Geriatrics Commons^™

The Landscape Of Malignant Transition: Unraveling Cancer Cell-Of-Origin And Heterogeneous Tissue Microenvironment, Ruihan Luo, Jiajia Liu, Tiangang Wang, Weiling Zhao, Yanfei Wang, Jianguo Wen, Hongyu Wang, Shanli Ding, Xiaobo Zhou

Faculty, Staff and Student Publications

Understanding disease progression and sophisticated tumor ecosystems is imperative for investigating tumorigenesis mechanisms and developing novel prevention strategies. Here, we dissected heterogeneous microenvironments during malignant transitions by leveraging data from 1396 samples spanning 13 major tissues. Within transitional stem-like subpopulations highly enriched in precancers and cancers, we identified 30 recurring cellular states strongly linked to malignancy, including hypoxia and epithelial senescence, revealing a high degree of plasticity in epithelial stem cells. By characterizing dynamics in stem-cell crosstalk with the microenvironment along the pseudotime axis, we found differential roles of ANXA1 at different stages of tumor development. In precancerous stages, reduced …

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 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.

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 …

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 …

Towards A Remote Patient Monitoring Platform For Comprehensive Risk Evaluations For People With Diabetic Foot Ulcers, Gozde Cay, M G Finco, Jason Garcia, Jill L Mcnitt-Gray, David G Armstrong, Bijan Najafi

Center on Aging Staff Publications

Diabetic foot ulcers (DFUs) significantly affect the lives of patients and increase the risk of hospital stays and amputation. We suggest a remote monitoring platform for better DFU care. This system uses digital health metrics (scaled from 0 to 10, where higher scores indicate a greater risk of slow healing) to provide a comprehensive overview through a visual interface. The platform features smart offloading devices that capture behavioral metrics such as offloading adherence, daily steps, and cadence. Coupled with remotely measurable frailty and phenotypic metrics, it offers an in-depth patient profile. Additional demographic data, characteristics of the wound, and clinical …

Correlational Analysis Of Sarcopenia And Multimorbidity Among Older Inpatients, Wenjing Xia, Kang Luo, Ziwei Gu, Jianping Hu, Xintong Liu, Qian Xiao

Faculty, Staff and Student Publications

BACKGROUND: Sarcopenia and multimorbidity are common in older adults, and most of the available clinical studies have focused on the relationship between specialist disorders and sarcopenia, whereas fewer studies have been conducted on the relationship between sarcopenia and multimorbidity. We therefore wished to explore the relationship between the two.

METHODS: The study subjects were older patients (aged ≥ 65 years) who were hospitalized at the Department of Geriatrics of the First Affiliated Hospital of Chongqing Medical University between March 2016 and September 2021. Their medical records were collected. Based on the diagnostic criteria of the Asian Sarcopenia Working Group in …

Risk Factors For Post-Discharge Adverse Outcomes Following Hospitalization Among Older Adults Diagnosed With Elder Mistreatment, Monique R Pappadis, Leila Wood, Allen Haas, Jordan Westra, Yong-Fang Kuo, Charles P Mouton

Faculty, Staff and Student Publications

Using 100% Medicare data files, this study explored whether primary elder mistreatment (EM) diagnosis, EM type, and facility type were associated with 3-year mortality and 1-year unplanned hospital readmission among older patients diagnosed with EM with hospital discharge from 10/01/2015 through 12/31/2018 (n = 11,023). We also examined outcome differences between older patients diagnosed with EM and matched non-EM patient controls. Neglect by others was the most common EM diagnosis. Three-year mortality was 56.7% and one-year readmission rate was 53.8%. Compared to matched non-EM patient controls, older EM patients were at an increased risk of mortality and readmission. Among …

Association Of Risk Factors And Comorbidities With Chronic Pain In The Elderly Population, Neil Mookerjee, Nicole Schmalbach, Gianna Antinori, Subhadra Thampi, Dylan Windle-Puente, Amy Gilligan, Ha Huy, Megha Andrews, Angela Sun, Roshni Gandhi, William Benedict, Austin Chang, Ben Sanders, Justin Nguyen, Maanika Reddy Keesara, Janet Aliev, Aneri Patel, Isaiah Hughes, Ian Millstein, Krystal Hunter, Satyajeet Roy

Faculty, Staff and Student Publications

INTRODUCTION/OBJECTIVE: Chronic pain disorders affect about 20% of adults in the United States, and it disproportionately affects individuals living in the neighborhoods of extreme socioeconomic disadvantage. In many instances, chronic pain has been noted to arise from an aggregation of multiple risk factors and events. Therefore, it is of importance to recognize the modifiable risk factors. The aim of this study was to investigate the comorbid medical conditions and risk factors associated with chronic pain disorders in patients aged 65 years and older.

METHODS: Our team retrospectively reviewed medical records of elderly patients (65 years and older) who were evaluated …

Association Of Interleukin-6 And Interleukin-18 With Cardiovascular Disease In Older Adults: Atherosclerosis Risk In Communities Study, Xiaoming Jia, Leo Buckley, Caroline Sun, Mahmoud Al Rifai, Bing Yu, Vijay Nambi, Salim S Virani, Elizabeth Selvin, Kunihiro Matsushita, Ron C Hoogeveen, Josef Coresh, Amil M Shah, Christie M Ballantyne

Faculty, Staff and Students Publications

AIMS: Interleukin-6 (IL-6) and interleukin-18 (IL-18), important cytokines implicated in atherosclerosis and inflammaging, were assessed for associations with global cardiovascular disease (CVD), atrial fibrillation (AF), and death in older adults.

METHODS AND RESULTS: Participants from Atherosclerosis Risk in Communities study Visit 5 (mean age 75.4 ± 5.1 years) with IL-6 and IL-18 measurements were included (n = 5672). Cox regression models were used to assess associations of IL-6 and IL-18 with coronary heart disease (CHD), ischaemic stroke, heart failure (HF) hospitalization, global CVD (composite of CHD, stroke, and HF), AF, and all-cause death. Over a median follow-up of 7.2 years, …

Age-Related Differences In The Contribution Of Systolic Blood Pressure And Biomarkers To Cardiovascular Disease Risk Prediction: The Atherosclerosis Risk In Communities (Aric) Study, Mahmoud Al Rifai, George E Taffet, Kunihiro Matsushita, Salim S Virani, James De Lemos, Amit Khera, Jarrett Berry, Chiadi Ndumele, David Aguilar, Caroline Sun, Ron C Hoogeveen, Elizabeth Selvin, Christie M Ballantyne, Vijay Nambi

Faculty, Staff and Students Publications

We sought to determine how biomarkers known to be associated with hypertension-induced end-organ injury complement the use of systolic blood pressure (SBP) for cardiovascular disease (CVD) risk prediction at different ages. Using data from visits 2 (1990 to 1992) and 5 (2011 to 2013) of the Atherosclerosis Risk in Communities (ARIC) study, 3 models were used to predict CVD (composite of coronary heart disease, stroke, and heart failure). Model A included traditional risk factors (TRFs) except SBP, model B-TRF plus SBP, and model C-TRF plus biomarkers (high-sensitivity troponin T [hsTnT] and N-terminal pro-B-type natriuretic peptide [NT-proBNP]). Harrel's C-statistics were used …

Assessing The Contributions Of Modifiable Risk Factors To Serious Falls And Fragility Fractures Among Older Persons Living With Hiv, Julie A Womack, Terrence E Murphy, Linda Leo-Summers, Jonathan Bates, Samah Jarad, Thomas M Gill, Evelyn Hsieh, Maria C Rodriguez-Barradas, Phyllis C Tien, Michael T Yin, Cynthia A Brandt, Amy C Justice

Faculty, Staff and Students Publications

BACKGROUND: Although 50 years represents middle age among uninfected individuals, studies have shown that persons living with HIV (PWH) begin to demonstrate elevated risk for serious falls and fragility fractures in the sixth decade; the proportions of these outcomes attributable to modifiable factors are unknown.

METHODS: We analyzed 21,041 older PWH on antiretroviral therapy (ART) from the Veterans Aging Cohort Study from 01/01/2010 through 09/30/2015. Serious falls were identified by Ecodes and a machine-learning algorithm applied to radiology reports. Fragility fractures (hip, vertebral, and upper arm) were identified using ICD9 codes. Predictors for both models included a serious fall within …

Cardiovascular Disease Risk Factors Among Middle-Aged And Older Adult Vietnamese American Members Of A Northern California Health Plan, Donna B Haysbert, Joan C Lo, Nirmala D Ramalingam, Nancy P Gordon

Faculty, Staff and Student Publications

OBJECTIVE: There is increasing recognition that cardiovascular disease (CVD) risk factors vary by Asian subgroups. We examined CVD risk factor prevalence among Vietnamese adults in a northern California health plan.

METHODS: We used electronic health record data to examine smoking, overweight/obesity (body mass index ≥23.0 kg/m

RESULTS: Current smoking prevalence was 20.3% for middle-aged men, 7.0% for older men, and

CONCLUSIONS: Study results suggest that more research on health conditions, lifestyle, and social factors among Vietnamese American adults is needed to develop culturally competent interventions to reduce CVD risk in this growing ethnic group.

Comorbidities And Risk Factors Associated With Insomnia In The Elderly Population, Neil Mookerjee, Nicole Schmalbach, Gianna Antinori, Subhadra Thampi, Dylan Windle-Puente, Amy Gilligan, Ha Huy, Megha Andrews, Angela Sun, Roshni Gandhi, William Benedict, Austin Chang, Ben Sanders, Justin Nguyen, Maanika Reddy Keesara, Janet Aliev, Aneri Patel, Isaiah Hughes, Ian Millstein, Krystal Hunter, Satyajeet Roy

Faculty, Staff and Student Publications

INTRODUCTION/OBJECTIVES: Sleep disorders affect around 50 to 70 million Americans, with chronic insomnia being the most common, especially in the elderly population. With an 11-fold increase in the US office visits due to insomnia, from 0.8 to 9.4 million, between 1993 and 2015, it is imperative to identify the modifiable risk factors. The aim of our study was to examine the association of risk factors and comorbid medical conditions with insomnia in patients 65 years, and older.

METHODS: We performed a retrospective electronic medical record review of the patients aged 65 years and older, who visited our suburban internal medicine …

The Gpcr–Gαs–Pka Signaling Axis Promotes T Cell Dysfunction And Cancer Immunotherapy Failure, Heather R Kregel, Lillian S Kao, Thaddeus J Puzio

Faculty, Staff and Student Publications

No abstract provided.

Ags And Nia Bench-To Bedside Conference Summary: Cancer And Cardiovascular Disease, Supriya Mohile, Caroline S Blaum, Peter M Abadir, William Dale, Daniel E Forman, Chunkit Fung, Holly M Holmes, Javid Moslehi, Karen M Mustian, Michael W Rich, Heather E Whitson

Faculty, Staff and Student Publications

This report summarizes the presentations, discussions, and recommendations of the most recent American Geriatrics Society and National Institute on Aging research conference, "Cancer and Cardiovascular Disease," on October 18-19, 2021. The purpose of this virtual meeting was to address the interface between cancer and heart disease, which are the two leading causes of death among older Americans. Age-related physiologic changes are implicated in the pathogenesis of both conditions. Emerging data suggest that cancer-related cardiovascular disease (CVD) involves disrupted cell signaling and cellular senescence. The risk factors for CVD are also risk factors for cancer and an increased likelihood of cancer …

Tdp-43 Proteinopathy In Aging: Associations With Risk-Associated Gene Variants And With Brain Parenchymal Thyroid Hormone Levels, Peter T. Nelson, Zsombor Gal, Wang-Xia Wang, Dana M. Niedowicz, Sergey C. Artiushin, Samuel Wycoff, Angela Wei, Gregory A. Jicha, David W. Fardo

Pathology and Laboratory Medicine Faculty Publications

TDP-43 proteinopathy is very prevalent among the elderly (affecting at least 25% of individuals over 85 years of age) and is associated with substantial cognitive impairment. Risk factors implicated in age-related TDP-43 proteinopathy include commonly inherited gene variants, comorbid Alzheimer's disease pathology, and thyroid hormone dysfunction. To test parameters that are associated with aging-related TDP-43 pathology, we performed exploratory analyses of pathologic, genetic, and biochemical data derived from research volunteers in the University of Kentucky Alzheimer's Disease Center autopsy cohort (n = 136 subjects). Digital pathologic methods were used to discriminate and quantify both neuritic and intracytoplasmic TDP-43 pathology …

Identification Strategies For The Very High Fall Risk Patient In An Acute Inpatient Psychiatric Unit, P6 Inpatient Geri-Med Psychiatry, Haley Pelletier, Suneela Nayak, Stephen Tyzik, Ruth Hanselman

MaineHealth Maine Medical Center

Patients falling as a result of geriatric and psychiatric impairments are at a much higher risk than the average patient population. An acute care inpatient psychiatric team used baseline metrics to demonstrate increasing fall rates per month that surpassed the unit’s target number. As a result, a quality improvement project around falls was felt to be warranted.

The overall goal of this study was to improve patient safety by reducing falls for their very high risk fall population. A root cause analysis determined that this population was not being properly identified and several tools were developed and employed to better …

Csf Protein Changes Associated With Hippocampal Sclerosis Risk Gene Variants Highlight Impact Of Grn/Pgrn, David W. Fardo, Yuriko Katsumata, John S. K. Kauwe, Yuetiva Deming, Oscar Harari, Carlos Cruchaga, Alzheimer’S Disease Neuroimaging Initiative, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Objective—Hippocampal sclerosis of aging (HS-Aging) is a common cause of dementia in older adults. We tested the variability in cerebrospinal fluid (CSF) proteins associated with previously identified HS-Aging risk single nucleotide polymorphisms (SNPs).

Methods—Alzheimer’s Disease Neuroimaging Initiative cohort (ADNI; n=237) data, combining both multiplexed proteomics CSF and genotype data, were used to assess the association between CSF analytes and risk SNPs in four genes (SNPs): GRN (rs5848), TMEM106B (rs1990622), ABCC9 (rs704180), and KCNMB2 (rs9637454). For controls, non-HS-Aging SNPs in APOE (rs429358/rs7412) and MAPT (rs8070723) were also analyzed against Aβ1-42 and total tau CSF analytes.

Results—The GRN risk …

Adverse Events And Treatment Discontinuations Of Antimuscarinics For The Treatment Of Overactive Bladder In Older Adults: A Systematic Review And Meta-Analysis, Scott Martin Vouri, Clark D. Kebodeaux, Paul M. Stranges, Besu F. Teshome

Pharmacy Practice and Science Faculty Publications

Introduction

Antimuscarinics should be used with caution in older adults with overactive bladder (OAB) due to anticholinergic adverse events (AEs). Systematic reviews and meta-analyses (SRMAs) have analyzed safety-related outcomes but have not specified risk in the elderly, the population at highest risk for AEs. The aim of this review is to explore and evaluate AEs and treatment discontinuations in adults 65 or older taking antimuscarinics for OAB.

Methods

Keywords were searched in MEDLINE, EMBASE, SCOPUS, and Cochrane Central Register for Controlled Trials. Randomized controlled trials (RCTs) along with sub-analyses and pooled analyses that compared antimuscarinics to placebo or another antimuscarinic …

Reassessment Of Risk Genotypes (Grn, Tmem106b, And Abcc9 Variants) Associated With Hippocampal Sclerosis Of Aging Pathology, Peter T. Nelson, Wang-Xia Wang, Amanda B. Partch, Sarah E. Monsell, Otto Valladares, Sally R. Ellingson, Bernard R. Wilfred, Adam C. Naj, Li-San Wang, Walter A. Kukull, David W. Fardo

Pathology and Laboratory Medicine Faculty Publications

Hippocampal sclerosis of aging (HS-Aging) is a common high-morbidity neurodegenerative condition in elderly persons. To understand the risk factors for HS-Aging, we analyzed data from the Alzheimer’s Disease Genetics Consortium and correlated the data with clinical and pathologic information from the National Alzheimer’s Coordinating Center database. Overall, 268 research volunteers with HS-Aging and 2,957 controls were included; detailed neuropathologic data were available for all. The study focused on single-nucleotide polymorphisms previously associated with HS-Aging risk: rs5848 ( GRN ), rs1990622 ( TMEM106B ), and rs704180 ( ABCC9 ). Analyses of a subsample that was not previously evaluated (51 HS-Aging cases …

Self-Reported Memory Complaints: Implications From A Longitudinal Cohort With Autopsies, Richard J. Kryscio, Erin L. Abner, Gregory E. Cooper, David W. Fardo, Greg A. Jicha, Peter T. Nelson, Charles D. Smith, Linda J. Van Eldik, Lijie Wan, Frederick A. Schmitt

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVE: We assessed salience of subjective memory complaints (SMCs) by older individuals as a predictor of subsequent cognitive impairment while accounting for risk factors and eventual neuropathologies.

METHODS: Subjects (n = 531) enrolled while cognitively intact at the University of Kentucky were asked annually if they perceived changes in memory since their last visit. A multistate model estimated when transition to impairment occurred while adjusting for intervening death. Risk factors affecting the timing and probability of an impairment were identified. The association between SMCs and Alzheimer-type neuropathology was assessed from autopsies (n = 243).

RESULTS: SMCs were …

Self-Reported Head Injury And Risk Of Late-Life Impairment And Ad Pathology In An Ad Center Cohort, Erin L. Abner, Peter T. Nelson, Frederick A. Schmitt, Steven R. Browning, David W. Fardo, Lijie Wan, Gregory A. Jicha, Gregory E. Cooper, Charles D. Smith, Allison M. Caban-Holt, Linda J. Van Eldik, Richard J. Kryscio

Sanders-Brown Center on Aging Faculty Publications

Aims: To evaluate the relationship between self-reported head injury and cognitive impairment, dementia, mortality, and Alzheimer's disease (AD)-type pathological changes. Methods: Clinical and neuropathological data from participants enrolled in a longitudinal study of aging and cognition (n = 649) were analyzed to assess the chronic effects of self-reported head injury. Results: The effect of self-reported head injury on the clinical state depended on the age at assessment: for a 1-year increase in age, the OR for the transition to clinical mild cognitive impairment (MCI) at the next visit for participants with a history of head injury was 1.21 and 1.34 …

Ageing – The Independent Risk Indicator, Saba Sohail

Department of Radiology

No abstract provided.