Medical Specialties Commons^™

A Stool Based Qpcr For The Diagnosis Of Tb In Children And People Living With Hiv In Uganda, Eswatini And Mozambique (Stool4tb): A Protocol For A Multicenter Diagnostic Evaluation, Lucia Carratala-Castro, Willy Ssengooba, Alex Kay, Sozinho Acácio, Joanna Ehrlich, Andrew R Dinardo, Nosisa Shiba, Joachim K Nsubuga, Shilzia Munguambe, Belén Saavedra-Cervera, Patricia Manjate, Durbbin Mulengwa, Busizwe Sibandze, Mangaliso Ziyane, George Kasule, Edson Mambuque, Moorine Penninah Sekadde, Eric Wobudeya, Moses L Joloba, Jan Heyckendorf, Christoph Lange, Sabine Hermans, Anna Mandalakas, Alberto L García-Basteiro, Elisa Lopez-Varela, Stool4tb Global Partnership

Faculty, Staff and Students Publications

BACKGROUND: Tuberculosis (TB) is a major cause of mortality worldwide. Children and people living with HIV (PLHIV) have an increased risk of mortality, particularly in the absence of rapid diagnosis. The main challenges of diagnosing TB in these populations are due to the unspecific and paucibacillary disease presentation and the difficulty of obtaining respiratory samples. Thus, novel diagnostic strategies, based on non-respiratory specimens could improve clinical decision making and TB outcomes in high burden TB settings. We propose a multi-country, prospective diagnostic evaluation study with a nested longitudinal cohort evaluation to assess the performance of a new stool-based qPCR, developed …

Progestin-Associated Meningiomatosis With Unusual Schwannoma-Like Morphology, Katherine A Krause, Jared K Woods, Alexandra J Golby, Eudocia Q Lee, Shyam Tanguturi, Zachary Spigelman, Azra H Ligon, Umberto De Girolami, Matthew Torre

Duncan NRI Faculty and Staff Publications

No abstract provided.

Orbital And Periocular Complications In Patients With Sinonasal Tumours With Orbital Invasion, Jiawei Zhao, Xinyang Jiang, Ehab Hanna, Shirley Y Su, Amy Moreno, Brandon Gunn, Steven Jay Frank, Renata Ferrarotto, Jing Ning, Bita Esmaeli

Faculty, Staff and Student Publications

Aims: The purpose of this study was to determine the frequency and associated risk factors of orbital/periocular complications in patients with sinonasal tumour with orbital invasion managed with eye-sparing treatments.

Methods: A retrospective case series of patients with primary sinonasal tumour with orbital invasion from January 2008 to December 2018. Patient factors were compared between the following groups: (1)patients with orbital/periocular complications versus those who did not and (2) patients who needed secondary oculoplastic surgical procedures versus those who did not.

Results: Out of 80 patients, 48 had eye-sparing surgery, 8 had orbital exenteration and 24 were managed non-surgically. The …

Data Encoding For Healthcare Data Democratization And Information Leakage Prevention, Anshul Thakur, Tingting Zhu, Vinayak Abrol, Jacob Armstrong, Yujiang Wang, David A Clifton

Faculty, Staff and Student Publications

The lack of data democratization and information leakage from trained models hinder the development and acceptance of robust deep learning-based healthcare solutions. This paper argues that irreversible data encoding can provide an effective solution to achieve data democratization without violating the privacy constraints imposed on healthcare data and clinical models. An ideal encoding framework transforms the data into a new space where it is imperceptible to a manual or computational inspection. However, encoded data should preserve the semantics of the original data such that deep learning models can be trained effectively. This paper hypothesizes the characteristics of the desired encoding …

Collagen Type Xii Is Undetectable In Keratoconus Bowman’S Layer, Mohammed Rigi, Hyeck-Soo Son, Loren Moon, Mario Matthaei, Divya Srikumaran, Albert S Jun, Charles G Eberhart, Uri S Soiberman

Faculty, Staff and Student Publications

PURPOSE: Corneal biomechanical failure is the hallmark of keratoconus (KC); however, the cause of this failure remains elusive. Collagen type XII (

METHODS: TaqMan quantitative PCR was performed on 31 corneal epithelium samples of progressive KC and myopic control eyes. Tissue microarrays were constructed using full-thickness corneas from 61 KC cases during keratoplasty and 18 non-KC autopsy eyes and stained with an antibody specific to COL12A1. Additionally,

RESULTS: COL12A1 expression was reduced at transcript levels in KC epithelium compared to controls (ratio: 0.58, p<0.03). Immunohistochemical studies demonstrated that COL12A1 protein expression in BL was undetectable, with reduced expression in KC epithelium, basement membrane, and stroma.

CONCLUSIONS: The apparent absence of COL12A1 in KC BL, together with the functional importance that

Impact Of Immunopathy And Coagulopathy On Multi-Organ Failure And Mortality In A Lethal Porcine Model Of Controlled And Uncontrolled Hemorrhage, Milomir O Simovic, James Bynum, Bin Liu, Jurandir J Dalle Lucca, Yansong Li

Faculty, Staff and Student Publications

Uncontrolled hemorrhage is a major preventable cause of death in patients with trauma. However, the majority of large animal models of hemorrhage have utilized controlled hemorrhage rather than uncontrolled hemorrhage to investigate the impact of immunopathy and coagulopathy on multi-organ failure (MOF) and mortality. This study evaluates these alterations in a severe porcine controlled and uncontrolled hemorrhagic shock (HS) model. Anesthetized female swine underwent controlled hemorrhage and uncontrolled hemorrhage by partial splenic resection followed with or without lactated Ringer solution (LR) or Voluven® resuscitation. Swine were surveyed 6 h after completion of splenic hemorrhage or until death. Blood chemistry, physiologic …

The Effects Of Covid-19 Mrna Vaccine On Adolescence Gynecological Well-Being, Shih-Chiao Tseng, Dana Cherry, Mansoo Ko, Steven R Fisher, Michael Furtado, Shuo-Hsiu Chang

Faculty, Staff and Student Publications

PURPOSE: Evidence suggests that transcranial direct current stimulation (tDCS) can enhance motor performance and learning of hand tasks in persons with chronic stroke (PCS). However, the effects of tDCS on the locomotor tasks in PCS are unclear. This pilot study aimed to: (1) determine aggregate effects of anodal tDCS combined with step training on improvements of the neural and biomechanical attributes of stepping initiation in a small cohort of persons with chronic stroke (PCS) over a 4-week training program; and (2) assess the feasibility and efficacy of this novel approach for improving voluntary stepping initiation in PCS.

METHODS: A total …

Degree Of Uncertainty In Reporting Imaging Findings For Necrotizing Enterocolitis: A Secondary Analysis From A Pilot Randomized Diagnostic Trial., Alain Cuna, Disa Rathore, Kira Bourret, Erin K. Opfer, Sherwin S. Chan

Manuscripts, Articles, Book Chapters and Other Papers

Diagnosis of necrotizing enterocolitis (NEC) relies heavily on imaging, but uncertainty in the language used in imaging reports can result in ambiguity, miscommunication, and potential diagnostic errors. To determine the degree of uncertainty in reporting imaging findings for NEC, we conducted a secondary analysis of the data from a previously completed pilot diagnostic randomized controlled trial (2019-2020). The study population comprised sixteen preterm infants with suspected NEC randomized to abdominal radiographs (AXRs) or AXR + bowel ultrasound (BUS). The level of uncertainty was determined using a four-point Likert scale. Overall, we reviewed radiology reports of 113 AXR and 24 BUS …

De Novo Microdeletion Spanning Ywhae And Crk In An Individual With Intellectual Disability And Stunted Growth, Eden E. Pope, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

In this report, we present a case of a 20-year-old female with congenital intellectual disability, stunted growth, and hypothyroidism. Competitive genetic hybridization (CHG) revealed a loss of a portion of 17p13.3 at least 195 Kb in size, not present in either parent. This area of chromosome 17 is associated with Miller-Dieker Syndrome (MDS) and Isolated Lissencephaly Sequence (ILS), but these conditions are related predominantly to PAFAH1B1, which is not included in the patient’s deletion.

Investigating The Interplay Between Glucose Regulation, Neural Activity, And Motivation: A Novel Approach Utilizing Vibration Stimulation, Blake D. Harris, Patrick Tanner Brain, Alessandra Maisie Rivera, Tiffany Nguyen, James Barber, Amar Paul, John Dougherty Jr., Matthew Jennings, Bridger Gunter, David W. Sant, Christina A. Small, Scott Steffenson, Kyle B. Bills

Annual Research Symposium

This research explores the intricate relationship between glucose regulation, neural activity, and motivation in key brain regions, including the hypothalamus, basal ganglia, ventral tegmental area (VTA), and nucleus accumbens (NA). We aim to unravel the potential relationship of these factors on dopamine (DA) release and the broader implications for mental health, glucose regulation, well-being, and overall health. Our innovative approach involves using a chair that causes heterodyned whole-body vibration designed to stimulate DA release from the VTA and NA, areas associated with motivation and rewards.

Exploring The Interconnected Role Of The Oral Microbiome And Periodontal Disease In The Development And Progression Of Oral Squamous Cell Carcinoma, Malak Al-Regib, Claudia M. Tellez Freitas

Annual Research Symposium

This comprehensive review explores the complex linkage among the oral microbiome, periodontal disease, and the onset and progression of oral squamous cell carcinoma (OSCC).

What Did We Learn About Vads In 2023?, Maya Guglin

The VAD Journal

This is our 10^th annual literature review on mechanical circulatory support (MCS) devices. All of our previous reports were well received by the readers.^1-9

In this paper, we summarized the most interesting and important, from our standpoint, publications from 2023. There may be some slight overlap with the end of 2022, because some papers were published online first, and the year of publication changed when they became available in print.

For the seventh time this year, we wrote a section on extracorporeal membrane oxygenation (ECMO), which primarily addresses new developments in veno-arterial ECMO.

Readers who wish to supplement …

Ocular Syphilis: A Case Report And Public Health Discussion, Andrew L. Fine, Hope V. Daskalakis, Rutwik Pradeep Sharma M.D., Mirna Ogeilat M.D.

Advances in Clinical Medical Research and Healthcare Delivery

Ocular Syphilis describes a localized manifestation of a systemic treponema pallidum infection. It most commonly presents with decreased visual acuity due to uveitis and can occur at any time throughout the disease course. This report describes a case of undiagnosed syphilis that was serendipitously diagnosed with blood product screening. This case highlights the need for better public education and outreach pertaining to sexually transmitted infections. This report will detail this patient's clinical course and discuss how healthcare providers can aid in early disease detection to improve both patient outcomes and overall public health.

New Onset Positive Autoantibodies Following Covid-19 Infection, David Hernandez, Adnaan Sheikh, Shakira Laing, Mariana Adieb, Omar Siddiqui, Rohail Baig, Annabel Antonini, James Vienneau, Camden Burns

Advances in Clinical Medical Research and Healthcare Delivery

The World Health Organization (WHO) declared the novel coronavirus (COVID-19) outbreak a global pandemic on March 11, 2020. Since the original outbreak in December 2019, over 100 million people have been confirmed to have been infected by COVID-19 and over two million people have died. The presentation seen in patients may vary widely based on multiple factors. Fever has been reported in up to 99% of patients, while other common symptoms seen are dyspnea, fatigue, anosmia, and myalgia. Around 80% of COVID-19 patients present with a mild respiratory illness that can be managed at home, while around 15% need basic …

Uncommon Presentation Of Kaposi Sarcoma In An Hiv-Negative Patient: A Case Report And Review Of The Literature, Hope Daskalakis, Nina M. Ventura, Joy Anne Lowry, Mara Weinstein Velez

Advances in Clinical Medical Research and Healthcare Delivery

Kaposi Sarcoma (KS) is a multifocal systemic disease first identified in 1872. It most commonly involves the skin, mucous membranes, lymph nodes, and gastrointestinal tract. There are four clinically distinct subtypes of KS that have been identified: Chronic or classic KS, African endemic KS, KS due to iatrogenic immunosuppression, and AIDS-related epidemic KS. The human herpesvirus 8 (HHV-8) has been implicated in all subtypes of KS. We present a unique case of KS in a 79-year-old male with a widespread distribution of skin lesions on his palms, soles, chest, and back. This case report highlights a novel presentation of classical …

A Case Of Streptococcus Constellatus Bacteremia Secondary To Respiratory Syncytial Virus Bronchiolitis In A Neonate, Ronald G. Lott Iii, Samantha M. Lavertue, Xavier Zonna, Samuel Wlasowicz, Roland Zhang, Ravi Kavuda

Advances in Clinical Medical Research and Healthcare Delivery

Common causes of bacteremia in the neonatal period include group B streptococcus, listeria, and E. coli. We report a rare case of neonatal bacteremia with culture-positive Streptococcus constellatus. Streptococcus constellatus is part of the normal flora of the orogenital regions of the body; when found elsewhere, it causes pyogenic abscesses in the brain and digestive tract. In this case, the Streptococcus constellatus bacteremia was secondary to prolonged hospitalization in a patient with respiratory syncytial virus (RSV) bronchiolitis. This report serves to make physicians aware of and to define treatment options for Streptococcus constellatus as a rarely isolated organism that …

A Rare Appendiceal Mucocele Of The Appendix Captured On The Ultrasound: Case Report, Vera Shulgina, Meghan Single, Joel Thompson

Advances in Clinical Medical Research and Healthcare Delivery

Appendiceal mucocele is a rare disease which results from an accumulation of mucus in the lumen of the appendix, leading to distension and obstruction of the lumen. Clinical diagnosis is often delayed, as the presenting symptoms are usually non-specific. Even with the use of imaging, preoperative diagnosis is difficult. The treatment is surgical, with the extent determined by the surgical specimen. Definitive diagnosis is by histopathology. Our case report presents a rare case of appendiceal mucocele originally captured by ultrasound. The aim of this paper is to further understand the clinical presentation, discuss key ultrasound findings, and examine the proper …

Covid-19-Associated Myocarditis: Screening For Early Diagnosis, Yousuf Khan, Salmman Ahmed, Samuel John Wlasowicz, Ronald G. Lott Iii, Xavier C. Zonna

Advances in Clinical Medical Research and Healthcare Delivery

The SARS-CoV-2 virus (causing COVID-19), has infected about 770 million people, and caused the death of about 6.9 million people worldwide in the span of three years (John Hopkins Resource Center). Common symptoms of a patient infected with the virus include shortness of breath, fever, chills, fatigue, loss of taste or smell, and muscle aches. However, recent studies have also shown a prevalence of patients presenting with cardiac inflammation (endocarditis, myocarditis or pericarditis) as a potential comorbidity, both during the infectious stage as well as after the infection has subsided. A pattern of specific clinical markers may be indicative of …

Intracystic Hemorrhage In A Simple Liver Cyst Due To Dual Anti-Platelet Therapy After Percutaneous Coronary Intervention, Nauman Naeem, Andrew Takla, Saarwaani Vallabhajosyula, Nagesh R. Jadhav

Advances in Clinical Medical Research and Healthcare Delivery

Hemorrhage into a simple hepatic cyst often results in development of a complex cystic lesion, which makes this identical to a cystic tumor. We present a striking example of this decision-making in a patient with suspected intracystic hemorrhage from recent anti-platelet medication use post-percutaneous coronary intervention (PCI). 83-year-old male presented to the hospital with acute right upper quadrant (RUQ) abdominal pain, severe and constant. This was associated with nausea and constipation. Medical history was significant for recent PCI and initiation of dual anti-platelet therapy (DAPT) ten days ago, and chronic thrombocytopenia. Ultrasound and CT confirmed complex 12.8 x 11.4 x …

Predictive Modeling And Cryo-Em: A Synergistic Approach To Modeling Macromolecular Structure, Michael R Corum, Harikanth Venkannagari, Corey F Hryc, Matthew L Baker

Faculty, Staff and Student Publications

Over the last 15 years, structural biology has seen unprecedented development and improvement in two areas: electron cryo-microscopy (cryo-EM) and predictive modeling. Once relegated to low resolutions, single-particle cryo-EM is now capable of achieving near-atomic resolutions of a wide variety of macromolecular complexes. Ushered in by AlphaFold, machine learning has powered the current generation of predictive modeling tools, which can accurately and reliably predict models for proteins and some complexes directly from the sequence alone. Although they offer new opportunities individually, there is an inherent synergy between these techniques, allowing for the construction of large, complex macromolecular models. Here, we …

Evaluation Of Outcomes Between The Top-Down Versus The Bottom-Up Approach For Retropubic Midurethral Sling, Vidushri Mehrotra, John Pearl, David Sheyn, Susan D. Wherley

Student Scholarship

Introduction and hypothesis: Retropubic midurethral sling (MUS) placement is the gold standard for the treatment of stress urinary incontinence in the USA. The procedure can be approached from either a top-down or a bottom-up direction, but there is a paucity of contemporary data regarding outcomes between these approaches. The aim of this study was to provide updated clinical outcomes data. Methods: This was a retrospective cohort study of women undergoing the retropubic MUS procedure alone or at the time of pelvic organ prolapse repair between 2010 and 2020 at a single academic medical center. The electronic medical record was used …

The Pathogenicity Of Vancomycin-Resistant Enterococcus Faecalis To Colon Cancer Cells, Li Zhang, Mingxia Deng, Jing Liu, Jiajie Zhang, Fangyu Wang, Wei Yu

Faculty, Staff and Student Publications

BACKGROUND: The aim of this study was to investigate the pathogenicity of vancomycin-resistant Enterococcus faecalis (VREs) to human colon cells in vitro.

METHODS: Three E. faecalis isolates (2 VREs and E. faecalis ATCC 29212) were cocultured with NCM460, HT-29 and HCT116 cells. Changes in cell morphology and bacterial adhesion were assessed at different time points. Interleukin-8 (IL-8) and vascular endothelial growth factor A (VEGFA) expression were measured via RT-qPCR and enzyme-linked immunosorbent assay (ELISA), respectively. Cell migration and human umbilical vein endothelial cells (HUVECs) tube formation assays were used for angiogenesis studies. The activity of PI3K/AKT/mTOR signaling pathway was measured …

Multivalent Cytomegalovirus Glycoprotein B Nucleoside Modified Mrna Vaccines Did Not Demonstrate A Greater Antibody Breadth, Hsuan-Yuan Wang, Leike Li, Cody S Nelson, Richard Barfield, Sarah Valencia, Cliburn Chan, Hiromi Muramatsu, Paulo J C Lin, Norbert Pardi, Zhiqiang An, Drew Weissman, Sallie R Permar

Faculty, Staff and Student Publications

Human cytomegalovirus (HCMV) remains the most common congenital infection and infectious complication in immunocompromised patients. The most successful HCMV vaccine to date, an HCMV glycoprotein B (gB) subunit vaccine adjuvanted with MF59, achieved 50% efficacy against primary HCMV infection. A previous study demonstrated that gB/MF59 vaccinees were less frequently infected with HCMV gB genotype strains most similar to the vaccine strain than strains encoding genetically distinct gB genotypes, suggesting strain-specific immunity accounted for the limited efficacy. To determine whether vaccination with multiple HCMV gB genotypes could increase the breadth of anti-HCMV gB humoral and cellular responses, we immunized 18 female …

Recombinant Rod Domain Of Vimentin Reduces Sars-Cov-2 Viral Replication By Blocking Spike Protein-Ace2 Interactions, Fong Wilson Lam, Cameron August Brown, Shannon Elizabeth Ronca

Faculty, Staff and Students Publications

Although the SARS-CoV-2 vaccination is the primary preventive intervention, there are still few antiviral therapies available, with current drugs decreasing viral replication once the virus is intracellular. Adding novel drugs to target additional points in the viral life cycle is paramount in preventing future pandemics. The purpose of this study was to create and test a novel protein to decrease SARS-CoV-2 replication. We created the recombinant rod domain of vimentin (rhRod) in E. coli and used biolayer interferometry to measure its affinity to the SARS-CoV-2 S1S2 spike protein and the ability to block the SARS-CoV-2–ACE2 interaction. We performed plaque assays …

Association Of Lifestyle Intervention With Risk For Cardiovascular Events Differs By Level Of Glycated Hemoglobin, Michael P Bancks, Scott J Pilla, Ashok Balasubramanyam, Hsin-Chieh Yeh, Karen C Johnson, Joseph Rigdon, Lynne E Wagenknecht, Mark A Espeland

Faculty, Staff and Students Publications

Purpose: We reevaluated the Action for Health in Diabetes (Look AHEAD) intensive lifestyle intervention (ILI) to assess whether the effect of ILI on cardiovascular disease (CVD) prevention differed by baseline glycated hemoglobin (HbA1c).

Methods: Look AHEAD randomized 5145 adults, aged 45 to 76 years with type 2 diabetes and overweight/obesity to ILI or a diabetes support and education (DSE) control group for a median of 9.6 years. ILI focused on achieving weight loss through decreased caloric intake and increased physical activity. We assessed the parent trial's primary composite CVD outcome. We evaluated additive and multiplicative heterogeneity of the intervention on …

Inhibition Of Csf1r And Kit With Pexidartinib Reduces Inflammatory Signaling And Cell Viability In Endometriosis, Timothy N Dunn, Dominique I Cope, Suni Tang, Tirupataiah Sirupangi, Sydney E Parks, Zian Liao, Fei Yuan, Chad J Creighton, Ramya P Masand, Linda Alpuing Radilla, Xiaoming Guan, Laura Detti, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

Endometriosis is a common and debilitating disease, affecting ∼170 million women worldwide. Affected patients have limited therapeutic options such as hormonal suppression or surgical excision of the lesions, though therapies are often not completely curative. Targeting receptor tyrosine kinases (RTKs) could provide a nonhormonal treatment option for endometriosis. We determined that 2 RTKs, macrophage-colony stimulating factor 1 receptor (CSF1R) and mast/stem cell growth factor receptor KIT (KIT), are overexpressed in endometriotic lesions and could be novel nonhormonal therapeutic targets for endometriosis. The kinase activity of CSF1R and KIT is suppressed by pexidartinib, a small molecule inhibitor that was recently approved …

Current Strategies For Increasing Knock-In Efficiency In Crispr/Cas9-Based Approaches, Andrés Felipe Leal, Angelica María Herreno-Pachón, Eliana Benincore-Flórez, Amali Karunathilaka, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Since its discovery in 2012, the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) system has supposed a promising panorama for developing novel and highly precise genome editing-based gene therapy (GT) alternatives, leading to overcoming the challenges associated with classical GT. Classical GT aims to deliver transgenes to the cells via their random integration in the genome or episomal persistence into the nucleus through lentivirus (LV) or adeno-associated virus (AAV), respectively. Although high transgene expression efficiency is achieved by using either LV or AAV, their nature can result in severe side effects in humans. For instance, …

Molecular, Metabolic, And Subcellular Mapping Of The Tumor Immune Microenvironment Via 3d Targeted And Non-Targeted Multiplex Multi-Omics Analyses, Sammy Ferri-Borgogno, Jared K Burks, Erin H Seeley, Trevor D Mckee, Danielle L Stolley, Akshay V Basi, Javier A Gomez, Basant T Gamal, Shamini Ayyadhury, Barrett C Lawson, Melinda S Yates, Michael J Birrer, Karen H Lu, Samuel C Mok

Faculty, Staff and Student Publications

Most platforms used for the molecular reconstruction of the tumor-immune microenvironment (TIME) of a solid tumor fail to explore the spatial context of the three-dimensional (3D) space of the tumor at a single-cell resolution, and thus lack information about cell-cell or cell-extracellular matrix (ECM) interactions. To address this issue, a pipeline which integrated multiplex spatially resolved multi-omics platforms was developed to identify crosstalk signaling networks among various cell types and the ECM in the 3D TIME of two FFPE (formalin-fixed paraffin embedded) gynecologic tumor samples. These platforms include non-targeted mass spectrometry imaging (glycans, metabolites, and peptides) and Stereo-seq (spatial transcriptomics) …

Circulating Microrna Biomarkers Of Thiazide Response In Hypertension, Lakshmi Manasa S Chekka, Marwa Tantawy, Taimour Langaee, Danxin Wang, Rolf Renne, Arlene B Chapman, John G Gums, Eric Boerwinkle, Rhonda M Cooper-Dehoff, Julie A Johnson

Faculty, Staff and Student Publications

Background: Thiazide diuretics are the second most frequently prescribed class of antihypertensives, but up to 50% of patients with hypertension have minimal antihypertensive response to thiazides. We explored circulating microRNAs (miRNAs) in search of predictive biomarkers of thiazide response.

Methods and results: We profiled 754 miRNAs in baseline plasma samples of 36 hypertensive European American adults treated with hydrochlorothiazide, categorized into responders (n=18) and nonresponders (n=18) on the basis of diastolic blood pressure response to hydrochlorothiazide. miRNAs with ≥2.5-fold differential expression between responders and nonresponders were considered for validation in 3 cohorts (n=50 each): hydrochlorothiazide-treated European Americans, chlorthalidone-treated European Americans, …

An Extended Bayesian Semi-Mechanistic Dose-Finding Design For Phase I Oncology Trials Using Pharmacokinetic And Pharmacodynamic Information, Chao Yang, Yisheng Li

Faculty, Staff and Student Publications

We propose a model-based, semi-mechanistic dose-finding (SDF) design for phase I oncology trials that incorporates pharmacokinetic/pharmacodynamic (PK/PD) information when modeling the dose-toxicity relationship. This design is motivated by a phase Ib/II clinical trial of anti-CD20/CD3 T cell therapy in non-Hodgkin lymphoma patients; it extends a recently proposed SDF model framework by incorporating measurements of a PD biomarker relevant to the primary dose-limiting toxicity (DLT). We propose joint Bayesian modeling of the PK, PD, and DLT outcomes. Our extensive simulation studies show that on average the proposed design outperforms some common phase I trial designs, including modified toxicity probability interval (mTPI) …