Digital Commons Network^™

Inhibition Of Cathepsin S In Autoimmune Cd25ko Mouse Improves Sjögren Disease-Like Lacrimal Gland Pathology, Kaitlin K Scholand, Jeremias Galletti, Wolfgang Haap, Tiago Santos-Ferreira, Christoph Ullmer, Cintia S De Paiva

Faculty, Staff and Students Publications

PURPOSE: CD25KO mice are a model of Sjögren disease (SjD) driven by autoreactive T cells. Cathepsin S (CTSS) is a protease crucial for major histocompatibility complex class II presentation that primes T cells. We investigated if a diet containing CTSS inhibitor would improve autoimmune signs in CD25KO mice.

METHODS: Four-week female CD25KO mice were randomly chosen to receive chow containing a CTSS inhibitor (R05461111, 262.5 mg/kg chow) or standard chow for 4 weeks. Cornea sensitivity was measured. Inflammatory score was assessed in lacrimal gland (LG) histologic sections. Flow cytometry of LG and ocular draining lymph nodes (dLNs) investigated expression of …

Plasmacytoid Dendritic Cells Control Homeostasis Of Megakaryopoiesis, Florian Gaertner, Marco Colonna, Et Al.

2020-Current year OA Pubs

Platelet homeostasis is essential for vascular integrity and immune defence

Depressive Symptoms Are Associated With C-Reactive Protein In Older Adults With Obesity, Henry D Heisey, Clifford Qualls, Dennis T Villareal, Martha Belen Segoviano-Escobar, Maria Liza Duremdes Nava, Jennifer R Gatchel, Mark E Kunik

Faculty, Staff and Students Publications

OBJECTIVES: To test the hypothesis that depressive symptoms vary with high-sensitivity C-reactive protein (hs-CRP), among older adults with obesity.

METHODS: This was a cross-sectional, secondary analysis of baseline data from two related lifestyle intervention trials. The study sample comprises 148 consecutively recruited, community-dwelling older adults (age >=65 years) without severe psychiatric illness and with body mass index >=30 kg/m

RESULTS: Sample mean GDS score was 2.7 (SD 3.0, range 0 - 14). A significant multivariate model of GDS scores (R

CONCLUSIONS: In older adults with obese BMI, male sex and higher hs-CRP are associated with depression, even in a group …

Homozygous Missense Variants In Ykt6 Result In Loss Of Function And Are Associated With Developmental Delay, With Or Without Severe Infantile Liver Disease And Risk For Hepatocellular Carcinoma, Mengqi Ma, Mythily Ganapathi, Yiming Zheng, Kai-Li Tan, Oguz Kanca, Kevin E Bove, Norma Quintanilla, Sebnem O Sag, Sehime G Temel, Charles A Leduc, Amanda J Mcpartland, Elaine M Pereira, Yufeng Shen, Jacob Hagen, Christie P Thomas, Nhu Thao Nguyen Galván, Xueyang Pan, Shenzhao Lu, Jill A Rosenfeld, Daniel G Calame, Michael F Wangler, James R Lupski, Davut Pehlivan, Paula M Hertel, Wendy K Chung, Hugo J Bellen

Faculty, Staff and Students Publications

PURPOSE: YKT6 plays important roles in multiple intracellular vesicle trafficking events but has not been associated with Mendelian diseases.

METHODS: We report 3 unrelated individuals with rare homozygous missense variants in YKT6 who exhibited neurological disease with or without a progressive infantile liver disease. We modeled the variants in Drosophila. We generated wild-type and variant genomic rescue constructs of the fly ortholog dYkt6 and compared their ability in rescuing the loss-of-function phenotypes in mutant flies. We also generated a dYkt6

RESULTS: Two individuals are homozygous for YKT6 [NM_006555.3:c.554A>G p.(Tyr185Cys)] and exhibited normal prenatal course followed by failure to thrive, …

Healthy Dietary Patterns Are Associated With Exposure To Environmental Chemicals In A Pregnancy Cohort, Guoqi Yu, Ruijin Lu, Jiaxi Yang, Mohammad L Rahman, Ling-Jun Li, Dong D Wang, Qi Sun, Wei Wei Pang, Claire Guivarch, Anna Birukov, Jagteshwar Grewal, Zhen Chen, Cuilin Zhang

2020-Current year OA Pubs

Healthy dietary patterns, such as the alternate Mediterranean diet and alternate Healthy Eating Index, benefit cardiometabolic health. However, several food components of these dietary patterns are primary sources of environmental chemicals. Here, using data from a racially and ethnically diverse US cohort, we show that healthy dietary pattern scores were positively associated with plasma chemical exposure in pregnancy, particularly for the alternate Mediterranean diet and alternate Healthy Eating Index with polychlorinated biphenyls and per- and poly-fluoroalkyl substances. The associations appeared stronger among Asian and Pacific Islanders. These findings suggest that optimizing the benefits of a healthy diet requires concerted regulatory …

Integrating Multisector Molecular Characterization Into Personalized Peptide Vaccine Design For Patients With Newly Diagnosed Glioblastoma, Tanner M Johanns, Elizabeth A R Garfinkle, Katherine E Miller, Alexandra J Livingstone, Kaleigh F Roberts, Lakshmi P Rao Venkata, Joshua L Dowling, Michael R Chicoine, Ralph G Dacey, Gregory J Zipfel, Albert H Kim, Elaine R Mardis, Gavin P Dunn

2020-Current year OA Pubs

PURPOSE: Outcomes for patients with glioblastoma (GBM) remain poor despite multimodality treatment with surgery, radiation, and chemotherapy. There are few immunotherapy options due to the lack of tumor immunogenicity. Several clinical trials have reported promising results with cancer vaccines. To date, studies have used data from a single tumor site to identify targetable antigens, but this approach limits the antigen pool and is antithetical to the heterogeneity of GBM. We have implemented multisector sequencing to increase the pool of neoantigens across the GBM genomic landscape that can be incorporated into personalized peptide vaccines called NeoVax.

PATIENTS AND METHODS: In this …

Exome Sequencing Identifies Novel Genes Underlying Primary Congenital Glaucoma In The National Birth Defects Prevention Study, Elizabeth E Blue, Kristin J Moore, Kari E North, Tania A Desrosiers, Suzan L Carmichael, Janson J White, Jessica X Chong, Michael J Bamshad, Mary M Jenkins, Lynn M Almli, Lawrence C Brody, Sharon F Freedman, Jennita Reefhuis, Paul A Romitti, Gary M Shaw, Martha Werler, Denise M Kay, Marilyn L Browne, Marcia L Feldkamp, Richard H Finnell, Wendy N Nembhard, Faith Pangilinan, Andrew F Olshan, National Institutes Of Health Intramural Sequencing Center, University Of Washington Center For Mendelian Genomics, National Birth Defects Prevention Study

Faculty, Staff and Students Publications

Background: Primary congenital glaucoma (PCG) affects approximately 1 in 10,000 live born infants in the United States (U.S.). PCG has a autosomal recessive inheritance pattern, and variable expressivity and reduced penetrance have been reported. Likely causal variants in the most commonly mutated gene, CYP1B1, are less prevalent in the U.S., suggesting that alternative genes may contribute to the condition. This study utilized exome sequencing to investigate the genetic architecture of PCG in the U.S. and to identify novel genes and variants.

Methods: We studied 37 family trios where infants had PCG and were part of the National Birth Defects Prevention …

The Role Of Transoral Incisionless Fundoplication (Tif) In The Management Of Gastroesophageal Reflux Disease (Gerd) Following Peroral Endoscopic Myotomy (Poem): A Pilot, Prospective, Patient-Driven Study, Fares Ayoub, Tara Keihanian, Noor Zabad, Salmaan Jawaid, Kalpesh Patel, Mohamed O Othman

Faculty, Staff and Students Publications

BACKGROUND: Gastroesophageal reflux (GERD) is a concern after peroral endoscopic myotomy (POEM). Transoral incisionless fundoplication (TIF) has been recently described as a possible therapy for post-POEM GERD in case series.

METHODS: We prospectively enrolled patients undergoing POEM who agreed to participate in objective post-procedure GERD evaluation. Patients with objective evidence of GERD and suitable anatomy were offered TIF vs. proton pump inhibitor (PPI) only. Patients who underwent TIF were compared to those on PPI-only therapy after follow-up.

RESULTS: Of 21 enrolled POEM patients with objective testing, GERD was found in 11 (52%). Of those eligible for TIF, 4 (40%) opted …

Thrombosis Risk Prediction In Lymphoma Patients: A Multi-Institutional, Retrospective Model Development And Validation Study, Shengling Ma, Jennifer La, Kaitlin N Swinnerton, Danielle Guffey, Raka Bandyo, Giordana De Las Pozas, Katy Hanzelka, Xiangjun Xiao, Cristhiam M Rojas-Hernandez, Christopher I Amos, Vipul Chitalia, Katya Ravid, Kelly W Merriman, Christopher R Flowers, Nathanael Fillmore, Ang Li

Faculty, Staff and Students Publications

Venous thromboembolism (VTE) poses a significant risk to cancer patients receiving systemic therapy. The generalizability of pan-cancer models to lymphomas is limited. Currently, there are no reliable risk prediction models for thrombosis in patients with lymphoma. Our objective was to create a risk assessment model (RAM) specifically for lymphomas. We performed a retrospective cohort study to develop Fine and Gray sub-distribution hazard model for VTE and pulmonary embolism (PE)/ lower extremity deep vein thrombosis (LE-DVT) respectively in adult lymphoma patients from the Veterans Affairs national healthcare system (VA). External validations were performed at the Harris Health System (HHS) and the …

Study Of A Pst-Trained Voice-Enabled Artificial Intelligence Counselor For Adults With Emotional Distress (Speac-2): Design And Methods, Corina R Ronneberg, Thomas Kannampallil, Et Al.

2020-Current year OA Pubs

BACKGROUND: Novel and scalable psychotherapies are urgently needed to address the depression and anxiety epidemic. Leveraging artificial intelligence (AI), a voice-based virtual coach named Lumen was developed to deliver problem solving treatment (PST). The first pilot trial showed promising changes in cognitive control measured by functional neuroimaging and improvements in depression and anxiety symptoms.

METHODS: To further validate Lumen in a 3-arm randomized clinical trial, 200 participants with mild-to-moderate depression and/or anxiety will be randomly assigned in a 2:1:1 ratio to receive Lumen-coached PST, human-coached PST as active treatment comparison, or a waitlist control condition where participants can receive Lumen …

Survival Disparities In Rural Versus Urban Patients With Pancreatic Neuroendocrine Tumor: A Multi-Institutional Study From The Us Neuroendocrine Tumor Study Group, Muhammad Bilal Mirza, Jordan J Baechle, Paula Marincola Smith, Mary Dillhoff, George Poultsides, Flavio G Rocha, Clifford S Cho, Emily R Winslow, Ryan C Fields, Shishir K Maithel, Kamran Idrees

2020-Current year OA Pubs

BACKGROUND: Pancreatic Neuroendocrine Tumors (PNETs) are indolent malignancies that often have a prolonged clinical course. This study assesses disparities in outcomes between PNET patients who live in urban (UA) and rural areas (RA).

METHODS: A retrospective cohort study was performed using the US Neuroendocrine Tumor Study Group database. PNET patients with a home zip code recorded were included and categorized as RA or UA according to the Federal Office of Rural Health Policy. Overall survival (OS) was analyzed by Kaplan-Meier method, log-rank test, and logistical regression.

RESULTS: Of the 1176 PNET patients in the database, 1126 (96%) had zip code …

Cognitive Control Training With Domain-General Response Inhibition Does Not Change Children's Brains Or Behavior, Keertana Ganesan, Abigail Thompson, Claire R Smid, Roser Cañigueral, Yongjing Li, Grace Revill, Vanessa Puetz, Boris C Bernhardt, Nico U F Dosenbach, Rogier Kievit, Nikolaus Steinbeis

2020-Current year OA Pubs

Cognitive control is required to organize thoughts and actions and is critical for the pursuit of long-term goals. Childhood cognitive control relates to other domains of cognitive functioning and predicts later-life success and well-being. In this study, we used a randomized controlled trial to test whether cognitive control can be improved through a pre-registered 8-week intervention in 235 children aged 6-13 years targeting response inhibition and whether this leads to changes in multiple behavioral and neural outcomes compared to a response speed training. We show long-lasting improvements of closely related measures of cognitive control at the 1-year follow-up; however, training …

Association Of High-Density Lipoprotein Parameters And Risk Of Heart Failure: A Multicohort Analysis, Ambarish Pandey, Kershaw V Patel, Matthew W Segar, Michael D Shapiro, Christie M Ballantyne, Salim S Virani, Vijay Nambi, Erin D Michos, Michael J Blaha, Khurram Nasir, Miguel Cainzos-Achirica, Colby R Ayers, B Daan Westenbrink, Jose L Flores-Guerrero, Stephan J L Bakker, Margery A Connelly, Robin P F Dullaart, Anand Rohatgi

Faculty, Staff and Students Publications

Background: High-density lipoprotein (HDL) is commonly characterized by its cholesterol concentration (HDL-C) and inverse association with atherosclerotic cardiovascular disease.

Objectives: The authors sought to evaluate the association of HDL particle concentration (HDL-P), HDL particle size (HDL-size), HDL-C, and cholesterol content per particle (HDL-C/HDL-P) with risk of overall heart failure (HF) and subtypes.

Methods: Participants from the Atherosclerosis Risk In Communities Study, Dallas Heart Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-stage Disease studies without HF history were included. Associations of HDL-P, HDL-size, HDL-C, and HDL-C/HDL-P with risk of overall HF, HF with reduced and preserved ejection …

Pregnancy Outcomes Of Nifedipine Compared With Labetalol For Oral Treatment Of Mild Chronic Hypertension, Ayodeji A Sanusi, Justin Leach, Kim Boggess, Lorraine Dugoff, Baha Sibai, Kirsten Lawrence, Brenna L Hughes, Joseph Bell, Kjersti Aagaard, Rodney K Edwards, Kelly S Gibson, David M Haas, Lauren Plante, Torri D Metz, Brian Casey, Sean Esplin, Sherri Longo, Matthew K Hoffman, George R Saade, Kara K Hoppe, Janelle Foroutan, Methodius Tuuli, Michelle Y Owens, Hyagriv N Simhan, Heather Frey, Todd Rosen, Anna Palatnik, Susan Baker, Phyllis August, Uma M Reddy, Emily J Su, Iris Krishna, Nguyet A Nguyen, Mary E Norton, Daniel Skupski, Yasser Y El-Sayed, Dotun Ogunyemi, Zorina S Galis, Lorie Harper, Namasivayam Ambalavanan, Nancy L Geller, Hui-Chien Kuo, Rachel G Sinkey, Ronald Librizzi, Leonardo Pereira, Everett F Magann, Mounira Habli, Shauna Williams, Giancarlo Mari, Gabriella Pridjian, David S Mckenna, Marc Parrish, Eugene Chang, Sarah Osmundson, Joanne Quinones, Jeff M Szychowski, Alan T N Tita

Faculty, Staff and Students Publications

Objective: To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial.

Methods: We conducted a planned secondary analysis of CHAP, an open-label, multicenter, randomized trial of antihypertensive treatment compared with standard care (no treatment unless severe hypertension developed) in pregnant patients with mild chronic hypertension (blood pressure 140-159/90-104 mm Hg before 20 weeks of gestation) and singleton pregnancies. We performed three comparisons based on medications prescribed at enrollment: labetalol compared with standard care, nifedipine compared with standard care, and labetalol compared with nifedipine. Although active compared with standard care …

Mean Arterial Pressure And Neonatal Outcomes In Pregnancies Complicated By Mild Chronic Hypertension, Matthew D Moore, Hui-Chien Kuo, Rachel G Sinkey, Kim Boggess, Lorraine Dugoff, Baha Sibai, Kirsten Lawrence, Brenna L Hughes, Joseph Bell, Kjersti Aagaard, Rodney K Edwards, Kelly S Gibson, David M Haas, Lauren Plante, Torri D Metz, Brian Casey, Sean Esplin, Sherri Longo, Matthew K Hoffman, George R Saade, Kara K Hoppe, Janelle Foroutan, Methodius Tuuli, Michelle Y Owens, Hyagriv N Simhan, Heather A Frey, Todd Rosen, Anna Palatnik, Susan Baker, Phyllis August, Uma M Reddy, Wendy Kinzler, Emily J Su, Iris Krishna, Nguyet A Nguyen, Mary E Norton, Daniel Skupski, Yasser Y El-Sayed, Dotun Ogunyemi, Ronald Librizzi, Leonardo Pereira, Everett F Magann, Mounira Habli, Shauna Williams, Giancarlo Mari, Gabriella Pridjian, David S Mckenna, Marc Parrish, Eugene Chang, Sarah Osmundson, Joanne N Quiñones, Justin Leach, Ayodeji Sanusi, Zorina S Galis, Lorie Harper, Namasivayam Ambalavanan, Jeff M Szychowski, Alan T N Tita

Faculty, Staff and Students Publications

Objective: To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial.

Methods: A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 …

Utility Of Cystatin C-Based Equation For The Estimation Of Glomerular Filtration Rate In A Pediatric Population, Ridwan B Ibrahim, Poyyapakkam Srivaths, Estella Tam, Sridevi Devaraj

Faculty, Staff and Students Publications

Background: The accurate assessment of kidney function is vital for the early detection of kidney damage. The estimated glomerular filtration rate GFR (eGFR) from serum cystatin C (CysC) and creatinine-based equations are commonly used in clinical practice as an alternative to the invasive measured glomerular filtration rate (mGFR), which is the usually accepted overall best index of kidney function in health and disease. Recently the CKiD under 25 (CkiD U25) equations have been shown to perform well in children and young adults with chronic kidney disease (CKD). In this focused report, we evaluated the performance of the CkiD U25 equations …

Progressive Thrombocytopenia, Splenomegaly, And Abnormal Tone In An Infant With Growth Faltering, Gal Barak, Gail Demmler-Harrison, Linda Rossetti, Venée N Tubman, Ameya S Walimbe, Rathi Asaithambi

Faculty, Staff and Students Publications

A 4-month-old full-term female presented with growth faltering associated with progressive feeding difficulty, rash, abdominal distension, and developmental delays. She was found to have disconjugate gaze, abnormal visual tracking, mixed tone, bruising, and splenomegaly on examination. Initial workup was notable for thrombocytopenia and positive cytomegalovirus (CMV) immunoglobulin G and immunoglobulin M antibodies. She initially presented to the infectious diseases CMV clinic, where she was noted to have severe malnutrition, prompting referral to the emergency department for hospital admission to optimize nutrition with nasogastric tube feeding and facilitate additional evaluation. An active CMV infection with viruria and viremia was confirmed, but …

Pecarn Prediction Rule For Cervical Spine Imaging Of Children Presenting To The Emergency Department With Blunt Trauma: A Multicentre Prospective Observational Study, Julie C Leonard, Monica Harding, Lawrence J Cook, Jeffrey R Leonard, Kathleen M Adelgais, Fahd A Ahmad, Lorin R Browne, Rebecca K Burger, Pradip P Chaudhari, Daniel J Corwin, Nicolaus W Glomb, Lois K Lee, Sylvia Owusu-Ansah, Lauren C Riney, Alexander J Rogers, Daniel M Rubalcava, Robert E Sapien, Matthew A Szadkowski, Leah Tzimenatos, Caleb E Ward, Kenneth Yen, Nathan Kuppermann

Faculty, Staff and Students Publications

Background: Cervical spine injuries in children are uncommon but potentially devastating; however, indiscriminate neck imaging after trauma unnecessarily exposes children to ionising radiation. The aim of this study was to derive and validate a paediatric clinical prediction rule that can be incorporated into an algorithm to guide radiographic screening for cervical spine injury among children in the emergency department.

Methods: In this prospective observational cohort study, we screened children aged 0-17 years presenting with known or suspected blunt trauma at 18 specialised children's emergency departments in hospitals in the USA affiliated with the Pediatric Emergency Care Applied Research Network (PECARN). …

Durable Responses With Mosunetuzumab In Relapsed/Refractory Indolent And Aggressive B-Cell Non-Hodgkin Lymphomas: Extended Follow-Up Of A Phase I/Ii Study, Lihua E Budde, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

No abstract provided.

Alcohol Milestones And Internalizing, Externalizing, And Executive Function: Longitudinal And Polygenic Score Associations, Sarah E Paul, David A A Baranger, Joshua J Jackson, Aaron J Gorelik, Alexander S Hatoum, Michael Strube, Andrey P Anokhin, Arpana Agrawal, Kathleen K Bucholz, Ryan Bogdan, Et Al.

2020-Current year OA Pubs

BACKGROUND: Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.

METHODS: Data came from the Collaborative Study on the Genetics of Alcoholism (

RESULTS: Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe …

Il2 Targeted To Cd8+ T Cells Promotes Robust Effector T-Cell Responses And Potent Antitumor Immunity, Kelly D Moynihan, Hussein Sultan, Robert D Schreiber, Et Al.

2020-Current year OA Pubs

IL2 signals pleiotropically on diverse cell types, some of which contribute to therapeutic activity against tumors, whereas others drive undesired activity, such as immunosuppression or toxicity. We explored the theory that targeting of IL2 to CD8+ T cells, which are key antitumor effectors, could enhance its therapeutic index. To this aim, we developed AB248, a CD8 cis-targeted IL2 that demonstrates over 500-fold preference for CD8+ T cells over natural killer and regulatory T cells (Tregs), which may contribute to toxicity and immunosuppression, respectively. AB248 recapitulated IL2's effects on CD8+ T cells in vitro and induced selective expansion of CD8+T cells …

A Phase Ii Trial Of The Wee1 Inhibitor Adavosertib In Setd2-Altered Advanced Solid Tumor Malignancies (Nci 10170), Edward Maldonado, Nikolaos A Trikalinos, Et Al.

2020-Current year OA Pubs

UNLABELLED: We sought to evaluate the efficacy of WEE1 inhibitor adavosertib in patients with solid tumor malignancies (cohort A) and clear cell renal cell carcinoma (ccRCC; cohort B). NCT03284385 was a parallel cohort, Simon two-stage, phase II study of adavosertib (300 mg QDAY by mouth on days 1-5 and 8-12 of each 21-day cycle) in patients with solid tumor malignancies harboring a pathogenic SETD2 mutation. The primary endpoint was the objective response rate. Correlative assays evaluated the loss of H3K36me3 by IHC, a downstream consequence of SETD2 loss, in archival tumor tissue. Eighteen patients were enrolled (9/cohort). The median age …

Epigenetic Developmental Mechanisms Underlying Sex Differences In Cancer, Joshua B. Rubin, Tamara Abou-Antoun, Joseph E. Ippolito, Lorida Llaci, Camryn T. Marquez, Jason P. Wong, Lihua Yang

2020-Current year OA Pubs

Cancer risk is modulated by hereditary and somatic mutations, exposures, age, sex, and gender. The mechanisms by which sex and gender work alone and in combination with other cancer risk factors remain underexplored. In general, cancers that occur in both the male and female sexes occur more commonly in XY compared with XX individuals, regardless of genetic ancestry, geographic location, and age. Moreover, XY individuals are less frequently cured of their cancers, highlighting the need for a greater understanding of sex and gender effects in oncology. This will be necessary for optimal laboratory and clinical cancer investigations. To that end, …

Suicide In Us Preteens Aged 8 To 12 Years, 2001 To 2022, Donna A Ruch, Lisa M Horowitz, Jennifer L Hughes, Katherine Sarkisian, Joan L Luby, Cynthia A Fontanella, Jeffrey A Bridge

2020-Current year OA Pubs

No abstract provided.

Open-Label, Dose-Escalation Fight-101 Study Of Pemigatinib Combined With Targeted Therapy, Chemotherapy, Or Immunotherapy In Patients With Advanced Malignancies, M Saleh, M Barve, V Subbiah, K P Papadopoulos, D Morgensztern, N B Mettu, S Roychowdhury, I Spanggaard, M L Veronese, C Tian, I M Silverman, M Gutierrez

2020-Current year OA Pubs

BACKGROUND: Pemigatinib is an oral, potent, selective fibroblast growth factor receptor (FGFR) 1-3 inhibitor. FIGHT-101, a three-part, open-label, first-in-human, phase I/II study (NCT02393248), evaluated pemigatinib in patients with advanced solid tumors. In parts 1 and 2, pemigatinib monotherapy had a manageable safety profile and antitumor activity in FGFR-altered tumors. Part 3 (pemigatinib combination therapies) results are presented here.

PATIENTS AND METHODS: Patients received 9, 13.5, or 20 mg oral once-daily pemigatinib on continuous or intermittent schedules with gemcitabine and cisplatin (pemi/gem/cis), docetaxel (pemi/doc), trastuzumab (pemi/tras), pembrolizumab (pemi/pembro), or retifanlimab (pemi/reti) irrespective of whether the tumor was confirmed as FGFR altered. …

A Risk Is Not A Harm: Abortion Exceptions In State Laws, Trevor M Bibler, Alison Suen

Center for Medical Ethics and Health Policy Staff Publications

This letter responds to the article "Beneath the Sword of Damocles: Moral Obligations of Physicians in a Post-Dobbs Landscape," by Anne Drapkin Lyerly, Ruth R. Faden, and Michelle M. Mello, in the May-June 2024 issue of the Hastings Center Report.

Perinatal Mental Healthcare Utilization Among Patients With Placenta Accreta Spectrum, Sarah R Casey, Alison N Goulding, Christina C Reed, Amir A Shamshirsaz, Hennie A Lombaard, Michael A Belfort, Lisa M Noll, Karin A Fox

Faculty, Staff and Students Publications

No abstract provided.

Genome-Wide Association Study Identifies High-Impact Susceptibility Loci For Hcc In North America, Manal M Hassan, Donghui Li, Younghun Han, Jinyoung Byun, Rikita I Hatia, Erping Long, Jiyeon Choi, Robin Kate Kelley, Sean P Cleary, Anna S Lok, Paige Bracci, Jennifer B Permuth, Roxana Bucur, Jian-Min Yuan, Amit G Singal, Prasun K Jalal, R Mark Ghobrial, Regina M Santella, Yuko Kono, Dimpy P Shah, Mindie H Nguyen, Geoffrey Liu, Neehar D Parikh, Richard Kim, Hui-Chen Wu, Hashem El-Serag, Ping Chang, Yanan Li, Yun Shin Chun, Sunyoung S Lee, Jian Gu, Ernest Hawk, Ryan Sun, Chad Huff, Asif Rashid, Hesham M Amin, Laura Beretta, Robert A Wolff, Samuel O Antwi, Yehuda Patt, Lu-Yu Hwang, Alison P Klein, Karen Zhang, Mikayla A Schmidt, Donna L White, John A Goss, Saira A Khaderi, Jorge A Marrero, Francisco G Cigarroa, Pankil K Shah, Ahmed O Kaseb, Lewis R Roberts, Christopher I Amos

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP).

APPROACH AND RESULTS: We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a …

The Road To Tailored Adjuvant Chemotherapy For All Four Non-Pancreatic Periampullary Cancers: An International Multimethod Cohort Study, Bas A Uijterwijk, Daniël H Lemmers, Michele Ghidini, Johanna W Wilmink, Alberto Zaniboni, Giuseppe Kito Fusai, Alessandro Zerbi, Bas Groot Koerkamp, Misha Luyer, Poya Ghorbani, Roberto Salvia, Steven White, Benedetto Ielpo, Brian K P Goh, Ugo Boggi, Geert Kazemier, Michael G House, Vasileios K Mavroeidis, Bergthor Björnsson, Michele Mazzola, Mario Serradilla, Dimitris Korkolis, Adnan Alseidi, Keith J Roberts, Zahir Soonawalla, Patrick Pessaux, William E Fisher, Sharnice Koek, Tara S Kent, Miljana Vladimirov, Louisa Bolm, Nigel Jamieson, Raffaele Dalla Valle, Jorg Kleeff, Alessandro Mazzotta, Miguel Angel Suarez Muñoz, Santiago Sánchez Cabús, Chad G Ball, Adam C Berger, Clarissa Ferarri, Marc G Besselink, Mohammed Abu Hilal, International Study Group On Non-Pancreatic Periampullary Cancer (Isgaca)

Center for Medical Ethics and Health Policy Staff Publications

Background: Despite differences in tumour behaviour and characteristics between duodenal adenocarcinoma (DAC), the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype of ampullary adenocarcinoma and distal cholangiocarcinoma (dCCA), the effect of adjuvant chemotherapy (ACT) on these cancers, as well as the optimal ACT regimen, has not been comprehensively assessed. This study aims to assess the influence of tailored ACT on DAC, dCCA, AmpIT, and AmpPB.

Patients and methods: Patients after pancreatoduodenectomy for non-pancreatic periampullary adenocarcinoma were identified and collected from 36 tertiary centres between 2010 - 2021. Per non-pancreatic periampullary tumour type, the effect of adjuvant chemotherapy and the main relevant regimens …

Trans-Ancestral Genetic Risk Factors For Treatment-Related Type 2 Diabetes Mellitus In Survivors Of Childhood Cancer, Cindy Im, Achal Neupane, Jessica L Baedke, Brian Lenny, Angela Delaney, Stephanie B Dixon, Eric J Chow, Sogol Mostoufi-Moab, Tianzhong Yang, Melissa A Richard, M Monica Gramatges, Philip J Lupo, Noha Sharafeldin, Smita Bhatia, Gregory T Armstrong, Melissa M Hudson, Kirsten K Ness, Leslie L Robison, Yutaka Yasui, Carmen L Wilson, Yadav Sapkota

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Type 2 diabetes mellitus (T2D) is a prevalent long-term complication of treatment in survivors of childhood cancer, with marked racial/ethnic differences in burden. In this study, we investigated trans-ancestral genetic risks for treatment-related T2D.

Patients and methods: Leveraging whole-genome sequencing data from the St Jude Lifetime Cohort (N = 3,676, 304 clinically ascertained cases), we conducted ancestry-specific genome-wide association studies among survivors of African and European genetic ancestry (AFR and EUR, respectively) followed by trans-ancestry meta-analysis. Trans-/within-ancestry replication including data from the Childhood Cancer Survivor Study (N = 5,965) was required for prioritization. Three external general population T2D polygenic …