Medical Specialties Commons^™

Outcomes Of Standard-Risk Multiple Myeloma Patients Who Undergo Upfront Autologous Hematopoietic Stem Cell Transplantation, Oren Pasvolsky, Curtis Marcoux, Zhongya Wang, Denái R Milton, Babar Pal, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Guilin Tang, Naureen Syed, Yosra Aljawai, Hans C Lee, Krina K Patel, Melody R Becnel, Christine Ye, Partow Kebriaei, Sheeba K Thomas, Robert Z Orlowski, Richard E Champlin, Elizabeth J Shpall, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Patients with multiple myeloma (MM) without high-risk cytogenetic abnormalities are classified as having standard-risk MM (SRMM), and data focusing on their outcomes after autologous hematopoietic stem cell transplantation (autoHCT) are limited. We sought to evaluate survival outcomes for patients with SRMM receiving autoHCT, and to elucidate factors that impact these outcomes. This was a single-center retrospective analysis that included consecutive MM patients who received upfront autoHCT between 2013 and 2021, had available cytogenetic information and had no high-risk chromosomal abnormalities on fluorescence in situ hybridization, defined as t(4;14), t(14;16), del(17p) or 1q21 gain or amplification. A total of 1000 SRMM …

Loncastuximab In High-Risk And Heavily Pretreated Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Realworld Analysis From 21 Us Centers, Viktoriya Zelikson, Ashwath Gurumurthi, Yazeed Sawalha, Kaitlin Annunzio, Aditi Saha, Ning Dong, David Qualls, Behzad Amoozgar, Brad Kahl, John Baird, Pavan Challa, Scott F Huntington, Jennifer Santos, Steven Bair, Mayur Narkhede, Shuning Li, Zachary Frosch, Carrie Ho, Stephen D Smith, Allison Winter, Daniel Landsburg, Fateeha Furqan, Mehdi Hamadani, Katelin Baird, Jason Romancik, Hanan Alharthy, Jennie Law, Leyla Bojanini, Ranjana Advani, Boyu Hu, Patrick Connor Johnson, Natalie S Grover, Mwanasha Merril, Jennifer L Crombie, Nazila Shafagati, Cole Sterling, Loretta J Nastoupil, Narendranath Epperla, Emily C Ayers

Faculty, Staff and Student Publications

Outcomes in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) are poor. Loncastuximab- teserine (Lonca) is an antibody-drug conjugate which was approved by the Food and Drug Administration for the treatment of patients with R/R DLBCL who have received at least two prior lines of therapy, based on the results of the LOTIS-2 trial. However, there are limited data regarding its efficacy in the real-world setting. This retrospective study included 21 US centers and evaluated outcomes of patients with R/R DLBCL treated with Lonca. Our analysis comprises 187 patients with notably higher-risk baseline features compared to those of the …

Combining Radioembolization And Immune Checkpoint Inhibitors For The Treatment Of Hepatocellular Carcinoma: The Quest For Synergy, Christopher D Malone, Suryansh Bajaj, Aiwu He, Kabir Mody, Ryan M Hickey, Ammar Sarwar, Sunil Krishnan, Tushar C Patel, Beau B Toskich

Faculty, Staff and Student Publications

Hepatocellular carcinoma is a leading and increasing contributor to cancer-related death worldwide. Recent advancements in both liver-directed therapies in the form of yttrium-90 (90Y) radioembolization (RE) and systemic therapy in the form of immune checkpoint inhibitors (ICI) have expanded treatment options for patients with an otherwise poor prognosis. Despite these gains, ICIs and 90Y-RE each have key limitations with low objective response rates and persistent hazard of out-of-field recurrence, respectively, and overall survival remains low. However, each therapy's strength may mitigate the other's weakness, making them potentially ideal partners for combination treatment strategies. This review discusses the scientific and clinical …

Spetzler-Martin Grade I And Ii Cerebral Arteriovenous Malformations: A Propensity-Score Matched Analysis Of Resection And Stereotactic Radiosurgery In Adult Patients, Salem Tos, Mahmoud Osama, Georgios Mantziaris, Bardia Hajikarimloo, Nimer Adeeb, Sandeep Kandregula, Adam Dmytriw, Hamza Adel Salim, Basel Musmar, Kareem El Naamani, Christopher Ogilvy, Douglas Kondziolka, Ahmed Abdelsalam, Deepak Kumbhare, Sanjeev Gummadi, Cagdas Ataoglu, Ufuk Erginoglu, Muhammed Amir Essibayi, Abdullah Keles, Sandeep Muram, Daniel Sconzo, Howard Riina, Arwin Rezai, Johannes Pöppe, Rajeev Sen, Omar Alwakaa, Christoph Griessenauer, Pascal Jabbour, Stavropoula Tjoumakaris, Jan-Karl Burkhardt, Robert Starke, Mustafa Baskaya, Laligam Sekhar, Michael Levitt, David Altschul, Neil Haranhalli, Malia Mcavoy, Assala Aslan, Abdallah Abushehab, Christian Swaid, Adib Abla, Christopher Stapleton, Matthew Koch, Visish M Srinivasan, Peng Chen, Spiros Blackburn, Mark Dannenbaum, Omar Choudhri, Bryan Pukenas, Darren Orbach, Edward Smith, Markus Möhlenbruch, Ali Alaraj, Ali Aziz-Sultan, Aman Patel, Hugo Cuellar, Michael Lawton, Jacques Morcos, Bharat Guthikonda, Jason Sheehan

Department of Neurosurgery Faculty Papers

Cerebral arteriovenous malformations (AVMs) are congenital vascular anomalies that can lead to severe complications, including hemorrhage and neurological deficits. This study compares the outcomes of microsurgical resection and stereotactic radiosurgery (SRS) for SM grade I and II AVMs. Out of a large multicenter registry, we identified 180 matched patients with SM grade I and II AVMs treated with either microsurgical resection or SRS between 2010 and 2023. The primary outcomes were AVM obliteration rates and complications; secondary outcomes included neurological status and functional outcomes measured by the modified Rankin Scale (mRS). Propensity score matching (PSM) was utilized to ensure comparability …

Spetzler-Martin Grade I And Ii Cerebral Arteriovenous Malformations: A Propensity-Score Matched Analysis Of Resection And Stereotactic Radiosurgery In Adult Patients, Salem M Tos, Mahmoud Osama, Georgios Mantziaris, Bardia Hajikarimloo, Nimer Adeeb, Sandeep Kandregula, Adam A Dmytriw, Hamza Adel Salim, Basel Musmar, Kareem El Naamani, Christopher Ogilvy, Douglas Kondziolka, Ahmed Abdelsalam, Deepak Kumbhare, Sanjeev Gummadi, Cagdas Ataoglu, Ufuk Erginoglu, Muhammed Amir Essibayi, Abdullah Keles, Sandeep Muram, Daniel Sconzo, Howard Riina, Arwin Rezai, Johannes Pöppe, Rajeev D Sen, Omar Alwakaa, Christoph J Griessenauer, Pascal Jabbour, Stavropoula I Tjoumakaris, Jan-Karl Burkhardt, Robert M Starke, Mustafa Baskaya, Laligam N Sekhar, Michael R Levitt, David J Altschul, Neil Haranhalli, Malia Mcavoy, Assala Aslan, Abdallah Abushehab, Christian Swaid, Adib Abla, Christopher Stapleton, Matthew Koch, Visish M Srinivasan, Peng R Chen, Spiros Blackburn, Mark J Dannenbaum, Omar Choudhri, Bryan Pukenas, Darren Orbach, Edward Smith, Markus Möhlenbruch, Ali Alaraj, Ali Aziz-Sultan, Aman B Patel, Hugo H Cuellar, Michael Lawton, Jacques Morcos, Bharat Guthikonda, Jason Sheehan

Faculty, Staff and Student Publications

Cerebral arteriovenous malformations (AVMs) are congenital vascular anomalies that can lead to severe complications, including hemorrhage and neurological deficits. This study compares the outcomes of microsurgical resection and stereotactic radiosurgery (SRS) for SM grade I and II AVMs. Out of a large multicenter registry, we identified 180 matched patients with SM grade I and II AVMs treated with either microsurgical resection or SRS between 2010 and 2023. The primary outcomes were AVM obliteration rates and complications; secondary outcomes included neurological status and functional outcomes measured by the modified Rankin Scale (mRS). Propensity score matching (PSM) was utilized to ensure comparability …

Impact Of Measurable Residual Disease Clearance Kinetics In Patients With Aml Undergoing Intensive Chemotherapy, Wei-Ying Jen, Koji Sasaki, Farhad Ravandi, Tapan M Kadia, Sa A Wang, Wei Wang, Sanam Loghavi, Naval G Daver, Courtney D Dinardo, Ghayas C Issa, Hussein A Abbas, Cedric Nasnas, Alex Bataller, Samuel Urrutia, Omer S Karrar, Sherry Pierce, Hagop M Kantarjian, Nicholas J Short

Faculty, Staff and Student Publications

The prognostic impact of measurable residual disease (MRD) in acute myeloid leukemia (AML) is unequivocal; however, the optimal time point for achieving undetectable MRD is unclear. We retrospectively studied patients with newly diagnosed (ND) AML who achieved remission with frontline intensive chemotherapy and had MRD assessed by flow cytometry after induction (time point 1 [TP1]) and after cycles 2 or 3 (TP2). Cases were grouped into MRD negative (Neg)/Neg, positive (Pos)/Neg, or Pos/Pos at TP1 and TP2, respectively. Of 1980 patients with ND AML, 277 met the inclusion criteria and were included in this analysis. The median relapse-free survival (RFS) …

Incidence And Predictors Of Woven Endobridge (Web) Shape Modification Following Treatment Of Intracranial Aneurysms In A Large Multicenter Study, Nimer Adeeb, Hamza Adel Salim, Basel Musmar, Assala Aslan, Christian Swaid, Miguel Cuellar, Mahmoud Dibas, Nicole Cancelliere, Jose Danilo Bengzon Diestro, Oktay Algin, Sherief Ghozy, Sovann Lay, Adrien Guenego, Leonardo Renieri, Joseph Carnevale, Guillaume Saliou, Panagiotis Mastorakos, Kareem El Naamani, Eimad Shotar, Markus Möhlenbruch, Michael Kral, Charlotte Chung, Mohamed Salem, Ivan Lylyk, Paul Foreman, Hamza Shaikh, Vedran Župančić, Muhammad U Hafeez, Joshua Catapano, Muhammad Waqas, Muhammet Arslan, Onur Ergun, James Rabinov, Yifan Ren, Clemens Schirmer, Mariangela Piano, Anna Kühn, Caterina Michelozzi, Robert Starke, Ameer Hassan, Mark Ogilvie, Anh Nguyen, Jesse Jones, Waleed Brinjikji, Marie Nawka, Marios Psychogios, Christian Ulfert, Bryan Pukenas, Jan-Karl Burkhardt, Thien Huynh, Juan Carlos Martinez-Gutierrez, Muhammed Amir Essibayi, Sunil Sheth, Diana Slawski, Rabih Tawk, Benjamin Pulli, Boris Lubicz, Pietro Panni, Ajit Puri, Guglielmo Pero, Eytan Raz, Christoph Griessenauer, Hamed Asadi, Adnan Siddiqui, Elad Levy, Neil Haranhalli, David Altschul, Andrew Ducruet, Felipe Albuquerque, Robert Regenhardt, Christopher Stapleton, Peter Kan, Vladimir Kalousek, Pedro Lylyk, Srikanth Boddu, Jared Knopman, Stavropoula Tjoumakaris, Pascal Jabbour, Frédéric Clarençon, Nicola Limbucci, Vivek Yedavalli, Max Wintermark, Vitor Mendes Pereira, Aman Patel, Hugo Cuellar-Saenz, Adam Dmytriw

Department of Neurosurgery Faculty Papers

The Woven EndoBridge (WEB) device is FDA-approved for the treatment of bifurcation aneurysms. Despite its wide popularity, it has been under scrutiny for its association with potential aneurysm recanalization and retreatment due to device shape modification. This study aims to analyze the shape modification rate of WEB devices and identify factors associated with this phenomenon, as well as its correlation with aneurysm retreatment. We conducted a retrospective review of the WorldWide WEB Consortium database, including adult patients treated for intracranial aneurysms with the WEB device. We assessed aneurysm occlusion using the WEB Occlusion Scale and defined WEB shape modification as …

Continued Nintedanib In Patients With Systemic Sclerosis-Associated Interstitial Lung Disease: 3-Year Data From Senscis-On, Yannick Allanore, Madelon C Vonk, Oliver Distler, Arata Azuma, Maureen D Mayes, Alexandra James, Veronika Kohlbrenner, Margarida Alves, Dinesh Khanna, Kristin B Highland

Faculty, Staff and Student Publications

Objective: We assessed adverse events and changes in forced vital capacity (FVC) in patients treated with open-label nintedanib over 148 weeks of SENSCIS-ON, the extension of the SENSCIS trial.

Methods: Adverse events and changes in FVC over 148 weeks of SENSCIS-ON were assessed in patients who received nintedanib in SENSCIS and continued nintedanib in SENSCIS-ON ('continued nintedanib' group) and in patients who received placebo in SENSCIS or received nintedanib for ≤28 days in a drug-drug interaction study and then received nintedanib in SENSCIS-ON ('initiated nintedanib' group).

Results: The continued nintedanib group comprised 197 patients, and the initiated nintedanib group comprised …

Immune Checkpoint Inhibitors Plus Debulking Surgery For Patients With Metastatic Renal Cell Carcinoma: Clinical Outcomes And Immunological Correlates Of A Prospective Pilot Trial, Sangeeta Goswami, Jianjun Gao, Sreyashi Basu, Daniel D Shapiro, Jose A Karam, Rebecca Slack Tidwell, Kamran Ahrar, Matthew T Campbell, Yu Shen, Alexandro E Trevino, Aaron T Mayer, Alexsandra B Espejo, Christian Seua, Marc D Macaluso, Yulong Chen, Wenbin Liu, Zhong He, Shalini S Yadav, Ying Wang, Priya Rao, Li Zhao, Jianhua Zhang, Sonali Jindal, Nizar M Tannir, Andrew Futreal, Linghua Wang, Padmanee Sharma

Faculty, Staff and Student Publications

Surgical removal of primary tumors reverses tumor-mediated immune suppression in pre-clinical models with metastatic disease. However, how cytoreductive surgery in the metastatic setting modulates the immune responses in patients, especially in the context of immune checkpoint therapy (ICT), is not understood. We report the first prospective, pilot, non-comparative clinical trial (NCT02210117) to evaluate the feasibility, clinical benefits, and immunologic changes of combining three different ICT-containing strategies with cytoreductive surgery or biopsy for patients with metastatic clear cell renal cell carcinoma. Primary safety endpoint of this trial has been met, with 43 patients completing cytoreductive surgery, 36 patients undergoing …

Next-Generation Sequencing-Based Msi Scoring Predicts Benefit In Mismatch Repair-Deficient Tumors Treated With Nivolumab: Follow-Up On Nci-Match Arm Z1d, Jonathan D Schoenfeld, Nilofer S Azad, Jacob Gross, Li Chen, Michael J Overman, Katrina Kao, Latifa Jackson, Donna Brunnquell, Xiangning Bu, Christina Coppola, Ping Guan, Jennifer Lee, David Sims, Rebecca Fuchs, Jason L Weirather, Kathleen L Pfaff, Lauren Gunasti, Srin Ranasinghe, Stanley R Hamilton, Victoria Wang, Peter J O'Dwyer, Catherine J Wu, Scott J Rodig, David R Patton, Lyndsay Harris

Faculty, Staff and Student Publications

Purpose: Mismatch repair-deficient (dMMR) tumors have demonstrated favorable responses to immune checkpoint inhibition targeting PD-1. However, more in-depth identification of predictors of response could further refine patient selection for immunotherapy treatment.

Patients and methods: We undertook integrated evaluation performed on samples collected from 28 of 42 patients enrolled on the NCI-Molecular Analysis for Therapy Choice arm Z1D trial that evaluated PD-1 inhibition treatment with nivolumab in patients with noncolorectal dMMR tumors. Genomic analyses were performed using next-generation sequencing (NGS), whole-exome sequencing, and RNA sequencing and supplemented by multiplex immunofluorescence performed on tissue samples.

Results: In this dMMR population, more extensive …

Treatment Of Small Intracranial Aneurysms Using The Smallss Scoring System: A Novel System For Decision Making, Mira Salih, Michael Young, Thomas B. Fodor, Alexander Andreev, Samuel D. Pettersson, Joanna M. Roy, Basel Musmar, Max Shutran, Phillip Taussky, Christopher S. Ogilvy

Department of Neurosurgery Faculty Papers

BACKGROUND: Treatment of unruptured intracranial aneurysms (UIA) less than 7 mm is controversial. We created a scoring system to guide decision making and validated the system utilizing over 700 cases treated with microsurgery or endovascular procedures.

METHODS: The scoring system SMALLSS included Size, (4-7 mm: 1 point, < 3.9 mm: 0 point), Multiple aneurysms (yes: 1, no: 0), Anatomic location (posterior: 1, anterior: 0), Lineage- family history of aneurysm (yes:1, no: 0), Lifetime risk (age < 65: 1, age > 65: 0), Smoking history (yes: 1, no: 0 ), Shape (irregular:1, smooth:0 ). Validation of this system was performed through retrospective review of prospectively maintained data for UIA patients treated between 2014 and 2021. We then performed an external validation of a cohort of 200 small aneurysms < 7 mm treated at a high volume cerebrovascular center.

RESULTS: A total of 1152 cases …

Glucagon-Like Peptide-1 Receptor Agonists Improve Metabolic Dysfunction-Associated Steatotic Liver Disease Outcomes, Brandon Havranek, Rebecca Loh, Beatriz Torre, Rachel Redfield, Dina Halegoua-De Marzio

Division of Gastroenterology and Hepatology Faculty Papers

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease and is associated with significant cardiovascular morbidity and mortality. This study aims to investigate the association of glucagon-like peptide-1 (GLP-1) agonists with major cardiovascular events, clinically significant portal hypertension events, and all-cause mortality in patients with MASLD. A large, population-based retrospective cohort study was conducted using the TriNetX platform, which provided real-time access to electronic health records of 634,265 adult patients with MASLD/MASH. Propensity score matching (PSM) was employed to create two cohorts: A GLP-1 agonists group and a control group without GLP-1 agonists usage. Hazard …

Large-Bore Mechanical Thrombectomy Versus Catheter-Directed Thrombolysis In The Management Of Intermediate-Risk Pulmonary Embolism: Primary Results Of The Peerless Randomized Controlled Trial., Wissam A Jaber, Carin F Gonsalves, Stefan Stortecky, Samuel Horr, Orestis Pappas, Ripal T Gandhi, Keith Pereira, Jay Giri, Sameer J Khandhar, Khawaja Afzal Ammar, David M Lasorda, Brian Stegman, Lucas Busch, David J Dexter, Ezana M Azene, Nikhil Daga, Fakhir Elmasri, Chandra R Kunavarapu, Mark E Rea, Joseph S Rossi, Joseph Campbell, Jonathan Lindquist, Adam Raskin, Jason C Smith, Thomas M Tamlyn, Gabriel A Hernandez, Parth Rali, Torrey R Schmidt, Jeffrey T Bruckel, Juan C Camacho, Jun Li, Samy Selim, Catalin Toma, Sukhdeep Singh Basra, Brian A Bergmark, Bhavraj Khalsa, David M Zlotnick, Jordan Castle, David J O'Connor, C Michael Gibson

Heart and Vascular Articles

BACKGROUND: There are a lack of randomized controlled trial data comparing outcomes of different catheter-based interventions for intermediate-risk pulmonary embolism.

METHODS: PEERLESS is a prospective, multicenter, randomized controlled trial that enrolled 550 patients with intermediate-risk pulmonary embolism with right ventricular dilatation and additional clinical risk factors randomized 1:1 to treatment with large-bore mechanical thrombectomy (LBMT) or catheter-directed thrombolysis (CDT). The primary end point was a hierarchal win ratio composite of the following (assessed at the sooner of hospital discharge or 7 days after the procedure): (1) all-cause mortality, (2) intracranial hemorrhage, (3) major bleeding, (4) clinical deterioration and/or escalation to …

Large-Bore Mechanical Thrombectomy Versus Catheter-Directed Thrombolysis In The Management Of Intermediate-Risk Pulmonary Embolism: Primary Results Of The Peerless Randomized Controlled Trial, Wissam Jaber, Carin Gonsalves, Stefan Stortecky, Samuel Horr, Orestis Pappas, Ripal Gandhi, Keith Pereira, Jay Giri, Sameer Khandhar, Khawaja Afzal Ammar, David Lasorda, Brian Stegman, Lucas Busch, David Dexter, Ezana Azene, Nikhil Daga, Fakhir Elmasri, Chandra Kunavarapu, Mark Rea, Joseph Rossi, Joseph Campbell, Jonathan Lindquist, Adam Raskin, Jason Smith, Thomas Tamlyn, Gabriel Hernandez, Parth Rali, Torrey Schmidt, Jeffrey Bruckel, Juan Camacho, Jun Li, Samy Selim, Catalin Toma, Sukhdeep Singh Basra, Brian Bergmark, Bhavraj Khalsa, David Zlotnick, Jordan Castle, David O'Connor, C. Michael Gibson

Department of Radiology Faculty Papers

BACKGROUND: There are a lack of randomized controlled trial data comparing outcomes of different catheter-based interventions for intermediate-risk pulmonary embolism.

METHODS: PEERLESS is a prospective, multicenter, randomized controlled trial that enrolled 550 patients with intermediate-risk pulmonary embolism with right ventricular dilatation and additional clinical risk factors randomized 1:1 to treatment with large-bore mechanical thrombectomy (LBMT) or catheter-directed thrombolysis (CDT). The primary end point was a hierarchal win ratio composite of the following (assessed at the sooner of hospital discharge or 7 days after the procedure): (1) all-cause mortality, (2) intracranial hemorrhage, (3) major bleeding, (4) clinical deterioration and/or escalation to …

A Randomized, Double-Blind, Placebo-Controlled Trial Of Il-7 In Critically Ill Patients With Covid-19, Manu Shankar-Hari, Bruno Francois, Kenneth E Remy, Cristina Gutierrez, Stephen Pastores, Thomas Daix, Robin Jeannet, Jane Blood, Andrew H Walton, Reinaldo Salomao, Georg Auzinger, David Striker, Robert S Martin, Nitin J Anand, James Bosanquet, Teresa Blood, Scott Brakenridge, Lyle L Moldawer, Vidula Vachharajani, Cassian Yee, Felipe Dal-Pizzol, Michel Morre, Frederique Berbille, Marcel Van Den Brink, Richard Hotchkiss

Faculty, Staff and Student Publications

Background: Lymphopenia and failure of lymphocytes to mount an early IFN-γ response correlate with increased mortality in COVID-19. Given the essential role of CD4 helper and CD8 cytotoxic cells in eliminating viral pathogens, this profound loss in lymphocytes may impair patients' ability to eliminate the virus. IL-7 is a pleiotropic cytokine that is obligatory for lymphocyte survival and optimal function.

Methods: We conducted a prospective, double-blind, randomized, placebo-controlled trial of CYT107, recombinant human IL-7, in 109 critically ill, patients with lymphopenia who have COVID-19. The primary endpoint was to assess CYT107's effect on lymphocyte recovery with secondary clinical endpoints including …

Large-Bore Mechanical Thrombectomy Versus Catheter-Directed Thrombolysis In The Management Of Intermediate-Risk Pulmonary Embolism: Primary Results Of The Peerless Randomized Controlled Trial, Wissam A Jaber, Carin F Gonsalves, Stefan Stortecky, Samuel Horr, Orestis Pappas, Ripal T Gandhi, Keith Pereira, Jay Giri, Sameer J Khandhar, Khawaja Afzal Ammar, David M Lasorda, Brian Stegman, Lucas Busch, David J Dexter, Ezana M Azene, Nikhil Daga, Fakhir Elmasri, Chandra R Kunavarapu, Mark E Rea, Joseph S Rossi, Joseph Campbell, Jonathan Lindquist, Adam Raskin, Jason C Smith, Thomas M Tamlyn, Gabriel A Hernandez, Parth Rali, Torrey R Schmidt, Jeffrey T Bruckel, Juan C Camacho, Jun Li, Samy Selim, Catalin Toma, Sukhdeep Singh Basra, Brian A Bergmark, Bhavraj Khalsa, David M Zlotnick, Jordan Castle, David J O'Connor, C Michael Gibson, Peerless Committees And Investigators

Faculty, Staff and Student Publications

Background: There are a lack of randomized controlled trial data comparing outcomes of different catheter-based interventions for intermediate-risk pulmonary embolism.

Methods: PEERLESS is a prospective, multicenter, randomized controlled trial that enrolled 550 patients with intermediate-risk pulmonary embolism with right ventricular dilatation and additional clinical risk factors randomized 1:1 to treatment with large-bore mechanical thrombectomy (LBMT) or catheter-directed thrombolysis (CDT). The primary end point was a hierarchal win ratio composite of the following (assessed at the sooner of hospital discharge or 7 days after the procedure): (1) all-cause mortality, (2) intracranial hemorrhage, (3) major bleeding, (4) clinical deterioration and/or escalation to …

Safety And Tolerability Of Letetresgene Autoleucel (Gsk3377794): Pilot Studies In Patients With Advanced Non-Small Cell Lung Cancer, Mehmet Altan, Gilberto Lopes, T Jeroen N Hiltermann, Ramaswamy Govindan, Liza C Villaruz, Emiliano Calvo, Martin J Edelman, Muhammad Furqan, Joel Neal, Enriqueta Felip, Jennifer W Carlisle, John V Heymach, Róisín Eilish O'Cearbhaill, Marjorie Zauderer, Michael Chisamore, Ellie Corigliano, Ioanna Eleftheriadou, Stefan Zajic, Ben Jenkins, Sophia Goodison, Sunil Suchindran, Natalia Ramos-Hernandez, Nidale Tarek, Adam J Schoenfeld

Faculty, Staff and Student Publications

Purpose: The study aims to evaluate the safety, tolerability, and antitumor response of letetresgene autoleucel (lete-cel), genetically modified autologous T cells expressing a T-cell receptor specific for New York esophageal squamous cell carcinoma 1 (NY-ESO-1)/LAGE-1a shared epitope, alone or in combination with pembrolizumab, in HLA-A*02-positive (HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06) patients with NY-ESO-1- and/or LAGE-1a-positive non-small cell lung cancer.

Patients and methods: Study 208749 was a single-arm study of lete-cel alone. Study 208471 was a multiarm study of lete-cel alone or in combination with pembrolizumab in patients with advanced or recurrent non-small cell lung cancer.

Results: More than 2,500 patients were …

Rescue Stenting For Failed Mechanical Thrombectomy In Acute Basilar Artery Occlusions: Analysis Of The Pc-Search Registry., Santiago Ortega-Gutierrez, Aaron Rodriguez-Calienes, Adam T Mierzwa, Milagros Galecio-Castillo, Mahmoud Dibas, Sami Al Kasab, Ashley Nelson, Ashutosh P Jadhav, Shashvat Desai, Gabor Toth, Anas Alrohimi, Mohamad Abdalkader, Piers Klein, Thanh N Nguyen, Hisham Salahuddin, Aditya Pandey, Sravanthi Koduri, Niraj Vora, Nameer Aladamat, Khaled Gharaibeh, Ehad Afreen, Syed Zaidi, Mouhammad Jumaa

Neuroscience Articles

BACKGROUND: We aimed to investigate whether rescue stenting (RS) following failed mechanical thrombectomy (MT) for acute basilar artery occlusion results in superior functional outcomes and enhanced safety compared with the natural history of failed MT.

METHODS: This retrospective cohort study utilized data from the Posterior Circulation Ischemic Stroke Evaluation: Analyzing Radiographic and Intra-Procedural Predictors for Mechanical Thrombectomy registry, encompassing 8 high-volume centers in the United States and covering the period from 2015 to 2021. Patients with basilar artery occlusion who experienced failed MT (modified Thrombolysis in Cerebral Infarction score of 0-2a after at least 1 attempt of clot retrieval) were …

Emapalumab Treatment In Patients With Rheumatologic Disease-Associated Hemophagocytic Lymphohistiocytosis In The United States: A Retrospective Medical Chart Review Study, Shanmuganathan Chandrakasan, Carl E Allen, Deepika Bhatla, John Carter, May Chien, Robert Cooper, Lauren Draper, Olive S Eckstein, Rabi Hanna, J Allyson Hays, Michelle L Hermiston, Ashley P Hinson, Patricia M Hobday, Michael S Isakoff, Michael B Jordan, Jennifer W Leiding, Renee Modica, Taizo A Nakano, Abiola Oladapo, Sachit A Patel, Priti Pednekar, Mona Riskalla, Susmita N Sarangi, Prakash Satwani, Anand Tandra, Kelly J Walkovich, John D Yee, Adi Zoref-Lorenz, Edward M Behrens

Faculty, Staff and Students Publications

Objective: Rheumatologic disease-associated hemophagocytic lymphohistiocytosis (HLH), a rare, life-threatening, systemic hyperinflammatory syndrome, occurs as a complication of underlying rheumatologic disease. Real-world evidence is lacking on emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon-γ, approved for treating patients with primary HLH.

Methods: REAL-HLH, a retrospective medical chart review study conducted across 33 US hospitals, assessed real-world treatment patterns and outcomes in patients with HLH treated with one or more dose of emapalumab between November 20, 2018, and October 31, 2021. Data are presented for the subset of patients with rheumatologic disease-associated HLH.

Results: Fifteen of 105 patients …

Magnesium Sulfate In The Management Of Acute Ischemic Stroke: A Review Of The Literature And Future Directions, Maximillian S Feygin, Alex Brenner, Omar Tanweer

Faculty, Staff and Students Publications

Background: The management of acute ischemic stroke (AIS) was revolutionized within the last 15 years with the introduction of mechanical thrombectomy (MT) to standard of care. Despite the success of mechanical thrombectomy (MT) in achieving high recanalization rates for large vessel occlusion, functional independence post-treatment remains suboptimal. The current limitations of MT prompt evaluation of the role of adjunctive pharmacologic neuroprotective therapies to prevent excitotoxicity, cellular apoptosis, and inflammation that cause irreversible neuronal damage during AIS. Magnesium (MgSO4) provides an attractive neuroprotectant profile, having many different effects, and is inexpensive, readily available, and has a long-established safety and tolerability profile …

Five-Year Outcomes Of Lenadogene Nolparvovec Gene Therapy In Leber Hereditary Optic Neuropathy, Patrick Yu-Wai-Man, Nancy Newman, Valérie Biousse, Valerio Carelli, Mark Moster, Catherine Vignal-Clermont, Thomas Klopstock, Alfredo Sadun, Robert C Sergott, Rabih Hage, Simona Degli Esposti, Chiara La Morgia, Claudia Priglinger, Rustum Karanja, Magali Taiel, José-Alain Sahel

Department of Neurology Faculty Papers

IMPORTANCE: Limited studies have assessed the long-term benefit/risk of gene therapy for Leber hereditary optic neuropathy (LHON).

OBJECTIVE: To determine the safety and efficacy of lenadogene nolparvovec in patients with LHON due to the MT-ND4 gene variant for up to 5 years after administration.

DESIGN, SETTING, AND PARTICIPANTS: The RESCUE and REVERSE Long-Term Follow-up Study (RESTORE), conducted from 2018 to 2022, is the 5-year follow-up study of the 2 phase 3 clinical studies RESCUE (Efficacy Study of Lenadogene Nolparvovec for the Treatment of Vision Loss Up to 6 Months From Onset in LHON Due to the MT-ND4 Mutation) and REVERSE …

Patient-Reported Outcomes: Comparing Functional Avoidance And Standard Thoracic Radiation Therapy In Lung Cancer, Spencer Poiset, Joseph Lombardo, Edward Castillo, Richard Castillo, Bernard Jones, Moyed Miften, Brian Kavanagh, Adam Dicker, Cullen Boyle, Nicole Simone, Benjamin Movsas, Inga Grills, Chad Rusthoven, Yevgeniy Vinogradskiy, Lydia Wilson

Department of Radiation Oncology Faculty Papers

PURPOSE: Novel methods generate functional images using image processing techniques combined with four-dimensional computed tomography (4DCT) data (4DCT-ventilation). 4DCT-ventilation was implemented in a phase II, multicenter functional avoidance clinical trial. The work compares functional avoidance patient-reported outcomes (PROs) against historical standards.

METHODS: Patients with locally advanced lung cancer undergoing curative-intent chemoradiation were accrued. 4DCT-ventilation imaging was generated and functional avoidance treatment plans created reduced dose to functional lung. PRO instruments included Functional Assessment of Cancer Therapy Lung questionnaire and accompanying subscales (including the Trial Outcome Index [TOI]), EuroQol-5 Dimension (EQ-5D), and EQ-Visual Analog Scale (EQ-VAS). The average change from baseline …

Outcomes Of Patients With Treated Secondary Acute Myeloid Leukemia: A High-Risk Subtype That Warrants An Independent Prognostic Designation, Jayastu Senapati, Hagop M Kantarjian, Fadi G Haddad, Nicholas J Short, Gautam Borthakur, Rashmi Kanagal-Shamanna, Guilin Tang, Elias Jabbour, Courtney D Dinardo, Naval Daver, Guillermo Montalban-Bravo, Vishrut Shah, Amin Alousi, Elizabeth Shpall, Uday Popat, Guillermo Garcia-Manero, Farhad Ravandi, Tapan M Kadia

Faculty, Staff and Student Publications

Patients who develop acute myeloid leukemia (AML) after having received treatment for myelodysplastic syndrome (MDS) or related conditions have particularly poor outcomes. This study analyzed adult patients with newly diagnosed AML who previously had MDS, chronic myelomonocytic leukemia (CMML), or MDS/myeloproliferative neoplasm (MPN) overlap syndrome, and who had received hypomethylating agents, chemotherapy, and/or allogeneic stem cell transplantation (HSCT) for these antecedent disorders. From January 2012 to August 2023, we included 673 patients with a median age of 70 years (range, 19-94); 536 (80%) had transformed from MDS, and the remainder from CMML or MDS-MPN. Additionally, 149 patients (22%) had prior …

Association Between Early Immunosuppression Center Variability And One-Year Outcomes After Pediatric Liver Transplant., Vikram K. Raghu, Scott D. Rothenberger, James E. Squires, Elizabeth Eisenberg, Anna L. Peters, Jennifer Halma, Swati Antala, Irini D. Batsis, Ke-You Zhang, Amy G. Feldman, Daniel H. Leung, Steven J. Lobritto, John Bucuvalas, Simon P. Horslen, George V. Mazariegos, Emily R. Perito

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Despite the existence of institutional protocols, liver transplant centers often have variability in early immunosuppression practices. We aimed to measure within-center variability in early immunosuppression after pediatric liver transplant (LT) and examine its association with one-year outcomes.

METHODS: We analyzed pediatric LTs from 2013 to 2018 in the United Network for Organ Sharing registry, with data aggregated by center. We categorized induction regimen as corticosteroids only vs. T-cell depleting antibody vs. non-T-cell depleting antibody. Primary exposures were coefficient of immunosuppression variability (CIV) in (1) induction and (2) mycophenolate mofetil (MMF) use. Primary outcomes were one-year graft survival, patient survival, …

Radiotherapy In The Treatment Of Primary Cutaneous Cd4+ Small/Medium T-Cell Lymphoproliferative Disorder, Susan Y Wu, Ethan P Damron, Jie Xu, Penny Q Fang, Julia Dai, Ranjit Nair, Luis E Malpica Castillo, Luis E Fayad, Carlos A Torres-Cabala, L Jeffrey Medeiros, Francisco Vega, Roberto N Miranda, Madeleine Duvic, Chelsea C Pinnix, Bouthaina S Dabaja, Swaminathan P Iyer, Auris O Huen, Jillian R Gunther

Faculty, Staff and Student Publications

Background: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (PCSM-LPD) is an increasingly recognized entity with heterogeneous management strategies that may include radiotherapy.

Objective: Our aim was to characterize treatment options for PCSM-LPD, with a focus on the role of radiotherapy.

Methods: This is a retrospective review of 46 patients seen in the Cutaneous Lymphoma Program at the University of Texas MD Anderson Cancer Center, with a clinicopathologic review consistent with PCSM-LPD. All patients were biopsied and underwent observation, topical/intralesional steroids, and/or radiotherapy. Patients were confirmed to have residual disease prior to radiotherapy.

Results: All patients achieved a complete response (CR). …

Pexidartinib And Standard Neoadjuvant Therapy In The Adaptively Randomized I-Spy2 Trial For Early Breast Cancer, Hope S Rugo, Mike Campbell, Christina Yau, A Jo Chien, Anne M Wallace, Claudine Isaacs, Judy C Boughey, Hyo S Han, Meredith Buxton, Julia L Clennell, Smita M Asare, Katherine Steeg, Amy Wilson, Ruby Singhrao, Jeffrey B Matthews, Jane Perlmutter, W Fraser Symmans, Nola M Hylton, Angela M Demichele, Douglas Yee, Laura J Van't Veer, Donald A Berry, Laura J Esserman

Faculty, Staff and Student Publications

Purpose: We investigated the small-molecule receptor tyrosine kinase-inhibitor of colony-stimulating factor-1 receptor pexidartinib in the stage II/III breast cancer in the I-SPY2 platform trial.

Methods: I-SPY2 is an adaptive platform trial that features multiple arms of experimental agents administered on a background of standard neoadjuvant therapy with paclitaxel and adriamycin/cyclophosphamide, followed by definitive surgery. The adaptive randomization engine preferentially assigns patients based upon cumulative performance of each agent in a given breast cancer subtype based on hormone receptor and HER2 receptor status. The study endpoint is pathologic complete response.

Results: A total of 9 participants were randomized to receive pexidartinib …

Stereotactic Body Radiotherapy Vs Sorafenib Alone In Hepatocellular Carcinoma: The Nrg Oncology/Rtog 1112 Phase 3 Randomized Clinical Trial, Laura A Dawson, Kathryn A Winter, Jennifer J Knox, Andrew X Zhu, Sunil Krishnan, Chandan Guha, Lisa A Kachnic, Michael T Gillin, Theodore S Hong, Timothy D Craig, Terence M Williams, Ali Hosni, Eric Chen, Anne M Noonan, Eugene J Koay, Rishi Sinha, Michael I Lock, Nitin Ohri, Jennifer A Dorth, Guila Delouya, Anand Swaminath, Jennifer Moughan, Christopher H Crane

Faculty, Staff and Student Publications

Importance: Most patients with locally advanced hepatocellular carcinoma (HCC) recur within the liver following systemic therapy.

Objective: To determine whether stereotactic body radiation therapy (SBRT) improves outcomes in patients with locally advanced HCC compared with sorafenib alone.

Design, setting, and participants: This multicenter phase 3 randomized clinical trial randomized patients with HCC 1:1 to sorafenib or SBRT followed by sorafenib, stratified by performance status, liver function, degree of metastases, and macrovascular invasion. Eligible patients had HCC unsuitable for or refractory to standard local-regional therapies and were candidates for first-line systemic therapy. Data were collected from April 2013 to March 2021, …

Performance And Safety Of The Extravascular Implantable Cardioverter Defibrillator Through Long-Term Follow-Up: Final Results From The Pivotal Study., Paul Friedman, Francis Murgatroyd, Lucas V A Boersma, Jaimie Manlucu, Bradley P Knight, Nicolas Clémenty, Christophe Leclercq, Anish Amin, Béla Merkely, Ulrika Maria Birgersdotter-Green, Joseph Yat Sun Chan, Mauro Biffi, Reinoud Elwin Knops, Gregory Engel, Ignacio Muñoz Carvajal, Laurence M Epstein, Venkata Sagi, Jens Brock Johansen, Maciej Sterliński, Clemens Steinwender, Troy Hounshell, Richard Abben, Amy E Thompson, Yan Zhang, Christopher Wiggenhorn, Sarah Willey, Ian Crozier

Heart and Vascular Articles

BACKGROUND: Substernal lead placement of the extravascular implantable cardioverter defibrillator (EV ICD) permits both defibrillation at thresholds similar to those seen with transvenous implantable cardioverter defibrillators and effective anti-tachycardia pacing (ATP) while avoiding the vasculature and associated complications. The global Pivotal study has shown the EV ICD system to be safe and effective through 6 months, but long-term experience has yet to be published. Our aim was to report the performance and safety of the EV ICD system throughout the study.

METHODS: The EV ICD Pivotal study was a prospective, global, single-arm, premarket clinical study. Individuals with a Class I …

A Randomized, Placebo-Controlled, Cross-Over Trial Of Ketamine In Rett Syndrome, Kathleen Campbell, Jeffrey L Neul, David N Lieberman, Elizabeth Berry-Kravis, Tim A Benke, Cary Fu, Alan Percy, Bernhard Suter, David Morris, Randall L Carpenter, Eric D Marsh, Jana Von Hehn

Faculty, Staff and Students Publications

BACKGROUND: Preclinical studies and anecdotal case reports support the potential therapeutic benefit of low-dose oral ketamine as a treatment of clinical symptoms in Rett syndrome (RTT); however, no controlled studies have been conducted in RTT to evaluate safety, tolerability and efficacy.

DESIGN: This was a sequentially initiated, dose-escalating cohort, placebo-controlled, double blind, randomized sequence, cross-over study of oral ketamine in 6-12-year-old girls with RTT to evaluate short-term safety and tolerability and explore efficacy.

METHODS: Participants were randomized to either five days treatment with oral ketamine or matched placebo, followed by a nine-day wash-out period and then crossed-over to the opposite …

Pediatric Papillary Thyroid Carcinoma: Outcomes After Surgery Without Adjuvant Radioactive Iodine, Luz E Castellanos, Mark E Zafereo, Erich M Sturgis, Jennifer R Wang, Anita K Ying, Steven G Waguespack

Faculty, Staff and Students Publications

Context: Pediatric papillary thyroid carcinoma (PTC) is usually treated with total thyroidectomy followed by radioactive iodine (RAI). Recently, RAI has been used more selectively based on surgical pathology and postoperative dynamic risk stratification (DRS).

Objective: To describe patients with pediatric PTC not initially treated with RAI and their disease outcomes.

Methods: This was an ambispective study at a tertiary cancer center of patients < 19 years diagnosed from January 1, 1990, to December 31, 2021, with stage 1 PTC who intentionally were not treated with RAI within a year of diagnosis. We assessed clinical characteristics, management, and disease outcomes using DRS.

Results: Of 490 PTC patients, we identified 93 eligible patients (median age at diagnosis 16 years; 87% female), including 46 (49%) with cervical lymph node metastases. Initial management included total thyroidectomy ± neck dissection (n = 69, …