Publications by authors named "Taemin Oh"

60 Publications

Multiple Tumor-Associated Intracranial Aneurysms Adjacent to a Suprasellar Germ Cell Tumor: Case Report and Review of Literature.

Pediatr Neurosurg 2021 Jul 28:1-10. Epub 2021 Jul 28.

Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.

Introduction: Tumor-associated intracranial aneurysms are rare and not well understood.

Case Presentation: We describe a 4-year-old female with multiple intracranial aneurysms intimately associated with a suprasellar germ cell tumor (GCT). We provide the clinical history, medical, and surgical treatment course, as well as a comprehensive and concise synthesis of the literature on tumor-associated aneurysms.

Discussion: We discuss mechanisms for aneurysm formation with relevance to the current case, including cellular and paracrine signaling pertinent to suprasellar GCTs and possible molecular pathways involved. We review the complex multidisciplinary treatment required for complex tumor and cerebrovascular interactions.
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http://dx.doi.org/10.1159/000517890DOI Listing
July 2021

A Case of Torticollis in an 8-Month-Old Infant Caused by Posterior Fossa Arachnoid Cyst: An Important Entity for Differential Diagnosis.

Pediatr Rep 2021 Apr 12;13(2):197-202. Epub 2021 Apr 12.

Department of Neurosurgery, University of California San Francisco, San Francisco, CA 94122, USA.

Torticollis is a clinical diagnosis with heterogeneous causes. We present an unusual case of acquired torticollis in an 8-month-old female infant with a large cerebellopontine angle arachnoid cyst. Symptoms resolved after surgical fenestration. Non-traumatic acquired or new-onset torticollis requires brain imaging, and posterior fossa lesions are an important entity in the differential for pediatric clinicians.
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http://dx.doi.org/10.3390/pediatric13020027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167635PMC
April 2021

Pathologic Findings Associated With a Case of Acute Flaccid Myelitis.

J Neuropathol Exp Neurol 2021 Apr;80(5):484-487

Department of Neurological Surgery, University of California, San Francisco, California, USA.

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http://dx.doi.org/10.1093/jnen/nlab031DOI Listing
April 2021

Plurihormonal PIT-1-Positive Pituitary Adenomas: A Systematic Review and Single-Center Series.

World Neurosurg 2021 Jul 20;151:e185-e191. Epub 2021 Apr 20.

Department of Neurological Surgery, University of California, San Francisco, School of Medicine, San Francisco, California, USA. Electronic address:

Objective: The 2017 World Health Organization classification of pituitary adenomas identified the plurihormonal PIT-1-positive (PP1) adenoma as a distinct subtype. The reported data suggest that PP1 adenomas encompass the former class of silent subtype 3 (SS3) adenomas and might have an aggressive phenotype. In the present study, we summarized the current clinical data on PP1 and SS3 adenomas and compared the reported data with the data from a single institutional cohort.

Methods: Medline and Google Scholar were searched from 1990 to 2020 for clinical series of PP1 and SS3 adenomas in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. Studies were included if they had reported pituitary pathology as PP1 or SS3 adenomas and had reported the clinical outcomes after surgical intervention. To better define the PP1 phenotype compared with non-PP1 adenomas, we also reviewed the adenomas treated surgically at our institution from 2012 to 2019.

Results: Of all the tumors reported in the studies as PP1 or SS3, 99% were macroadenomas and 18% were giant adenomas (>4 cm). Of the reported patients, 31.8% had received radiotherapy, and 22.9% had undergone multiple surgeries for their pituitary tumor. In our single-center experience, 20 patients had an adenoma that met the criteria for a PP1 adenoma. Compared with the 1146 non-PP1 tumors, the PP1 tumors did not show statistically significant differences in the extent of resection, size, number of previous surgeries, future reoperations, rate of radiotherapy, p53 staining, or MIB-1 labeling index.

Conclusions: The findings from the present large, single-center study comparing PP1 and non-PP1 adenomas do not suggest that PP1 tumors are more aggressive. Further work is warranted to identify the pathologic subtypes of pituitary adenomas that are consistently more clinically aggressive.
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http://dx.doi.org/10.1016/j.wneu.2021.04.003DOI Listing
July 2021

Selection of the Lowest Instrumented Vertebra and Relative Odds Ratio of Distal Adding-on for Lenke Type 1A and 2A Curves in Adolescent Idiopathic Scoliosis: A Systematic Review and Meta-analysis.

Neurospine 2020 Dec 31;17(4):902-909. Epub 2020 Dec 31.

Department of Orthopedics, Tri-Service General Hospital, Taipei City, Taiwan.

Objective: To examine existing literature and pool the data to determine the relative odds ratio of "adding-on" (AO) based on various reported criteria for lower instrumented vertebra (LIV) selection in Lenke type 1A and 2A curves.

Methods: Using electronic databases, studies reporting on AO and LIV selection in Lenke type 1A and 2A curves were identified. Studies were excluded if they failed to meet the following criteria: ≥ 30 patients, Lenke type 1A or 2A curves, thoracic-only fusions, and inclusion of outcome differences in AO and non-AO groups. Review articles, letters, and case reports were excluded.

Results: Six studies were identified reporting on 732 patients with either Lenke type 1A or 2A curves treated with thoracic-only fusions. Five different landmarks were used for LIV selection in these studies including the stable vertebra (SV) -1, end vertebra (EV) +1, neutral vertebra (NV), touched vertebra (TV), and substantially touched vertebra (STV) versus nonsubstantially touched vertebra (nSTV) +1. The pooled odds ratios of AO for choosing LIV at levels above the afore landmarks (i.e. , ending the construct "short") versus at the landmarks were 2.59 (SV-1), 2.43 (EV+1), 3.05 (NV), 3.40 (TV), and 4.52 (STV/nSTV+1), all at 95% confidence interval.

Conclusion: Five landmarks shared a similar characteristic in that the incidence of AO was significantly higher if the LIV was proximal to the chosen landmark. In addition, choosing STV/(nSTV+1) as the LIV have the lowest absolute risk of AO and the greatest risk reduction. If additional levels were fused (i.e. , LIV distal to the landmark), there was no statistically significant benefit in further reducing the risk of AO. Selection of the optimal LIV is a complex issue and spine surgeons must balance the risk of AO with the need for motion preservation in young patients.
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http://dx.doi.org/10.14245/ns.2040234.117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788412PMC
December 2020

A Type II Split Cord Malformation in an Adult Patient: An Operative Case Report.

Oper Neurosurg (Hagerstown) 2021 01;20(2):E148-E151

Division of Pediatric Neurosurgery, UCSF Benioff Children's Hospital, San Francisco, California.

Background And Importance: Split cord malformations (SCMs) are rare conditions in which the spinal cord is split into two hemicords within either a single thecal sac or two separate thecal sacs. The hemicords are typically split by a bony or fibrous structure. We present an adult patient who presented with a type II SCM with tethered cord. This is the first case of such a presentation with an accompanying intraoperative video. Unusual features of the case were the presence of an incomplete fibrous septum and lack of a discrete filum terminale.

Clinical Presentation: A 50-yr-old woman presented with back pain, radiculopathy, urinary urgency, and episodic fecal incontinence. Her exam was notable for weakness of the right extensor hallicus longus. Imaging showed an SCM extending from L3 to S1, a fibrous septum located at L4-5, and a low-lying conus at S4. She was treated with a decompressive L3-S4 laminectomy and disconnection of all the dural attachment points. She required lumbar drain placement postoperatively and reoperation for wound dehiscence and persistent pseudomeningocele. At the time of last follow-up, she was neurologically intact with improvement in bowel/bladder function.

Conclusion: SCM is an uncommon presentation in adults and is often accompanied by findings of skin stigmata, tethered cord, and other central nervous system/skeletal anomalies. Obtaining full multimodal imaging is critical to understanding subtle anatomic variations that can pose operative challenges. We report the treatment of an adult patient with type II SCM, and provide an intraoperative video demonstrating the removal of an incomplete midline fibrous septum.
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http://dx.doi.org/10.1093/ons/opaa334DOI Listing
January 2021

Recurrent brainstem cavernous malformations following primary resection: blind spots, fine lines, and the right-angle method.

J Neurosurg 2020 Nov 20:1-12. Epub 2020 Nov 20.

1Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and.

Objective: Proximity of brainstem cavernous malformations (BSCMs) to tracts and cranial nerve nuclei make it costly to transgress normal tissue in accessing the lesion or disrupting normal tissue adjacent to the lesion in the separation plane. This interplay between tissue sensitivity and extreme eloquence makes it difficult to avoid leaving a remnant on occasion. Recurrences require operative intervention, which may increase morbidity, lengthen recovery, and add to overall costs. An approximately 20-year experience with patients with recurrent BSCM lesions following primary microsurgical resection was reviewed.

Methods: A prospectively maintained database of 802 patients who underwent microsurgical resection of cerebral cavernous malformations during 1997-2018 was queried to identify 213 patients with BSCMs. A retrospective chart review was conducted for patients with recurrent BSCM after primary resection who required a second surgery.

Results: Fourteen of 213 patients (6.6%) underwent repeat resection for recurrent BSCM. Thirty-four hemorrhagic events were observed among these 14 patients over 576 patient-years (recurrent hemorrhage rate, 5.9% per year; median discrete hemorrhagic events, 2; median time to rehemorrhage, 897 days). BSCM occurred in the pons in 10 cases, midbrain in 2 cases, and medulla in 2 cases. A blind spot in the operative corridor was the most common cause of residual BSCM (9 patients). All recurrent BSCMs were removed completely, although 2 patients each required 2 operations to treat recurrence. Twelve patients had unchanged or improved modified Rankin Scale scores at last clinical evaluation compared with admission, and 2 patients had worse scores. Recurrence was more common among patients who were operated on in the first versus the second half of the series (8.5% vs 4.7%).

Conclusions: The 6.6% rate of BSCM recurrence requiring reoperation reflects the fine lines between complete resection and recurrence and between safe and harmful surgery. The detection of remnants is difficult postoperatively and remains so even at 6 months when the resection bed has healed. The 5.9% annual hemorrhage risk associated with recurrent BSCM in this experience is consistent with that reported for unoperated BSCMs. The right-angle method helps to anticipate blind spots and meticulously inspect the resection cavity for residual BSCM during surgery. A low percentage of recurrent BSCM (5%-10%) ensures ongoing effort toward an acceptable balance of safety and completeness.
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http://dx.doi.org/10.3171/2020.6.JNS201555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134603PMC
November 2020

Cerebrovascular complications of coccidioidomycosis meningitis: Case report and systematic review.

J Clin Neurosci 2020 Oct 2;80:282-289. Epub 2020 Oct 2.

Department of Medicine, University of California San Francisco, 505 Parnassus Avenue, Room M1498, Box 0119, San Francisco, CA 94117, USA.

Coccidioidomycosis exposure is common in the southwest United States and northern Mexico. Dissemination to the meninges is the most severe form of progression. Although ischemic strokes are well-reported in these patients, other cerebrovascular complications of coccidioidomycosis meningitis (CM), as well as their treatment options and outcomes, have not been systematically studied. We present a uniquely severe case of CM with several cerebrovascular complications. We also systematically queried PubMed and EMBASE databases, including articles published before April 2020 reporting human patients with CM-induced cerebrovascular pathology other than ischemic infarcts. Sixteen articles met inclusion criteria, which describe 6 patients with aneurysmal hemorrhage, 10 with non-aneurysmal hemorrhage, one with vasospasm, and one with transient ischemic attacks. CM-associated aneurysms invariably presented with hemorrhage. These were universally fatal until the past decade, when advances in surgical clipping and/or combined surgical and endovascular treatment have improved outcomes. We found that non-aneurysmal intracranial hemorrhages were limited to male patients, involved a diverse set of intracranial vasculature, and had a mortality rate surpassing 80%. Vasospasm was reported once, and was treated with percutaneous transluminal angioplasty. Transient ischemic attacks were reported once, and were successfully treated with fluconazole and dexamethasone. This review suggests that CM can present with a wide array of cerebrovascular complications, including ischemic infarcts, aneurysmogenesis, non-aneurysmal intracranial hemorrhage, vasospasm, and transient ischemic attacks. Mortality has improved over time due to advances in surgical and endovascular treatment modalities. The exception is non-aneurysmal intracranial hemorrhage, which remains associated with high mortality rates and few targeted therapeutic options.
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http://dx.doi.org/10.1016/j.jocn.2020.08.007DOI Listing
October 2020

Higher cytolytic score correlates with an immunosuppressive tumor microenvironment and reduced survival in glioblastoma.

Sci Rep 2020 10 16;10(1):17580. Epub 2020 Oct 16.

Department of Neurological Surgery, University of California San Francisco, San Francisco, USA.

Cytolytic score (CYT), calculated from mRNA expression levels of granzyme and perforin, positively correlates with CD8+ T cell infiltration/activity in a variety of cancers. Unlike other cancers, higher CYT has been associated with worse prognosis in glioblastoma (GBM). To address this discrepancy, we sought to investigate the relationship between CYT and immune checkpoint gene score (ICGscore), as well as their correlation with patient survival and tumor immune cell infiltration. Clinical and RNA-sequencing data for patients with newly diagnosed GBM were obtained from The Cancer Genome Atlas. Maximally-selected rank statistics was used to dichotomize subgroups. CIBERSORT was used to estimate abudence of immune cell-types. Spearman correlation was used to characterize the relationship between CYT and ICGscore. Kaplan-Meier curves were generated for survival analysis. Overall, 28/151 patients had high CYT. High CYT was associated with a mesenchymal subtype (p < 0.001) and worse survival (7.45 vs. 12.2 months, p < 0.001). There were no differences in patient demographics, IDH/MGMT mutation status, or treatment. On subgroup analysis, patients with high CYT/ICGscore had significantly increased CD8+ infiltration (p < 0.001), as expected, and worse survival (HR 0.445, p < 0.01). Furthermore, CYT strongly correlated with ICGscore (R = 0.675, p < 0.001). The high CYT/ICGscore subgroup was associated with greater infiltration of M2 macrophages (p = 0.011) and neutrophils (p = 0.055). Our study highlights a multidimensional immunosuppressive GBM microenvironment in patients with higher CYT and potentially identifies patients with high CYT/ICGscore as a subgroup that may particularly benefit from multi-faceted immunotherapies, given their already elevated tumor CD8+ T cell levels.
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http://dx.doi.org/10.1038/s41598-020-73793-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567862PMC
October 2020

Clinical characteristics and outcomes in elderly patients undergoing transsphenoidal surgery for nonfunctioning pituitary adenoma.

Neurosurg Focus 2020 10;49(4):E19

Departments of2Neurological Surgery and.

Objective: Life expectancy has increased over the past century, causing a shift in the demographic distribution toward older age groups. Elderly patients comprise up to 14% of all patients with pituitary tumors, with most lesions being nonfunctioning pituitary adenomas (NFPAs). Here, the authors evaluated demographics, outcomes, and postoperative complications between nonelderly adult and elderly NFPA patients.

Methods: A retrospective review of 908 patients undergoing transsphenoidal surgery (TSS) for NFPA at a single institution from 2007 to 2019 was conducted. Clinical and surgical outcomes and postoperative complications were compared between nonelderly adult (age ≥ 18 and ≤ 65 years) and elderly patients (age > 65 years).

Results: There were 614 and 294 patients in the nonelderly and elderly groups, respectively. Both groups were similar in sex (57.3% vs 60.5% males; p = 0.4), tumor size (2.56 vs 2.46 cm; p = 0.2), and cavernous sinus invasion (35.8% vs 33.7%; p = 0.6). Regarding postoperative outcomes, length of stay (1 vs 2 days; p = 0.5), extent of resection (59.8% vs 64.8% gross-total resection; p = 0.2), CSF leak requiring surgical revision (4.3% vs 1.4%; p = 0.06), 30-day readmission (8.1% vs 7.3%; p = 0.7), infection (3.1% vs 2.0%; p = 0.5), and new hypopituitarism (13.9% vs 12.0%; p = 0.3) were similar between both groups. Elderly patients were less likely to receive adjuvant radiation (8.7% vs 16.3%; p = 0.009), undergo future reoperation (3.8% vs 9.5%; p = 0.003), and experience postoperative diabetes insipidus (DI) (3.7% vs 9.4%; p = 0.002), and more likely to have postoperative hyponatremia (26.7% vs 16.4%; p < 0.001) and new cranial nerve deficit (1.9% vs 0.0%; p = 0.01). Subanalysis of elderly patients showed that patients with higher Charlson Comorbidity Index scores had comparable outcomes other than higher DI rates (8.1% vs 0.0%; p = 0.006). Elderly patients' postoperative sodium peaked and troughed on postoperative day 3 (POD3) (mean 138.7 mEq/L) and POD9 (mean 130.8 mEq/L), respectively, compared with nonelderly patients (peak POD2: mean 139.9 mEq/L; trough POD8: mean 131.3 mEq/L).

Conclusions: The authors' analysis revealed that TSS for NFPA in elderly patients is safe with low complication rates. In this cohort, more elderly patients experienced postoperative hyponatremia, while more nonelderly patients experienced postoperative DI. These findings, combined with the observation of higher DI in patients with more comorbidities and elderly patients experiencing later peaks and troughs in serum sodium, suggest age-related differences in sodium regulation after NFPA resection. The authors hope that their results will help guide discussions with elderly patients regarding risks and outcomes of TSS.
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http://dx.doi.org/10.3171/2020.7.FOCUS20524DOI Listing
October 2020

Ventriculoperitoneal shunt infection rates using a standard surgical technique, including topical and intraventricular vancomycin: the Children's Hospital Oakland experience.

J Neurosurg Pediatr 2020 Jul 24:1-9. Epub 2020 Jul 24.

1Department of Neurological Surgery, University of California, San Francisco; and.

Objective: Ventriculoperitoneal (VP) shunt infections are common complications after shunt operations. Despite the use of intravenous antibiotics, the incidence of infections remains high. Though antibiotic-impregnated catheters (AICs) are commonly used, another method of infection prophylaxis is the use of intraventricular (IVT) antibiotics. The authors describe their single-institution experience with a standard shunt protocol utilizing prophylactic IVT and topical vancomycin administration and report the incidence of pediatric shunt infections.

Methods: Three hundred two patients undergoing VP shunt procedures with IVT and topical vancomycin between 2006 and 2016 were included. Patients were excluded if their age at surgery was greater than 18 years. Shunt operations were performed at a single institution following a standard shunt protocol implementing IVT and topical vancomycin. No AICs were used. Clinical data were retrospectively collected from the electronic health records.

Results: Over the 11-year study period, 593 VP shunt operations were performed with IVT and topical vancomycin, and a total of 19 infections occurred (incidence 3.2% per procedure). The majority of infections (n = 10, 52.6%) were caused by Staphylococcus epidermidis. The median time to shunt infection was 3.7 weeks. On multivariate analysis, the presence of a CSF leak (OR 31.5 [95% CI 8.8-112.6]) and age less than 6 months (OR 3.6 [95% CI 1.2-10.7]) were statistically significantly associated with the development of a shunt infection. A post hoc analysis comparing infection rates after procedures that adhered to the shunt protocol and those that did not administer IVT and topical vancomycin, plus historical controls, revealed a difference in infection rates (3.2% vs 6.9%, p = 0.03).

Conclusions: The use of a standardized shunt operation technique that includes IVT and topical vancomycin is associated with a total shunt infection incidence of 3.2% per procedure, which compares favorably with the reported rates of shunt infection in the literature. The majority of infections occurred within 2 months of surgery and the most common causative organism was S. epidermidis. Young age (< 6 months) at the time of surgery and the presence of a postoperative CSF leak were statistically significantly associated with postoperative shunt infection on multivariate analysis. The results are hypothesis generating, and the authors propose that IVT and topical administration of vancomycin as part of a standardized shunt operation protocol may be an appropriate option for preventing pediatric shunt infections.
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http://dx.doi.org/10.3171/2020.4.PEDS209DOI Listing
July 2020

Clinical characteristics and outcomes of null-cell versus silent gonadotroph adenomas in a series of 1166 pituitary adenomas from a single institution.

Neurosurg Focus 2020 06;48(6):E13

3Department of Neurological Surgery, University of California, San Francisco, California.

Objective: Nonfunctioning pituitary adenomas present without biochemical or clinical signs of hormone excess and are the second most common type of pituitary adenomas. The 2017 WHO classification scheme of pituitary adenomas differentiates null-cell adenomas (NCAs) and silent gonadotroph adenomas (SGAs). The present study sought to highlight the differences in patient characteristics and clinical outcomes between NCAs and SGAs.

Methods: The records of 1166 patients who underwent transsphenoidal surgery for pituitary adenoma between 2012 and 2019 at a single institution were retrospectively reviewed. Patient demographics and clinical outcomes were collected.

Results: Of the overall pituitary adenoma cohort, 12.8% (n = 149) were SGAs and 9.2% (n = 107) NCAs. NCAs were significantly more common in female patients than SGAs (61.7% vs 26.8%, p < 0.001). There were no differences in patient demographics, initial tumor size, or perioperative and short-term clinical outcomes. There was no significant difference in the amount of follow-up between patients with NCAs and those with SGAs (33.8 months vs 29.1 months, p = 0.237). Patients with NCAs had significantly higher recurrence (p = 0.021), adjuvant radiation therapy usage (p = 0.002), and postoperative diabetes insipidus (p = 0.028). NCA pathology was independently associated with tumor recurrence (HR 3.64, 95% CI 1.07-12.30; p = 0.038), as were cavernous sinus invasion (HR 3.97, 95% CI 1.04-15.14; p = 0.043) and anteroposterior dimension of the tumor (HR 2.23, 95% CI 1.09-4.59; p = 0.030).

Conclusions: This study supports the definition of NCAs and SGAs as separate subgroups of nonfunctioning pituitary adenomas, and it highlights significant differences in long-term clinical outcomes, including tumor recurrence and the associated need for adjuvant radiation therapy, as well as postoperative diabetes insipidus. The authors also provide insight into independent risk factors for these outcomes in the adenoma population studied, providing clinicians with additional predictors of patient outcomes. Follow-up studies will hopefully uncover mechanisms of biological aggressiveness in NCAs and associated molecular targets.
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http://dx.doi.org/10.3171/2020.3.FOCUS20114DOI Listing
June 2020

Risk factors for deep surgical site infection following thoracolumbar spinal surgery

J Neurosurg Spine 2019 Nov 1;32(2):292-301. Epub 2019 Nov 1.

Department of Neurological Surgery, University of California, San Francisco, California

Objective: Surgical site infection (SSI) following spine surgery causes major morbidity and greatly impedes functional recovery. In the modern era of advanced operative techniques and improved perioperative care, SSI remains a problematic complication that may be reduced with institutional practices. The objectives of this study were to 1) characterize the SSI rate and microbial etiology following spine surgery for various thoracolumbar diseases, and 2) identify risk factors that were associated with SSI despite current perioperative management.

Methods: All patients treated with thoracic or lumbar spine operations on the neurosurgery service at the University of California, San Francisco from April 2012 to April 2016 were formally reviewed for SSI using the National Healthcare Safety Network (NHSN) guidelines. Preoperative risk variables included age, sex, BMI, smoking, diabetes mellitus (DM), coronary artery disease (CAD), ambulatory status, history of malignancy, use of preoperative chlorhexidine gluconate (CHG) showers, and the American Society of Anesthesiologists (ASA) classification. Operative variables included surgical pathology, resident involvement, spine level and surgical technique, instrumentation, antibiotic and steroid use, estimated blood loss (EBL), and operative time. Multivariable logistic regression was used to evaluate predictors for SSI. Odds ratios and 95% confidence intervals were reported.

Results: In total, 2252 consecutive patients underwent thoracolumbar spine surgery. The mean patient age was 58.6 ± 13.8 years and 49.6% were male. The mean hospital length of stay was 6.6 ± 7.4 days. Sixty percent of patients had degenerative conditions, and 51.9% underwent fusions. Sixty percent of patients utilized presurgery CHG showers. The mean operative duration was 3.7 ± 2 hours, and the mean EBL was 467 ± 829 ml. Compared to nonfusion patients, fusion patients were older (mean 60.1 ± 12.7 vs 57.1 ± 14.7 years, p < 0.001), were more likely to have an ASA classification > II (48.0% vs 36.0%, p < 0.001), and experienced longer operative times (252.3 ± 120.9 minutes vs 191.1 ± 110.2 minutes, p < 0.001). Eleven patients had deep SSI (0.49%), and the most common causative organisms were methicillin-sensitive Staphylococcus aureus and methicillin-resistant S. aureus. Patients with CAD (p = 0.003) or DM (p = 0.050), and those who were male (p = 0.006), were predictors of increased odds of SSI, and presurgery CHG showers (p = 0.001) were associated with decreased odds of SSI.

Conclusions: This institutional experience over a 4-year period revealed that the overall rate of SSI by the NHSN criteria was low at 0.49% following thoracolumbar surgery. This was attributable to the implementation of presurgery optimization, and intraoperative and postoperative measures to prevent SSI across the authors’ institution. Despite prevention measures, having a history of CAD or DM, and being male, were risk factors associated with increased SSI, and presurgery CHG shower utilization decreased SSI risk in patients.

Abbreviations: ASA = American Society of Anesthesiologists; CAD = coronary artery disease; CHG = chlorhexidine gluconate; CI = confidence interval; DM = diabetes mellitus; EBL = estimated blood loss; LOS = length of stay; MIS = minimally invasive surgery; MRSA = methicillin-resistant Staphylococcus aureus; MRSE = methicillin-resistant Staphylococcus epidermidis; MSSA = methicillin-sensitive S. aureus; MSSE = methicillin-sensitive S. epidermidis; NHSN = National Healthcare Safety Network; OR = odds ratio; SSI = surgical site infection.
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November 2019

A middle cerebral artery ischemic stroke occurring in a child with a large prolactinoma.

Childs Nerv Syst 2020 04 18;36(4):853-856. Epub 2019 Dec 18.

Department of Pediatric Neurosurgery, Valley Children's Healthcare, 9300 Valley Children's Place, Madera, CA, 93636, USA.

Pituitary adenomas are rare in children, and often present with symptoms of headache, nausea or emesis, visual disturbance, or hormonal hypersecretion. With large tumors, mass effect from the lesion can lead to severe endocrinopathy and compression of intracranial neurovascular structures. In this case report, we describe an unusual presentation of an ischemic stroke in the territory of the right middle cerebral artery resulting from a prolactin-secreting macroadenoma. The patient's primary symptoms were headache, left facial droop, and left hemibody weakness. She was successfully managed with cabergoline, a dopamine agonist, with a reduction in the size of the tumor and normalization of serum prolactin levels. She remained clinically stable throughout her hospitalization, and was safely discharged without surgical intervention. In her recent 2-year follow-up, her tumor and prolactin levels were stable and she had dramatic improvements in her left-sided muscle strength.
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http://dx.doi.org/10.1007/s00381-019-04446-zDOI Listing
April 2020

Cone Beam Intraoperative Computed Tomography-based Image Guidance for Minimally Invasive Transforaminal Interbody Fusion.

J Vis Exp 2019 08 6(150). Epub 2019 Aug 6.

Department of Neurological Surgery, University of California, San Francisco.

Transforaminal lumbar interbody fusion (TLIF) is commonly used for the treatment of spinal stenosis, degenerative disc disease, and spondylolisthesis. Minimally invasive surgery (MIS) approaches have been applied to this technique with an associated decrease in estimated blood loss (EBL), length of hospital stay, and infection rates, while preserving outcomes with traditional open surgery. Previous MIS TLIF techniques involve significant fluoroscopy that subjects the patient, surgeon, and operating room staff to non-trivial levels of radiation exposure, particularly for complex multi-level procedures. We present a technique that utilizes an intraoperative computed tomography (CT) scan to aid in placement of pedicle screws, followed by traditional fluoroscopy for confirmation of cage placement. Patients are positioned in the standard fashion and a reference arc is placed in the posterior superior iliac spine (PSIS) followed by intraoperative CT scan. This allows for image-guidance-based placement of pedicle screws through a one-inch skin incision on each side. Unlike traditional MIS-TLIF that requires significant fluoroscopic imaging during this stage, the operation can now be performed without any additional radiation exposure to the patient or operating room staff. After completion of the facetectomy and discectomy, final TLIF cage placement is confirmed with fluoroscopy. This technique has the potential to decrease operative time and minimize total radiation exposure.
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http://dx.doi.org/10.3791/57830DOI Listing
August 2019

Chlorhexidine Showers are Associated With a Reduction in Surgical Site Infection Following Spine Surgery: An Analysis of 4266 Consecutive Surgeries.

Neurosurgery 2019 12;85(6):817-826

Department of Neurosurgery, University of California, San Francisco, San Francisco, California.

Background: Surgical site infection (SSI) is a common complication following spinal surgery. Prevention is critical to maintaining safe patient care and reducing additional costs associated with treatment.

Objective: To determine the efficacy of preoperative chlorhexidine (CHG) showers on SSI rates following fusion and nonfusion spine surgery.

Methods: A mandatory preoperative CHG shower protocol was implemented at our institution in November 2013. A cohort comparison of 4266 consecutive patients assessed differences in SSI rates for the pre- and postimplementation periods. Subgroup analysis was performed on the type of spinal surgery (eg, fusion vs nonfusion). Data represent all spine surgeries performed between April 2012 and April 2016.

Results: The overall mean SSI rate was 0.4%. There was no significant difference between the pre- (0.7%) and postimplementation periods (0.2%; P = .08). Subgroup analysis stratified by procedure type showed that the SSI rate for the nonfusion patients was significantly lower in the post- (0.1%) than the preimplementation group (0.7%; P = .02). There was no significant difference between SSI rates for the pre- (0.8%) and postimplementation groups (0.3%) for the fusion cohort (P = .21). In multivariate analysis, the implementation of preoperative CHG showers were associated with significantly decreased odds of SSI (odds ratio = 0.15, 95% confidence interval [0.03-0.55], P < .01).

Conclusion: This is the largest study investigating the efficacy of preoperative CHG showers on SSI following spinal surgery. In adjusted multivariate analysis, CHG showering was associated with a significant decrease in SSI following spinal surgery.
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http://dx.doi.org/10.1093/neuros/nyy568DOI Listing
December 2019

Development of a validated computer-based preoperative predictive model for pseudarthrosis with 91% accuracy in 336 adult spinal deformity patients.

Neurosurg Focus 2018 11;45(5):E11

1Department of Neurological Surgery, University of California, San Francisco, California.

OBJECTIVEPseudarthrosis can occur following adult spinal deformity (ASD) surgery and can lead to instrumentation failure, recurrent pain, and ultimately revision surgery. In addition, it is one of the most expensive complications of ASD surgery. Risk factors contributing to pseudarthrosis in ASD have been described; however, a preoperative model predicting the development of pseudarthrosis does not exist. The goal of this study was to create a preoperative predictive model for pseudarthrosis based on demographic, radiographic, and surgical factors.METHODSA retrospective review of a prospectively maintained, multicenter ASD database was conducted. Study inclusion criteria consisted of adult patients (age ≥ 18 years) with spinal deformity and surgery for the ASD. From among 82 variables assessed, 21 were used for model building after applying collinearity testing, redundancy, and univariable predictor importance ≥ 0.90. Variables included demographic data along with comorbidities, modifiable surgical variables, baseline coronal and sagittal radiographic parameters, and baseline scores for health-related quality of life measures. Patients groups were determined according to their Lenke radiographic fusion type at the 2-year follow-up: bilateral or unilateral fusion (union) or pseudarthrosis (nonunion). A decision tree was constructed, and internal validation was accomplished via bootstrapped training and testing data sets. Accuracy and the area under the receiver operating characteristic curve (AUC) were calculated to evaluate the model.RESULTSA total of 336 patients were included in the study (nonunion: 105, union: 231). The model was 91.3% accurate with an AUC of 0.94. From 82 initial variables, the top 21 covered a wide range of areas including preoperative alignment, comorbidities, patient demographics, and surgical use of graft material.CONCLUSIONSA model for predicting the development of pseudarthrosis at the 2-year follow-up was successfully created. This model is the first of its kind for complex predictive analytics in the development of pseudarthrosis for patients with ASD undergoing surgical correction and can aid in clinical decision-making for potential preventative strategies.
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http://dx.doi.org/10.3171/2018.8.FOCUS18246DOI Listing
November 2018

Navigation-Assisted Minimally Invasive Surgery Deformity Correction.

Neurosurg Clin N Am 2018 Jul;29(3):439-451

Department of Neurological Surgery, University of California San Francisco, 505 Parnassus Avenue, Room M779, San Francisco, CA 94143-0112, USA.

Surgical correction of deformity is a complex endeavor. Although more traditional, open techniques remain important, minimally invasive surgery (MIS) techniques have been increasingly studied as an alternative approach. In particular, the circumferential MIS approach, which may incorporate a lateral/anterior as well as a subsequent posterior approach, has been investigated as a promising algorithm/protocol. Utilization of navigation guidance during MIS deformity correction is an important intraoperative tool for the surgeon.
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http://dx.doi.org/10.1016/j.nec.2018.03.002DOI Listing
July 2018

Potential of predictive computer models for preoperative patient selection to enhance overall quality-adjusted life years gained at 2-year follow-up: a simulation in 234 patients with adult spinal deformity.

Neurosurg Focus 2017 Dec;43(6):E2

Department of Neurological Surgery, University of California, San Francisco, California.

OBJECTIVE Patients with adult spinal deformity (ASD) experience significant quality of life improvements after surgery. Treatment, however, is expensive and complication rates are high. Predictive analytics has the potential to use many variables to make accurate predictions in large data sets. A validated minimum clinically important difference (MCID) model has the potential to assist in patient selection, thereby improving outcomes and, potentially, cost-effectiveness. METHODS The present study was a retrospective analysis of a multiinstitutional database of patients with ASD. Inclusion criteria were as follows: age ≥ 18 years, radiographic evidence of ASD, 2-year follow-up, and preoperative Oswestry Disability Index (ODI) > 15. Forty-six variables were used for model training: demographic data, radiographic parameters, surgical variables, and results on the health-related quality of life questionnaire. Patients were grouped as reaching a 2-year ODI MCID (+MCID) or not (-MCID). An ensemble of 5 different bootstrapped decision trees was constructed using the C5.0 algorithm. Internal validation was performed via 70:30 data split for training/testing. Model accuracy and area under the curve (AUC) were calculated. The mean quality-adjusted life years (QALYs) and QALYs gained at 2 years were calculated and discounted at 3.5% per year. The QALYs were compared between patients in the +MCID and -MCID groups. RESULTS A total of 234 patients met inclusion criteria (+MCID 129, -MCID 105). Sixty-nine patients (29.5%) were included for model testing. Predicted versus actual results were 50 versus 40 for +MCID and 19 versus 29 for -MCID (i.e., 10 patients were misclassified). Model accuracy was 85.5%, with 0.96 AUC. Predicted results showed that patients in the +MCID group had significantly greater 2-year mean QALYs (p = 0.0057) and QALYs gained (p = 0.0002). CONCLUSIONS A successful model with 85.5% accuracy and 0.96 AUC was constructed to predict which patients would reach ODI MCID. The patients in the +MCID group had significantly higher mean 2-year QALYs and QALYs gained. This study provides proof of concept for using predictive modeling techniques to optimize patient selection in complex spine surgery.
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http://dx.doi.org/10.3171/2017.9.FOCUS17494DOI Listing
December 2017

Radiation exposure with hybrid image-guidance-based minimally invasive transforaminal lumbar interbody fusion.

J Clin Neurosci 2018 Feb 11;48:122-127. Epub 2017 Nov 11.

Department of Neurological Surgery, University of California, San Francisco, United States. Electronic address:

The transforaminal lumbar interbody fusion (TLIF) is used for the treatment of back and leg pain secondary to spinal stenosis, degenerative disc disease, and spondylolisthesis. Minimally invasive surgery (MIS) is associated with less estimated blood loss (EBL), decreased length of stay, lower infection rates, and similar outcomes compared to the traditional TLIF. Fluoroscopy time has been reported with MIS-TLIF, but there are limited data on specific radiation dosages. We performed a retrospective analysis of a prospectively acquired cohort of patients undergoing MIS-TLIF. A total of 50 patients were included. Mean age was 53 years with 60% women and mean BMI of 30 (range 21-41). Diagnoses were as follows: 45 stenosis (90%), 29 spondylolisthesis (58%), 5 facet cysts (10%), 3 scoliosis (6%), and 1 cauda equina syndrome (2%). A single level was fused in 33 cases (66%), two levels in 15 (30%), three levels in 2 (4%). Average cage height was 10 mm with mean EBL of 80 ml and operative time of 240 min. The average radiation doses from intraoperative CT scan and fluoroscopy were 35.3 and 26.5 mGy, respectively. Average CT scan and fluoroscopy times were 5.2 and 37.1 s, respectively, for a total of 42.2 s. Average length of stay was 3 days (range 1-7 days). Although these data represent a preliminary experience, by streamlining the timing of intraoperative CT scan and minimizing the amount of intraoperative fluoroscopy, this protocol has the potential for decreasing operative time and radiation exposure.
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http://dx.doi.org/10.1016/j.jocn.2017.09.026DOI Listing
February 2018

Comparing Quality of Life in Cervical Spondylotic Myelopathy with Other Chronic Debilitating Diseases Using the Short Form Survey 36-Health Survey.

World Neurosurg 2017 Oct 5;106:699-706. Epub 2017 Jan 5.

Department of Neurological Surgery, UCSF, San Francisco, California, USA.

Background: Although cervical spondylotic myelopathy (CSM) can be devastating, its relative impact on general health remains unclear. Patient responses to the Short Form Survey 36-Health Survey (SF-36) Physical Component Summary (PCS)/Mental Component Summary (MCS) were compared between CSM and other diseases to evaluate their respective impacts on quality of life. The objective of this study was to compare SF-36 PCS/MCS scores in CSM with population and disease-specific norms.

Methods: Retrospective analysis of a prospective, multicenter AOSpine North American CSM Study database. Inclusion criteria were symptomatic disease, age older than 18 years, cord compression on magnetic resonance imaging or computed tomography myelography, and baseline SF-36 values. SF-36 PCS/MCS scores in CSM were compared with national normative values and disease-specific norms using Student t test. Analysis of variance was used to assess differences across age groups and offsets from age-matched controls. Threshold for significance was P < 0.05.

Results: There were 285 patients who met the inclusion criteria. The mean age was 56.6 ± 12.0 years, with male predominance (60%). SF-36 scores revealed significant baseline disability (PCS: 34.5 ± 9.8; MCS: 41.5 ± 14.4). Although there were no differences across age groups, when compared with age-matched normative data, younger patients had a larger PCS offset than older patients. CSM caused worse physical disability than most diseases except heart failure. Only back pain/sciatica induced worse mental disability.

Conclusions: CSM affects quality of life to an extent greater than diabetes or cancer. Although mean impact of CSM does not vary with age, younger patients suffer from greater differences in baseline function. This study highlights the impact of myelopathy on patient function, particularly among younger age groups, and suggests that CSM merits a similar caliber of healthy policy attention as more well-studied diseases.
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http://dx.doi.org/10.1016/j.wneu.2016.12.124DOI Listing
October 2017

Pleomorphic Xanthoastrocytoma with Anaplastic Features: Retrospective Case Series.

World Neurosurg 2016 Nov 28;95:368-374. Epub 2016 Jul 28.

Department of Neurological Surgery, Division of Neuropathology, University of California, San Francisco, California, USA.

Objective: Pleomorphic xanthoastrocytoma (PXA) is a unique meningocerebral glioma with a relatively favorable prognosis. PXA also possesses a variant with anaplastic features (aPXA), which is associated with poor outcomes. To date, few studies have examined the clinicopathologic importance of these anaplastic features.

Methods: From 1999-2012, 8 patients with aPXA were treated at the University of California, San Francisco, California, United States. Cases were reconfirmed by neuropathology, and clinical information regarding patient demographics, tumor characteristics, and treatment outcomes was assembled. Tumors were classified as aPXA according to the World Health Organization diagnostic criteria established in 2007.

Results: There were 5 female and 3 male patients in our cohort, ranging in age from 4-74 years at initial diagnosis. Seizure was the most common presenting symptom (50%), and the majority of tumors arose in the frontal or temporal lobes (88%). Six patients received subtotal resection (STR), and all suffered from progression despite adjuvant radiotherapy and chemotherapy. Median time to progression was 20 months, with a 1-year progression-free survival rate of 57%. Three aPXA patients expired with a median survival of 87 months. Four patients developed disseminated disease. Three of 8 (38%) showed BRAF mutation.

Conclusion: aPXA is associated with poorer clinical outcomes compared with PXA. Gross total resection should be the goal of initial treatment. It remains unclear whether adjuvant radiation and chemotherapy are able to prevent progression or dissemination. Long-term monitoring of all patients is a critical step in management due to the potential for tumors to transform into higher-grade lesions.
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http://dx.doi.org/10.1016/j.wneu.2016.07.068DOI Listing
November 2016

Results of Spinal Fusion After Spinal Nerve Sheath Tumor Resection.

World Neurosurg 2016 Jun 21;90:6-13. Epub 2016 Jan 21.

Department of Neurological Surgery, University of California, San Francisco, California; Department of Orthopedic Surgery, University of California, San Francisco, California.

Introduction: Intradural extramedullary spine tumors, approximately one-half of which are peripheral nerve sheath tumors (PNSTs), comprise two-thirds of primary spinal neoplasms. Given the rarity of PNSTs and the restricted indications for adding fusion to laminectomy for tumor resection, analyses of spinal fusion outcomes are limited.

Methods: Demographics, clinical presentation, tumor characteristics, extent of resection, spinal fusion, complications, and clinical follow-up were recorded retrospectively.

Results: A total of 221 tumors in 199 patients were identified (53 neurofibromas, 163 schwannomas, 5 malignant PNSTs); 78 patients underwent fusion (70 instrumented; 8 noninstrumented). Fusion rates were higher for extradural versus intradural lesions (60% vs. 29%; P = 0.001) and for tumors involving the cervicothoracic junction (88% vs. 31%, P < 0.001). There was no difference in fusion rates based on pathology. Rates of new or worsening sensory (19% in fusion vs. 13% in nonfused) or motor deficits (8% in fused vs. 4% in nonfused), wound infection (3% in fused vs. 6% in nonfused) and cerebrospinal fluid (CSF) leak or pseudomeningocele (6% in fused vs. 4% in nonfused) were not statistically different. There were 10 fusion-related complications: 6 adjacent segment disease, 3 implant failures, and 1 pseudoarthrosis. Mean time from surgery to last follow-up was 32 months.

Conclusions: In this cohort, PNSTs in the cervical spine, spanning the cervicothoracic junction, and extradural tumors were associated with higher rates of spinal fusion. Fusion was not associated with new or worsening motor/sensory deficits, CSF leak, pseudomeningocele, wound infection, or spinal deformity. Overall, spinal fusions were well tolerated and did not increase the risk of postoperative complications.
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http://dx.doi.org/10.1016/j.wneu.2016.01.015DOI Listing
June 2016

Surgery is cost-effective treatment for young patients with vestibular schwannomas: decision tree modeling of surgery, radiation, and observation.

Neurosurg Focus 2014 Nov;37(5):E8

Department of Neurological Surgery, Northwestern University, Chicago, Illinois.

Object: Vestibular schwannomas (VSs) are managed in 3 ways: observation ("wait and scan"); Gamma Knife surgery (GKS); or microsurgery. Whereas there is considerable literature regarding which management approach is superior, there are only a few studies addressing the cost of treating VSs, and there are no cost-utility analyses in the US to date.

Methods: In this study, the authors used the University of California at San Francisco medical record and hospital accounting databases to determine total hospital charges and costs for 33 patients who underwent open surgery, 42 patients who had GKS, and 12 patients who were observed between 2010 and 2013. The authors then performed decision-tree analysis to determine which treatment paradigm produces the highest quality-adjusted life years and to calculate the incremental cost-effectiveness ratio, depending on the patient's age at VS diagnosis.

Results: The average total hospital cost over a 3-year period for surgically treated patients was $80,074 (± $49,678) versus $9737 (± $5522) for patients receiving radiosurgery and $1746 (± $2792) for patients who were observed. When modeling the most debilitating symptoms and worst outcomes of VSs (vertigo and death) at different ages at diagnosis, radiation is dominant to observation at all ages up to 70 years. Surgery is cost-effective when compared with radiation (incremental cost-effectiveness ratio < $150,000) at younger ages at diagnosis (< 45 years old).

Conclusions: In this model, surgery is a cost-effective alternative to radiation when VS is diagnosed in patients at < 45 years. For patients ≥ 45 years, radiation is the most cost-effective treatment option.
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http://dx.doi.org/10.3171/2014.8.FOCUS14435DOI Listing
November 2014

Cervical compensatory alignment changes following correction of adult thoracic deformity: a multicenter experience in 57 patients with a 2-year follow-up.

J Neurosurg Spine 2015 Jun 20;22(6):658-65. Epub 2015 Mar 20.

9Neurological Surgery, University of California, San Francisco, California;

OBJECT Alignment changes in the cervical spine that occur following surgical correction for thoracic deformity remain poorly understood. The purpose of this study was to evaluate such changes in a cohort of adults with thoracic deformity treated surgically. METHODS The authors conducted a multicenter retrospective analysis of consecutive patients with thoracic deformity. Inclusion criteria for this study were as follows: corrective osteotomy for thoracic deformity, upper-most instrumented vertebra (UIV) between T-1 and T-4, lower-most instrumented vertebra (LIV) at or above L-5 (LIV ≥ L-5) or at the ilium (LIV-ilium), and a minimum radiographic follow-up of 2 years. Sagittal radiographic parameters were assessed preoperatively as well as at 3 months and 2 years postoperatively, including the C-7 sagittal vertical axis (SVA), C2-7 cervical lordosis (CL), C2-7 SVA, T-1 slope (T1S), T1S minus CL (T1S-CL), T2-12 thoracic kyphosis (TK), apical TK, lumbar lordosis (LL), pelvic incidence (PI), PI-LL, pelvic tilt (PT), and sacral slope (SS). RESULTS Fifty-seven patients with a mean age of 49.1 ± 14.6 years met the study inclusion criteria. The preoperative prevalence of increased CL (CL > 15°) was 48.9%. Both 3-month and 2-year apical TK improved from baseline (p < 0.05, statistically significant). At the 2-year follow-up, only the C2-7 SVA increased significantly from baseline (p = 0.01), whereas LL decreased from baseline (p < 0.01). The prevalence of increased CL was 35.3% at 3 months and 47.8% at 2 years, which did not represent a significant change. Postoperative cervical alignment changes were not significantly different from preoperative values regardless of the LIV (LIV ≥ L-5 or LIV-ilium, p > 0.05 for both). In a subset of patients with a maximum TK ≥ 60° (35 patients) and 3-column osteotomy (38 patients), no significant postoperative cervical changes were seen. CONCLUSION Increased CL is common in adult spinal deformity patients with thoracic deformities and, unlike after lumbar corrective surgery, does not appear to normalize after thoracic corrective surgery. Cervical sagittal malalignment (C2-7 SVA) also increases postoperatively. Surgeons should be aware that spontaneous cervical alignment normalization might not occur following thoracic deformity correction.
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http://dx.doi.org/10.3171/2014.10.SPINE14829DOI Listing
June 2015

Survival impact of time to initiation of chemoradiotherapy after resection of newly diagnosed glioblastoma.

J Neurosurg 2015 May 13;122(5):1144-50. Epub 2015 Mar 13.

Department of Neurological Surgery, University of California, San Francisco, California; and.

OBJECT There are few and conflicting reports on the effects of delayed initiation of chemoradiotherapy on the survival of patients with glioblastoma. The standard of care for newly diagnosed glioblastoma is concurrent radiotherapy and temozolomide chemotherapy after maximal safe resection; however, the optimal timing of such therapy is poorly defined. Given the lack of consensus in the literature, the authors performed a retrospective analysis of The Cancer Genome Atlas (TCGA) database to investigate the effect of time from surgery to initiation of therapy on survival in newly diagnosed glioblastoma. METHODS Patients with primary glioblastoma diagnosed since 2005 and treated according to the standard of care were identified from TCGA database. Kaplan-Meier and multivariate Cox regression analyses were used to compare overall survival (OS) and progression-free survival (PFS) between groups stratified by postoperative delay to initiation of radiation treatment. RESULTS There were 218 patients with newly diagnosed glioblastoma with known time to initiation of radiotherapy identified in the database. The median duration until therapy was 27 days. Delay to radiotherapy longer than the median was not associated with worse PFS (HR = 0.918, p = 0.680) or OS (HR = 1.135, p = 0.595) in multivariate analysis when controlling for age, sex, KPS score, and adjuvant chemotherapy. Patients in the highest and lowest quartiles for delay to therapy (≤ 20 days vs ≥ 36 days) did not statistically differ in PFS (p = 0.667) or OS (p = 0.124). The small subset of patients with particularly long delays (> 42 days) demonstrated worse OS (HR = 1.835, p = 0.019), but not PFS (p = 0.74). CONCLUSIONS Modest delay in initiation of postoperative chemotherapy and radiation does not appear to be associated with worse PFS or OS in patients with newly diagnosed glioblastoma, while significant delay longer than 6 weeks may be associated with worse OS.
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http://dx.doi.org/10.3171/2014.9.JNS14193DOI Listing
May 2015

Proportional upregulation of CD97 isoforms in glioblastoma and glioblastoma-derived brain tumor initiating cells.

PLoS One 2015 25;10(2):e0111532. Epub 2015 Feb 25.

Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.

CD97 is a novel glioma antigen that confers an invasive phenotype and poor survival in patients with glioblastoma (GBM), the most aggressive primary malignant brain tumor. The short isoform of CD97, known as EGF(1,2,5), has been shown to promote invasion and metastasis, but its role in gliomas and GBM-derived brain tumor initiating cells (BTICs) has not been studied. We sought to characterize CD97 expression among gliomas and identify the specific isoforms expressed. The short isoform of CD97 was identified in GBM and GBM-derived BTICs, but not low grade or anaplastic astrocytomas. All samples expressing the EGF(1,2,5) isoform were also found to express the EGF(1,2,3,5) isoform. These isoforms are believed to possess similar ligand binding patterns and interact with chondroitin sulfate, a component of the extracellular matrix, and the integrin α5β1. Using data acquired from the Cancer Genome Atlas (TCGA), we show that CD97 is upregulated among the classical and mesenchymal subtypes of GBM and significantly decreased among IDH1 mutant GBMs. Given its proven roles in tumor invasion, expression among aggressive genetic subtypes of GBM, and association with overall survival, CD97 is an attractive therapeutic target for patients with GBM.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0111532PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340952PMC
January 2016

Evidence-Based Medicine of Traumatic Thoracolumbar Burst Fractures: A Systematic Review of Operative Management across 20 Years.

Global Spine J 2015 Feb 24;5(1):73-82. Epub 2014 Nov 24.

Department of Neurological Surgery, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, United States.

Study Design Systematic literature review. Objective The management of traumatic thoracolumbar burst fractures (TLBF) remains challenging, and analyzing the levels of evidence (LOEs) for treatment practices can reform the decision-making process. However, no review has yet evaluated the operative management of traumatic thoracolumbar burst fractures with particular attention placed on LOE from an established methodology. The objective of the present study was to characterize the literature evidence for TLBF, specifically for operative management. Methods A comprehensive search of the English literature over the past 20 years was conducted using PubMed (MEDLINE). The inclusion criteria consisted of (1) traumatic burst fractures (2) in the thoracic or lumbar spine. Exclusion criteria included (1) osteoporotic burst fractures, (2) pathologic burst fractures, (3) cervical fractures, (4) biomechanical studies or those involving cadavers, and (5) computer-based studies. Studies were assigned an LOE and those meeting level 1 or 2 were included. Results From 1,138 abstracts, 272 studies met the criteria. Twenty-three studies (8.5%) met level 1 (n = 4, 1.5%) or 2 (n = 19, 7.0%) criteria. All 23 studies were reported. Conclusions The literature contains a high LOE to support the operative management of traumatic thoracolumbar burst fractures. For patients who are neurologically intact, a high LOE demonstrated similar functional outcomes, lower complication rates, and less costs with conservative management when compared with surgical management. There is a high LOE for short- or long-segment pedicle instrumentation without fusion and less invasive (percutaneous and paraspinal) approaches. Furthermore, the posterior approaches are associated with lower complications as opposed to the anterior or combined approaches.
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http://dx.doi.org/10.1055/s-0034-1396047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303483PMC
February 2015

Stable luciferase expression does not alter immunologic or in vivo growth properties of GL261 murine glioma cells.

J Transl Med 2014 Dec 3;12:345. Epub 2014 Dec 3.

Department of Neurological Surgery, Northwestern University, Feinberg School of Medicine, 676 N. St. Clair St., Suite 2210, Chicago, IL, 60611-2922, USA.

Background: GL261 cells are murine glioma cells that demonstrate proliferation, invasion, and angiogenesis when implanted in syngeneic C57BL/6 mice, providing a highly useful immunocompetent animal model of glioblastoma. Modification of tumor cells for luciferase expression enables non-invasive monitoring of orthotopic tumor growth, and has proven useful for studying glioblastoma response to novel therapeutics. However, tumor modification for luciferase has the potential for evoking host immune response against otherwise syngeneic tumor cells, thereby mitigating the tumor cells' value for tumor immunology and immunotherapy studies.

Methods: GL261 cells were infected with lentivirus containing a gene encoding firefly luciferase (GL261.luc). In vitro proliferation of parental (unmodified) GL261 and GL261.luc was measured on days 0, 1, 2, 4, and 7 following plating, and the expression of 82 mouse cytokines and chemokines were analyzed by RT-PCR array. Cell lines were also evaluated for differences in invasion and migration in modified Boyden chambers. GL261 and GL261.luc cells were then implanted intracranially in C57BL/6 mice, with GL261.luc tumor growth monitored by quantitative bioluminescence imaging, and all mice were followed for survival to compare relative malignancy of tumor cells.

Results: No difference in proliferation was indicated for GL261 vs. GL261.luc cells (p>0.05). Of the 82 genes examined by RT-PCR array, seven (9%) exhibited statistically significant change after luciferase modification. Of these, only three changed by greater than 2-fold: BMP-2, IL-13, and TGF-β2. No difference in invasion (p=0.67) or migration (p=0.26) was evident between modified vs. unmodified cells. GL261.luc cell luminescence was detectable in the brains of C57BL/6 mice at day 5 post-implantation, and tumor bioluminescence increased exponentially to day 19. Median overall survival was 20.2 days versus 19.7 days for mice receiving implantation with GL261 and GL261.luc, respectively (p=0.62). Histopathologic analysis revealed no morphological difference between tumors, and immunohistochemical analysis showed no significant difference for staining of CD3, Ki67, or CD31 (p>0.05 for all).

Conclusions: Luciferase expression in GL261 murine glioma cells does not affect GL261 proliferation, invasion, cytokine expression, or in vivo growth. Luciferase modification increases their utility for studying tumor immunology and immunotherapeutic approaches for treating glioblastoma.
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http://dx.doi.org/10.1186/s12967-014-0345-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4258256PMC
December 2014
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