Medicine and Health Sciences Commons^™

Surgical And Blood-Based Minimal Residual Disease In Patients With Ovarian Cancer After First-Line Therapy: Clinical Outcomes And Translational Opportunities, Anne Knisely, Yibo Dai, Graham L Barlow, Sanghoon Lee, Barrett Lawson, Helen Clark, Bryan Fellman, Ying Yuan, Wei Lu, Idania Carolina Lubo Julio, Rossana N Lazcano, Manoj Chelvanambi, Brenda Melendez, Bharat Singh, Bhavana Singh, Khalida Wani, Jianfeng Chen, Chih-Chen Yeh, Jianjun Gao, Sean Barnes, Ou Shi, Khaja B Khan, Alejandra G Serrano, Lorena I Gomez-Bolanos, Carly Bess Scalise, Samantha K Cheung, Punashi Dutta, Sharlene Velichko, Adam C Elnaggar, Minetta C Liu, Roni N Wilke, Jeffrey How, Lois M Ramondetta, David M Boruta, Gwyn Richardson, Aaron Shafer, Shannon N Westin, Travis Sims, Anil K Sood, Pedro T Ramirez, Alexander J Lazar, Pamela T Soliman, Karen Lu, Cara L Haymaker, Luisa M Solis Soto, Jennifer A Wargo, Rachel Grisham, Kai W Wucherpfennig, Linghua Wang, Amir A Jazaeri

Faculty, Staff and Student Publications

Purpose: Minimal residual disease (MRD) after first-line treatment of advanced-stage ovarian cancer remains a long-standing barrier to cure. We investigated the prognostic and translational value of MRD detection by second-look laparoscopy (SLL) and ctDNA at the completion of first-line therapy.

Experimental design: Patients with high-grade epithelial ovarian cancer who had a complete clinical response to first-line therapy and underwent SLL and plasma collection for ctDNA were included. Progression-free survival (PFS) and overall survival (OS) were estimated based on MRD and clinicopathologic status. Spatial transcriptomics (GeoMx and Visium) and proteomics (CODEX) profiling were performed on serial samples from select patients.

Results: …

Bipolar Spinal Correction Reduces Transfusion Rate And Hospital Stay Compared With Traditional Posterior Spinal Fusion In Children With Scoliosis Secondary To Cerebral Palsy, Kristopher Lundine, Matthias Lu, Timothy C Borden, Samuel Yoon, Mia Percival, Michael B Johnson

Faculty, Staff and Student Publications

Purpose: Patients with neuromuscular scoliosis due to Cerebral Palsy (CP) are complex due to their curve severity and associated medical comorbidities. Spinal fusion is associated with high risk of peri-operative complications and large blood loss requiring allogenic red blood cell (RBC) transfusion. In June 2017, our tertiary paediatric institution implemented a new minimally-invasive approach for the treatment of neuromuscular scoliosis, Bipolar Spinal Correction (Bipolar), a technique first published by Miladi et al. in 2018. This study represents an analysis of the initial experience of this technique to see if it achieves the goal of minimally invasive surgery by decreasing surgical …

Morphometric Analysis Of Spina Bifida After Fetal Repair Shows New Subtypes With Associated Outcomes, L K Mann, S Pandiri, N Agarwal, H Northrup, K S Au, E Grundberg, E P Bergh, M T Austin, R Patel, B Miller, S Zhu, J S Feinberg, D Lai, K Tsao, S A Fletcher, R Papanna

Faculty, Staff and Student Publications

Objectives: The binary classification of spina bifida lesions as myelomeningocele (with sac) or myeloschisis (without sac) belies a spectrum of morphologies. This study aimed to characterize types of spina bifida lesion and correlate them with preoperative presentation and postoperative outcome.

Methods: This was a secondary analysis of a prospective cohort of patients referred for fetal spina bifida who underwent fetoscopic repair between 2020 and 2023 at a single center. We evaluated lesion morphology on high-resolution intraoperative images and videos to categorize lesions based on placode exposure and nerve root stretching. The reproducibility of lesion classification was assessed using the Kappa …

Treatment-Related Adverse Events And Associated Outcomes In Patients With Advanced Urothelial Carcinoma Treated With Enfortumab Vedotin: Analysis Of The Unite Study, Amanda Nizam, Charles B Nguyen, Jinju Li, Emily C Zabor, Pavlos Msaouel, Cindy Y Jiang, Omar Alhalabi, Eugene Oh, Matthew P Davidsohn, Ilana B Epstein, Dimitra Rafailia Bakaloudi, Rafee Talukder, Tanya Jindal, Amy K Taylor, Michael J Glover, Ali Raza Khaki, Emily Lemke, Hannah Mabey, Bashar Abuqayas, Albert Jang, Jason R Brown, Sean T Evans, Cameron Pywell, Arnab Basu, Mehmet A Bilen, Pedro C Barata, Yousef Zakharia, Matthew I Milowsky, Deepak Kilari, Christopher J Hoimes, Sumit A Shah, Hamid Emamekhoo, Nancy B Davis, Shilpa Gupta, Petros Grivas, Joaquim Bellmunt, Matthew T Campbell, Ajjai S Alva, Vadim S Koshkin

Faculty, Staff and Students Publications

Introduction: Enfortumab vedotin-ejfv (EV), an antibody-drug conjugate approved for advanced urothelial carcinoma (aUC), has limited real-world safety data and no validated predictive biomarkers. Retrospective studies suggest higher objective response rates (ORR) among patients developing EV-related dermatologic toxicities, but survival implications remain unclear. This analysis assessed the safety of EV monotherapy and the impact of dermatologic and neurologic toxicities on efficacy outcomes in a multi-institutional cohort.

Materials and methods: UNITE is a multicenter, retrospective study across 16 US sites of patients with aUC treated with targeted agents, including EV. Primary endpoints were the incidence of EV treatment-related adverse events (TRAEs, any …

Tirzepatide For The Maintenance Of Body Weight Reduction: Rationale, Design, And Baseline Characteristics Of Surmount-Maintain, Deborah B Horn, Louis J Aronne, Sean Wharton, Harold E Bays, Elisa Gomez-Valderas, Avigdor D Arad, Palash Sharma, Julia P Dunn, Cagri Senyucel, Clare J Lee

Faculty, Staff and Student Publications

Objective: SURMOUNT-MAINTAIN aims to evaluate the efficacy and safety of reducing the tirzepatide dose and/or continuing the maximum tolerated dose (MTD) versus placebo in maintaining body weight (BW) reduction achieved with tirzepatide MTD.

Methods: This Phase 3b, multicenter, randomized, parallel-arm, double-blinded, placebo-controlled, 52-week clinical trial is in progress comparing treatment with once weekly tirzepatide (5 mg and/or MTD of 15 mg or 10 mg) versus placebo in achieving BW reduction maintenance from the initial 60-week open-label weight-loss period on tirzepatide MTD, in adults with obesity (BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with ≥ 1 obesity-related comorbidity, excluding type …

Imaging- And Tumor Biomarker-Based Multivariable Model For Early Prediction Of Pathologic Complete Response To Neoadjuvant Systemic Therapy In Triple-Negative Breast Cancer, Beatriz E Adrada, Mary S Guirguis, Lei Huo, Clinton Yam, Debu Tripathy, Rosalind Candelaria, Wei Yang, Miral Patel, Tanya Moseley, Gary J Whitman, Jessica W T Leung, Huong Le-Petross, Deanna L Lane, Nour Abuhadra, Jennifer Litton, Vicente Valero, Kelly K Hunt, Banu Arun, Rania Mohamed, Jia Sun, Anil Korkut, Sanaz Pashapoor, Jason White, Alastair Thompson, Peng Wei, Jingfei Ma, Stacy Moulder, Gaiane M Rauch

Faculty, Staff and Student Publications

Purpose: The response of triple-negative breast cancer (TNBC) to neoadjuvant therapy (NAT) varies widely. This study aimed to determine the performance of clinicopathologic biomarkers and volumetric changes on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting pathologic complete response (pCR) to NAT in patients with TNBC.

Patients and methods: This study included 264 patients with stage I to III TNBC enrolled in a prospective clinical trial. These patients underwent DCE-MRI at baseline and after two and/or after four cycles of dose-dense anthracycline and cyclophosphamide. Tumor volume (TV) was calculated by measuring three tumor dimensions at each time point. Clinicopathologic markers …

Lesion Absorbed Dose-Response Relationship In Patients With Metastatic Castration-Resistant Prostate Cancer Undergoing [177lu]Lu-Psma-617 Radiopharmaceutical Therapy, Milan Grkovski, Simone S Krebs, Joseph A O'Donoghue, Jonathan Kuten, Audrey Mauguen, Parnian Shobeiri, Daniel Lafontaine, Maria Thor, Finn Augensen, Josef J Fox, Neeta Pandit-Taskar, Mark P Dunphy, Lisa Bodei, John L Humm, Heiko Schöder

Faculty, Staff and Student Publications

The relationship between lesion absorbed dose (AD) and response in patients with metastatic castration-resistant prostate cancer undergoing [177Lu]Lu-PSMA-617 radiopharmaceutical therapy (RPT) remains poorly understood. The objective of this work was to investigate the AD-response relationship at both the patient and lesion levels.

Methods: Sixty-five patients underwent serial SPECT/CT imaging after receiving 7.31 ± 0.27 GBq of [177Lu]Lu-PSMA-617. Single-time-point (STP) (Hänscheid approximation at 72 h) and multiple-time-point voxelwise dosimetry were performed. Patient response was evaluated by changes in serum prostate-specific antigen level before and after cycle 1 of RPT. The response of individual lesions was evaluated by the change in the …

Endoscopic Submucosal Dissection For Previously Attempted Colorectal Lesions: An International Multicenter Experience., Suchapa Arayakarnkul, Hiroyuki Aihara, Alessandro Repici, Roberta Maselli, Antonio Capogreco, Leonardo Da Rio, Fabio Shiguehissa Kawaguti, Fauze Maluf-Filho, Makoto Nishimura, Sera Satoi, Sayaka Nagao, Shai Friedland, Robert Bechara, Norio Fukami, Sonmoon Mohapatra, Amit Bhatt, Abel Joseph, Alex Schlachterman, Anand Kumar, Andrew Y Wang, Ross C D Buerlein, Louis M Wong Kee Song, Fnu Deepali, Dennis Yang, Muhammad K Hasan, Nikhil A Kumta, David L Diehl, Edward J Despott, Alberto Murino, Alessandro Rimondi, Laura Lucaciu, Neil R Sharma, Christina Zelt, Ashley Rumple Rn, Bsn, David Leslie Carr-Locke, Reem Z Sharaiha, Srihari Mahadev, Kamal M Hassan, Mohamad-Noor Abu-Hammour, Carlos Robles-Medranda, Martha Arevalo-Mora, Juan Alcivar-Vasquez, Vivek Kumbhari, Jongkyu Park, Salmaan Jawaid, Mai A Khalaf, Kasenee Tiankanon, Sarah S Al Ghamdi, Mohamed O Othman, Saowanee Ngamruengphong

PCI Publications and Projects

BACKGROUND & AIMS: Salvage endoscopic submucosal dissection (ESD) has been proposed for previously attempted colorectal lesions (PACLs), yet the extensive submucosal fibrosis impacts procedural difficulty and resection outcomes. The aim of this study was to evaluate the efficacy and safety of salvage ESD for the treatment of PACLs.

METHODS: This international, multicenter study enrolled consecutive patients who underwent ESD to manage PACLs. Rates of en bloc, R0 resection, and local recurrence were assessed for efficacy. Safety was assessed by adverse events (AEs), procedure-related mortality, and the need for surgical management.

RESULTS: Of 415 lesions, en bloc rate was 83.4%, the …

Ibrutinib Added To Standard Conditioning And As Maintenance Therapy Following Autologous Hematopoietic Stem Cell Transplantation For Relapsed Or Refractory Activated-B-Cell Type Diffuse Large B-Cell Lymphoma: Primary Analysis Of The Us Intergroup Double-Blind Randomized Phase Iii Study Alliance A051301/Bmt-Ctn 1201, Charalambos Andreadis, Brad S Kahl, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

To improve outcomes in relapsed or refractory activated B-cell type Diffuse Large B-cell Lymphoma (ABC-DLBCL), we launched a randomized phase 3 trial evaluating 2-year progression free survival (2yPFS) with the addition of ibrutinib to autologous transplant. Patients received ibrutinib 560 mg or placebo with conditioning and for 12 additional cycles. Accrual was adversely affected by implementation of the ABC classifier in this setting and the changing treatment landscape of DLBCL. In all, 39 patients on ibrutinib and 38 on placebo were evaluable. 2yPFS was 57.6% on ibrutinib versus 40.8% on placebo (

Effects Of Olfactory Enrichment On Perioperative Neurocognitive Disorders In Elderly Patients Undergoing Orthopedic Surgery: A Study Protocol Of A Multi-Center Randomized Controlled Trial, Xinchun Mei, Jiayi Wang, Zihan Ni, Yanyan Wang, Binglei Zhao, Daniel I Sessler, Zhongcong Xie, Yuan Shen

Faculty, Staff and Student Publications

Background: Neurocognitive disorders are prevalent among older surgical patients, yet their underlying mechanisms and effective interventions remain largely unknown. Studies in rodents and patients suggest a connection between olfactory impairment and perioperative neurocognitive disorder (PND). Previous work in mice demonstrates that anesthesia and surgery can lead to both olfactory impairment and cognitive deficits. Olfactory enrichment, which is also referred to as olfactory training (i.e., daily exposure to multiple odorants), may prove helpful. For example, olfactory enrichment appears to reduce PND-like behaviors in mice, possibly by mitigating anesthesia- and surgery-induced reductions in olfactory receptor neurons. Additionally, olfactory enrichment increases the volume …

Poziotinib For Egfr Exon 20-Insertion Nsclc: Clinical Efficacy Of The Phase 2 Zenith Trial And Differential Impact Of Egfr Exon 20 Insertion Location On Sensitivity, Xiuning Le, Jacqulyne P Robichaux, Monique Nilsson, R S K Vijayan, Ashwin Ravichandran, Jia Wu, Yasir Y Elamin, Lingzhi Hong, Jun Pei, Jun He, Sonia Patel, Hibiki Udagawa, Sriramvignesh Mani, Chang Woon Jang, Jeffrey M Clarke, Nishan Tchekmedyian, Jonathan W Goldman, Mark Socinski, Gajanan Bhat, Sharon Leu, Veronica Bunn, Zhenqiang Su, Sylvie Vincent, John W Lawson, Jason B Cross, John V Heymach

Faculty, Staff and Student Publications

EGFRex20 insertions (EGFRex20ins) can be classified as near- and far-loop based on the insertion location, however, the impact of location on responses to various EGFR tyrosine kinase inhibitors (TKIs) is poorly understood. In vitro studies show that afatinib, poziotinib, and zipalertinib more potently inhibited near-loop than far-loop insertions, whereas mobocertinib has similar IC50 in both groups. Molecular dynamics simulations reveal that near-loop insertions have multiple conformational states and lower transitional energy than far-loop insertions. ZENITH20 trial cohort 1 (NCT03318939) evaluates poziotinib in EGFRex20 NSCLC patients (n = 115) and demonstrates an objective response rate of 14.8% (95% Confidence …

Efficacy And Safety Of Rigosertib In Patients With Recessive Dystrophic Epidermolysis Bullosa-Associated Advanced/Metastatic Cutaneous Squamous Cell Carcinoma, Martin Laimer, Andrew P. South, Elisabeth Mayr, Sophie Kitzmueller, Lauren Banner, Michael Alexander, Linda Hosler, Henry Yang, Matthew Parris, Meena Arora, Georg Zimmermann, Gregor Schweighofer-Zwink, Johann Bauer, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is an epithelial fragility disease primarily affecting the skin and is caused by variants in the COL7A1 gene. Individuals with RDEB are predisposed to develop highly aggressive cutaneous squamous cell carcinomas (SCCs) which are the most common cause of premature death. There is a lack of effective prevention or treatment options for patients with RDEB-SCC.

OBJECTIVES: To evaluate the antitumour activity and safety of the polo-like kinase-1 (PLK1) inhibitor, rigosertib, two investigator-initiated open-label, single-arm phase II studies were opened in Europe and the USA and enrolled five patients with RDEB diagnosed with locally advanced …

Development Of A Patient-Centered Outcome Tool For Blepharospasm: A Stepwise Modified Delphi Study, Brian D Berman, Fares Qeadan, Amanda D Henderson, Andrew R Harrison, Giovanni Defazio, Mark Hallett, Gamze Kilic-Berkmen, Laura Wright, Samantha Pentecost, Paul Reyes, Anna Tingin, Joseph Jankovic, Jane Boyd, Charlene Hudgins, Janet Hieshetter, Joel S Perlmutter, Hyder A Jinnah, Sarah Pirio Richardson

Faculty, Staff and Students Publications

Blepharospasm (BSP) is characterized by excessive orbicularis oculi muscle activity leading to abnormal blinking and involuntary eyelid closure. Botulinum neurotoxin (BoNT) injections are the main treatment for BSP, but they only partially and transiently relieve symptoms, leading to a waxing and waning therapeutic response. A patient-centered outcome (PCO) tool that measures BSP symptoms in a simple and efficient way could inform the development of better treatments. Using a stepwise modified Delphi approach, potential PCO items were first identified using the Dystonia Coalition Database with data from over 200 individuals with BSP who had provided responses to existing clinical assessment scales. …

Development Of A Patient-Centered Outcome Tool For Blepharospasm: A Stepwise Modified Delphi Study, Brian D Berman, Laura Wright, Joel S Perlmutter, Et Al.

2020-Current year OA Pubs

Blepharospasm (BSP) is characterized by excessive orbicularis oculi muscle activity leading to abnormal blinking and involuntary eyelid closure. Botulinum neurotoxin (BoNT) injections are the main treatment for BSP, but they only partially and transiently relieve symptoms, leading to a waxing and waning therapeutic response. A patient-centered outcome (PCO) tool that measures BSP symptoms in a simple and efficient way could inform the development of better treatments. Using a stepwise modified Delphi approach, potential PCO items were first identified using the Dystonia Coalition Database with data from over 200 individuals with BSP who had provided responses to existing clinical assessment scales. …

Up-Front Alternative Donor Hct In Severe Aplastic Anemia: Gaps And Opportunities To Translate Evidence Into Practice., Neel S Bhatt, Azra Borogovac, Yvonne A Efebera, Anna Desalvo, Steven M Devine, Amy Foley, Valerie Greco-Stewart, Betty K Hamilton, Mykala Heuer, Todd Molfenter, John P Plastaras, Brittany K Ragon, Sarah A Wall, Larisa Broglie, Mark B Juckett, Nandita Khera, Mary M Horowitz, Amy E Dezern

Oncology Articles

Severe aplastic anemia (SAA) is a rare and life-threatening bone marrow failure disorder. Immunosuppressive therapy (IST) with antithymocyte globulin and cyclosporine has long been a frontline treatment option in SAA; however, its limited durability and risk of long-term complications such as secondary malignancies remain a drawback in this treatment modality. Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative option with significantly improved outcomes over the long term, particularly with HLA-matched related donors. However, the use of alternative donors, such as haploidentical, mismatched, or matched unrelated donors, has previously been limited due to increased transplant-related morbidity, particularly graft-versus-host disease (GVHD). …

Evaluation Of In Vivo Car Transgene Levels In Tisagenlecleucel-Treated Patients With Relapsed/Refractory B-All And Dlbcl., Rakesh Awasthi, Stephan A. Grupp, Edward R. Waldron, Gregory A. Yanik, Constantine S. Tam, Susana Rives, Joseph P. Mcguirk, Michael A. Pulsipher, Ulrich Jaeger, Douglas Myers, Peter Borchmann, Stephen J. Schuster, Heather E. Stefanski, Michael R. Bishop, Abhijit Chakraborty, Aisha Masood, André Baruchel, Edmund K. Waller

Manuscripts, Articles, Book Chapters and Other Papers

Tisagenlecleucel is a CD19-directed autologous chimeric antigen receptor (CAR) T-cell therapy. Quantitative polymerase chain reaction assays are highly sensitive in defining in vivo kinetics by measuring CAR transgene in peripheral blood. This study aimed to identify clinically meaningful CAR T-cell blood levels that correlated with response/relapse. In pediatric/young adult patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), maximum CAR T-cell blood levels were higher in patients with ongoing complete remission and in patients with CD19- relapse relative to those with CD19+ relapse. In adult patients with R/R diffuse large B-cell lymphoma (DLBCL), no apparent association between in vivo kinetics …

A Phase 2 Study Of Obinutuzumab Combined With Lenalidomide In Previously Untreated High Tumor Burden Follicular Lymphoma, Neha Akkad, Lei Feng, Jason R Westin, Fredrick B Hagemeister, Hun Ju Lee, Luis Fayad, Sairah Ahmed, Ranjit Nair, Maria Alma Rodriguez, Paolo Strati, Dai Chihara, Christopher R Flowers, Linda Claret, Karina Ibanez, Michael Wang, Nathan H Fowler, Jared Henderson, R Eric Davis, Sattva S Neelapu, Michael Green, Loretta J Nastoupil

Faculty, Staff and Student Publications

Follicular lymphoma (FL) has a clinical course that is often characterized by high response rates to first-line therapy, followed by multiple relapses over a prolonged natural history. Currently, there are multiple possible approaches to frontline therapy for untreated advanced-stage FL, but there is an ongoing debate around what is the preferred approach. Based on the benefits seen with combining lenalidomide, an immunomodulatory agent, with rituximab, an anti-CD20 antibody, we aimed to evaluate the safety and efficacy of lenalidomide in combination with obinuzutumab, an anti-CD20 antibody with enhanced antibody-dependent cellular cytotoxicity. The eligibility criteria included a diagnosis of FL, grade 1 …

Periprocedural Results And Right Ventricular Outcomes Of Computer Assisted Vacuum Thrombectomy Treatment Of Acute Pulmonary Embolism: Interim Analysis Of 300 Patients From The Strike-Pe Study, John M. Moriarty, Brian J. Schiro, Suhail Y. Dohad, Houman Tamaddon, Hugh C. Davis, David M. Shavelle, George S. Chrysant, Elias A. Iliadis, David J. Dexter, Juan J. Ciampi Dopazo, Andrew Holden, Frances M. West, Brent Keeling, Andrew S. P. Sharp, Ido Weinberg

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

BACKGROUND: Pulmonary embolism (PE) can be a life-threatening condition. Endovascular treatment is emerging as a promising treatment to restore hemodynamic stability and reverse right ventricular (RV) dysfunction in PE; however, more studies are needed to elucidate the effects on the right ventricle after endovascular treatment. This analysis reports the effects of computer assisted vacuum thrombectomy on RV function.

METHODS: Eligible patients for the single-arm, prospective, international, multicenter STRIKE-PE (A Prospective, Multicenter Study of the Indigo Aspiration System Seeking to Evaluate the Long-Term Safety and Outcomes of Treating Pulmonary Embolism) cohort study are adults with acute PE with symptoms for ≤14 …

Functional Connectivity Predicting Transdiagnostic Treatment Outcomes In Internalizing Psychopathologies, Kai Zhang, Heide Klumpp, Jagan Jimmy, K Luan Phan, Mohammed R Milad, Zhenfu Wen

Faculty, Staff and Student Publications

Importance: Predicting treatment outcomes for internalizing psychopathologies (IPs), such as depression and anxiety, holds promise for advancing precision medicine. The extent to which whole-brain functional connectivity (FC) can predict treatment responses for patients with IPs across different therapeutic modalities remains unclear.

Objective: To examine whether pretreatment FC patterns predict multidimensional treatment outcomes in patients with IPs and whether predictive performance generalizes across diagnoses and treatment modalities.

Design, setting, and participants: This prognostic study analyzed baseline neuroimaging and clinical data from patients with IPs enrolled in 1 of 2 randomized clinical trials (conducted from December 2013 to February 2018 and September …

Clinical Phenotype And Outcomes In Autoimmune Encephalitis After Herpes Simplex Virus Encephalitis: A Systematic Review And Meta-Analysis, Jonathan Cleaver, Renetta Chungath, Amy Gimson, Christine Strippel, Bryan Ceronie, Babak Soleimani, Thomas Johnson, Eyal Muscal, Kristen Fisher, Yike Jiang, Timothy A Erickson, Kristy O Murray, Siv Tonje Faret Hovet, Charlotte Aaberg Poulsen, Anna Søgaard Magnussen, Pauline Dumez, Shannon Ronca, Martin Häusler, Annegret Quade, Andrew Swayne, Morten Blaabjerg, Mette Nissen, Alexander J Sandweiss, Jerome Honnorat, Russell Dale, Ming Lim, Michael Eyre, Margherita Nosadini, Lahiru Handunnetthi, Sarosh R Irani, Adam E Handel

Faculty, Staff and Students Publications

Background: Autoimmune encephalitis after herpes simplex virus encephalitis (HSVE-AE) represents the intersection of central nervous system infection and autoimmunity. Defining the phenotype and the safety and effectiveness of immunotherapy in HSVE-AE would help identify immunotherapy candidates, optimise therapeutic strategies, and improve patient outcomes.

Methods: We systematically searched Embase, Medline, PubMed, and Web of Science (2007-2024) for cases meeting consensus criteria for AE after confirmed HSVE. Demographics, phenotype, treatment and outcome data were extracted. Dimensionality reduction, network analysis, and multivariate logistic regression was used to explore age- and diagnosis-specific patterns and outcome predictors.

Results: From 2259 articles screened, 78 studies (225 …

Comparative Effectiveness Of Less Vs More Frequent Hydrocortisone Dosing In Septic Shock, Alan Hao, Tianshi David Wu, Keegan Collins, Danielle Guffey, Rebecca Kessinger, Meghna Vallabh, Ali Omranian

Faculty, Staff and Students Publications

Objectives: Guidelines recommend hydrocortisone as an adjunctive treatment in septic shock, but the optimal dosing regimen is unknown. A national shortage of hydrocortisone in 2023 prompted a change in institutional practice for hydrocortisone administration from 50 mg every 6 hours to 100 mg every 12 hours in an effort to reduce waste and conserve vials, creating an opportunity to evaluate the comparative effectiveness of these two regimens. The primary efficacy outcome was time to shock resolution, and secondary outcomes evaluated in this study were mortality, renal replacement therapy (RRT), medication costs, and maximum vasopressor dose attained.

Design: Single-center, retrospective cohort …

Preoperative Focused Echocardiography On Patients With Fractured Neck Of Femur. Echonof-Iii Trial: Study Protocol For A Multicenter Randomized Controlled Trial, Ximena Cid-Serra, Alistair Royse, Andrea Bowyer, David Canty, Daniel Sessler, Sandy Clarke-Errey, Andre Denault, Dina Logiudice, Guy Ludbrook, D-Yin Lin, Yang Yang, Kavi Haji, Lisa Zucherrelli, Andrew J Palmer, Benjamin Piper, Thar Nyan Lwin, Stefan Dieleman, David Eccleston, Alwin Chuan, Richard Cooper, Gregory Henderson, Colin Royse

Faculty, Staff and Student Publications

Background: Hip fractures are common in older people and are associated with high perioperative mortality. Prompt surgical intervention within the first 48 h of fraction reduces complications; however, surgical urgency often precludes a comprehensive preoperative cardiac evaluation. Preliminary data suggests that performing a focused cardiac ultrasound (FCU) before surgery may reduce postoperative complications. We therefore propose to test the primary hypothesis that FCU reduces a 30-day composite of mortality and serious complications.

Methods: We plan a definitive multicenter pragmatic randomized trial that will enroll 2000 adults with hip fractures. Participants will be randomized before surgery to either receive FCU as …

Contemporary Characteristics And Outcomes Of Pediatric Oncology Patients Participating In Early Phase Clinical Trials., Avina Rami, Kira Bona, Suzanne Shusterman, Karen Wright, Andrew E. Place, Puja J. Umaretiya, Ketki Bhushan, Steven G. Dubois, Kevin Campbell

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Phase 1 or phase 1/2 trials are a first step in pediatric cancer drug development. Currently, there is a paucity of information regarding contemporary outcomes for pediatric patients enrolled in these trials. We describe characteristics and outcomes of patients enrolled in pediatric phase 1 clinical trials over a 9-year period at a single institution.

METHODS: We queried our clinical trials management system to generate a list of patients enrolled and treated on pediatric phase 1 or phase 1/2 trials from 2011 to 2019. We collected baseline demographics, clinical data, efficacy, and safety endpoints post-enrollment including: time to death, objective …

A Prospective, Randomized, Controlled Clinical Trial Of High-Frequency Electromagnetic Coupling Powered Permanent Peripheral Nerve Stimulator For The Treatment Of Chronic Craniofacial Pain, Salim M Hayek, Nameer Haider, Ashwin Viswanathan, Mehul Desai, Jeffrey Rosenberg, Niek E Vanquathem

Faculty, Staff and Students Publications

than one-fifth of the US population. While various medications and conservative treatment modalities are available for this condition, many patients have refractory symptoms. These patients suffer from social impairment, reduced quality of life, and increased financial burdens.

Objective: The objective of this study was to examine the clinical outcomes of patients receiving a permanent, high-frequency electromagnetic coupling (HF-EMC) powered peripheral nerve stimulator (PNS) system for the treatment of chronic craniofacial neuropathic pain.

Study design: This study was a multicenter, randomized, controlled clinical trial conducted under an investigational device exemption (IDE).

Setting: This study was conducted in 7 clinical sites in …

Variational Temporal Deconfounder Network For Individualized Treatment Effect Estimation With Longitudinal Observational Data, Hao Dai, Yu Huang, Yuxi Liu, Xing He, Jingchuan Guo, Mattia Prosperi, Jiang Bian

Faculty, Staff and Student Publications

Objective: By leveraging real-world electronic health record (EHR) data, this study set out to estimate individualized treatment effects (ITE) in longitudinal observational settings to advance personalized medicine, addressing key challenges that are often observed in real-world clinical scenarios and pose statistical challenges, including hidden confounding and dynamic treatment regimens.

Methods: We propose the Variational Temporal Deconfounder Network (VTDNet), a novel framework designed to account for time-varying hidden confounding using a variational recurrent transformer-based autoencoder. Specifically, VTDNet comprises three critical components: a temporal Encoder-Decoder structure to capture hidden representation, a Treatment Block that captures interdependencies among multiple treatments, and a Potential …

Outcomes In Systemic Sclerosis-Associated Interstitial Lung Disease Based On Serological Profiles With A Focus On Anticentromere And Anti-Rna Polymerase Iii Antibodies, Elizabeth R Volkmann, Shervin Assassi, Christopher P Denton, Rozeta Simonovska, Steven Sambevski, Margarida Alves, Elana J Bernstein

Faculty, Staff and Student Publications

Objective: We aimed to compare the progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD) based on serological status.

Methods: In a posthoc analysis of the SENSCIS trial (nintedanib vs placebo in SSc-ILD; ClinicalTrials.gov: NCT02597933), we analyzed the rate of decline in forced vital capacity (FVC) over 52 weeks in 3 subsets: (1) positive for anticentromere antibody (ACA), (2) positive for anti-RNA polymerase III antibody (ARA), and (3) negative for ACA, ARA, and antitopoisomerase I antibody (ATA).

Results: Among study participants who underwent baseline serological evaluation, 32/549 (5.8%) were ACA positive, 98/528 (18.6%) were ARA positive, and 127/526 (24.1%) were …

Ixekizumab Improves Signs, Symptoms, And Quality Of Life In Patients With Axial Spondyloarthritis Irrespective Of Symptom Duration, Victoria Navarro-Compán, John D Reveille, Proton Rahman, José A Maldonado-Cocco, Marina Magrey, Rebecca Bolce, Tommaso Panni, Andris Kronbergs, Martin Rudwaleit

Faculty, Staff and Student Publications

Introduction: The objective of this study was to assess treatment response to ixekizumab, an interleukin-17A antagonist, by shorter versus longer symptom duration (< 5 years vs. ≥ 5 years) in patients with radiographic axial spondyloarthritis (r-axSpA) and non-radiographic axial spondyloarthritis (nr-axSpA) up to 52 weeks.

Methods: This post hoc analysis used data from three randomized, placebo-controlled trials including patients with r-axSpA from COAST-V [biologic disease-modifying anti-rheumatic drug (bDMARD)-naïve] and COAST-W (tumor necrosis factor inhibitor-experienced) and patients with nr-axSpA from COAST-X (bDMARD-naïve). Patients received ixekizumab (80 mg every 2 or 4 weeks) or placebo through Week 16 and ixekizumab to Week 52. Assessments included the Assessment in SpondyloArthritis international Society 40% improvement (ASAS40) and Axial Spondyloarthritis Disease Activity Score (ASDAS) low disease activity …

One-Year Outcomes From The Pivotal Trial Of A Four-Branch Off-The-Shelf Solution To Treat Pararenal And Extent Iv Thoracoabdominal Aortic Aneurysms, Mark A Farber, Sukgu Han, Michel S Makaroun, Jon S Matsumura, Bernardo C Mendes, Gustavo S Oderich, Luis A Sanchez, Bjoern D Suckow, Carlos H Timaran

Faculty, Staff and Students Publications

Objective: To report 1-year primary-arm outcomes of the GORE EXCLUDER Thoracoabdominal Branch Endoprosthesis pivotal trial.

Methods: The multicenter, nonrandomized, prospective study included patients with extent IV thoracoabdominal aortic aneurysms (TAAAs) and pararenal aortic aneurysms (PRAAs). All-cause and adjudicated lesion-related mortality were assessed at 12 months. Core-lab-reported, imaging-dependent outcomes included aneurysm size, endoleaks assessed through 1-year follow-up window, and target vessel instability (defined as occlusion, stenosis, type Ic/IIIc endoleak, or reintervention) at 1 year.

Results: One hundred two patients were treated; 59 patients had an extent IV TAAA and 43 had a PRAA. The mean maximum aneurysm diameter was 59.4 ± …

Five-Year Pivotal Trial Outcomes Of The Gore Excluder Conformable Endoprosthesis Implanted In Abdominal Aortic Aneurysms With Short Non-Angulated Infrarenal Seal Zones, Bjoern D Suckow, Gustavo S Oderich, Mahmoud W Almadani, Dai Yamanouchi, Alyssa J Pyun, Erin Moore, Patrick E Muck, Robert Y Rhee

Faculty, Staff and Students Publications

Objective: The GORE EXCLUDER Conformable Abdominal Aortic Aneurysm Endoprosthesis with Active Control System (EXCC) is approved in the United States (U.S.) for treatment of AAAs and highly angulated (≤90°) and short (≥10 mm) infrarenal aortic proximal seal zones (necks). Reported here are the 5-year outcomes of the EXCC U.S. pivotal clinical trial in the short, non-angulated cohort (SNA).

Methods: The EXCC investigational device exemption prospective pivotal trial short neck sub-study across 31 sites included patients with infrarenal necks measuring ≥10 mm length and ≤60° angulation. Five-year outcomes assessed by Core lab and adjudicated by independent review committee included patient safety …

Steroids For Pediatric Adenotonsillectomy Pain-A Prospective Multicenter Randomized Trial, Kevin D Pereira, Wiktoria A Gocal, Anna V Borodianski, Mary E Williamson, Hengameh K Behzadpour, Sonal Saraiya, Diego A Preciado, Amal Isaiah

Faculty, Staff and Students Publications

Objective: To compare postoperative caregiver-reported pain control of two steroid regimens following pediatric adenotonsillectomy. Secondary objectives assessed differences in analgesic use, return to normal diet, caregiver calls, adverse effects, and emergency room (ER) visits.

Study design: Prospective randomized pragmatic trial.

Setting: Three academic tertiary care children's hospitals.

Methods: Healthy children aged 3 to 10 undergoing adenotonsillectomy were recruited and randomly assigned to receive either 0.6 mg/kg dexamethasone on postoperative day 3 or prednisolone 0.5 mg/kg days 1 to 3. Both groups continued standard weight-based regimens of acetaminophen and ibuprofen. A blinded research team member performed postoperative telephone surveys using the …