Neurosurgery Commons^™

Endovascular Thrombectomy With And Without Preceding Thrombolysis In Posterior Circulation Stroke-Insights From Star, Ev-Christin Heide, Sami Al Kasab, Ali Alawieh, Adam Arthur, Waleed Brinjikji, Shakeel Chowdhry, Roberto Crosa, Hugo Cuellar, Reade De Leacy, Travis Dumont, Marielle Ernst, Mohamad Ezzeldin, Isabel Fragata, Brian Howard, Pascal Jabbour, Peter Kan, Joon-Tae Kim, Michael R Levitt, Justin Mascitelli, Charles Matouk, Mark Moss, Pedro Navia, Joshua Osbun, Min S Park, Adam Polifka, Marios-Nikos Psychogios, Ansaar Rai, Daniele G Romano, Amir Shaban, Robert M Starke, Omar Tanweer, Richard Williamson, Stacey Q Wolfe, Shinichi Yoshimura, Alejandro M Spiotta, Ilko L Maier

Faculty, Staff and Students Publications

Background: Multiple randomized trials could not establish the noninferiority of endovascular thrombectomy (EVT) alone without preceding intravenous thrombolysis (IVT) or superiority of IVT followed by EVT in anterior circulation large-vessel occlusion stroke. The role of prior IVT in posterior circulation large-vessel occlusion remains controversial.

Methods: In this multicenter, retrospective study, patients with stroke with large-vessel occlusion in the posterior circulation who received EVT alone or with IVT were selected from the stroke thrombectomy and aneurysm registry between 2013 and 2022. Effects of IVT followed by thrombectomy on favorable functional outcome (defined as modified Rankin scale≤3 at 90 days) and safety …

Pathophysiology In Brain Arteriovenous Malformations: Focus On Endothelial Dysfunctions And Endothelial-To-Mesenchymal Transition, Jae Yeong Jeong, Adrian E Bafor, Bridger H Freeman, Peng R Chen, Eun S Park, Eunhee Kim

Faculty, Staff and Student Publications

Brain arteriovenous malformations (bAVMs) substantially increase the risk for intracerebral hemorrhage (ICH), which is associated with significant morbidity and mortality. However, the treatment options for bAVMs are severely limited, primarily relying on invasive methods that carry their own risks for intraoperative hemorrhage or even death. Currently, there are no pharmaceutical agents shown to treat this condition, primarily due to a poor understanding of bAVM pathophysiology. For the last decade, bAVM research has made significant advances, including the identification of novel genetic mutations and relevant signaling in bAVM development. However, bAVM pathophysiology is still largely unclear. Further investigation is required to …

Dissociation Of Reading And Naming In Ventral Occipitotemporal Cortex, Oscar Woolnough, Nitin Tandon

Faculty, Staff and Student Publications

Lesions in the language-dominant ventral occipitotemporal cortex (vOTC) can result in selective impairment of either reading or naming, resulting in alexia or anomia. Yet, functional imaging studies that show differential activation for naming and reading do not reveal activity exclusively tuned to one of these inputs. To resolve this dissonance in the functional architecture of the vOTC, we used focused stimulation to the vOTC in 49 adult patients during reading and naming, and generated a population-level, probabilistic map to evaluate if reading and naming are clearly dissociable within individuals. Language mapping (50 Hz, 2829 stimulations) was performed during passage reading …

The Role Of Occipital Condyle And Atlas Anomalies On Occipital Cervical Fusion Outcomes In Chiari Malformation Type I With Syringomyelia: A Study From The Park-Reeves Syringomyelia Research Consortium, Alexander T Yahanda, Joyce Koueik, Laurie L Ackerman, P David Adelson, Gregory W Albert, Philipp R Aldana, Tord D Alden, Richard C E Anderson, David F Bauer, Tammy Bethel-Anderson, Karin Bierbrauer, Douglas L Brockmeyer, Joshua J Chern, Daniel E Couture, David J Daniels, Brian J Dlouhy, Susan R Durham, Richard G Ellenbogen, Ramin Eskandari, Herbert E Fuchs, Gerald A Grant, Patrick C Graupman, Stephanie Greene, Jeffrey P Greenfield, Naina L Gross, Daniel J Guillaume, Todd C Hankinson, Gregory G Heuer, Mark Iantosca, Bermans J Iskandar, Eric M Jackson, George I Jallo, James M Johnston, Bruce A Kaufman, Robert F Keating, Nickalus R Khan, Mark D Krieger, Jeffrey R Leonard, Cormac O Maher, Francesco T Mangano, Jonathan Martin, J Gordon Mccomb, Sean D Mcevoy, Thanda Meehan, Arnold H Menezes, Michael S Muhlbauer, Brent R O'Neill, Greg Olavarria, John Ragheb, Nathan R Selden, Manish N Shah, Chevis N Shannon, Joshua S Shimony, Matthew D Smyth, Scellig S D Stone, Jennifer M Strahle, Mandeep S Tamber, James C Torner, Gerald F Tuite, Elizabeth C Tyler-Kabara, Scott D Wait, John C Wellons, William E Whitehead, Tae Sung Park, David D Limbrick, Raheel Ahmed

Faculty, Staff and Student Publications

Objective: Congenital anomalies of the atlanto-occipital articulation may be present in patients with Chiari malformation type I (CM-I). However, it is unclear how these anomalies affect the biomechanical stability of the craniovertebral junction (CVJ) and whether they are associated with an increased incidence of occipitocervical fusion (OCF) following posterior fossa decompression (PFD). The objective of this study was to determine the prevalence of condylar hypoplasia and atlas anomalies in children with CM-I and syringomyelia. The authors also investigated the predictive contribution of these anomalies to the occurrence of OCF following PFD (PFD+OCF).

Methods: The authors analyzed the prevalence of condylar …

Anti-Acetylated-Tau Immunotherapy Is Neuroprotective In Tauopathy And Brain Injury, Celeste Parra Bravo, Karen Krukowski, Sarah Barker, Chao Wang, Yaqiao Li, Li Fan, Edwin Vázquez-Rosa, Min-Kyoo Shin, Man Ying Wong, Louise D Mccullough, Ryan S Kitagawa, H Alex Choi, Angela Cacace, Subhash C Sinha, Andrew A Pieper, Susanna Rosi, Xu Chen, Li Gan

Faculty, Staff and Student Publications

BACKGROUND: Tau is aberrantly acetylated in various neurodegenerative conditions, including Alzheimer's disease, frontotemporal lobar degeneration (FTLD), and traumatic brain injury (TBI). Previously, we reported that reducing acetylated tau by pharmacologically inhibiting p300-mediated tau acetylation at lysine 174 reduces tau pathology and improves cognitive function in animal models.

METHODS: We investigated the therapeutic efficacy of two different antibodies that specifically target acetylated lysine 174 on tau (ac-tauK174). We treated PS19 mice, which harbor the P301S tauopathy mutation that causes FTLD, with anti-ac-tauK174 and measured effects on tau pathology, neurodegeneration, and neurobehavioral outcomes. Furthermore, PS19 mice received treatment post-TBI to evaluate the …

Incidence And Factors In Delayed Neurological Deficits After Subarachnoid Hemorrhage In Mice, William Wroe, Ari Dienel, Sungha Hong, Kanako Matsumura, Jose Guzman, Kiara Torres, Angelica Bernal, Hussein A Zeineddine, Peeyush Thankamani Pandit, Spiros L Blackburn, Devin W Mcbride

Faculty, Staff and Student Publications

Background: Delayed cerebral ischemia (DCI) is one of the most feared complications in aneurysmal subarachnoid hemorrhage (SAH). Animal models are crucial to studying the disease mechanisms and potential treatments. DCI in rodents was thought to not exist; herein we examine literature and our experience with DCI in rodents.

Methods: Daily behavioral performance was assessed every day from day 1 to up to 7 days post-SAH on mice from 5 different studies that used the endovascular perforation model. Performance was graded using an 8-test sensorimotor neuroscore previously described. The daily neuroscore was then used to identify the incidence and timing of …

Endovascular Treatment Of Acute Ischemic Stroke Patients With Tandem Lesions: Antegrade Versus Retrograde Approach, Milagros Galecio-Castillo, Michael Abraham, Mudassir Farooqui, Ameer E Hassan, Afshin A Divani, Mouhammad A Jumaa, Marc Ribo, Nils Petersen, Johanna Fifi, Waldo R Guerrero, Amer M Malik, James E Siegler, Thanh N Nguyen, Sunil A Sheth, Albert J Yoo, Guillermo Linares, Nazli Janjua, Darko Quispe-Orozco, Abid Qureshi, Wondwossen G Tekle, Asad Ikram, Syed F Zaidi, Cynthia B Zevallos, Belen Taborda, Alex Devarajan, Linda Zhang, Mohamad Abdalkader, Sergio Salazar-Marioni, Jazba Soomro, Weston Gordon, Aaron Rodriguez-Calienes, Juan Vivanco-Suarez, Katrina Woolfolk, Maxim Mokin, Dileep R Yavagal, Santiago Ortega-Gutierrez

Faculty, Staff and Student Publications

Objective: The optimal technique for treating tandem lesions (TLs) with endovascular therapy is debatable. The authors evaluated the functional, safety, and procedural outcomes of different approaches in a multicenter study.

Methods: Anterior circulation TL patients treated from January 2015 to December 2020 were divided on the basis of antegrade versus retrograde approach and included. The evaluated outcomes were favorable modified Rankin Scale (mRS) score (mRS score 0-2) at 3 months, ordinal shift in mRS score, successful recanalization, excellent recanalization, first-pass effect (FPE), time from groin puncture to successful recanalization, symptomatic intracranial hemorrhage (sICH), and 90-day mortality.

Results: Among 691 patients …

Transport Of Non-Classical Light Mediated By Topological Domain Walls In A Ssh Photonic Lattice, Gabriel O'Ryan Pérez, Joaquín Medina Dueñas, Diego Guzmán-Silva, Luis E F Foa Torres, Carla Hermann-Avigliano

Faculty, Staff and Student Publications

Advancements in photonics technologies have significantly enhanced their capability to facilitate experiments involving quantum light, even at room temperature. Nevertheless, fully integrating photonic chips that include quantum light sources, effective manipulation and transport of light minimizing losses, and appropriate detection systems remains an ongoing challenge. Topological photonic systems have emerged as promising platforms to protect quantum light properties during propagation, beyond merely preserving light intensity. In this work, we delve into the dynamics of non-classical light traversing a Su-Schrieffer-Heeger photonic lattice with topological domain walls. Our focus centers on how topology influences the quantum properties of light as it moves …

Ras G-Domains Allosterically Contribute To The Recognition Of Lipid Headgroups And Acyl Chains, Neha Arora, Huanwen Mu, Hong Liang, Wenting Zhao, Yong Zhou

Faculty, Staff and Student Publications

Mutant RAS are major contributors to cancer and signal primarily from nanoclusters on the plasma membrane (PM). Their C-terminal membrane anchors are main features of membrane association. However, the same RAS isoform bound to different guanine nucleotides spatially segregate. Different RAS nanoclusters all enrich a phospholipid, phosphatidylserine (PS). These findings suggest more complex membrane interactions. Our electron microscopy-spatial analysis shows that wild-types, G12V mutants, and membrane anchors of isoforms HRAS, KRAS4A, and KRAS4B prefer distinct PS species. Mechanistically, reorientation of KRAS4B G-domain exposes distinct residues, such as Arg 135 in orientation state 1 (OS1) and Arg 73/Arg 102 in OS2, …

Chelation Enables Selectivity Control In Enantioconvergent Suzuki-Miyaura Cross-Couplings On Acyclic Allylic Systems, Violeta Stojalnikova, Stephen J Webster, Ke Liu, Stephen P Fletcher

Faculty, Staff and Student Publications

Asymmetric Suzuki-Miyaura cross-couplings with aryl boronic acids and allylic electrophiles are a powerful method to convert racemic mixtures into enantioenriched products. Currently, enantioconvergent allylic arylations are limited to substrates that are symmetrical about the allylic unit, and the absence of strategies to control regio-, E/Z- and enantioselectivity in acyclic allylic systems is a major restriction. Here, using a system capable of either conjugate addition or allylic arylation, we have discovered the structural features and experimental conditions that allow an acyclic system to undergo chemo- and regioselective, enantioconvergent allylic Suzuki-Miyaura-type arylation. A wide variety of boronic acid coupling partners can be …

Prevalence And Associations Of Dural Arteriovenous Fistulae In Cerebral Venous Thrombosis: Analysis Of Action-Cvt, Aaron Shoskes, Liqi Shu, Thanh N Nguyen, Mohamad Abdalkader, James Giles, Jordan Amar, James E Siegler, Nils Henninger, Marwa Elnazeir, Sami Al Kasab, Piers Klein, Mirjam R Heldner, Kateryna Antonenko, Marios Psychogios, David S Liebeskind, Thalia Field, Ava Liberman, Charles Esenwa, Alexis Simpkins, Grace Li, Jennifer Frontera, Lindsey Kuohn, Aaron Rothstein, Ossama Khazaal, Yasmin Aziz, Eva Mistry, Pooja Khatri, Setareh Salehi Omran, Adeel S Zubair, Richa Sharma, Robert M Starke, Jacques J Morcos, Jose G Romano, Shadi Yaghi, Negar Asdaghi

Faculty, Staff and Student Publications

No abstract provided.

Vitamin A Status Modulates Epithelial Mesenchymal Transition In The Lung: The Role Of Furin, M Teresa Cabezuelo, Luis Torres, Elena Ortiz-Zapater, Gerardo López-Rodas, M Pilar Marín, Joaquín Timoneda, Juan R Viña, Rosa Zaragozá, Teresa Barber

Faculty, Staff and Student Publications

Vitamin A deficiency (VAD) induced TGF-β hyperactivation and reduced expression of cell adhesion proteins in the lung, suggesting that the disruption of retinoic acid (RA) signaling leads to epithelial-mesenchymal transition (EMT). To elucidate the role of lung vitamin A status in EMT, several EMT markers and the expression of the proprotein convertase furin, which activates TGF-β, were analyzed in two experimental models. Our in vivo model included control rats, VAD rats, and both control rats and VAD rats, treated with RA. For the in vitro studies, human bronchoalveolar epithelial cells treated with RA were used. Our data show that EMT …

Photophobia Is Associated With Lower Sleep Quality In Individuals With Migraine: Results From The American Registry For Migraine Research (Armr), Nina Sharp, Mark J Burish, Kathleen B Digre, Jessica Ailani, Mahya Fani, Sophia Lamp, Todd J Schwedt

Faculty, Staff and Student Publications

BACKGROUND: Patients with migraine often have poor sleep quality between and during migraine attacks. Furthermore, extensive research has identified photophobia as the most common and most bothersome symptom in individuals with migraine, second only to headache. Seeking the comfort of darkness is a common strategy for managing pain during an attack and preventing its recurrence between episodes. Given the well-established effects of daily light exposure on circadian activity rhythms and sleep quality, this study aimed to investigate the relationship between photophobia symptoms and sleep quality in a cohort of patients with migraine.

METHODS: A cross-sectional observational study was conducted using …

It's About Time! Timing In Epilepsy Evaluation And Treatment, Heather Ravvin Mckee, Jorge Vidaurre, Dave Clarke, Janelle Wagner, Jeffrey W Britton, Linda Laux, Eugen Trinka, Clio Rubinos, Tanya J W Mcdonald, Fred A Lado, Martina Bebin, Christos Papadelis, Aaron F Struck, Carolina B Maciel, Ana L Velasco, Arjun Chandran, Sandipan Pati, Nitin Tandon, Guadalupe Fernandez-Baca Vaca, Madison M Berl, Ahsan N Moosa

Faculty, Staff and Student Publications

The 2023 American Epilepsy Society Annual Course "It's About Time" addressed timing in epilepsy evaluation and treatment with respect to health disparity and vulnerable populations and diagnostic, clinical, and epilepsy surgery evaluation. This comprehensive course included topics on gaps in epilepsy care and optimization of behavioral health for patients with epilepsy. The summary details current knowledge in areas of seizure forecasting and epileptogenesis. Intricacies and controversies over timing were discussed for treatment of nonconvulsive seizures and ictal-interictal patterns, acute symptomatic seizures, neuromodulation versus surgery, and epilepsy surgery in status epilepticus. Timing regarding clinical care in autoimmune-associated epilepsy, developmental and epileptic …

Effectiveness Of A Training Program For The Management Of Risky Alcohol Use In Primary Care Professionals Based On Motivational Interviewing, Celia Pérula-Jiménez, Esperanza Romero-Rodríguez, Juan Manuel Parras-Rejano, Ana González De La Rubia, Juan Baleato Gómez, Luis Angel Pérula De Torres

Faculty, Staff and Student Publications

OBJECTIVE: To assess the effectiveness of a training program for Primary Care (PC) professionals developed to increase knowledge, attitudes, and skills for managing patients with risky alcohol use and in the motivational interview.

DESIGN: Multicenter, two-arm parallel, randomized, open-label controlled clinical trial.

SETTING: PC of the Andalusian Health Service.

PARTICIPANTS: The study was completed by 80 healthcare professionals from 31 PC centers.

INTERVENTIONS: In both experimental and control groups, a workshop on managing patients with risky alcohol consumption and the resolution of two videotaped clinical cases with standardized patients were conducted. The experimental group attended a workshop on motivational interviewing. …

Minimally Invasive Anterior Cervical Foraminotomy For Unilateral Radiculopathy, Duncan J Trimble, Dallas L Sheinberg, Joseph A Cochran

Faculty, Staff and Student Publications

Anterior cervical foraminotomy (ACF) is an alternative surgical option for the treatment of refractory unilateral radiculopathy due to disc herniation or spondylosis. The efficacy and adverse event rate in experienced practitioners are comparable to those of anterior cervical discectomy and fusion, total disc arthroplasty, and posterior foraminotomy. However, this technique has not been widely adopted, likely because of the proximity of the working zone and the vertebral artery. The authors present a detailed operative video of a patient successfully treated with an ACF. They also present a review of the ACF literature.

The video can be found here: https://stream.cadmore.media/r10.3171/2024.1.FOCVID23196

Endovascular Thrombectomy For Large Ischemic Stroke Across Ischemic Injury And Penumbra Profiles, Amrou Sarraj, Ameer E Hassan, Michael G Abraham, Santiago Ortega-Gutierrez, Scott E Kasner, Muhammad Shazam Hussain, Michael Chen, Leonid Churilov, Hannah Johns, Clark W Sitton, Vignan Yogendrakumar, Felix C Ng, Deep K Pujara, Spiros Blackburn, Sophia Sundararajan, Yin C Hu, Nabeel A Herial, Juan F Arenillas, Jenny P Tsai, Ronald F Budzik, William J Hicks, Osman Kozak, Bernard Yan, Dennis J Cordato, Nathan W Manning, Mark W Parsons, Andrew Cheung, Ricardo A Hanel, Amin N Aghaebrahim, Teddy Y Wu, Pere Cardona Portela, Chirag D Gandhi, Fawaz Al-Mufti, Natalia Pérez De La Ossa, Joanna D Schaafsma, Jordi Blasco, Navdeep Sangha, Steven Warach, Timothy J Kleinig, Faris Shaker, Faisal Al Shaibi, Gabor Toth, Mohammad A Abdulrazzak, Gagan Sharma, Abhishek Ray, Jeffrey Sunshine, Amanda Opaskar, Kelsey R Duncan, Wei Xiong, Edgar A Samaniego, Laith Maali, Colleen G Lechtenberg, Arturo Renú, Nirav Vora, Thanh Nguyen, Johanna T Fifi, Stavropoula I Tjoumakaris, Pascal Jabbour, Georgios Tsivgoulis, Vitor Mendes Pereira, Maarten G Lansberg, Michael Degeorgia, Cathy A Sila, Nicholas Bambakidis, Michael D Hill, Stephen M Davis, Lawrence Wechsler, James C Grotta, Marc Ribo, Greg W Albers, Bruce C Campbell

Faculty, Staff and Student Publications

Importance: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain.

Objective: To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect.

Design, setting, and participants: An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 …

The Pug Flap: Conjoined Profunda Artery Perforator And Upper Gracilis Flap For Breast Reconstruction, Isra Abdulwadood, Lacey R Pflibsen, Nicholas R Jarvis, Sebastian Winocour, Alanna M Rebecca, William J Casey, Edward M Reece

Faculty, Staff and Students Publications

Abdominal-based free flaps are the mainstay of autologous breast reconstruction; however, the region may not be ideal for patients with inadequate soft tissue or history of abdominal surgery. This case describes the use of a novel conjoined flap based on the profunda artery perforator and upper gracilis pedicles, named the perforator and upper gracilis (PUG) flap. This flap design aims to maximize medial thigh flap volume while ensuring robust tissue perforation. Here, we present our experience with the PUG flap in a breast cancer patient undergoing autologous reconstruction. The patient was a 41-year-old woman seeking nipple-sparing mastectomy and immediate autologous …

Experience With A Hybrid Recruitment Approach Of Patient-Facing Web Portal Screening And Subsequent Phone And Medical Record Review For A Neurosurgical Intervention Trial For Chronic Ischemic Stroke Disability (Pisces Iii), Brad J Kolls, Keith W Muir, Sean I Savitz, Lawrence R Wechsler, Julie G Pilitsis, Scott Rahimi, Richard L Beckman, Vincent Holmes, Peng R Chen, David S Albers, Daniel T Laskowitz

Faculty, Staff and Student Publications

BACKGROUND: Recruitment of participants is the greatest risk to completion of most clinical trials, with 20-40% of trials failing to reach the targeted enrollment. This is particularly true of trials of central nervous system (CNS) therapies such as intervention for chronic stroke. The PISCES III trial was an invasive trial of stereotactically guided intracerebral injection of CTX0E03, a fetal derived neural stem cell line, in patients with chronic disability due to ischemic stroke. We report on the experience using a novel hybrid recruitment approach of a patient-facing portal to self-identify and perform an initial screen for general trial eligibility (tier …

Thsd1 Suppresses Autophagy-Mediated Focal Adhesion Turnover By Modulating The Fak-Beclin 1 Pathway, Zhen Xu, Jiayi Lu, Song Gao, Yan-Ning Rui

Faculty, Staff and Student Publications

Focal adhesions (FAs) play a crucial role in cell spreading and adhesion, and their autophagic degradation is an emerging area of interest. This study investigates the role of Thrombospondin Type 1 Domain-Containing Protein 1 (THSD1) in regulating autophagy and FA stability in brain endothelial cells, shedding light on its potential implications for cerebrovascular diseases. Our research reveals a physical interaction between THSD1 and FAs. Depletion of THSD1 significantly reduces FA numbers, impairing cell spreading and adhesion. The loss of THSD1 also induces autophagy independently of changes in mTOR and AMPK activation, implying that THSD1 primarily governs FA dynamics rather than …

Kinase-Impaired Btk Mutations Are Susceptible To Clinical-Stage Btk And Ikzf1/3 Degrader Nx-2127, Skye Montoya, Jessie Bourcier, Mark Noviski, Hao Lu, Meghan C Thompson, Alexandra Chirino, Jacob Jahn, Anya K Sondhi, Stefan Gajewski, Ying Siow May Tan, Stephanie Yung, Aleksandra Urban, Eric Wang, Cuijuan Han, Xiaoli Mi, Won Jun Kim, Quinlan Sievers, Paul Auger, Hugo Bousquet, Nivetha Brathaban, Brandon Bravo, Melissa Gessner, Cristiana Guiducci, James N Iuliano, Tim Kane, Ratul Mukerji, Panga Jaipal Reddy, Janine Powers, Mateo Sanchez Garcia De Los Rios, Jordan Ye, Carla Barrientos Risso, Daniel Tsai, Gabriel Pardo, Ryan Q Notti, Alejandro Pardo, Maurizio Affer, Vindhya Nawaratne, Tulasigeri M Totiger, Camila Pena-Velasquez, Joanna M Rhodes, Andrew D Zelenetz, Alvaro Alencar, Lindsey E Roeker, Sanjoy Mehta, Ralph Garippa, Adam Linley, Rajesh Kumar Soni, Sigrid S Skånland, Robert J Brown, Anthony R Mato, Gwenn M Hansen, Omar Abdel-Wahab, Justin Taylor

Faculty, Staff and Student Publications

INTRODUCTION:

Bruton’s tyrosine kinase (BTK) is a nonreceptor kinase in the B cell receptor (BCR) signaling cascade critical for B cell survival. As such, chronic lymphocytic leukemia (CLL) and other B cell cancers are sensitive to inhibition of BTK. Covalent and noncovalent inhibitors of BTK have revolutionized the treatment of these cancers. Therefore, understanding mechanisms by which acquired mutation in BTK confer drug resistance and developing new therapies to overcome resistance are critically important.

RATIONALE:

We recently discovered BTK mutations that confer resistance across covalent and noncovalent BTK inhibitors. In this study, we found that a group of these mutants …

It's Not That We Care Less: Insights Into Health Care Utilization For Comorbid Diabetes And Depression Among Latinos, Sharon Borja, Miriam G Valdovinos, Kenia M Rivera, Natalia Giraldo-Santiago, Robin E Gearing, Luis R Torres

Faculty, Staff and Student Publications

Despite robust knowledge regarding the socio-economic and cultural factors affecting Latino* access to healthcare, limited research has explored service utilization in the context of comorbid conditions like diabetes and depression. This qualitative study, embedded in a larger mixed-methods project, aimed to investigate perceptions held by Latinos and their social support systems (i.e., family members) regarding comorbid diabetes and depression and to identify barriers and facilitators to their help-seeking behaviors and treatment engagement. Bilingual and bicultural researchers conducted eight focus groups with 94 participants in a large U.S. metropolitan area and were primarily conducted in Spanish. The participants either had a …

Important Features For Protein Foldings In Two Acyl Carrier Proteins From Enterococcus Faecalis, Seoyeong Yoo, Jiwon Yeon, Eunhee Kim, Yangmee Kim

Faculty, Staff and Student Publications

The emergence of multi-drug resistant Enterococcus faecalis raises a serious threat to global public health. E. faecalis is a gram-positive intestinal commensal bacterium found in humans. E. faecalis can endure extreme environments such as high temperature, pressure, and high salt, which facilitates them to cause infection in hospitals. E. faecalis has two acyl carrier proteins, AcpA (EfAcpA) in de novo fatty acid synthesis (FAS) and AcpB (EfAcpB) which utilizes exogenous fatty acids. Previously, we determined the tertiary structures of these two ACPs and investigated their structure-function relationships. Solution structures revealed that overall folding of these two ACPs is similar to …

Intratumoral Biosynthesis Of Gold Nanoclusters By Pancreatic Cancer To Overcome Delivery Barriers To Radiosensitization, Aaron S Schwartz-Duval, Yuri Mackeyev, Iqbal Mahmud, Philip L Lorenzi, Mihai Gagea, Sunil Krishnan, Konstantin V Sokolov

Faculty, Staff and Student Publications

Nanoparticle delivery to solid tumors is a prime challenge in nanomedicine. Here, we approach this challenge through the lens of biogeochemistry, the field that studies the flow of chemical elements within ecosystems as manipulated by living cellular organisms and their environments. We leverage biogeochemistry concepts related to gold cycling against pancreatic cancer, considering mammalian organisms as drivers for gold nanoparticle biosynthesis. Sequestration of gold nanoparticles within tumors has been demonstrated as an effective strategy to enhance radiotherapy; however, the desmoplasia of pancreatic cancer impedes nanoparticle delivery. Our strategy overcomes this barrier by applying an atomic-scale agent, ionic gold, for intratumoral …

The Geriatric Nutritional Risk Index As A Predictor Of Complications In Geriatric Trauma Patients, Daniel H Wang, Yoko Fujita, Antonio Dono, Ana G Rodriguez Armendariz, Mauli Shah, Nagireddy Putluri, Pavel S Pichardo-Rojas, Chirag B Patel, Jay-Jiguang Zhu, Jason T Huse, Brittany C Parker Kerrigan, Frederick F Lang, Yoshua Esquenazi, Leomar Y Ballester

Faculty, Staff and Student Publications

Cerebrospinal fluid (CSF) analysis is underutilized in patients with glioblastoma (GBM), partly due to a lack of studies demonstrating the clinical utility of CSF biomarkers. While some studies show the utility of CSF cell-free DNA analysis, studies analyzing CSF metabolites in patients with glioblastoma are limited. Diffuse gliomas have altered cellular metabolism. For example, mutations in isocitrate dehydrogenase enzymes (e.g., IDH1 and IDH2) are common in diffuse gliomas and lead to increased levels of D-2-hydroxyglutarate in CSF. However, there is a poor understanding of changes CSF metabolites in GBM patients. In this study, we performed targeted metabolomic analysis of CSF …

Surgical Management Of Choanal Atresia: Two Classic Cases And Review Of The Literature, Philipp Karschnia, Jorg Dietrich, Francesco Bruno, Antonio Dono, Stephanie T Juenger, Nico Teske, Jacob S Young, Tommaso Sciortino, Levin Häni, Martin Van Den Bent, Michael Weller, Michael A Vogelbaum, Ramin A Morshed, Alexander F Haddad, Annette M Molinaro, Nitin Tandon, Juergen Beck, Oliver Schnell, Lorenzo Bello, Shawn Hervey-Jumper, Niklas Thon, Stefan J Grau, Yoshua Esquenazi, Roberta Rudà, Susan M Chang, Mitchel S Berger, Daniel P Cahill, Joerg-Christian Tonn

Faculty, Staff and Student Publications

BACKGROUND: Resection of the contrast-enhancing (CE) tumor represents the standard of care in newly diagnosed glioblastoma. However, some tumors ultimately diagnosed as glioblastoma lack contrast enhancement and have a 'low-grade appearance' on imaging (non-CE glioblastoma). We aimed to (a) volumetrically define the value of non-CE tumor resection in the absence of contrast enhancement, and to (b) delineate outcome differences between glioblastoma patients with and without contrast enhancement.

METHODS: The RANO resect group retrospectively compiled a global, eight-center cohort of patients with newly diagnosed glioblastoma per WHO 2021 classification. The associations between postoperative tumor volumes and outcome were analyzed. Propensity score-matched …

Phase 1 Trial Of Tpi 287, A Microtubule Stabilizing Agent, In Combination With Bevacizumab In Adults With Recurrent Glioblastoma, Samuel A Goldlust, Louis B Nabors, Sigmund Hsu, Nimish Mohile, Paul J Duic, Tara Benkers, Samuel Singer, Mayank Rao, Lori Cappello, Sandra L Silberman, George Farmer

Faculty, Staff and Student Publications

BACKGROUND: Recurrent glioblastoma (rGBM) has limited treatment options. This phase 1 protocol was designed to study the safety and preliminary efficacy of TPI 287, a central nervous system penetrant microtubule stabilizer, in combination with bevacizumab (BEV) for the treatment of rGBM.

METHODS: GBM patients with up to 2 prior relapses without prior exposure to anti-angiogenic therapy were eligible. A standard 3 + 3 design was utilized to determine the maximum tolerated dose (MTD) of TPI 287. Cohorts received TPI 287 at 140-220 mg/m

RESULTS: Twenty-four patients were enrolled at 6 centers. Treatment was generally well tolerated. Fatigue, myelosuppression, and peripheral …

20-Year Inflation-Adjusted Medicare Reimbursements (Years: 2000-2020) For Common Lumbar And Cervical Degenerative Disc Disease Procedures, Pedram Honarpisheh, Samantha L Parker, Christopher R Conner, Sami Anjum, Jessica R Stark, John C Quinn, John M Caridi

Faculty, Staff and Student Publications

OBJECTIVE: Reimbursement trends for common procedures have persistently declined over the past 2 decades. Spinal instrumentational and fusion procedures are increasingly utilized and have increased in clinical complexity, yet longitudinal inflation-adjusted data for Medicare reimbursements of these procedures have not been evaluated.

METHODS: The Centers for Medicare and Medicaid Services (CMS) Physician Fee Schedule Look-Up Tool was used to extract Medicare reimbursements for the 5 most common spinal procedures and associated instrumentations from 2000-2020. Current Procedural Terminology (CPT) codes include 22551, 22600, 22633, 63030, and 63047 as well as instrumentation CPT codes 22840 and 22842-6. The nominal values were adjusted …

Updates Of The Role Of B-Cells In Ischemic Stroke, Silin Wu, Sidra Tabassum, Cole T Payne, Heng Hu, Aaron M Gusdon, Huimahn A Choi, Xuefang S Ren

Faculty, Staff and Student Publications

Ischemic stroke is a major disease causing death and disability in the elderly and is one of the major diseases that seriously threaten human health and cause a great economic burden. In the early stage of ischemic stroke, neuronal structure is destroyed, resulting in death or damage, and the release of a variety of damage-associated pattern molecules induces an increase in neuroglial activation, peripheral immune response, and secretion of inflammatory mediators, which further exacerbates the damage to the blood-brain barrier, exacerbates cerebral edema, and microcirculatory impairment, triggering secondary brain injuries. After the acute phase of stroke, various immune cells initiate …

Mir-29 And Mir-140 Regulate Trail-Induced Drug Tolerance In Lung Cancer, Suyeon Kim, Ki Wook Lee, Yongjin Yoo, Sang Hee Park, Ji Won Lee, Suhyun Jeon, Shaginyan Illia, Pooja Joshi, Hyun Woo Park, Han-En Lo, Jimin Seo, Yeonwoo Kim, Min Chang, Tae Jin Lee, Jong Bae Seo, Sung-Hak Kim, Carlo M Croce, Inki Kim, Sung-Suk Suh, Young-Jun Jeon

Faculty, Staff and Student Publications

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has chemotherapeutic potential as a regulator of an extrinsic apoptotic ligand, but its effect as a drug is limited by innate and acquired resistance. Recent findings suggest that an intermediate drug tolerance could mediate acquired resistance, which has made the main obstacle for limited utility of TRAIL as an anti-cancer therapeutics. We propose miRNA-dependent epigenetic modification drives the drug tolerant state in TRAIL-induced drug tolerant (TDT). Transcriptomic analysis revealed miR-29 target gene activation in TDT cells, showing oncogenic signature in lung cancer. Also, the restored TRAIL-sensitivity was associated with miR-29ac and 140-5p expressions, which …