Medical Specialties Commons^™

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

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 …

Development And Validation Of Risk Stratification For Heart Failure After Acute Coronary Syndrome Based On Dynamic S100a8/A9 Levels, Jie Ma, Ke Ma, Jing Chen, Xinying Yang, Fei Gao, Hai Gao, Hui Zhang, Xin-Liang Ma, Jie Du, Ping Li, Yulin Li

Department of Emergency Medicine Faculty Papers

BACKGROUND: The early assessment of heart failure (HF) risk in patients with acute coronary syndrome (ACS) can help reduce mortality. S100A8/A9 is not only rapidly released after myocardial ischemia, but is also involved in reperfusion injury, which is an important predictor of HF after ACS. We attempted to construct a reliable HF risk stratification tool for evaluating patients with ACS after reperfusion therapy based on S100A8/A9 dynamic changes.

METHODS AND RESULTS: This prospective study included 3 independent cohorts of patients with ACS who received reperfusion therapy. The discovery cohort was divided into 2 subgroups: the longitudinal subgroup (n=264) with serum …

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 …

Antitumor Activity And Biomarker Analysis For Trop2 Antibody-Drug Conjugate Datopotamab Deruxtecan In Patient-Derived Breast Cancer Xenograft Models, Funda Meric-Bernstam, Erkan Yuca, Kurt W Evans, Ming Zhao, Takanori Maejima, Tsuyoshi Karibe, Maria Gabriela Raso, Ximing Tang, Xiaofeng Zheng, Yasmeen Qamar Rizvi, Argun Akcakanat, Stephen M Scott, Bailiang Wang, Lauren A Byers, Debu Tripathy, Daisuke Okajima, Senthil Damodaran

Faculty, Staff and Student Publications

PURPOSE: Datopotamab deruxtecan (Dato-DXd) is a humanized anti-trophoblast cell-surface antigen-2 (TROP2) IgG1 mAb linked to a potent topoisomerase I inhibitor payload (DXd). Dato-DXd has already shown antitumor activity in breast cancer; however, the determinants of response, including the importance of TROP2 expression, remain unclear. We tested the activity of Dato-DXd in a panel of breast cancer patient-derived xenografts (BCX) varying in TROP2 expression.

EXPERIMENTAL DESIGN: The antitumor activity of Dato-DXd and isotype-control-DXd (IgG-DXd) was assessed against 11 BCXs varying in TROP2 expression, 10 representing tumors postneoadjuvant chemotherapy. Pharmacodynamic effects were assessed at 24 and 72 hours. The effects of TROP2 …

Phase I/Ii Study Of The Aurora Kinase A Inhibitor Alisertib And Pembrolizumab In Refractory, Rb-Deficient Head And Neck Squamous Cell Carcinomas, Faye M Johnson, Madison P O'Hara, Lacin Yapindi, Peixin Jiang, Hai T Tran, Alexandre Reuben, Weihong Xiao, Maura L Gillison, Xiaowen Sun, Alexander Khalaf, J Jack Lee, Jagannadha K Sastry, Soma Ghosh

Faculty, Staff and Student Publications

Purpose: Effective therapy for recurrent head and neck squamous cell carcinoma (HNSCC) that is refractory to chemotherapy and immunotherapy is a considerable need. Aurora kinase A inhibition leads to apoptosis and immunogenic cell death in preclinical models of human papilloma virus (HPV)-driven cancers.

Patients and methods: Alisertib was administered orally twice daily on days 1-7 and pembrolizumab on day 1 of a 21-day cycle to adults with advanced solid tumors (phase I) or with immunotherapy- and platinum-resistant, HPV-positive HNSCC (phase II).

Results: The recommended phase II alisertib dose was 40 mg, which had only the expected toxicity including cytopenia that …

Plant-Nanoparticles Enhance Anti-Pd-L1 Efficacy By Shaping Human Commensal Microbiota Metabolites, Yun Teng, Chao Luo, Xiaolan Qiu, Jingyao Mu, Mukesh K Sriwastva, Qingbo Xu, Minmin Liu, Xin Hu, Fangyi Xu, Lifeng Zhang, Juw Won Park, Jae Yeon Hwang, Maiying Kong, Zhanxu Liu, Xiang Zhang, Raobo Xu, Jun Yan, Michael L Merchant, Craig J Mcclain, Huang-Ge Zhang

Faculty, Staff and Student Publications

Diet has emerged as a key impact factor for gut microbiota function. However, the complexity of dietary components makes it difficult to predict specific outcomes. Here we investigate the impact of plant-derived nanoparticles (PNP) on gut microbiota and metabolites in context of cancer immunotherapy with the humanized gnotobiotic mouse model. Specifically, we show that ginger-derived exosome-like nanoparticle (GELN) preferentially taken up by Lachnospiraceae and Lactobacillaceae mediated by digalactosyldiacylglycerol (DGDG) and glycine, respectively. We further demonstrate that GELN aly-miR159a-3p enhances anti-PD-L1 therapy in melanoma by inhibiting the expression of recipient bacterial phospholipase C (PLC) and increases the accumulation of docosahexaenoic acid …

The Landscape Of Ctdna In Appendiceal Adenocarcinoma, Michael G White, Mohammad A Zeineddine, Eleanor A Fallon, Fadl A Zeineddine, Julia Dansby, Saikat Chowdhury, Nicholas Hornstein, Abdelrahman Yousef, Mahmoud Yousef, Neal Bhutiani, Yue Gu, Bryan Kee, Arvind Dasari, Michael J Overman, Kanwal Raghav, Scott Kopetz, Abhineet Uppal, Melissa Taggart, Timothy Newhook, Keith Fournier, Beth Helmink, Leylah M Drusbosky, John Paul Shen

Faculty, Staff and Student Publications

Purpose: Appendiceal adenocarcinoma is a rare malignancy with distinct histopathologic subtypes and a natural history with metastasis primarily limited to the peritoneum. Little is known about the molecular pathogenesis of appendiceal adenocarcinoma relative to common tumors.

Experimental design: We analyzed molecular data for patients within the Guardant Health database with appendix cancer (n = 718). We then identified patients with appendiceal adenocarcinoma at our institution (from October 2004-September 2022) for whom ctDNA mutation profiling (liquid biopsy) was performed (n = 168) and extracted clinicopathologic and outcomes data. Of these 168 patients, 57 also had tissue-based tumor mutational profiling, allowing for …

Characterizing The Genetic Basis For Inherited Retinal Disease: Lessons Learned From The Foundation Fighting Blindness Clinical Consortium's Gene Poll, Kari Branham, Lassana Samarakoon, Isabelle Audo, Allison R Ayala, Janet K Cheetham, Stephen P Daiger, Patty Dhooge, Jacque L Duncan, Todd A Durham, Abigail T Fahim, Rachel M Huckfeldt, Robert B Hufnagel, Susanne Kohl, Ramiro S Maldonado, Michele Melia, Michel Michaelides, Mark E Pennesi, José-Alain Sahel, Juliana M Ferraz Sallum, Mandeep S Singh, Dror Sharon, Kimberly Stepien, Kaylie Jones, Christina Y Weng

Faculty, Staff and Students Publications

PURPOSE: The Foundation Fighting Blindness (FFB) Consortium is a collaboration of 41 international clinical centers that manage patients affected with inherited retinal diseases (IRDs). The annual Consortium gene poll was initiated in 2020 to capture the genetic cause of disease in patients with IRD and associated clinical practices of Consortium sites. Data from the 2022 gene poll are reported here.

METHODS: In 2022, academic, private practice, and government ophthalmology clinics that are members of the Consortium centers were polled to identify per-case IRD genetic causality from a list of 387 syndromic and nonsyndromic IRD genes. The survey also assessed how …

Cardiovascular Disease In Adults With Osteogenesis Imperfecta: Clinical Characteristics, Care Recommendations, And Research Priorities Identified Using A Modified Delphi Technique, Lars Folkestad, Siddharth K Prakash, Sandesh C S Nagamani, Niels Holmark Andersen, Erin Carter, Jannie Dahl Hald, Riley J Johnson, Bente Langdahl, Eleanor M Perfetto, Cathleen Raggio, Stuart H Ralston, Robert A Sandhaus, Oliver Semler, Laura Tosi, Eric Orwoll

Faculty, Staff and Student Publications

Osteogenesis imperfecta (OI) is a multisystem disorder most often caused by pathogenic variants in genes that encode type I collagen. Type I collagen is abundant not only in bone but also in multiple tissues including skin, tendons, cornea, blood vessels, and heart. Thus, OI can be expected to affect cardiovascular system, and there are numerous reports of cardiovascular disease (CVD) in people with OI. However, there is no consensus on how CVD in OI should be assessed or managed. To fill this gap, a multidisciplinary group was convened to develop clinical guidance. The work included a systematic review of the …

Dairy Consumption And The Colonic Mucosa-Associated Gut Microbiota In Humans-A Preliminary Investigation, Ellie Chen, Nadim J Ajami, Donna L White, Yanhong Liu, Shawn Gurwara, Kristi Hoffman, David Y Graham, Hashem B El-Serag, Joseph F Petrosino, Li Jiao

Faculty, Staff and Students Publications

Background: Dairy consumption has been associated with various health outcomes that may be mediated by changes in gut microbiota.

Methods: This cross-sectional study investigated the association between the colonic mucosa-associated gut microbiota and the self-reported intake of total dairy, milk, cheese, and yogurt. A total of 97 colonic mucosal biopsies collected from 34 polyp-free individuals were analyzed. Dairy consumption in the past year was assessed using a food frequency questionnaire. The 16S rRNA gene V4 region was amplified and sequenced. Operational taxonomic unit (OTU) classification was performed using the UPARSE and SILVA databases. OTU diversity and relative abundance were compared …

Prediction Of Lacosamide Concentrations To Support Dose Optimization During Pregnancy, Jessica M. Barry, Sílvia M. Illamola, Page B. Pennell, Catherine M.T. Sherwin, Kimford J. Meador, Angela K. Birnbaum

Pediatrics Faculty Publications

Objective: We aimed to quantify and predict lacosamide exposure during pregnancy by developing a pregnancy physiologically-based pharmacokinetic model, allowing the prediction of potential dose increases to support maintaining a patient's preconception lacosamide concentrations. Methods: Models for nonpregnant adults and pregnant female patients were constructed using physiochemical and pharmacological parameters identified from literature review. Evaluation of plasma concentration data from human males was digitized froM.T.he literature. Concentration data in nonpregnant and pregnant human females were available froM.T.he Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study, a longitudinal observational study which followed 11 nonpregnant and 16 pregnant women receiving lacosamide. …

Prediction Models Of Basal Energy Expenditure In Children And Adolescents Across The Bmi Spectrum Based On Room Calorimetry: A Cross-Sectional Cohort Study, Maurice Puyau, Roman Shypailo, Nancy F Butte, Salma Musaad, Fida Bacha

Children’s Nutrition Research Center Staff Publications

Background: Existing equations for prediction of basal energy expenditure (BEE) may not be accurate in children with overweight or obesity (OW/OB).

Objectives: We aimed to develop BEE prediction equations applicable to children and adolescents across a wide BMI spectrum using gold standard room calorimetry.

Methods: We measured weight, height, waist and hip circumferences, body composition (DXA), and BEE (whole room calorimetry) in a cross-sectional cohort of 1155 healthy children, 5-19 years of age. 67% of the males and 51% of the females were classified as OW/OB. We applied multiple linear regression analyses to develop BEE prediction models for each sex. …

Association Between Maternal Stress And Child Sleep Quality: A Nationwide Echo Prospective Cohort Study, Sarah Dee Geiger, Aruna Chandran, Marie L Churchill, Maxwell Mansolf, Cai Zhang, Salma Musaad, Courtney K Blackwell, Stephanie M Eick, Dana E Goin, Susan Korrick, Akram Alshawabkeh, Patricia A Brennan, Carrie V Breton, Jose F Cordero, Sean Deoni, Viren D'Sa, Anne L Dunlop, Amy J Elliott, Assiamira Ferrara, Arlene Keddie, Monique Lebourgeois, Kaja Z Lewinn, Daphne Koinis-Mitchell, Maristella Lucchini, Sara S Nozadi, Thomas O'Connor, Yeyi Zhu, Emily Zimmerman, Susan L Schantz

Children’s Nutrition Research Center Staff Publications

Background: Childhood sleep quality is associated with physical, cognitive, and behavioral health and predicts later sleep quality; it has many determinants, including developmental exposures.

Objectives: To examine associations between maternal stress during pregnancy and childhood sleep quality and determine whether postnatal stress mediates the association.

Method: Data from the Environmental Influences on Child Health Outcomes cohort were used. Perceived Stress Scale (PSS) T-scores were the exposure measure. Outcome measures were preschool Child Behavior Checklist (CBCL) sleep syndrome scale and Patient-Reported Outcomes Measurement Information System Sleep Disturbance Parent Proxy short form 4a (PSD4a) T-scores at ages 4-8 years. Linear mixed-effects regression …

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 …

Phase Ii Study Of Copanlisib In Patients With Pten Loss: Results From Nci-Match Ecog-Acrin Trial (Eay131) Subprotocols Z1g And Z1h, Mohamed A Gouda, Zihan Wei, Jordi Rodon, Michael A Davies, Filip Janku, Robert J Gray, Victoria Wang, Lisa M Mcshane, Larry V Rubinstein, David R Patton, P Mickey Williams, Stanley R Hamilton, Raymond Liu, Daniela A Bota, Paul L Swiecicki, Gary L Buchschacher, James V Tricoli, Barbara A Conley, Carlos L Arteaga, Lyndsay N Harris, Peter J O'Dwyer, Alice P Chen, Keith T Flaherty

Faculty, Staff and Student Publications

Purpose: Copanlisib, a pan-class phosphatidylinositol 3-kinase (PI3K) inhibitor with activity predominantly against the PI3K-delta and PI3K-alpha isoforms, has shown promising results in preclinical cancer models with PTEN loss. Herein, we report the activity and safety data from the Z1G and Z1H subprotocols, which included patients with PTEN loss, of the National Cancer Institute Molecular Analysis for Therapy Choice trial.

Methods: Patients with complete loss of cytoplasmic and nuclear PTEN as determined by immunohistochemistry regardless of PTEN mutation or deletion status were included in subprotocol Z1G, and patients with a deleterious mutation in the PTEN gene and retained expression of PTEN …

A Qualitative Assessment Of Changes In Occupational Exposures Among Healthcare Facility Workers, David Gimeno Ruiz De Porras, Jenil Patel, Sadie Conway, Lisa Pompeii, Laura E Mitchell, Arch Carson, Lawrence W Whitehead, Inkyu Han, Jan-Paul Zock, Paul K Henneberger, Riddhi Patel, Joy De Los Reyes, George L Delclos

Faculty, Staff and Student Publications

Adult-onset asthma, notably prevalent among healthcare professionals, especially nurses, is often attributed to occupational factors such as exposure to cleaning agents. Studies consistently underscore the substantial role of such exposure in work-related asthma among hospital staff. We aimed to (a) identify and characterize current practices in cleaning and aerosolized medication administration; (b) assess changes in practices since a similar 2003 study of Texas healthcare workers; and (c) identify factors contributing to diverse exposures within healthcare job categories. We conducted focus groups with 38 participants in 6 healthcare settings, analyzing current practices, changes since 2003, and factors contributing to exposure diversity. …

Evidence For Alpha-Synuclein Aggregation In Older Individuals With Hyposmia: A Cross-Sectional Study, Kenneth Marek, David S Russell, Luis Concha-Marambio, Seung Ho Choi, Danna Jennings, Michael C Brumm, Christopher S Coffey, Ethan Brown, John Seibyl, Matthew Stern, Claudio Soto, Andrew Siderowf

Faculty, Staff and Student Publications

Background: Synuclein pathology in neurodegenerative diseases, such as Parkinson's disease (PD) and Dementia with Lewy bodies (DLB), begins years before motor or cognitive symptoms arise. Alpha-Synuclein seed amplification assays (α-syn SAA) may detect aggregated synuclein before symptoms occur.

Methods: Data from the Parkinson Associated Risk Syndrome Study (PARS) have shown that individuals with hyposmia, without motor or cognitive symptoms, are enriched for dopamine transporter imaging (DAT) deficit and are at high risk to develop clinical parkinsonism or related synucleinopathies. α-syn aggregates in CSF were measured in 100 PARS participants using α-syn SAA.

Findings: CSF α-syn SAA was positive in 48% …

Plasma Proteomic Characterization Of Motoric Cognitive Risk And Mild Cognitive Impairment, Gabriela T Gomez, Sanish Sathyan, Jingsha Chen, Myriam Fornage, Pascal Schlosser, Zhongsheng Peng, Jenifer Cordon, Priya Palta, Kevin J Sullivan, Adrienne Tin, B Gwen Windham, Rebecca F Gottesman, Nir Barzilai, Sofiya Milman, Joe Verghese, Josef Coresh, Keenan A Walker

Faculty, Staff and Student Publications

INTRODUCTION: Motoric cognitive risk (MCR) is a pre-dementia syndrome characterized by mobility and cognitive dysfunction. This study conducted a proteome-wide study of MCR and compared the proteomic signatures of MCR to that of mild cognitive impairment (MCI).

METHODS: Participants were classified as MCR using a memory questionnaire and 4-meter walk. We measured 4877 plasma proteins collected during late-life and midlife. Multivariable logistic regression related each protein to late-life MCR/MCI. MCR-associated proteins were replicated internally at midlife and in an external cohort.

RESULTS: Proteome-wide analysis (n = 4076) identified 25 MCR-associated proteins. Eight of these proteins remained associated with late-life MCR …

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 …

Human Hypofunctional Ncf1 Variants Promote Pulmonary Fibrosis In The Bleomycin-Induced Mouse Model And Patients With Systemic Sclerosis Via Expansion Of Spphuman Hypofunctional Ncf1 Variants Promote Pulmonary Fibrosis In The Bleomycin-Induced Mouse Model And Systemic Sclerosis Patients Via Expansion Of Spp1+ Monocytes-Derived Macrophages, Xinran Yuan, Xiaodong Qin, Kenji Takemoto, Jian Zhao, Matthew Sanderson, Xue Xu, Yu Zhang, Kristi L Helke, Bethany Jacobs Wolf, Joel M Guthridge, Judith A James, Xiaodong Zhou, Shervin Assassi, Carol Feghali-Bostwick, Dandan Wang, Lingyun Sun, Betty P Tsao

Faculty, Staff and Student Publications

Objective: We assessed the role of a systemic lupus erythematosus causal hypofunctional variant, neutrophil cytosolic factor 1 (NCF1)-p.Arg90His (p.R90H) substitution, in systemic sclerosis (SSc).

Methods: Association of NCF1-H90 with SSc was performed in case-control cohorts, bleomycin (BLM)-treated Ncf1-R90 C57BL/6 wildtype and Ncf1-H90 knock-in (KI) littermates. Peripheral blood mononuclear cell (PBMC) subsets were analysed by cytometry by time-of-flight.

Results: The NCF1-H90 allele is associated with risk for diffuse cutaneous SSc (dcSSc) in Chinese and European Americans, and lung fibrosis in Chinese patients with SSc (OR=2.09, p=7.96E-10). Low copy number of NCF1 associated with lung fibrosis in European Americans (OR=4.33, p=2.60E-2). BLM-treated …

Association Of Systemic Inflammation And Long-Term Dysfunction In Covid-19 Patients: A Prospective Cohort, Felipe Dal-Pizzol, Bruno Kluwe-Schiavon, Henrique Ritter Dal-Pizzol, Gabriele Da Silveira Prestes, Diogo Dominguini, Carolina Saibro Girardi, Lucas Santos, José Cláudio Fonseca Moreira, Daniel Pens Gelain, Roger Walz, Tatiana Barichello, Cristiane Ritter

Faculty, Staff and Student Publications

COVID-19 has significant long-term impacts, including a chronic syndrome known as long-COVID, characterized by persistent symptoms post-recovery. The inflammatory response during acute infection is hypothesized to influence long-term outcomes. This study aimed to identify inflammatory biomarkers predictive of functional outcomes one year after hospital discharge. A prospective cohort study was conducted with 213 COVID-19 patients admitted to ICUs in Southern Brazil between June and November 2020. After exclusions and follow-ups, 109 patients were evaluated for one-year post-discharge. Plasma levels of Th1 (TNF-α, INF-γ, IL-12), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), and Th17 (IL-17, IL-22) cytokines were measured. Functional outcomes in …

Immunogenomic Determinants Of Exceptional Response To Immune Checkpoint Inhibition In Renal Cell Carcinoma, Tejas Jammihal, Renee Maria Saliby, Chris Labaki, Hanna Soulati, Juan Gallegos, Arnau Peris, Dustin Mccurry, Chunlei Yu, Valisha Shah, Deepak Poduval, Talal El Zarif, Nourhan El Ahmar, Yasmin Nabil Laimon, Marc Eid, Aseman Bagheri Sheshdeh, Katherine M Krajewski, Florian A Büttner, Matthias Schwab, Daniel Heng, Rafael C Casellas, Kunal Rai, Niki M Zacharias Millward, Pavlos Msaouel, Jose Karam, Sabina Signoretti, Eliezer Van Allen, Toni K Choueiri, David A Braun, Sachet A Shukla

Faculty, Staff and Student Publications

Immune checkpoint inhibitors can lead to 'exceptional', durable responses in a subset of persons. However, the molecular basis of exceptional response (ER) to immunotherapy in metastatic clear cell renal cell carcinoma (mccRCC) has not been well characterized. Here we analyzed pretherapy genomic and transcriptomic data in treatment-naive persons with mccRCC treated with standard-of-care immunotherapies: (1) combination of programmed cell death protein and ligand 1 (PD1/PDL1) and cytotoxic T lymphocyte-associated protein 4 inhibitors (IO/IO) or (2) combination of PD1/PDL1 and vascular endothelial growth factor (VEGF) receptor inhibitors (IO/VEGF). In the IO/IO cohort, clonal neoantigen load was significantly higher in persons with …

Community Outreach, Engagement, And Mentoring Program For Underrepresented Scholars In Cancer Health Disparities, Lorna H Mcneill, Cassandra L Harris, Terrence R Adams, Berta R Salazar, Crystal L Roberson, Leonetta B Thompson, Kamisha H Escoto, Kayce D Solari Williams, Shine Chang, Tzuan A Chen, Birnur Buzcu-Guven, Lorraine R Reitzel

Faculty, Staff and Student Publications

Objective:

Racial/ethnic minorities and women are affected by cancer and cancer risk factors at higher rates; however, they are largely underrepresented in scientific professions focused on health disparities. One way to reduce disparities is to increase diversity within the workforce by planning training activities for minority scholars, paying close attention to community outreach. This paper describes the outcomes of a robust community outreach plan engaging communities in education, research, and clinical trials to increase the number of underrepresented student scholars in cancer disparities research through research training, mentorship, and service-learning activities provided within local organizations.

Methods:

The program provided two …

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, …

National Prescribing Practices For Pediatric Dystonia Among Providers In The United States., Sarah Paige Davis, Natalie J. Kane, Haley E. Botteron, Rose N. Gelineau-Morel

Manuscripts, Articles, Book Chapters and Other Papers

While multiple oral medications are used to treat dystonia, limited information exists on current prescribing practices. This study analyzes real-world prescribing practices for pediatric dystonia in the United States, evaluating prescription frequency, dosing, and the impact of comorbidities. Oracle electronic health record real-world data were queried from 2014 to 2019 for encounters of patients under age 18 with a dystonia diagnosis and available medication records. Information was extracted on prescriptions for dystonia medications (baclofen, clonidine, carbidopa-levodopa, gabapentin, tetrabenazine, trihexyphenidyl, and select benzodiazepines), dosing, and comorbid diagnoses of cerebral palsy (CP), epilepsy, or spasticity. A total of 4010 pediatric patients with …

Improvement On The Slopes: The Impact Of An Adaptive Snow Sports Program On Children And Young Adults With Disabilities., Stephanie M. Barton, Matthew J. Mclaughlin, Mark T. Fisher

Manuscripts, Articles, Book Chapters and Other Papers

PurposeThis retrospective cohort study sought to examine participant skill and functional progression in an adaptive snow sports program for children and young adults with disabilities.MethodsOne hundred twelve individuals, majority male, who participated in at least 2 adapted ski or snowboard sessions were evaluated by trained adaptive instructors. The primary outcome measure was standardized skill level ranging from 1-novice to 9-expert. Secondary outcome measures of cognitive, emotional, social, physical, and independence scores, were rated on a scale from 1-5, with 5 being the highest.ResultsThe median number of sessions per participant was 4 (range 2-65 sessions) and median participation duration was 2 …

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). …

Healthcare Costs In The United States By Demographic Characteristics And Comorbidity Status, Naomi N Adjei, Allen Haas, Charlotte C Sun, Hui Zhao, Paul G Yeh, Sharon H Giordano, Iakovos Toumazis, Larissa A Meyer

Faculty, Staff and Student Publications

Objectives: Current, real-world healthcare cost information is needed to project future expenditures and inform policy. We estimated the healthcare costs for adults in 2019 in the United States by age, sex, race/ethnicity, geographic region, and comorbidity.

Methods: We aggregated and summarized the healthcare costs in 2021 US dollars using claims data derived from Optum's deidentified Clinformatics® Data Mart Database, which includes inpatient, outpatient, and prescription claims for commercial and Medicare Advantage beneficiaries nationwide.

Results: A total of 9 227 901 adults were included in the analysis. The largest group represented was 71 to 75 years old (13%), female (53%), White …

Cost Of Ovarian Cancer By The Phase Of Care In The United States, Naomi N Adjei, Allen M Haas, Charlotte C Sun, Hui Zhao, Paul G Yeh, Sharon H Giordano, Iakovos Toumazis, Larissa A Meyer

Faculty, Staff and Student Publications

Background: Ovarian cancer is associated with delayed diagnosis and poor survival; thus, interest is high in identifying predictive and prognostic biomarkers and novel therapeutic agents. Although the costs of ovarian cancer care are likely to increase as newer, more effective, but more expensive treatment regimens become available, information on the current costs of care for ovarian cancer-across the care continuum from diagnosis to the end of life-are lacking.

Objective: This study aimed to estimate real-world mean and median costs of ovarian cancer care within the first 5 years after diagnosis by patients' phase of care, age, race/ethnicity, and geographic region. …