Neurosurgery Commons^™

A General Catalyst Controlled Route To Prostaglandin F2a, Laura Cunningham, Sourabh Mishra, Leon Matthews, Stephen P Fletcher

Faculty, Staff and Student Publications

We report a general, catalyst-controlled route to prostaglandin F2_α and its analogues. The approach uses a Rh-catalyzed dynamic kinetic asymmetric Suzuki–Miyaura coupling reaction between a racemic bicyclic allyl chloride and alkenyl boronic esters bearing chiral alcohols to give cyclopentyl intermediates bearing 3 contiguous stereocenters. The route provides advanced intermediates in 99% ee as a single diastereoisomer in all cases examined, with the absolute stereochemistry of the cyclopentane core controlled by the ligand. Intermediates that could be used to produce prostaglandin analogues such as bimatoprost, latanoprost, fluprostenol, and cloprostenol were synthesized. The final two stereocenters were installed via Pd-catalyzed Tsuji–Trost …

Sources Of Calcium At Connexin 36 Gap Junctions In The Retina, Pui Man Rosalind Lai, Jee-Yeon Ryu, Sang-Cheol Park, Bradley A Gross, Lawrence D Dickinson, Sarajune Dagen, Mohammad Ali Aziz-Sultan, Alan S Boulos, Daniel L Barrow, H Hunt Batjer, Spiros Blackburn, Edward F Chang, P Roc Chen, Geoffrey P Colby, Garth Rees Cosgrove, Carlos A David, Arthur L Day, Kai U Frerichs, Mika Niemela, Steven G Ojemann, Nirav J Patel, Xiangen Shi, Edison P Valle-Giler, Anthony C Wang, Babu G Welch, Edie E Zusman, Scott T Weiss, Rose Du

Faculty, Staff and Student Publications

Background and Objectives

While somatic mutations have been well-studied in cancer, their roles in other complex traits are much less understood. Our goal is to identify somatic variants that may contribute to the formation of saccular cerebral aneurysms.

Methods

We performed whole-exome sequencing on aneurysm tissues and paired peripheral blood. RNA sequencing and the CRISPR/Cas9 system were then used to perform functional validation of our results.

Results

Somatic variants involved in supervillin (SVIL) or its regulation were found in 17% of aneurysm tissues. In the presence of a mutation in the SVIL gene, the expression level of SVIL …

Intraoperative Localization And Preservation Of Reading In Ventral Occipitotemporal Cortex, Oscar Woolnough, Kathryn M Snyder, Cale W Morse, Meredith J Mccarty, Samden D Lhatoo, Nitin Tandon

Faculty, Staff and Student Publications

OBJECTIVE: Resective surgery in language-dominant ventral occipitotemporal cortex (vOTC) carries the risk of causing impairment to reading. Because it is not on the lateral surface, it is not easily accessible for intraoperative mapping, and extensive stimulation mapping can be time-consuming. Here the authors assess the feasibility of using task-based electrocorticography (ECoG) recordings intraoperatively to help guide stimulation mapping of reading in vOTC.

METHODS: In 11 patients undergoing extraoperative, intracranial seizure mapping, the authors recorded induced broadband gamma activation (70-150 Hz) during a visual category localizer. In 2 additional patients, whose pathologies necessitated resections in language-dominant vOTC, task-based functional mapping was …

Uncloaking Cell-Impermeant Gold Nanorods Via Tumor Microenvironmental Cathepsin B Facilitates Cancer Cell Penetration And Potent Radiosensitization, Subhiksha Raghuram, Yuri Mackeyev, Jessica Symons, Yasmin Zahra, Valeria Gonzalez, Krishnan K Mahadevan, Katherinne I Requejo, Anton Liopo, Paul Derry, Eugene Zubarev, Onur Sahin, Joseph Byung-Kyu Kim, Pankaj K Singh, Sang Hyun Cho, Sunil Krishnan

Faculty, Staff and Student Publications

Major impediments to conveyance of intravenously administered drugs to tumors are biofouling, opsonization, and rapid clearance from the circulation by macrophages and reticuloendothelial phagocytes. Cloaking nanoparticles with stealth epilayers partly overcomes these hurdles but it also foils interactions with tumor cells. Here, we describe the synthesis, characterization, and validation of smart gold nanorods (GNRs) that spontaneously transform from inert passengers in the blood stream to active cell-penetrating nanoparticles within tumors to potently sensitize tumors to radiation therapy. Intrinsically cationic and cell-penetrating GNRs were shielded from phagocytosis with a cloaking polyethylene glycol epilayer containing an intervening cleavable peptide. In the absence …

A Phase Ii Randomized Double Blinded Trial Evaluating The Efficacy Of Curcumin With Pre-Operative Chemoradiation For Rectal Cancer, Jillian R Gunther, Awalpreet S Chadha, Sushovan Guha, Gottumukkala S Raju, Dipen M Maru, Mark F Munsell, Yan Jiang, Peiying Yang, Edd Felix, Marilyn Clemons, Geena George Mathew, Pankaj K Singh, John M Skibber, Miguel A Rodriguez-Bigas, George J Chang, Cathy Eng, Marc E Delclos, Christopher H Crane, Prajnan Das, Sunil Krishnan

Faculty, Staff and Student Publications

Background

In vivo studies demonstrate that curcumin increases radioresponse of colorectal cancers. To demonstrate efficacy in humans, we performed a randomized double-blind study of locally advanced rectal cancer (LARC) patients receiving pre-operative chemoradiation therapy (CRT) ± curcumin. We used pathologic complete response (pCR) rate as a surrogate for clinical outcome.

Methods

From 2008–2010, LARC patients were randomized to placebo/curcumin in a 1:2 ratio. Patients received CRT [50.4 gray in 28 fractions; capecitabine (825 mg/m² twice daily)] followed by surgery. Curcumin (4 grams orally, twice daily) or placebo was given throughout CRT and 6 weeks afterward. Toxicity was monitored weekly. …

Endovascular Repair Of Intercostal Patch Aneurysms In A Patient With Loyes-Dietz Syndrome, Guilherme B Lima, Laura Ocasio, Marina Dias-Neto, Emanuel R Tenorio, Thanila A Macedo, Gustavo S Oderich

Faculty, Staff and Student Publications

No abstract provided.

Amplification Of The Plag-Family Genes-Plagl1 And Plagl2-Is A Key Feature Of The Novel Tumor Type Cns Embryonal Tumor With Plagl Amplification, Michaela-Kristina Keck, Martin Sill, Andrea Wittmann, Piyush Joshi, Damian Stichel, Pengbo Beck, Konstantin Okonechnikow, Philipp Sievers, Annika K. Wefers, Nasir Uddin

Department of Pathology and Laboratory Medicine

Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal …

Scale-Up Of A Rh-Catalyzed Asymmetric Sp3–Sp2 Suzuki–Miyaura-Type Reaction, Laura Cunningham, Mireia Sidera Portela, Stephen P Fletcher

Faculty, Staff and Student Publications

Csp²–Csp² Suzuki–Miyaura couplings (SMCs) are ubiquitous in the synthesis of small molecules, but analogous Csp²–Csp³ bond-forming SMCs are rare, especially asymmetric variants. Recently, we developed a series of Rh-catalyzed couplings between racemic sp³-hybridized allyl chlorides and heteroaryl boronic acids. Here, we demonstrate that these catalytic asymmetric reactions can be scaled-up to give over 100 g of a product. The reaction we chose to test couples a heteroaromatic boronic acid derivative and a racemic bicyclic electrophile to give a product with three contiguous stereogenic centers. The SMC product was obtained as a single …

Pancreatic Tumor Microenvironmental Acidosis And Hypoxia Transform Gold Nanorods Into Cell-Penetrant Particles For Potent Radiosensitization, Pradipta Ranjan Rauta, Yuri Mackeyev, Keith Sanders, Joseph B K Kim, Valeria V Gonzalez, Yasmin Zahra, Muhammad A Shohayeb, Belal Abousaida, Geraldine V Vijay, Okan Tezcan, Paul Derry, Anton V Liopo, Eugene R Zubarev, Rickey Carter, Pankaj Singh, Sunil Krishnan

Faculty, Staff and Student Publications

Coating nanoparticles with stealth epilayers increases circulation time by evading opsonization, macrophage phagocytosis, and reticuloendothelial sequestration. However, this also reduces internalization by cancer cells upon reaching the tumor. We designed gold nanorods (GNRs) with an epilayer that retains stealth properties in circulation but transforms spontaneously in the acidotic tumor microenvironment to a cell-penetrating particle. We used a customized stoichiometric ratio of l-glutamic acid and l-lysine within an amphiphilic polymer of poly(l-glutamic acid-co-l-lysine), or P(Glu-co-Lys), to effect this transformation in acidotic environments. P(Glu-co-Lys)-GNRs were internalized by cancer cells to facilitate potent in vitro radiosensitization. When administered intravenously in mice, they accumulate …

Antibody-Drug Conjugates For The Treatment Of Her2-Positive Breast Cancer, Mariana K Najjar, Sara G Manore, Angelina T Regua, Hui-Wen Lo

Faculty, Staff and Student Publications

Human epidermal growth factor receptor 2 (HER2) receptor tyrosine kinase is overexpressed in 20–30% of breast cancers and is associated with poor prognosis and worse overall patient survival. Most women with HER2-positive breast cancer receive neoadjuvant chemotherapy plus HER2-targeted therapies. The development of HER2-directed therapeutics is an important advancement in targeting invasive breast cancer. Despite the efficacy of anti-HER2 monoclonal antibodies, they are still being combined with adjuvant chemotherapy to improve overall patient outcomes. Recently, significant progress has been made towards the development of a class of therapeutics known as antibody-drug conjugates (ADCs), which leverage the high specificity of HER2-targeted …

Human Amniotic Membrane As A Dural Substitute In Neurosurgery: A Systematic Review, Zara Shah, Saqib Kamran Bakhshi, Mohammad Hamza Bajwa, Mujtaba Khalil, Michael C. Dewan, Muhammad Shahzad Shamim

Medical College Documents

Background: Several studies have highlighted the use of human amniotic membrane (HAM) in neurosurgical procedures as an effective dural substitute. HAM has inherent antifibrotic and anti-inflammatory properties and exhibits immunomodulatory effect that makes it an ideal dural substitute. Other advantages including easy availability, low cost of procurement, and storage also render it a promising dural substitute especially in low- and middle-income countries.
Methods: A systematic literature search was performed using PubMed, Scopus, and Google Scholar databases, using the search terms "human amniotic membrane," "dural repair," and "neurosurgery." To be eligible for inclusion in our review, papers had to report primary …

What Do We Know So Far About Ofatumumab For Relapsing Multiple Sclerosis? A Meta-Analytical Study, Hafiza Munazza Taj, Maryam Talib, Sania Siddiqa, Azza Sarfraz, Zouina Sarfraz, Karla Robles-Velasco, Ivan Cherrez-Ojeda

Department of Paediatrics and Child Health

Ofatumumab is a monoclonal antibody that reduces the level of B cells that alter the progression of relapsing multiple sclerosis. Originally approved by the Food and Drug Administration (FDA) in August 2020, this meta-analysis determines the outcomes of four randomized controlled trials (RCTs) for endline outcomes of Gadolinium-enhancing T1 lesions on MRI scans reported as Cohen's d and relapse rate reported as risk ratio. All four RCTs reported favorable findings of gadolinium-enhancing T1 lesions (Cohen's d = -0.44, p < 0.00001). The relapse rate was reduced by 46% post ofatumumab administration (RR = 0.54, p < 0.00001). With 14 ongoing trials in this area, more data is required to consolidate our findings.

Venous Sinus Stenting For Low Pressure Gradient Stenoses In Idiopathic Intracranial Hypertension, Mehmet Enes Inam, Juan Carlos Martinez-Gutierrez, Matthew J Kole, Francisco Sanchez, Elvira Lekka, Van Thi Thanh Truong, Victor Lopez-Rivera, Faheem G Sheriff, Laura A Zima, Claudia Pedroza, Rosa Tang, Ore-Ofe Adesina, Allison Engstrom, Sunil A Sheth, Peng Roc Chen

Faculty, Staff and Student Publications

BACKGROUND: Medically refractory idiopathic intracranial hypertension (IIH) is frequently treated with venous sinus stenosis stenting with high success rates. Patient selection has been driven almost exclusively by identification of supraphysiological venous pressure gradients across stenotic regions based on theoretical assessment of likelihood of response.

OBJECTIVE: To explore the possibility of benefit in low venous pressure gradient patients.

METHODS: Using a single-center, prospectively maintained registry of patients with IIH undergoing venous stenting, we defined treatment groups by gradient pressures of ≤4, 5 to 8, and >8 mmHg based on the most frequently previously published thresholds for stenting. Baseline demographics, clinical, and …

Ten-Year Review Of Antihypertensive Prescribing Practices After Stroke And The Associated Disparities From The Florida Stroke Registry, Amanda J Taylor, Jung Hwan Kim, David Ress

Faculty, Staff and Student Publications

The hemodynamic response function (HRF) measured with functional magnetic resonance imaging is generated by vascular and metabolic responses evoked by brief (<4 s) stimuli. It is known that the human HRF varies across cortex, between subjects, with stimulus paradigms, and even between different measurements in the same cortical location. However, our results demonstrate that strong HRFs are remarkably repeatable across sessions separated by time intervals up to 3 months. In this study, a multisensory stimulus was used to activate and measure the HRF across the majority of cortex (>70%, with lesser reliability observed in some areas of prefrontal cortex). HRFs were measured with high spatial resolution (2‐mm voxels) in central gray matter to minimize variations caused by partial‐volume effects. HRF amplitudes and temporal dynamics were highly repeatable across four sessions in 20 subjects. Positive and negative HRFs were consistently observed across sessions and subjects. Negative HRFs were generally weaker and, thus, more variable than positive HRFs. Statistical measurements showed that across‐session variability is highly correlated to …

Use Of High-Resolution Ultrasound To Guide Alcohol Neurolysis For Chronic Pain, Russell A. Reeves, Cole J. Miller, Dajie Wang, Andrew Ng, Joshua E. Heller, Levon N. Nazarian

Department of Radiology Faculty Papers

BACKGROUND: The diagnosis and treatment of neuropathic pain is often clinically challenging, with many patients requiring treatments beyond oral medications. To improve our percutaneous treatments, we established a clinical pathway that utilized ultrasound (US) guidance for steroid injection and alcohol ablation for patients with painful neuropathy.

OBJECTIVES: To describe a collaborative neuropathy treatment pathway developed by a neurosurgeon, pain physicians, and a sonologist, describing early clinical experiences and patient-reported outcomes.

STUDY DESIGN: A retrospective case series was performed.

METHODS: Patients that received percutaneous alcohol ablation with US guidance for neuropathy were identified through a retrospective review of a single provider's …

Neurodevelopment And Recovery From Wasting, Harriet M. Babikako, Celine Bourdon, Emmie Mbale, Peace Aber, Annet Birabwa, Josephine Chimoyo, Wieger Voskuijl, Zaubina Kazi, John Mukisa, Ali Faisal Saleem

Department of Paediatrics and Child Health

Background and objectives: Acute illness with malnutrition is a common indication for hospitalization among children in low- and middle-income countries. We investigated the association between wasting recovery trajectories and neurodevelopmental outcomes in young children 6 months after hospitalization for an acute illness.
Methods: Children aged 2 to 23 months were enrolled in a prospective observational cohort of the Childhood Acute Illness & Nutrition Network, in Uganda, Malawi, and Pakistan between January 2017 and January 2019. We grouped children on the basis of their wasting recovery trajectories using change in mid-upper arm circumference for age z-score. Neurodevelopment was assessed with the …

Intraoperative Changes In Somatosensory Evoked Potentials As A Predictor Of Perioperative Stroke In Carotid Endarterectomy, Justin W. Meinert Bphil, Parthatharasy D. Thirumala Md, Jeffrey R. Balzer Phd, Donald J. Crammond Phd, Eyad E. Saca Md

Tower Health Research Day

No abstract provided.

Cases In Psychiatric Neurosurgery, Wael Asaad, Michael Staudt, Darin Dougherty, Wayne Goodman, Robert M. Richardson, Sameer Sheth

Conference Presentation Abstracts

In this session, multidisciplinary teams - surgeon plus psychiatrist - will discuss their own cases and approaches to the innovative management of psychiatric disorders.

The Value Of High-Resolution Imaging In An Occult Peroneal Intraneural Ganglion Cyst: Illustrative Case., Karina A Lenartowicz, Kimberly K Amrami, Jeffrey A Strakowski, B Matthew Howe, Robert J Spinner

Ambulatory and Primary Care Articles

BACKGROUND: Foot drop is a common complaint with a broad differential diagnosis making imaging a key part of the diagnostic workup. The authors present a patient with an occult peroneal intraneural ganglion cyst who underwent imaging with high-frequency ultrasound (US) and high-resolution magnetic resonance imaging (MRI) to highlight the role of such techniques in cases of peroneal neuropathy.

OBSERVATIONS: Intraneural ganglion cysts are emerging as a common cause of common peroneal neuropathy. Imaging with US and MRI is a valuable tool used to illustrate the pertinent anatomy and identify the articular branch joint connection and cyst as part of the …

Wide-Necked Middle Cerebral Artery Aneurysm Clipping Following Failed Occlusion After Woven Endobridge Placement: 2-Dimensional Operative Video, Stephen Capone, Anil Roy, Matthew Kole, Spiros L Blackburn

Faculty, Staff and Student Publications

No abstract provided.