Medical Specialties Commons^™

Anthracycline-Containing And Taxane-Containing Chemotherapy For Early-Stage Operable Breast Cancer: A Patient-Level Meta-Analysis Of 100 000 Women From 86 Randomised Trials, Early Breast Cancer Trialists’ Collaborative Group (Ebctcg)

Faculty, Staff and Student Publications

BACKGROUND: Anthracycline-taxane chemotherapy for early-stage breast cancer substantially improves survival compared with no chemotherapy. However, concerns about short-term and long-term side-effects of anthracyclines have led to increased use of taxane chemotherapy without anthracycline, which could compromise efficacy. We aimed to better characterise the benefits and risks of including anthracycline, and the comparative benefits of different anthracycline-taxane regimens.

METHODS: We did an individual patient-level meta-analysis of randomised trials comparing taxane regimens with versus without anthracycline, and updated our previous meta-analysis of anthracycline regimens with versus without taxane, as well as analysing 44 trials in six related comparisons. We searched databases, including …

Phase Ii Study Of Palbociclib (Pd-0332991) In Ccnd1, 2, Or 3 Amplification: Results From The Nci-Match Ecog-Acrin Trial (Eay131) Subprotocol Z1b, Amy S Clark, Fangxin Hong, Richard S Finn, Angela M Demichele, Edith P. Mitchell, James Zwiebel, Fernanda I Arnaldez, Robert J Gray, Victoria Wang, Lisa M Mcshane, Larry V Rubinstein, David Patton, P Mickey Williams, Stanley R Hamilton, Mehmet S Copur, Samer S Kasbari, Ravneet Thind, Barbara A Conley, Carlos L Arteaga, Peter J O'Dwyer, Lyndsay N Harris, Alice P Chen, Keith T Flaherty

Department of Medical Oncology Faculty Papers

Purpose: Cyclin D/CDK4/6 is critical in controlling the G1 to S checkpoint. CCND, the gene encoding cyclin D, is known to be amplified in a variety of solid tumors. Palbociclib is an oral CDK4/6 inhibitor, approved in advanced breast cancer in combination with endocrine therapy. We explored the efficacy of palbociclib in patients with nonbreast solid tumors containing an amplification in CCND1, 2, or 3.

Patients and methods: Patients with tumors containing a CCND1, 2, or 3 amplification and expression of the retinoblastoma protein were assigned to subprotocol Z1B and received palbociclib 125 mg once daily for 21 days of …

Pertuzumab, Trastuzumab, And An Aromatase Inhibitor For Her2-Positive And Hormone Receptor-Positive Metastatic Or Locally Advanced Breast Cancer: Pertain Final Analysis, Grazia Arpino, Juan De La Haba Rodríguez, Jean-Marc Ferrero, Sabino De Placido, C Kent Osborne, Dirk Klingbiel, Valentine Revelant, Christine Wohlfarth, Raf Poppe, Mothaffar F Rimawi

Faculty, Staff and Students Publications

PURPOSE: In PERTAIN's primary analysis (31 months' median follow-up), adding pertuzumab to trastuzumab and an aromatase inhibitor (AI) with/without chemotherapy significantly improved progression-free survival (PFS) in patients with previously untreated HER2-positive and hormone receptor-positive metastatic or locally advanced breast cancer (M/LABC). A potentially enhanced treatment effect was observed in patients with no induction chemotherapy. We present the final analysis (>6 years' median follow-up).

PATIENTS AND METHODS: Patients (N = 258) were randomized 1:1 to pertuzumab (loading/maintenance: 840/420 mg) plus trastuzumab (loading/maintenance: 8/6 mg/kg) every 3 weeks and an AI (1 mg anastrozole or 2.5 mg letrozole daily; Arm A), …

Upper Age Limits For Us Male Human Papillomavirus Vaccination For Oropharyngeal Cancer Prevention: A Microsimulation-Based Modeling Study, Rebecca Landy, Gregory Haber, Barry I Graubard, Nicole G Campos, Stephen Sy, Jane J Kim, Emily A Burger, Li C Cheung, Hormuzd A Katki, Maura L Gillison, Anil K Chaturvedi

Faculty, Staff and Student Publications

BACKGROUND: Human papillomavirus (HVP)-positive oropharyngeal cancer is the most common HPV-associated cancer in the United States. The age at acquisition of oral HPV infections that cause oropharyngeal cancer (causal infections) is unknown; consequently, the benefit of vaccination of US men aged 27-45 years remains uncertain.

METHODS: We developed a microsimulation-based, individual-level, state-transition model of oral HPV16 and HPV16-positive oropharyngeal cancer among heterosexual US men aged 15-84 years, calibrated to population-level data. We estimated the benefit of vaccination of men aged 27-45 years for prevention of oropharyngeal cancer, accounting for direct- and indirect effects (ie, herd effects) of male and female …

Rank Is A Poor Prognosis Marker And A Therapeutic Target In Er-Negative Postmenopausal Breast Cancer, Marina Ciscar, Eva M Trinidad, Gema Perez-Chacon, Mansour Alsaleem, Maria Jimenez, Maria J Jimenez-Santos, Hector Perez-Montoyo, Adrian Sanz-Moreno, Andrea Vethencourt, Michael Toss, Anna Petit, Maria T Soler-Monso, Victor Lopez, Jorge Gomez-Miragaya, Clara Gomez-Aleza, Lacey E Dobrolecki, Michael T Lewis, Alejandra Bruna, Silvana Mouron, Miguel Quintela-Fandino, Fatima Al-Shahrour, Antonio Martinez-Aranda, Angels Sierra, Andrew R Green, Emad Rakha, Eva Gonzalez-Suarez

Faculty, Staff and Students Publications

Despite strong preclinical data, the therapeutic benefit of the RANKL inhibitor, denosumab, in breast cancer patients, beyond the bone, is unclear. Aiming to select patients who may benefit from denosumab, we hereby analyzed RANK and RANKL protein expression in more than 2,000 breast tumors (777 estrogen receptor-negative, ER- ) from four independent cohorts. RANK protein expression was more frequent in ER- tumors, where it associated with poor outcome and poor response to chemotherapy. In ER- breast cancer patient-derived orthoxenografts (PDXs), RANKL inhibition reduced tumor cell proliferation and stemness, regulated tumor immunity and metabolism, and improved response to chemotherapy. Intriguingly, tumor …

Targeting The Mevalonate Pathway Suppresses Arid1a-Inactivated Cancers By Promoting Pyroptosis, Wei Zhou, Heng Liu, Zhe Yuan, Joseph Zundell, Martina Towers, Jianhuang Lin, Simona Lombardi, Hao Nie, Brennah Murphy, Tyler Yang, Chen Wang, Liping Liao, Aaron R Goldman, Toshitha Kannan, Andrew V Kossenkov, Ronny Drapkin, Luis J Montaner, Daniel T Claiborne, Nan Zhang, Shuai Wu, Rugang Zhang

Faculty, Staff and Student Publications

ARID1A, encoding a subunit of the SWI/SNF complex, is mutated in ∼50% of clear cell ovarian carcinoma (OCCC) cases. Here we show that inhibition of the mevalonate pathway synergizes with immune checkpoint blockade (ICB) by driving inflammasome-regulated immunomodulating pyroptosis in ARID1A-inactivated OCCCs. SWI/SNF inactivation downregulates the rate-limiting enzymes in the mevalonate pathway such as HMGCR and HMGCS1, which creates a dependence on the residual activity of the pathway in ARID1A-inactivated cells. Inhibitors of the mevalonate pathway such as simvastatin suppresses the growth of ARID1A mutant, but not wild-type, OCCCs. In addition, simvastatin synergizes with anti-PD-L1 antibody in a genetic OCCC …

Bi-Allelic Snapc4 Variants Dysregulate Global Alternative Splicing And Lead To Neuroregression And Progressive Spastic Paraparesis, F Graeme Frost, Marie Morimoto, Prashant Sharma, Lyse Ruaud, Newell Belnap, Daniel G Calame, Yuri Uchiyama, Naomichi Matsumoto, Machteld M Oud, Elise A Ferreira, Vinodh Narayanan, Sampath Rangasamy, Matt Huentelman, Lisa T Emrick, Ikuko Sato-Shirai, Satoko Kumada, Nicole I Wolf, Peter J Steinbach, Yan Huang, Undiagnosed Diseases Network, Barbara N Pusey, Sandrine Passemard, Jonathan Levy, Séverine Drunat, Marie Vincent, Agnès Guet, Emanuele Agolini, Antonio Novelli, Maria Cristina Digilio, Jill A Rosenfeld, Jennifer L Murphy, James R Lupski, Gilbert Vezina, Ellen F Macnamara, David R Adams, Maria T Acosta, Cynthia J Tifft, William A Gahl, May Christine V Malicdan

Faculty, Staff and Students Publications

The vast majority of human genes encode multiple isoforms through alternative splicing, and the temporal and spatial regulation of those isoforms is critical for organismal development and function. The spliceosome, which regulates and executes splicing reactions, is primarily composed of small nuclear ribonucleoproteins (snRNPs) that consist of small nuclear RNAs (snRNAs) and protein subunits. snRNA gene transcription is initiated by the snRNA-activating protein complex (SNAPc). Here, we report ten individuals, from eight families, with bi-allelic, deleterious SNAPC4 variants. SNAPC4 encoded one of the five SNAPc subunits that is critical for DNA binding. Most affected individuals presented with delayed motor development …

Parp Inhibitors For The Treatment Of Brca1/2-Mutated Metastatic Breast Cancer: A Systematic Review And Meta-Analysis, Ranju Kunwor, Daniel P. Silver, Maysa Abu-Khalaf

Kimmel Cancer Center Faculty Papers

BACKGROUND: The PARP inhibitors (PARPis) olaparib and talazoparib are currently approved for the treatment of deleterious germline BRCA1/2-mutated (gBRCA+) metastatic breast cancer (MBC). These approvals were based on improvements in progression-free survival (PFS) observed in two randomized controlled trials (RCTs). Other PARPis, such as veliparib and niraparib, have also been studied. We conducted this meta-analysis of RCTs to assess the PFS and overall survival (OS) benefits of PARPis in gBRCA + MBC.

METHODS: We performed a systematic search for RCTs using the Cochrane Library, PubMed, Embase, and Web of Science databases up to March 2021. Only phase II and III …

Large-Scale Analysis Of Structural Brain Asymmetries In Schizophrenia Via The Enigma Consortium, Dick Schijven, Merel C Postema, Masaki Fukunaga, Junya Matsumoto, Kenichiro Miura, Sonja M C De Zwarte, Neeltje E M Van Haren, Wiepke Cahn, Hilleke E Hulshoff Pol, René S Kahn, Rosa Ayesa-Arriola, Víctor Ortiz-García De La Foz, Diana Tordesillas-Gutierrez, Javier Vázquez-Bourgon, Benedicto Crespo-Facorro, Dag Alnæs, Andreas Dahl, Lars T Westlye, Ingrid Agartz, Ole A Andreassen, Erik G Jönsson, Peter Kochunov, Jason M Bruggemann, Stanley V Catts, Patricia T Michie, Bryan J Mowry, Yann Quidé, Paul E Rasser, Ulrich Schall, Rodney J Scott, Vaughan J Carr, Melissa J Green, Frans A Henskens, Carmel M Loughland, Christos Pantelis, Cynthia Shannon Weickert, Thomas W Weickert, Lieuwe De Haan, Katharina Brosch, Julia-Katharina Pfarr, Kai G Ringwald, Frederike Stein, Andreas Jansen, Tilo T J Kircher, Igor Nenadić, Bernd Krämer, Oliver Gruber, Theodore D Satterthwaite, Juan Bustillo, Daniel H Mathalon, Adrian Preda, Vince D Calhoun, Judith M Ford, Steven G Potkin, Jingxu Chen, Yunlong Tan, Zhiren Wang, Hong Xiang, Fengmei Fan, Fabio Bernardoni, Stefan Ehrlich, Paola Fuentes-Claramonte, Maria Angeles Garcia-Leon, Amalia Guerrero-Pedraza, Raymond Salvador, Salvador Sarró, Edith Pomarol-Clotet, Valentina Ciullo, Fabrizio Piras, Daniela Vecchio, Nerisa Banaj, Gianfranco Spalletta, Stijn Michielse, Therese Van Amelsvoort, Erin W Dickie, Aristotle N Voineskos, Kang Sim, Simone Ciufolini, Paola Dazzan, Robin M Murray, Woo-Sung Kim, Young-Chul Chung, Christina Andreou, André Schmidt, Stefan Borgwardt, Andrew M Mcintosh, Heather C Whalley, Stephen M Lawrie, Stefan Du Plessis, Hilmar K Luckhoff, Freda Scheffler, Robin Emsley, Dominik Grotegerd, Rebekka Lencer, Udo Dannlowski, Jesse T Edmond, Kelly Rootes-Murdy, Julia M Stephen, Andrew R Mayer, Linda A Antonucci, Leonardo Fazio, Giulio Pergola, Alessandro Bertolino, Covadonga M Díaz-Caneja, Joost Janssen, Noemi G Lois, Celso Arango, Alexander S Tomyshev, Irina Lebedeva, Simon Cervenka, Carl M Sellgren, Foivos Georgiadis, Matthias Kirschner, Stefan Kaiser, Tomas Hajek, Antonin Skoch, Filip Spaniel, Minah Kim, Yoo Bin Kwak, Sanghoon Oh, Jun Soo Kwon, Anthony James, Geor Bakker, Christian Knöchel, Michael Stäblein, Viola Oertel, Anne Uhlmann, Fleur M Howells, Dan J Stein, Henk S Temmingh, Ana M Diaz-Zuluaga, Julian A Pineda-Zapata, Carlos López-Jaramillo, Stephanie Homan, Ellen Ji, Werner Surbeck, Philipp Homan, Simon E Fisher, Barbara Franke, David C Glahn, Ruben C Gur, Ryota Hashimoto, Neda Jahanshad, Eileen Luders, Sarah E Medland, Paul M Thompson, Jessica A Turner, Theo G M Van Erp, Clyde Francks

Faculty, Staff and Students Publications

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small …

Assessment Of Psychosocial And Neonatal Risk Factors For Trajectories Of Behavioral Dysregulation Among Young Children From 18 To 72 Months Of Age., Julie A. Hofheimer, Monica Mcgrath, Rashelle Musci, Guojing Wu, Sarah Polk, Courtney K. Blackwell, Annemarie Stroustrup, Robert D. Annett, Judy Aschner, Brian S. Carter, Jennifer Check, Elisabeth Conradt, Lisa A. Croen, Anne L. Dunlop, Amy J. Elliott, Andrew Law, Leslie D. Leve, Jenae M. Neiderhiser, T Michael O'Shea, Amy L. Salisbury, Sheela Sathyanarayana, Rachana Singh, Lynne M. Smith, Andréa Aguiar, Jyoti Angal, Hannah Carliner, Cindy Mcevoy, Steven J. Ondersma, Barry Lester, Program Collaborators For Environmental Influences On Child Health Outcomes

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Emotional and behavioral dysregulation during early childhood are associated with severe psychiatric, behavioral, and cognitive disorders through adulthood. Identifying the earliest antecedents of persisting emotional and behavioral dysregulation can inform risk detection practices and targeted interventions to promote adaptive developmental trajectories among at-risk children.

OBJECTIVE: To characterize children's emotional and behavioral regulation trajectories and examine risk factors associated with persisting dysregulation across early childhood.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study examined data from 20 United States cohorts participating in Environmental influences on Child Health Outcomes, which included 3934 mother-child pairs (singleton births) from 1990 to 2019. Statistical analysis …

Lecanemab For Patients With Early Alzheimer Disease: Bayesian Analysis Of A Phase 2b Dose-Finding Randomized Clinical Trial, Donald A Berry, Shobha Dhadda, Michio Kanekiyo, David Li, Chad J Swanson, Michael Irizarry, Lynn D Kramer, Scott M Berry

Faculty, Staff and Student Publications

IMPORTANCE: Bayesian clinical trial designs are increasingly common; given their promotion by the US Food and Drug Administration, the future use of the bayesian approach will only continue to increase. Innovations possible when using the bayesian approach improve the efficiency of drug development and the accuracy of clinical trials, especially in the context of substantial data missingness.

OBJECTIVE: To explain the foundations, interpretations, and scientific justification of the bayesian approach in the setting of lecanemab trial 201, a bayesian-designed phase 2 dose-finding trial; to demonstrate the efficiency of using a bayesian design; and to show how it accommodates innovations in …

Renal-Hepatic-Pancreatic Dysplasia Type 2: Perinatal Lethal Condition Or A Multisystemic Disorder With Variable Expressivity, Kathryn Gunther, Essam M Imseis, Joyce P Samuel, Elizabeth A Hillman, Tiina H Ojala, Timo Jahnukainen, Paul R Hillman

Faculty, Staff and Student Publications

BACKGROUND: Renal-hepatic-pancreatic dysplasia type 2 (RHPD2) is a rare condition that has been described in the literature disproportionately in perinatal losses. The main features of liver and kidney involvement are well described, with cardiac malformations and cardiomyopathy adding additional variation to the phenotype. Many patients reported are within larger cohorts of congenital anomalies of kidney and urinary tract (CAKUT) or liver failure, and with minimal phenotypic and clinical course data.

METHODS: An independent series of phenotypes and prognosis was aggregated from the literature. In this literature review, we describe an additional patient with RHPD2, provide a clinical update on the …

Autologous Stem Cell Transplantation For Patients With Multiple Myeloma With Translocation (4;14): The Md Anderson Cancer Center Experience, Oren Pasvolsky, Mahmoud R Gaballa, Denái R Milton, Adeel Masood, Sophiya S Sami, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Jeremy Ramdial, Yago Nieto, Guilin Tang, Pei Lin, Hans C Lee, Krina K Patel, Partow Kebriaei, Sheeba K Thomas, Donna M Weber, Robert Z Orlowski, Elizabeth J Shpall, Richard E Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Translocation between chromosomes 4 and 14, t(4;14), has been reported in 15% of patients with multiple myeloma (MM) and is considered a high-risk cytogenetic abnormality associated with inferior outcomes. Autologous hematopoietic stem cell transplantation (auto-HCT) is standard of care for patients with high-risk MM, yet there are scarce data on post-transplantation outcomes of patients with t(4;14) MM. The aim of the present study was to evaluate outcomes of MM patients with t(4;14) who underwent auto-HCT and received contemporary anti-myeloma agents for induction and post-transplantation maintenance. We conducted a retrospective analysis of MM patients with t(4;14), detected by fluorescence in situ …

Fear Of Recurrence, Emotional Well-Being And Quality Of Life Among Long-Term Advanced Ovarian Cancer Survivors, Kathryn Osann, Lari Wenzel, Chelsea Mckinney, Lynne Wagner, David Cella, Giulia Fulci, Mary J Scroggins, Heather A Lankes, Victoria Wang, Kenneth P Nephew, George L Maxwell, Samuel C Mok, Thomas P Conrads, Austin Miller, Michael Birrer

Faculty, Staff and Student Publications

OBJECTIVE: Although advanced stage epithelial ovarian cancer is widely considered life-threatening, 17% of women with advanced disease will survive long-term. Little is known about the health-related quality of life (QOL) of long-term ovarian cancer survivors, or how fear of recurrence might affect QOL.

METHODS: 58 long-term survivors with advanced disease participated in the study. Participants completed standardized questionnaires to capture cancer history, QOL, and fear of recurrent disease (FOR). Statistical analyses included multivariable linear models.

RESULTS: Participants averaged 52.8 years at diagnosis and had survived >8 years (mean:13.5); 64% had recurrent disease. Mean FACT-G, FACT-O, and FACT-O-TOI (TOI) scores were …

Diet, Physical Activity, And Stress Among Wheelchair Users With Multiple Sclerosis: Examining Individual And Co-Occurring Behavioral Risk Factors, Stephanie L Silveira, Brenda Jeng, Gary Cutter, Robert W Motl

Faculty, Staff and Student Publications

OBJECTIVE: This study examined individual and co-occurring behavioral risk factors (diet, exercise, and stress) in wheelchair users with multiple sclerosis (MS) and potential association with MS symptoms (ie, fatigue, depression, anxiety, pain, sleep, and health-related quality of life [HRQOL]).

DESIGN: Survey.

SETTING: General Community.

PARTICIPANTS: One hundred twenty-three wheelchair users with MS completed this study (N=123).

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: Participants were mailed instructions for accessing online questionnaires (demographic and clinical characteristics, Godin Leisure-Time Exercise Questionnaire, Perceived Stress Scale, Automated Self-Administered 24-Hour Dietary Assessment Tool, and MS symptoms).

RESULTS: Standard cut-points were used to categorize behavioral risk factors …

Prospective, Early Longitudinal Assessment Of Lymphedema-Related Quality Of Life Among Patients With Locally Advanced Breast Cancer: The Foundation For Building A Patient-Centered Screening Program, Anusha Gandhi, Tianlin Xu, Sarah M Desnyder, Grace L Smith, Ruitao Lin, Carlos H Barcenas, Michael C Stauder, Karen E Hoffman, Eric A Strom, Susan Ferguson, Benjamin D Smith, Wendy A Woodward, George H Perkins, Melissa P Mitchell, Desmond Garner, Chelain R Goodman, Melissa Aldrich, Marigold Travis, Susan Lilly, Isabelle Bedrosian, Simona F Shaitelman

Faculty, Staff and Student Publications

BACKGROUND: We examined how breast cancer-related lymphedema (BCRL) affects health-related quality of life (HRQOL), productivity, and compliance with therapeutic interventions to guide structuring BCRL screening programs.

METHODS: We prospectively followed consecutive breast cancer patients who underwent axillary lymph node dissection (ALND) with arm volume screening and measures assessing patient-reported health-related quality of life (HRQOL) and perceptions of BCRL care. Comparisons by BCRL status were made with Mann-Whitney U, Chi-square, Fisher's exact, or t tests. Trends over time from ALND were assessed with linear mixed-effects models.

RESULTS: With a median follow-up of 8 months in 247 patients, 46% self-reported ever having …

Knowledge, Attitudes, And Beliefs About Colorectal Cancer Screening In Puerto Rico, Vivian Colón-López, Ileska M Valencia-Torres, Elsa I Ríos, Josheili Llavona, Camille Vélez-Álamo, María E Fernández

Faculty, Staff and Student Publications

The purpose of this study was to describe the psychosocial factors influencing participation in colorectal cancer screening (CRCS) among Puerto Rican men and women. We conducted seven focus groups in metropolitan and rural areas of Puerto Rico (PR) with men and women (using gender specific groups) aged 50 to 80 years (n = 51) who were non-adherent to CRC guidelines. The focus group guide included questions related to colorectal cancer (CRC) and CRC screening knowledge, attitudes, and beliefs. We analyzed data using a modified grounded theory approach to identify emergent themes. Focus groups revealed seven major themes that represented barriers …

The Brief Case: A New Feature In Journal Of Clinical Microbiology, Makayla M Bavis, Allison M Nicholas, Alexandria J Tobin, Sherri L Christian, Robert J Brown

Faculty, Staff and Student Publications

The energy demand of breast cancers is in part met through the β-oxidation of exogenous fatty acids. Fatty acids may also be used to aid in cell signaling and toward the construction of new membranes for rapidly proliferating tumor cells. A significant quantity of fatty acids comes from the hydrolysis of lipoprotein triacylglycerols and phospholipids by lipoprotein lipase (LPL). The lipid obtained via LPL in the breast tumor microenvironment may thus promote breast tumor growth and development. In this hypothesis article, we introduce LPL, provide a meta-analysis of RNAseq data showing that LPL is associated with poor prognosis, and explain …

Long-Term Maternal Metabolic And Cardiovascular Phenotypes After A Pregnancy Complicated By Mild Gestational Diabetes Mellitus Or Obesity, Ashley N Battarbee, Lisa Mele, Mark B Landon, Michael W Varner, Brian M Casey, Uma M Reddy, Ronald J Wapner, Dwight J Rouse, John M Thorp, Edward K Chien, George Saade, Beth A Plunkett, Sean C Blackwell

Faculty, Staff and Student Publications

Objective:

To evaluate the association of mild gestational diabetes (GDM) and obesity with metabolic and cardiovascular markers 5-10 years after pregnancy.

Study Design:

This was a secondary analysis of 5-10 year follow-up study of a mild GDM treatment trial and concurrent observational cohort of participants ineligible for the trial with abnormal 1-hour glucose challenge test only. Participants with 2-hour glucose tolerance test at follow-up were included. The primary exposures were mild GDM and obesity. The outcomes were insulinogenic index (IGI), 1/HOMA-IR, and cardiovascular markers VEGF, VCAM-1, CD40L, GDF-15, and ST-2. Multivariable linear regression estimated the association of GDM and obesity …

Racial And Ethnic Disparities In Adverse Perinatal Outcomes At Term, Jacqueline G Parchem, Madeline Murguia Rice, William A Grobman, Jennifer L Bailit, Ronald J Wapner, Michelle P Debbink, John M Thorp, Steve N Caritis, Mona Prasad, Alan T N Tita, George R Saade, Yoram Sorokin, Dwight J Rouse, Jorge E Tolosa

Faculty, Staff and Student Publications

Objective: This study aimed to evaluate whether racial and ethnic disparities in adverse perinatal outcomes exist at term.

Study design: We performed a secondary analysis of a multicenter observational study of 115,502 pregnant patients and their neonates (2008-2011). Singleton, nonanomalous pregnancies delivered from 37 to 41 weeks were included. Race and ethnicity were abstracted from the medical record and categorized as non-Hispanic White (White; referent), non-Hispanic Black (Black), non-Hispanic Asian (Asian), or Hispanic. The primary outcome was an adverse perinatal composite defined as perinatal death, Apgar score < 4 at 5 minutes, ventilator support, hypoxic-ischemic encephalopathy, subgaleal hemorrhage, skeletal fracture, infant stay greater than maternal stay (by ≥ 3 days), brachial plexus palsy, or facial nerve palsy.

Results: Of the 72,117 patients included, 48% were White, 20% Black, 5% Asian, …

Dietary Intake Of Total, Heme And Non-Heme Iron And The Risk Of Colorectal Cancer In A European Prospective Cohort Study, Elom K Aglago, Amanda J Cross, Elio Riboli, Veronika Fedirko, David J Hughes, Agnes Fournier, Paula Jakszyn, Heinz Freisling, Marc J Gunter, Christina C Dahm, Kim Overvad, Anne Tjønneland, Cecilie Kyrø, Marie-Christine Boutron-Ruault, Joseph A Rothwell, Gianluca Severi, Verena Katzke, Bernard Srour, Matthias B Schulze, Clemens Wittenbecher, Domenico Palli, Sabina Sieri, Fabrizio Pasanisi, Rosario Tumino, Fulvio Ricceri, Bas Bueno-De-Mesquita, Jeroen W G Derksen, Guri Skeie, Torill Enget Jensen, Marko Lukic, Maria-Jose Sánchez, Pilar Amiano, Sandra Colorado-Yohar, Aurelio Barricarte, Ulrika Ericson, Bethany Van Guelpen, Keren Papier, Anika Knuppel, Corinne Casagrande, Inge Huybrechts, Alicia K Heath, Konstantinos K Tsilidis, Mazda Jenab

Faculty, Staff and Student Publications

BACKGROUND: Iron is an essential micronutrient with differing intake patterns and metabolism between men and women. Epidemiologic evidence on the association of dietary iron and its heme and non-heme components with colorectal cancer (CRC) development is inconclusive.

METHODS: We examined baseline dietary questionnaire-assessed intakes of total, heme, and non-heme iron and CRC risk in the EPIC cohort. Sex-specific multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox regression. We modelled substitution of a 1 mg/day of heme iron intake with non-heme iron using the leave one-out method.

RESULTS: Of 450,105 participants (318,680 women) followed for 14.2 …

Impact Of Common Vitamin D-Binding Protein Isoforms On Supplemental Vitamin D3 And/Or Calcium Effects On Colorectal Adenoma Recurrence Risk: A Secondary Analysis Of A Randomized Clinical Trial, David Corley Gibbs, Elizabeth L Barry, Veronika Fedirko, John A Baron, Roberd M Bostick

Faculty, Staff and Student Publications

IMPORTANCE: Variants in the vitamin D-binding protein (DBP) gene (GC) encode DBP isoforms that may affect vitamin D metabolism. However, whether these isoforms modify the effects of vitamin D3 and/or calcium supplementation on colorectal adenoma recurrence is unclear. We hypothesized that supplementation effects may be stronger among those with the DBP2 isoform (encoded by the rs4588*A allele), which is associated with vitamin D deficiency and modified the associations of circulating vitamin D with risk for colorectal neoplasms in observational studies.

OBJECTIVE: To estimate supplemental vitamin D3 and/or calcium effects on colorectal adenoma recurrence according to 3 common DBP isoforms (DBP1s, …

Artificial Intelligence-Based Ct Assessment Of Bronchiectasis: The Copdgene Study, Alejandro A Díaz, Pietro Nardelli, Wei Wang, Rubén San José Estépar, Andrew Yen, Seth Kligerman, Diego J Maselli, Wojciech R Dolliver, Andrew Tsao, José L Orejas, Stefano Aliberti, Timothy R Aksamit, Kendra A Young, Gregory L Kinney, George R Washko, Edwin K Silverman, Raúl San José Estépar

Faculty, Staff and Student Publications

Background

CT is the standard method used to assess bronchiectasis. A higher airway-to-artery diameter ratio (AAR) is typically used to identify enlarged bronchi and bronchiectasis; however, current imaging methods are limited in assessing the extent of this metric in CT scans.

Purpose

To determine the extent of AARs using an artificial intelligence–based chest CT and assess the association of AARs with exacerbations over time.

Materials and Methods

In a secondary analysis of ever-smokers from the prospective, observational, multicenter COPDGene study, AARs were quantified using an artificial intelligence tool. The percentage of airways with AAR greater than 1 (a measure of …

Assessment Of Predictors Of Early Postoperative Complications After Primary Robotically Assisted Roux-En-Y Gastric Bypass: A Multicenter, Retrospective Cohort Study, Pouya Iranmanesh, Shinil K Shah, Mickael Chevallay, Christian Toso, Stefan P Mönig, Monika E Hagen, Erik B Wilson, Minoa K Jung

Faculty, Staff and Student Publications

BACKGROUND: Robotic Roux-en-Y gastric bypass (RRYGB) is performed in an increasing number of bariatric centers worldwide. Previous studies have identified a number of demographic and clinical variables as predictors of postoperative complications after laparoscopic Roux-en-Y gastric bypass (LRYGB). Some authors have suggested better early postoperative outcomes after RRYGB compared to LRYGB. The objective of the present study was to assess potential predictors of early postoperative complications after RRYGB.

METHODS: A retrospective analysis of two prospective databases containing patients who underwent RRYGB between 2006 and 2019 at two high volumes, accredited bariatric centers was performed. Primary outcome was rate of 30 …

Renal-Hepatic-Pancreatic Dysplasia Type 2: Perinatal Lethal Condition Or A Multisystemic Disorder With Variable Expressivity, Kathryn Gunther, Essam M Imseis, Joyce P Samuel, Elizabeth A Hillman, Tiina H Ojala, Timo Jahnukainen, Paul R Hillman

Faculty, Staff and Student Publications

BACKGROUND: Renal-hepatic-pancreatic dysplasia type 2 (RHPD2) is a rare condition that has been described in the literature disproportionately in perinatal losses. The main features of liver and kidney involvement are well described, with cardiac malformations and cardiomyopathy adding additional variation to the phenotype. Many patients reported are within larger cohorts of congenital anomalies of kidney and urinary tract (CAKUT) or liver failure, and with minimal phenotypic and clinical course data.

METHODS: An independent series of phenotypes and prognosis was aggregated from the literature. In this literature review, we describe an additional patient with RHPD2, provide a clinical update on the …

Evaluating The Causal Effect Of Tobacco Smoking On White Matter Brain Aging: A Two-Sample Mendelian Randomization Analysis In Uk Biobank, Chen Mo, Jingtao Wang, Zhenyao Ye, Hongjie Ke, Song Liu, Kathryn Hatch, Si Gao, Jessica Magidson, Chixiang Chen, Braxton D Mitchell, Peter Kochunov, L Elliot Hong, Tianzhou Ma, Shuo Chen

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Tobacco smoking is a risk factor for impaired brain function, but its causal effect on white matter brain aging remains unclear. This study aimed to measure the causal effect of tobacco smoking on white matter brain aging.

DESIGN: Mendelian randomization (MR) analysis using two non-overlapping data sets (with and without neuroimaging data) from UK Biobank (UKB). The group exposed to smoking and control group consisted of current smokers and never smokers, respectively. Our main method was generalized weighted linear regression with other methods also included as sensitivity analysis.

SETTING: United Kingdom.

PARTICIPANTS: The study cohort included 23 …

Ablative Margins Of Colorectal Liver Metastases Using Deformable Ct Image Registration And Autosegmentation, Yuan-Mao Lin, Iwan Paolucci, Caleb S O'Connor, Brian M Anderson, Bastien Rigaud, Bryan M Fellman, Kyle A Jones, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Background

Confirming ablation completeness with sufficient ablative margin is critical for local tumor control following colorectal liver metastasis (CLM) ablation. An image-based confirmation method considering patient- and ablation-related biomechanical deformation is an unmet need.

Purpose

To evaluate a biomechanical deformable image registration (DIR) method for three-dimensional (3D) minimal ablative margin (MAM) quantification and the association with local disease progression following CT-guided CLM ablation.

Materials and Methods

This single-institution retrospective study included patients with CLM treated with CT-guided microwave or radiofrequency ablation from October 2015 to March 2020. A biomechanical DIR method with AI-based autosegmentation of liver, tumors, and ablation zones …

Short-Term Neonatal Outcomes Of Pregnancies Complicated By Maternal Obesity, Mara J Dinsmoor, Lynda G Ugwu, Jennifer L Bailit, Uma M Reddy, Ronald J Wapner, Michael W Varner, John M Thorp, Steve N Caritis, Mona Prasad, Alan T N Tita, George R Saade, Yoram Sorokin, Dwight J Rouse, Sean C Blackwell, Jorge E Tolosa, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Maternal-Fetal Medicine Units (Mfmu) Network

Faculty, Staff and Student Publications

BACKGROUND: Maternal obesity complicates a high number of pregnancies. The degree to which neonatal outcomes are adversely affected is unclear.

OBJECTIVE: This study aimed to evaluate neonatal outcomes of pregnancies complicated by maternal obesity.

STUDY DESIGN: This study was a secondary analysis of a cohort of deliveries occurring on randomly selected days at 25 hospitals from 2008 to 2011. Data were collected by certified abstractors. This analysis included singleton deliveries between 24 and 42 weeks of gestation. Body mass index was calculated on the basis of maternal height and most recent weight before delivery. Normal and overweight (reference group; body …

The Association Of Smoking And Coffee Consumption With Occurrence Of Upper Gastrointestinal Symptoms In Patients With Active Helicobacter Pylori Infection In Jazan City: A Cross-Sectional Study, Anna Palatnik, Paula Mcgee, Jennifer L Bailit, Ronald J Wapner, Michael W Varner, John M Thorp, Steve N Caritis, Mona Prasad, Alan T N Tita, George R Saade, Dwight J Rouse, Sean C Blackwell, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Maternal-Fetal Medicine Units (Mfmu) Networ

Faculty, Staff and Student Publications

Objective:

To examine whether there are racial disparities in severe maternal morbidity in patients with hypertensive disorder of pregnancy (HDP).

Study Design:

Secondary analysis of an observational study of 115,502 patients who had a live birth at ≥ 20 weeks in 25 hospitals in the US from 2008 to 2011. Only patients with HDP were included in this analysis. Race and ethnicity were categorized as non-Hispanic White, non-Hispanic Black and Hispanic and were abstracted from the medical charts. Patients of other races and ethnicities were excluded. Associations were estimated between race and ethnicity and the primary outcome of severe maternal …

A Ring-Like Accretion Structure In M87 Connecting Its Black Hole And Jet, Ru-Sen Lu, Keiichi Asada, Thomas P Krichbaum, Jongho Park, Fumie Tazaki, Hung-Yi Pu, Masanori Nakamura, Andrei Lobanov, Kazuhiro Hada, Kazunori Akiyama, Jae-Young Kim, Ivan Marti-Vidal, José L Gómez, Tomohisa Kawashima, Feng Yuan, Eduardo Ros, Walter Alef, Silke Britzen, Michael Bremer, Avery E Broderick, Akihiro Doi, Gabriele Giovannini, Marcello Giroletti, Paul T P Ho, Mareki Honma, David H Hughes, Makoto Inoue, Wu Jiang, Motoki Kino, Shoko Koyama, Michael Lindqvist, Jun Liu, Alan P Marscher, Satoki Matsushita, Hiroshi Nagai, Helge Rottmann, Tuomas Savolainen, Karl-Friedrich Schuster, Zhi-Qiang Shen, Pablo De Vicente, R Craig Walker, Hai Yang, J Anton Zensus, Juan Carlos Algaba, Alexander Allardi, Uwe Bach, Ryan Berthold, Dan Bintley, Do-Young Byun, Carolina Casadio, Shu-Hao Chang, Chih-Cheng Chang, Song-Chu Chang, Chung-Chen Chen, Ming-Tang Chen, Ryan Chilson, Tim C Chuter, John Conway, Geoffrey B Crew, Jessica T Dempsey, Sven Dornbusch, Aaron Faber, Per Friberg, Javier González García, Miguel Gómez Garrido, Chih-Chiang Han, Kuo-Chang Han, Yutaka Hasegawa, Ruben Herrero-Illana, Yau-De Huang, Chih-Wei L Huang, Violette Impellizzeri, Homin Jiang, Hao Jinchi, Taehyun Jung, Juha Kallunki, Petri Kirves, Kimihiro Kimura, Jun Yi Koay, Patrick M Koch, Carsten Kramer, Alex Kraus, Derek Kubo, Cheng-Yu Kuo, Chao-Te Li, Lupin Chun-Che Lin, Ching-Tang Liu, Kuan-Yu Liu, Wen-Ping Lo, Li-Ming Lu, Nicholas Macdonald, Pierre Martin-Cocher, Hugo Messias, Zheng Meyer-Zhao, Anthony Minter, Dhanya G Nair, Hiroaki Nishioka, Timothy J Norton, George Nystrom, Hideo Ogawa, Peter Oshiro, Nimesh A Patel, Ue-Li Pen, Yurii Pidopryhora, Nicolas Pradel, Philippe A Raffin, Ramprasad Rao, Ignacio Ruiz, Salvador Sanchez, Paul Shaw, William Snow, T K Sridharan, Ranjani Srinivasan, Belén Tercero, Pablo Torne, Efthalia Traianou, Jan Wagner, Craig Walther, Ta-Shun Wei, Jun Yang, Chen-Yu Yu

Faculty, Staff and Student Publications

The nearby radio galaxy M87 is a prime target for studying black hole accretion and jet formation1,2. Event Horizon Telescope observations of M87 in 2017, at a wavelength of 1.3 mm, revealed a ring-like structure, which was interpreted as gravitationally lensed emission around a central black hole3. Here we report images of M87 obtained in 2018, at a wavelength of 3.5 mm, showing that the compact radio core is spatially resolved. High-resolution imaging shows a ring-like structure of 8.4+0.5−1.1 Schwarzschild radii in diameter, approximately 50% larger than that seen at 1.3 mm. The outer …