Medicine and Health Sciences Commons^™

Rethinking Immune Check Point Inhibitors Use In Liver Transplantation: Implications And Resistance, Vivian Ortiz, Emilien Loeuillard

2020-Current year OA Pubs

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, including the two most common liver tumors, hepatocellular carcinoma and cholangiocarcinoma, but their use in the peri-transplantation period is controversial. ICI therapy aims to heighten cytotoxic T lymphocytes response against tumors. However, tumor recurrence is common owing to tumor immune response escape involving ablation of CTL response by interfering with antigen presentation, triggering CLT apoptosis and inducing epigenetic changes that promote ICI therapy resistance. ICI can also affect tissue resident memory T cell population, impact tolerance in the post-transplant period, and induce acute inflammation risking graft survival post-transplant. Their interaction with immunosuppression …

Poor Sleep Is Common In Treatment-Resistant Late-Life Depression And Associated With Poorer Antidepressant Response: Findings From The Optimum Clinical Trial, Michael S B Mak, Marie Anne Gebara, Eric J Lenze, Daniel M Blumberger, Patrick J Brown, Pilar Cristancho, Alastair J Flint, Jordan F Karp, Helen Lavretsky, J Philip Miller, Charles F Reynolds 3rd, Steven P Roose, Benoit H Mulsant, Sarah T Stahl

2020-Current year OA Pubs

BACKGROUND: Adults with treatment-resistant late-life depression (TRLLD) have high rates of sleep problems; however, little is known about the occurrence and change in sleep during pharmacotherapy of TRLLD. This analysis examined: (1) the occurrence of insufficient sleep among adults with TRLLD; (2) how sleep changed during pharmacotherapy; and (3) whether treatment outcomes differed among participants with persistent insufficient sleep, worsened sleep, improved sleep, or persistent sufficient sleep.

METHODS: Secondary analysis of data from 634 participants age 60+ years in the OPTIMUM clinical trial for TRLLD. Sleep was assessed using the sleep item from the Montgomery-Asberg Depression Rating Scale at the …

Reliability Of Wrist Arthroscopy In The Diagnosis And Treatment Of Triangular Fibrocartilage Complex Tears, Elizabeth A Graesser, Lindley B Wall, Sanjeev Kakar, Jeffrey Yao, Marc J Richard, R Glenn Gaston, Charles A Goldfarb

2020-Current year OA Pubs

PURPOSE: Wrist arthroscopy is considered the gold standard for diagnosis of intra-articular wrist conditions including triangular fibrocartilage complex (TFCC) tears; however, the ability to reliably diagnose TFCC pathology during wrist arthroscopy is unclear. The purpose of this study was to assess the reliability of the diagnosis of TFCC tears on wrist arthroscopy videos.

METHODS: Five hand surgeons reviewed 43 cases on a secure web-based platform at two time points separated by 4-6 weeks. Each case included a deidentified clinical vignette and wrist radiographs with ulnar variance measurements and an arthroscopy video of ulnar wrist pathology, averaging 42 seconds. Surgeons were …

Molecular Regulation And Therapeutic Targeting Of Vldl Production In Cardiometabolic Disease, Kendall H Burks, Nathan O Stitziel, Nicholas O Davidson

2020-Current year OA Pubs

There exists a complex relationship between steatotic liver disease (SLD) and atherosclerotic cardiovascular disease (CVD). CVD is a leading cause of morbidity and mortality among individuals with SLD, particularly those with metabolic dysfunction-associated SLD (MASLD), a significant proportion of whom also exhibit features of insulin resistance. Recent evidence supports an expanded role of very low-density lipoprotein (VLDL) in the pathogenesis of CVD in patients, both with and without associated metabolic dysfunction. VLDL represents the major vehicle for exporting neutral lipid from hepatocytes, with each particle containing one molecule of apolipoproteinB100 (APOB100). VLDL production becomes dysregulated under conditions characteristic of MASLD …

Costs Of Non-Metastatic Prostate Cancer Treatment Among Privately Insured Men In The United States, Ashley J. Housten, Su-Hsin Chang, Hannah E. Rice, Allison J. L'Hotta, Eric H. Kim, Bettina F. Drake, Joanna L. Buss, Mary C. Politi

2020-Current year OA Pubs

BACKGROUND: Our objective was to quantify the cumulative total and out-of-pocket (OOP) costs for 3 non-metastatic prostate cancer treatment modalities: radiation, surgery, and conservative management at intervals of 1-, 3-, and 5-years post-diagnosis. We predicted these cumulative costs for a typical patient to improve cost transparency, facilitate conversations about potential costs, and to help advance non-metastatic prostate cancer cost evaluation.

METHODS: We used Merative™ MarketScan® Commercial Database data from 2007-2020. The cumulative total costs evaluated from the healthcare sector perspective were patient, clinician, and system/facility costs. We used descriptive statistics to summarize the sociodemographic characteristics of the cohort and a …

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 …

First Successful Ovarian Cortex Allotransplant To A Turner Syndrome Patient Requiring Immunosuppression: Wide Implications, Sherman J Silber, Sierra Goldsmith, Benjamin Rubinoff, Eduardo Kelly, Rowena Delos Santos, Anibal Melo, Daniel Brennan

2020-Current year OA Pubs

OBJECTIVE: To determine whether we can safely and successfully transplant an ovary tissue allograft from a nonidentical donor to her Turner syndrome sister.

DESIGN: Transplantation of cryopreserved ovary tissue, as well as fresh transplantation of ovarian tissue between identical twins, is now well established with numerous reported successful cases. However, there have not yet been any ovary transplants between nonidentical women requiring immunosuppression (ovary allotransplant). This could be a much more common indication for ovary tissue transplantation if safe and reliable immunosuppression were available.

PATIENT(S): A 20-year-old amenorrheic woman with nonmosaic 45-XO Turner syndrome requested ovary tissue transplantation from her …

A Holistic Ecosystem Model To Diversify The Physician Workforce And Enhance Health, Erik J Porfeli, Sunny Nakae, Leila Amiri, Leila E Harrison, Will Ross

2020-Current year OA Pubs

IMPORTANCE: The U.S. medical education system attracts and trains the next generation of physicians to advance the health care needs of a growing and increasingly diverse nation. This system can be credited for supplying a physician workforce achieving remarkable growth and innovation, yielding one of the world's most technologically advanced health care systems on the planet. This system, unfortunately, also contributes to educational, workforce, and health disparities.

OBSERVATIONS: The successes and challenges of the medical education and health care system align with broader economic, health, and educational patterns in the United States. An ecological model can be employed to unite …

Baseline Clinical Characterization Of Participants In The Accelerating Medicines Partnership Schizophrenia Program, Jean Addington, Daniel Mamah, Et Al.

2020-Current year OA Pubs

BACKGROUND: This paper focuses on the baseline clinical characterization of the participants in the Accelerating Medicines Partnership Schizophrenia (AMP SCZ) program. The AMP SCZ program is designed to investigate a wide array of clinical variables and biomarkers in a total of 2040 clinical high-risk (CHR) participants and 652 community control (CC) participants.

METHODS: The dataset analyzed includes 1642 individuals at clinical high risk for psychosis and 519 CCs. Key measures include the Positive Symptoms and Diagnostic Criteria for the Comprehensive Assessment of At-Risk Mental States Harmonized with the Structured Interview for Psychosis-Risk Syndromes, which determined CHR criteria and the severity …

Sample Ascertainment And Recruitment Sources In The Accelerating Medicines Partnership Schizophrenia Program, Jean Addington, Daniel Mamah, Et Al.

2020-Current year OA Pubs

BACKGROUND: This paper presents the recruitment sources of clinical high-risk (CHR) and community controls (CC) from the Accelerating Medicines Partnership Schizophrenia (AMP SCZ) program, which aims to study various clinical variables and biomarkers in 2040 CHR and 652 CC participants.

METHODS: A total of 1640 CHR and 514 CC had recruitment source data. The Positive Symptoms and Diagnostic Criteria for the Comprehensive Assessment of At-Risk Mental States Harmonized with the SIPS was utilized to assess CHR criteria and severity of attenuated psychotic symptoms (APSs), and the Global Functioning: Social Scale was used for social functioning. Participants were recruited through various …

An Explainable Ai Approach For Mapping Multivariate Regional Brain Age And Clinical Severity Patterns In Alzheimer's Disease, Gauri Darekar, Taslim Murad, Hui-Yuan Miao, Deepa S Thakuri, Alzheimer’S Disease Neuroimaging Initiative, Ganesh B Chand

2020-Current year OA Pubs

Age is a significant risk factor for mild cognitive impairment (MCI) and Alzheimer's disease (AD) and identifying brain age patterns is critical for comprehending the normal aging and MCI/AD processes. Prior studies have widely established the univariate relationships between brain regions and age, while multivariate associations remain largely unexplored. Herein, various artificial intelligence (AI) models were used to perform brain age prediction using an MRI dataset (

Sociodemographic Factors Predict Outcomes And Reveal Spatial Tumor Patterns In Glioblastoma, Patrick H Luckett, Michael Olufawo, Noah Naddaff-Slocum, Ki Yun Park, Bidhan Lamichhane, Donna Dierker, Gabriel Trevino Verastegui, John J Lee, Peter Yang, Albert Kim, Omar H Butt, Milan G Chheda, Abraham Z Snyder, Joshua S Shimony, Eric C Leuthardt

2020-Current year OA Pubs

BACKGROUND: Glioblastoma (GBM) is the deadliest malignant glioma of the central nervous system. Postsurgical functional impairment correlates with survival and is estimated using metrics such as extent and location of resection. This study uses machine learning to evaluate the predictive ability of baseline sociodemographic and lifestyle factors for forecasting postoperative functional outcomes in GBM patients.

METHODS: Glioblastoma patients (

RESULTS: Utilizing decision trees with age, SVI/SES, sex, tobacco use, alcohol use, obesity, and race as predictors, we achieved 88% accuracy in classifying median KPS and 85% accuracy in classifying KPS slope. Socioeconomic factors were the strongest predictors. Age, sex, and …

Preliminary Investigation Of Obstructive Sleep Apnea And Alzheimer's Disease In Down Syndrome, Dasoo M Yoon, David T Plante, Victoria Fleming, Benjamin Handen, Patrick Lao, Jamie Peven, Bradley Christian, Ozioma Okonkwo, Charles Laymon, Beau Ances, Christy Hom, Brian Helsel, Sigan L Hartley

2020-Current year OA Pubs

This study provided a preliminary examination of indices of obstructive sleep apsnea (OSA) and sleep disruptions in adults with Down syndrome (DS), and their associations with Alzheimer's disease (AD) pathology and symptomatology. A total of 93 adults with DS (aged 25-61 years) from the Alzheimer Biomarker Consortium-DS completed cognitive assessments, MRI and positron emission tomography (PET) scans (assessing amyloid-beta [Aβ] and tau), and a one-night home sleep study using the WatchPAT-300 device. Study partners also reported on depressive symptoms and diagnoses. Correlational analyses examined relationships between sleep variables, PET biomarkers, and AD symptomatology (cognitive functioning and depressive mood), controlling for …

Thalamic And Visual Network Dysfunction Relates To Tremor Response In Thalamic Deep Brain Stimulation, Aimee E Morris, Babatunde Adeyemo, Meghan C Campbell, Abraham Z Snyder, Joel S Perlmutter, Jonathan W Mink, Scott A Norris

2020-Current year OA Pubs

BACKGROUND: Essential tremor (ET) is the most common movement disorder in adults, but its pathogenesis is incompletely understood. Deep brain stimulation of the ventral intermediate thalamic nucleus (VIM DBS) provides effective treatment for medically-refractory cases. We aimed to determine how pre-surgical resting-state functional connectivity (FC) in medically-refractory ET relates to VIM DBS clinical response.

METHODS: We analyzed resting-state FC MRI in 21 participants with medically-refractory ET who subsequently underwent VIM DBS and 34 matched controls. We applied rigorous quality assurance to minimize motion artifact. Whole-brain correlation matrices were computed across 300 cortical, subcortical, and cerebellar regions and compared across groups …