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Article ; Online: Artificial Intelligence in Clinical Neurosurgery: More than Machinery.

Tewarie, Ishaan Ashwini / Hulsbergen, Alexander F C / Gormley, William B / Peul, Wilco C / Broekman, Marike L D

2021 Volume 149, Page(s) 302–303

MeSH term(s)	Algorithms ; Artificial Intelligence/trends ; Deep Learning/trends ; Humans ; Machine Learning/trends ; Neurosurgical Procedures/methods ; Neurosurgical Procedures/trends
Language	English
Publishing date	2021-04-30
Publishing country	United States
Document type	Letter
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2021.02.057
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Article ; Online: Risk Factors of Second Local Recurrence in Surgically Treated Recurrent Brain Metastases: An Exploratory Analysis.

Tewarie, Ishaan Ashwini / Hulsbergen, Alexander F C / Jessurun, Charissa A C / Rendon, Luis F / Mekary, Rania A / Smith, Timothy R / Broekman, Marike L D

World neurosurgery

2022 Volume 167, Page(s) e639–e647

Abstract: Background: A first local recurrence is common after resection or radiotherapy for brain metastasis (BM). However, patients with BMs can develop multiple local recurrences over time. Published data on second local recurrences are scarce. This study ... ...

Abstract	Background: A first local recurrence is common after resection or radiotherapy for brain metastasis (BM). However, patients with BMs can develop multiple local recurrences over time. Published data on second local recurrences are scarce. This study aimed to report predictors associated with a second local recurrence in patients with BMs who underwent a craniotomy for a first locally recurrent BM. Methods: Patients were identified from a database at Brigham and Women's Hospital in Boston. Hazard ratios and 95% confidence intervals for predictors of a second local recurrence were computed using a Cox proportional hazards model. Results: Of 170 identified surgically treated first locally recurrent lesions, 74 (43.5%) progressed to second locally recurrent lesions at a median of 7 months after craniotomy. Subtotal resection of the first local BM recurrence was significantly associated with shorter time to second local recurrence (hazard ratio = 2.09; 95% confidence interval, 1.27-3.45). Infratentorial location was associated with a worse second local recurrence prognosis (hazard ratio = 2.22; 95% confidence interval, 1.24-3.96). Conclusions: A second local recurrence occurred after 43.5% of craniotomies for first recurrent lesions. Subtotal resection and infratentorial location were the strongest risk factors for worse second local recurrence prognosis following resection of first recurrent BM.
MeSH term(s)	Humans ; Female ; Neoplasm Recurrence, Local/epidemiology ; Neoplasm Recurrence, Local/surgery ; Neoplasm Recurrence, Local/pathology ; Prognosis ; Risk Factors ; Brain Neoplasms/surgery ; Brain Neoplasms/secondary ; Recurrence ; Retrospective Studies
Language	English
Publishing date	2022-08-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2022.08.066
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Article ; Online: The effect of smoking on survival in lung carcinoma patients with brain metastasis: a systematic review and meta-analysis.

Chawla, Shreya / Tewarie, Ishaan A / Zhang, Qingwei O / Hulsbergen, Alexander F C / Mekary, Rania A / Broekman, Marike L D

Neurosurgical review

2022 Volume 45, Issue 5, Page(s) 3055–3066

Abstract: The effects of smoking on survival in BM patients have yet to be reviewed and meta-analysed. However, previous studies have shown that smokers had a greater risk of dying from lung cancer compared to non-smokers. This meta-analysis, therefore, aimed to ... ...

Abstract	The effects of smoking on survival in BM patients have yet to be reviewed and meta-analysed. However, previous studies have shown that smokers had a greater risk of dying from lung cancer compared to non-smokers. This meta-analysis, therefore, aimed to analyse the effects of cigarette smoking on overall survival (OS) and progression-free survival (PFS) in lung cancer BM patients. PubMed, Embase, Web of Science, Cochrane and Google Scholar were searched for comparative studies regarding the effects of smoking on incidence and survival in brain metastases patients up to December 2020. Three independent reviewers extracted overall survival (OS) and progression-free survival data (PFS). Random-effects models were used to pool multivariate-adjusted hazard ratios (HR). Out of 1890 studies, fifteen studies with a total of 2915 patients met our inclusion criteria. Amongst lung carcinoma BM patients, those who were smokers (ever or yes) had a worse overall survival (HR: 1.34, 95% CI 1.13, 1.60, I2: 72.1%, p-heterogeneity < 0.001) than those who were non-smokers (never or no). A subgroup analysis showed the association to remain significant in the ever/never subgroup (HR: 1.34, 95% CI 1.11, 1.63) but not in the yes/no smoking subgroup (HR: 1.30, 95% CI 0.44, 3.88). This difference between the two subgroups was not statistically significant (p = 0.91). Amongst lung carcinoma BM patients, smoking was associated with a worse OS and PFS. Future studies examining BMs should report survival data stratified by uniform smoking status definitions.
MeSH term(s)	Brain Neoplasms ; Carcinoma ; Humans ; Lung/pathology ; Lung Neoplasms/pathology ; Smoking/adverse effects ; Smoking/epidemiology
Language	English
Publishing date	2022-07-14
Publishing country	Germany
Document type	Journal Article ; Meta-Analysis ; Review ; Systematic Review
ZDB-ID	6907-3
ISSN	1437-2320 ; 0344-5607
ISSN (online)	1437-2320
ISSN	0344-5607
DOI	10.1007/s10143-022-01832-1
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Article ; Online: Unnecessary Diagnostics in Neurosurgery: Finding the Ethical Balance.

Hulsbergen, Alexander F C / Muskens, Ivo S / Gormley, William B / Broekman, Marike L D

World neurosurgery

2019 Volume 125, Page(s) 527–528

Language	English
Publishing date	2019-09-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2019.02.085
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Article ; Online: Predicting leptomeningeal disease spread after resection of brain metastases using machine learning.

Tewarie, Ishaan Ashwini / Senko, Alexander W / Jessurun, Charissa A C / Zhang, Abigail Tianai / Hulsbergen, Alexander F C / Rendon, Luis / McNulty, Jack / Broekman, Marike L D / Peng, Luke C / Smith, Timothy R / Phillips, John G

Journal of neurosurgery

2022 , Page(s) 1–9

Abstract: ... prognosticated evenly by the random forest algorithm and the Cox proportional hazards model (C-index = 0.76 ...

Abstract	Objective: The incidence of leptomeningeal disease (LMD) has increased as treatments for brain metastases (BMs) have improved and patients with metastatic disease are living longer. Sample sizes of individual studies investigating LMD after surgery for BMs and its risk factors have been limited, ranging from 200 to 400 patients at risk for LMD, which only allows the use of conventional biostatistics. Here, the authors used machine learning techniques to enhance LMD prediction in a cohort of surgically treated BMs. Methods: A conditional survival forest, a Cox proportional hazards model, an extreme gradient boosting (XGBoost) classifier, an extra trees classifier, and logistic regression were trained. A synthetic minority oversampling technique (SMOTE) was used to train the models and handle the inherent class imbalance. Patients were divided into an 80:20 training and test set. Fivefold cross-validation was used on the training set for hyperparameter optimization. Patients eligible for study inclusion were adults who had consecutively undergone neurosurgical BM treatment, had been admitted to Brigham and Women's Hospital from January 2007 through December 2019, and had a minimum of 1 month of follow-up after neurosurgical treatment. Results: A total of 1054 surgically treated BM patients were included in this analysis. LMD occurred in 168 patients (15.9%) at a median of 7.05 months after BM diagnosis. The discrimination of LMD occurrence was optimal using an XGboost algorithm (area under the curve = 0.83), and the time to LMD was prognosticated evenly by the random forest algorithm and the Cox proportional hazards model (C-index = 0.76). The most important feature for both LMD classification and regression was the BM proximity to the CSF space, followed by a cerebellar BM location. Lymph node metastasis of the primary tumor at BM diagnosis and a cerebellar BM location were the strongest risk factors for both LMD occurrence and time to LMD. Conclusions: The outcomes of LMD patients in the BM population are predictable using SMOTE and machine learning. Lymph node metastasis of the primary tumor at BM diagnosis and a cerebellar BM location were the strongest LMD risk factors.
Language	English
Publishing date	2022-10-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	3089-2
ISSN	1933-0693 ; 0022-3085
ISSN (online)	1933-0693
ISSN	0022-3085
DOI	10.3171/2022.8.JNS22744
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Article ; Online: The ethical and legal status of neurosurgical guidelines: the neurosurgeon's golden fleece or Achilles' heel?

Tewarie, Ishaan Ashwini / Hulsbergen, Alexander F C / Volovici, Victor / Broekman, Marike L D

Neurosurgical focus

2020 Volume 49, Issue 5, Page(s) E14

Abstract: Neurosurgical guidelines are fundamental for evidence-based practice and have considerably increased both in number and content over the last decades. Yet, guidelines in neurosurgery are not without limitations, as they are overwhelmingly based on low- ... ...

Abstract	Neurosurgical guidelines are fundamental for evidence-based practice and have considerably increased both in number and content over the last decades. Yet, guidelines in neurosurgery are not without limitations, as they are overwhelmingly based on low-level evidence. Such recommendations have in the past been occasionally overturned by well-designed randomized controlled trials (RCTs), demonstrating the volatility of poorly underpinned evidence. Furthermore, even RCTs in surgery come with several limitations; most notably, interventions are often insufficiently standardized and assume a homogeneous patient population, which is not always applicable to neurosurgery. Lastly, guidelines are often outdated by the time they are published and smaller fields such as neurosurgery may lack a sufficient workforce to provide regular updates. These limitations raise the question of whether it is ethical to use low-level evidence for guideline recommendations, and if so, how strictly guidelines should be adhered to from an ethical and legal perspective. This article aims to offer a critical approach to the ethical and legal status of guidelines in neurosurgery. To this aim, the authors discuss: 1) the current state of neurosurgical guidelines and the evidence they are based on; 2) the degree of implementation of these guidelines; 3) the legal status of guidelines in medical disciplinary cases; and 4) the ethical balance between confident and critical use of guidelines. Ultimately, guidelines are neither laws that should always be followed nor purely academic efforts with little practical use. Every patient is unique, and tailored treatment defined by the surgeon will ensure optimal care; guidelines play an important role in creating a solid base that can be adhered to or deviated from, depending on the situation. From a research perspective, it is inevitable to rely on weaker evidence initially in order to generate more robust evidence later, and clinician-researchers have an ethical duty to contribute to generating and improving neurosurgical guidelines.
MeSH term(s)	Humans ; Neurosurgeons ; Neurosurgery ; Neurosurgical Procedures
Language	English
Publishing date	2020-09-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2026589-X
ISSN	1092-0684 ; 1092-0684
ISSN (online)	1092-0684
ISSN	1092-0684
DOI	10.3171/2020.8.FOCUS20597
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Beta-blockers and glioma: a systematic review of preclinical studies and clinical results.

Tewarie, Ishaan Ashwini / Senders, Joeky T / Hulsbergen, Alexander F C / Kremer, Stijn / Broekman, Marike L D

Neurosurgical review

2020 Volume 44, Issue 2, Page(s) 669–677

Abstract: Given the median survival of 15 months after diagnosis, novel treatment strategies are needed for glioblastoma. Beta-blockers have been demonstrated to inhibit angiogenesis and tumor cell proliferation in various cancer types. The aim of this study was ... ...

Abstract	Given the median survival of 15 months after diagnosis, novel treatment strategies are needed for glioblastoma. Beta-blockers have been demonstrated to inhibit angiogenesis and tumor cell proliferation in various cancer types. The aim of this study was to systematically review the evidence on the effect of beta-blockers on glioma growth. A systematic literature search was performed in the PubMed, Embase, Google Scholar, Web of Science, and Cochrane Central to identify all relevant studies. Preclinical studies concerning the pharmacodynamic effects of beta-blockers on glioma growth and proliferation were included, as well as clinical studies that studied the effect of beta-blockers on patient outcomes according to PRISMA guidelines. Among the 980 citations, 10 preclinical studies and 1 clinical study were included after title/abstract and full-text screening. The following potential mechanisms were identified: reduction of glioma cell proliferation (n = 9), decrease of glioma cell migration (n = 2), increase of drug sensitivity (n = 1), induction of glioma cell death (n = 1). Beta-blockers affect glioma proliferation by inducing a brief reduction of cAMP and a temporary cell cycle arrest in vitro. Contrasting results were observed concerning glioma cell migration. The identified clinical study did not find an association between beta-blockers and survival in glioma patients. Although preclinical studies provide scarce evidence for the use of beta-blockers in glioma, they identified potential pathways for targeting glioma. Future studies are needed to clarify the effect of beta-blockers on clinical endpoints including survival outcomes in glioma patients to scrutinize the value of beta-blockers in glioma care.
MeSH term(s)	Adrenergic beta-Antagonists/therapeutic use ; Brain Neoplasms/diagnosis ; Brain Neoplasms/drug therapy ; Cell Death/drug effects ; Cell Death/physiology ; Cell Proliferation/drug effects ; Cell Proliferation/physiology ; Clinical Trials as Topic/methods ; Drug Evaluation, Preclinical/methods ; Glioblastoma/diagnosis ; Glioblastoma/drug therapy ; Glioma/diagnosis ; Glioma/drug therapy ; Humans ; Neovascularization, Pathologic/diagnosis ; Neovascularization, Pathologic/drug therapy
Chemical Substances	Adrenergic beta-Antagonists
Language	English
Publishing date	2020-03-14
Publishing country	Germany
Document type	Journal Article ; Systematic Review
ZDB-ID	6907-3
ISSN	1437-2320 ; 0344-5607
ISSN (online)	1437-2320
ISSN	0344-5607
DOI	10.1007/s10143-020-01277-4
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Article ; Online: Leptomeningeal disease in neurosurgical brain metastases patients: A systematic review and meta-analysis.

Tewarie, Ishaan Ashwini / Jessurun, Charissa A C / Hulsbergen, Alexander F C / Smith, Timothy R / Mekary, Rania A / Broekman, Marike L D

Neuro-oncology advances

2021 Volume 3, Issue 1, Page(s) vdab162

Abstract: Background: Leptomeningeal disease (LMD) is a complication distinguished by progression of metastatic disease into the leptomeninges and subsequent spread via cerebrospinal fluid (CSF). Although treatments for LMD exist, it is considered fatal with a ... ...

Abstract	Background: Leptomeningeal disease (LMD) is a complication distinguished by progression of metastatic disease into the leptomeninges and subsequent spread via cerebrospinal fluid (CSF). Although treatments for LMD exist, it is considered fatal with a median survival of 2-4 months. A broader overview of the risk factors that increase the brain metastasis (BM) patient's risk of LMD is needed. This meta-analysis aimed to systematically review and quantitatively assess risk factors for LMD after surgical resection for BM. Methods: A systematic literature search was performed on 7 May 2021. Pooled effect sizes were calculated using a random-effects model for variables reported by three or more studies. Results: Among 503 studies, thirteen studies met the inclusion criteria with a total surgical sample size of 2105 patients, of which 386 patients developed LMD. The median incidence of LMD across included studies was 16.1%. Eighteen unique risk factors were reported as significantly associated with LMD occurrence, including but not limited to: larger tumor size, infratentorial BM location, proximity of BM to cerebrospinal fluid spaces, ventricle violation during surgery, subtotal or piecemeal resection, and postoperative stereotactic radiosurgery. Pooled results demonstrated that breast cancer as the primary tumor location (HR = 2.73, 95% CI: 2.12-3.52) and multiple BMs (HR = 1.37, 95% CI: 1.18-1.58) were significantly associated with a higher risk of LMD occurrence. Conclusion: Breast cancer origin and multiple BMs increase the risk of LMD occurrence after neurosurgery. Several other risk factors which might play a role in LMD development were also identified.
Language	English
Publishing date	2021-11-10
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	3009682-0
ISSN	2632-2498 ; 2632-2498
ISSN (online)	2632-2498
ISSN	2632-2498
DOI	10.1093/noajnl/vdab162
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Article ; Online: Practice Variation in Perioperative Steroid Dosing for Brain Tumor Patients: An International Survey.

Jessurun, Charissa A C / Hulsbergen, Alexander F C / Lamba, Nayan / Nandoe Tewarie, Rishi D S / Smith, Timothy R / Broekman, Marike L D

World neurosurgery

2021 Volume 159, Page(s) e431–e441

Abstract: Objective: Steroids are commonly used to treat peritumoral edema and increased intracranial pressure in patients with brain tumors. Despite widespread use of steroids, relatively little evidence is available about their optimal perioperative dosing ... ...

Abstract	Objective: Steroids are commonly used to treat peritumoral edema and increased intracranial pressure in patients with brain tumors. Despite widespread use of steroids, relatively little evidence is available about their optimal perioperative dosing scheme. This study aimed to increase insight into practice variation of perioperative steroid dosing and tapering schedules used in the neurosurgical community. Methods: An electronic survey comprising 27 questions regarding steroid dosing, tapering schedules, and adverse events was administered to neurosurgeons between December 6, 2019, and June 1, 2020. The survey was distributed through the European Association of Neurosurgical Societies and social media platforms. Collected data were assessed for quantitative and qualitative analysis. Results: The survey obtained 175 responses from 55 countries across 6 continents, including 30 from low- or middle-income countries; 152 (87%) respondents completed all questions. Of respondents, 130 (80%) indicated prescribing perioperative steroids. Reported doses ranged from 2 to 64 mg/day in schedules ranging from 1 to 4 times daily. The most prescribed steroid was dexamethasone in doses of 16 mg/day (n = 49; 31%), 12 mg/day (n = 31; 20%), and 8 mg/day (n = 18; 12%). No significant association was found between prescribed dose and physician and institutional characteristics. Conclusions: Steroids are commonly prescribed perioperatively in patients with brain tumors. However, there is great practice variation in dosing and schedules among neurosurgeons. Future investigation in a prospective and preferably randomized manner is needed to identify an optimal dosing scheme and implement international/national guidelines for steroid use.
MeSH term(s)	Brain Neoplasms/drug therapy ; Brain Neoplasms/surgery ; Europe ; Humans ; Neurosurgeons ; Perioperative Care ; Practice Patterns, Physicians' ; Prospective Studies ; Steroids/adverse effects ; Surveys and Questionnaires
Chemical Substances	Steroids
Language	English
Publishing date	2021-12-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2021.12.067
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Article ; Online: Routine Blood Tests for Severe Traumatic Brain Injury: Can They Predict Outcomes?

Dolmans, Rianne G F / Hulsbergen, Alexander F C / Gormley, William B / Broekman, Marike L D

World neurosurgery

2019 Volume 136, Page(s) e60–e67

Abstract: ... ubiquitin C-terminal hydrolase-L1, and tau. Routine blood tests are regularly performed in patients ...

Abstract	Objective: Outcome prediction in severe traumatic brain injury (sTBI) has been studied using clinical and radiographic measurements and by using biomarkers such as glial fibrillary acidic protein, ubiquitin C-terminal hydrolase-L1, and tau. Routine blood tests are regularly performed in patients with sTBI and could be used to predict outcomes. This study aims to investigate whether routine blood tests on admission can be predictive of outcome in patients with sTBI. Methods: Patients with sTBI were selected from 2 institutional databases based on International Classification of Diseases Ninth and Tenth Revision codes for traumatic brain injury (TBI), ventilatory assistance >24 hours, intracranial pressure monitoring, and Glasgow Coma Score (GCS) score ≤8. Laboratory parameters included blood urea nitrogen, creatinine, glucose, hematocrit, hemoglobin, red blood cells, white blood cells, monocytes, lymphocytes, neutrophils, neutrophil lymphocyte ratio, platelets, international normalized ratio, prothrombin time, sodium, and potassium. Clinical outcome was measured as hospital length of stay, 30-day mortality, and favorable versus unfavorable outcome based on Glasgow Outcome Scale at 3 months. Results: A total of 255 adult patients were selected. Median Injury Severity Score was 14.00 (interquartile range, 9.00-22.00). Of patients, 25.9% died within 30 days and 56.1% had an unfavorable outcome at 3 months. On multivariate analysis, low sodium level was significant for 30-day mortality and high sodium level was significant for unfavorable outcome at 3 months. However, after correction for multiple testing, no routine blood test remained significant. Conclusions: No routine blood tests measured on admission were significant predictors of outcome in patients with sTBI. Other clinical and radiologic factors may be better suited to predicting outcomes in this patient population.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Biomarkers/blood ; Brain Injuries, Traumatic/blood ; Brain Injuries, Traumatic/diagnosis ; Female ; Hematologic Tests ; Humans ; Injury Severity Score ; Length of Stay ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Young Adult
Chemical Substances	Biomarkers
Language	English
Publishing date	2019-10-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2019.10.086
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