Medical Specialties Commons^™

Immuno-Molecular Targeted Therapy Use And Survival Benefit In Patients With Stage Ivb Cervical Carcinoma In Commission On Cancer, Collin A Sitler, Chunqiao Tian, Chad A Hamilton, Michael T Richardson, John K Chan, Daniel S Kapp, Charles A Leath, Yovanni Casablanca, Christina Washington, Nicole P Chappell, Ann H Klopp, Craig D Shriver, Christopher M Tarney, Nicholas W Bateman, Thomas P Conrads, George Larry Maxwell, Neil T Phippen, Kathleen M Darcy

Faculty, Staff and Student Publications

PURPOSE: To investigate IMT use and survival in real-world stage IVB cervical cancer patients outside randomized clinical trials.

METHODS: Patients diagnosed with stage IVB cervical cancer during 2013-2019 in the National Cancer Database and treated with chemotherapy (CT) ± external beam radiation (EBRT) ± intracavitary brachytherapy (ICBT) ± IMT were studied. The adjusted hazard ratio (AHR) and 95% confidence interval (CI) for risk of death were estimated in patients treated with vs. without IMT after applying propensity score analysis to balance the clinical covariates.

RESULTS: There were 3164 evaluable patients, including 969 (31%) who were treated with IMT. The use …

Caldendrin Is A Repressor Of Piezo2 Channels And Touch Sensation In Mice, Josue A Lopez, Luis O Romero, Wai-Lin Kaung, J Wesley Maddox, Valeria Vásquez, Amy Lee

Faculty, Staff and Student Publications

The sense of touch is crucial for cognitive, emotional, and social development and relies on mechanically activated (MA) ion channels that transduce force into an electrical signal. Despite advances in the molecular characterization of these channels, the physiological factors that control their activity are poorly understood. Here, we used behavioral assays, electrophysiological recordings, and various mouse strains (males and females analyzed separately) to investigate the role of the calmodulin-like Ca2+ sensor, caldendrin, as a key regulator of MA channels and their roles in touch sensation. In mice lacking caldendrin (Cabp1 KO), heightened responses to tactile stimuli correlate with enlarged …

Transcriptomic, Proteomic, And Genomic Mutational Fraction Differences Based On Hpv Status Observed In Patient-Derived Xenograft Models Of Penile Squamous Cell Carcinoma, Niki M Zacharias, Luis Segarra, Keiko Akagi, Natalie Wall Fowlkes, Huiqin Chen, Angelita Alaniz, Carolyn De La Cerda, Pedro Pesquera, Yuanxin Xi, Jing Wang, Jad Chahoud, Xin Lu, Priya Rao, Magaly Martinez-Ferrer, Curtis A Pettaway

Faculty, Staff and Student Publications

Simple Summary

Penile cancer is a rare but aggressive cancer. After it metastasizes, the median survival time is less than 12 months. The overall response rate to common first-line combination chemotherapy treatments is approximately 50%. There is an urgent need in advanced-penile-cancer treatment to find novel therapies that would generate better response rates than standard chemotherapy thus far and have less toxicity. Partially due to its rarity, there are few animal models and cell lines of penile cancer. We report on the generation of seven penile cancer animal models that were created by directly implanting human tumor tissue into immunocompromised …

Geographic Distribution Of Human Infections With Zoonotic Ancylostoma Ceylanicum And Anthropophilic Hookworms In Ecuador: A Retrospective Analysis Of Archived Stool Samples, Dayana Aguilar-Rodríguez, Victor Seco-Hidalgo, Andrea Lopez, Natalia Romero-Sandoval, Manuel Calvopiña, Angel Guevara, Lucy Baldeón, Alejandro Rodríguez, Rojelio Mejia, Thomas B Nutman, William J Sears, Philip J Cooper

Faculty, Staff and Students Publications

Zoonotic human infections with Ancylostoma ceylanicum have recently been reported in the Americas. We used archived human stool samples to study the geographic distribution of human infections with A. ceylanicum and anthropophilic hookworms in different geoclimatic regions (coastal, Andean, and Amazon) of Ecuador. We analyzed retrospectively archived human stool samples from five studies previously screened for hookworm infection by microscopy, of which four included hookworm-positive samples only and one involved hookworm-negative samples to increase geographic distribution of sampling. Stools were analyzed using multi-parallel quantitative polymerase chain reaction (qPCR) assays to detect Necator americanus, Ancylostoma duodenale, A. ceylanicum, Ascaris lumbricoides, Trichuris …

A Systematic Review Of Naldemedine And Naloxegol For The Treatment Of Opioid-Induced Constipation In Cancer Patients, Ursula K Braun, Leanne K Jackson, Mary A Garcia, Syed N Imam

Center for Medical Ethics and Health Policy Staff Publications

Background: Opioid-induced constipation (OIC) is a pervasive and distressing side effect of chronic opioid therapy in patients with cancer pain, significantly impacting their quality of life. Peripherally acting μ-opioid receptor antagonists (PAMORAS) were developed for treatment-resistant OIC but most studies were conducted with non-cancer patients.

Objective: to discuss two oral formulations of PAMORAs, naldemedine and naloxegol, and to review available evidence of the effectiveness of these drugs for OIC in cancer patients.

Methods: a comprehensive search to identify primary literature for either naldemedine or naloxegol for OIC in cancer patients.

Results: Only three prospective randomized, double-blind, placebo-controlled clinical trials for …

Enhancing Prognostic Power In Multiple Myeloma Using A Plasma Cell Signature Derived From Single-Cell Rna Sequencing, Jian-Rong Li, Shahram Arsang-Jang, Yan Cheng, Fumou Sun, Anita D'Souza, Binod Dhakal, Parameswaran Hari, Quillan Huang, Paul Auer, Yong Li, Raul Urrutia, Fenghuang Zhan, John D Shaughnessy, Siegfried Janz, Jing Dong, Chao Cheng

Faculty, Staff and Students Publications

Multiple myeloma (MM) is a heterogenous plasma cell malignancy, for which the established prognostic models exhibit limitations in capturing the full spectrum of outcome variability. Leveraging single-cell RNA-sequencing data, we developed a novel plasma cell gene signature. We evaluated and validated the associations of the resulting plasma cell malignancy (PBM) score with disease state, progression and clinical outcomes using data from five independent myeloma studies consisting of 2115 samples (1978 MM, 65 monoclonal gammopathy of undetermined significance, 35 smoldering MM, and 37 healthy controls). Overall, a higher PBM score was significantly associated with a more advanced stage within the spectrum …

Inactivation Of Adenosine Receptor 2a Suppresses Endothelial-To-Mesenchymal Transition And Inhibits Subretinal Fibrosis In Mice, Qiuhua Yang, Yongfeng Cai, Qian Ma, Albert Xiong, Peishan Xu, Zhidan Zhang, Jiean Xu, Yaqi Zhou, Zhiping Liu, Dingwei Zhao, John Asara, Wei Li, Huidong Shi, Ruth B Caldwell, Akrit Sodhi, Yuqing Huo

Faculty, Staff and Students Publications

Anti–vascular endothelial growth factor therapy has had a substantial impact on the treatment of choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (nAMD), the leading cause of vision loss in older adults. Despite treatment, many patients with nAMD still develop severe and irreversible visual impairment because of the development of subretinal fibrosis. We recently reported the anti-inflammatory and antiangiogenic effects of inhibiting the gene encoding adenosine receptor 2A (Adora2a), which has been implicated in cardiovascular disease. Here, using two mouse models of subretinal fibrosis (mice with laser injury–induced CNV or mice with a deficiency in the …

Rational Prescribing Of Pancreatic Enzymes For Patients With Pancreatic Cancer, Mary Acelle G Garcia, Syed Imam, Ursula K Braun, Leanne K Jackson

Center for Medical Ethics and Health Policy Staff Publications

Most patients with pancreatic cancer at some point present with symptoms related to exocrine pancreatic insufficiency (EPI). These include diarrhea, abdominal bloating, indigestion, steatorrhea, weight loss, and anorexia. Even though up to 80% of pancreatic cancer patients eventually present with symptoms related to exocrine pancreatic insufficiency, only 21% are prescribed pancreatic enzyme replacement therapy (PERT). Its effectiveness is also highly dependent on its proper timing of administration, and patients must be thoroughly educated about this. The impact of symptoms of EPI can lead to poorer overall well-being. Pharmacists play a crucial role in properly educating patients on the correct use …

Correction: Jiménez-Ortigosa Et Al Cryo-Electron Tomography Of Candida Glabrata Plasma Membrane Proteins J Fungi 2021, 7, 120, Cristina Jiménez-Ortigosa, Jennifer Jiang, Muyuan Chen, Xuyuan Kuang, Kelley R Healey, Paul Castellano, Nikpreet Boparai, Steven J Ludtke, David S Perlin, Wei Dai

Faculty, Staff and Students Publications

The authors wish to update the article title to "Cryo-Electron Tomography of Candida glabrata Plasma Membrane Proteins" [...].

Muc20 Regulated By Extrachromosomal Circular Dna Attenuates Proteasome Inhibitor Resistance Of Multiple Myeloma By Modulating Cuproptosis, Xiaobin Wang, Yingqing Shi, Hua Shi, Xiaoyu Liu, Aijun Liao, Zhuogang Liu, Robert Z Orlowski, Rui Zhang, Huihan Wang

Faculty, Staff and Student Publications

BACKGROUND: Proteasome inhibitors (PIs) are one of the most important classes of drugs for the treatment of multiple myeloma (MM). However, almost all patients with MM develop PI resistance, resulting in therapeutic failure. Therefore, the mechanisms underlying PI resistance in MM require further investigation.

METHODS: We used several MM cell lines to establish PI-resistant MM cell lines. We performed RNA microarray and EccDNA-seq in MM cell lines and collected human primary MM samples to explore gene profiles. We evaluated the effect of MUC20 on cuproptosis of PI-resistant MM cells using Co-immunoprecipitation (Co-IP), Seahorse bioenergetic profiling and in vivo assay.

RESULTS: …

Hypertension In Pregnancy Among Immigrant And Swedish Women: A Cohort Study Of All Pregnant Women In Sweden, Per Wändell, Casey Crump, Xinjun Li, Nouha Saleh Stattin, Axel C Carlsson, Jan Sundquist, Kristina Sundquist

Faculty, Staff and Student Publications

BACKGROUND: Little is known about risks of hypertensive disorders of pregnancy in both first- and second-generation immigrant women in Europe and other Western countries; such knowledge may help elucidate the influence of genetic versus social factors on such risks. We aimed to study both first- and second-generation immigrant women for the presence of all types of hypertension (preexisting hypertension, gestational hypertension, preeclampsia, and eclampsia) during pregnancy.

METHODS AND RESULTS: A cohort study was conducted using data derived from the Swedish National Birth Register, the National Patient Register, and the total Population Register. We used Cox regression analysis to compute hazard …

Potential Protein Signatures For Recurrence Prediction Of Ischemic Stroke, Chengyi Zhang, Yang Liu, Huimin Zhu, Xinying Huang, Cang Guo, Si Cheng, Meng Yuan, Yong Jiang, Xia Meng, S Claiborne Johnston, Yongjun Wang, Wei-Na Jin, Fu-Dong Shi

Faculty, Staff and Student Publications

Background: Acute ischemic stroke is a major cause of mortality and disability worldwide, with approximately 7.4% to 7.7% recurrence within the first 3 months. This study aimed to identify potential biomarkers for predicting stroke recurrence.

Methods and results: We conducted a nested case-control study using a hospital-based cohort from the Third China National Stroke Registry selecting 214 age- and sex-matched patients with ischemic stroke with hypertension and no history of diabetes or heart disease. Using data-independent acquisition for discovery and multiple reaction monitoring for quantitative validation, we identified 26 differentially expressed proteins in large-artery atherosclerosis (Causative Classification of Ischemic Stroke …

Sex Differences In Revascularization, Treatment Goals, And Outcomes Of Patients With Chronic Coronary Disease: Insights From The Ischemia Trial, Harmony R Reynolds, Derek D Cyr, C Noel Bairey Merz, Leslee J Shaw, Bernard R Chaitman, William E Boden, Karen P Alexander, Yves D Rosenberg, Sripal Bangalore, Gregg W Stone, Claes Held, John Spertus, Kaatje Goetschalckx, Olga Bockeria, Jonathan D Newman, Jeffrey S Berger, Ahmed Elghamaz, Renato D Lopes, James K Min, Daniel S Berman, Michael H Picard, Raymond Y Kwong, Robert A Harrington, Boban Thomas, Sean M O'Brien, David J Maron, Judith S Hochman, Ischemia Research Group

Faculty, Staff and Student Publications

BACKGROUND: Women with chronic coronary disease are generally older than men and have more comorbidities but less atherosclerosis. We explored sex differences in revascularization, guideline-directed medical therapy, and outcomes among patients with chronic coronary disease with ischemia on stress testing, with and without invasive management.

METHODS AND RESULTS: The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial randomized patients with moderate or severe ischemia to invasive management with angiography, revascularization, and guideline-directed medical therapy, or initial conservative management with guideline-directed medical therapy alone. We evaluated the primary outcome (cardiovascular death, myocardial infarction, or hospitalization for …

Endovascular Thrombectomy For Large Ischemic Stroke Across Ischemic Injury And Penumbra Profiles, Amrou Sarraj, Ameer E Hassan, Michael G Abraham, Santiago Ortega-Gutierrez, Scott E Kasner, Muhammad Shazam Hussain, Michael Chen, Leonid Churilov, Hannah Johns, Clark W Sitton, Vignan Yogendrakumar, Felix C Ng, Deep K Pujara, Spiros Blackburn, Sophia Sundararajan, Yin C Hu, Nabeel A Herial, Juan F Arenillas, Jenny P Tsai, Ronald F Budzik, William J Hicks, Osman Kozak, Bernard Yan, Dennis J Cordato, Nathan W Manning, Mark W Parsons, Andrew Cheung, Ricardo A Hanel, Amin N Aghaebrahim, Teddy Y Wu, Pere Cardona Portela, Chirag D Gandhi, Fawaz Al-Mufti, Natalia Pérez De La Ossa, Joanna D Schaafsma, Jordi Blasco, Navdeep Sangha, Steven Warach, Timothy J Kleinig, Faris Shaker, Faisal Al Shaibi, Gabor Toth, Mohammad A Abdulrazzak, Gagan Sharma, Abhishek Ray, Jeffrey Sunshine, Amanda Opaskar, Kelsey R Duncan, Wei Xiong, Edgar A Samaniego, Laith Maali, Colleen G Lechtenberg, Arturo Renú, Nirav Vora, Thanh Nguyen, Johanna T Fifi, Stavropoula I Tjoumakaris, Pascal Jabbour, Georgios Tsivgoulis, Vitor Mendes Pereira, Maarten G Lansberg, Michael Degeorgia, Cathy A Sila, Nicholas Bambakidis, Michael D Hill, Stephen M Davis, Lawrence Wechsler, James C Grotta, Marc Ribo, Greg W Albers, Bruce C Campbell

Faculty, Staff and Student Publications

Importance: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain.

Objective: To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect.

Design, setting, and participants: An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 …

Unraveling The Intraday Variations In The Tear Fluid Proteome, Garrett Jones, Jeremy Altman, Saleh Ahmed, Tae Jin Lee, Wenbo Zhi, Shruti Sharma, Ashok Sharma

Faculty, Staff and Student Publications

PURPOSE: Tear fluid is a complex and dynamic biological fluid that plays essential roles in maintaining ocular homeostasis and protecting against the external environment. Owing to the small sample volume, studying the tear proteome is challenging. However, advances in high-resolution mass spectrometry have expanded tear proteome profiling, revealing >500 unique proteins. Tears are emerging as a noninvasive source of biomarkers for both ocular and systemic diseases; nevertheless, intraday variability of proteins in tear fluid remains questionable. This study investigates intraday variations in the tear fluid proteome to identify stable proteins that could act as candidate biomarkers.

METHODS: Tear samples from …

Eef1a2 Promotes Pten-Gsk3Β-Scf Complex-Dependent Degradation Of Aurora Kinase A And Is Inactivated In Breast Cancer, Warapen Treekitkarnmongkol, Luisa M Solis, Deivendran Sankaran, Mihai Gagea, Pankaj K Singh, Ragini Mistry, Tristian Nguyen, Kazuharu Kai, Jiajun Liu, Kaori Sasai, Yoshimi Jitsumori, Jianwen Liu, Norio Nagao, Fabio Stossi, Michael A Mancini, Ignacio I Wistuba, Alastair M Thompson, Jonathan M Lee, Juan Cadiñanos, Kwong-Kwok Wong, Catherine M Abbott, Aysegul A Sahin, Suyu Liu, Hiroshi Katayama, Subrata Sen

Faculty, Staff and Student Publications

The translation elongation factor eEF1A promotes protein synthesis. Its methylation by METTL13 increases its activity, supporting tumor growth. However, in some cancers, a high abundance of eEF1A isoforms is associated with a good prognosis. Here, we found that eEF1A2 exhibited oncogenic or tumor-suppressor functions depending on its interaction with METTL13 or the phosphatase PTEN, respectively. METTL13 and PTEN competed for interaction with eEF1A2 in the same structural domain. PTEN-bound eEF1A2 promoted the ubiquitination and degradation of the mitosis-promoting Aurora kinase A in the S and G2 phases of the cell cycle. eEF1A2 bridged the interactions between the SKP1-CUL1-FBXW7 (SCF) ubiquitin …

Kidney Function Trajectories And Right Heart Failure Following Lvad Implantation, Carl P Walther, Andrew B Civitello, Harveen K Lamba, Nandan K Mondal, Sankar D Navaneethan

Faculty, Staff and Students Publications

BACKGROUND: Preoperative kidney dysfunction is a risk factor for right heart failure (RHF) after implantation of a left ventricular assist device (LVAD). However, characteristic kidney function trajectories before and after post-LVAD RHF are uncertain, so we investigated this.

METHODS AND RESULTS: We identified individuals who received primary continuous-flow LVAD implantation from July 1, 2014 to December 31, 2017 in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) data set. Incident RHF was ascertained using the INTERMACS definition at 1 and 3 months and classified as transient or persistent. Kidney function trajectories before and after RHF onset, and relationships of …

Consensus-Based Development Of A Pediatric Echocardiography Complexity Score: Design, Rationale, And Results Of A Quality Improvement Collaborative, Sowmya Balasubramanian, Sunkyung Yu, Sarina K Behera, Aarti H Bhat, Joseph A Camarda, Nadine F Choueiter, Pei-Ni Jone, Leo Lopez, Shobha S Natarajan, David A Parra, Anitha Parthiban, Ritu Sachdeva, Shubhika Srivastava, Elif Seda Selamet Tierney

Faculty, Staff and Students Publications

BACKGROUND: The complexity of congenital heart disease has been primarily stratified on the basis of surgical technical difficulty, specific diagnoses, and associated outcomes. We report on the refinement and validation of a pediatric echocardiography complexity (PEC) score.

METHODS AND RESULTS: The American College of Cardiology Quality Network assembled a panel from 12 centers to refine a previously published PEC score developed in a single institution. The panel refined complexity categories and included study modifiers to account for complexity related to performance of the echocardiogram. Each center submitted data using the PEC scoring tool on 15 consecutive inpatient and outpatient echocardiograms. …

Hippo Cooperates With P53 To Maintain Foregut Homeostasis And Suppress The Malignant Transformation Of Foregut Basal Progenitor Cells, Yu Jiang, Haidi Huang, Jiangying Liu, Dan Luo, Rongzi Mu, Jianghong Yuan, Jihong Lin, Qiyue Chen, Wufan Tao, Ling Yang, Man Zhang, Pingping Zhang, Fengqin Fang, Jianming Xu, Qingqiu Gong, Zhiping Xie, Yongchun Zhang

Faculty, Staff and Students Publications

Basal progenitor cells serve as a stem cell pool to maintain the homeostasis of the epithelium of the foregut, including the esophagus and the forestomach. Aberrant genetic regulation in these cells can lead to carcinogenesis, such as squamous cell carcinoma (SCC). However, the underlying molecular mechanisms regulating the function of basal progenitor cells remain largely unknown. Here, we use mouse models to reveal that Hippo signaling is required for maintaining the homeostasis of the foregut epithelium and cooperates with p53 to repress the initiation of foregut SCC. Deletion of

High Clinical Exome Sequencing Diagnostic Rates And Novel Phenotypic Expansions For Nonisolated Microphthalmia, Anophthalmia, And Coloboma, Bhavana Kunisetty, Bailey A Martin-Giacalone, Xiaonan Zhao, Pamela N Luna, Brian P Brooks, Robert B Hufnagel, Chad A Shaw, Jill A Rosenfeld, A J Agopian, Philip J Lupo, Daryl A Scott

Faculty, Staff and Student Publications

PURPOSE: A molecular diagnosis is only made in a subset of individuals with nonisolated microphthalmia, anophthalmia, and coloboma (MAC). This may be due to underutilization of clinical (whole) exome sequencing (cES) and an incomplete understanding of the genes that cause MAC. The purpose of this study is to determine the efficacy of cES in cases of nonisolated MAC and to identify new MAC phenotypic expansions.

METHODS: We determined the efficacy of cES in 189 individuals with nonisolated MAC. We then used cES data, a validated machine learning algorithm, and previously published expression data, case reports, and animal models to determine …

The Epigenetic Evolution Of Glioma Is Determined By The Idh1 Mutation Status And Treatment Regimen, Tathiane M Malta, Thais S Sabedot, Natalia S Morosini, Indrani Datta, Luciano Garofano, Wies Vallentgoed, Frederick S Varn, Kenneth Aldape, Fulvio D'Angelo, Spyridon Bakas, Jill S Barnholtz-Sloan, Hui K Gan, Mohammad Hasanain, Ann-Christin Hau, Kevin C Johnson, Simona Cazacu, Ana C Decarvalho, Mustafa Khasraw, Emre Kocakavuk, Mathilde C M Kouwenhoven, Simona Migliozzi, Simone P Niclou, Johanna M Niers, D Ryan Ormond, Sun Ha Paek, Guido Reifenberger, Peter A Sillevis Smitt, Marion Smits, Lucy F Stead, Martin J Van Den Bent, Erwin G Van Meir, Annemiek Walenkamp, Tobias Weiss, Michael Weller, Bart A Westerman, Bauke Ylstra, Pieter Wesseling, Anna Lasorella, Pim J French, Laila M Poisson, Consortium The Glass, Roel G W Verhaak, Antonio Iavarone, Houtan Noushmehr

Faculty, Staff and Student Publications

Tumor adaptation or selection is thought to underlie therapy resistance in glioma. To investigate longitudinal epigenetic evolution of gliomas in response to therapeutic pressure, we performed an epigenomic analysis of 132 matched initial and recurrent tumors from patients with IDH-wildtype (IDHwt) and IDH-mutant (IDHmut) glioma. IDHwt gliomas showed a stable epigenome over time with relatively low levels of global methylation. The epigenome of IDHmut gliomas showed initial high levels of genome-wide DNA methylation that was progressively reduced to levels similar to those of IDHwt tumors. Integration of epigenomics, gene expression, and functional genomics identified HOXD13 as a master regulator of …

Differential Treatment Effects Of Subgroup Analyses In Phase 3 Oncology Trials From 2004 To 2020, Alexander D Sherry, Andrew W Hahn, Zachary R Mccaw, Joseph Abi Jaoude, Ramez Kouzy, Timothy A Lin, Bruce Minsky, C David Fuller, Tomer Meirson, Pavlos Msaouel, Ethan B Ludmir

Faculty, Staff and Student Publications

IMPORTANCE: Subgroup analyses are often performed in oncology to investigate differential treatment effects and may even constitute the basis for regulatory approvals. Current understanding of the features, results, and quality of subgroup analyses is limited.

OBJECTIVE: To evaluate forest plot interpretability and credibility of differential treatment effect claims among oncology trials.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included randomized phase 3 clinical oncology trials published prior to 2021. Trials were screened from ClinicalTrials.gov.

MAIN OUTCOMES AND MEASURES: Missing visual elements in forest plots were defined as a missing point estimate or use of a linear x-axis scale for hazard …

Efficacy Of Single-Agent Chemotherapy In Endocrine Therapy-Refractory Metastatic Invasive Lobular Carcinoma, Jason A Mouabbi, Wei Qaio, Yu Shen, Akshara Singareeka Raghavendra, Debasish Tripathy, Rachel M Layman

Faculty, Staff and Student Publications

Background: Hormone receptor (HR)-positive, HER2-negative metastatic invasive lobular breast cancer (mILC) is distinct from invasive ductal cancer (IDC) in clinicopathologic and molecular characteristics, impacting its response to systemic therapy. While endocrine therapy (ET) combined with targeted therapies has shown efficacy in ET-sensitive mILC, data on chemotherapy in ET-refractory mILC remain limited. We investigated the efficacy of single-agent capecitabine (CAP) versus taxanes (TAX) in ET-refractory HR+ HER2-negative patients with mILC.

Materials and methods: Using data from the MD Anderson prospectively collected breast cancer database, we identified patients with HR+ HER2-negative mILC who received prior ET and first-time chemotherapy in the metastatic …

Differential Treatment Effects Of Subgroup Analyses In Phase 3 Oncology Trials From 2004 To 2020, Alexander D Sherry, Andrew W Hahn, Zachary R Mccaw, Joseph Abi Jaoude, Ramez Kouzy, Timothy A Lin, Bruce Minsky, C David Fuller, Tomer Meirson, Pavlos Msaouel, Ethan B Ludmir

Faculty, Staff and Student Publications

Importance: Subgroup analyses are often performed in oncology to investigate differential treatment effects and may even constitute the basis for regulatory approvals. Current understanding of the features, results, and quality of subgroup analyses is limited.

Objective: To evaluate forest plot interpretability and credibility of differential treatment effect claims among oncology trials.

Design, setting, and participants: This cross-sectional study included randomized phase 3 clinical oncology trials published prior to 2021. Trials were screened from ClinicalTrials.gov.

Main outcomes and measures: Missing visual elements in forest plots were defined as a missing point estimate or use of a linear x-axis scale for hazard …

Adaptive Darwinian Off-Target Resistance Mechanisms To Selective Ret Inhibition In Ret Driven Cancer, Vivek Subbiah, Mohamed A Gouda, J Bryan Iorgulescu, Ramona Dadu, Keyur Patel, Steven Sherman, Maria Cabanillas, Mimi Hu, Luz E Castellanos, Behrang Amini, Funda Meric-Bernstam, Tao Shen, Jie Wu

Faculty, Staff and Student Publications

Patients treated with RET protein tyrosine kinase inhibitors (TKIs) selpercatinib or pralsetinib develop RET TKI resistance by secondary RET mutations or alterative oncogenes, of which alterative oncogenes pose a greater challenge for disease management because of multiple potential mechanisms and the unclear tolerability of drug combinations. A patient with metastatic medullary thyroid carcinoma (MTC) harboring a RET activation loop D898_E901del mutation was treated with selpercatinib. Molecular alterations were monitored with tissue biopsies and cfDNA during the treatment. The selpercatinib-responsive MTC progressed with an acquired ETV6::NTRK3 fusion, which was controlled by selpercatinib plus the NTRK inhibitor larotrectinib. Subsequently, tumor progressed with …

Surgery Of The Palatomaxillary Structure, Jessica R Burgess, Kathleen C Heneghan, Tarra G Barot, Jonah J Stulberg

Faculty, Staff and Student Publications

BACKGROUND: Patients with opioid use disorder (OUD) are increasing, challenging surgeons to adjust post-operative pain management guidelines. A literature review identified limited information on how to best care for these patients. The purpose of this study was to determine surgical perioperative management of OUD, challenges, and support needed for optimal care.

METHODS: This study utilized an anonymous voluntary survey that was distributed to members of the American College of Surgeons through the association's electronic weekly newsletter. The survey was advertised weekly for three consecutive weeks. The survey included questions regarding surgeons' management of perioperative pain in patients with opioid use …

Development Of A Follow-Up Measure To Ensure Complete Screening For Colorectal Cancer, Elizabeth L Ciemins, Jeff T Mohl, Carlos A Moreno, Francis Colangelo, Robert A Smith, Mary Barton

Faculty, Staff and Student Publications

IMPORTANCE: The current quality performance measure for colorectal cancer (CRC) screening is limited to initial screening. Despite low rates, there is no measure for appropriate follow-up with colonoscopy after receipt of an abnormal result of a stool-based screening test (SBT) for CRC. A quality performance measure is needed.

OBJECTIVE: To develop and test a quality performance measure for follow-up colonoscopy within 6 months of an abnormal result of an SBT for CRC.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective quality improvement study examined data from January 1, 2016, to December 31, 2020, with 2018 plus 6 months of follow-up as the …

A Genotyping Array For The Globally Invasive Vector Mosquito, Aedes Albopictus, Luciano Veiga Cosme, Margaret Corley, Thomas Johnson, Dave W Severson, Guiyun Yan, Xiaoming Wang, Nigel Beebe, Andrew Maynard, Mariangela Bonizzoni, Ayda Khorramnejad, Ademir Jesus Martins, José Bento Pereira Lima, Leonard E Munstermann, Sinnathamby N Surendran, Chun-Hong Chen, Kevin Maringer, Isra Wahid, Shomen Mukherjee, Jiannon Xu, Michael C Fontaine, Elizabet L Estallo, Marina Stein, Todd Livdahl, Patricia Y Scaraffia, Brendan H Carter, Motoyoshi Mogi, Nobuko Tuno, James W Mains, Kim A Medley, David E Bowles, Richard J Gill, Roger Eritja, Ranulfo González-Obando, Huynh T T Trang, Sébastien Boyer, Ann-Marie Abunyewa, Kayleigh Hackett, Tina Wu, Justin Nguyễn, Jiangnan Shen, Hongyu Zhao, Jacob E Crawford, Peter Armbruster, Adalgisa Caccone

Faculty, Staff and Student Publications

BACKGROUND: Although whole-genome sequencing (WGS) is the preferred genotyping method for most genomic analyses, limitations are often experienced when studying genomes characterized by a high percentage of repetitive elements, high linkage, and recombination deserts. The Asian tiger mosquito (Aedes albopictus), for example, has a genome comprising up to 72% repetitive elements, and therefore we set out to develop a single-nucleotide polymorphism (SNP) chip to be more cost-effective. Aedes albopictus is an invasive species originating from Southeast Asia that has recently spread around the world and is a vector for many human diseases. Developing an accessible genotyping platform is essential in …

Craniofacial Bone Anomalies Related To Cholesterol Synthesis Defects, Chihiro Iwaya, Akiko Suzuki, Junbo Shim, Aemin Kim, Junichi Iwata

Faculty, Staff and Student Publications

DHCR7 and SC5D are enzymes crucial for cholesterol biosynthesis, and mutations in their genes are associated with developmental disorders, which are characterized by craniofacial deformities. We have recently reported that a loss of either Dhcr7 or Sc5d results in a failure in osteoblast differentiation. However, it remains unclear to what extent a loss of function in either DHCR7 or SC5D affects craniofacial skeletal formation. Here, using micro computed tomography (μCT), we found that the bone phenotype differs in Dhcr7

Postconcussive Symptoms After Early Childhood Concussion, Dominique Dupont, Ken Tang, Cindy Beaudoin, Fanny Dégeilh, Isabelle Gagnon, Keith Owen Yeates, Sean C Rose, Jocelyn Gravel, Brett Burstein, Antonia S Stang, Rachel M Stanley, Roger L Zemek, Miriam H Beauchamp, Perc Koala Study

Faculty, Staff and Student Publications

IMPORTANCE: Research on postconcussive symptoms (PCS) following early childhood concussion has been hindered by a lack of measures suitable for this age group, resulting in a limited understanding of their evolution in young children.

OBJECTIVE: To document PCS in the first 3 months after early childhood concussion using a developmentally appropriate measure.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data collected at 3 Canadian and 1 US urban pediatric emergency departments (EDs) and 8 Canadian daycares from December 2018 to December 2022 as part of the Kids' Outcomes and Long-Term Abilities (KOALA) project, a prospective, multicenter, longitudinal cohort study. …