Medical Specialties Commons^™

Systemic Sclerosis Associated Interstitial Lung Disease: A Conceptual Framework For Subclinical, Clinical And Progressive Disease, David Roofeh, Kevin K Brown, Ella A Kazerooni, Donald Tashkin, Shervin Assassi, Fernando Martinez, Athol U Wells, Ganesh Raghu, Christopher P Denton, Lorinda Chung, Anna-Maria Hoffmann-Vold, Oliver Distler, Kerri A Johannson, Yannick Allanore, Eric L Matteson, Leticia Kawano-Dourado, John D Pauling, James R Seibold, Elizabeth R Volkmann, Simon L F Walsh, Chester V Oddis, Eric S White, Shaney L Barratt, Elana J Bernstein, Robyn T Domsic, Paul F Dellaripa, Richard Conway, Ivan Rosas, Nitin Bhatt, Vivien Hsu, Francesca Ingegnoli, Bashar Kahaleh, Puneet Garcha, Nishant Gupta, Surabhi Khanna, Peter Korsten, Celia Lin, Stephen C Mathai, Vibeke Strand, Tracy J Doyle, Virginia Steen, Donald F Zoz, Juan Ovalles-Bonilla, Ignasi Rodriguez-Pinto, Padmanabha D Shenoy, Andrew Lewandoski, Elizabeth Belloli, Alain Lescoat, Vivek Nagaraja, Wen Ye, Suiyuan Huang, Toby Maher, Dinesh Khanna

Faculty, Staff and Students Publications

OBJECTIVES: To establish a framework by which experts define disease subsets in systemic sclerosis associated interstitial lung disease (SSc-ILD).

METHODS: A conceptual framework for subclinical, clinical and progressive ILD was provided to 83 experts, asking them to use the framework and classify actual SSc-ILD patients. Each patient profile was designed to be classified by at least four experts in terms of severity and risk of progression at baseline; progression was based on 1-year follow-up data. A consensus was reached if ≥75% of experts agreed. Experts provided information on which items were important in determining classification.

RESULTS: Forty-four experts (53%) completed …

Adiposity-Associated Atrial Fibrillation: Molecular Determinants, Mechanisms, And Clinical Significance, Monika Gawałko, Arnela Saljic, Na Li, Issam Abu-Taha, Thomas Jespersen, Dominik Linz, Stanley Nattel, Jordi Heijman, Anke Fender, Dobromir Dobrev

Faculty, Staff and Students Publications

Obesity is an important contributing factor to the pathophysiology of atrial fibrillation (AF) and its complications by causing systemic changes, such as altered haemodynamic, increased sympathetic tone, and low-grade chronic inflammatory state. In addition, adipose tissue is a metabolically active organ that comprises various types of fat deposits with discrete composition and localization that show distinct functions. Fatty tissue differentially affects the evolution of AF, with highly secretory active visceral fat surrounding the heart generally having a more potent influence than the rather inert subcutaneous fat. A variety of proinflammatory, profibrotic, and vasoconstrictive mediators are secreted by adipose tissue, particularly …

Outcomes Of The "Brca Quality Improvement Dissemination Program": An Initiative To Improve Patient Receipt Of Cancer Genetics Services At Five Health Systems., Erica M Bednar, Minxing Chen, Michael T Walsh, Amanda L Eppolito, Molly H Klein, Kelly Teed, Brittany Hodge, Jordan Hunter, Han Gill Chao, Dillon Davis, Wilshauna Serchion, Cara Yobbi, Rebekah Krukenberg, Sandra B Jenkinson, Jennifer J Moore, Cassandra Garcia, Fatimaeliza Gonzalez, Towanna Murray, Linda D Nielsen, Brenda Ho, Megan Haas, Sarah B Greenzweig, Abby Anderson, Christina Johnson, Nichole A Morman, Elizabeth Bowdish, Emaline Wise, Julia N Cooper, Pauline Kefalas Russ, Katelyn Tondo-Steele, Buonarotti F De Gracia, Brooke Levin, Kristin Mattie, Kathryn Zarnawski, Molly Kalasinski, Jennifer Stone, Caitlin O'Brien, Alexa Bream, Aidan M Kennedy, Rachel A Paul, Michelle Bilbao, Maureen Romero, Rebecca L Carr, Jennifer M Siettmann, Anna K Vercruyssen, Kaycee Leon, Banu K Arun, Andrew V Grainger, David P Warshal, Erin Bowman, Timothy A Goedde, Deepa Halaharvi, Kellie Rath, Generosa Grana, Lida Mina, Karen H Lu

Oncology Articles

OBJECTIVE: A quality improvement initiative (QII) was conducted with five community-based health systems' oncology care centers (sites A-E). The QII aimed to increase referrals, genetic counseling (GC), and germline genetic testing (GT) for patients with ovarian cancer (OC) and triple-negative breast cancer (TNBC).

METHODS: QII activities occurred at sites over several years, all concluding by December 2020. Medical records of patients with OC and TNBC were reviewed, and rates of referral, GC, and GT of patients diagnosed during the 2 years before the QII were compared to those diagnosed during the QII. Outcomes were analyzed using descriptive statistics, two-sample t-test, …

The Impact Of Maternal Diabetes On Birth To Placental Weight Ratio And Umbilical Cord Oxygen Values With Implications For Fetal-Placental Development, Sheryl Choo, Barbra De Vrijer, Timothy R H Regnault, Hilary K Brown, Larry Stitt, Bryan S Richardson

Obstetrics & Gynaecology Publications

Introduction

We determined the impact of gestational diabetes (GDM) and pre-existing diabetes (DM) on birth/placental weight and cord oxygen values with implications for placental efficiency and fetal-placental growth and development.

Methods

A hospital database was used to obtain birth/placental weight, cord PO₂ and other information on patients delivering between Jan 1, 1990 and Jun 15, 2011 with GA >34 weeks (N = 69,854). Oxygen saturation was calculated from the cord PO₂ and pH data, while fetal O₂ extraction was calculated from the oxygen saturation data. The effect of diabetic status on birth/placental weight and cord oxygen values …

Families' Knowledge Change In Paediatric Drug Resistant Epilepsy: A Novel Clinic Model, Michelle Kregel, Sherry Coulson, Maryam N Nouri, Rochelle Sorzano, Andrea Andrade

Paediatrics Publications

BACKGROUND: Epilepsy is a chronic condition that affects approximately 95,000 Ontarians, of whom approximately 15,000 are children under the age of 18. Drug resistant epilepsy (DRE) will affect around 30% of these children who will require more advanced care due to their medical complexities. The purpose of this study is to determine if receiving care in a paediatric Comprehensive Epilepsy Clinic (CEC) is associated with positive outcomes for children living with DRE and their families by looking at three health outcomes: 1) families' knowledge of their child's diagnosis and treatment plan, 2) navigational access to both the hospital and community …

Does The Type Of Chronic Heart Failure Impact In-Hospital Outcomes For Aortic Valve Replacement Procedures?, Talha Mubashir, John Zaki, Sin Yeong An, Ismael A Salas De Armas, Yafen Liang, Travis Markham, Han Feng, Mehmet H Akay, Angelo Nascimbene, Bindu Akkanti, George W Williams, Fabricio Zasso, Maria Patarroyo Aponte, Igor D Gregoric, Biswajit Kar

Faculty, Staff and Student Publications

BACKGROUND: This study assessed in-hospital outcomes of patients with chronic systolic, diastolic, or mixed heart failure (HF) undergoing transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR).

METHODS: The Nationwide Inpatient Sample database was used to identify patients with aortic stenosis and chronic HF who underwent TAVR or SAVR between 2012 and 2015. Propensity score matching and multivariate logistic regression were used to determine outcome risk.

RESULTS: A cohort of 9,879 patients with systolic (27.2%), diastolic (52.2%), and mixed (20.6%) chronic HF were included. No statistically significant differences in hospital mortality were noted. Overall, patients with diastolic HF …

Use, Durability, And Risks For Discontinuation Of Initial And Subsequent Biologics In A Large Pediatric-Onset Ibd Cohort., Jess L. Kaplan, Chunyan Liu, Eileen C. King, Julie A. Bass, Ashish S. Patel, Jeanne Tung, Shiran Chen, Trevor Lissoos, Ninfa Candela, Shehzad Saeed, Richard B. Colletti, Improvecarenow Network

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Biologic medications are recommended for treatment of moderately-to-severely active Crohn disease (CD) or ulcerative colitis (UC) in children. However, many patients require sequential biologic treatment because of nonresponse or loss of response to the initial biologic.

METHODS: We analyzed pediatric inflammatory bowel disease (IBD) data from the ImproveCareNow Network registry between May 2006 and September 2016, including time to biologic initiation, choice of first subsequent biologics, biologic durability, and reasons for discontinuation.

RESULTS: Of 17,649 patients with IBD [CD: 12,410 (70%); UC: 5239 (30%)], 7585 (43%) were treated with a biologic agent before age 18 (CD: 50%; UC: 25%). …

Real-World Experience Of Pediatric Patients Treated With Peanut (Arachis Hypogaea) Allergen Powder-Dnfp., Jay M. Portnoy, Jodi Shroba, Stephen Tilles, Hela Romdhani, Sarah M. Donelson, Dominick Latremouille-Viau, Rebecca Bungay, Kathleen Chen, William Mccann

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) is the first oral immunotherapy indicated for children aged 4 to 17 years with peanut allergy. There are limited real-world data on patients treated with PTAH.

OBJECTIVE: To characterize pediatric patients treated with PTAH and associated treatment patterns in US clinical practice.

METHODS: US-based physicians with allergy and immunology training treating patients with peanut allergy aged 4 to 17 years with PTAH were recruited from an existing physician panel and completed an online case report form (October to December 2021) with data abstracted from patient medical charts. Physician practice circumstances, patient characteristics, and …

Analysis Of Vein Grafting Versus Arteriovenous Loop In Microvascular Head And Neck Reconstruction: Multicenter Series Of 36 Patients, Kaitlynne Y. Pak, Spencer R. Anderson, Tyler L. Langenfeld, Kenneth Tan, Allison Slijepcevic, Sunishka Wimalawansa, Yadranko Ducic, Mark K. Wax, Sameep P. Kadakia

Orthopaedic Surgery Faculty Publications

Background: The utilization of an arteriovenous loop is an underreported technique that affords the creation of reliable vascular options. Understanding the efficacy and impacting variables of microvascular reconstruction with an arteriovenous loop can be critical to its use.

Methods: Multi-institutional study of 36 patients who underwent vein grafting or AV loop with free tissue transfer.

Results: 58.3% of patients received prior radiation and 38.9% prior flap reconstruction. Flap success for vein grafting was 76% and AV loop was 100% (p = 0.16). Success for the radiated cohort was 90.5% and non-radiated 80% (p = 0.63). Flap success for the radiated, …

Therapies In Stiff-Person Syndrome: Advances And Future Prospects Based On Disease Pathophysiology, Marinos Dalakas

Department of Neurology Faculty Papers

Among the glutamic acid decarboxylase (GAD)-antibody-spectrum disorders, the most common phenotypic subset is the stiff-person syndrome (SPS), caused by impaired GABAergic inhibitory neurotransmission and autoimmunity characterized by very high titers of GAD antibodies and increased GAD-IgG intrathecal synthesis. If not properly treated or untreated because of delayed diagnosis, SPS progresses leading to disability; it is therefore fundamental to apply the best therapeutic schemes from the outset. This article is focused on the rationale of specific therapeutic strategies based on the SPS pathophysiology targeting both the impaired reciprocal GABAergic inhibition to symptomatically improve the main clinical manifestations of stiffness in the …

Fully Human Monoclonal Antibody Targeting Activated Adam10 On Colorectal Cancer Cells, Nayanendu Saha, Du-San Baek, Rachelle P Mendoza, Dorothea Robev, Yan Xu, Yehuda Goldgur, M Jason De La Cruz, Elisa De Stanchina, Peter W Janes, Kai Xu, Dimiter S Dimitrov, Dimitar B Nikolov

Faculty, Staff and Student Publications

Metastasis and chemoresistance in colorectal cancer are mediated by certain poorly differentiated cancer cells, known as cancer stem cells, that are maintained by Notch downstream signaling initiated upon Notch cleavage by the metalloprotease ADAM10. It has been shown that ADAM10 overexpression correlates with aberrant signaling from Notch, erbBs, and other receptors, as well as a more aggressive metastatic phenotype, in a range of cancers including colon, gastric, prostate, breast, ovarian, uterine, and leukemia. ADAM10 inhibition, therefore, stands out as an important and new approach to deter the progression of advanced CRC. For targeting the ADAM10 substrate-binding region, which is located …

Efficacy Of Alternative Dose Regimens Of Exemestane In Postmenopausal Women With Stage 0 To Ii Estrogen Receptor-Positive Breast Cancer: A Randomized Clinical Trial, Davide Serrano, Sara Gandini, Parjhitham Thomas, Katherine D Crew, Nagi B Kumar, Lana A Vornik, J Jack Lee, Paolo Veronesi, Giuseppe Viale, Aliana Guerrieri-Gonzaga, Matteo Lazzeroni, Harriet Johansson, Mauro D'Amico, Flavio Guasone, Stefano Spinaci, Bjørn-Erik Bertelsen, Gunnar Mellgren, Isabelle Bedrosian, Diane Weber, Tawana Castile, Eileen Dimond, Brandy M Heckman-Stoddard, Eva Szabo, Powel H Brown, Andrea Decensi, Bernardo Bonanni

Faculty, Staff and Student Publications

IMPORTANCE: Successful therapeutic cancer prevention requires definition of the minimal effective dose. Aromatase inhibitors decrease breast cancer incidence in high-risk women, but use in prevention and compliance in adjuvant settings are hampered by adverse events.

OBJECTIVE: To compare the noninferiority percentage change of estradiol in postmenopausal women with estrogen receptor-positive breast cancer given exemestane, 25 mg, 3 times weekly or once weekly vs a standard daily dose with a noninferiority margin of -6%.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, presurgical, double-blind phase 2b randomized clinical trial evaluated 2 alternative dosing schedules of exemestane. Postmenopausal women with estrogen receptor-positive breast cancer …

Outcomes Following Extracorporeal Membrane Oxygenation For Severe Covid-19 In Pregnancy Or Post Partum, John J Byrne, Amir A Shamshirsaz, Alison G Cahill, Mark A Turrentine, Angela R Seasely, Joe Eid, Caroline E Rouse, Michael Richley, Nandini Raghuraman, Mariam Naqvi, Yasser Y El-Sayed, Martina L Badell, Cece Cheng, James Liu, Emily H Adhikari, Soha S Patel, Erika R O'Neil, Patrick S Ramsey

Faculty, Staff and Student Publications

IMPORTANCE: Existing reports of pregnant patients with COVID-19 disease who require extracorporeal membrane oxygenation (ECMO) are limited, with variable outcomes noted for the maternal-fetal dyad.

OBJECTIVE: To examine maternal and perinatal outcomes associated with ECMO used for COVID-19 with respiratory failure during pregnancy.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective multicenter cohort study examined pregnant and postpartum patients who required ECMO for COVID-19 respiratory failure at 25 hospitals across the US. Eligible patients included individuals who received care at one of the study sites, were diagnosed with SARS-CoV-2 infection during pregnancy or up to 6 weeks post partum by positive nucleic …

Advances In The Treatment Of Invasive Fungal Disease, Zhuan Zhang, Gerald F Bills, Zhiqiang An

Faculty, Staff and Student Publications

With over 300 million severe cases and 1.5 million deaths annually, invasive fungal diseases (IFDs) are a major medical burden and source of global morbidity and mortality. The World Health Organization (WHO) recently released the first-ever fungal priority pathogens list including 19 fungal pathogens, considering the perceived public health importance. Most of the pathogenic fungi are opportunistic and cause diseases in patients under immunocompromised conditions such as HIV infection, cancer, chemotherapy, transplantation, and immune suppressive drug therapy. Worryingly, the morbidity and mortality caused by IFDs are continuously on the rise due to the limited available antifungal therapies, the emergence of …

Comparison Of Reconstructed Prompt Gamma Emissions Using Maximum Likelihood Estimation And Origin Ensemble Algorithms For A Compton Camera System Tailored To Proton Range Monitoring, Ingrid Valencia Lozano, George Dedes, Steve Peterson, Dennis Mackin, Andreas Zoglauer, Sam Beddar, Stephen Avery, Jerimy Polf, Katia Parodi

Faculty, Staff and Student Publications

Compton-based prompt gamma (PG) imaging is being investigated by several groups as a potential solution for in vivo range monitoring in proton therapy. The performance of this technique depends on the detector system as well as the ability of the reconstruction method to obtain good spatial resolution to establish a quantitative correlation between the PG emission and the proton beam range in the patient. To evaluate the feasibility of PG imaging for range monitoring, we quantitatively evaluated the emission distributions reconstructed by a Maximum Likelihood Expectation Maximization (MLEM) and a Stochastic Origin Ensemble (SOE) algorithm. To this end, we exploit …

Outcomes Of The “Brca Quality Improvement Dissemination Program”: An Initiative To Improve Patient Receipt Of Cancer Genetics Services At Five Health Systems, Erica M Bednar, Minxing Chen, Michael T Walsh, Amanda L Eppolito, Molly H Klein, Kelly Teed, Brittany Hodge, Jordan Hunter, Han Gill Chao, Dillon Davis, Wilshauna Serchion, Cara Yobbi, Rebekah Krukenberg, Sandra B Jenkinson, Jennifer J Moore, Cassandra Garcia, Fatimaeliza Gonzalez, Towanna Murray, Linda D Nielsen, Brenda Ho, Megan Haas, Sarah B Greenzweig, Abby Anderson, Christina Johnson, Nichole A Morman, Elizabeth Bowdish, Emaline Wise, Julia N Cooper, Pauline Kefalas Russ, Katelyn Tondo-Steele, Buonarotti F De Gracia, Brooke Levin, Kristin Mattie, Kathryn Zarnawski, Molly Kalasinski, Jennifer Stone, Caitlin O'Brien, Alexa Bream, Aidan M Kennedy, Rachel A Paul, Michelle Bilbao, Maureen Romero, Rebecca L Carr, Jennifer M Siettmann, Anna K Vercruyssen, Kaycee Leon, Banu K Arun, Andrew V Grainger, David P Warshal, Erin Bowman, Timothy A Goedde, Deepa Halaharvi, Kellie Rath, Generosa Grana, Lida Mina, Karen H Lu

Faculty, Staff and Student Publications

OBJECTIVE: A quality improvement initiative (QII) was conducted with five community-based health systems' oncology care centers (sites A-E). The QII aimed to increase referrals, genetic counseling (GC), and germline genetic testing (GT) for patients with ovarian cancer (OC) and triple-negative breast cancer (TNBC).

METHODS: QII activities occurred at sites over several years, all concluding by December 2020. Medical records of patients with OC and TNBC were reviewed, and rates of referral, GC, and GT of patients diagnosed during the 2 years before the QII were compared to those diagnosed during the QII. Outcomes were analyzed using descriptive statistics, two-sample t-test, …

A Parathyroid Hormone/Salt-Inducible Kinase Signaling Axis Controls Renal Vitamin D Activation And Organismal Calcium Homeostasis, Sung-Hee Yoon, Mark B Meyer, Carlos Arevalo, Murat Tekguc, Chengcheng Zhang, Jialiang S Wang, Christian D Castro Andrade, Katelyn Strauss, Tadatoshi Sato, Nancy A Benkusky, Seong Min Lee, Rebecca Berdeaux, Marc Foretz, Thomas B Sundberg, Ramnik J Xavier, Charles H Adelmann, Daniel J Brooks, Anthony Anselmo, Ruslan I Sadreyev, Ivy A Rosales, David E Fisher, Navin Gupta, Ryuji Morizane, Anna Greka, J Wesley Pike, Michael Mannstadt, Marc N Wein

Faculty, Staff and Student Publications

The renal actions of parathyroid hormone (PTH) promote 1,25-vitamin D generation; however, the signaling mechanisms that control PTH-dependent vitamin D activation remain unknown. Here, we demonstrated that salt-inducible kinases (SIKs) orchestrated renal 1,25-vitamin D production downstream of PTH signaling. PTH inhibited SIK cellular activity by cAMP-dependent PKA phosphorylation. Whole-tissue and single-cell transcriptomics demonstrated that both PTH and pharmacologic SIK inhibitors regulated a vitamin D gene module in the proximal tubule. SIK inhibitors increased 1,25-vitamin D production and renal Cyp27b1 mRNA expression in mice and in human embryonic stem cell–derived kidney organoids. Global- and kidney-specific Sik2/Sik3 mutant mice showed Cyp27b1 upregulation, …

A Protocol For A Cluster Randomized Trial Of Care Delivery Models To Improve The Quality Of Smoking Cessation And Shared Decision Making For Lung Cancer Screening, Lisa M Lowenstein, Ya-Chen Tina Shih, Jennifer Minnix, Maria A Lopez-Olivo, Kristin G Maki, George Kypriotakis, Viola B Leal, Sanjay S Shete, James Fox, Shawn P Nishi, Paul M Cinciripini, Robert J Volk

Faculty, Staff and Student Publications

BACKGROUND: Patients eligible for lung cancer screening (LCS) are those at high risk of lung cancer due to their smoking histories and age. While screening for LCS is effective in lowering lung cancer mortality, primary care providers are challenged to meet beneficiary eligibility for LCS from the Centers for Medicare & Medicaid Services, including a patient counseling and shared decision-making (SDM) visit with the use of patient decision aid(s) prior to screening.

METHODS: We will use an effectiveness-implementation type I hybrid design to: 1) identify effective, scalable smoking cessation counseling and SDM interventions that are consistent with recommendations, can be …

P53 And Ovarian Carcinoma Survival: An Ovarian Tumor Tissue Analysis Consortium Study, Martin Köbel, Eun-Young Kang, Ashley Weir, Peter F Rambau, Cheng-Han Lee, Gregg S Nelson, Prafull Ghatage, Nicola S Meagher, Marjorie J Riggan, Jennifer Alsop, Michael S Anglesio, Matthias W Beckmann, Christiani Bisinotto, Michelle Boisen, Jessica Boros, Alison H Brand, Angela Brooks-Wilson, Michael E Carney, Penny Coulson, Madeleine Courtney-Brooks, Kara L Cushing-Haugen, Cezary Cybulski, Suha Deen, Mona A El-Bahrawy, Esther Elishaev, Ramona Erber, Sian Fereday, Aocs Group, Anna Fischer, Simon A Gayther, Arantzazu Barquin-Garcia, Aleksandra Gentry-Maharaj, C Blake Gilks, Helena Gronwald, Marcel Grube, Paul R Harnett, Holly R Harris, Andreas D Hartkopf, Arndt Hartmann, Alexander Hein, Joy Hendley, Brenda Y Hernandez, Yajue Huang, Anna Jakubowska, Mercedes Jimenez-Linan, Michael E Jones, Catherine J Kennedy, Tomasz Kluz, Jennifer M Koziak, Jaime Lesnock, Jenny Lester, Jan Lubiński, Teri A Longacre, Maria Lycke, Constantina Mateoiu, Bryan M Mccauley, Valerie Mcguire, Britta Ney, Alexander Olawaiye, Sandra Orsulic, Ana Osorio, Luis Paz-Ares, Teresa Ramón Y Cajal, Joseph H Rothstein, Matthias Ruebner, Minouk J Schoemaker, Mitul Shah, Raghwa Sharma, Mark E Sherman, Yurii B Shvetsov, Naveena Singh, Helen Steed, Sarah J Storr, Aline Talhouk, Nadia Traficante, Chen Wang, Alice S Whittemore, Martin Widschwendter, Lynne R Wilkens, Stacey J Winham, Javier Benitez, Andrew Berchuck, David D Bowtell, Francisco J Candido Dos Reis, Ian Campbell, Linda S Cook, Anna Defazio, Jennifer A Doherty, Peter A Fasching, Renée T Fortner, María J García, Marc T Goodman, Ellen L Goode, Jacek Gronwald, David G Huntsman, Beth Y Karlan, Linda E Kelemen, Stefan Kommoss, Nhu D Le, Stewart G Martin, Usha Menon, Francesmary Modugno, Paul Dp Pharoah, Joellen M Schildkraut, Weiva Sieh, Annette Staebler, Karin Sundfeldt, Anthony J Swerdlow, Susan J Ramus, James D Brenton

Faculty, Staff and Student Publications

Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were …

Combining Physics-Based Models With Deep Learning Image Synthesis And Uncertainty In Intraoperative Cone-Beam Ct Of The Brain, Xiaoxuan Zhang, Alejandro Sisniega, Wojciech B Zbijewski, Junghoon Lee, Craig K Jones, Pengwei Wu, Runze Han, Ali Uneri, Prasad Vagdargi, Patrick A Helm, Mark Luciano, William S Anderson, Jeffrey H Siewerdsen

Faculty, Staff and Student Publications

BACKGROUND: Image-guided neurosurgery requires high localization and registration accuracy to enable effective treatment and avoid complications. However, accurate neuronavigation based on preoperative magnetic resonance (MR) or computed tomography (CT) images is challenged by brain deformation occurring during the surgical intervention.

PURPOSE: To facilitate intraoperative visualization of brain tissues and deformable registration with preoperative images, a 3D deep learning (DL) reconstruction framework (termed DL-Recon) was proposed for improved intraoperative cone-beam CT (CBCT) image quality.

METHODS: The DL-Recon framework combines physics-based models with deep learning CT synthesis and leverages uncertainty information to promote robustness to unseen features. A 3D generative adversarial network …

High-Dose Once-Daily Thoracic Radiotherapy In Limited-Stage Small-Cell Lung Cancer: Calgb 30610 (Alliance)/Rtog 0538, Jeffrey Bogart, Xiaofei Wang, Gregory Masters, Junheng Gao, Ritsuko Komaki, Laurie E Gaspar, John Heymach, James Bonner, Charles Kuzma, Saiama Waqar, William Petty, Thomas E Stinchcombe, Jeffrey D Bradley, Everett Vokes

Faculty, Staff and Student Publications

PURPOSE: Although level 1 evidence supports 45-Gy twice-daily radiotherapy as standard for limited-stage small-cell lung cancer, most patients receive higher-dose once-daily regimens in clinical practice. Whether increasing radiotherapy dose improves outcomes remains to be prospectively demonstrated.

METHODS: This phase III trial, CALGB 30610/RTOG 0538 (ClinicalTrials.gov identifier: NCT00632853), was conducted in two stages. In the first stage, patients with limited-stage disease were randomly assigned to receive 45-Gy twice-daily, 70-Gy once-daily, or 61.2-Gy concomitant-boost radiotherapy, starting with either the first or second (of four total) chemotherapy cycles. In the second stage, allocation to the 61.2-Gy arm was discontinued following planned interim toxicity …

National Cancer Control Plan Of The Korea: Current Status And The Fourth Plan (2021-2025), Kyu-Tae Han, Jae Kwan Jun, Jeong-Soo Im

Faculty, Staff and Student Publications

Cancer management has become a major policy goal for the government of the Korea. As such, the government introduced the National Cancer Control Plan (NCCP) to reduce the individual and social burdens caused by cancer and to promote national health. During the past 25 years, 3 phases of the NCCP have been completed. During this time, the NCCP has changed significantly in all aspects of cancer control from prevention to survival. The targets for cancer control are increasing, and although some blind spots remain, new demands are emerging. The government initiated the fourth NCCP in March 2021, with the vision …

Targeting Pd-L2-Rgmb Overcomes Microbiome-Related Immunotherapy Resistance, Joon Seok Park, Francesca S Gazzaniga, Meng Wu, Amalia K Luthens, Jacob Gillis, Wen Zheng, Martin W Lafleur, Sarah B Johnson, Golnaz Morad, Elizabeth M Park, Yifan Zhou, Stephanie S Watowich, Jennifer A Wargo, Gordon J Freeman, Dennis L Kasper, Arlene H Sharpe

Faculty, Staff and Student Publications

The gut microbiota is a crucial regulator of anti-tumour immunity during immune checkpoint inhibitor therapy. Several bacteria that promote an anti-tumour response to immune checkpoint inhibitors have been identified in mice1-6. Moreover, transplantation of faecal specimens from responders can improve the efficacy of anti-PD-1 therapy in patients with melanoma7,8. However, the increased efficacy from faecal transplants is variable and how gut bacteria promote anti-tumour immunity remains unclear. Here we show that the gut microbiome downregulates PD-L2 expression and its binding partner repulsive guidance molecule b (RGMb) to promote anti-tumour immunity and identify bacterial species that mediate this effect. PD-L1 and …

Combining Mendelian Randomization And Network Deconvolution For Inference Of Causal Networks With Gwas Summary Data, Zhaotong Lin, Haoran Xue, Wei Pan

Faculty, Staff and Student Publications

Mendelian randomization (MR) has been increasingly applied for causal inference with observational data by using genetic variants as instrumental variables (IVs). However, the current practice of MR has been largely restricted to investigating the total causal effect between two traits, while it would be useful to infer the direct causal effect between any two of many traits (by accounting for indirect or mediating effects through other traits). For this purpose we propose a two-step approach: we first apply an extended MR method to infer (i.e. both estimate and test) a causal network of total effects among multiple traits, then we …

Philadelphia-Like Genetic Rearrangements In Adults With B-Cell All: Refractoriness To Chemotherapy And Response To Tyrosine Kinase Inhibitor In Abl Class Rearrangements, Jayastu Senapati, Elias Jabbour, Marina Konopleva, Nicholas J Short, Guilin Tang, Naval Daver, Partow Kebriaei, Tapan Kadia, Naveen Pemmaraju, Koichi Takahashi, Courtney Dinardo, Koji Sasaki, Gautam Borthakur, Beenu Thakral, Rashmi Kanagal-Shamanna, Keyur Patel, Farhad Ravandi, Kathryn Roberts, Charles Mullighan, Hagop Kantarjian, Nitin Jain

Faculty, Staff and Student Publications

PURPOSE: Philadelphia-like (Ph-like) B-cell ALL is a high-risk subtype of B-cell ALL that shares a gene expression profile with Ph-positive ALL, but without a

PATIENTS AND METHODS: We performed a retrospective review of patients with B-cell ALL treated at MD Anderson Cancer Center to identify recurrent genetic fusions commonly seen in Ph-like ALL and focus on patients treated with TKI.

RESULTS: We identified 23 patients with recurrent genetic fusions commonly seen in Ph-like ALL; 14 had

CONCLUSION: Understanding the genomics of B-cell ALL is important for disease prognostication and for precise treatment planning. Besides conventional cytogenetics and directed FISH testing, …

Critical Role Of The Ventral Temporal Lobe In Naming, Kathryn M Snyder, Kiefer J Forseth, Cristian Donos, Patrick S Rollo, Simon Fischer-Baum, Joshua Breier, Nitin Tandon

Faculty, Staff and Student Publications

OBJECTIVE: Lexical retrieval deficits are characteristic of a variety of different neurological disorders. However, the exact substrates responsible for this are not known. We studied a large cohort of patients undergoing surgery in the dominant temporal lobe for medically intractable epilepsy (n = 95) to localize brain regions that were associated with anomia.

METHODS: We performed a multivariate voxel-based lesion-symptom mapping analysis to correlate surgical lesions within the temporal lobe with changes in naming ability. Additionally, we used a surface-based mixed-effects multilevel analysis to estimate group-level broadband gamma activity during naming across a subset of patients with electrocorticographic recordings and …

Aapm Task Group Report 305: Guidance For Standardization Of Vendor-Neutral Reject Analysis In Radiography, Kevin Little, Ingrid Reiser, Bruce Apgar, Poonam Dalal, Jaydev Dave, Ryan Fisher, Katie Hulme, Mary Ellen Jafari, Emily Marshall, Stephen Meyer, Quentin Moore, Nicole Murphy, Thomas Nishino, Katelyn Nye, Kevin O'Donnell, John Sabol, Adrian Sanchez, William Sensakovic, Lawrence Tarbox, Robert Uzenoff, Alisa Walz-Flannigan, Charles Willis, Jie Zhang

Faculty, Staff and Student Publications

Reject rate analysis is considered an integral part of a diagnostic radiography quality control (QC) program. A rejected image is a patient radiograph that was not presented to a radiologist for diagnosis and that contributes unnecessary radiation dose to the patient. Reject rates that are either too high or too low may suggest systemic department shortcomings in QC mechanisms. Due to the lack of standardization, reject data often cannot be easily compared between radiography systems from different vendors. The purpose of this report is to provide guidance to help standardize data elements that are required for comprehensive reject analysis and …

Phase I Trial Of Autologous Rna-Electroporated Cmet-Directed Car T Cells Administered Intravenously In Patients With Melanoma And Breast Carcinoma, Payal D Shah, Alexander C Huang, Xiaowei Xu, Robert Orlowski, Ravi K Amaravadi, Lynn M Schuchter, Paul Zhang, Julia Tchou, Tina Matlawski, Amanda Cervini, Joanne Shea, Joan Gilmore, Lester Lledo, Karen Dengel, Amy Marshall, E John Wherry, Gerald P Linette, Andrea Brennan, Vanessa Gonzalez, Irina Kulikovskaya, Simon F Lacey, Gabriela Plesa, Carl H June, Robert H Vonderheide, Tara C Mitchell

Faculty, Staff and Student Publications

PURPOSE: Treatments are limited for metastatic melanoma and metastatic triple-negative breast cancer (mTNBC). This pilot phase I trial (NCT03060356) examined the safety and feasibility of intravenous RNA-electroporated chimeric antigen receptor (CAR) T cells targeting the cell-surface antigen cMET.

EXPERIMENTAL DESIGN: Metastatic melanoma or mTNBC subjects had at least 30% tumor expression of cMET, measurable disease and progression on prior therapy. Patients received up to six infusions (1 × 10e8 T cells/dose) of CAR T cells without lymphodepleting chemotherapy. Forty-eight percent of prescreened subjects met the cMET expression threshold. Seven (3 metastatic melanoma, 4 mTNBC) were treated.

RESULTS: Mean age was …

Prospective Study Of Perioperative Circulating Tumor Dna Dynamics In Patients Undergoing Hepatectomy For Colorectal Liver Metastases, Timothy E Newhook, Michael J Overman, Yun Shin Chun, Arvind Dasari, Ching-Wei D Tzeng, Hop S Tran Cao, Victoria Raymond, Christine Parseghian, Benny Johnson, Yujiro Nishioka, Yoshikuni Kawaguchi, Abhineet Uppal, Timothy J Vreeland, Ariel Jaimovich, Elsa M Arvide, Jenilette V Cristo, Steven H Wei, Kanwal P Raghav, Van K Morris, Jeffrey E Lee, Scott Kopetz, Jean-Nicolas Vauthey

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate the association of perioperative ctDNA dynamics on outcomes after hepatectomy for CLM.

SUMMARY BACKGROUND DATA: Prognostication is imprecise for patients undergoing hepatectomy for CLM, and ctDNA is a promising biomarker. However, clinical implications of perioperative ctDNA dynamics are not well established.

METHODS: Patients underwent curative-intent hepatectomy after preoperative chemotherapy for CLM (2013-2017) with paired prehepatectomy/postoperative ctDNA analyses via plasma-only assay. Positivity was determined using a proprietary variant classifier. Primary endpoint was recurrence-free survival (RFS). Median follow-up was 55 months.

RESULTS: Forty-eight patients were included. ctDNA was detected before and after surgery (ctDNA+/+) in 14 (29%), before but …

Neural Network Based Ensemble Model To Predict Radiation Induced Lymphopenia After Concurrent Chemo-Radiotherapy For Non-Small Cell Lung Cancer From Two Institutions, Yejin Kim, Ibrahim Chamseddine, Yeona Cho, Jin Sung Kim, Radhe Mohan, Nadya Shusharina, Harald Paganetti, Steven Lin, Hong In Yoon, Seungryong Cho, Clemens Grassberger

Faculty, Staff and Student Publications

The use of adjuvant Immune Checkpoint Inhibitors (ICI) after concurrent chemo-radiation therapy (CCRT) has become the standard of care for locally advanced non-small cell lung cancer (LA-NSCLC). However, prolonged radiotherapy regimens are known to cause radiation-induced lymphopenia (RIL), a long-neglected toxicity that has been shown to correlate with response to ICIs and survival of patients treated with adjuvant ICI after CCRT. In this study, we aim to develop a novel neural network (NN) approach that integrates patient characteristics, treatment related variables, and differential dose volume histograms (dDVH) of lung and heart to predict the incidence of RIL at the end …