Medical Specialties Commons^™

High-Dose Chemotherapy And Autologous Stem Cell Transplantation For Relapsed Or Refractory Primary Mediastinal Large B-Cell Lymphoma, Hanan Alkhaldi, Alec Reinhardt, Melissa Barnett, Suprateek Kundu, Chitra Hosing, Jeremy Ramdial, Neeraj Saini, Samer Srour, Amin Alousi, Partow Kebriaei, Uday Popat, Muzaffar Qazilbash, Richard Champlin, Elizabeth J Shpall, Allison Gulbis, Terri Lynn Shigle, Bouthaina Dabaja, Chelsea Pinnix, Sairah Ahmed, Raphael Steiner, Borje S Andersson, Yago Nieto

Faculty, Staff and Student Publications

Primary mediastinal large B-cell lymphoma (PMBCL) is an uncommon, aggressive type of non-Hodgkin lymphoma. Rituximab-containing chemoimmunotherapy with or without radiation therapy (RT) is standard first-line treatment. Relapsed or refractory (R/R) disease has long been treated with salvage chemotherapy followed by high-dose chemotherapy (HDC), with autologous stem cell transplantation (ASCT) in appropriate patients. We retrospectively analyzed all patients with R/R PMBCL treated with HDC/ASCT at our center between January 2000 and August 2022. The 60 study patients received either rituximab-BEAM (n = 37) or rituximab-gemcitabine/busulfan/melphalan (R-GemBuMel) with or without vorinostat (n = 23), followed by ASCT. Forty-six patients received mediastinal RT, …

Care After Premenopausal Risk-Reducing Salpingo-Oophorectomy In High-Risk Women: Scoping Review And International Consensus Recommendations, Denise R Nebgen, Susan M Domchek, Joanne Kotsopoulos, Joanne A De Hullu, Emma J Crosbie, Vincent Singh Paramanandam, Monique M A Brood-Van Zanten, Barbara M Norquist, Theresa Guise, Serge Rozenberg, Allison W Kurian, Holly J Pederson, Nese Yuksel, Rachel Michaelson-Cohen, Sharon L Bober, Agnaldo Lopes Da Silva Filho, Nora Johansen, F Guidozzi, D Gareth Evans, Usha Menon, Sheryl A Kingsberg, C Bethan Powell, Giovanni Grandi, Claudia Marchetti, Michelle Jacobson, Donal J Brennan, Martha Hickey

Faculty, Staff and Student Publications

Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short- and long-term health and provides evidence-based international consensus recommendations for care from preoperative counselling to long-term disease prevention. This includes the efficacy and safety of hormonal and non-hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease.

Opioid-Free Discharge After Pancreatic Resection Through A Learning Health System Paradigm, Artem Boyev, Anish J Jain, Timothy E Newhook, Laura R Prakash, Yi-Ju Chiang, Morgan L Bruno, Elsa M Arvide, Whitney L Dewhurst, Michael P Kim, Jessica E Maxwell, Naruhiko Ikoma, Rebecca A Snyder, Jeffrey E Lee, Matthew H G Katz, Ching-Wei D Tzeng

Faculty, Staff and Student Publications

Importance: Postoperative opioid overprescribing leads to persistent opioid use and excess pills at risk for misuse and diversion. A learning health system paradigm using risk-stratified pancreatectomy clinical pathways (RSPCPs) may lead to reduction in inpatient and discharge opioid volume.

Objective: To analyze the outcomes of 2 iterative RSPCP updates on inpatient and discharge opioid volumes.

Design, setting, and participants: This cohort study included 832 consecutive adult patients at an urban comprehensive cancer center who underwent pancreatic resection between October 2016 and April 2022, comprising 3 sequential pathway cohorts (version [V] 1, October 1, 2016, to January 31, 2019 [n = …

Supportive Care For Dual Caregivers Who Care For Their Partner With Cancer And Their Young Children, Sujin Ann-Yi, Kathrin Milbury, Morgan Jones, Victoria Necroto, Meagan Whisenant, Yisheng Li, Eduardo Bruera

Faculty, Staff and Student Publications

Purpose: Advanced cancer patients and their spouses who parent minor children report parenting concerns and increased psychological distress. This single-arm trial examined the feasibility and initial evidence for efficacy of a novel parent support program.

Methods: Patients with a metastatic solid malignancy and their spouses completed self-reported assessments of psychological distress (HADS), parenting concerns (PCQ) and efficacy (CaPSE) at baseline. Both patients and spouses jointly attended the first two sessions addressing illness communication and family routines. Spouses individually attended two additional sessions focusing on caregiver support and death preparedness. All four sessions were delivered via videoconference by a licensed psychological …

Remotely Delivered Cancer Genetic Testing In The Making Genetic Testing Accessible (Magenta) Trial: A Randomized Clinical Trial, Elizabeth M Swisher, Nadine Rayes, Deborah Bowen, Christine B Peterson, Barbara M Norquist, Tara Coffin, Kathleen Gavin, Deborah Polinsky, Jamie Crase, Jamie N Bakkum-Gamez, Stephanie V Blank, Mark F Munsell, Denise Nebgen, Gini F Fleming, Olufunmilayo I Olopade, Sherman Law, Alicia Zhou, Douglas A Levine, Alan D'Andrea, Karen H Lu

Faculty, Staff and Student Publications

Importance: Requiring personalized genetic counseling may introduce barriers to cancer risk assessment, but it is unknown whether omitting counseling could increase distress.

Objective: To assess whether omitting pretest and/or posttest genetic counseling would increase distress during remote testing.

Design, setting, and participants: Making Genetic Testing Accessible (MAGENTA) was a 4-arm, randomized noninferiority trial testing the effects of individualized pretest and/or posttest genetic counseling on participant distress 3 and 12 months posttest. Participants were recruited via social and traditional media, and enrollment occurred between April 27, 2017, and September 29, 2020. Participants were women aged 30 years or older, English-speaking, US …

Ascertainment Of Minimal Clinically Important Differences In The Diabetes Distress Scale-17: A Secondary Analysis Of A Randomized Clinical Trial, Jack Banks, Amber B Amspoker, Elizabeth M Vaughan, Lechauncy Woodard, Aanand D Naik

Faculty, Staff and Student Publications

IMPORTANCE: The Diabetes Distress Scale-17 (DDS-17) is a common measure of diabetes distress. Despite its popularity, there are no agreed-on minimal clinically important difference (MCID) values for the DDS-17.

OBJECTIVE: to establish a distribution-based metric for MCID in the DDS-17 and its 4 subscale scores (interpersonal distress, physician distress, regimen distress, and emotional distress).

DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of a randomized clinical trial used baseline and postintervention data from a hybrid (implementation-effectiveness) trial evaluating Empowering Patients in Chronic Care (EPICC) vs an enhanced form of usual care (EUC). Participants included adults with uncontrolled type 2 diabetes (glycated …

Health-Related Quality Of Life In A Systematically Assessed Cohort Of Children And Adults With Urea Cycle Disorders, Chaya N Murali, John R Barber, Robert Mccarter, Anqing Zhang, Natalie Gallant, Kara Simpson, Naghmeh Dorrani, Greta N Wilkening, Ron D Hays, Uta Lichter-Konecki, Members Of The Urea Cycle Disorders Consortium, Lindsay C Burrage, Sandesh C S Nagamani

Faculty, Staff and Students Publications

PURPOSE: Individuals with urea cycle disorders (UCDs) may develop recurrent hyperammonemia, episodic encephalopathy, and neurological sequelae which can impact Health-related Quality of Life (HRQoL). To date, there have been no systematic studies of HRQoL in people with UCDs.

METHODS: We reviewed HRQoL and clinical data for 190 children and 203 adults enrolled in a multicenter UCD natural history study. Physical and psychosocial HRQoL in people with UCDs were compared to HRQoL in healthy people and people with phenylketonuria (PKU) and diabetes mellitus. We assessed relationships between HRQoL, UCD diagnosis, and disease severity. Finally, we calculated sample sizes required to detect …

Geographic Variation In Late-Stage Cervical Cancer Diagnosis, Itunu O Sokale, Aaron P Thrift, Jane Montealegre, Victor Adekanmbi, Onyema G Chido-Amajuoyi, Ann Amuta, Lorraine R Reitzel, Abiodun O Oluyomi

Faculty, Staff and Students Publications

IMPORTANCE: There are stark disparities in cervical cancer burden in the United States, notably by race and ethnicity and geography. Late-stage diagnosis is an indicator of inadequate access to and utilization of screening.

OBJECTIVE: To identify geospatial clusters of late-stage cervical cancer at time of diagnosis in Texas.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cross-sectional study used incident cervical cancer data from the Texas Cancer Registry from 2014 to 2018 of female patients aged 18 years or older. Late-stage cervical cancer cases were geocoded at the census tract level (n = 5265) using their residential coordinates (latitude and longitude) at …

Feasibility Of A Dietary Intervention To Modify Gut Microbial Metabolism In Patients With Hematopoietic Stem Cell Transplantation, Mary M Riwes, Jonathan L Golob, John Magenau, Mengrou Shan, Gregory Dick, Thomas Braun, Thomas M Schmidt, Attaphol Pawarode, Sarah Anand, Monalisa Ghosh, John Maciejewski, Darren King, Sung Choi, Gregory Yanik, Marcus Geer, Ethan Hillman, Costas A Lyssiotis, Muneesh Tewari, Pavan Reddy

Faculty, Staff and Students Publications

Evaluation of the impact of dietary intervention on gastrointestinal microbiota and metabolites after allogeneic hematopoietic stem cell transplantation (HCT) is lacking. We conducted a feasibility study as the first of a two-phase trial. Ten adults received resistant potato starch (RPS) daily from day −7 to day 100. The primary objective was to test the feasibility of RPS and its effect on intestinal microbiome and metabolites, including the short-chain fatty acid butyrate. Feasibility met the preset goal of 60% or more, adhering to 70% or more doses; fecal butyrate levels were significantly higher when participants were on RPS than when they …

Relationships Among Intragastric Meal Distribution During Gastric Emptying Scintigraphy, Water Consumption During Water Load Satiety Testing, And Symptoms Of Gastroparesis, Henry P Parkman, Laura A Wilson, Paul Silver, Alan H Maurer, Irene Sarosiek, Robert S Bulat, Braden Kuo, Madhusudan Grover, Gianrico Farrugia, Bruno P Chumpitazi, Robert J Shulman, Zubair Malik, Laura A Miriel, James Tonascia, Frank Hamilton, Thomas L Abell, Pankaj J Pasricha, Richard W Mccallum, Kenneth L Koch, Niddk Gastroparesis Clinical Research Consortium

Faculty, Staff and Students Publications

Gastric emptying scintigraphy (GES) measures total gastric retention after a solid meal and can assess intragastric meal distribution (IMD). Water load satiety test (WLST) measures gastric capacity. Both IMD immediately after meal ingestion [ratio of proximal gastric counts after meal ingestion to total gastric counts at time 0 (IMD⁰)] and WLST (volume of water ingested over 5 min) are indirect measures of gastric accommodation. In this study, IMD⁰ and WLST were compared with each other and to symptoms of gastroparesis to gauge their clinical utility for assessing patients with symptoms of gastroparesis. Patients with symptoms of gastroparesis …

The Development, Content And Response Process Validation Of A Caregiver-Reported Severity Measure For Cdkl5 Deficiency Disorder, Sonja I Ziniel, Alexandra Mackie, Jacinta Saldaris, Helen Leonard, Peter Jacoby, Eric D Marsh, Bernhard Suter, Elia Pestana-Knight, Heather E Olson, Dana Price, Judith Weisenberg, Rajsekar Rajaraman, Gina Vanderveen, Tim A Benke, Jenny Downs, Scott Demarest

Faculty, Staff and Students Publications

BACKGROUND: CDKL5 Deficiency Disorder (CDD) is a severe X-linked developmental and epileptic encephalopathy. Existing developmental outcome measures have floor effects and cannot capture incremental changes in symptoms. We modified the caregiver portion of a CDD clinical severity assessment (CCSA) and assessed content and response-process validity.

METHODS: We conducted cognitive interviews with 15 parent caregivers of 1-39-year-old children with CDD. Caregivers discussed their understanding and concerns regarding appropriateness of both questions and answer options. Item wording and questionnaire structure were adjusted iteratively to ensure questions were understood as intended.

RESULTS: The CCSA was refined during three rounds of cognitive interviews into …

A New Dietary Fiber Can Enhance Satiety And Reduce Postprandial Blood Glucose In Healthy Adults: A Randomized Cross-Over Trial, Simou Wu, Wen Jia, Huimin He, Jun Yin, Huilin Xu, Chengyuan He, Qinqiu Zhang, Yue Peng, Ruyue Cheng

Faculty, Staff and Student Publications

BACKGROUND: Dietary fiber plays a potential role in regulating energy intake and stabilizing postprandial blood glucose levels. Soluble dietary fiber has become an important entry point for nutritional research on the regulation of satiety.

METHODS: this was a double-blind, randomized cross-over trial enrolling 12 healthy subjects to compare the effects of RPG (R+PolyGly) dietary fiber products (bread, powder, and capsule) and pectin administered with a standard meal on satiety, blood glucose, and serum insulin level.

RESULTS: Adding 3.8% RPG dietary fiber to bread significantly increased the volume, water content, hardness, and chewiness of bread compared to 3.8% pectin bread and …

Targeted Therapy With Nanatinostat And Valganciclovir In Recurrent Ebv-Positive Lymphoid Malignancies: A Phase 1b/2 Study, Bradley Haverkos, Onder Alpdogan, Robert Baiocchi, Jonathan E. Brammer, Tatyana A. Feldman, Marcelo Capra, Elizabeth A. Brem, Santosh Nair, Phillip Scheinberg, Juliana Pereira, Leyla Shune, Erel Joffe, Patricia Young, Susan Spruill, Afton Katkov, Robert Mcrae, Ivor Royston, Douglas V. Faller, Lisa Rojkjaer, Pierluigi Porcu

Department of Medical Oncology Faculty Papers

Lymphomas are not infrequently associated with the Epstein-Barr virus (EBV), and EBV positivity is linked to worse outcomes in several subtypes. Nanatinostat is a class-I selective oral histone deacetylase inhibitor that induces the expression of lytic EBV BGLF4 protein kinase in EBV+ tumor cells, activating ganciclovir via phosphorylation, resulting in tumor cell apoptosis. This phase 1b/2 study investigated the combination of nanatinostat with valganciclovir in patients aged ≥18 years with EBV+ lymphomas relapsed/refractory to ≥1 prior systemic therapy with no viable curative treatment options. In the phase 1b part, 25 patients were enrolled into 5 dose escalation cohorts to determine …

Identification Of Dual Strn-Ntrk2 Rearrangements In A High Grade Sarcoma, With Good Clinical Response To First-Line Larotrectinib Therapy, Ruihe Lin, Atrayee Basu Mallick, Zi-Xuan Wang, Phd, Scot Andrew Brown, Bo Lu, Md, Wei Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Among the three NTRK genes, NTRK2 possesses a tremendous structural complexity and involves tumorigenesis of several types of tumors. To date, only STRN and RBPMS are identified in the fusion with NTRK2 in adult soft tissue tumors. More recently, the highly selective Trk tyrosine kinases inhibitors, including larotrectinib and entrectinib, have shown significant efficacy for treating tumors harboring NTRK fusions and were approved by FDA.

CASE PRESENTATION: We report a case of sarcoma in a 35-year-old female harboring two STRN-NTRK2 gene fusions, with a good clinical response to first-line larotrectinib treatment. Core biopsy of the 16.5 cm gluteal mass …

Early Resveratrol Treatment Mitigates Joint Degeneration And Dampens Pain In A Mouse Model Of Pseudoachondroplasia (Psach), Jacqueline T Hecht, Alka C Veerisetty, Debabrata Patra, Mohammad G Hossain, Frankie Chiu, Claire Mobed, Francis H Gannon, Karen L Posey

Faculty, Staff and Student Publications

Pseudoachondroplasia (PSACH), a severe dwarfing condition associated with early-onset joint degeneration and lifelong joint pain, is caused by mutations in cartilage oligomeric matrix protein (COMP). The mechanisms underlying the mutant-COMP pathology have been defined using the MT-COMP mouse model of PSACH that has the common D469del mutation. Mutant-COMP protein does not fold properly, and it is retained in the rough endoplasmic reticulum (rER) of chondrocytes rather than being exported to the extracellular matrix (ECM), driving ER stress that stimulates oxidative stress and inflammation, driving a self-perpetuating cycle. CHOP (ER stress signaling protein) and TNFα inflammation drive high levels of mTORC1 …

Lower Versus Higher Oxygen Targets For Out-Of-Hospital Cardiac Arrest: A Systematic Review And Meta-Analysis, Xin Cheng, Yu Zhang, Haidong Deng, Yuning Feng, Weelic Chong, Yang Hai, Pengfei Hao, Jialing He, Tiangui Li, Liyuan Peng, Peng Wang, Yangchun Xiao, Fang Fang

Student Papers, Posters & Projects

BACKGROUND: Supplemental oxygen is commonly administered to patients after out-of-hospital cardiac arrest. However, the findings from studies on oxygen targeting for out-of-hospital cardiac arrest are inconclusive. Thus, we conducted a systematic review and meta-analysis to evaluate the impact of lower oxygen target compared with higher oxygen target on patients after out-of-hospital cardiac arrest.

METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, from inception to February 6, 2023, for randomized controlled trials comparing lower and higher oxygen target in adults (aged ≥ 18 years) after out-of-hospital cardiac arrest. We screened studies and extracted data independently. The primary …

Endothelial Dysfunction And Cardiometabolic Risk Factors In Mexican American Adults: The Cameron County Hispanic Cohort, Enrique Garcia-Sayan, Miryoung Lee, James R Stone, Danielle M Stone, Beverly Smulevitz, David D Mcpherson, Susan P Fisher-Hoch, Joseph B Mccormick, Susan T Laing

Faculty, Staff and Students Publications

Endothelial dysfunction assessed by impaired brachial flow-mediated dilation (FMD) predicts incident cardiovascular disease (CVD). We have previously shown that clustering of diabetes mellitus, obesity, and metabolic syndrome in young Hispanic patients was associated with subclinical atherosclerosis. This study aimed to assess determinants of impaired FMD response (%FMD), an earlier marker of atherosclerosis, in a population-based sample of asymptomatic Mexican Americans. Cardiometabolic biomarkers and FMD were obtained from 960 Cameron County Hispanic Cohort participants. Gender-specific median values of %FMD were used to categorize participants into those with %FMD below or above the median. The sample was further stratified into those younger …

Tuberculosis Presentation And Outcomes In Older Hispanic Adults From Tamaulipas, Mexico, Belinda A Medrano, Miryoung Lee, Gretchen Gemeinhardt, Javier E Rodríguez-Herrera, Moncerrato García-Viveros, Blanca I Restrepo

Faculty, Staff and Student Publications

Older people are at high risk of developing and dying from pulmonary infections like tuberculosis (TB), but there are few studies among them, particularly in Hispanics. To address these gaps, we sought to identify host factors associated with TB and adverse treatment outcomes in older Hispanics by conducting a cross-sectional study of TB surveillance data from Tamaulipas, Mexico (2006-2013; n = 8381). Multivariable logistic regressions were assessed for older adults (OA ≥65 years) when compared to young (YA, 18-39 years) and middle-aged adults (40-64 years). We found that the OA had features associated with a less complicated TB (e.g., lower …

Immune-Depleted Tumor Microenvironment Is Associated With Poor Outcomes And Btk Inhibitor Resistance In Mantle Cell Lymphoma, Preetesh Jain, Krystle Nomie, Nikita Kotlov, Vitaiy Segodin, Holly Hill, Chi Young Ok, Ahmed Fetooh, Rashmi Kanagal-Shamanna, Francisco Vega, Alexander Bagaev, Nathan Fowler, Christopher R Flowers, Michael Wang

Faculty, Staff and Student Publications

Mantle cell lymphoma (MCL) is a generally aggressive B cell non-Hodgkin lymphoma (B-NHL). Outcomes of patients have improved in the era of Bruton’s tyrosine kinase inhibitors (BTKi). However, MCL patients can develop resistance to BTKi over time and can progress [1]. Ibrutinib resistance in MCL is correlated with an overexpression of OXPHOS, MYC and PI3K/AKT/m-TOR pathways. Somatic mutations in TP53, KMT2D, NSD2, SMARCA4, CCND1, TRAF2, NFKBIE genes are reported with ibrutinib resistance [2]. A few reports have also demonstrated that a decrease in T cell numbers [3, 4] or a downregulation of effector/cytotoxic …

Complete Loss Of Tp53 And Rb1 Is Associated With Complex Genome And Low Immune Infiltrate In Pleomorphic Rhabdomyosarcoma, Hannah C Beird, Chia-Chin Wu, Michael Nakazawa, Davis Ingram, Joseph R Daniele, Rossana Lazcano, Latasha Little, Christopher Davies, Najat C Daw, Khalida Wani, Wei-Lien Wang, Xingzhi Song, Curtis Gumbs, Jianhua Zhang, Brian Rubin, Anthony Conley, Adrienne M Flanagan, Alexander J Lazar, P Andrew Futreal

Faculty, Staff and Student Publications

Rhabdomyosarcoma accounts for roughly 1% of adult sarcomas, with pleomorphic rhabdomyosarcoma (PRMS) as the most common subtype. Survival outcomes remain poor for patients with PRMS, and little is known about the molecular drivers of this disease. To better characterize PRMS, we performed a broad array of genomic and immunostaining analyses on 25 patient samples. In terms of gene expression and methylation, PRMS clustered more closely with other complex karyotype sarcomas than with pediatric alveolar and embryonal rhabdomyosarcoma. Immune infiltrate levels in PRMS were among the highest observed in multiple sarcoma types and contrasted with low levels in other rhabdomyosarcoma subtypes. …

A Proof-Of-Concept Pilot Test Of A Behavioral Intervention To Improve Adherence To Dietary Recommendations For Cancer Prevention, Meghan Butryn, Charlotte Hagerman, Nicole Crane, Marny Ehmann, Evan Forman, Brandy-Joe Milliron, Nicole L. Simone

Department of Radiation Oncology Faculty Papers

OBJECTIVES: Prevention programs that can help adults improve the quality of their diets to reduce cancer risk are needed. This Phase IIa study prospectively tested a mHealth intervention designed to improve adherence to dietary quality guidelines for cancer prevention.

METHODS: All participants (N = 62) received nutrition education and a self-regulation skills curriculum, with a primary target of changing grocery shopping behavior. Using a randomized, factorial design, the study varied whether each of the following 4 components were added to the 20-week intervention: (1) location-triggered app messaging, delivered when individuals arrived at grocery stores, (2) reflections on benefits of change, …

First-In-Human, Phase I Dose-Escalation And Dose-Expansion Study Of Trophoblast Cell-Surface Antigen 2-Directed Antibody-Drug Conjugate Datopotamab Deruxtecan In Non-Small-Cell Lung Cancer: Tropion-Pantumor01, Toshio Shimizu, Jacob Sands, Kiyotaka Yoh, Alexander Spira, Edward B Garon, Satoru Kitazono, Melissa L Johnson, Funda Meric-Bernstam, Anthony W Tolcher, Noboru Yamamoto, Jon Greenberg, Yui Kawasaki, Hong Zebger-Gong, Fumiaki Kobayashi, Penny Phillips, Aaron E Lisberg, Rebecca S Heist

Faculty, Staff and Student Publications

PURPOSE: This first-in-human, dose-escalation and dose-expansion study evaluated the safety, tolerability, and antitumor activity of datopotamab deruxtecan (Dato-DXd), a novel trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugate in solid tumors, including advanced non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS: Adults with locally advanced/metastatic NSCLC received 0.27-10 mg/kg Dato-DXd once every 3 weeks during escalation or 4, 6, or 8 mg/kg Dato-DXd once every 3 weeks during expansion. Primary end points were safety and tolerability. Secondary end points included objective response rate (ORR), survival, and pharmacokinetics.

RESULTS: Two hundred ten patients received Dato-DXd, including 180 in the 4-8 mg/kg dose-expansion cohorts. …

Nasal Iodophor Antiseptic Vs Nasal Mupirocin Antibiotic In The Setting Of Chlorhexidine Bathing To Prevent Infections In Adult Icus: A Randomized Clinical Trial, Susan S Huang, Edward J Septimus, Ken Kleinman, Lauren T Heim, Julia A Moody, Taliser R Avery, Laura Mclean, Syma Rashid, Katherine Haffenreffer, Lauren Shimelman, Whitney Staub-Juergens, Caren Spencer-Smith, Selsebil Sljivo, Ed Rosen, Russell E Poland, Micaela H Coady, Chi Hyun Lee, Eunice J Blanchard, Kimberly Reddish, Mary K Hayden, Robert A Weinstein, Brandon Carver, Kimberly Smith, Jason Hickok, Karen Lolans, Nadia Khan, S Gwynn Sturdevant, Sujan C Reddy, John A Jernigan, Kenneth E Sands, Jonathan B Perlin, Richard Platt

Faculty, Staff and Student Publications

IMPORTANCE: Universal nasal mupirocin plus chlorhexidine gluconate (CHG) bathing in intensive care units (ICUs) prevents methicillin-resistant Staphylococcus aureus (MRSA) infections and all-cause bloodstream infections. Antibiotic resistance to mupirocin has raised questions about whether an antiseptic could be advantageous for ICU decolonization.

OBJECTIVE: To compare the effectiveness of iodophor vs mupirocin for universal ICU nasal decolonization in combination with CHG bathing.

DESIGN, SETTING, AND PARTICIPANTS: Two-group noninferiority, pragmatic, cluster-randomized trial conducted in US community hospitals, all of which used mupirocin-CHG for universal decolonization in ICUs at baseline. Adult ICU patients in 137 randomized hospitals during baseline (May 1, 2015-April 30, 2017) …

Ccdc50 Promotes Tumor Growth Through Regulation Of Lysosome Homeostasis, Penghui Jia, Tian Tian, Zibo Li, Yicheng Wang, Yuxin Lin, Weijie Zeng, Yu Ye, Miao He, Xiangrong Ni, Ji'an Pan, Xiaonan Dong, Jian Huang, Chun-Mei Li, Deyin Guo, Panpan Hou

Faculty, Staff and Student Publications

The maintenance of lysosome homeostasis is crucial for cell growth. Lysosome-dependent degradation and metabolism sustain tumor cell survival. Here, we demonstrate that CCDC50 serves as a lysophagy receptor, promoting tumor progression and invasion by controlling lysosomal integrity and renewal. CCDC50 monitors lysosomal damage, recognizes galectin-3 and K63-linked polyubiquitination on damaged lysosomes, and specifically targets them for autophagy-dependent degradation. CCDC50 deficiency causes the accumulation of ruptured lysosomes, impaired autophagic flux, and superfluous reactive oxygen species, consequently leading to cell death and tumor suppression. CCDC50 expression is associated with malignancy, progression to metastasis, and poor overall survival in human melanoma. Targeting CCDC50 …

Müllerian-Type Clear Cell Carcinoma Of Donor Origin In A Male Patient With A Kidney Transplant: Ascertained By Molecular Testing, J Bryan Iorgulescu, Leah K Shaw, Asif Rashid, Priya Rao, Sreedhar Mandayam, Keyur P Patel, Kathleen M Schmeler, Richard K Yang, Pavlos Msaouel

Faculty, Staff and Student Publications

Clear cell carcinomas of Müllerian origin have a strong female predominance and only extremely rarely will arise within the kidney, presumably due to ectopic Müllerian embryogenesis. Herein, we report a unique case of metastatic Müllerian type clear cell carcinoma in a 37-year-old patient who had previously received a transplanted kidney from his father at age 11 (due to severe bilateral vesicoureteral reflux) and remained on chronic immunosuppression. The tumor was highly aggressive and demonstrated somatic mutations in NF2 and SETD2. Imaging of the transplanted kidney did not reveal any clear evidence of malignancy. However, targeted multigene sequencing and short tandem …

Pls3 Missense Variants Affecting The Actin-Binding Domains Cause X-Linked Congenital Diaphragmatic Hernia And Body-Wall Defects, Florence Petit, Mauro Longoni, Julie Wells, Richard S Maser, Eric L Bogenschutz, Matthew J Dysart, Hannah T M Contreras, Frederic Frénois, Barbara R Pober, Robin D Clark, Philip F Giampietro, Hilger H Ropers, Hao Hu, Maria Loscertales, Richard Wagner, Xingbin Ai, Harrison Brand, Anne-Sophie Jourdain, Marie-Ange Delrue, Brigitte Gilbert-Dussardier, Louise Devisme, Boris Keren, David J Mcculley, Lu Qiao, Rebecca Hernan, Julia Wynn, Tiana M Scott, Daniel G Calame, Zeynep Coban-Akdemir, Patricia Hernandez, Andres Hernandez-Garcia, Hagith Yonath, James R Lupski, Yufeng Shen, Wendy K Chung, Daryl A Scott, Carol J Bult, Patricia K Donahoe, Frances A High

Faculty, Staff and Student Publications

Congenital diaphragmatic hernia (CDH) is a relatively common and genetically heterogeneous structural birth defect associated with high mortality and morbidity. We describe eight unrelated families with an X-linked condition characterized by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. Using linkage analysis and exome or genome sequencing, we found that missense variants in plastin 3 (PLS3), a gene encoding an actin bundling protein, co-segregate with disease in all families. Loss-of-function variants in PLS3 have been previously associated with X-linked osteoporosis (MIM: 300910), so we used in silico protein modeling and a mouse model to address these seemingly disparate clinical …

Vertebral Tortuosity Is Associated With Increased Rate Of Cardiovascular Events In Vascular Ehlers-Danlos Syndrome, Sara B Stephens, Sherene Shalhub, Nicholas Dodd, Jesse Li, Michael Huang, Seitaro Oda, Kalyan Kancherla, Tam T Doan, Siddharth K Prakash, Justin D Weigand, Federico M Asch, Taylor Beecroft, Alana Cecchi, Teniola Shittu, Liliana Preiss, Scott A Lemaire, Richard B Devereux, Reed E Pyeritz, Kathryn W Holmes, Mary J Roman, Ronald V Lacro, Ralph V Shohet, Rajesh Krishnamurthy, Kim Eagle, Peter Byers, Dianna M Milewicz, Shaine A Morris

Faculty, Staff and Student Publications

Background Arterial tortuosity is associated with adverse events in Marfan and Loeys-Dietz syndromes but remains understudied in Vascular Ehlers-Danlos syndrome. Methods and Results Subjects with a pathogenic

Association Of Parental Status And Gender With Burden Of Multidisciplinary Tumor Boards Among Oncology Physicians, Brittney L Chau, Jonnby S Laguardia, Sungjin Kim, Samuel C Zhang, Eric Pletcher, Nina N Sanford, Ann C Raldow, Lisa Singer, Jun Gong, Sukhmani K Padda, Mitchell Kamrava, Tara Cohen, Devarati Mitra, Katelyn M Atkins

Faculty, Staff and Student Publications

IMPORTANCE: Tumor boards are integral to the care of patients with cancer. However, data investigating the burden of tumor boards on physicians are limited.

OBJECTIVE: To investigate what physician-related and tumor board-related factors are associated with higher tumor board burden among oncology physicians.

DESIGN, SETTING, AND PARTICIPANTS: Tumor board burden was assessed by a cross-sectional convenience survey posted on social media and by email to Cedars-Sinai Medical Center cancer physicians between March 3 and April 3, 2022. Tumor board start times were independently collected by email from 22 top cancer centers.

MAIN OUTCOMES AND MEASURES: Tumor board burden was measured …

Safety And Tolerability Of A Novel Anti-Her2 Antibody-Drug Conjugate (Pf-06804103) In Patients With Her2-Expressing Solid Tumors: A Phase 1 Dose-Escalation Study, Funda Meric-Bernstam, Emiliano Calvo, Keun Seok Lee, Victor Moreno, Yeon Hee Park, Sun Young Rha, Pavani Chalasani, Wei Zhong, Li Zhou, Steven Pirie-Shepherd, Abraham C F Leung, Giuseppe Curigliano

Faculty, Staff and Student Publications

PF-06804103 is an anti-HER2 antibody–drug conjugate with auristatin payload. We evaluated its safety, tolerability, and antitumor activity in patients with advanced/unresectable or metastatic breast and gastric cancers. This multicenter, open-label, first-in-human, phase 1 study (NCT03284723) comprised dose escalation (P1) and dose expansion (P2). In P1, adults with HER2+ breast or gastric cancer received PF-06804103 0.15–5.0 mg/kg intravenously once/21 days (Q3W); in P2, patients with HER2+ or HER2-low (IHC 1+ or IHC 2+/ISH−) breast cancer received 3.0 or 4.0 mg/kg Q3W. The primary endpoints were dose-limiting toxicities (DLT) and safety (P1), and objective response rate (ORR) assessed using RECIST v1.1 (P2). …

Pretibial Myxedema: An Unusual Presentation, Dāsha Giger, Christina E. Borchers, Samia Borchers

Dermatology Faculty Publications

Pretibial myxedema presents with indurated nodules or plaques that can be erythematous or vary in color from purple-brown to yellow. It is noted that a peau d’orange appearanceis a characteristic finding. These lesions are typically located on the anterolateral aspect of the lower legs. Non-pitting edema of the shins that evolves into elephantiasis is anotherpotential presentation seen in pretibial myxedema. It is often associated with hyperthyroidism, particularly Graves disease and is more commonly seen in women than men.Typically, it presents during the third or fourth decade of life. Differential diagnoses include but are not limited to stasis dermatitis, hypertrophic lichen …