Publications by authors named "Rushikesh S Joshi"

15 Publications

  • Page 1 of 1

State-of-the-art reviews predictive modeling in adult spinal deformity: applications of advanced analytics.

Spine Deform 2021 May 18. Epub 2021 May 18.

Department of Neurological Surgery, University of California, San Francisco, 400 Parnassus Avenue, A850, San Francisco, CA, 94143, USA.

Adult spinal deformity (ASD) is a complex and heterogeneous disease that can severely impact patients' lives. While it is clear that surgical correction can achieve significant improvement of spinopelvic parameters and quality of life measures in adults with spinal deformity, there remains a high risk of complication associated with surgical approaches to adult deformity. Over the past decade, utilization of surgical correction for ASD has increased dramatically as deformity correction techniques have become more refined and widely adopted. Along with this increase in surgical utilization, there has been a massive undertaking by spine surgeons to develop more robust models to predict postoperative outcomes in an effort to mitigate the relatively high complication rates. A large part of this revolution within spine surgery has been the gradual adoption of predictive analytics harnessing artificial intelligence through the use of machine learning algorithms. The development of predictive models to accurately prognosticate patient outcomes following ASD surgery represents a dramatic improvement over prior statistical models which are better suited for finding associations between variables than for their predictive utility. Machine learning models, which offer the ability to make more accurate and reproducible predictions, provide surgeons with a wide array of practical applications from augmenting clinical decision making to more wide-spread public health implications. The inclusion of these advanced computational techniques in spine practices will be paramount for improving the care of patients, by empowering both patients and surgeons to more specifically tailor clinical decisions to address individual health profiles and needs.
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http://dx.doi.org/10.1007/s43390-021-00360-0DOI Listing
May 2021

Artificial intelligence for adult spinal deformity: Current state and future directions.

Spine J 2021 May 8. Epub 2021 May 8.

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

As we experience a technological revolution unlike any other time in history, spinal surgery as a discipline is poised to undergo a dramatic transformation. As enormous amounts of data become digitized and more readily available, medical professionals approach a critical juncture with respect to how advanced computational techniques may be incorporated into clinical practices. Within neurosurgery, spinal disorders in particular, represent a complex and heterogeneous disease entity that can vary dramatically in its clinical presentation and how it may impact patients' lives. The spectrum of pathologies is extremely diverse, including many different etiologies such as trauma, oncology, spinal deformity, infection, inflammatory conditions, and degenerative disease among others. The decision to perform spine surgery, especially complex spine surgery, involves several nuances due to the interplay of biomechanical forces, bony composition, neurologic deficits, and the patient's desired goals. Adult spinal deformity as an example is one of the most complex, given its involvement of not only the spine, but rather the entirety of the skeleton in order to appreciate radiographic completeness. With the vast array of variables contributing to spinal disorders, treatment algorithms can vary significantly, and it is very difficult for surgeons to predict how patients will respond to surgery. As such, it will become imperative for spine surgeons to utilize the burgeoning availability of advanced computational tools to process unprecedented amounts of data and provide novel insights into spinal disease. These tools range from predictive models built using machine learning algorithms, to deep learning methods for imaging analysis, to natural language processing that can mine text from electronic medical records or transcribed patient visits - all to better treat the intricacies of spinal disorders. The adoption of such techniques will empower patients and propel spine surgeons into the era of personalized medicine, by allowing clinical plans to be tailored to address individual patients' needs. This paper, which exists in the context of a larger body of literatutre, provides a comprehensive review of the current state and future of artificial intelligence and machine learning with a particular emphasis on Adult spinal deformity surgery.
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http://dx.doi.org/10.1016/j.spinee.2021.04.019DOI Listing
May 2021

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

World Neurosurg 2021 Apr 20. 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
April 2021

The Role of Cancer-Associated Fibroblasts in Tumor Progression.

Cancers (Basel) 2021 Mar 19;13(6). Epub 2021 Mar 19.

Department of Neurological Surgery, University of California, San Francisco, CA 94143, USA.

In the era of genomic medicine, cancer treatment has become more personalized as novel therapeutic targets and pathways are identified. Research over the past decade has shown the increasing importance of how the tumor microenvironment (TME) and the extracellular matrix (ECM), which is a major structural component of the TME, regulate oncogenic functions including tumor progression, metastasis, angiogenesis, therapy resistance, and immune cell modulation, amongst others. Within the TME, cancer-associated fibroblasts (CAFs) have been identified in several systemic cancers as critical regulators of the malignant cancer phenotype. This review of the literature comprehensively profiles the roles of CAFs implicated in gastrointestinal, endocrine, head and neck, skin, genitourinary, lung, and breast cancers. The ubiquitous presence of CAFs highlights their significance as modulators of cancer progression and has led to the subsequent characterization of potential therapeutic targets, which may help advance the cancer treatment paradigm to determine the next generation of cancer therapy. The aim of this review is to provide a detailed overview of the key roles that CAFs play in the scope of systemic disease, the mechanisms by which they enhance protumoral effects, and the primary CAF-related markers that may offer potential targets for novel therapeutics.
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http://dx.doi.org/10.3390/cancers13061399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003545PMC
March 2021

An integrated disease-specific graded prognostic assessment scale for melanoma: contributions of KPS, CITV, number of metastases, and BRAF mutation status.

Neurooncol Adv 2021 Jan-Dec;3(1):vdaa152. Epub 2020 Nov 12.

Department of Neurosurgery, University of Minnesota, Minneapolis, Minnesota, USA.

Background: Stereotactic radiosurgery (SRS) remains a mainstay therapy in the treatment of melanoma brain metastases (BM). While prognostic scales have been developed for melanoma patients who underwent SRS treatment for BM, the pertinence of these scales in the context of molecularly targeted therapies remains unclear.

Methods: Through a multi-institutional collaboration, we collated the survival patterns of 331 melanoma BM patients with known BRAF mutation status treated with SRS. We established a prognostic scale that was validated in an independent cohort of 174 patients. All patients with BRAF mutations in this series were treated with BRAF inhibitors. Prognostic utility was assessed using Net Reclassification Index (NRI > 0) and integrated discrimination improvement (IDI) metrics.

Results: In a multivariate Cox proportional hazards model, BRAF mutation status, KPS, number of metastases, and cumulative intracranial tumor volume (CITV) independently contributed to survival prognostication for melanoma patients with SRS-treated BM ( < .05 for all variables). These variables were incorporated into a prognostic scale using the disease-specific graded prognostic assessment (ds-GPA) framework. This integrated melanoma ds-GPA scale was validated in 2 independent cohorts collated through a multi-institutional collaboration. In terms of order of prognostic importance, BRAF mutation status exerted the greatest influence on survival, while KPS, the number of metastases, and CITV exhibited comparable, lesser impacts.

Conclusions: Optimal survival prognostication for SRS-treated patients with melanoma BM requires an integrated assessment of patient characteristics (KPS), tumor characteristics (CITV and number of metastases), and the mutational profile of the melanoma (BRAF mutation status).
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http://dx.doi.org/10.1093/noajnl/vdaa152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810198PMC
November 2020

Risk factors for determining length of intensive care unit and hospital stays following correction of cervical deformity: evaluation of early severe adverse events.

J Neurosurg Spine 2020 Oct 23:1-12. Epub 2020 Oct 23.

Departments of1Neurological Surgery and.

Objective: Correction of rigid cervical deformities can be associated with high complication rates and result in prolonged intensive care unit (ICU) and hospital stays. In this study, the authors aimed to examine the risk factors contributing to length of stay (LOS) in both the hospital and ICU following adult cervical deformity (ACD) surgery and to identify severe adverse events that occurred in this setting.

Methods: A retrospective review of ACD patients who underwent posterior-based osteotomies for deformity correction from 2010 to 2019 was performed. Inclusion criteria were cervical kyphosis > 20° and/or cervical sagittal vertical axis (cSVA) > 4 cm. Multivariate analysis was used to identify risk factors independently associated with ICU and hospital LOS.

Results: A total of 107 patients were included. The mean age was 63.5 years, and 61.7% were female. Over half (52.3%) underwent 3-column osteotomies, while 47.7% underwent posterior column osteotomies. There was significant correction of all cervical parameters: cSVA (6.0 vs 3.6 cm, p < 0.001), cervical lordosis (8.2° vs -5.3°, p < 0.001), cervical scoliosis (6.5° vs 2.2°, p < 0.001), and T1-slope (40.2° vs 34.5°, p < 0.001). There were also reciprocal changes to the distal spine: thoracic kyphosis (54.4° vs 46.4°, p < 0.001), lumbar lordosis (49.9° vs 45.8°, p = 0.003), and thoracolumbar scoliosis (13.9° vs 11.1°, p = 0.009). Overall, 4 patients (3.7%) suffered aspiration-related complications, 3 patients (2.8%) experienced dysphagia requiring a feeding tube, and 4 patients (3.7%) had compromised airways, with 1 resulting in death. The mean ICU and hospital LOS were 2.8 days and 7.9 days, respectively. Multivariate analysis identified three factors independently associated with longer ICU LOS: female sex (3.0 vs 2.4 days, p = 0.004), ≥ 12 segments fused (3.5 vs 1.9 days, p = 0.002), and postoperative complication (4.0 vs 1.9 days, p = 0.017). These same factors were independently associated with longer hospital LOS as well: female sex (8.3 vs 7.3 days, p = 0.013), ≥ 12 segments fused (9.4 vs 6.2 days, p = 0.001), and complication (9.7 vs 6.7 days, p = 0.026).

Conclusions: Posterior-based osteotomies are very effective for the correction of ACD, but postoperative hospital stays are relatively longer than those following surgery for degenerative disease. Risk factors for prolonged ICU and hospital LOS consist of both nonmodifiable (female sex) and modifiable (≥ 12 segments fused and presence of complication) risk factors. Additional multicenter prospective studies will be needed to validate these findings.
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http://dx.doi.org/10.3171/2020.6.SPINE20826DOI 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

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

Comparison of perioperative complications following posterior column osteotomy versus posterior-based 3-column osteotomy for correction of rigid cervicothoracic deformity: a single-surgeon series of 95 consecutive cases.

J Neurosurg Spine 2020 May 8:1-10. Epub 2020 May 8.

Departments of1Neurological Surgery and.

Objective: The correction of severe cervicothoracic sagittal deformities can be very challenging and can be associated with significant morbidity. Often, soft-tissue releases and osteotomies are warranted to achieve the desired correction. There is a paucity of studies that examine the difference in morbidity and complication profiles for Smith-Petersen osteotomy (SPO) versus 3-column osteotomy (3CO) for cervical deformity correction.

Methods: A retrospective comparison of complication profiles between posterior-based SPO (Ames grade 2 SPO) and 3CO (Ames grade 5 opening wedge osteotomy and Ames grade 6 closing wedge osteotomy) was performed by examining a single-surgeon experience from 2011 to 2018. Patients of interest were individuals who had a cervical sagittal vertical axis (cSVA) > 4 cm and/or cervical kyphosis > 20° and who underwent corrective surgery for cervical deformity. Multivariate analysis was utilized.

Results: A total of 95 patients were included: 49 who underwent 3CO and 46 who underwent SPO. Twelve of the SPO patients underwent an anterior release procedure. The patients' mean age was 63.2 years, and 60.0% of the patients were female. All preoperative radiographic parameters showed significant correction postoperatively: cSVA (6.2 cm vs 4.5 cm [preoperative vs postoperative values], p < 0.001), cervical lordosis (6.8° [kyphosis] vs -7.5°, p < 0.001), and T1 slope (40.9° and 35.2°, p = 0.026). The overall complication rate was 37.9%, and postoperative neurological deficits were seen in 16.8% of patients. The surgical and medical complication rates were 17.9% and 23.2%, respectively. Overall, complication rates were higher in patients who underwent 3CO compared to those who underwent SPO, but this was not statistically significant (total complication rate 42.9% vs 32.6%, p = 0.304; surgical complication rate 18.4% vs 10.9%, p = 0.303; and new neurological deficit rate 20.4% vs 13.0%, p = 0.338). Medical complication rates were similar between the two groups (22.4% [3CO] vs 23.9% [SPO], p = 0.866). Independent risk factors for surgical complications included male sex (OR 10.88, p = 0.014), cSVA > 8 cm (OR 10.36, p = 0.037), and kyphosis > 20° (OR 9.48, p = 0.005). Combined anterior-posterior surgery was independently associated with higher odds of medical complications (OR 10.30, p = 0.011), and preoperative kyphosis > 20° was an independent risk factor for neurological deficits (OR 2.08, p = 0.011).

Conclusions: There was no significant difference in complication rates between 3CO and SPO for cervicothoracic deformity correction, but absolute surgical and neurological complication rates for 3CO were higher. A preoperative cSVA > 8 cm was a risk factor for surgical complications, and kyphosis > 20° was a risk factor for both surgical and neurological complications. Additional studies are warranted on this topic.
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http://dx.doi.org/10.3171/2020.3.SPINE191330DOI Listing
May 2020

Clonal ZEB1-Driven Mesenchymal Transition Promotes Targetable Oncologic Antiangiogenic Therapy Resistance.

Cancer Res 2020 04 10;80(7):1498-1511. Epub 2020 Feb 10.

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

Glioblastoma (GBM) responses to bevacizumab are invariably transient with acquired resistance. We profiled paired patient specimens and bevacizumab-resistant xenograft models pre- and post-resistance toward the primary goal of identifying regulators whose targeting could prolong the therapeutic window, and the secondary goal of identifying biomarkers of therapeutic window closure. Bevacizumab-resistant patient specimens and xenografts exhibited decreased vessel density and increased hypoxia versus pre-resistance, suggesting that resistance occurs despite effective therapeutic devascularization. Microarray analysis revealed upregulated mesenchymal genes in resistant tumors correlating with bevacizumab treatment duration and causing three changes enabling resistant tumor growth in hypoxia. First, perivascular invasiveness along remaining blood vessels, which co-opts vessels in a VEGF-independent and neoangiogenesis-independent manner, was upregulated in novel biomimetic 3D bioengineered platforms modeling the bevacizumab-resistant microenvironment. Second, tumor-initiating stem cells housed in the perivascular niche close to remaining blood vessels were enriched. Third, metabolic reprogramming assessed through real-time bioenergetic measurement and metabolomics upregulated glycolysis and suppressed oxidative phosphorylation. Single-cell sequencing of bevacizumab-resistant patient GBMs confirmed upregulated mesenchymal genes, particularly glycoprotein YKL-40 and transcription factor ZEB1, in later clones, implicating these changes as treatment-induced. Serum YKL-40 was elevated in bevacizumab-resistant versus bevacizumab-naïve patients. CRISPR and pharmacologic targeting of ZEB1 with honokiol reversed the mesenchymal gene expression and associated stem cell, invasion, and metabolic changes defining resistance. Honokiol caused greater cell death in bevacizumab-resistant than bevacizumab-responsive tumor cells, with surviving cells losing mesenchymal morphology. Employing YKL-40 as a resistance biomarker and ZEB1 as a target to prevent resistance could fulfill the promise of antiangiogenic therapy. SIGNIFICANCE: Bevacizumab resistance in GBM is associated with mesenchymal/glycolytic shifts involving YKL-40 and ZEB1. Targeting ZEB1 reduces bevacizumab-resistant GBM phenotypes. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/7/1498/F1.large.jpg.
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http://dx.doi.org/10.1158/0008-5472.CAN-19-1305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236890PMC
April 2020

Artificial Intelligence for Adult Spinal Deformity.

Neurospine 2019 Dec 31;16(4):686-694. Epub 2019 Dec 31.

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

Adult spinal deformity (ASD) is a complex disease that significantly affects the lives of many patients. Surgical correction has proven to be effective in achieving improvement of spinopelvic parameters as well as improving quality of life (QoL) for these patients. However, given the relatively high complication risk associated with ASD correction, it is of paramount importance to develop robust prognostic tools for predicting risk profile and outcomes. Historically, statistical models such as linear and logistic regression models were used to identify preoperative factors associated with postoperative outcomes. While these tools were useful for looking at simple associations, they represent generalizations across large populations, with little applicability to individual patients. More recently, predictive analytics utilizing artificial intelligence (AI) through machine learning for comprehensive processing of large amounts of data have become available for surgeons to implement. The use of these computational techniques has given surgeons the ability to leverage far more accurate and individualized predictive tools to better inform individual patients regarding predicted outcomes after ASD correction surgery. Applications range from predicting QoL measures to predicting the risk of major complications, hospital readmission, and reoperation rates. In addition, AI has been used to create a novel classification system for ASD patients, which will help surgeons identify distinct patient subpopulations with unique risk-benefit profiles. Overall, these tools will help surgeons tailor their clinical practice to address patients' individual needs and create an opportunity for personalized medicine within spine surgery.
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http://dx.doi.org/10.14245/ns.1938414.207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944987PMC
December 2019

Artificial Intelligence and the Future of Spine Surgery.

Neurospine 2019 Dec 31;16(4):637-639. Epub 2019 Dec 31.

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

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http://dx.doi.org/10.14245/ns.1938410.205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944989PMC
December 2019

Prognostic Importance of Cumulative Intracranial Tumor Volume in Patients with Gastrointestinal Brain Metastasis Treated with Stereotactic Radiosurgery.

World Neurosurg 2019 Jan 9;121:e747-e754. Epub 2018 Oct 9.

Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, Minnesota, USA. Electronic address:

Background: The disease-specific Graded Prognostic Assessment (ds-GPA) for patients with gastrointestinal (GI) tract cancer brain metastases (BM) suggests Karnofsky Performance Status (KPS) as the only pertinent prognostic factor. We evaluated the prognostic importance of cumulative intracranial tumor volume (CITV).

Methods: KPS, CITV, and overall survival were collected from consecutive patients with stereotactic radiosurgery-treated GI BM. Patients were grouped into 2 independent cohorts for development and validation of the model (termed "exploratory" and "validation" cohorts). Analyses were performed using logistic regression, Cox proportional hazards models, Net Reclassification Index (NRI >0), integrated discrimination improvement (IDI >0), and Akaike information criterion.

Results: In univariable logistic regression models, both CITV and KPS were independently associated with patient survival. The association between CITV and overall survival remained robust after controlling for KPS (P < 0.001) in a multivariable Cox proportional hazards model. Based on NRI analysis of the exploratory cohort, we found that a CITV cutoff of 12 cm best augments the prognostic accuracy of GI-ds-GPA. In this analysis, incorporation of CITV (as < or ≥12 cm) improved prognostication of the GI-specific GPA model by NRI >0 of 0.397 (95% confidence interval [CI], 0.165-0.630; P < 0.001) and IDI of 0.019 (95% CI, 0.004-0.033; P = 0.013). We confirmed the prognostic usefulness of the CITV-incorporated GI-ds-GPA in an independent validation cohort, in which CITV incorporation improved prognostic usefulness with an NRI >0 of 0.478 (95% CI, 0.257-0.699; P < 0.001) and IDI of 0.028 (95% CI, 0.014-0.043; P < 0.001).

Conclusions: CITV is an important prognostic variable in patients with stereotactic radiosurgery-treated GI BM and augments the prognostic accuracy of the GI-ds-GPA index.
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http://dx.doi.org/10.1016/j.wneu.2018.09.209DOI Listing
January 2019

Cystic Formation After Stereotactic Radiosurgery of Brain Metastasis.

World Neurosurg 2018 Jun 16;114:e719-e728. Epub 2018 Mar 16.

Department of Neurosurgery, University of Minnesota, Minneapolis, Minnesota, USA. Electronic address:

Background: Limited information is available on the natural history and etiology of cystic formation after stereotactic radiosurgery (SRS) for brain metastases (BM). We aimed to characterize the natural history of cyst formation after SRS of BM and analyze potential risk factors.

Methods: We retrospectively reviewed 214 consecutive patients who underwent a total of 1106 SRSs for BM. Demographic, clinical, dosimetric, and magnetic resonance imaging MRI data were reviewed. Statistical analysis was accomplished using Student's t test, and univariate and multivariate logistic regression.

Results: The median patient age was 61 years (range, 19-91 years), and the median duration of follow-up was 424 days (range, 91-2934 days). Eleven cases of cyst formation (0.9% of 1106 treated lesions) were identified at SRS-treated BM sites among 9 patients (2 patients developed cysts at independent sites). The median interval between first SRS and first evidence of cyst was 218 days. Seven of the 9 patients (78%) sustained progressive cyst expansion and neurologic decline requiring steroid treatment. Four of these 7 patients (57%) experienced continued neurologic decline and needed surgical fenestration. On univariate analysis, receipt of >4 rounds of SRS was the sole variable associated with an increased risk of cyst formation (odds ratio, 16.58; P = 0.001). This association remained robust after adjusting for duration of follow-up (odds ratio, 13.59; P = 0.003).

Conclusions: In our experience with 1106 SRS-treated cases of BM, cyst formation was a rare phenomenon. However, 1 in 3 patients who underwent >4 rounds of SRS sustained cyst formation. A high proportion (78%) of SRS-associated cysts progressively expanded and required medical or surgical treatment.
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http://dx.doi.org/10.1016/j.wneu.2018.03.066DOI Listing
June 2018