Internal Medicine Commons^™

Stranger Things: New Roles And Opportunities For Androgen Receptor In Oncology Beyond Prostate Cancer, Javier Leo, Eleonora Dondossola, Kaitlin J Basham, Nathaniel R Wilson, Omar Alhalabi, Jianjun Gao, Katherine C Kurnit, Michael G White, Jennifer L Mcquade, Shannon N Westin, Elizabeth A Wellberg, Daniel E Frigo

Faculty, Staff and Student Publications

The androgen receptor (AR) is one of the oldest therapeutic targets in oncology and continues to dominate the treatment landscape for advanced prostate cancer, where nearly all treatment regimens include some form of AR modulation. In this regard, AR remains the central driver of prostate cancer cell biology. Emerging preclinical and clinical data implicate key roles for AR in additional cancer types, thereby expanding the importance of this drug target beyond prostate cancer. In this mini-review, new roles for AR in other cancer types are discussed as well as their potential for treatment with AR-targeted agents. Our understanding of these …

Initiating And Imaging Cavitation From Infused Echo Contrast Agents Through The Ekosonic Catheter, Sonya R Kennedy, Maxime Lafond, Kevin J Haworth, Daniel Suarez Escudero, Dan Ionascu, Brion Frierson, Shaoling Huang, Melvin E Klegerman, Tao Peng, David D Mcpherson, Curtis Genstler, Christy K Holland

Faculty, Staff and Student Publications

Ultrasound-enhanced delivery of therapeutic-loaded echogenic liposomes is under development for vascular applications using the EkoSonic Endovascular System. In this study, fibrin-targeted echogenic liposomes loaded with an anti-inflammatory agent were characterized before and after infusion through an EkoSonic catheter. Cavitation activity was nucleated by Definity or fibrin-targeted, drug-loaded echogenic liposomes infused and insonified with EkoSonic catheters. Passive cavitation imaging was used to quantify and map bubble activity in a flow phantom mimicking porcine arterial flow. Cavitation was sustained during 3-min infusions of Definity or echogenic liposomes along the distal 6 cm treatment zone of the catheter. Though the EkoSonic catheter was …

Update On The Role Of Feno In Asthma Management, Neveda Murugesan, Damini Saxena, Arundhati Dileep, Muhammad Adrish, Nicola A Hanania

Faculty, Staff and Students Publications

Asthma is a heterogenous disorder characterized by presence of different phenotypes and endotypes. Up to 10% of the individuals suffer from severe asthma and are at increased risk of morbidity and mortality. Fractional exhaled nitric oxide (FeNO) is a cost-effective, point of care biomarker that is used to detect type 2 airway inflammation. Guidelines have proposed to measure FeNO as an adjunct to diagnostic evaluation in individuals with suspected asthma and to monitor airway inflammation. FeNO has lower sensitivity, suggesting that it may not be a good biomarker to rule out asthma. FeNO may also be used to predict response …

The Type 2 Diabetes Knowledge Portal: An Open Access Genetic Resource Dedicated To Type 2 Diabetes And Related Traits, Maria C Costanzo, Marcin Von Grotthuss, Jeffrey Massung, Dongkeun Jang, Lizz Caulkins, Ryan Koesterer, Clint Gilbert, Ryan P Welch, Parul Kudtarkar, Quy Hoang, Andrew P Boughton, Preeti Singh, Ying Sun, Marc Duby, Annie Moriondo, Trang Nguyen, Patrick Smadbeck, Benjamin R Alexander, Mackenzie Brandes, Mary Carmichael, Peter Dornbos, Todd Green, Kenneth C Huellas-Bruskiewicz, Yue Ji, Alexandria Kluge, Aoife C Mcmahon, Josep M Mercader, Oliver Ruebenacker, Sebanti Sengupta, Dylan Spalding, Daniel Taliun, Philip Smith, Melissa K Thomas, Beena Akolkar, M Julia Brosnan, Andriy Cherkas, Audrey Y Chu, Eric B Fauman, Caroline S Fox, Tania Nayak Kamphaus, Melissa R Miller, Lynette Nguyen, Afshin Parsa, Dermot F Reilly, Hartmut Ruetten, David Wholley, Norann A Zaghloul, Gonçalo R Abecasis, David Altshuler, Thomas M Keane, Mark I Mccarthy, Kyle J Gaulton, Jose C Florez, Michael Boehnke, Noël P Burtt, Jason Flannick

Faculty, Staff and Student Publications

Associations between human genetic variation and clinical phenotypes have become a foundation of biomedical research. Most repositories of these data seek to be disease-agnostic and therefore lack disease-focused views. The Type 2 Diabetes Knowledge Portal (T2DKP) is a public resource of genetic datasets and genomic annotations dedicated to type 2 diabetes (T2D) and related traits. Here, we seek to make the T2DKP more accessible to prospective users and more useful to existing users. First, we evaluate the T2DKP's comprehensiveness by comparing its datasets with those of other repositories. Second, we describe how researchers unfamiliar with human genetic data can begin …

Emt-Activated Secretory And Endocytic Vesicular Trafficking Programs Underlie A Vulnerability To Pi4k2a Antagonism In Lung Cancer, Xiaochao Tan, Guan-Yu Xiao, Shike Wang, Lei Shi, Yanbin Zhao, Xin Liu, Jiang Yu, William K Russell, Chad J Creighton, Jonathan M Kurie

Faculty, Staff and Students Publications

Hypersecretory malignant cells underlie therapeutic resistance, metastasis, and poor clinical outcomes. However, the molecular basis for malignant hypersecretion remains obscure. Here, we showed that epithelial-mesenchymal transition (EMT) initiates exocytic and endocytic vesicular trafficking programs in lung cancer. The EMT-activating transcription factor zinc finger E-box-binding homeobox 1 (ZEB1) executed a PI4KIIIβ-to-PI4KIIα (PI4K2A) dependency switch that drove PI4P synthesis in the Golgi and endosomes. EMT enhanced the vulnerability of lung cancer cells to PI4K2A small-molecule antagonists. PI4K2A formed a MYOIIA-containing protein complex that facilitated secretory vesicle biogenesis in the Golgi, thereby establishing a hypersecretory state involving osteopontin (SPP1) and other prometastatic ligands. …

Primary Diffuse Large B-Cell Lymphoma Of The Bone, Binoy Yohannan, Adan Rios

Faculty, Staff and Student Publications

Primary lymphoma of the bone (PLB) is a rare lymphoproliferative neoplasm that can present either as solitary or multiple bone lesions. We report four patients with PLB who were successfully treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by consolidative radiotherapy. All patients achieved a complete remission and had excellent long-term outcomes. PLB has a favorable response to combined modality treatment with chemoimmunotherapy and radiation. Long-term outcomes of PLB tend to be better than those of non-osseous diffuse large B-cell lymphoma.

Effect Of Thromboprophylaxis On Clinical Outcomes After Covid-19 Hospitalization, Tracy Y Wang, Abdus S Wahed, Alison Morris, Lisa Baumann Kreuziger, John G Quigley, Gervasio A Lamas, Alexandra J Weissman, Jose Lopez-Sendon, M Margaret Knudson, Deborah M Siegal, Raj S Kasthuri, Andrew J Alexander, Lana Wahid, Bassel Atassi, Peter J Miller, Janice W Lawson, Bela Patel, Jerry A Krishnan, Nancy L Shapiro, Deborah E Martin, Andrei L Kindzelski, Eric S Leifer, Jungnam Joo, Lingyun Lyu, Annie Pennella, Brendan M Everett, Mark W Geraci, Kevin J Anstrom, Thomas L Ortel, Activ-4c Study Group

Faculty, Staff and Student Publications

BACKGROUND: Patients hospitalized with COVID-19 have an increased incidence of thromboembolism. The role of extended thromboprophylaxis after hospital discharge is unclear.

OBJECTIVE: To determine whether anticoagulation is superior to placebo in reducing death and thromboembolic complications among patients discharged after COVID-19 hospitalization.

DESIGN: Prospective, randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT04650087).

SETTING: Done during 2021 to 2022 among 127 U.S. hospitals.

PARTICIPANTS: Adults aged 18 years or older hospitalized with COVID-19 for 48 hours or more and ready for discharge, excluding those with a requirement for, or contraindication to, anticoagulation.

INTERVENTION: 2.5 mg of apixaban versus placebo twice daily for …

Following The Map For Improved Kidney Function In Hepatorenal Syndrome, Matthew R Thau, Pavan K Bhatraju

Faculty, Staff and Student Publications

No abstract provided.

Drivers Of Cost In Primary Single-Level Lumbar Fusion Surgery, Raymond W Hwang, Samuel W Golenbock, David H Kim

Faculty, Staff and Student Publications

STUDY DESIGN: Retrospective cohort.

OBJECTIVES: Allocating cost is challenging with traditional hospital accounting. Time-driven activity-based costing (TDABC) is an efficient method to accurately assign cost. We sought to characterize the variation in direct total hospital cost (THC) among both lumbar fusion approaches and surgeons.

METHODS: Patients were treated with single-level anterior interbody (ALIF), lateral interbody (LLIF), transforaminal interbody (TLIF), instrumented posterolateral (PLF) or in-situ fusion (ISF) for degenerative disease. Process maps were developed for preoperative, intraoperative and postoperative care. THC was composed of implant, medication, other supply, and personnel costs. Linear regression and descriptive statistics were used to analyze THC …

Just-In-Time Decision Making: Preliminary Findings Of A Goals Of Care Rapid Response Team, Donna S Zhukovsky, Yvonne Heung, Parema Enriquez, Nelda Itzep, Zhanni Lu, Nico Nortje, Penny Stanton, Angelique Wong, Eduardo Bruera

Faculty, Staff and Student Publications

CONTEXT: The COVID-19 pandemic placed the issue of resource utilization front and center. Our comprehensive cancer center developed a Goals of Care Rapid Response Team (GOC RRT) to optimize resource utilization balanced with goal-concordant patient care.

OBJECTIVES: Primary study objective was to evaluate feasibility of the GOC RRT by describing the frequency of consultations that occurred from those requested. Secondary objectives included adherence to consultation processes in terms of core team member participation and preliminary efficacy in limiting care escalation.

METHODS: We conducted a retrospective chart review of patients referred to GOC RRT (3/23/2020-9/30/2020). Analysis was descriptive. Categorical variables were …

An Antibody-Drug Conjugate Targeting Gpr56 Demonstrates Efficacy In Preclinical Models Of Colorectal Cancer, Joan Jacob, Liezl E Francisco, Treena Chatterjee, Zhengdong Liang, Shraddha Subramanian, Qingyun J Liu, Julie H Rowe, Kendra S Carmon

Faculty, Staff and Student Publications

BACKGROUND: Long-term prognosis remains poor for colorectal cancer (CRC) patients with advanced disease due to treatment resistance. The identification of novel targets is essential for the development of new therapeutic approaches. GPR56, an adhesion GPCR, is highly expressed in CRC tumours and correlates with poor survival. Here, we describe the generation and preclinical evaluation of a novel ADC consisting of an anti-GPR56 antibody (10C7) conjugated with the DNA-damaging payload duocarmycin.

METHODS: RNA-seq dataset analysis was performed to determine GPR56 expression in CRC subtypes. The specificity of binding, epitope mapping, and internalisation of 10C7 was examined. 10C7 was conjugated to payload …

Heart Failure-Type Symptom Score Trajectories In Ckd: Findings From The Chronic Renal Insufficiency Cohort (Cric) Study, Carl P Walther, Julia S Benoit, Nisha Bansal, Vijay Nambi, Sankar D Navaneethan, Cric Study Investigators

Faculty, Staff and Students Publications

RATIONALE & OBJECTIVE: Quality of life in chronic kidney disease (CKD) is impaired by a large burden of symptoms including some that overlap with the symptoms of heart failure (HF). We studied a group of individuals with CKD to understand the patterns and trajectories of HF-type symptoms in this setting.

STUDY DESIGN: Prospective cohort study.

SETTING & PARTICIPANTS: 3,044 participants in the Chronic Renal Insufficiency Cohort (CRIC) without prior diagnosis of HF.

PREDICTORS: Sociodemographics, medical history, medications, vital signs, laboratory values, echocardiographic and electrocardiographic parameters.

OUTCOME: Trajectory over 5.5 years of a HF-type symptom score (modified Kansas City Cardiomyopathy Questionnaire …

Lobar Pneumonia Presenting As Fever, Headaches, And A Negative Chest Radiograph, David R Rendon, Jason Shiau, Stephanie V Sherman

Faculty, Staff and Students Publications

No abstract provided.

Monogenic Early-Onset Lymphoproliferation And Autoimmunity: Natural History Of Stat3 Gain-Of-Function Syndrome, Jennifer W Leiding, Tiphanie P Vogel, Valentine G J Santarlas, Rahul Mhaskar, Madison R Smith, Alexandre Carisey, Alexander Vargas-Hernández, Manuel Silva-Carmona, Maximilian Heeg, Anne Rensing-Ehl, Bénédicte Neven, Jérôme Hadjadj, Sophie Hambleton, Timothy Ronan Leahy, Kornvalee Meesilpavikai, Charlotte Cunningham-Rundles, Cullen M Dutmer, Svetlana O Sharapova, Mervi Taskinen, Ignatius Chua, Rosie Hague, Christian Klemann, Larysa Kostyuchenko, Tomohiro Morio, Akaluck Thatayatikom, Ahmet Ozen, Anna Scherbina, Cindy S Bauer, Sarah E Flanagan, Eleonora Gambineri, Lisa Giovannini-Chami, Jennifer Heimall, Kathleen E Sullivan, Eric Allenspach, Neil Romberg, Sean G Deane, Benjamin T Prince, Melissa J Rose, John Bohnsack, Talal Mousallem, Rohith Jesudas, Maria Marluce Dos Santos Vilela, Michael O'Sullivan, Jana Pachlopnik Schmid, Štěpánka Průhová, Adam Klocperk, Matthew Rees, Helen Su, Sami Bahna, Safa Baris, Lisa M Bartnikas, Amy Chang Berger, Tracy A Briggs, Shannon Brothers, Vanessa Bundy, Alice Y Chan, Shanmuganathan Chandrakasan, Mette Christiansen, Theresa Cole, Matthew C Cook, Mukesh M Desai, Ute Fischer, David A Fulcher, Silvanna Gallo, Amelie Gauthier, Andrew R Gennery, José Gonçalo Marques, Frédéric Gottrand, Bodo Grimbacher, Eyal Grunebaum, Emma Haapaniemi, Sari Hämäläinen, Kaarina Heiskanen, Tarja Heiskanen-Kosma, Hal M Hoffman, Luis Ignacio Gonzalez-Granado, Anthony L Guerrerio, Leena Kainulainen, Ashish Kumar, Monica G Lawrence, Carina Levin, Timi Martelius, Olaf Neth, Peter Olbrich, Alejandro Palma, Niraj C Patel, Tamara Pozos, Kahn Preece, Saúl Oswaldo Lugo Reyes, Mark A Russell, Yael Schejter, Christine Seroogy, Jan Sinclair, Effie Skevofilax, Daniel Suan, Daniel Suez, Paul Szabolcs, Helena Velasco, Klaus Warnatz, Kelly Walkovich, Austen Worth, Stat3 Gof Working Group Members, Mikko R J Seppänen, Troy R Torgerson, Georgios Sogkas, Stephan Ehl, Stuart G Tangye, Megan A Cooper, Joshua D Milner, Lisa R Forbes Satter

Faculty, Staff and Students Publications

BACKGROUND: In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity.

OBJECTIVE: This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants.

METHODS: We identified 191 patients from 33 countries with 72 unique mutations. Inclusion criteria included symptoms of immune dysregulation and a biochemically confirmed germline heterozygous GOF variant in STAT3.

RESULTS: Overall survival was 88%, median age at onset of symptoms was 2.3 years, and median …

Naive T Cells Inhibit The Outgrowth Of Intractable Antigen-Activated Memory T Cells: Implications For T-Cell Immunotherapy, Sandhya Sharma, Mae Woods, Naren U Mehta, Tim Sauer, Kathan S Parikh, Michael Schmuck-Henneresse, Huimin Zhang, Birju Mehta, Malcolm K Brenner, Helen E Heslop, Cliona M Rooney

Faculty, Staff and Students Publications

BACKGROUND: The wider application of T cells targeting viral tumor-antigens via their native receptors is hampered by the failure to expand potent tumor-specific T cells from patients. Here, we examine reasons for and solutions to this failure, taking as our model the preparation of Epstein-Barr virus (EBV)-specific T cells (EBVSTs) for the treatment of EBV-positive lymphoma. EBVSTs could not be manufactured from almost one-third of patients, either because they failed to expand, or they expanded, but lacked EBV specificity. We identified an underlying cause of this problem and established a clinically feasible approach to overcome it.

METHODS: CD45RO+CD45RA- memory compartment …

Ultralow-Dose Binary Oncolytic/Helper-Dependent Adenovirus Promotes Antitumor Activity In Preclinical And Clinical Studies, Daniel Wang, Caroline E Porter, Bora Lim, Amanda Rosewell Shaw, Catherine S Robertson, Mae L Woods, Ya Xu, Greyson G W Biegert, Daisuke Morita, Tao Wang, Bambi J Grilley, Helen Heslop, Malcolm K Brenner, Masataka Suzuki

Faculty, Staff and Students Publications

We show that a binary oncolytic/helper-dependent adenovirus (CAdVEC) that both lyses tumor cells and locally expresses the proinflammatory cytokine IL-12 and PD-L1 blocking antibody has potent antitumor activity in humanized mouse models. On the basis of these preclinical studies, we treated four patients with a single intratumoral injection of an ultralow dose of CAdVEC (NCT03740256), representing a dose of oncolytic adenovirus more than 100-fold lower than used in previous trials. While CAdVEC caused no significant toxicities, it repolarized the tumor microenvironment with increased infiltration of CD8 T cells. A single administration of CAdVEC was associated with both locoregional and abscopal …

Gingival Transcriptomic Patterns Of Macrophage Polarization During Initiation, Progression, And Resolution Of Periodontitis, Octavio A Gonzalez, Sreenatha S Kirakodu, Linh M Nguyen, Jeffrey L Ebersole

Faculty, Staff and Student Publications

Phenotypic and functional heterogeneity of macrophages is clearly a critical component of their effective functions in innate and adaptive immunity. This investigation hypothesized that altered profiles of gene expression in gingival tissues in health, disease, and resolution would reflect changes in macrophage phenotypes occurring in these tissues. The study used a nonhuman primate model to evaluate gene expression profiles as footprints of macrophage variation using a longitudinal experimental model of ligature-induced periodontitis in animals from 3 to 23 years of age to identify aging effects on the gingival environment. Significant differences were observed in distribution of expressed gene levels for …

Cc16 Augmentation Reduces Exaggerated Copd-Like Disease In Cc16-Deficient Mice, Joselyn Rojas-Quintero, Maria Eugenia Laucho-Contreras, Xiaoyun Wang, Quynh-Anh Fucci, Patrick R Burkett, Se-Jin Kim, Duo Zhang, Yohannes Tesfaigzi, Yuhong Li, Abhiram R Bhashyam, Zhang Li, Haider Khamas, Bartolome Celli, Aprile L Pilon, Francesca Polverino, Caroline A Owen

Faculty, Staff and Students Publications

Low Club Cell 16 kDa protein (CC16) plasma levels are linked to accelerated lung function decline in patients with chronic obstructive pulmonary disease (COPD). Cigarette smoke-exposed (CS-exposed) Cc16-/- mice have exaggerated COPD-like disease associated with increased NF-κB activation in their lungs. It is unclear whether CC16 augmentation can reverse exaggerated COPD in CS-exposed Cc16-/- mice and whether increased NF-κB activation contributes to the exaggerated COPD in CS-exposed Cc16-/- lungs. CS-exposed WT and Cc16-/- mice were treated with recombinant human CC16 (rhCC16) or an NF-κB inhibitor versus vehicle beginning at the midpoint of the exposures. COPD-like disease and NF-κB activation were …

Acupuncture Treatment For Post-Stroke Depression: Intestinal Microbiota And Its Role, Hailun Jiang, Shizhe Deng, Jieying Zhang, Junjie Chen, Boxuan Li, Weiming Zhu, Menglong Zhang, Chao Zhang, Zhihong Meng

Faculty, Staff and Student Publications

Stroke-induced depression is a common complication and an important risk factor for disability. Besides psychiatric symptoms, depressed patients may also exhibit a variety of gastrointestinal symptoms, and even take gastrointestinal symptoms as the primary reason for medical treatment. It is well documented that stress may disrupt the balance of the gut microbiome in patients suffering from post-stroke depression (PSD), and that disruption of the gut microbiome is closely related to the severity of the condition in depressed patients. Therefore, maintaining the balance of intestinal microbiota can be the focus of research on the mechanism of acupuncture in the treatment of …

The Association Between Medication Use In Older Women With Early-Stage Operable Primary Breast Cancer And Decision Regarding Primary Treatment, Natalie Tse, Ruth M Parks, Holly M Holmes, Kwok-Leung Cheung

Faculty, Staff and Student Publications

Background: Polypharmacy is one factor contributing to increased mortality, hospitalization, and adverse drug reactions in older adults. The aim of this study was to measure the prevalence of polypharmacy in a cohort of older women with early-stage operable primary breast cancer and the relationship of polypharmacy to primary treatment decision and functional status.

Methods: A total of 139 patients with a new diagnosis of early-stage operable primary breast cancer proven histologically were recruited as part of a prospective study. The average age was 77 years. Assessment using a cancer-specific Comprehensive Geriatric Assessment (CGA) tool was conducted within 6 weeks of …

Partnering With Patients And Families Living With Chronic Conditions To Coproduce Diagnostic Safety Through Ourdx: A Previsit Online Engagement Tool, Sigall K Bell, Zhiyong J Dong, Catherine M Desroches, Nicholas Hart, Stephen Liu, Brianna Mahon, Long H Ngo, Eric J Thomas, Fabienne Bourgeois

Faculty, Staff and Student Publications

OBJECTIVE: Patients and families are key partners in diagnosis, but methods to routinely engage them in diagnostic safety are lacking. Policy mandating patient access to electronic health information presents new opportunities. We tested a new online tool ("OurDX") that was codesigned with patients and families, to determine the types and frequencies of potential safety issues identified by patients/families with chronic health conditions and whether their contributions were integrated into the visit note.

METHODS: Patients/families at 2 US healthcare sites were invited to contribute, through an online previsit survey: (1) visit priorities, (2) recent medical history/symptoms, and (3) potential diagnostic concerns. …

Disparity In Checkpoint Inhibitor Utilization Among Commercially Insured Adult Patients With Metastatic Lung Cancer, Meng Li, Kaiping Liao, Alice J Chen, Tina Cascone, Yu Shen, Qian Lu, Ya-Chen Tina Shih

Faculty, Staff and Student Publications

BACKGROUND: There is a lack of evidence from nationwide samples on the disparity of initiating immune checkpoint inhibitors (ICIs) after metastatic lung cancer diagnosis.

METHODS: We identified metastatic lung cancer patients diagnosed between 2015 and 2020 from a large, nationwide commercial claims database. We analyzed the time from metastatic lung cancer diagnosis to ICI therapy using Cox proportional hazard models. Independent variables included county-level measures (quintiles of percentage of racialized population, quintiles of percentage of population below poverty, urbanity, and density of medical oncologists) and patient characteristics (age, sex, Charlson comorbidity index, Medicare Advantage, and year of diagnosis). All tests …

Health Disparities Experienced By Hispanic Americans With Multiple Myeloma: A Systematic Review, Andrea Anampa-Guzmán, Sara Taveras Alam, Inas Abuali, Samer Al Hadidi

Faculty, Staff and Student Publications

Health disparities in multiple myeloma (MM) disproportionately affect minorities. Characterization of health disparities encountered by Hispanic Americans with MM is necessary to identify gaps and inform future strategies to eliminate them. We performed a systematic review of publications that described health disparities relevant to Hispanic Americans with MM through December 2021. We included all original studies which compared incidence, treatment, and/or outcomes of Hispanic Americans with other ethnic groups. Eight hundred and sixty-eight articles were identified of which 22 original study articles were included in our systematic review. The number of publications varied over time with the highest number of …

Ideal Cardiovascular Health, Biomarkers, And Coronary Artery Disease In Persons With Hiv, Pamela S Douglas, Sara Mccallum, Michael T Lu, Triin Umbleja, Kathleen V Fitch, Borek Foldyna, Markella V Zanni, Evelynne S Fulda, Gerald S Bloomfield, Carl J Fichtenbaum, Edgar T Overton, Judith A Aberg, Carlos D Malvestutto, Tricia H Burdo, Roberto C Arduino, Ken S Ho, Michael T Yin, Heather J Ribaudo, Steven K Grinspoon

Faculty, Staff and Student Publications

OBJECTIVE: To investigate relationships between Life's Simple 7 (LS7), an assessment of cardiovascular health (CVH), and coronary plaque among people with HIV (PWH).

DESIGN: Cross-sectional.

METHODS: Coronary computed tomography angiography, immune/inflammatory biomarkers, and characterization of LS7 were collected among a subset of ART-treated PWH enrolled in REPRIEVE, a primary prevention trial. Analyses adjusted for cardiovascular disease risk (ASCVD score).

RESULTS: Median age of the 735 participants was 51(±6) years, 16% female, and median (Q1-Q3) CVD risk was 4.5% (2.6-6.9). Forty percent had poor (≤2 ideal components), 51% had intermediate (three or four ideal components), and only 9% had ideal CVH …

Building The Foundation For A Community-Generated National Research Blueprint For Inherited Bleeding Disorders: Research Priorities To Transform The Care Of People With Hemophilia, Duc Q Tran, Craig C Benson, Judith A Boice, Meera Chitlur, Amy L Dunn, Miguel A Escobar, Kalpna Gupta, Jill M Johnsen, James Jorgenson, Scott D Martin, Suzanne Martin, Shannon L Meeks, Alfredo A Narvaez, Doris V Quon, Mark T Reding, Ulrike M Reiss, Brittany Savage, Kim Schafer, Bruno Steiner, Courtney Thornburg, Lena M Volland, Annette Von Drygalski

Faculty, Staff and Student Publications

BACKGROUND: Decades of research have transformed hemophilia from severely limiting children's lives to a manageable disorder compatible with a full, active life, for many in high-income countries. The direction of future research will determine whether exciting developments truly advance health equity for all people with hemophilia (PWH). National Hemophilia Foundation (NHF) and American Thrombosis and Hemostasis Network conducted extensive inclusive all-stakeholder consultations to identify the priorities of people with inherited bleeding disorders and those who care for them.

RESEARCH DESIGN AND METHODS: Working group (WG) 1 of the NHF State of the Science Research Summit distilled the community-identified priorities for …

Transabdominal Cerclage During Pregnancy: A Retrospective Single Operator Series Over A Quarter Century, David R Hall, Mari Van De Vyver

Faculty, Staff and Student Publications

OBJECTIVE: To describe the pregnancy outcomes and complications observed in a series of cases of transabdominal cerclage (TAC), which is reserved for highly selected women with recurrent mid-trimester pregnancy loss, due to cervical insufficiency.

METHODS: A retrospective audit covering 25 years (January 1, 1997 to December 31, 2021) was performed at the Obstetric Special Care division, Tygerberg Academic Hospital in Cape Town, South Africa. All 118 pregnancies from 94 procedures, operated and managed by the principal author were included for descriptive analysis.

RESULTS: Eighty-four (91.3%) of the 92 first pregnancies after first insertion had successful outcomes. All second and third …

Epstein-Barr Virus-Associated Lymphoepithelial Carcinoma Arising In The Parotid Gland: A Case Report And Literature Review, Akinobu Kubota, Nobuyuki Bandoh, Takashi Goto, Ken-Ichi Matsumoto, Tomomi Yamaguchi-Ishochi, Yasutaka Kato, Hiroshi Nishihara, Hidehiro Takei

Faculty, Staff and Student Publications

A 60-year-old woman presented with a 3-year history of a slow-growing, painless mass in their left parotid gland. Ultrasonography revealed a well-circumscribed, lobulated, hypoechoic mass measuring 19x12x10 mm in the left parotid gland. Computed tomography revealed a well-circumscribed, solid mass with homogeneous enhancement. Fluorodeoxyglucose-positron emission tomography revealed uptake by the tumor but no uptake in other organs, including the nasopharynx. The patient underwent superficial parotidectomy with adequate safety margins and selective neck dissection followed by radiotherapy. No facial paralysis or recurrence of the tumor had been observed as of 20 months post-operation. Histologically, the tumor was composed of sheets of …

Crk2 Controls Cytoskeleton Morphogenesis In Trypanosoma Brucei By Phosphorylating Β-Tubulin To Regulate Microtubule Dynamics, Kyu Joon Lee, Qing Zhou, Ziyin Li

Faculty, Staff and Student Publications

Microtubules constitute a vital part of the cytoskeleton in eukaryotes by mediating cell morphogenesis, cell motility, cell division, and intracellular transport. The cytoskeleton of the parasite Trypanosoma brucei contains an array of subpellicular microtubules with their plus-ends positioned toward the posterior cell tip, where extensive microtubule growth and cytoskeleton remodeling take place during early cell cycle stages. However, the control mechanism underlying microtubule dynamics at the posterior cell tip remains elusive. Here, we report that the S-phase cyclin-dependent kinase-cyclin complex CRK2-CYC13 in T. brucei regulates microtubule dynamics by phosphorylating β-tubulin on multiple evolutionarily conserved serine and threonine residues to inhibit …

Eczema Monkeypoxicum In A Female Patient With Atopic Dermatitis, Emma Napoli, Madeline Frizzell, Clark Gravell, Sergio Vallejo, Shasta Theodore, Karen Chen, Huma Siddiqui, Justin Dunn, Dora Marrufo, Jose Cadena, Patrick J Danaher

Faculty, Staff and Student Publications

A female patient with atopic dermatitis who had recently received a tattoo presented with severe right ear pain and several vesiculopustular lesions. Over 1 week, she developed approximately 80 widely distributed lesions. Laboratory testing confirmed mpox (previously monkeypox) virus, and no further lesions developed after initiation of oral tecovirimat.

Invasive Mold Infections Following Hurricane Harvey-Houston, Texas, Mitsuru Toda, Samantha Williams, Brendan R Jackson, Sebastian Wurster, Jose A Serpa, Masayuki Nigo, Carolyn Z Grimes, Robert L Atmar, Tom M Chiller, Luis Ostrosky-Zeichner, Dimitrios P Kontoyiannis

Faculty, Staff and Student Publications

BACKGROUND: Characterizing invasive mold infection (IMI) epidemiology in the context of large flooding events is important for public health planning and clinical decision making.

METHODS: We assessed IMI incidence (per 10 000 healthcare encounters) 1 year before and after Hurricane Harvey at 4 hospitals in Houston, Texas. Potential IMI cases were assigned as proven or probable cases using established definitions, and surveillance cases using a novel definition. We used rate ratios to describe IMI incidence and multivariable logistic regression to examine patient characteristics associated with IMI case status.

RESULTS: IMI incidence was significantly higher posthurricane (3.69 cases) than prehurricane (2.50 …