; P < 0.0001), hemorrhage (OR, 37.12; 95% CI, 4.79-287.58; P = 0.0001), thromboembolic (OR, 8.57; 95% CI, 1.31-56.19; P = 0.025), and neurologic complication (OR, 64.64; 95% CI, 1.39-3010.2; P = 0.033) were all independently associated with increased risk of developing hydrocephalus.

Conclusions: Our study using the Nationwide Emergency Department Sample database shows that various demographic, hospital, and clinical risk factors are associated with the development of hydrocephalus after traumatic brain injury.
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http://dx.doi.org/10.1016/j.wneu.2020.04.216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484270PMC
September 2020

Influence of gender on discharge disposition after spinal fusion for adult spine deformity correction.

Clin Neurol Neurosurg 2020 07 1;194:105875. Epub 2020 May 1.

Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.

Objectives: Gender has been shown to impact several aspects of spine surgical care. However, the influence of gender disparities on discharge disposition after adult spine deformity correction (ASD) is relatively understudied. The aim of this study was to investigate the influence of gender on discharge disposition after elective spinal fusion involving ≥4 levels for ASD correction.

Patients And Methods: The Nationwide Inpatient Sample database (2011-2014) was queried for patients with ASD (≥26 years-old) and elective spine fusion surgery involving ≥4 levels using ICD-9 codes. Patients were stratified by gender: Male or Female. Multivariate linear and logistic regressions were used to assess the impact of gender on length of hospital stay and discharge disposition.

Results: A total of 4972 patients were identified of which 3282 (66.0%) were Female and 1690 (34.0%) were Male. The Male cohort had a higher prevalence of comorbidities than the Female cohort. There was a difference in the number of levels operated on between cohorts, with the Female cohort having fewer 4-8-level fusions (77.6% vs. 86.8%) and more 9+-level fusions (23.0% vs. 13.6%) compared to Males. The Female cohort had greater rates of postoperative UTI (5.5% vs. 2.5%) and surgical site hematomas (2.6% vs. 1.3%), while the Male cohort had more postoperative MI (5.4% vs. 1.5%). The Female cohort spent slightly more time in the hospital than Male cohort (6.2 days vs. 5.9 days, P = 0.035). Female patients had a significantly greater proportion of non-routine discharge disposition (F: 48.5% vs. M: 40.3%, P < 0.001) compared to Male patients. However, in a multivariate analysis including patient and hospital factors, gender was not an independent predictor of discharge disposition (OR: 0.976, CI: 0.865-1.101, P = 0.688), but was independently associated with increased LOS [female (RR: 0.331, CI: 0.106-0.556, P = 0.004)].

Conclusion: Our study suggests gender disparities may not have a significant impact on discharge disposition after spinal fusion for ASD involving four levels or greater. Further studies are necessary to understand risk factors for non-routine discharges in ASD patients to improve quality of patient care and reduced healthcare costs.
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http://dx.doi.org/10.1016/j.clineuro.2020.105875DOI Listing
July 2020

The CSF Diversion via Lumbar Drainage to Treat Dialysis Disequilibrium Syndrome in the Critically Ill Neurological Patient.

Neurocrit Care 2020 08;33(1):312-316

Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Yale School of Medicine, 15 York Street, LCI Room 1004D, Box 208018, New Haven, CT, 06520, USA.

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http://dx.doi.org/10.1007/s12028-020-00972-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223300PMC
August 2020

A novel germline gain-of-function HIF2A mutation in hepatocellular carcinoma with polycythemia.

Aging (Albany NY) 2020 04 1;12(7):5781-5791. Epub 2020 Apr 1.

State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou City, China.

Hypoxia-inducible factors (HIFs) regulate oxygen sensing and expression of genes involved in angiogenesis and erythropoiesis. Polycythemia has been observed in patients with hepatocellular carcinoma (HCC), but the underlying molecular basis remains unknown. Liver tissues from 302 HCC patients, including 104 with polycythemia, were sequenced for mutations. A germline mutation was detected in one HCC patient with concurrent polycythemia. Three additional family members carried this mutation, but none exhibited polycythemia or were diagnosed with HCC. The gain-of-function mutation resulted in a HIF-2α protein that was transcribed normally but resistant to degradation. HIF-2α target genes , , , and were significantly upregulated in the tumor bed but not in the surrounding liver tissue. Polycythemia resolved upon total resection of the tumor tissue. This newly described mutation may promote HCC oncogenesis.
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http://dx.doi.org/10.18632/aging.102967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185130PMC
April 2020

Risk Factors Portending Extended Length of Stay After Suboccipital Decompression for Adult Chiari I Malformation.

World Neurosurg 2020 06 5;138:e515-e522. Epub 2020 Mar 5.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut. Electronic address:

Objective: For adult patients undergoing surgical decompression for Chiari malformation type I (CM-I), the patient-level factors that influence extended length of stay (LOS) are relatively unknown. The aim of this study was to investigate the impact of patient-baseline comorbidities, demographics, and postoperative complications on extended LOS after intervention after adult CM-I decompression surgery.

Methods: A retrospective cohort study using the National Inpatient Sample years 2010-2014 was performed. Adults (≥18 years) with a primary diagnosis of CM-I undergoing surgical decompression were identified. Weighted patient demographics, comorbidities, complications, LOS, disposition, and total cost were recorded. A multivariate logistic regression was used to determine the odds ratio for risk-adjusted LOS.

Results: A total of 29,961 patients were identified, 6802 of whom (22.7%) had extended LOS. The extended LOS cohort had a significantly greater overall complication rate (normal LOS, 10.6% vs. extended LOS, 29.1%; P < 0.001) and total cost (normal LOS, $14,959 ± $6037 vs. extended LOS, $25,324 ± $21,629; P < 0.001) compared with the normal LOS cohort. On multivariate logistic regression, black race, income quartiles, private insurance, obstructive hydrocephalus, lack of coordination, fluid and electrolyte disorders, and paralysis were all independently associated with extended LOS. Additional duraplasty (P = 0.132) was not significantly associated with extended LOS after adjusting for other variables. The odds ratio for extended LOS was 2.07 (95% confidence interval, 1.59-2.71) for patients with 1 complication and 9.47 (95% confidence interval, 5.86-15.30) for patients with >1 complication.

Conclusions: Our study shows that extended LOS after adult CM-I decompression surgery may be influenced by multiple patient-level factors.
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http://dx.doi.org/10.1016/j.wneu.2020.02.158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379177PMC
June 2020

MRI-Guided Laser Interstitial Thermal Therapy for Radiation Necrosis in Previously Irradiated Brain Arteriovenous Malformations.

Pract Radiat Oncol 2020 Jul - Aug;10(4):e298-e303. Epub 2020 Feb 14.

Departments of Neurosurgery, Yale School of Medicine, New Haven, Connecticut; Departments of Radiology & Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut.

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http://dx.doi.org/10.1016/j.prro.2020.02.003DOI Listing
March 2021

Laser Interstitial Thermotherapy for Treatment of Symptomatic Peritumoral Edema After Radiosurgery for Meningioma.

World Neurosurg 2020 Apr 27;136:295-300. Epub 2020 Jan 27.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA; Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut, USA. Electronic address:

Background: Symptomatic peritumoral edema (PTE) is a known complication after radiosurgical treatment of meningiomas. Although the edema in most patients can be successfully managed conservatively with corticosteroid therapy or bevacizumab, some medically refractory cases may require surgical resection of the underlying lesion when feasible. Laser interstitial thermotherapy (LITT) continues to gain traction as an effective therapeutic modality for the treatment of radiation necrosis where its biggest impact is through the control of peritumoral edema.

Case Description: A 56-year-old woman with neurofibromatosis 2 presented with a symptomatic, regrowing left frontotemporal lesion that had previously been radiated, then resected with confirmed recurrence of grade I meningioma, and subsequently radiated again for lesion recurrence. Given her history of 2 prior same-side craniotomies, including a complication of wound infection, she was not a candidate for further open surgical resection. Having failed conservative management, she underwent LITT with intraoperative biopsy demonstrating viable grade I meningioma. Postoperatively, she demonstrated radiographic marked, serial reduction of PTE and experienced resolution of her symptoms.

Conclusions: This case demonstrates that LITT may be a viable alternative treatment for patients with meningioma with symptomatic PTE who have failed medical therapy and require surgical intervention.
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http://dx.doi.org/10.1016/j.wneu.2020.01.143DOI Listing
April 2020

Novel EWSR1-VGLL1 fusion in a pediatric neuroepithelial neoplasm.

Clin Genet 2020 05 16;97(5):791-792. Epub 2020 Jan 16.

Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut.

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http://dx.doi.org/10.1111/cge.13703DOI Listing
May 2020

Geographic Variation in Outcomes and Costs After Spinal Fusion for Adolescent Idiopathic Scoliosis.

World Neurosurg 2020 Apr 7;136:e347-e354. Epub 2020 Jan 7.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA. Electronic address:

Objective: The aim of this study was to evaluate regional variations in the management, complications, and total cost of admission for adolescent idiopathic scoliosis (AIS) treated by elective posterior spinal surgery (PSF, ≥4 levels).

Methods: The Kids' Inpatient Database year 2012 was queried and adolescent patients (age 10-17 years old) with AIS undergoing elective PSF (≥4 levels) were selected. The primary outcome was regional variations for intraoperative and postoperative complications, length of surgery, and total cost of admission after elective PSF intervention.

Results: In our cohort of 3759 adolescent patients identified, 704 (18.7%) patients were treated in the Northeast, 917 (24.4%) in the Midwest, 1329 (35.4%) in the South, and 809 (21.5%) in the West (Northeast: n = 704; Midwest: n = 917; South: n = 1329; West: n = 809). The Northeast had the greatest complication rate, followed by the Midwest, South, and West region cohorts (Northeast: 27.7% vs. Midwest: 24.5% vs. South: 23.0% vs. West: 17.2%, P < 0.001). On average, length of surgery was shortest in the South (Northeast: 5.3 ± 2.7 days vs. Midwest: 5.3 ± 3.1 days vs. South: 4.9 ± 3.1 days vs. West: 5.3 ± 2.1 days, P < 0.001), while the total cost of admission was greatest in the West (Northeast: $51,760 ± $25,177 vs. Midwest: $55,201 ± $23,750 vs. South: $58,847 ± $28,227 vs. West: $60,636 ± $29,372, P < 0.001).

Conclusions: Our study suggests that there may be regional variations in health care resource utilization in AIS patients undergoing multilevel posterior spinal fusions. Further study is warranted to determine the specific factors contributing to disparities in regional outcomes.
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http://dx.doi.org/10.1016/j.wneu.2019.12.175DOI Listing
April 2020