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2024

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Full-Text Articles in Medicine and Health Sciences

Cell-Free Dna For The Detection Of Kidney Allograft Rejection, Olivier Aubert, Tarek Alhamad, Raja Dandamudi, Vikas R Dharnidharka, Et Al. Aug 2024

Cell-Free Dna For The Detection Of Kidney Allograft Rejection, Olivier Aubert, Tarek Alhamad, Raja Dandamudi, Vikas R Dharnidharka, Et Al.

2020-Current year OA Pubs

Donor-derived cell-free DNA (dd-cfDNA) is an emerging noninvasive biomarker that has the potential to detect allograft injury. The capacity of dd-cfDNA to detect kidney allograft rejection and its added clinical value beyond standard of care patient monitoring is unclear. We enrolled 2,882 kidney allograft recipients from 14 transplantation centers in Europe and the United States in an observational population-based study. The primary analysis included 1,134 patients. Donor-derived cell-free DNA levels strongly correlated with allograft rejection, including antibody-mediated rejection (P < 0.0001), T cell-mediated rejection (P < 0.0001) and mixed rejection (P < 0.0001). In multivariable analysis, circulating dd-cfDNA was significantly associated with allograft rejection (odds ratio 2.275; 95% confidence interval (CI) 1.902-2.739; P < 0.0001) independently of standard of care patient monitoring parameters. The inclusion of dd-cfDNA to a standard of care prediction model showed improved discrimination (area under the curve 0.777 (95% CI 0.741-0.811) to 0.821 (95% CI 0.784-0.852); P = 0.0011) and calibration. These results were confirmed in the external validation cohorts (n = 1,748) including a cohort of African American patients (n = 439). Finally, dd-cfDNA showed high predictive value to detect subclinical rejection in stable patients. Our study provides insights on the potential value of assessing dd-cfDNA, in addition to standard of care monitoring, to improve the detection of allograft rejection. ClinicalTrials.gov registration: NCT05995379 .


Community-Based Participatory Research And System Dynamics Modeling For Improving Retention In Hypertension Care, Jiancheng Ye, Ikechukwu A Orji, Michelle A Birkett, Lisa R Hirschhorn, Theresa L Walunas, Justin D Smith, Namratha R Kandula, Gabriel L Shedul, Mark D Huffman, Dike B Ojji Aug 2024

Community-Based Participatory Research And System Dynamics Modeling For Improving Retention In Hypertension Care, Jiancheng Ye, Ikechukwu A Orji, Michelle A Birkett, Lisa R Hirschhorn, Theresa L Walunas, Justin D Smith, Namratha R Kandula, Gabriel L Shedul, Mark D Huffman, Dike B Ojji

2020-Current year OA Pubs

IMPORTANCE: The high prevalence of hypertension calls for broad, multisector responses that foster prevention and care services, with the goal of leveraging high-quality treatment as a means of reducing hypertension incidence. Health care system improvements require stakeholder input from across the care continuum to identify gaps and inform interventions that improve hypertension care service, delivery, and retention; system dynamics modeling offers a participatory research approach through which stakeholders learn about system complexity and ways to model sustainable system-level improvements.

OBJECTIVE: To assess the association of simulated interventions with hypertension care retention rates in the Nigerian primary health care system using …


Potential Us Health Care Savings Based On Clinician Views Of Feasible Site-Of-Care Shifts, Nikhil R Sahni, Crosbie Marine, David M Cutler, Laura N Medford-Davis, Melvin Mezue, Omar Kattan, Ed Levine, Karen E Joynt Maddox Aug 2024

Potential Us Health Care Savings Based On Clinician Views Of Feasible Site-Of-Care Shifts, Nikhil R Sahni, Crosbie Marine, David M Cutler, Laura N Medford-Davis, Melvin Mezue, Omar Kattan, Ed Levine, Karen E Joynt Maddox

2020-Current year OA Pubs

IMPORTANCE: Shifting care to alternative sites when clinically appropriate may be associated with reduced US health care spending, improved access, and, in some cases, improved care outcomes.

OBJECTIVE: To fill 2 main gaps in the current literature on site-of-care shifts: (1) understanding the clinician perspective on appropriateness of alternative care sites, given the central role they play in referrals and patient trust and (2) considering all potential sites where care could shift and calculating net savings potential.

DESIGN, SETTING, AND PARTICIPANTS: In this survey study, physicians (MDs and DOs), nurse practitioners, physician assistants, nurse anesthetists, radiology and imaging technicians, and …


Plasma Proteomic Signature Predicts Myeloid Neoplasm Risk, Duc Tran, J Scott Beeler, Jie Liu, Brian Wiley, Irenaeus C C Chan, Zilan Xin, Michael H Kramer, Armel L Batchi-Bouyou, Xiaoyu Zong, Matthew J Walter, Giulia E M Petrone, Sarantis Chlamydas, Francesca Ferraro, Stephen T Oh, Daniel C Link, Ben Busby, Yin Cao, Kelly L Bolton Aug 2024

Plasma Proteomic Signature Predicts Myeloid Neoplasm Risk, Duc Tran, J Scott Beeler, Jie Liu, Brian Wiley, Irenaeus C C Chan, Zilan Xin, Michael H Kramer, Armel L Batchi-Bouyou, Xiaoyu Zong, Matthew J Walter, Giulia E M Petrone, Sarantis Chlamydas, Francesca Ferraro, Stephen T Oh, Daniel C Link, Ben Busby, Yin Cao, Kelly L Bolton

2020-Current year OA Pubs

PURPOSE: Clonal hematopoiesis (CH) is thought to be the origin of myeloid neoplasms (MN). Yet, our understanding of the mechanisms driving CH progression to MN and clinical risk prediction of MN remains limited. The human proteome reflects complex interactions between genetic and epigenetic regulation of biological systems. We hypothesized that the plasma proteome might predict MN risk and inform our understanding of the mechanisms promoting MN development.

EXPERIMENTAL DESIGN: We jointly characterized CH and plasma proteomic profiles of 46,237 individuals in the UK Biobank at baseline study entry. During 500,036 person-years of follow-up, 115 individuals developed MN. Cox proportional hazard …


Expanding A Behavioral View On Digital Health Access: Drivers And Strategies To Promote Equity, Maura M Kepper, Lauren A Fowler, Isabelle S Kusters, Jean W Davis, Manal Baqer, Sara Sagui-Henson, Yunyu Xiao, Adati Tarfa, Jean C Yi, Bryan Gibson, Kristin E Heron, Nicole M Alberts, Marissa Burgermaster, Veronica Ps Njie-Carr, Lisa M Klesges Aug 2024

Expanding A Behavioral View On Digital Health Access: Drivers And Strategies To Promote Equity, Maura M Kepper, Lauren A Fowler, Isabelle S Kusters, Jean W Davis, Manal Baqer, Sara Sagui-Henson, Yunyu Xiao, Adati Tarfa, Jean C Yi, Bryan Gibson, Kristin E Heron, Nicole M Alberts, Marissa Burgermaster, Veronica Ps Njie-Carr, Lisa M Klesges

2020-Current year OA Pubs

The potential and threat of digital tools to achieve health equity has been highlighted for over a decade, but the success of achieving equitable access to health technologies remains challenging. Our paper addresses renewed concerns regarding equity in digital health access that were deepened during the COVID-19 pandemic. Our viewpoint is that (1) digital health tools have the potential to improve health equity if equitable access is achieved, and (2) improving access and equity in digital health can be strengthened by considering behavioral science-based strategies embedded in all phases of tool development. Using behavioral, equity, and access frameworks allowed for …


Opportunities To Improve Antibiotic Prescribing For Adults With Acute Sinusitis, United States, 2016–2020, Axel A Vazquez Deida, Destani J Bizune, Christine Kim, John M Sahrmann, Guillermo V Sanchez, Adam L Hersh, Anne M Butler, Lauri A Hicks, Sarah Kabbani Aug 2024

Opportunities To Improve Antibiotic Prescribing For Adults With Acute Sinusitis, United States, 2016–2020, Axel A Vazquez Deida, Destani J Bizune, Christine Kim, John M Sahrmann, Guillermo V Sanchez, Adam L Hersh, Anne M Butler, Lauri A Hicks, Sarah Kabbani

2020-Current year OA Pubs

BACKGROUND: Better understanding differences associated with antibiotic prescribing for acute sinusitis can help inform antibiotic stewardship strategies. We characterized antibiotic prescribing patterns for acute sinusitis among commercially insured adults and explored differences by patient- and prescriber-level factors.

METHODS: Outpatient encounters among adults aged 18 to 64 years diagnosed with sinusitis between 2016 and 2020 were identified by national administrative claims data. We classified antibiotic agents-first-line (amoxicillin-clavulanate or amoxicillin) and second-line (doxycycline, levofloxacin, or moxifloxacin)-and ≤7-day durations as guideline concordant based on clinical practice guidelines. Modified Poisson regression was used to examine the association between patient- and prescriber-level factors and guideline-concordant …


Eliciting Clinician Perspectives On Asymptomatic Bacteriuria To Identify Targets For Antimicrobial Stewardship Education And Decision Support, Michael J Durkin, Viktoria Schmitz, Kevin Hsueh, Katheryn Ney, Mary C Politi Aug 2024

Eliciting Clinician Perspectives On Asymptomatic Bacteriuria To Identify Targets For Antimicrobial Stewardship Education And Decision Support, Michael J Durkin, Viktoria Schmitz, Kevin Hsueh, Katheryn Ney, Mary C Politi

2020-Current year OA Pubs

BACKGROUND: The aim of this study was to elicit clinicians' perspectives to help reduce antibiotic prescribing for asymptomatic bacteriuria and improve a patient-centered educational brochure for older adults with urinary tract infections or asymptomatic bacteriuria.

METHODS: Between October 2023 and April 2024, we conducted semi-structured qualitative interviews of clinicians who treat patients aged ≥65 years for urinary tract infections or bacteria in the urine, at infectious disease clinics, community senior living facilities, memory care clinics, and general practice. We developed an interview guide based on a behavior change framework and thematically analyzed written transcripts of audio-recorded interviews using inductive and …


Residential Street Trees And Cardiovascular Disease Among Urban-Dwelling Mexican Adults, Christine Campbell Aug 2024

Residential Street Trees And Cardiovascular Disease Among Urban-Dwelling Mexican Adults, Christine Campbell

Walden Dissertations and Doctoral Studies

Cardiovascular diseases (CVDs) are a significant public health burden in Mexico despite national efforts to address traditional risk factors. With growing evidence that elements of nature can improve physical and mental health of people living in cities, this quantitative epidemiological study of secondary data examined the relationship between the presence of street trees in Mexican metropolitan areas and self-reported CVD in adults over age 40. The integrated socio-environmental model of health and well-being provided the conceptual framework for the study. A secondary data analysis was performed using combined individual health data from Mexico’s 2012 National Health and Nutrition Survey and …


Obicetrapib On Top Of Maximally Tolerated Lipid-Modifying Therapies In Participants With Or At High Risk For Atherosclerotic Cardiovascular Disease: Rationale And Designs Of Broadway And Brooklyn, Stephen J Nicholls, Adam J Nelson, Marc Ditmarsch, John J P Kastelein, Christie M Ballantyne, Kausik K Ray, Ann Marie Navar, Steven E Nissen, Anne C Goldberg, Liam R Brunham, Danielle Curcio, Erin Wuerdeman, Annie Neild, Douglas Kling, Andrew Hsieh, Mary R Dicklin, Brian A Ference, Ulrich Laufs, Maciej Banach, Roxana Mehran, Alberico L Catapano, Michael H Davidson Aug 2024

Obicetrapib On Top Of Maximally Tolerated Lipid-Modifying Therapies In Participants With Or At High Risk For Atherosclerotic Cardiovascular Disease: Rationale And Designs Of Broadway And Brooklyn, Stephen J Nicholls, Adam J Nelson, Marc Ditmarsch, John J P Kastelein, Christie M Ballantyne, Kausik K Ray, Ann Marie Navar, Steven E Nissen, Anne C Goldberg, Liam R Brunham, Danielle Curcio, Erin Wuerdeman, Annie Neild, Douglas Kling, Andrew Hsieh, Mary R Dicklin, Brian A Ference, Ulrich Laufs, Maciej Banach, Roxana Mehran, Alberico L Catapano, Michael H Davidson

Faculty, Staff and Students Publications

Background: Obicetrapib, a novel, selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), LDL particles, apolipoprotein (Apo) B, and lipoprotein(a) [Lp(a)] and increases high-density lipoprotein cholesterol (HDL-C) when added to statins with or without ezetimibe. By substantially reducing LDL-C, obicetrapib has the potential to lower atherogenic lipoproteins in patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) whose LDL-C levels remain high despite treatment with available maximally tolerated lipid-modifying therapies, addressing an unmet medical need in a patient population at high risk for cardiovascular events.

Methods and results: BROADWAY (NCT05142722) and BROOKLYN ( …


Comparative Effectiveness Research Trial For Antidepressant Incomplete And Non-Responders With Treatment Resistant Depression (Ascertain-Trd) A Randomized Clinical Trial, George I Papakostas, Madhukar H Trivedi, Richard C Shelton, Dan V Iosifescu, Michael E Thase, Manish K Jha, Sanjay J Mathew, Charles Debattista, Mehmet E Dokucu, Olga Brawman-Mintzer, Glenn W Currier, William Vaughn Mccall, Mandana Modirrousta, Matthew Macaluso, Alexander Bystritsky, Fidel Vila Rodriguez, Erik B Nelson, Albert S Yeung, Anna Feeney, Leslie C Macgregor, Thomas Carmody, Maurizio Fava Aug 2024

Comparative Effectiveness Research Trial For Antidepressant Incomplete And Non-Responders With Treatment Resistant Depression (Ascertain-Trd) A Randomized Clinical Trial, George I Papakostas, Madhukar H Trivedi, Richard C Shelton, Dan V Iosifescu, Michael E Thase, Manish K Jha, Sanjay J Mathew, Charles Debattista, Mehmet E Dokucu, Olga Brawman-Mintzer, Glenn W Currier, William Vaughn Mccall, Mandana Modirrousta, Matthew Macaluso, Alexander Bystritsky, Fidel Vila Rodriguez, Erik B Nelson, Albert S Yeung, Anna Feeney, Leslie C Macgregor, Thomas Carmody, Maurizio Fava

Staff and Researcher Publications

Further research is needed to help improve both the standard of care and the outcome for patients with treatment-resistant depression. A particularly critical evidence gap exists with respect to whether pharmacological or non-pharmacological augmentation is superior to antidepressant switch, or vice-versa. The objective of this study was to compare the effectiveness of augmentation with aripiprazole or repetitive transcranial magnetic stimulation versus switching to the antidepressant venlafaxine XR (or duloxetine for those not eligible to receive venlafaxine) for treatment-resistant depression. In this multi-site, 8-week, randomized, open-label study, 278 subjects (196 females and 82 males, mean age 45.6 years (SD 15.3)) with …


Complement C3ar Signaling: Immune And Metabolic Modulation And Its Impact On Alzheimer’S Disease, Manasee Gedam, Hui Zheng Aug 2024

Complement C3ar Signaling: Immune And Metabolic Modulation And Its Impact On Alzheimer’S Disease, Manasee Gedam, Hui Zheng

Center on Aging Staff Publications

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia among the elderly population. Despite its widespread prevalence, our comprehension of the intricate mechanisms governing the pathogenesis of the disease remains incomplete, posing a challenge for the development of efficient therapies. Pathologically characterized by the presence of amyloid β plaques and neurofibrillary tau tangles, AD is also accompanied by the hyperactivation of glial cells and the immune system. The complement cascade, the evolutionarily conserved innate immune pathway, has emerged as a significant contributor to AD. This review focuses on one of the complement components, the …


Secondary Endpoint Utilization And Publication Rate Among Phase Iii Oncology Trials, Esther J Beck, Alexander D Sherry, Marcus A Florez, Ramez Kouzy, Joseph Abi Jaoude, Timothy A Lin, Avital M Miller, Adina H Passy, Gabrielle S Kupferman, Roshal R Patel, Fumiko Chino, Victoria Serpas Higbie, Christine M Parseghian, Michael J Overman, Bruce D Minsky, Charles R Thomas, Chad Tang, Pavlos Msaouel, Ethan B Ludmir Aug 2024

Secondary Endpoint Utilization And Publication Rate Among Phase Iii Oncology Trials, Esther J Beck, Alexander D Sherry, Marcus A Florez, Ramez Kouzy, Joseph Abi Jaoude, Timothy A Lin, Avital M Miller, Adina H Passy, Gabrielle S Kupferman, Roshal R Patel, Fumiko Chino, Victoria Serpas Higbie, Christine M Parseghian, Michael J Overman, Bruce D Minsky, Charles R Thomas, Chad Tang, Pavlos Msaouel, Ethan B Ludmir

Faculty, Staff and Student Publications

UNLABELLED: Secondary endpoints (SEP) provide crucial information in the interpretation of clinical trials, but their features are not yet well understood. Thus, we sought to empirically characterize the scope and publication rate of SEPs among late-phase oncology trials. We assessed SEPs for each randomized, published phase III oncology trial across all publications and ClinicalTrials.gov, performing logistic regressions to evaluate associations between trial characteristics and SEP publication rates. After screening, a total of 280 trials enrolling 244,576 patients and containing 2,562 SEPs met the inclusion criteria. Only 22% of trials (62/280) listed all SEPs consistently between ClinicalTrials.gov and the trial protocol. …


Chick Embryo Chorioallantoic Membrane As A Platform For Assessing The In Vivo Efficacy Of Chimeric Antigen Receptor T-Cell Therapy In Solid Tumors, Allison J Nipper, Emilie A K Warren, Kershena S Liao, Hsuan-Chen Liu, Chieko Michikawa, Caroline E Porter, Gabrielle A Wells, Mariana Villanueva, Fabio Henrique Brasil Da Costa, Ratna Veeramachaneni, Hugo Villanueva, Masataka Suzuki, Andrew G Sikora Aug 2024

Chick Embryo Chorioallantoic Membrane As A Platform For Assessing The In Vivo Efficacy Of Chimeric Antigen Receptor T-Cell Therapy In Solid Tumors, Allison J Nipper, Emilie A K Warren, Kershena S Liao, Hsuan-Chen Liu, Chieko Michikawa, Caroline E Porter, Gabrielle A Wells, Mariana Villanueva, Fabio Henrique Brasil Da Costa, Ratna Veeramachaneni, Hugo Villanueva, Masataka Suzuki, Andrew G Sikora

Faculty, Staff and Student Publications

The fertilized chicken egg chorioallantoic membrane (CAM), a highly vascularized membrane nourishing the developing embryo, also supports rapid growth of three-dimensional vascularized tumors from engrafted cells and tumor explants. Because murine xenograft models suffer limitations of time, cost, and scalability, we propose CAM tumors as a rapid, efficient screening tool for assessing anti-tumor efficacy of chimeric Ag receptor (CAR) T cells against solid tumors. We tested the efficacy of human epidermal growth factor receptor 2 (HER2)-specific CAR T cells against luminescent, HER2-expressing (FaDu, SCC-47) or HER2-negative (MDA-MB-468) CAM-engrafted tumors. Three days after tumor engraftment, HER2-specific CAR T cells were applied …


Modern Perspectives On Hypertrophic Cardiomyopathy-No One Size Fits All, Brett Doliner, Hadeel Gaddar, Ramsey Kalil, Alexander Postalian Aug 2024

Modern Perspectives On Hypertrophic Cardiomyopathy-No One Size Fits All, Brett Doliner, Hadeel Gaddar, Ramsey Kalil, Alexander Postalian

The Texas Heart Institute Journal

Despite substantial advances in the management of hypertrophic cardiomyopathy, advanced heart failure remains a major cause of morbidity in this patient population. This narrative review presents the case of a patient with hypertrophic obstructive cardiomyopathy who underwent alcohol septal ablation to frame a discussion of modern therapies for hypertrophic cardiomyopathy. The current treatment landscape includes medications, both old and new, and surgical and procedural interventions to relieve mechanical obstruction. Several promising new modalities for relieving obstruction are in the nascent stages of development.


Increasing Incidence Of Streptococcus Anginosus Group Intracranial Infections Associated With Sinusitis, Otitis Media, And Mastoiditis In Children, Elisabeth A Hoyer, Marritta Joseph, James Dunn, Howard L Weiner, Amy Dimachkieh, Anthony R Flores, Misu A Sanson, Hossaena Ayele, Blake M Hanson, Sheldon L Kaplan, Jesus G Vallejo, J Chase Mcneil Aug 2024

Increasing Incidence Of Streptococcus Anginosus Group Intracranial Infections Associated With Sinusitis, Otitis Media, And Mastoiditis In Children, Elisabeth A Hoyer, Marritta Joseph, James Dunn, Howard L Weiner, Amy Dimachkieh, Anthony R Flores, Misu A Sanson, Hossaena Ayele, Blake M Hanson, Sheldon L Kaplan, Jesus G Vallejo, J Chase Mcneil

Faculty, Staff and Student Publications

BACKGROUND: The Streptococcus anginosus group (SAG) pathogens have the potential to cause head and neck space infections, including intracranial abscesses. Several centers noted an increase in intracranial abscesses in children during the SARS-CoV-2 pandemic, prompting a Centers for Disease Control and Prevention health alert in May 2022. We examined the epidemiology of pediatric intracranial abscesses at a tertiary care center with a focus on SAG pre- and post-pandemic.

METHODS: Cases of intracranial abscesses of any microbiologic etiology admitted from January 2011 to December 2022 were identified using International Classification of Diseases 10 codes. Subjects were cross-referenced with culture results from …


Active Mutual Conjoint Estimation Of Multiple Contrast Sensitivity Functions, Dom C P Marticorena, Quinn Wai Wong, Jake Browning, Ken Wilbur, Pinakin Gunvant Davey, Aaron R Seitz, Jacob R Gardner, Dennis L Barbour Aug 2024

Active Mutual Conjoint Estimation Of Multiple Contrast Sensitivity Functions, Dom C P Marticorena, Quinn Wai Wong, Jake Browning, Ken Wilbur, Pinakin Gunvant Davey, Aaron R Seitz, Jacob R Gardner, Dennis L Barbour

2020-Current year OA Pubs

Recent advances in nonparametric contrast sensitivity function (CSF) estimation have yielded a new tradeoff between accuracy and efficiency not available to classical parametric estimators. An additional advantage of this new framework is the ability to independently tune multiple aspects of the estimator to seek further improvements. Machine learning CSF estimation with Gaussian processes allows for design optimization in the kernel, acquisition function, and underlying task representation, to name a few. This article describes a novel kernel for CSF estimation that is more flexible than a kernel based on strictly functional forms. Despite being more flexible, it can result in a …


Maldi-Tof Mass Spectrometry Misidentification Of Cutibacterium Namnetense And Cutibacterium Modestum: Implications For Multiplex Pcr Phylotyping Of Cutibacterium Acnes, Joseph Mclaughlin, Carey-Ann D Burnham, Andrew Mcdowell Aug 2024

Maldi-Tof Mass Spectrometry Misidentification Of Cutibacterium Namnetense And Cutibacterium Modestum: Implications For Multiplex Pcr Phylotyping Of Cutibacterium Acnes, Joseph Mclaughlin, Carey-Ann D Burnham, Andrew Mcdowell

2020-Current year OA Pubs

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) can misidentify Cutibacterium namnetense and Cutibacterium modestum as Cutibacterium acnes. We now describe how such MALDI-TOF MS misidentification explains previous reports of C. acnes isolates that could not be characterised using a multiplex PCR phylotyping assay.


Augustus Waller's Foresight Realized: Sarm1 In Peripheral Neuropathies, Stefanie Geisler Aug 2024

Augustus Waller's Foresight Realized: Sarm1 In Peripheral Neuropathies, Stefanie Geisler

2020-Current year OA Pubs

Peripheral neuropathy is a common neurodegenerative condition characterized by numbness, tingling, pain, and weakness that frequently starts in the distal limbs. Arising from multiple etiologies, many peripheral neuropathies exhibit a slowly progressive course due to axon degeneration for which no effective treatments exist. During the past decade, numerous crucial insights into mechanisms of axon degeneration in peripheral neuropathies emerged from experiments involving nerve-cutting procedures, revealing the central role of the SARM1 axon degeneration pathway in both. Here I review commonalities and differences in the role of SARM1 after nerve cut and in several acquired and inherited peripheral neuropathies. This new …


Local Complement Activation And Modulation In Mucosal Immunity, Devesha H Kulkarni, Marick Starick, Rafael Aponte Alburquerque, Hrishikesh S Kulkarni Aug 2024

Local Complement Activation And Modulation In Mucosal Immunity, Devesha H Kulkarni, Marick Starick, Rafael Aponte Alburquerque, Hrishikesh S Kulkarni

2020-Current year OA Pubs

The complement system is an evolutionarily conserved arm of innate immunity, which forms one of the first lines of host response to pathogens and assists in the clearance of debris. A deficiency in key activators/amplifiers of the cascade results in recurrent infection, whereas a deficiency in regulating the cascade predisposes to accelerated organ failure, as observed in colitis and transplant rejection. Given that there are over 60 proteins in this system, it has become an attractive target for immunotherapeutics, many of which are United States Food and Drug Administration-approved or in multiple phase 2/3 clinical trials. Moreover, there have been …


Analytical Validation Of The Multitarget Stool Rna Test For Colorectal Cancer Screening, Erica K Barnell, Jack Land, Kimberly Kruse, Maya C Scott, Ben Wedeking, Catherine Morrison, Clayton Grass, Ann Zuniga, Elizabeth M Wurtzler, Eric J Duncavage Aug 2024

Analytical Validation Of The Multitarget Stool Rna Test For Colorectal Cancer Screening, Erica K Barnell, Jack Land, Kimberly Kruse, Maya C Scott, Ben Wedeking, Catherine Morrison, Clayton Grass, Ann Zuniga, Elizabeth M Wurtzler, Eric J Duncavage

2020-Current year OA Pubs

The multitarget stool RNA (mt-sRNA) test (ColoSense) is a noninvasive diagnostic test that screens for colorectal cancer and advanced adenomas in average-risk individuals aged 45 years and older. The mt-sRNA test incorporates a commercially available fecal immunochemical test, concentration of eight RNA transcripts, and participant-reported smoking status. As part of the CRC-PREVENT (Colorectal Cancer and Pre-Cancerous Adenoma Non-Invasive Detection Test) clinical trial, 12 analytical validation studies were conducted to assess analytical sensitivity, linearity, precision, interfering substances, cross-reactivity, carry-over, cross-contamination, and robustness. Analytical validation of the mt-sRNA test demonstrated limit of blank, limit of detection, and limit of quantification of < 0.6, < 0.7, and ≤2.5 copies/μL for all markers, respectively. The mt-sRNA test demonstrated linearity between 2.5 and 2500 copies/μL, and < 20% coefficient of variation, and/or ≥95% concordance with regard to precision, interfering substances, carry-over, cross-contamination, and robustness. There was no significant impact of cross-reactivity from non-colorectal cancer diseases. These data provide a framework for laboratories to complete analytical validation for RNA-based panels that require premarket approval as a class III medical device from the US Food and Drug Administration.


Thrombotic Microangiopathy In Pregnancy: Current Understanding And Management Strategies, Manuel Urra, Shannon Lyons, Corina Gabriela Teodosiu, Richard Burwick, Anuja Java Aug 2024

Thrombotic Microangiopathy In Pregnancy: Current Understanding And Management Strategies, Manuel Urra, Shannon Lyons, Corina Gabriela Teodosiu, Richard Burwick, Anuja Java

2020-Current year OA Pubs

Thrombotic microangiopathy (TMA) represents a heterogeneous group of disorders characterized by microvascular thrombosis and end-organ damage. Pregnancy-associated thrombotic microangiopathy (p-TMA) has emerged as a distinct clinical entity with unique diagnostic challenges. Identifying the specific form of p-TMA is critical for appropriate and timely management. This review offers a comprehensive overview of the various forms of thrombotic microangiopathies associated with pregnancy, highlighting our current understanding of their pathophysiology and the evolving landscape of diagnosis and treatment for each.


Racial And Geographic Disparities In Neonatal Brain Care, Zachary A Vesoulis, Stephanie Diggs, Cherise Brackett, Brynne Sullivan Aug 2024

Racial And Geographic Disparities In Neonatal Brain Care, Zachary A Vesoulis, Stephanie Diggs, Cherise Brackett, Brynne Sullivan

2020-Current year OA Pubs

In this review, we explore race-based disparities in neonatology and their impact on brain injury and neurodevelopmental outcomes. We discuss the historical context of healthcare discrimination, focusing on the post-Civil War era and the segregation of healthcare facilities. We highlight the increasing disparity in infant mortality rates between Black and White infants, with premature birth being a major contributing factor, and emphasize the role of prenatal factors such as metabolic syndrome and toxic stress in affecting neonatal health. Furthermore, we examine the geographic and historical aspects of racial disparities, including the consequences of redlining and limited access to healthcare facilities …


Advances In Blood Biomarkers For Alzheimer Disease (Ad): A Review, Araya Dimtsu Assfaw, Suzanne E Schindler, John C Morris Aug 2024

Advances In Blood Biomarkers For Alzheimer Disease (Ad): A Review, Araya Dimtsu Assfaw, Suzanne E Schindler, John C Morris

2020-Current year OA Pubs

Alzheimer disease (AD) and Alzheimer Disease and Related Dementias (AD/ADRD) are growing public health challenges globally affecting millions of older adults, necessitating concerted efforts to advance our understanding and management of these conditions. AD is a progressive neurodegenerative disorder characterized pathologically by amyloid plaques and tau neurofibrillary tangles that are the primary cause of dementia in older individuals. Early and accurate diagnosis of AD dementia is crucial for effective intervention and treatment but has proven challenging to accomplish. Although testing for AD brain pathology with cerebrospinal fluid (CSF) or positron emission tomography (PET) has been available for over 2 decades, …


Head And Neck Squamous Cell Carcinomas Of Unknown Primary: Can Ancillary Studies Help Identify More Primary Tumor Sites?, Troy Hutchens, Wade Thorstad, Xiaowei Wang, Yuanxiang Li, Eric J Duncavage, Lulu Sun, Rebecca D Chernock Aug 2024

Head And Neck Squamous Cell Carcinomas Of Unknown Primary: Can Ancillary Studies Help Identify More Primary Tumor Sites?, Troy Hutchens, Wade Thorstad, Xiaowei Wang, Yuanxiang Li, Eric J Duncavage, Lulu Sun, Rebecca D Chernock

2020-Current year OA Pubs

A subset of head and neck squamous cell carcinomas present solely as metastatic disease in the neck and are of unknown primary origin (SCCUP). Most primary tumors will ultimately be identified, usually in the oropharynx. In a minority of cases, the primary site remains elusive. Here, we examine the role of ancillary testing, including mutational signature analysis (MSA), to help identify likely primary sites in such cases. Twenty-two cases of SCCUP in the neck, collected over a 10-year period, were classified by morphology and viral status; including human papillomavirus (HPV) testing by p16 immunohistochemistry (IHC) and RT-qPCR, as well as …


Nlrp1 Inflammasome Promotes Senescence And Senescence-Associated Secretory Phenotype, Inés Muela-Zarzuela, Juan Miguel Suarez-Rivero, Andrea Gallardo-Orihuela, Chun Wang, Kumi Izawa, Marta De Gregorio-Procopio, Isabelle Couillin, Bernhard Ryffel, Jiro Kitaura, Alberto Sanz, Thomas Von Zglinicki, Gabriel Mbalaviele, Mario D Cordero Aug 2024

Nlrp1 Inflammasome Promotes Senescence And Senescence-Associated Secretory Phenotype, Inés Muela-Zarzuela, Juan Miguel Suarez-Rivero, Andrea Gallardo-Orihuela, Chun Wang, Kumi Izawa, Marta De Gregorio-Procopio, Isabelle Couillin, Bernhard Ryffel, Jiro Kitaura, Alberto Sanz, Thomas Von Zglinicki, Gabriel Mbalaviele, Mario D Cordero

2020-Current year OA Pubs

BACKGROUND: Senescence is a cellular aging-related process triggered by different stresses and characterized by the secretion of various inflammatory factors referred to as senescence-associated secretory phenotype (SASP), some of which are produced by the NLRP3 inflammasome. Here, we present evidence that the NLRP1 inflammasome is a DNA damage sensor and a key mediator of senescence.

METHODS: Senescence was induced in fibroblasts in vitro and in mice. Cellular senescence was assessed by Western blot analysis of several proteins, including p16, p21, p53, and SASP factors, released in the culture media or serum. Inflammasome components, including NLRP1, NLRP3 and GSDMD were knocked …


Poly-Basic Peptides And Polymers As New Drug Candidates Against Plasmodium Falciparum, Roshan Sivakumar, Katherine Floyd, Jessey Erath, Alex Jacoby, Jenny Kim Kim, Peter O Bayguinov, James A J Fitzpatrick, Dennis Goldfarb, Marko Jovanovic, Abhai Tripathi, Sergej Djuranovic, Slavica Pavlovic-Djuranovic Aug 2024

Poly-Basic Peptides And Polymers As New Drug Candidates Against Plasmodium Falciparum, Roshan Sivakumar, Katherine Floyd, Jessey Erath, Alex Jacoby, Jenny Kim Kim, Peter O Bayguinov, James A J Fitzpatrick, Dennis Goldfarb, Marko Jovanovic, Abhai Tripathi, Sergej Djuranovic, Slavica Pavlovic-Djuranovic

2020-Current year OA Pubs

BACKGROUND: Plasmodium falciparum, the malaria-causing parasite, is a leading cause of infection-induced deaths worldwide. The preferred treatment approach is artemisinin-based combination therapy, which couples fast-acting artemisinin derivatives with longer-acting drugs, such as lumefantrine, mefloquine, and amodiaquine. However, the urgency for new treatments has risen due to the parasite's growing resistance to existing therapies. In this study, a common characteristic of the P. falciparum proteome-stretches of poly-lysine residues, such as those found in proteins related to adhesion and pathogenicity-is investigated for its potential to treat infected erythrocytes.

METHODS: This study utilizes in vitro culturing of intra-erythrocytic P. falciparum to assess the …


A Training Protocol Compliance Of 13% Was Observed In A Research Study Of Clinical Research Professionals, Erin D Solomon, Jessica Mozersky, Meredith V Parsons, Kari Baldwin, Melody Goodman, James M Dubois Aug 2024

A Training Protocol Compliance Of 13% Was Observed In A Research Study Of Clinical Research Professionals, Erin D Solomon, Jessica Mozersky, Meredith V Parsons, Kari Baldwin, Melody Goodman, James M Dubois

2020-Current year OA Pubs

OBJECTIVE: We attempted to conduct a randomized controlled trial of three different informed consent training formats to evaluate their effectiveness. We recruited 503 clinical research professionals, who received $50 for participation. Incidental findings showed unexpectedly low rates of compliance with completing the study training protocols, resulting in insufficient statistical power to test our original hypotheses. In this report, we conducted a secondary analysis of the data in which we characterize and evaluate the observed low compliance. This involved using literature on average reading times, speed-reading times, and video play speeds to calculate the timeframes required to complete the three training …


Treatment Patterns In Women With Postmenopausal Osteoporosis Using Abaloparatide: A Real-World Observational Study, Deborah T Gold, Tammy Beckett, Chad Deal, Andrew L James, Mahshid Mohseni, Abigail Mcmillan, Tom Bailey, Leny Pearman, John Caminis, Yamei Wang, Setareh A Williams, Jacqueline M Kernaghan Aug 2024

Treatment Patterns In Women With Postmenopausal Osteoporosis Using Abaloparatide: A Real-World Observational Study, Deborah T Gold, Tammy Beckett, Chad Deal, Andrew L James, Mahshid Mohseni, Abigail Mcmillan, Tom Bailey, Leny Pearman, John Caminis, Yamei Wang, Setareh A Williams, Jacqueline M Kernaghan

2020-Current year OA Pubs

UNLABELLED: Review of medical records from 173 women with osteoporosis who received abaloparatide treatment revealed that 96.0% had at least one visit for osteoporosis management and 55.5% had medication support group access. The most common reasons for discontinuing treatment were financial (31.2%) and tolerability (22.8%). Most patients (64.8%) completed treatment as prescribed.

PURPOSE: Abaloparatide is approved for the treatment of women with postmenopausal osteoporosis at high risk for fracture. This study evaluated real-world treatment patterns for patients new to abaloparatide, regardless of osteoporosis treatment history.

METHODS: Data for patients with ≥ 1 prescription for abaloparatide were collected retrospectively from six …


Cone-Beam Computed Tomography (Cbct)-Guided Adaptive Boost Radiotherapy For A Patient With Locally Advanced Cervical Cancer Ineligible For Brachytherapy, Alice E. Silberstein, Joshua P. Schiff, Robbie Beckert, Xiaodong Zhao, Eric Laugeman, Stephanie Markovina, Jessika A. Contreras Aug 2024

Cone-Beam Computed Tomography (Cbct)-Guided Adaptive Boost Radiotherapy For A Patient With Locally Advanced Cervical Cancer Ineligible For Brachytherapy, Alice E. Silberstein, Joshua P. Schiff, Robbie Beckert, Xiaodong Zhao, Eric Laugeman, Stephanie Markovina, Jessika A. Contreras

2020-Current year OA Pubs

Brachytherapy is a critical component of locally advanced cervical cancer treatment, and patients ineligible for brachytherapy historically have poor outcomes. Delivery of boost with stereotactic body radiation therapy (SBRT) has been studied, though toxicity is a concern. Recent case reports have explored adaptive radiation boost, which can adjust plans for inter-fraction motion using magnetic resonance guidance. Herein, we report the first patient with locally advanced cervical cancer ineligible for brachytherapy who was treated with a cone-beam computed tomography (CBCT)-guided adaptive boost following completion of chemoradiation. A 71-year-old female with locally advanced cervical cancer was treated with chemoradiation and was deemed …


The Invisible Co-Afflicted: Caregivers Of Rectal Cancer Survivors, Qi Chen Aug 2024

The Invisible Co-Afflicted: Caregivers Of Rectal Cancer Survivors, Qi Chen

Publications and Research

Formal survivorship care after successful rectal cancer treatment is lacking, and this burden falls to caregivers. Caregivers, many of whom have no healthcare training, are asked to take on management of bowel function difficulties, ostomy care, while providing tangible, emotional, and financial support for rectal cancer survivors. The rise of young-onset rectal cancer also adds new survivorship care needs, such as family planning and returning to workplace, which compounds existing caregiver responsibilities and burdens.