Neurosurgery Commons^™

Impact Of Timing To Initiate Adjuvant Therapy On Survival Of Elderly Glioblastoma Patients Using The Seer-Medicare And National Cancer Databases, Ping Zhu, Xianglin L Du, Lu-Yu Hwang, David Lairson, Ruosha Li, Yoshua Esquenazi, Jay-Jiguang Zhu

Faculty, Staff and Student Publications

The optimal time to initiate adjuvant therapy (AT) in elderly patients with glioblastoma (GBM) remains unclear. We investigated the impact of timing to start AT on overall survival (OS) using two national-scale datasets covering elderly GBM populations in the United States. A total of 3159 and 8161 eligible elderly GBM patients were derived from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked dataset (2004-2013) and the National Cancer Database (NCDB) (2004-2014), respectively. The intervals in days from the diagnosis to the initiation of AT were categorized based on two scenarios: Scenario I (quartiles), ≤ 15, 16-26, 27-37, and ≥ 38 …

Stand By Me: Using An Enhanced Recovery After Surgery (Eras) Checklist To Guide Early Mobility Of Postoperative Craniotomy Patients On A Progressive Care Unit, Jerome Codilla, Alyssa Mooney, Joanna Arraiza, Sohl Chapman, Nkiru Chukwudi, Ronald Rosales

Providence Nursing Research Conference 2023 – Present

No abstract provided.

Positioning Transclival Tumor-Treating Fields For The Treatment Of Diffuse Intrinsic Pontine Gliomas, Walid Ibn Essayed, Casey A Jarvis, Joshua D Bernstock, Anna Slingerland, John Albanese, Gregory K Friedman, Omar Arnaout, Lissa Baird

Faculty, Staff and Student Publications

Diffuse intrinsic pontine glioma (DIPG) carries an extremely poor prognosis, with 2-year survival rates of <10% despite the maximal radiation therapy. DIPG cells have previously been shown to be sensitive to low-intensity electric fields in vitro. Accordingly, we sought to determine if the endoscopic endonasal (EE) implantation of an electrode array in the clivus would be feasible for the application of tumor-treating fields (TTF) in DIPG. Anatomic constraints are the main limitation in pediatric EE approaches. In our Boston Children’s Hospital’s DIPG cohort, we measured the average intercarotid distance (1.68 ± 0.36 cm), clival width (1.62 ± 0.19 cm), and clival length from the base of the sella (1.43 ± 0.69 cm). Using a linear regression model, we found that only clival length and sphenoid pneumatization were significantly associated with age (R² = 0.568, p = 0.005 *; R² = 0.605, p = 0.0002 *). Critically, neither of these parameters represent limitations to the implantation of a device within the dimensions of those currently available. Our findings confirm that the anatomy present within this age group is amenable to the placement of a 2 × 1 cm electrode array in 94% of patients examined. Our work serves to demonstrate the feasibility of implantable transclival devices for the provision of TTFs as a novel adjunctive therapy …

Depatuxizumab Mafodotin In Egfr-Amplified Newly Diagnosed Glioblastoma: A Phase Iii Randomized Clinical Trial, Andrew B Lassman, Stephanie L Pugh, Tony J C Wang, Kenneth Aldape, Hui K Gan, Matthias Preusser, Michael A Vogelbaum, Erik P Sulman, Minhee Won, Peixin Zhang, Golnaz Moazami, Marian S Macsai, Mark R Gilbert, Earle E Bain, Vincent Blot, Peter J Ansell, Suvajit Samanta, Madan G Kundu, Terri S Armstrong, Jeffrey S Wefel, Clemens Seidel, Filip Y De Vos, Sigmund Hsu, Andrés F Cardona, Giuseppe Lombardi, Dmitry Bentsion, Richard A Peterson, Craig Gedye, Véronique Bourg, Antje Wick, Walter J Curran, Minesh P Mehta

Faculty, Staff and Student Publications

BACKGROUND: Approximately 50% of newly diagnosed glioblastomas (GBMs) harbor epidermal growth factor receptor gene amplification (EGFR-amp). Preclinical and early-phase clinical data suggested efficacy of depatuxizumab mafodotin (depatux-m), an antibody-drug conjugate comprised of a monoclonal antibody that binds activated EGFR (overexpressed wild-type and EGFRvIII-mutant) linked to a microtubule-inhibitor toxin in EGFR-amp GBMs.

METHODS: In this phase III trial, adults with centrally confirmed, EGFR-amp newly diagnosed GBM were randomized 1:1 to radiotherapy, temozolomide, and depatux-m/placebo. Corneal epitheliopathy was treated with a combination of protocol-specified prophylactic and supportive measures. There was 85% power to detect a hazard ratio (HR) ≤0.75 for overall survival …

Hemiparkinsonism Caused By A Lateral Sphenoid Wing Meningioma, With Tractography Analysis: Illustrative Case, Attill Saemann, Stefan Busch, Ethan Taub, Birgit Westermann, Cristina Granziera, Raphael Guzman, Luigi Mariani, Jehuda Soleman, Jonathan Rychen

Faculty, Staff and Student Publications

BACKGROUND: The etiologies of parkinsonism are diverse. A possible and rare cause of hemiparkinsonism is mechanical compression of the basal ganglia and its connecting white matter tracts. The authors present a case of hemiparkinsonism caused by a lateral sphenoid wing meningioma, discuss the underlying pathophysiology based on tractography, and systematically review the existing literature.

OBSERVATIONS: A 59-year-old female was referred for a left-sided tremor of the hand, accompanied by a cogwheel rigidity of the left arm. Symptomatology appeared 1 year earlier and worsened in the previous 6 months, finally also showing involvement of the left leg. Magnetic resonance imaging (MRI) …

Machine Learning And Acute Stroke Imaging, Sunil A Sheth, Luca Giancardo, Marco Colasurdo, Visish M Srinivasan, Arash Niktabe, Peter Kan

Faculty, Staff and Student Publications

BACKGROUND: In recent years, machine learning (ML) has had notable success in providing automated analyses of neuroimaging studies, and its role is likely to increase in the future. Thus, it is paramount for clinicians to understand these approaches, gain facility with interpreting ML results, and learn how to assess algorithm performance.

OBJECTIVE: To provide an overview of ML, present its role in acute stroke imaging, discuss methods to evaluate algorithms, and then provide an assessment of existing approaches.

METHODS: In this review, we give an overview of ML techniques commonly used in medical imaging analysis and methods to evaluate performance. …

Middle Meningeal Artery Embolization For Chronic Subdural Hematomas With Concurrent Antithrombotics, Juan Carlos Martinez-Gutierrez, Hussein A Zeineddine, Michael I Nahhas, Matthew J Kole, Youngran Kim, Hyun Woo Kim, Salvatore A D'Amato, Peng Roc Chen, Spiros L Blackburn, Gary Spiegel, Sunil A Sheth, Ryan S Kitagawa, Mark J Dannenbaum

Faculty, Staff and Student Publications

BACKGROUND: Chronic subdural hematoma (CSDH) is an increasingly prevalent disease in the aging population. Patients with CSDH frequently suffer from concurrent vascular disease or develop secondary thrombotic complications requiring antithrombotic treatment.

OBJECTIVE: To determine the safety and impact of early reinitiation of antithrombotics after middle meningeal artery embolization for chronic subdural hematoma.

METHODS: This is a single-institution, retrospective study of patients who underwent middle meningeal artery (MMA) embolizations for CSDH. Patient with or without antithrombotic initiation within 5 days postembolization were compared. Primary outcome was the rate of recurrence within 60 days. Secondary outcomes included rate of reoperation, reduction in …

Association Of Endovascular Thrombectomy Vs Medical Management With Functional And Safety Outcomes In Patients Treated Beyond 24 Hours Of Last Known Well, Amrou Sarraj, Timothy J Kleinig, Ameer E Hassan, Pere Cardona Portela, Santiago Ortega-Gutierrez, Michael G Abraham, Nathan W Manning, James E Siegler, Nitin Goyal, Laith Maali, Spiros Blackburn, Teddy Y Wu, Jordi Blasco, Arturu Renú, Navdeep S Sangha, Juan F Arenillas, Margy E Mccullough-Hicks, Adam Wallace, Daniel Gibson, Deep K Pujara, Faris Shaker, Mercedes De Lera Alfonso, Marta Olivé-Gadea, Mudassir Farooqui, Juan S Vivanco Suarez, Zachary Iezzi, Jane Khalife, Colleen G Lechtenberg, Syed K Qadri, Rami B Moussa, Mohammad A Abdulrazzak, Tareq S Almaghrabi, Osman Mir, James Beharry, Balaji Krishnaiah, Megan Miller, Najwa Khalil, Gagan J Sharma, Aristeidis H Katsanos, Ali Fadhil, Kelsey R Duncan, Yin Hu, Sheryl B Martin-Schild, Georgios K Tsivgoulis, Dennis Cordato, Anthony Furlan, Leonid Churilov, Peter J Mitchell, Adam S Arthur, Mark W Parsons, James C Grotta, Clark W Sitton, Marc Ribo, Gregory W Albers, Bruce C V Campbell

Faculty, Staff and Student Publications

IMPORTANCE: The role of endovascular thrombectomy is uncertain for patients presenting beyond 24 hours of the time they were last known well.

OBJECTIVE: To evaluate functional and safety outcomes for endovascular thrombectomy (EVT) vs medical management in patients with large-vessel occlusion beyond 24 hours of last known well.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective observational cohort study enrolled patients between July 2012 and December 2021 at 17 centers across the United States, Spain, Australia, and New Zealand. Eligible patients had occlusions in the internal carotid artery or middle cerebral artery (M1 or M2 segment) and were treated with EVT or …

Exploring The Past, Present, And Future Of Anti-Angiogenic Therapy In Glioblastoma., Ashley B. Zhang, Khashayar Mozaffari, Brian Aguirre, Victor Li, Rohan Kubba, Nilay C Desai, Darren Wei, Isaac Yang, Madhuri Wadehra

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Glioblastoma, a WHO grade IV astrocytoma, constitutes approximately half of malignant tumors of the central nervous system. Despite technological advancements and aggressive multimodal treatment, prognosis remains dismal. The highly vascularized nature of glioblastoma enables the tumor cells to grow and invade the surrounding tissue, and vascular endothelial growth factor-A (VEGF-A) is a critical mediator of this process. Therefore, over the past decade, angiogenesis, and more specifically, the VEGF signaling pathway, has emerged as a therapeutic target for glioblastoma therapy. This led to the FDA approval of bevacizumab, a monoclonal antibody designed against VEGF-A, for treatment of recurrent glioblastoma. Despite the …

Protocol For Validation Of The Global Scales For Early Development (Gsed) For Children Under 3 Years Of Age In Seven Countries, Vanessa Cavallera, Gillian Lancaster, Melissa Gladstone, Maureen M. Black, Gareth Mccray, Ambreen Nizar, Salahuddin Ahmed, Muhammad Imran Nisar, Farzana Begum, Fyezah Jehan

Department of Paediatrics and Child Health

Introduction: Children's early development is affected by caregiving experiences, with lifelong health and well-being implications. Governments and civil societies need population-based measures to monitor children's early development and ensure that children receive the care needed to thrive. To this end, the WHO developed the Global Scales for Early Development (GSED) to measure children's early development up to 3 years of age. The GSED includes three measures for population and programmatic level measurement: (1) short form (SF) (caregiver report), (2) long form (LF) (direct administration) and (3) psychosocial form (PF) (caregiver report). The primary aim of this protocol is to validate …

Thrombectomy Outcomes With General Vs Nongeneral Anesthesia: A Pooled Patient-Level Analysis From The Extend-Ia Trials And Select Study, Amrou Sarraj, Gregory W Albers, Peter J Mitchell, Ameer E Hassan, Michael G Abraham, Spiros Blackburn, Gagan Sharma, Nawaf Yassi, Timothy J Kleinig, Darshan G Shah, Teddy Y Wu, Muhammad Shazam Hussain, Wondwoseen G Tekle, Santiago Ortega Gutierrez, Amin Nima Aghaebrahim, Diogo C Haussen, Gabor Toth, Deep Pujara, Ronald F Budzik, William Hicks, Nirav Vora, Randall C Edgell, Sabreena Slavin, Colleen G Lechtenberg, Laith Maali, Abid Qureshi, Lee Rosterman, Mohammad Ammar Abdulrazzak, Tareq Almaghrabi, Faris Shaker, Osman Mir, Ashish Arora, Sheryl Martin-Schild, Clark W Sitton, Leonid Churilov, Rishi Gupta, Maarten G Lansberg, Raul G Nogueira, James C Grotta, Geoffrey Alan Donnan, Stephen M Davis, Bruce C V Campbell

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: The effect of anesthesia choice on endovascular thrombectomy (EVT) outcomes is unclear. Collateral status on perfusion imaging may help identify the optimal anesthesia choice.

METHODS: In a pooled patient-level analysis of EXTEND-IA, EXTEND-IA TNK, EXTEND-IA TNK part II, and SELECT, EVT functional outcomes (modified Rankin Scale score distribution) were compared between general anesthesia (GA) vs non-GA in a propensity-matched sample. Furthermore, we evaluated the association of collateral flow on perfusion imaging, assessed by hypoperfusion intensity ratio (HIR) - Tmax > 10 seconds/Tmax > 6 seconds (good collaterals - HIR < 0.4, poor collaterals - HIR ≥ 0.4) on the association between anesthesia type and EVT outcomes.

RESULTS: Of 725 treated with EVT, 299 (41%) received GA …

Lack Of Better Functional Outcome In Young Border Hispanic Patients With Acute Ischemic Stroke After Endovascular Thrombectomy Compared To Older Patients: A Retrospective Chart Review, Saisree Ravi, Sohum Desai, Sherief Ghozy, Wondwossen Tekle, Ameer E. Hassan

MEDI 9331 Scholarly Activities Clinical Years

Shortened Abstract:

Previous data indicates that young acute ischemic stroke patients have better prognosis after endovascular thrombectomy, while Hispanic patients are associated with poorer outcomes. Our goal is to study the interaction between age and Hispanic status to assess functional outcomes after endovascular thrombectomy in young versus older patients in a predominantly Hispanic population with a high prevalence of diabetes mellitus and obesity.

Our Hispanic population demonstrates no differences in sICH, mortality, and functional independence between young and older acute ischemic stroke patients after endovascular thrombectomy.

Copy Number Alterations Of Aggressive Pituitary Neuroendocrine Tumors, Grace Zhang

Scripps Senior Theses

Pituitary neuroendocrine tumors (PitNETs) are tumors of the pituitary gland. Although most are benign, they can cause severe morbidity if compression of surrounding tissue and/or endocrinopathies occur.

Aggressive PitNETs are notably detrimental and difficult to predict, and their effects are further exacerbated by challenges in treatment. Although histological studies can detect certain markers of tumor aggressiveness, they are insufficient at wholly predicting PitNET aggressiveness, making the clinical behavior of PitNETs challenging to determine. Since treatment of aggressive tumors also remains suboptimal, this further results in negative impacts on health and quality of life.

Genetic markers, such as copy number variations …

Premature Senescence And Cardiovascular Disease Following Cancer Treatments: Mechanistic Insights, Ashita Jain, Diego Casanova, Alejandra Valdivia Padilla, Angelica Paniagua Bojorges, Sivareddy Kotla, Kyung Ae Ko, Venkata S K Samanthapudi, Khanh Chau, Minh T H Nguyen, Jake Wen, Selina L Hernandez Gonzalez, Shaefali P Rodgers, Elizabeth A Olmsted-Davis, Dale J Hamilton, Cielito Reyes-Gibby, Sai-Ching J Yeung, John P Cooke, Joerg Herrmann, Eduardo N Chini, Xiaolei Xu, Syed Wamique Yusuf, Momoko Yoshimoto, Philip L Lorenzi, Brain Hobbs, Sunil Krishnan, Efstratios Koutroumpakis, Nicolas L Palaskas, Guangyu Wang, Anita Deswal, Steven H Lin, Jun-Ichi Abe, Nhat-Tu Le

Faculty, Staff and Student Publications

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality, especially among the aging population. The "response-to-injury" model proposed by Dr. Russell Ross in 1999 emphasizes inflammation as a critical factor in atherosclerosis development, with atherosclerotic plaques forming due to endothelial cell (EC) injury, followed by myeloid cell adhesion and invasion into the blood vessel walls. Recent evidence indicates that cancer and its treatments can lead to long-term complications, including CVD. Cellular senescence, a hallmark of aging, is implicated in CVD pathogenesis, particularly in cancer survivors. However, the precise mechanisms linking premature senescence to CVD in cancer survivors remain …

Fatty Acid Therapy And Implications For Spinal Cord Injury Treatment: A Literature Review, Philippe J. Dentino

MEDI 9331 Scholarly Activities Clinical Years

Introduction: Spinal Cord Injuries (SCI) are catastrophic injury to spinal neurons that cause a tremendous socioeconomic and public health burden on individuals globally. The role of fatty acids in treatment of SCI is not well understood and poorly standardized across treatment provision. This review seeks to explore the role of fatty acids in neurorecovery and propose emerging themes in SCI treatment with fatty acids.

Methods: A PICO was designed and online databases were searched for relevant articles. A total of 55 studies were deemed appropriate for the review and summarized into thematic elements including ) Cellular Transport 2) Neuroprotection 3) …

Role Of Microrna-34a In Blood-Brain Barrier Permeability And Mitochondrial Function In Ischemic Stroke, Cole T Payne, Sidra Tabassum, Silin Wu, Heng Hu, Aaron M Gusdon, Huimahn A Choi, Xuefang S Ren

Faculty, Staff and Student Publications

Over the past decade, there has been an uptick in the number of studies conducting research on the role of microRNA (miRNA) molecules in stroke. Among these molecules, miR-34a has emerged as a significant player, as its levels have been observed to exhibit a substantial rise following ischemic events. Elevated levels of miR-34a have been found to have multiple effects, including the modulation of inflammatory molecules involved in the post-stroke recovery process, as well as negative effects on the blood-brain barrier (BBB) permeability. Interestingly, the increase of miR-34a appears to increase BBB permeability post stroke, through the negative effect on …

An Individual Data-Driven Virtual Resection Model Based On Epileptic Network Dynamics In Children With Intractable Epilepsy: A Magnetoencephalography Interictal Activity Application, Pablo Cuesta, Ricardo Bruña, Ekta Shah, Christopher Laohathai, Stephanie Garcia-Tarodo, Michael Funke, Gretchen Von Allmen, Fernando Maestú

Faculty, Staff and Student Publications

Epilepsy surgery continues to be a recommended treatment for intractable (medication-resistant) epilepsy; however, 30-70% of epilepsy surgery patients can continue to have seizures. Surgical failures are often associated with incomplete resection or inaccurate localization of the epileptogenic zone. This retrospective study aims to improve surgical outcome through in silico testing of surgical hypotheses through a personalized computational neurosurgery model created from individualized patient's magnetoencephalography recording and MRI. The framework assesses the extent of the epileptic network and evaluates underlying spike dynamics, resulting in identification of one single brain volume as a candidate for resection. Dynamic-locked networks were utilized for virtual …

From Shops To Bins: A Case Study Of Consumer Attitudes And Behaviours Towards Plastics In A Uk Coastal City, Stephanie Lucy Northen, Laura Karoliina Nieminen, Serena Cunsolo, Steven Kator Iorfa, Keiron Philip Roberts, Stephen Fletcher

Faculty, Staff and Student Publications

Understanding the use behaviours of plastic items within households is important to enable informed policy development, particularly with the emerging and developing global plastic treaty. A survey of 400 permanent residents in Portsmouth aimed to identify the general trends in single-use plastic product (SUPP) use and disposal, and their personal motivations and barriers to reducing and recycling plastic. This included identifying common influencers of attitudes such as environmental values, situational characteristics, psychological factors and the individual demographic characteristics of residents. Key factors in consumer behaviour were found to be product availability, affordability and convenience. Often, less conveniently recycled plastics more …

A Phase 3b Study For Management Of Ocular Side Effects In Patients With Epidermal Growth Factor Receptor-Amplified Glioblastoma Receiving Depatuxizumab Mafodotin, Colin J Vize, Stella K Kim, Tim Matthews, Marian Macsai, Ryan Merrell, Sigmund Hsu, Madan Gopal Kundu, Jennifer Yoon, Emma Kennedy, Madhavi Pai, Earle Bain, Andrew B Lassman, Golnaz Moazami

Faculty, Staff and Student Publications

INTRODUCTION: The Understanding New Interventions with GBM ThErapy (UNITE) study was designed to assess the effect of prophylaxis for ocular side effects (OSEs) in patients with glioblastoma receiving the antibody-drug conjugate (ADC) depatuxizumab mafodotin. UNITE (NCT03419403) was a phase 3b, open-label, randomized, exploratory study performed at 18 research sites in 5 countries.

METHODS: The study enrolled adult patients with epidermal growth factor receptor-amplified, histologically confirmed, newly diagnosed supratentorial glioblastoma or grade IV gliosarcoma, and a Karnofsky Performance Status ≥70, receiving depatuxizumab mafodotin. All patients were administered depatuxizumab mafodotin during concurrent radiotherapy and temozolomide and with adjuvant temozolomide. Ninety patients were …

Dual Enhancement In The Radiosensitivity Of Prostate Cancer Through Nanoparticles And Chemotherapeutics, Nolan Jackson, Iona Hill, Abdulaziz Alhussan, Kyle Bromma, Jessica Morgan, Belal Abousaida, Yasmin Zahra, Yuri Mackeyev, Wayne Beckham, Steven Herchko, Sunil Krishnan, Devika Basnagge Chithrani

Faculty, Staff and Student Publications

BACKGROUND: Radiotherapy (RT) is an essential component in the treatment regimens for many cancer patients. However, the dose escalation required to improve curative results is hindered due to the normal tissue toxicity that is induced. The introduction of radiosensitizers to RT treatment is an avenue that is currently being explored to overcome this issue. By introducing radiosensitizers into tumor sites, it is possible to preferentially enhance the local dose deposited. Gold nanoparticles (GNPs) are a potential candidate that have shown great promise in increasing the radiosensitivity of cancer cells through an enhancement in DNA damage. Furthermore, docetaxel (DTX) is a …