Digital Commons Network^™

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 …

Delayed Excretion Of High-Dose Methotrexate In Pediatric Acute Leukemia Correlates With Laxative And Constipation Management, Jennifer A Belsky, Ashley Chavana, Ankona Banerjee, Mark Zobeck, Eric S Schafer, Karen R Rabin, Monica Gramatges, Alex Sim, Audrey Leisinger, Trisha Reddy, Megan J Parod, Philip Lupo, Michael Scheurer, Austin L Brown, M Brooke Bernhardt

Faculty, Staff and Students Publications

Background: Delayed excretion of high-dose methotrexate (HD-MTX) in pediatric acute lymphoblastic leukemia (ALL) can result in significant morbidity. While methotrexate is primarily renally excreted, HD-MTX may overwhelm renal excretion and increase reliance on fecal elimination. This study evaluated the association between laxative use for constipation and delayed excretion of HD-MTX.

Methods: This multisite chart review included pediatric patients with ALL (2010-2020) who received HD-MTX (5 g/m2). Delayed excretion was defined as a serum MTX concentration greater than 0.4 µM at Hour 48. We identified use of laxative medications after each HD-MTX infusion, with receipt of two or more doses considered …

Exercise Mitigates High-Fat Diet-Induced Cardiac Dysfunction Via Apoe Genotype- And Immune-Dependent Mechanisms: A Photon-Counting Ct Study In Adult Mice, Rohan Nadkarni, Alex J Allphin, Darin P Clark, Yi Qi, Zay Yar Han, Ketan B Ghaghada, Alexandra Badea, Cristian T Badea

Faculty, Staff and Students Publications

Background: Cardiovascular dysfunction frequently accompanies aging and is often worsened by adverse lifestyle factors and genetic susceptibility. The apolipoprotein E (APOE) gene modulates susceptibility to cardiovascular disease, but how exercise and diet interact with APOE genotype remains insufficiently understood. We investigate the cardioprotective potential of exercise in humanized APOE-targeted replacement mice on control and high-fat diet, using photon-counting computed tomography (PCCT) and deep learning-based image segmentation.

Methods: This study included 251 male and female mice in mid-to-late life of APOE2, APOE3, and APOE4 genotypes with variation in humanized NOS2 (HN) mediated innate immune response, exercise status (exercised vs. sedentary) and …

Histone Deacetylase 6 Inhibition Promotes Microtubule Acetylation And Facilitates Autophagosome-Lysosome Fusion In Dystrophin-Deficient Mdx Mice, Akanksha Agrawal, Erin L Clayton, Courtney L Cavazos, Benjamin A Clayton, George G Rodney

Faculty, Staff and Students Publications

Aim: Duchenne muscular dystrophy is a progressive muscle-wasting disease caused by mutations in the dystrophin gene. Despite progress in dystrophin-targeted gene therapies, it is still a fatal disease requiring novel therapeutics that can be used synergistically or alternatively to emerging gene therapy. Defective autophagy and disorganized microtubule networks contribute to dystrophic pathogenesis, yet the mechanisms by which microtubule alterations regulate autophagy remain elusive. The present study was designed to uncover possible mechanisms underpinning the role of microtubules in regulating autophagy in dystrophic mice.

Methods: Mdx mice were also supplemented with Tubastatin A, a pharmacological inhibitor of histone deacetylase 6, and …

Igf-1 Impacts Neocortical Interneuron Connectivity In Epileptic Spasm Generation And Resolution, Carlos J Ballester-Rosado, John T Le, Trang T Lam, Anne E Anderson, James D Frost, John W Swann

Faculty, Staff and Students Publications

Little is known about the mechanisms that generate epileptic spasms following perinatal brain injury. Recent studies have implicated reduced levels of Insulin-like Growth Factor 1 (IGF-1) in these patients' brains. Other studies have reported low levels of the inhibitory neurotransmitter, GABA. In the TTX brain injury model of epileptic spasms, we undertook experiments to evaluate the impact of IGF-1 deficiencies on neocortical interneurons and their role in spasms. Quantitative immunohistochemical analyses revealed that neocortical interneurons that express glutamic acid decarboxylase, parvalbumin, or synaptotagmin 2 co-express IGF-1. In epileptic rats, expression of these three interneuron markers were reduced in the neocortex. …

Hypertriglyceridemia In New-Onset Type 1 Pediatric Diabetes, Colleen A Macke, Iman Al-Gadi, Nidhi Bansal, Sarah K Lyons, Aikaterini A Nella

Faculty, Staff and Students Publications

Hypertriglyceridemia (HTG) in the setting of newly diagnosed diabetes is common in both adult and pediatric populations, as insulin deficiency promotes lipolysis and impairs triglyceride (TG) clearance. Severe HTG (defined as TG levels above 1000 mg/dL) in pediatric patients with new-onset type 1 diabetes mellitus (T1D) is rare; the true incidence and sequela of this phenomenon have not been well characterized. We present a single-center experience on severe HTG in pediatric patients with new-onset T1D between 2013 and 2022 and summarize the cases previously reported in the literature. Our cases display variability in their presentation and in their association with …

Resilience Of The Gut Microbiome To Short Proton Pump Inhibitor Therapy With Or Without High-Dosage L Reuteri In H Pylori-Infected Adults, Stefano Bibbò, Gustav Ahlström, Giovanni Mario Pes, David Y Graham, Lars Engstrand, Elettra Merola, Maria Pina Dore

Faculty, Staff and Students Publications

Background: Helicobacter pylori eradication therapy typically consists of a combination of antibiotics and an antisecretory drug. Probiotics may be added to reduce side effects and possibly improve outcomes.

Materials and methods: We conducted a double-blind, randomized trial of pantoprazole plus either Lactobacillus reuteri (Gastrus) (high dose) or a matching placebo to assess the impact on the gut microbiota of H. pylori-positive adults. Fecal samples were collected at baseline and after one and 2 months for shotgun metagenomic sequencing.

Results: A total of 26 patients were recruited and completed therapy. L. reuteri was only detected in the group that received supplemental …

From Trials To Practice: Implementing A Clinical Intervention In Community Settings, Elizabeth M Vaughan, Xiaoying Yu, Victor J Cardenas, Craig A Johnston, Salim S Virani, Ashok Balasubramanyam, Christie M Ballantyne, Aanand D Naik

Faculty, Staff and Students Publications

Introduction/objectives: Diabetes increases the risk of complications, especially for vulnerable populations. Our previous randomized clinical trial (RCT), TIME (Telehealth-supported, Integrated Community Health Workers (CHWs), Medication access, group visit Education), showed the efficacy of CHW-led diabetes care. This study aimed to gather data on transitioning TIME from clinical trials to practical implementation.

Methods: We conducted a 12-month RCT at a nonprofit community clinic using the Consolidated Framework for Implementation Research (CFIR). Participants, Hispanic adults without insurance and with type 2 diabetes (N = 58; 29/arm), were randomized to TIME (intervention) or usual care (control). The intervention included monthly group visits and …

Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Purpose: Cyclic nucleotide-gated (CNG) channels are ligand-gated ion channels that transduce light signals into electrical signals in the retinal photoreceptors. Pathogenic variants in CNG channel genes are reported to cause inherited retinal dystrophies (IRDs). The current study used targeted panel sequencing to describe the mutational spectrum of CNG channel genes in familial cases of IRDs from eight consanguineous Pakistani families.

Methods: The current study included consanguineous Pakistani families with at least two affected members. DNA was extracted from whole blood samples by the phenol-chloroform method. Two affected members from each family were initially analyzed using targeted panel sequencing of 344 …

Med12 Loss-Of-Function Variants As A Cause Of Congenital Diaphragmatic Hernia In Females With Hardikar Syndrome And Nonspecific Intellectual Disability, Eric C Kao, Elizabeth A Mizerik, Carlos A Bacino, Hongzheng Dai, Liesbeth Vossaert, Daryl A Scott

Faculty, Staff and Students Publications

Mediator complex subunit 12 (MED12) is required for the assembly of the kinase module of Mediator, a regulatory complex that controls the formation of the RNA polymerase II-mediated preinitiation complex. MED12-related disorders display unique gender-specific genotype-phenotype associations and include X-linked recessive Opitz-Kaveggia syndrome, Lujan-Fryns syndrome, Ohdo syndrome, and nonspecific intellectual disability in males predominantly carrying missense variants, and X-linked dominant Hardikar syndrome and nonspecific intellectual disability in females known to predominantly carry de novo nonsense/frameshift and nonsense/missense variants, respectively. MED12 was previously identified as a low-penetrance candidate gene for non-isolated congenital diaphragmatic hernia (CDH+). At the time, however, there was …

Long-Term Anti-Sars-Cov-2 Antibody Trajectories After Neutralizing Monoclonal Antibody Treatment, Elizabeth S Munroe, Greg A Grandits, Robert C Hyzy, Hallie C Prescott, Thomas W Barrett, Robin L Dewar, Nicole Engen, Anna L Goodman, Timothy J Hatlen, Helene Highbarger, Thomas L Holland, Gareth Hughes, Tomas O Jensen, Muhammad A Khan, Ioannis Kalomenidis, Nayon Kang, Sylvain Laverdure, Prasad Manian, Vidya Menon, Ravi Patel, Srikanth Ramachandruni, Tauseef Rehman, Kathryn Shaw-Saliba, Birgit Thorup Røge, David M Vock, Amy C Weintrob, Barnaby E Young, Anne P Frosch, Strive Network And Therapeutics For Inpatients With Covid-19 (Tico) Study Groups

Faculty, Staff and Students Publications

Background: Neutralizing monoclonal antibodies (nMAbs) have been used to treat COVID-19 and are increasingly being used to treat other infections. However, there is concern that by neutralizing the SARS-CoV-2 virus, nMAbs may decrease the availability of antigens to the immune system, potentially impairing the endogenous polyclonal immune response and decreasing long-term immune protection.

Methods: We compared 28 and 90-day anti-SARS-CoV-2 spike protein neutralization activity and anti-SARS-CoV-2 nucleocapsid response for patients hospitalized with COVID-19 infection randomized to receive nMAbs or placebo in the large platform ACTIV-3/TICO trials. We pooled results from four trials of anti-spike nMAbs. For most tested agents, measurements …

Treatment Fidelity And Outcome In Cbt For Youth With Autism: The Meya Fidelity Scale, Bryce D Mcleod, Jeffrey J Wood, Jennifer Cecilione Herbst, Danielle Dunn, Philip C Kendall, Eric A Storch, An Chuen Cho, Kashia A Rosenau

Faculty, Staff and Students Publications

Objective: Assessing treatment fidelity in effectiveness research is critical to interpreting study findings. This paper details the development and initial psychometric evaluation of the Modular Evidence-Based Practices for Youth with Autism Fidelity Scale (MEYA-FS) designed to support the assessment of cognitive-behavioral treatments for youth with autism in effectiveness research.

Method: Recorded treatment sessions (N = 338) were randomly selected from 77 youth (M age = 9.65 years, SD = 1.87; 50.67% White; 85.33% male) who received the Schema, Emotion, and Behavior-Focused Therapy for Children (SEBASTIEN) (n = 51) or Coping Cat (n = 24) program.

Results: …

Commentary: Impact Of Resistance Training Intensity On Body Composition And Nutritional Intake Among College Women With Overweight And Obesity: A Cluster Randomized Controlled Trial, Joshua L Keller, Sarah E Deemer, Gian Luca Di Tanna, Sherri L Pals, Kevin R Fontaine, David B Allison

Children’s Nutrition Research Center Staff Publications

No abstract provided.

Circulating Tumor Hpv Dna, Antibodies To Hpv16 Early Proteins, And Oral Hpv16 Dna As Biomarkers For Hpv-Related Oropharyngeal Cancer Screening, Kristina R Dahlstrom, Andrew T Day, Victor M Alvarez, Samantha R Chirinos, Giselle Santillana, Ming Guo, Karen S Anderson, Erich M Sturgis

Faculty, Staff and Students Publications

Background: Oropharyngeal cancer rates continue to rise with no effective screening method. Persistent oral oncogenic human papillomavirus (HPV), antibodies to HPV16 early (E) oncoproteins, and circulating tumor HPV DNA (ctHPVDNA) are biomarkers that show promise for use in HPV-related cancer screening.

Objective: To assess the prevalence of biomarkers for HPV-related cancer and their agreement in middle-aged men.

Methods: Men aged 50–64 years from the general population provided oral rinse and blood samples as well as information about demographics, tobacco/alcohol exposure, sexual behavior, and HPV-related disease history. Oral rinse was tested for HPV16 DNA and plasma was tested for HPV16 E …

Vibrotactile Auricular Vagus Nerve Stimulation Alters Limbic System Connectivity In Humans: A Pilot Study, Kara M. Donovan, Joshua D. Adams, Ki Yun Park, Phillip Demarest, Gansheng Tan, Jon T. Willie, Peter Brunner, Jenna L. Gorlewicz, Eric C. Leuthardt

2020-Current year OA Pubs

Vibration offers a potential alternative modality for transcutaneous auricular vagus nerve stimulation (taVNS). However, mechanisms of action are not well-defined. The goal of this pilot study was to evaluate the potential of vibrotactile stimulation of the outer ear as a method for activating central brain regions similarly to established vagal nerve stimulation methods. Seven patients with intractable epilepsy undergoing stereotactic electroencephalography (sEEG) monitoring participated in the study. Vibrotactile taVNS was administered across five vibration frequencies (2, 6, 12, 20, and 40 Hz) following a randomized stimulation pattern with 30 trials per frequency. Spectral coherence during stimulation was analyzed across theta …

The Association Of Human Milk Intake And Outcomes In Biliary Atresia, Mary Elizabeth M Tessier, Jeremy M Schraw, Stacey Beer, Sanjiv Harpavat, M Kyle Jensen, John C Magee, Vicky Ng, Michael E Scheurer, Sarah A Taylor, Benjamin L Shneider

Faculty, Staff and Students Publications

Objectives: Human milk intake has many benefits which could influence outcomes in biliary atresia (BA). However, the role of human milk in BA has not been examined. We hypothesized that human milk intake would be associated with improved outcomes in BA.

Methods: We assessed the impact of any human milk (AHM) as compared to formula only (FO) intake before Kasai portoenterostomy (KP) on outcomes in 447 infants with BA using the PROBE database (NCT00061828) post hoc. The primary outcome was clearance of jaundice (COJ = total bilirubin (TB) < 2 mg/dL by 3 months post-KP). Secondary outcomes included 2-year survival with native liver (SNL), bilirubin levels, cholangitis, ascites, and growth. We assessed the fecal microbiome (n = 8) comparing AHM versus FO.

Results: At baseline, 211 infants received AHM and 215 received …

Evaluation Of Methotrexate Pharmacogenomic Variation To Predict Acute Neurotoxicity In Children With Acute Lymphoblastic Leukemia, Rachel D Harris, Olga A Taylor, M Monica Gramatges, Amy E Hughes, Mark Zobeck, Sandi Pruitt, M Brooke Bernhardt, Ashley Chavana, Van Huynh, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, Ashley Choi, Yuu Ohno, Melissa A Richard, Alanna C Morrison, Han Chen, Bing Yu, Philip J Lupo, Karen Rabin, Michael E Scheurer, Austin L Brown

Faculty, Staff and Students Publications

BACKGROUND: Methotrexate is an important component of curative therapy in childhood acute lymphoblastic leukemia (ALL), but the role of genetic variation influencing methotrexate clearance and transport in toxicity susceptibility in children with ALL is not well established. Therefore, we evaluated the association between suspected methotrexate pharmacogenomic variants and methotrexate-related neurotoxicity.

METHODS: This study included children (aged 2-20 years) diagnosed with ALL (2005-2019) at six treatment centers in the southwest United States. Clinical information was abstracted from medical records. Suspected neurotoxic events occurring within 21 days of intravenous and/or intrathecal methotrexate delivered between the end of induction and start of maintenance …

Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Purpose: Cyclic nucleotide-gated (CNG) channels are ligand-gated ion channels that transduce light signals into electrical signals in the retinal photoreceptors. Pathogenic variants in CNG channel genes are reported to cause inherited retinal dystrophies (IRDs). The current study used targeted panel sequencing to describe the mutational spectrum of CNG channel genes in familial cases of IRDs from eight consanguineous Pakistani families.

Methods: The current study included consanguineous Pakistani families with at least two affected members. DNA was extracted from whole blood samples by the phenol-chloroform method. Two affected members from each family were initially analyzed using targeted panel sequencing of 344 …

Nanoparticle Contrast-Enhanced Computed Tomography Of Sporadic Aortic Aneurysm And Dissection: Effect Of Nanoparticle Size And Contrast Agent Dose, Laxman Devkota, Chen Zhang, Deborah Vela, Poonam Sarkar, Prajwal Bhandari, Zbigniew Starosolski, Renuka Menon, Dianna M Milewicz, Ying H Shen, Scott A Lemaire, Ketan B Ghaghada

Faculty, Staff and Students Publications

Background: Aortopathies, such as aortic aneurysm and dissection (AAD), are associated with enhanced aortic wall permeability and endothelial dysfunction. We previously demonstrated that nanoparticle contrast-enhanced computed tomography (nCECT), which detects enhanced aortic wall permeability, could enable non-invasive detection of early AAD before its progresses to fatal aortic rupture. This study investigated the effect of nanoparticle contrast agent (NPCA) size and dose on detection of aortopathy by nCECT.

Methods: In vivo studies were performed in a mouse model of sporadic AAD induced by challenging animals with high fat diet (5 weeks) and angiotensin II infusion (last one week). The effects …

Assessing The Cardioprotective Effects Of Exercise In Apoe Mouse Models Using Deep Learning And Photon-Counting Micro-Ct, Alex J Allphin, Rohan Nadkarni, Zay Y Han, Darin P Clark, Ketan B Ghaghada, Alexandra Badea, Cristian T Badea

Faculty, Staff and Students Publications

Background: The allelic variations of the apolipoprotein E (APOE) gene play a critical role in regulating lipid metabolism and significantly impact cardiovascular disease risk (CVD). This study aimed to evaluate the impact of exercise on cardiac structure and function in mouse models expressing different APOE genotypes using photon-counting computed tomography (PCCT) and deep learning-based segmentation.

Methods: A total of 140 mice were grouped based on APOE genotype (APOE2, APOE3, APOE4), sex, and exercise regimen. All mice were maintained on a controlled diet to isolate the effects of exercise. Low dose cardiac photon counting micro-CT imaging with intrinsic gating was performed …

Testosterone Plus Lifestyle Therapy Improves Skeletal Muscle Glycolysis In Older Men With Obesity And Hypogonadism, Viola Viola, Marlene Aguilar, Maria Liza Duremdes Nava, Alessandra Celli, Reina Armamento-Villareal, Yoann Barnouin, Nicola Napoli, Nagireeddy Putluri, Clifford Qualls, Dennis T Villareal

Faculty, Staff and Students Publications

Objective: Weight loss in older men with obesity and hypogonadism accelerates musculoskeletal decline, yet the underlying metabolic mechanisms remain unclear. Testosterone replacement therapy (TRT), when added to lifestyle therapy (LT), mitigates this decline, but its metabolic basis has not been defined. We examined skeletal muscle metabolomic adaptations to LT with or without TRT, focusing on glycolysis, the pentose phosphate pathway (PPP), the tricarboxylic acid (TCA) cycle, and carnitine metabolism to identify dominant pathways of metabolic adaptation.

Design: Randomized, double-blind, placebo-controlled trial (LITROS).

Methods: Eighty-three men aged 65 years or older with obesity (BMI ≥30 kg/m2), hypogonadism (testosterone < 10.4 nmol/L), and frailty (Physical Performance Test score ≤31) were randomized to 26 weeks of LT plus TRT (LT+TRT) or LT plus placebo (LT+Pbo). A metabolomic substudy was performed in 44 participants, who underwent serial biopsies of the vastus lateralis for targeted LC-MS/MS analysis of intermediates in glycolysis, PPP, TCA cycle, and carnitine metabolism.

Results: Among the …

Ethical Implications Of Neurotechnology In Industry-Academia Partnerships: Insights From Patient And Research Participant Interviews, Meredith V. Parsons, Maya Skolnik, Judith Mwobobia, Erin D Solomon, James M. Dubois, Tristan Mcintosh

2020-Current year OA Pubs

BACKGROUND: Neurotechnologies often advance through industry-academia (IA) partnerships and offer insight into brain and nervous system functions, bringing improved diagnosis and treatment options to patients. Both neurotechnology and IA partnerships pose ethical challenges that can impact research participation experiences, patient treatment, and health outcomes.

METHODS: Investigators conducted interviews with 16 patients who used neurotechnology devices in therapeutic or research settings. Interviews explored participants' experiences using neurotechnology, perspectives on IA partnerships, preferences for neural data use and long-term care, and advice for future neurotechnology device users. Data were analyzed using inductive thematic analysis.

RESULTS: Participants were generally supportive of IA partnerships. …

Effects Of Vagus Nerve Stimulation On Daily Function And Quality Of Life In Markedly Treatment-Resistant Major Depression: Findings From A One-Year, Randomized, Sham-Controlled Trial, A John Rush, Charles R Conway, Et Al.

2020-Current year OA Pubs

BACKGROUND: Depression treatments aim to minimize symptom burden and optimize quality of life (QoL) and psychosocial function.

OBJECTIVE: Compare the effects of adjunctive versus sham vagus nerve stimulation (VNS) on QoL and function in markedly treatment-resistant depression (TRD).

METHODS: In this multicenter, double-blind, sham-controlled trial, 493 adults with TRD and ≥4 adequate but unsuccessful antidepressant treatment trials (current episode) were randomized to active (n = 249) or sham (n = 244) VNS (plus treatment as usual) over a 12-month observation period. Quarterly outcomes included QoL with the Q-LES-Q, Mini-Q-LES-Q, and EQ-5D-5L, and function with the WHODAS 2.0 and Work Productivity …

Feasibility Of Endobronchial Ultrasound Guided Miniforceps Biopsy For Pd-L1 Expression And Quantitative Tissue Analysis, Max T Wayne, Nathaniel G Moulton, Cody Weimholt, Praveen Chenna, Alexander C Chen

2020-Current year OA Pubs

BACKGROUND: Testing for targeting programmed death ligand 1 (PD-L1) is standard of care for patients with newly diagnosed non-small cell lung cancer (NSCLC) but is only approved for use with core biopsy specimens. Endobronchial ultrasound guided miniforceps biopsy (EBUS-MFB) is an approach to obtain core biopsy material but data assessing the ability of EBUS-MFB to adequately test for PD-L1 is lacking. We evaluate the feasibility of EBUS-MFB to acquire adequate tissue for PD-L1 testing and look to compare the quality of specimens between EBUS-MFB and endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) using a standard method of tissue analysis.

METHODS: …

Atherogenic Lipoproteins Associate With Loss Of Glycemic Control In Youth-Onset Type 2 Diabetes: Results From The Today Study, Lorraine E Levitt Katz, Samuel S Gidding, James D Otvos, Kimberly L Drews, Fida Bacha, Steven Willi, Santica Marcovina, Siripoom Mckay, Ruth S Weinstock, Today Study Group

Faculty, Staff and Students Publications

Background: Type 2 diabetes (T2D) in adolescents is associated with an unfavorable lipid profile, but lipoprotein particle subspecies and branched-chain amino acid (BCAA) data are scarce.

Objective: To evaluate lipoprotein particle distributions, lipoprotein insulin resistance index (LP-IR), and BCAA levels longitudinally and their relationships with sex, race/ethnicity, treatment, and loss of glycemic control in adolescents with youth-onset T2D.

Methods: Participants from the TODAY study (n = 348) had samples analyzed yearly for glycated hemoglobin and nuclear magnetic resonance lipoprotein and BCAA assessments.

Results: At baseline, participants with T2D were 13.7 years old with T2D, obesity, and from racial and ethnic …

Impact Of Elevated Serum Triglycerides On Children With Acute Recurrent Or Chronic Pancreatitis From Insppire-2, Zachary M Sellers, Matthew J Giefer, Fuchenchu Wang, Gretchen A Cress, Maisam A Abu-El-Haija, Ankur Chugh, Reuven Z Cohen, Elissa M Downs, Douglas S Fishman, A Jay Freeman, Cheryl E Gariepy, Tanja Y Gonska, Amit S Grover, Doug Lindblad, Quin Y Liu, Asim Maqbool, Jacob A Mark, Brian A Mcferron, Megha S Mehta, Veronique D Morinville, Kenneth Ng, Robert A Noel, Chee Y Ooi, Emily R Perito, Madhura Y Phadke, Wenly Ruan, Sarah Jane Schwarzenberg, David M Troendle, Michael Wilschanski, Yuhua Zheng, Ying Yuan, Mark E Lowe, Aliye Uc, Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer

Faculty, Staff and Students Publications

Objective: To determine if mild-moderate hypertriglyceridemia (HTG) is associated with increased development of chronic pancreatitis (CP) or pancreatitis-associated complications in children with acute recurrent or CP.

Study design: Longitudinal data from the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2) cohort of children with acute recurrent or CP (n = 559) were analyzed. Subjects were divided into normal triglycerides (< 150 mg/dL; 1.7 mmol/L), any HTG (≥150 mg/dL; ≥1.7 mmol/L), mild-moderate HTG (150-499 mg/dL; 1.7-5.6 mmol/L), moderate HTG (500-999 mg/dL; 5.6-11.3 mmol/L), and severe HTG groups (≥1000 mg/dL; ≥11.3 mmol/L), based on highest serum triglyceride value. Laboratory, imaging, pancreatitis and hospital events, complications, and quality of life data were analyzed.

Results: In children with acute recurrent or CP and HTG, there was no increase in the number of pancreatitis attacks per person-years, nor an increase in CP prevalence. However, HTG severity was associated with increased pancreatic …

Lipoprotein(A) Levels In A Population With Clinical Atherosclerotic Cardiovascular Disease In The United States: A Subanalysis From The Lp(A)Heritage Study, Michael D Shapiro, Tariq M Haddad, Howard S Weintraub, Seth J Baum, Khaled Abdul-Nour, Samiha Sarwat, Vadim Paluy, Wess Boatwright, Auris Browne, Imran Ayaz, Cheryl A Abbas, Christie M Ballantyne

Faculty, Staff and Students Publications

Background: Elevated lipoprotein(a) (Lp[a]) is the most common inherited dyslipidemia that is independently and causally associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. However, data from diverse populations with ASCVD are lacking.

Objective: To evaluate Lp(a) levels in a diverse, contemporary United States (US) population with ASCVD, stratified by race, ethnicity, and sex.

Methods: Lp(a)HERITAGE (NCT03887520) was a multicenter study that estimated the prevalence of elevated Lp(a) in adults (18-80 years) with ASCVD. US participants with Lp(a) measured in nmol/L pre- or post-enrollment were included in this subanalysis. This study was descriptive; therefore, no statistical comparisons were made. …

Simulation Model To Estimate Pretreatment (Baseline) Low-Density Lipoprotein Cholesterol Levels In People Living With Homozygous Familial Hypercholesterolemia, Jing Gu, Robert J Sanchez, Alexandra Koumas, Sandeep Tripathi, Harshit Dixit, Adam Amer, Laurence Sperling, Christie M Ballantyne

Faculty, Staff and Students Publications

Introduction: Pretreatment levels of low-density lipoprotein cholesterol (LDL-C) are a primary consideration for the clinical diagnosis of homozygous familial hypercholesterolemia (HoFH). However, determination of pretreatment LDL-C can be challenging in this population because many individuals begin lipid-lowering therapy (LLT) early in life before diagnosis of HoFH.

Methods: A previously developed simulation model was adapted to estimate pretreatment LDL-C in people living with HoFH, based on their treated LDL-C value and current LLT (statin, ezetimibe, alirocumab, evolocumab, and/or lipoprotein apheresis).

Results: The tool includes an interface for users to provide relevant details for estimating non-clinical pretreatment LDL-C, specifically for patients suspected …

Sodium-Glucose Cotransporter-2 Inhibitor And Glucagon-Like Peptide-1 Receptor Agonist Discontinuation In Patients With Ckd, L Parker Gregg, Peter A Richardson, Vijay Nambi, Laura A Petersen, Michael E Matheny, Salim S Virani, Sankar D Navaneethan

Faculty, Staff and Students Publications

Key Points:

1. Treatment discontinuation is common among patients with CKD prescribed sodium-glucose cotransporter-2 (SGLT2) inhibitors (discontinued in 37%) or glucagon-like peptide-1 receptor agonists (GLP-1 RA; discontinued in 47%).

2. Discontinuation of SGLT2 inhibitors and GLP-1 RA was associated with recent hospitalizations, Black race, Hispanic ethnicity, and vascular disease.

3. Discontinuation of both agents was associated with death and cardiovascular events.

Background: Little is known about the association of discontinuation of sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RA) with outcomes in patients with CKD.

Methods: We identified adults with CKD stages 3–4 from 2005 to 2022 in the Veterans …

Long-Term Mortality Following Sars-Cov-2 Infection In Rural Versus Urban Dwellers With Autoimmune Or Inflammatory Rheumatic Disease: A Retrospective Cohort Analysis From The National Covid Cohort Collaborative, A Jerrod Anzalone, Lesley E Jackson, Namrata Singh, Maria I Danila, Elizabeth Reisher, Rena C Patel, Jasvinder A Singh

Faculty, Staff and Students Publications

Objective: Autoimmune or inflammatory rheumatic diseases (AIRDs) increase the risk for poor COVID-19 outcomes. Although rurality is associated with higher post-COVID-19 mortality in the general population, whether rurality elevates this risk among people with AIRD is unknown. We assessed associations between rurality and post-COVID-19 all-cause mortality, up to two years post infection, among people with AIRD using a large nationally sampled US cohort.

Methods: This retrospective study used the National COVID Cohort Collaborative, a medical records repository containing COVID-19 patient data. We included adults with two or more AIRD diagnostic codes and a COVID-19 diagnosis documented between April 2020 and …