Medicine and Health Sciences Commons^™

A Rigorous Multi-Laboratory Study Of Known Pdac Biomarkers Identifies Increased Sensitivity And Specificity Over Ca19-9 Alone, Brian Haab, Lu Qian, Ben Staal, Maneesh Jain, Johannes Fahrmann, Christine Worthington, Denise Prosser, Liudmila Velokokhatnaya, Camden Lopez, Runlong Tang, Mark W Hurd, Gopalakrishnan Natarajan, Sushil Kumar, Lynette Smith, Sam Hanash, Surinder K Batra, Anirban Maitra, Anna Lokshin, Ying Huang, Randall E Brand

Faculty, Staff and Student Publications

A blood test that enables surveillance for early-stage pancreatic ductal adenocarcinoma (PDAC) is an urgent need. Independent laboratories have reported PDAC biomarkers that could improve biomarker performance over CA19-9 alone, but the performance of the previously reported biomarkers in combination is not known. Therefore, we conducted a coordinated case/control study across multiple laboratories using common sets of blinded training and validation samples (132 and 295 plasma samples, respectively) from PDAC patients and non-PDAC control subjects representing conditions under which surveillance occurs. We analyzed the training set to identify candidate biomarker combination panels using biomarkers across laboratories, and we applied the …

Astct And Usclc Clinical Practice Recommendations For Allogeneic Stem Cell Transplant In Mycosis Fungoides And Sézary Syndrome, Amrita Goyal, Daniel O'Leary, Bouthaina Dabaja, Wen-Kai Weng, Jasmine Zain, Corey Cutler, Joan Guitart, Youn H Kim, Larisa J Geskin, Richard T Hoppe, Lynn D Wilson, Anne W Beaven, Steve Horwitz, Pamela B Allen, Stefan K Barta, Kimberly Bohjanen, Jonathan E Brammer, Joi B Carter, Nneka Comfere, Jennifer A Desimone, Kathryn Dusenbery, Madeleine Duvic, Auris Huen, Deepa Jagadeesh, Chris R Kelsey, Michael S Khodadoust, Mary Jo Lechowicz, Neha Mehta-Shah, Alison J Moskowitz, Elise A Olsen, Christina Poh, Barbara Pro, Christiane Querfeld, Craig Sauter, Lubomir Sokol, Olayemi Sokumbi, Ryan A Wilcox, John A Zic, Mehdi Hamadani, Francine Foss

Faculty, Staff and Student Publications

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL). While MF generally follows an indolent course, a subset of patients will experience progressive and/or treatment-refractory disease; Sézary syndrome is an aggressive lymphoma associated with high morbidity and mortality. Although allogeneic hematopoietic cell transplant (allo-HCT) is the only currently available potentially curative treatment modality for MF/SS there is no published guidance on referral criteria, transplant timing orallo-HCT approach. To develop consensus clinical practice recommendations, we performed a Delphi survey of 32 specialists in dermatology (n = 9), transplant hematology/oncology (n = 10), non-transplant …

Epigenomic And Transcriptomic Profiling Of Solitary Fibrous Tumors Identifies Site-Specific Patterns And Candidate Genes Regulated By Dna Methylation, Hannah C Beird, Jeffrey M Cloutier, Nalan Gokgoz, Christopher Eeles, Anthony M Griffin, Davis R Ingram, Khalida M Wani, Rossana Lazcano Segura, Luca Cohen, Carl Ho, Jay S Wunder, Irene L Andrulis, P Andrew Futreal, Benjamin Haibe-Kains, Alexander J Lazar, Wei-Lien Wang, Joanna Przybyl, Elizabeth G Demicco

Faculty, Staff and Student Publications

A solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm that can arise at any anatomical site and is characterized by recurrent NAB2::STAT6 fusions and metastatic progression in 10% to 30%. The cell of origin has not been identified. Despite some progress in understanding the contribution of heterogeneous fusion types and secondary mutations to SFT biology, epigenetic alterations in extrameningeal SFT remain largely unexplored, and most sarcoma research to date has focused on the use of methylation profiling for tumor classification. We interrogated genome-wide DNA methylation in 79 SFTs to identify informative epigenetic changes. RNA-seq data from targeted panels and …

Intra-Tumoral And Peripheral Blood Tigit And Pd-1 As Immune Biomarkers In Nodular Lymphocyte Predominant Hodgkin Lymphoma, Jay Gunawardana, Soi C Law, Muhammed B Sabdia, Éanna Fennell, Aoife Hennessy, Ciara I Leahy, Paul G Murray, Karolina Bednarska, Sandra Brosda, Judith Trotman, Leanne Berkahn, Andreea Zaharia, Simone Birch, Melinda Burgess, Dipti Talaulikar, Justina N Lee, Emily Jude, Eliza A Hawkes, Sanjiv Jain, Karthik Nath, Cameron Snell, Fiona Swain, Joshua W D Tobin, Colm Keane, Mohamed Shanavas, Emily Blyth, Christian Steidl, Kerry Savage, Pedro Farinha, Merrill Boyle, Barbara Meissner, Michael R Green, Francisco Vega, Maher K Gandhi

Faculty, Staff and Student Publications

In classical Hodgkin lymphoma (cHL), responsiveness to immune-checkpoint blockade (ICB) is associated with specific tumor microenvironment (TME) and peripheral blood features. The role of ICB in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is not established. To gain insights into its potential in NLPHL, we compared TME and peripheral blood signatures between HLs using an integrative multiomic analysis. A discovery/validation approach in 121 NLPHL and 114 cHL patients highlighted >2-fold enrichment in programmed cell death-1 (PD-1) and T-cell Ig and ITIM domain (TIGIT) gene expression for NLPHL versus cHL. Multiplex imaging showed marked increase in intra-tumoral protein expression of PD-1+ (and/or …

Association Between Metformin Use In Early Gestational Or Type 2 Diabetes In Pregnancy And Preterm Preeclampsia, Maya Patel, Ashley N Battarbee, Jerrie S Refuerzo, Noelia Zork, Kacey Eichelberger, Gladys A Ramos, Gayle Olson, Celeste Durnwald, Mark B Landon, Kjersti M Aagaard, Kedra Wallace, Christina Scifres, Todd Rosen, Wadia Mulla, Amy Valent, Sherri Longo, Kim A Boggess

Faculty, Staff and Student Publications

Objective: To estimate the association between maternal metformin use for the treatment of early gestational or pre-existing type 2 diabetes and preterm preeclampsia.

Methods: This is a planned secondary analysis of the MOMPOD study (Medical Optimization of Management of Overt Type 2 Diabetes in Pregnancy), a randomized trial comparing the effect of adding metformin with insulin treatment on composite neonatal outcome in singleton pregnancies with early gestational or type 2 diabetes. Participants were randomized at 11-23 weeks of gestation to 1,000 mg metformin twice daily or placebo until delivery. A subset of participants had maternal blood collected at 24-30 weeks …

Effects Of Tranexamic Acid On Human Osteoblasts As Proxy For Fracture Healing, Alexander Abraham, D Nicole Meyers, William D Rieger, Ryan Anthony, Humberto Aparicio, Adam Y Park, James F Kellam, Catherine G Ambrose

Faculty, Staff and Student Publications

Objectives: To investigate the effect of tranexamic acid (TXA) through in vitro culture of primary human osteoblasts (HOB) and in vivo using an operative rat femur fracture model. It was hypothesized that there would not be any effect on fracture healing in both studies.

Methods: Primary HOBs were exposed to varying concentrations of TXA over different time periods. Cells were assessed for viability, metabolism, and mineralization. For the in vivo model, fractures were created in the femora of adult rats, exposed to either TXA or saline, and then assessed for healing at different time points. A modified radiographic union score …

Learning The Hard Way: The Business Of Hand Surgery, Noah M Raizman, James M Saucedo

Faculty, Staff and Student Publications

No abstract provided.

The Effect Of Smoking On Functional Outcomes And Implant Survival Of Anatomical Total Shoulder Arthroplasty, Isabella E Amador, Kevin A Hao, Timothy R Buchanan, Derek S Damrow, Keegan M Hones, Trevor Simcox, Bradley S Schoch, Kevin W Farmer, Thomas W Wright, Tyler J Lamonica, Joseph J King, Jonathan O Wright

Faculty, Staff and Student Publications

Aims: We sought to compare functional outcomes and survival between non-smokers, former smokers, and current smokers who underwent anatomical total shoulder arthroplasty (aTSA) in a large cohort of patients.

Methods: A retrospective review of a prospectively collected shoulder arthroplasty database was performed between August 1991 and September 2020 to identify patients who underwent primary aTSA. Patients were excluded for preoperative diagnoses of fracture, infection, or oncological disease. Three cohorts were created based on smoking status: non-smokers, former smokers, and current smokers. Outcome scores (American Shoulder and Elbow Surgeons (ASES), Constant-Murley score, Shoulder Pain and Disability Index (SPADI), Simple Shoulder Test …

Hu8f4-Car T Cells With Mutated Fc Spacer Segment Improve Target Specificity And Mediate Anti-Leukemia Activity In Vivo, Hong He, Rolando A Vedia, Sijie Lu, Qiaochuan Li, Kathryn R Cox, Lisa St John, Anna Sergeeva, Karen Clise-Dwyer, Gheath Alatrash, Elizabeth J Shpall, Qing Ma, Jeffrey J Molldrem

Faculty, Staff and Student Publications

Background aims: Hu8F4 is a T-cell receptor-like antibody with high affinity for the leukemia-associated antigen PR1/HLA-A2 epitope. Adapted into a chimeric antigen receptor (CAR) format, Hu8F4-CAR is composed of the Hu8F4 single-chain variable fragment, the human IgG1 CH2CH3 extracellular spacer domain, a human CD28 costimulatory domain and the human CD3ζ signaling domain. We have demonstrated high efficacy of Hu8F4-CAR-T cells against PR1/HLA-A2-expressing cell lines and leukemic blasts from patients with acute myeloid leukemia in vitro. Previous studies have shown that modification of the Fc domains of IgG4 CH2CH3 spacer regions can eliminate activation-induced cell death and off-target killing mediated by …

Diaphragmatic Myopathy Associated With Dual Immune Checkpoint Inhibitors In A Patient With Renal Cell Carcinoma, Jeremy R Walder, Saadia A Faiz, Sudhakar Tummala, Shiao-Pei Weathers, Nicolas L Palaskas, Maryam Buni, Ajay Sheshadri, Lara Bashoura

Faculty, Staff and Student Publications

Immune-related adverse events (irAEs) have become increasingly prevalent with immune checkpoint inhibitor (ICI) cancer treatment. We present a 79-year-old man with metastatic renal cell carcinoma who developed shortness of breath and hypercapnic respiratory insufficiency after his first cycle of nivolumab and ipilimumab. Laboratory data showed elevated creatinine kinase, troponins, and transaminases. Computed tomography of the chest demonstrated bilateral lower lobe atelectasis. Heart catheterization and endomyocardial biopsy were unremarkable. Electromyogram (EMG) and nerve conduction studies (NCS) of the limb muscles revealed mild diffuse myopathy, normal sensory nerve conductions, and low-amplitude motor responses. Subsequent diaphragmatic EMG and NCS demonstrated severe myopathy. ICI-mediated …

A Putative Camp-Binding Protein In Trypanosoma Brucei Cooperates With Flam3 To Promote Flagellar Connection And Cell Morphogenesis, Qing Zhou, Phu Van Nguyen, Ziyin Li

Faculty, Staff and Student Publications

Trypanosoma brucei is a flagellated parasitic protozoan, and within the insect vector the parasite transitions from the trypomastigote form to the epimastigote form by repositioning its mitochondrial genome and relocating the flagellum. The mechanisms underlying such morphology changes are still poorly understood, but several flagellum-localized proteins are involved in this process by modulating the flagellum attachment zone (FAZ) that adheres the flagellum to the cell membrane. We report here a putative cAMP-binding protein named cAMP-BP1, which promotes flagellar connection and morphology transition. cAMP-BP1 contains two cyclic nucleotide-binding domains and five calcium-binding C2 domains and localizes to the flagella connector and …

Discovery, Characterization, And Structure Of A Cofactor-Independent Histidine Racemase From The Oral Pathogen Fusobacterium Nucleatum, Tess Lamer, Pu Chen, Marie J Venter, Marco J Van Belkum, Anjalee Wijewardane, Chenggang Wu, M Joanne Lemieux, John C Vederas

Faculty, Staff and Student Publications

Fusobacterium nucleatum is an oral commensal bacterium that can act as an opportunistic pathogen and is implicated in diseases such as periodontitis, adverse pregnancy outcomes, colorectal cancer, and Alzheimer's disease. F. nucleatum synthesizes lanthionine for its peptidoglycan, rather than meso-2,6-diaminopimelic acid (DAP) used by most Gram-negative bacteria. Despite lacking the biosynthetic pathway for DAP, the genome of F. nucleatum ATCC 25586 encodes a predicted DAP epimerase. A recent study hypothesized that this enzyme may act as a lanthionine epimerase, but the authors found a very low turnover rate, suggesting that this enzyme likely has another more favored substrate. Here, we …

The Evolving Pathophysiology Of Tbi And The Advantages Of Temporally-Guided Combination Therapies, Laura Zima, Anthony N Moore, Paul Smolen, Nobuhide Kobori, Brian Noble, Dustin Robinson, Kimberly N Hood, Ryota Homma, Amar Al Mamun, John B Redell, Pramod K Dash

Faculty, Staff and Student Publications

Several clinical and experimental studies have demonstrated that traumatic brain injury (TBI) activates cascades of biochemical, molecular, structural, and pathological changes in the brain. These changes combine to contribute to the various outcomes observed after TBI. Given the breadth and complexity of changes, combination treatments may be an effective approach for targeting multiple detrimental pathways to yield meaningful improvements. In order to identify targets for therapy development, the temporally evolving pathophysiology of TBI needs to be elucidated in detail at both the cellular and molecular levels, as it has been shown that the mechanisms contributing to cognitive dysfunction change over …

Perceived Partner Responsiveness Alters The Association Between Marital Distress And Well-Being In Dementia Spousal Caregivers, Vincent D Lai, Jensine Paoletti-Hatcher, E Lydia Wu-Chung, Itee Mahant, Daniel L Argueta, Kelly N Brice, Bryan T Denny, Charles Green, Luis D Medina, Paul E Schulz, Jennifer M Stinson, Cobi J Heijnen, Christopher P Fagundes

Faculty, Staff and Student Publications

Caregivers for spouses with Alzheimer's disease and related dementias (ADRD) experience drastic changes in the marital relationship that may put them at risk for worsening well-being. Perceived partner responsiveness, or feeling cared for, understood, and appreciated by one's spouse, may help mitigate these effects. In this study, we investigated the associations between marital distress, perceived partner responsiveness, and psychological and physiological well-being indicators among ADRD spousal caregivers.

Method: A sample of 161 caregivers provided blood samples and completed self-report measures of marital distress, perceived partner responsiveness, and depressive symptoms. We tested hypotheses in our sample cross-sectionally based on two theoretical …

Peak Nasal Inspiratory Flow Assessment Of Polyp Size And Response From Synapse, Amber U Luong, Joshua M Levy, Ludger Klimek, Richard J Harvey, Jared Silver, Steven G Smith, Abby Fuller, Robert Chan, Peter W Hellings

Faculty, Staff and Student Publications

Background: In the phase III SYNAPSE study, mepolizumab plus standard of care reduced total endoscopic nasal polyp score (NPS) versus that with placebo in patients with chronic rhinosinusitis with nasal polyps.

Objective: Our aim was to investigate relationships between NPS and (1) peak nasal inspiratory flow (PNIF) and (2) patient-reported outcomes.

Methods: In this post hoc analysis, patients randomized 1:1 received mepolizumab, 100 mg, or placebo subcutaneously every 4 weeks (plus standard of care). Changes from baseline in PNIF (week 52), visual analog scale scores (overall symptoms, nasal obstruction, and loss of smell [weeks 49-52]), and total 22-Item Sino-Nasal Outcome …

Building Resilience: A Specialty Clinic Tailored To Older Adults At Risk For Violence And Abuse, Melba A Hernandez-Tejada, Deborah M Little, Madeline J Bruce, Sarly Butte, Jason Burnett, Leila Wood, Ron Acierno

Faculty, Staff and Student Publications

Objective: Both structural (e.g., ageism) and personal (e.g., stigma) barriers hinder older adults' access to and engagement with mental health care. These barriers are particularly problematic for those vulnerable to interpersonal violence and abuse (e.g., due to social isolation). This study presents a quality improvement program aimed at older adults who have experienced significant stressful events, particularly elder mistreatment, within a larger trauma specialty clinic. Leveraging home-based telemedicine, the clinic provides evidence-based psychotherapy tailored to the needs of older adults.

Methods: From 2021 through 2023, the authors retrospectively examined treatment initiation, engagement, completion, and clinical outcomes among 231 older adults …

Analyzing Llama 3-Based Approach For Axiom Translation From Ontologies, Xubing Hao, Licong Cui, Cui Tao, Kirk Roberts, Muhammad Amith

Faculty, Staff and Student Publications

Ontology development involves a top-down approach where ontology engineers and domain experts collaboratively define and evaluate ontological elements and axioms. Translating ontology axioms into natural language can significantly aid in ontology evaluation by making the content more understandable to subject matter experts who may lack a background in knowledge engineering. In this preliminary study, we investigate the potential of large language models (LLMs) in axiom translation from ontologies to facilitate ontology evaluation. We utilize Llama 3 to translate 1,192 ontology axioms across 19 distinct axiom types from five published ontologies. Results show that 163 (13.67%) of the Llama 3 translation …

Genetic Regulation Of Human Brain Proteome Reveals Proteins Implicated In Psychiatric Disorders, Jie Luo, Ling Li, Mingming Niu, Dehui Kong, Yi Jiang, Suresh Poudel, Annie W Shieh, Lijun Cheng, Gina Giase, Kay Grennan, Kevin P White, Chao Chen, Sidney H Wang, Dalila Pinto, Yue Wang, Chunyu Liu, Junmin Peng, Xusheng Wang

Faculty, Staff and Student Publications

Psychiatric disorders are highly heritable yet polygenic, potentially involving hundreds of risk genes. Genome-wide association studies have identified hundreds of genomic susceptibility loci with susceptibility to psychiatric disorders; however, the contribution of these loci to the underlying psychopathology and etiology remains elusive. Here we generated deep human brain proteomics data by quantifying 11,608 proteins across 268 subjects using 11-plex tandem mass tag coupled with two-dimensional liquid chromatography-tandem mass spectrometry. Our analysis revealed 788 cis-acting protein quantitative trait loci associated with the expression of 883 proteins at a genome-wide false discovery rate < 5%. In contrast to expression at the transcript level and complex diseases that are found to be mainly influenced by noncoding variants, we found protein expression level tends to be regulated by non-synonymous variants. We also provided evidence of 76 shared regulatory signals between gene expression and protein abundance. Mediation analysis revealed that for most (88%) of the colocalized genes, the expression levels of their corresponding proteins are regulated by cis-pQTLs via gene transcription. Using summary data-based Mendelian randomization analysis, we identified 4 proteins and 19 genes that are causally associated with schizophrenia. We further integrated multiple omics data with network analysis to prioritize candidate genes for schizophrenia risk loci. Collectively, our findings underscore the potential of proteome-wide linkage analysis in gaining mechanistic insights into the pathogenesis of psychiatric disorders.

Corpus Callosum Structure And Auditory Interhemispheric Transfer In Spina Bifida Myelomeningocele, Kailyn A Bradley, Jenifer J Juranek, H Julia Hannay, Paul T Cirino, Larry A Kramer, Jack M Fletcher

Faculty, Staff and Student Publications

Objective: Maldevelopment of the posterior corpus callosum is common in spina bifida myelomeningocele (SBM) due to hydrocephalus-related hypoplasia and congenital partial hypogenesis. This study examined the relations of macro- and microstructural integrity of the interhemispheric temporal tract in SBM and auditory interhemispheric transfer using consonant-vowel dichotic listening.

Method: We collected T₁-weighted and diffusion tensor imaging data from 46 individuals with SBM and 15 typically developing individuals. Probabilistic tractography was used to isolate the interhemispheric white matter connecting auditory processing regions in both hemispheres. Interhemispheric transfer was assessed with a dichotic listening task.

Results: Although the typically developing group and …

Genomic Alterations In Dna Mismatch Repair Genes Across Different Cancer Types, Vijaykumar R Holla, Michael P Kahle, Sun-Hee Kim, Arash Ronaghy, Richard K Yang, Keyur P Patel, Mark J Routbort, Michael J Overman, Ecaterina E Dumbrava, Kenna R Mills Shaw, Daniel D Karp, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Purpose: PD-1 inhibition is effective in patients with mismatch repair deficient (dMMR) solid tumors in a tumor-agnostic fashion. However, dMMR testing by immunohistochemistry (IHC) is not routinely performed across tumor types. By contrast, next-generation sequencing (NGS) for somatic genomic alterations is frequently performed across tumor types. We hypothesized that NGS would identify patients with alterations in mismatch repair (MMR) genes and that these patients would have higher rates of MMR protein loss by IHC. This would support the utility of IHC reflex testing after NGS and potential matching to approved therapeutic options.

Methods: From January 2016 to December 2021, 15,701 …

A Complementary Metaproteomic Approach To Interrogate Microbiome Cultivated From Clinical Colon Biopsies, Van-An Duong, Altai Enkhbayar, Nobel Bhasin, Lakmini Senavirathna, Eva C Preisner, Kristi L Hoffman, Richa Shukla, Robert R Jenq, Kai Cheng, Mary P Bronner, Daniel Figeys, Robert A Britton, Sheng Pan, Ru Chen

Faculty, Staff and Student Publications

The human gut microbiome plays a vital role in preserving individual health and is intricately involved in essential functions. Imbalances or dysbiosis within the microbiome can significantly impact human health and are associated with many diseases. Several metaproteomics platforms are currently available to study microbial proteins within complex microbial communities. In this study, we attempted to develop an integrated pipeline to provide deeper insights into both the taxonomic and functional aspects of the cultivated human gut microbiomes derived from clinical colon biopsies. We combined a rapid peptide search by MSFragger against the Unified Human Gastrointestinal Protein database and the taxonomic …

Self-Management Intervention Improves Patient Adherence To Swallowing Exercises During Radiation For Head And Neck Cancer, Eileen H Shinn, Adam S Garden, Minxing Chen, Karen Basen-Engquist, Bryan Fellman, Kate Hutcheson, William H Morrison, Susan Peterson, Liang Li

Faculty, Staff and Student Publications

Background: While preventive swallowing exercises reduce the risk of radiation-associated dysphagia in patients with head and neck cancer, strategies are needed to improve patient adherence.

Methods: Before radiation, all participants were taught preventive swallowing exercises and randomized to either an adherence intervention or enhanced usual care. During radiation, all participants met twice with a speech pathologist for swallowing assessment and reinforcement of exercises. Intervention participants met weekly with a counselor in-person or by phone. At 6-week post-radiation follow-up, all participants completed a follow-up assessment of self-reported adherence, which was then corroborated with medical record documentation.

Results: Newly diagnosed pharyngeal and …

Boosting Acetylcholine Signaling By Cannabidiol In A Murine Model Of Alzheimer's Disease, Hesam Khodadadi, Évila Lopes Salles, Sahar Emami Naeini, Bidhan Bhandari, Hannah M Rogers, Jules Gouron, William Meeks, Alvin V Terry, Anilkumar Pillai, Jack C Yu, John C Morgan, Kumar Vaibhav, David C Hess, Krishnan M Dhandapani, Lei P Wang, Babak Baban

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is a challenging medical issue that requires efficacious treatment options to improve long-term quality of life. Cannabidiol (CBD) is a cannabis-derived phytocannabinoid with potential health benefits, including reports from our laboratory and others showing a therapeutic role in the pre-clinical treatment of AD; however, the mechanisms whereby CBD affects AD progression remain undefined. Innate lymphoid cells (ILCs) are recently discovered immune cells that initiate and orchestrate inflammatory responses. ILC2, a sub-class of ILCs, is proposed to have a role in cognitive function via unknown mechanisms. In this present study, we explored whether CBD ameliorates AD symptoms via …

Use Of Peripheral Nerve Blocks For Total Hip Arthroplasty, Leon Grinman, Brett Elmore, Alberto E Ardon, Adnan Hussain, Mohammed Faysal Malik, Nadia Hernandez, Mackenzie Janice Jacoby

Faculty, Staff and Student Publications

Purpose of review: The purpose of this review is to summarize the recent literature regarding regional anesthesia (RA) techniques and outcomes for total hip arthroplasty (THA) in the face of changing surgical techniques and perioperative considerations.

Recent findings: Based on large meta-analyses, peripheral nerve blocks are indicated for THA. Each block has its own risks and benefits and data for outcomes for particular techniques are limited. New surgical techniques, improved use of multimodal analgesia, and improved ultrasound guided regional anesthetics lead to better pain control for patients undergoing THA with less associated risks. Block selection continues to be influenced by …

Increased Gremlin1 Expression In Pancreatic Ductal Adenocarcinoma Promotes A Fibrogenic Stromal Microenvironment, Rachel R Tindall, Erika Y Faraoni, Jiajing Li, Yinjie Zhang, Shun-Ming Ting, Beanna Okeugo, Xiurong Zhao, Yuying Liu, Mamoun Younes, Qiang Shen, Jennifer M Bailey-Lundberg, Yanna Cao, Tien C Ko

Faculty, Staff and Student Publications

Objective: Pancreatic ductal adenocarcinoma (PDAC) microenvironment is primarily composed of cancer-associated fibroblasts and immune cells. Gremlin1 (Grem1) is a profibrogenic factor that promotes tumorigenesis in several cancers. However, the role of Grem1 in the PDAC microenvironment is not defined.

Materials and methods: We correlated Grem1 levels with activated stroma and immune cells in human PDAC using The Cancer Genome Atlas RNA-sequencing data and characterized expression of Grem1 transcripts and isoforms in pancreatic cell lines and PDAC tissues. We assessed the role of Grem1 in the microenvironment by in vitro studies.

Results: Grem1 expression is associated with an activated stroma and …

Comparative Effectiveness Of Non-Compounded Polidocanol 1% Endovenous Microfoam (Varithena) Ablation Versus Endovenous Thermal Ablation Utilizing A Systematic Review And Network Meta-Analysis, Lowell S Kabnick, Juan Carlos Jimenez, Sheila M Coogan, Larry Gache, Diana Frame, Candace Gunnarsson, Kathleen Ozsvath

Faculty, Staff and Student Publications

Objective: We compared the effectiveness and safety of polidocanol 1% endovenous microfoam ablation vs endovenous thermal ablation with radiofrequency or laser energy for treatment of venous insufficiency caused by lower extremity truncal vein incompetence via network meta-analysis of published comparative evidence.

Methods: We conducted a systematic literature review following best practices, including a prospective protocol. We screened studies published in English from 2000 to 2023 for randomized and nonrandomized studies reporting direct or indirect comparisons between polidocanol 1% endovenous microfoam and endovenous thermal ablation. Thirteen studies met our eligibility criteria for the network meta-analysis. The co-primary effectiveness outcomes were the …

White Matter And Latency Of Visual Evoked Potentials During Maturation: A Miniature Pig Model Of Adolescent Development, Peter Kochunov, L Elliot Hong, Ann Summerfelt, Si Gao, P Leon Brown, Matthew Terzi, Ashley Acheson, Marty G Woldorff, Els Fieremans, Ali Abdollahzadeh, Korrapati V Sathyasaikumar, Sarah M Clark, Robert Schwarcz, Paul D Shepard, Greg I Elmer

Faculty, Staff and Student Publications

Background: Continuous myelination of cerebral white matter (WM) during adolescence overlaps with the formation of higher cognitive skills and the onset of many neuropsychiatric disorders. We developed a miniature-pig model of adolescent brain development for neuroimaging and neurophysiological assessment during this critical period. Minipigs have gyroencephalic brains with a large cerebral WM compartment and a well-defined adolescence period.

Methods: Eight Sinclair™ minipigs (Sus scrofa domestica) were evaluated four times during weeks 14-28 (40, 28 and 28 days apart) of adolescence using monocular visual stimulation (1 Hz)-evoked potentials and diffusion MRI (dMRI) of WM. The latency for the pre-positive 30 ms …

Increased White Blood Cell In Young Adults With Family Histories Of Alcohol And Other Substance Use Disorders, Mustafa N Mithaiwala, Nikki S Phillips, Dylan H Nguyen, Melanie S Beehler, Harrison S Ballard, Andrea S Vincent, William R Lovallo, Peter Kochunov, L Elliot Hong, Jason C O'Connor, Steve Cole, Ashley Acheson

Faculty, Staff and Student Publications

Individuals with a family history of alcohol or other substance use disorders (FH+) are at increased risk for developing alcohol and other substance use disorders (AUD/SUD) compared to individuals with no such family histories (FH-). FH+ young adults have blunted stress reactivity, lower cognitive performance and altered frontal white matter microstructure compared to FH- controls. We hypothesized that family history of AUD/SUD disrupts neuroendocrine regulation of the immune system in FH+ individuals, resulting in altered blood immune cell composition, inflammation and neurocognitive alterations that, ultimately, increases risk for AUD/SUD and associated psychopathology. We examined white blood cell (WBC) parameters derived …

Secondary Acquisition Of The Philadelphia Chromosome In Acute Lymphoblastic Leukemia, Qiudan Shen, Elias J Jabbour, Guilin Tang, Hong Fang, Wei Wang, Nicholas J Short, M James You, L Jeffrey Medeiros, Shimin Hu

Faculty, Staff and Student Publications

No abstract provided.

Contrasting Association Pattern Of Plasma Low-Density Lipoprotein With White Matter Integrity In Apoe4 Carriers Versus Non-Carriers, Zhenyao Ye, Yezhi Pan, Rozalina G Mccoy, Chuan Bi, Chen Mo, Li Feng, Jiaao Yu, Tong Lu, Song Liu, J Carson Smith, Minxi Duan, Si Gao, Yizhou Ma, Chixiang Chen, Braxton D Mitchell, Paul M Thompson, L Elliot Hong, Peter Kochunov, Tianzhou Ma, Shuo Chen

Faculty, Staff and Student Publications

Apolipoprotein E ε4 (APOE4) is a strong genetic risk factor of Alzheimer’s disease and metabolic dysfunction. However, whether APOE4 and markers of metabolic dysfunction synergistically impact the deterioration of white matter (WM) integrity in older adults remains unknown.

In the UK Biobank data, we conducted a multivariate analysis to investigate the interactions between APOE4 and 249 plasma metabolites (measured using nuclear magnetic resonance spectroscopy) with whole-brain WM integrity (measured by diffusion-weighted magnetic resonance imaging) in a cohort of 1,917 older adults (aged 65.0–81.0 years; 52.4% female).

Although no main association was observed between either APOE4 or metabolites with …