Geriatrics Commons^™

Tezepelumab's Effects On Patient-Reported Symptoms In Severe Asthma, Overall And With History Of Comorbid Chronic Rhinosinusitis With Nasal Polyps (Crswnp), Njira L. Lugogo, Joseph K. Han, Anju T. Peters, Stella E. Lee, Monica Kraft, Mary Kay Margolis, Sonia F. Shenoy, Nicole Martin, Shradha Chandarana, Christopher S. Ambrose

Department of Otolaryngology (ENT) Faculty Publications

Background

Tezepelumab (an anti-thymic stromal lymphopoietin monoclonal antibody) treatment resulted in reduced exacerbations and improved sino-nasal symptoms and health-related quality of life in patients with severe uncontrolled asthma (SUA) and chronic rhinosinusitis with nasal polyps (CRSwNP) in the NAVIGATOR study.

Objective

To evaluate the effect of tezepelumab versus placebo on sleep disturbances, activity levels, and physical exertion tolerance in NAVIGATOR patients with SUA overall and in those with past medical history of comorbid CRSwNP.

Methods

Patients (12-80 years old) with SUA were randomized to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Patient responses to …

Association Of Area Deprivation Index With Perinatal And Covid-19 Outcomes During The Early Pandemic: A Secondary Analysis Of A Prospective Cohort Study, Abigail Bell, Megan Foeller, Candice Woolfolk, Emily Diveley, Fan Zhang, Amy Scheffer, Ruizhi Huang, Daniel Jackson, Nandini Raghuraman, Ebony Carter, Indira U Mysorekar, Jeannie C Kelly

Center on Aging Staff Publications

Objective: We sought to evaluate the relationship between neighborhood-level deprivation and perinatal outcomes, particularly preterm birth, as well as COVID-19 outcomes among pregnant patients during the early pandemic.

Methods: We performed a secondary analysis of a prospective longitudinal cohort study that investigated the impact of prenatal COVID-19 exposure on perinatal outcomes. Pregnant patients were recruited 12/23/20-7/18/22 and serially assessed for COVID-19 exposure during pregnancy, with serum antibody testing, electronic medical record review, and patient report. For this secondary analysis, address at the time of delivery was used to categorize patients into low ADI (≤50th percentile Area Deprivation Index, indicating low …

Peritoneal Immunosurgery: Immunotherapy Augmented Surgery For The Treatment Of Peritoneal Cancers, Ada I Ozcan, Arianexys Aquino López, Mary K Mckenna, Malcolm K Brenner, Alastair M Thompson

Faculty, Staff and Students Publications

Peritoneal malignancy often indicates disruptions in multiple physiological systems resulting from widespread cancer. The heterogenous origin and dynamic nature of peritoneal cancer make it difficult to treat with standard approaches that fit into guidelines. We describe how successful treatment should address the underlying pathology, the systemic response to surgical treatments and target the immune perturbations that facilitate the establishment and propagation of this multifaceted disease.

The Causal Pivot: A Structural Approach To Genetic Heterogeneity And Variant Discovery In Complex Diseases, Chad A Shaw, C J Williams, Taotao Tan, Daniel Illera, Nicholas Di, Joshua M Shulman, John W Belmont

Center on Aging Staff Publications

We present the Causal Pivot (CP) as a structural causal model (SCM) for analyzing genetic heterogeneity in complex diseases. The CP leverages an established causal factor or factors to detect the contribution of additional suspected causes. Specifically, polygenic risk scores (PRSs) serve as known causes, while rare variants (RVs) or RV ensembles are evaluated as candidate causes. The CP incorporates outcome-induced association by conditioning on disease status. We derive a conditional maximum-likelihood procedure for binary and quantitative traits and develop the Causal Pivot likelihood ratio test (CP-LRT) to detect causal signals. Through simulations, we demonstrate the CP-LRT’s robust power and …

Deepmvp: Deep Learning Models Trained On High-Quality Data Accurately Predict Ptm Sites And Variant-Induced Alterations, Bo Wen, Chenwei Wang, Kai Li, Ping Han, Matthew V Holt, Sara R Savage, Jonathan T Lei, Yongchao Dou, Zhiao Shi, Yi Li, Bing Zhang

Center on Aging Staff Publications

Post-translational modifications (PTMs) are critical regulators of protein function, and their disruption is a key mechanism by which missense variants contribute to disease. Accurate PTM site prediction using deep learning can help identify PTM-altering variants, but progress has been limited by the lack of large, high-quality training datasets. Here, we introduce PTMAtlas, a curated compendium of 397,524 PTM sites generated through systematic reprocessing of 241 public mass-spectrometry datasets, and DeepMVP, a deep learning framework trained on PTMAtlas to predict PTM sites for phosphorylation, acetylation, methylation, sumoylation, ubiquitination and N-glycosylation. DeepMVP substantially outperforms existing tools across all six PTM types. Its …

Smartboot: Real-Time Monitoring Of Patient Activity Via Remote Edge Computing Technologies, Gozde Cay, Myeounggon Lee, David G Armstrong, Bijan Najafi

Center on Aging Staff Publications

Diabetic foot ulcers (DFUs) are a serious complication of diabetes, associated with high recurrence and amputation rates. Adherence to offloading devices is critical for wound healing but remains inadequately monitored in real-world settings. This study evaluates the SmartBoot edge-computing system-a wearable, real-time remote monitoring solution integrating an inertial measurement unit (Sensoria Core) and smartwatch-for its validity in quantifying cadence and step count as digital biomarkers of frailty, and for detecting adherence. Twelve healthy adults wore two types of removable offloading boots (Össur and Foot Defender) during walking tasks at varied speeds; system outputs were validated against a gold-standard wearable and …

Integrative Spatial Omics Reveals Distinct Tumor-Promoting Multicellular Niches And Immunosuppressive Mechanisms In Black American And White American Patients With Tnbc, Qian Zhu, Akhila Balasubramanian, Jaya Ruth Asirvatham, Megha Chatterjee, Badrajee Piyarathna, Jaspreet Kaur, Nada Mohamed, Ling Wu, Stacy Wang, Niloufar Pourfarrokh, Paula Danika Binsol, Mahak Bhargava, Uttam Rasaily, Yitian Xu, Junjun Zheng, Deborah Jebakumar, Arundhati Rao, Carolina Gutierrez, Angela R Omilian, Carl Morrison, Gokul M Das, Christine Ambrosone, Erin H Seeley, Shu-Hsia Chen, Yi Li, Eric Chang, Xiaoxian Li, Elizabeth Baker, Ritu Aneja, Xiang H-F Zhang, Arun Sreekumar

Center on Aging Staff Publications

Racial disparities in the clinical outcomes of triple-negative breast cancer (TNBC) have been well-documented, but the underlying biological mechanisms remain poorly understood. To investigate these disparities, we employed a multi-omic approach integrating imaging mass cytometry and spatial transcriptomics to characterize the tumor microenvironment (TME) in self-identified Black American (BA) and White American (WA) TNBC patients. Our analysis revealed that the TME in BA patients is marked by a network of endothelial cells, macrophages, and mesenchymal-like cells, which correlates with reduced patient survival. In contrast, the WA TNBC microenvironment is enriched in T-cells and neutrophils, indicative of T-cell exhaustion and suppressed …

The Somatic Mosaicism Across Human Tissues Network, Tim H H Coorens, Ji Won Oh, Yujin Angelina Choi, Nam Seop Lim, Boxun Zhao, Adam Voshall, Alexej Abyzov, Lucinda Antonacci-Fulton, Samuel Aparicio, Kristin G Ardlie, Thomas J Bell, James T Bennett, Bradley E Bernstein, Thomas G Blanchard, Alan P Boyle, Jason D Buenrostro, Kathleen H Burns, Fei Chen, Rui Chen, Sangita Choudhury, Harsha V Doddapaneni, Evan E Eichler, Gilad D Evrony, Melissa A Faith, Thomas G Fazzio, Robert S Fulton, Manuel Garber, Nils Gehlenborg, Soren Germer, Gad Getz, Richard A Gibbs, Raquel G Hernandez, Fulai Jin, Jan O Korbel, Dan A Landau, Heather A Lawson, Niall J Lennon, Heng Li, Yan Li, Po-Ru Loh, Gabor Marth, Michael J Mcconnell, Ryan E Mills, Stephen B Montgomery, Pradeep Natarajan, Peter J Park, Rahul Satija, Fritz J Sedlazeck, Diane D Shao, Hui Shen, Andrew B Stergachis, Hunter R Underhill, Alexander E Urban, Melissa W Vondran, Christopher A Walsh, Ting Wang, Tao P Wu, Chenghang Zong, Eunjung Alice Lee, Flora M Vaccarino

Center on Aging Staff Publications

From fertilization onwards, the cells of the human body acquire variations in their DNA sequence, known as somatic mutations. These postzygotic mutations arise from intrinsic errors in DNA replication and repair, as well as from exposure to mutagens. Somatic mutations have been implicated in some diseases, but a fundamental understanding of the frequency, type and patterns of mutations across healthy human tissues has been limited. This is primarily due to the small proportion of cells harbouring specific somatic variants within an individual, making them more challenging to detect than inherited variants. Here we describe the Somatic Mosaicism across Human Tissues …

Reduction Of Neuronal Activity Mediated By Blood-Vessel Regression In The Adult Brain, Xiaofei Gao, Xing-Jun Chen, Meng Ye, Jun-Liszt Li, Nannan Lu, Di Yao, Bo Ci, Fei Chen, Lijun Zheng, Yating Yi, Shiwen Zhang, Zhanying Bi, Xinwei Gao, Yuanlei Yue, Tingbo Li, Jiafu Lin, Ying-Chao Shi, Kaibin Shi, Nicholas E Propson, Yubin Huang, Katherine Poinsatte, Zhaohuan Zhang, Dale B Bosco, Shi-Bing Yang, Ralf H Adams, Volkhard Lindner, Fen Huang, Long-Jun Wu, Hui Zheng, Simon Hippenmeyer, Ann M Stowe, Bo Peng, Marta Margeta, Qingchun Guo, Xiaoqun Wang, Qiang Liu, Jakob Körbelin, Martin Trepel, Hui Lu, Guoen Cai, Bo O Zhou, Bo Shen, Ying-Mei Lu, Wenzhi Sun, Jie-Min Jia, Feng Han, Hu Zhao, Robert M Bachoo, Woo-Ping Ge

Center on Aging Staff Publications

The brain vasculature supplies neurons with glucose and oxygen, but little is known about how vascular plasticity contributes to brain function. Using longitudinal in vivo imaging, we report that a substantial proportion of blood vessels in the adult mouse brain sporadically occlude and regress. Their regression proceeds through sequential stages of blood-flow occlusion, endothelial cell collapse, relocation or loss of pericytes, and retraction of glial endfeet. Regressing vessels are found to be widespread in mouse, monkey and human brains. We further reveal that blood vessel regression cause a reduction of neuronal activity due to a dysfunction in mitochondrial metabolism and …

Managing Hypercholesterolemia In Adults Older Than 75 Years Without A History Of Atherosclerotic Cardiovascular Disease: An Expert Clinical Consensus From The National Lipid Association And The American Geriatrics Society, Vera Bittner, Sunny A Linnebur, Dave L Dixon, Daniel E Forman, Ariel R Green, Terry A Jacobson, Ariela R Orkaby, Joseph J Saseen, Salim S Virani

Faculty, Staff and Students Publications

The risk of atherosclerotic cardiovascular disease increases with advancing age. Elevated LDL-cholesterol and non-HDL-cholesterol levels remain predictive of incident atherosclerotic cardiovascular events among individuals older than 75 years. Risk prediction among older individuals is less certain because most current risk calculators lack specificity in those older than 75 years and do not adjust for co-morbidities, functional status, frailty, and cognition which significantly impact prognosis in this age group. Data on the benefits and risks of lowering LDL-cholesterol with statins in older patients without atherosclerotic cardiovascular disease are also limited since most primary prevention trials have included mostly younger patients. Available …

The Infected Diabetic Foot: Bacteraemia And Endocarditis Complicating Moderate And Severe Foot Infections, Mario C Reyes, Arthur N Tarricone, Mathew J Sideman, Michael C Siah, Bijan Najafi, Edgar J G Peters, Lawrence A Lavery

Center on Aging Staff Publications

To identify the incidence of blood stream infections (BSIs) and endocarditis in patients with diabetic foot infections (DFIs), risk factors and clinical outcomes. A post hoc analysis of 280 patients using pooled patient level data from three RTCs. Blood cultures were drawn at time of admission for DFI. Deep intraoperative cultures were obtained from infected foot wounds. Data from the 12-month follow-up were used to determine clinical outcomes. 77.1% (N = 216) had blood cultures of which 15.7% (n = 34) had BSI. One patient (3.3%) had endocarditis. Risk factors for BSI included Charcot Neuroarthropathy history (20.6% vs. 7.1%, p …

The Dialysis Foot- The Impact Of Presenting Estimated Glomerular Filtration Rate On Clinical Outcomes In Patients Hospitalized With Diabetic Foot Infections, Arthur Tarricone, Tyler L Coye, Allen Gee, Bijan Najafi, Michael C Siah, Lawrence A Lavery

Center on Aging Staff Publications

To evaluate the association between presenting estimated glomerular filtration rate (eGFR) and clinical outcomes in patients hospitalized with diabetic foot infections. This retrospective cohort study included 344 patients with moderate to severe diabetic foot infections. Patients were categorized into three groups based on presenting estimated eGFR: eGFR ≥60 (eGFR >60 mL/min), eGFR 30-60 (eGFR 30-60 mL/min) and eGFR < 30 (eGFR < 30 mL/min). Outcomes assessed included wound healing, time to heal, re-infection, amputation, mortality and re-hospitalization for infection. Compared with patients with eGFR < 30, patients with eGFR ≥60 had significantly lower rates of retinopathy, peripheral arterial disease and use of beta blockers or calcium channel blockers. Glycated haemoglobin levels were inversely related to eGFR, decreasing as eGFR severity increased. Haemoglobin levels were significantly lower, and inflammatory markers (ESR and CRP) were significantly higher in patients with eGFR < 30. There were no significant differences among eGFR groups in rates of wound healing, time to heal, re-infection or amputation. However, mortality increased with decreasing eGFR (1.9% in eGFR ≥60 vs. 3.2% in eGFR 30-60 vs. 8.1% in eGFR < 30; p = 0.04). Similarly, re-hospitalization for infection at a different site also increased with decreasing eGFR (20.5% in eGFR ≥60 vs. 28.1% in eGFR 30-60 vs. 48.4% in eGFR < 30; p <  0.01). In diabetic foot infections, presenting eGFR severity did not affect rates of wound healing, time to heal, re-infection or amputation. However, decreasing eGFR was associated with increased mortality and re-hospitalization for infection at a different site. In this study, presenting eGFR was not a predictive value for wound healing or time until healing, however was associated with rehospitalization and overall mortality this diabetic foot population.

Clonal Dynamics And Somatic Evolution Of Haematopoiesis In Mouse, Chiraag D Kapadia, Nicholas Williams, Kevin J Dawson, Caroline Watson, Matthew J Yousefzadeh, Duy Le, Kudzai Nyamondo, Sreeya Kodavali, Alex Cagan, Sarah Waldvogel, Xiaoyan Zhang, Josephine De La Fuente, Daniel Leongamornlert, Emily Mitchell, Marcus A Florez, Krzysztof Sosnowski, Rogelio Aguilar, Alejandra Martell, Anna Guzman, David Harrison, Laura J Niedernhofer, Katherine Y King, Peter J Campbell, Jamie Blundell, Margaret A Goodell, Jyoti Nangalia

Center on Aging Staff Publications

Haematopoietic stem cells maintain blood production throughout life1. Although extensively characterized using the laboratory mouse, little is known about clonal selection and population dynamics of the haematopoietic stem cell pool during murine ageing. We isolated stem cells and progenitors from young and old mice, identifying 221,890 somatic mutations genome-wide in 1,845 single-cell-derived colonies. Mouse stem cells and progenitors accrue approximately 45 somatic mutations per year, a rate only approximately threefold greater than human progenitors despite the vastly different organismal sizes and lifespans. Phylogenetic patterns show that stem and multipotent progenitor cell pools are established during embryogenesis, after which …

Inhibition Of Soluble Epoxide Hydrolase Confers Neuroprotection And Restores Microglial Homeostasis In A Tauopathy Mouse Model, Shuo Wang, Chuangye Qi, Chetan Rajpurohit, Baijayanti Ghosh, Wen Xiong, Baiping Wang, Yanyan Qi, Sung Hee Hwang, Bruce D Hammock, Hongjie Li, Li Gan, Hui Zheng

Center on Aging Staff Publications

Background: The epoxyeicosatrienoic acids (EETs) are derivatives of the arachidonic acid metabolism with anti-inflammatory activities. However, their efficacy is limited due to the rapid hydrolysis by soluble epoxide hydrolase (sEH). Inhibition of sEH has been shown to stabilize the EETs and reduce neuroinflammation in Aβ mouse models of Alzheimer's disease (AD). However, the role of the sEH-EET signaling pathway in other CNS cell types and neurodegenerative conditions are less understood.

Methods: Here we investigated the mechanisms and functional role of the sEH-EET axis in tauopathy by treating PS19 mice with a small molecule sEH inhibitor TPPU and by crossing the …

Impact Of Age On Biology, Presentation And Outcomes In Marginal Zone Lymphoma: Results From A Multicenter Cohort Study, Pallawi Torka, Natalie S. Grover, Timothy J. Voorhees, Reem Karmali, Kaitlin Annunzio, Marcus P. Watkins, Andrea Anampa-Guzmán, Heather Reves, Montreh Tavakkoli, Beth Christian, Colin Thomas, Stefan K. Barta, Praveen Ramakrishnan Geethakumari, Nancy L. Bartlett, Geoffrey Shouse, Adam J. Olszewski, Narendranath Epperla

Department of Medicine Faculty Papers

Given the paucity of age-specific data about biology, presentation, and treatment outcomes in adults with MZL, we sought to evaluate differences between younger (≤ 70 years) and older (> 70 years) patients with MZL in a large retrospective cohort treated in the contemporary era (2010 onwards). The primary objective was progression-free survival (PFS), while secondary objectives included the evaluation of overall survival (OS) and the cumulative incidence of transformation between the 2 groups. A total of 598 patients were included in the analysis and among these 32% were > 70 years of age. There were no age-based differences in the prevalence …

The Havcr1-Centric Host Factor Network Drives Zika Virus Vertical Transmission, Wenzhe Yu, Jun Tao, Hongmin Cao, Wanshan Zheng, Beiang Zhang, Yue Zhang, Peiqun Xu, Yiwei Zhang, Xuan Liu, Yinan Wang, Han Cai, Gang Liu, Fan Liu, Haibin Wang, Haiyan Zhao, Indira U Mysorekar, Xiaoqian Hu, Bin Cao

Center on Aging Staff Publications

Zika virus (ZIKV) vertical transmission results in devastating congenital malformations and pregnancy complications; however, the specific receptor and host factors facilitating ZIKV maternal-fetal transmission remain elusive. Here, we employ a genome-wide CRISPR screening and identify multiple placenta-intrinsic factors modulating ZIKV infection. Our study unveils that hepatitis A virus cellular receptor 1 (HAVCR1) serves as a primary receptor governing ZIKV entry in placental trophoblasts. The GATA3-HAVCR1 axis regulates heterogeneous cell tropism in the placenta. Notably, placenta-specific Havcr1 deletion in mice significantly impairs ZIKV transplacental transmission and associated adverse pregnancy outcomes. Mechanistically, the immunoglobulin variable-like domain of HAVCR1 binds to ZIKV via …

Using The 5ms Framework To Advance Aging-Responsive Care For Heart Failure With Reduced Ejection Fraction, Abigail Latimer, Debra K. Moser, Jia-Rong Wu, Kim K. Birtcher, Malachy J. Clancy, Jennifer D. Portz, Joanna Paladino, Daniel D. Matlock, Christopher E. Knoepke

Department of Occupational Therapy Faculty Papers

Complexity of care is the inevitable consequence of an aging population and is particularly true in instances where patients are managing chronic conditions such as heart failure with reduced ejection fraction (HFrEF). HFrEF itself is complex, with an undulating course of illness, increased risk of sudden cardiac death, and myriad accompanying treatment considerations. Generalist management of HFrEF among older patients is further complicated by competing comorbidities, potential for financial toxicity, potential for mental health symptoms, and risk of care with does not align with goals and preferences. The 5Ms (multicomplexity, mind, mobility, medications, and matters most) is a holistic conceptualization …

Quantitative Profiling Ph Heterogeneity Of Acidic Endolysosomal Compartments Using Fluorescence Lifetime Imaging Microscopy, Dinghuan Deng, Youchen Guan, Ayse Sena Mutlu, Baiping Wang, Shihong Max Gao, Hui Zheng, Meng C Wang

Center on Aging Staff Publications

The endolysosomal system plays a crucial role in maintaining cellular homeostasis and promoting organism fitness. The pH of its acidic compartments is a crucial parameter for proper function, and it is dynamically influenced by both intracellular and environmental factors. Here, we present a method based on fluorescence lifetime imaging microscopy (FLIM) for quantitatively analyzing the pH profiles of acidic endolysosomal compartments in diverse types of primary mammalian cells and in live organism Caenorhabditis elegans. This FLIM-based method exhibits high sensitivity in resolving subtle pH differences, thereby revealing heterogeneity within a cell and across cell types. This method enables rapid …

Associations Between Deficit Accumulation Frailty And Baseline Markers Of Lifestyle In The Us Pointer Trial, Mark A Espeland, Yitbarek N Demesie, Kayloni Olson, Samuel N Lockhart, Sarah E Tomaszewski Farias, Maryjo L Cleveland, Christy C Tangney, Lucia Crivelli, Heather M Snyder, Michele K York, Laura D Baker, Rachel A Whitmer, Rena R Wing, Katelyn R Garcia, Kathryn E Callahan

Faculty, Staff and Students Publications

BACKGROUND: Multidomain lifestyle interventions may have the potential to slow biological aging as captured by deficit accumulation frailty indices. We describe the distribution and composition of the 49-component frailty index developed by the U.S. POINTER clinical trial team of investigators and assess its cross-sectional associations with sociodemographic factors and markers chosen to be representative of behaviors targeted by the trial's multidomain interventions.

METHODS: We draw baseline data from the 2 111 volunteers enrolled in U.S. POINTER who were ages 60-79 years and at increased risk for cognitive decline. Frailty components were grouped into 9 domains. Associations that frailty index scores …

Multisociety Guidance For Infection Prevention And Control In Nursing Homes, Lona Mody, Sonali D. Advani, Muhammad Salman Ashraf, Allison H. Bartlett, Suzanne F. Bradley, Deborah P. Burdsall, Jennifer A. Hanrahan, Susan S. Huang, Robert L.P. Jump, Lindsay Nicolle, Mary-Claire Roghmann, Patricia Stone, Rekha K. Murthy

Department of Medicine Faculty Publications

This multisociety guidance was endorsed by SHEA, APIC, IDSA, PALTmed, and AGS. It provides recommendations for infection prevention and control (IPC) in the context of the complexity of nursing home care in the United States: increased medical acuity of residents, the spread of multidrug-resistant organisms, and the threat of emerging pathogens. Recommendations and implementation suggestions address IPC leadership, staffing, and resources, healthcare personnel and residents‘ adherence to precautions and effective hand hygiene, outbreak preparedness, training, occupational health, cleaning and disinfection in the care environment, and the involvement of IPC in the facility. The guidance also addresses the challenges of maintaining …

The Infected Diabetic Foot: Incidence And Risk Factors For Dehiscence After Surgery For Diabetic Foot Infections, Lawrence A Lavery, Mario C Reyes, Bijan Najafi, Tyler L Coye, Jayer Chung, Michael C Siah, Arthur N Tarricone

Center on Aging Staff Publications

Our objective was to assess the incidence, risk factors and clinical outcomes of dehiscence after foot surgery in diabetic patients. We used pooled patient‐level data from two randomised clinical trials with 240 diabetic patients who required foot surgery for infections. Most patients (n = 180, 75.0%) had surgical wound closure. We defined dehisced surgical wounds (DSW) when the surgical site was not completely epithelialized with no drainage after sutures/staples were removed with a 2‐week validation of healing. We evaluated the time to heal, re‐infection, re‐ulceration, hospital admissions and amputations. Moderate and severe infection was based on criteria of the …

Dental Care Trajectories Among Formerly Incarcerated Older Adults In The United States, Alexander Testa, Luis Mijares, Mateus Renno Santos, Vahed Maroufy, Dylan B Jackson, Rafael Samper-Ternent, Rahma Mungia, Ana C Neumann

Faculty, Staff and Student Publications

A growing body of research has documented an association between prior incarceration and lower dental care use, yet the longitudinal impact of prior incarceration on dental care patterns over time among older adults remains unexplored. This study aims to investigate whether prior incarceration is associated with differing trajectories of dental care use among older adults in the United States. Data were drawn from the 2012-2020 waves of the Health and Retirement Study (HRS), a nationally representative longitudinal survey of older adults in the United States (n =  5,893). Group-based trajectory modeling was used to estimate dental care use patterns over …

The Infected Diabetic Foot: Risk Factors For Re-Infection After Treatment For Diabetic Foot Osteomyelitis, Lawrence A Lavery, Mario C Reyes, Bijan Najafi, Tyler L Coye, Matthew Sideman, Michael C Siah, Arthur N Tarricone

Center on Aging Staff Publications

Our objective was to evaluate risk factors for re-infection in patients after treatment for diabetic foot osteomyelitis (OM). We used pooled patient level data from two RTCs that evaluated patients with diabetic foot infections. We evaluated 171 patients with OM. OM was confirmed with bone culture or histopathology. Data from the 12-month follow-up were used to determine clinical outcomes. Re-infection occurred in 47 (27.5%) patients. Risk factors for re-infection were Toe Brachial Index < 0.40 (25.7% vs. 9.8%, p = 0.02), skin perfusion pressure < 40 mmHg (6.3% vs. 5.9%, p = 0.04), wound healing (55.3% vs. 75.0%, p = 0.01), time to heal (156.0, 69.5-365 vs. 91.5, 38.8-365, p = 0.001), and history of MI (14.9% vs. 3.2%, p = 0.005). During 12-month follow-up, patients with re-infections were 198.8 times more likely to require a foot related hospitalisation (81.8% vs. 0.0%, p = 0.001), 10.4 times more likely have an all-cause hospitalisation (70.2% vs. 18.5%, p = 0.001) and 9.4 times more likely to need an amputation (36.2% vs. 5.6%, p = 0.001). Patients with re-infection had a significantly longer median length of hospitalisation (20.0, 13.5-34.5 vs. 14.0, 10.0-22.0, p = 0.003) and median length of antibiotic duration (55.0, 35.0-87.0 vs. 46.0, 22.8-68.0, p = 0.03). Patients with re-infection are less likely to heal and have more foot-related hospitalizations and amputations.

Efficacy And Feasibility Of Intradialytic Plantar Electrical Stimulation In Patients With Diabetes: A Randomized Double-Blind Controlled Trial, Myeounggon Lee, Abdullah Hamad, Mehrnaz Azarian, Jaewon Beom, Abderrahman Ouattas, Mohammad Dehghan Rouzi, Naima Rodriguez, Nhi Quach, Rania Ibrahim, Mincy Mathew, Talal Talal, Fadwa Al-Ali, Bijan Najafi

Center on Aging Staff Publications

Objective: This study investigates the efficacy and feasibility of electrical stimulation (E-Stim) on sensory fibers of the plantar region during hemodialysis sessions, aiming to improve mobility in patients with diabetes by providing a connection between E-Stim and enhanced mobility with minimal patient effort required.

Research design and methods: Participants aged ≥18 years with diabetes undergoing hemodialysis and able to walk at least 10 m with or without aid were recruited and divided into an intervention group receiving 1-h intradialytic E-Stim three times a week and a control group using an identical nonfunctional device for 12 weeks. Gait, physical activity, patient-reported …

Using Patient-Reported Experiences To Inform The Use Of Foam Dressings For Hard-To-Heal Wounds: Perspectives From A Wound Care Expert Panel, Kevin Woo, Nick Santamaria, Dimitri Beeckman, Paulo Alves, Breda Cullen, Amit Gefen, José Luis Lázaro-Martínez, Hadar Lev-Tov, Bijan Najafi, Andrew Sharpe, Terry Swanson

Center on Aging Staff Publications

Caring for patients with hard-to-heal (chronic) wounds requires a multifaceted approach that addresses their diverse needs, which can contribute to the complexity of care. Wound care providers must have a comprehensive understanding of the patient's comorbid conditions and psychosocial issues to provide personalised and effective treatment. Key quality indicators for effective wound care involves not only selecting appropriate local wound care products, such as foam dressings, but also addressing individual patient experiences of wound-related pain, odour, itch, excessive wound drainage, and self-care needs. The purpose of this review is to inculcate the wound care practice community, research scientists and healthcare …

Pkmyt1 Is A Marker Of Treatment Response And A Therapeutic Target For Cdk4/6 Inhibitor-Resistance In Er+ Breast Cancer, Anran Chen, Beom-Jun Kim, Aparna Mitra, Craig T Vollert, Jonathan T Lei, Diana Fandino, Meenakshi Anurag, Matthew V Holt, Xuxu Gou, Jacob B Pilcher, Matthew P Goetz, Donald W Northfelt, Susan G Hilsenbeck, C Gary Marshall, Marc L Hyer, Robert Papp, Shou-Yun Yin, Carmine De Angelis, Rachel Schiff, Suzanne A W Fuqua, Cynthia X Ma, Charles E Foulds, Matthew J Ellis

Faculty, Staff and Students Publications

Endocrine therapies (ET) with cyclin-dependent kinase 4/6 (CDK4/6) inhibition are the standard treatment for estrogen receptor-α-positive (ER+) breast cancer, however drug resistance is common. In this study, proteogenomic analyses of patient-derived xenografts (PDXs) from patients with 22 ER+ breast cancer demonstrated that protein kinase, membrane-associated tyrosine/threonine one (PKMYT1), a WEE1 homolog, is estradiol (E2) regulated in E2-dependent PDXs and constitutively expressed when growth is E2-independent. In clinical samples, high PKMYT1 mRNA levels associated with resistance to both ET and CDK4/6 inhibition. The PKMYT1 inhibitor lunresertib (RP-6306) with gemcitabine selectively and synergistically reduced the viability of ET and palbociclib-resistant ER+ breast …

Human Embryonic Genetic Mosaicism And Its Effects On Development And Disease, Sarah M Waldvogel, Jennifer E Posey, Margaret A Goodell

Center on Aging Staff Publications

Nearly every mammalian cell division is accompanied by a mutational event that becomes fixed in a daughter cell. When carried forward to additional cell progeny, a clone of variant cells can emerge. As a result, mammals are complex mosaics of clones that are genetically distinct from one another. Recent high-throughput sequencing studies have revealed that mosaicism is common, clone sizes often increase with age and specific variants can affect tissue function and disease development. Variants that are acquired during early embryogenesis are shared by multiple cell types and can affect numerous tissues. Within tissues, variant clones compete, which can result …

A Genome-Wide Association Meta-Analysis Of All-Cause And Vascular Dementia, Mega Vascular Cognitive Impairment And Dementia (Megavcid) Consortium

Faculty, Staff and Students Publications

INTRODUCTION: Dementia is a multifactorial disease with Alzheimer's disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD.

METHODS: We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD. Our dataset includes 800,597 individuals, with 46,902 and 8702 cases of ACD and VaD, respectively. Known AD loci for ACD and VaD were replicated. Bioinformatic analyses prioritized genes that are likely functionally relevant and shared with closely related traits and risk factors.

RESULTS: For ACD, novel loci identified were associated with energy transport (SEMA4D), neuronal excitability …

Methicillin-Resistant Staphylococcus Aureus In Diabetic And Non-Diabetic Foot Infections, Lawrence A Lavery, Mario C Reyes, Mehmet Suludere, Bijan Najafi, Matthew Sideman, Michael C Siah, Arthur N Tarricone

Center on Aging Staff Publications

To identify the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection, reinfection and clinical outcomes. Four hundred forty-six patients that were admitted to the hospital with moderate or severe foot infections were retrospectively reviewed. Tissue and bone cultures were obtained from the index hospital admission. Conversion was defined as methicillin susceptible Staphylococcus aureus in the first culture and subsequently MRSA when there was a reinfection. The incidence of MRSA was 7.8% (n = 35), with no significant difference between soft tissue infections (7.7%) and osteomyelitis (8.0%). MRSA incidence was 9.4 times higher in non-diabetics (23.8% vs. 3.2%, p = < 0.01). The incidence of reinfection was 40.8% (n = 182). Conversion to MRSA was seen in 2.2% (n = 4) total, occurring in 5.4%. Non-diabetics were 20.1 times more likely to have MRSA reinfection than people with diabetes (28.6% vs. 1.9%, p <  0.001). MRSA patients had a higher proportion of healed wounds (82.4% vs. 69.3%, p = 0.02). There were no differences in other clinical outcomes in MRSA vs. other infections in reinfection (28.6% vs. 24.3%, p = 0.11), amputation (48.6% vs. 52.0%, p = 0.69) or hospitalization (28.6% vs. 42.6, p = 0.11). The incidence of MRSA for the first infection (7.8%), reinfection (6.0%) and conversion to MRSA (2.2%) was low. MRSA was 9.4 times more common in people without diabetes.

Diabetes Technology Meeting 2023, Tiffany Tian, Rachel E Aaron, Ashley Y Dunova, Johan H Jendle, David Kerr, Eda Cengiz, Andjela Drincic, John C Pickup, Kong Y Chen, Naomi Schwartz, Douglas B Muchmore, Halis K Akturk, Carol J Levy, Signe Schmidt, Riccardo Bellazzi, Alan H B Wu, Elias K Spanakis, Bijan Najafi, James Geoffrey Chase, Jane Jeffrie Seley, David C Klonoff

Center on Aging Staff Publications

Diabetes Technology Society hosted its annual Diabetes Technology Meeting from November 1 to November 4, 2023. Meeting topics included digital health; metrics of glycemia; the integration of glucose and insulin data into the electronic health record; technologies for insulin pumps, blood glucose monitors, and continuous glucose monitors; diabetes drugs and analytes; skin physiology; regulation of diabetes devices and drugs; and data science, artificial intelligence, and machine learning. A live demonstration of a personalized carbohydrate dispenser for people with diabetes was presented.