Digital Commons Network^™

Segmental And Multifocal Isolated Dystonias: Similarities And Differences, Hyder A Jinnah, Vittorio Velucci, Daniele Belvisi, Gamze Kilic-Berkmen, Joel S Perlmutter, Laura J Wright, Christine Klein, Jeanne S Feuerstein, Steven Bellows, Joseph Jankovic, Cynthia Comella, Richard L Barbano, Aparna Wagle Shukla, Stephen G Reich, Mark S Ledoux, Alberto J Espay, Kevin R Duque, Florence C F Chang, Victor S C Fung, Sarah Pirio-Richardson, Carmen Terranova, Emile S Moukheiber, Sarah Idrissi, Barbara Vitucci, Susan H Fox, Samuel Frank, Natividad Stover, Brian D Berman, Rachel Saunders-Pullman, William G Ondo, Christopher L Groth, Marcello Esposito, Laura Avanzino, Francesco Bono, Roberto Erro, Marcello Mario Mascia, Antonella Muroni, Alfredo Berardelli, Giovanni Defazio

Faculty, Staff and Students Publications

Background: Whether the traditional distinction between segmental and multifocal dystonia is clinically or scientifically useful remains unclear.

Objective: To evaluate whether idiopathic isolated adult-onset segmental and multifocal dystonia can be differentiated based on clinical features other than the contiguity of affected body regions.

Methods: We compared data on segmental and multifocal dystonia from two large dystonia databases established in the USA and Italy that used similar criteria for patient recruitment and assessment.

Results: Compared to segmental dystonia, multifocal dystonia was characterized by a higher proportion of men, a younger age at dystonia onset, a greater frequency of upper limb dystonia, …

Impulsivity In Cerebellar Ataxia: An Online, Multidimensional Assessment, Brooke Chasalow, Yakov Flaumenhaft, Yael De Picciotto, Chi-Ying R Lin, Leila Montaser-Kouhsari, William Saban

Faculty, Staff and Students Publications

While considered a motor control structure, the cerebellum contributes to non-motor functions, including impulsivity. However, whether it contributes to impulsivity in a domain-specific manner remains unknown. Studies on cerebellar ataxia (CA), a common model for cerebellar dysfunction, typically have small sample sizes, limiting robustness. In a multicenter cross-sectional study, we investigated the cerebellum's role in various forms of impulsivity by comparing large cohorts of CA to age- and education-matched neurotypical healthy (NH) controls. Additionally, to examine the ability to identify individuals with CA using impulsivity features alone, we developed supervised machine learning (ML) models. In experiment 1 (CA = 140, …

How Does Frailty Impact Peri-Operative And Speech Recognition Outcomes For Cochlear Implants In Veterans?, Kaitlyn A Brooks, Benjamin D Lovin, Alex D Sweeney, Angela S Peng, Nathan R Lindquist

Faculty, Staff and Students Publications

Objective: To investigate the association of frailty with post-cochlear implant (CI) admission, morbidity, and CI-aided word recognition outcomes in veterans.

Study design: Retrospective cohort.

Setting: Single-institution tertiary care Veterans Health Administration (VHA) hospital.

Methods: Veterans who underwent cochlear implantation between 1998 to 2024 were included. The Modified 5-Item Frailty Index (mFI-5) score was used to characterize preoperative frailty. Outcomes of interest were admission from post-anesthesia care unit (PACU), relative risk (RR) of admission among frail patients, and relationship between frailty and post-CI word recognition score (WRS). Ordinal data were analyzed via logistic regression and Chi square tests; a multivariate linear …

Predominant Symptom In Gastroparesis: Relationships To Quality Of Life, Treatments, And Outcome, Henry P Parkman, Laura A Wilson, William L Hasler, Madhusudan Grover, Bruno P Chumpitazi, Helen Burton-Murray, Irene Sarosiek, Baha Moshiree, Geoffrey A Preidis, Robert J Shulman, Laura A Miriel, Dave Shade, Braden Kuo, Richard W Mccallum, Thomas L Abell, Pankaj J Pasricha

Faculty, Staff and Students Publications

Background: Patients with gastroparesis (Gp) can have a variety of symptoms. Apart from use of prokinetics, symptomatic therapies for the predominant symptom (PrS) are used.

Aims: (1) To classify Gp patients based on their PrS; (2) To determine differences in Gp symptoms, gastric emptying (GE), quality of life (QOL), treatments, and symptom improvement among Gp patients with different PrS.

Methods: Gp patients were enrolled in a multicenter registry and followed for 96-weeks. Patients recorded their PrS and completed questionnaires assessing symptoms and QOL at enrollment and at follow up visits.

Results: Of 1013 Gp patients (361 diabetic, 607 idiopathic, 45 …

Rural-Urban Differences In Use Of Mental Health Care For Serious Mental Illness At The Veterans Health Administration: A Retrospective Cohort Analysis, Alexandra B Caloudas, Amber B Amspoker, Ashley Smith, Liang Chen, Amy K Cuellar, Giselle Day, Alexandra Zingg, Julianna Hogan, Jan A Lindsay

Faculty, Staff and Students Publications

PURPOSE: Rural Veterans with serious mental illness (SMI) encounter significant barriers to accessing mental health care, related to SMI symptoms and rurality. A 2023 Government Accountability Office report found that rural Veterans used Veterans Health Administration (VHA) intensive mental health care for SMI less than urban Veterans relative to their population distributions. Our purpose was to deepen understanding of rural-urban differences in use of VHA mental health care among Veterans with SMI.

METHODS: Using VHA databases, we conducted a retrospective cohort analysis of 387,477 Veterans diagnosed with SMI, examining rurality as a predictor of intensive care for SMI and other …

Predictive Validity Of The Obsessive-Compulsive Inventory-4 And Florida Obsessive-Compulsive Inventory-Ii Severity Scale, Eric A Storch, Ryan J Mccarty, Maya Zehavi, Mahnoor Ahmad, Vanessa Zavala Cruz, Dayan Berrones, Josselyn S Muñoz, Diana Obando, Servando Rodriguez Barajas, Renee M Frederick, Jacey L Anderberg, Hannah C Moore, Marcos E Ochoa-Panaifo, Mayra C Martinez Mallen, Ogechi C Onyeka, Andrew D Wiese, Melisa N Sagarnaga, Joseph F Mcguire, Ygor Arzeno Ferrão, Latin American Trans-Ancestry Initiative For Ocd Genomics (Latino), Wayne K Goodman, James J Crowley, Brazilian Obsessive-Compulsive Spectrum Disorder Working Group (Gttoc)

Faculty, Staff and Students Publications

Efficient and accurate screening tools are crucial for improving early identification and treatment outcomes among individuals with obsessive-compulsive disorder (OCD). This study evaluated the sensitivity and specificity of two OCD screening measures: the Obsessive-Compulsive Inventory-4 (OCI-4) and the Florida Obsessive-Compulsive Inventory-II (FOCI-II) severity scale. The measures were administered in a large transnational sample of Spanish speaking Latin American adults (N = 1696) with elevated obsessive-compulsive symptomatology. Participants completed diagnostic interviews (MINI and Y-BOCS) and self-report assessments across 23 sites in 11 countries. Both measures significantly distinguished OCD from non-OCD cases, with the FOCI-II demonstrating somewhat better predictive performance (AUC = …

Application Of A Natural Language Processing Algorithm To Early Asthma Ascertainment For Adults In The Era Of Electronic Health Records, Chung-Il Wi, Thanai Pongdee, Hee Yun Seol, Sunghwan Sohn, Elham Sagheb, Bhavani Singh Agnikula Kshatriya, Shauna M Overgaard, Deepak K Sharma, Sungrim Moon, Elizabeth A Krusemark, Dave Watson, Sergio E Chiarella, Miguel A Park, Jason D Greenwood, Randy M Foss, Zhandong Liu, Meera Gupta, Carla M Davis, Wade Schulz, Hongfang Liu, Young J Juhn

Faculty, Staff and Students Publications

Background: The natural language processing (NLP) algorithm for predetermined asthma criteria (NLP-PAC) was successfully developed and validated for automatically ascertaining pediatric asthma from electronic health record (EHRs) systems. A scalable, efficient, and automated tool for ascertaining adult asthma status from EHRs remains nonexistent.

Objective: We validated NLP-PAC enabling ascertainment and early identification of adult asthma status in their EHRs.

Methods: We applied the validated NLP-PAC to EHRs of a convenient sample (adult cohorts who participated in our previous population-based studies) in which a reference standard (ie, asthma status defined by manual chart review) is available. The performance of NLP-PAC was …

The Impact Of Genetic Testing On Physician Practice In Specialized Cardiovascular Clinics, Arsalan Hamid, Tyler Sewell, Sucheta Bhatt, Scott Spencer, Damon Hostin, Ginger A Metcalf, Richard A Gibbs, Vijay Nambi, Layla A Abushamat, Christie M Ballantyne

Faculty, Staff and Students Publications

Background: Although familial hypercholesterolemia (FH) is a US Centers for Disease Control and Prevention tier 1 condition for genetic testing, the impact of testing on clinical outcomes is unclear.

Objective: We aimed to assess whether genetic testing alters lipid management in HeartCare participants.

Methods: For participants with pathogenic/likely pathogenic variants for FH observed at Baylor College of Medicine cardiology clinics, data on laboratory values, medication prescriptions, and diagnoses were collected and compared before and after genetic testing.

Results: In the 20 participants with APOB/LDLR variants and complete data, low-density lipoprotein cholesterol (LDL-C) was numerically lower but not significantly different before …

Comparing Observed With Self-Reported Hand Hygiene Adherence Among Bedside Nurses And Physicians At Two Hospitals In The United States, Prathit A Kulkarni, M Todd Greene, Sanjay Saint, Karen E Fowler, Serene Jacob, Laura Dillon, Michelle Espiritu, Nathan Houchens, Huberta T Cozart, Barbara W Trautner

Faculty, Staff and Students Publications

Background: Hand hygiene is a core component of infection prevention in healthcare settings. One potential reason for lack of adherence to recommended hand hygiene practices is erroneous self-perception. We aimed to compare perceptions about hand hygiene compliance with objective data.

Methods: Direct observations of hand hygiene performance by nurses and physicians during typical workflow in inpatient general medicine wards were conducted from 12 September 2022 to 27 October 2022 at two academic Veterans Affairs medical centers. Participants were surveyed regarding perceptions about their hand hygiene performance relative to recommended practices.

Results: Among nurses, hand hygiene was performed in 1,397/3,690 (37.9%) …

Active Bone Marrow Dose Reconstruction In A Large-Scale Cohort Study Of Cancer Patients Treated With Photon Radiotherapy, Keith T Griffin, Kishan J Pithadia, Yeon Soo Yeom, Lior Braunstein, Kelly L Bolton, Lindsay M Morton, Choonsik Lee

2020-Current year OA Pubs

BACKGROUND: Previous studies have investigated the dose-response relationship between external beam radiotherapy (EBRT) and leukemia by reconstructing the mean active bone marrow (ABM) dose as part of the exposure assessment. However, no prior study has leveraged electronic medical records (EMR) to reconstruct ABM dose and dose-volume in an EBRT patient population.

PURPOSE: To support future studies on the relationship between radiation exposure and adverse health effects among EBRT patients, we demonstrate methods to retrospectively calculate ABM dose and dose-volume metrics in a large patient cohort using EMR.

METHODS: We retrieved complete EMR for 639 individuals (five pediatric and 634 adult) …

Use Of A Cystatin C-Based Gfr Equation In A Population Pharmacokinetic Model Of Methotrexate Clearance In Adult Patients With Lymphoma., Zachary L. Taylor, Erin F. Barreto, Kristin C. Cole, Andrew D. Rule, Kianoush B. Kashani, Nelson Leung, Carrie A. Thompson, Thomas E. Witzig, Laura Ramsey, Jason N. Barreto

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: High-dose methotrexate (HDMTX) is a key treatment for lymphoma with central nervous system involvement. Whether incorporating cystatin C into glomerular filtration rate estimation improves methotrexate (MTX) clearance prediction remains unclear.

OBJECTIVES: We aimed to evaluate whether cystatin C-inclusive glomerular filtration rate equations improve MTX clearance prediction and to explore the relationship between MTX exposure and acute kidney injury (AKI) in adult patients with lymphoma receiving HDMTX.

METHODS: This was a prospective single-center study performed on 80 adult patients with lymphoma receiving HDMTX (1.5-8 g/m²) over a 4-h infusion. A population pharmacokinetic model was constructed using data from …

Impact Of Cyp2d6 Metabolizer Status On Ondansetron Efficacy In Early Pregnancy Induced Nausea And Vomiting: A Case Control Study., Michelle Liu, Megan M. Shuey, Sabrina E. Holley, Darlene F. Fountain, James Jaworski, Carol Griffin, Jeewoo Kim, Melissa Stec, Sudeep D. Sunthankar, Henry H. Ong, Srushti Gangireddy, Wei-Qi Wei, Andrea Gaedigk, Digna R. Velez Edwards, Vivian K. Kawai

Manuscripts, Articles, Book Chapters and Other Papers

Real-world data investigating CYP2D6 on the efficacy of ondansetron for nausea and vomiting in pregnancy (NVP) is lacking. Evidence shows CYP2D6 ultrarapid metabolizers are at risk of ondansetron nonresponse due to increased metabolism. We conducted a retrospective cohort study of early pregnant patients on ondansetron for NVP. Genotype data for 11 CYP2D6 variants and copy number variations were translated into activity score (AS) and metabolizer status: poor (PM), intermediate (IM), normal (NM), and ultrarapid (UM) metabolizers. A total of 264 women met inclusion/exclusion criteria (99 cases and 165 controls). Multivariate regression analyses of metabolizer status and AS were adjusted for …

Profiling The Genomic Landscape And Evolutionary History Of Polyploid Giant Cancer Cells In Undifferentiated Pleomorphic Sarcomas, Amy L Bowes, Sara Waise, Tom Lesluyes, Thomas Butters, Christie English, Haixi Yan, Annelien Verfaillie, Christopher Davies, Jianan Chen, Emma Nye, Richard Stone, Jiten Manji, Adrienne M Flanagan, Jonas Demeulemeester, Maxime Tarabichi, Nischalan Pillay, Peter Van Loo

Faculty, Staff and Student Publications

Polyploid giant cancer cells (PGCCs), characterised by multinucleation and atypical nuclear morphology, are a common feature of undifferentiated pleomorphic sarcomas. While PGCCs may be a critical substrate for cancer evolution, their formation pathways and genomic consequences remain underexplored. In this study, we characterise PGCCs in ten pleomorphic sarcomas and use topographic single-cell DNA sequencing (scDNA-seq) to investigate their genomic landscape. We selected PGCCs based on their nuclear morphology, including mononucleated or multinucleated bizarre, misshapen nuclei, and analysed them at single-cell resolution. Histopathological analysis showed that PGCCs were often randomly distributed throughout the tumour and did not appear in clusters, suggesting …

Profiling The Genomic Landscape And Evolutionary History Of Polyploid Giant Cancer Cells In Undifferentiated Pleomorphic Sarcomas, Amy L Bowes, Sara Waise, Tom Lesluyes, Thomas Butters, Christie English, Haixi Yan, Annelien Verfaillie, Christopher Davies, Jianan Chen, Emma Nye, Richard Stone, Jiten Manji, Adrienne M Flanagan, Jonas Demeulemeester, Maxime Tarabichi, Nischalan Pillay, Peter Van Loo

Faculty, Staff and Student Publications

Polyploid giant cancer cells (PGCCs), characterised by multinucleation and atypical nuclear morphology, are a common feature of undifferentiated pleomorphic sarcomas. While PGCCs may be a critical substrate for cancer evolution, their formation pathways and genomic consequences remain underexplored. In this study, we characterise PGCCs in ten pleomorphic sarcomas and use topographic single-cell DNA sequencing (scDNA-seq) to investigate their genomic landscape. We selected PGCCs based on their nuclear morphology, including mononucleated or multinucleated bizarre, misshapen nuclei, and analysed them at single-cell resolution. Histopathological analysis showed that PGCCs were often randomly distributed throughout the tumour and did not appear in clusters, suggesting …

Laser Interstitial Thermal Therapy And Adjuvant Pembrolizumab In Recurrent High-Grade Astrocytoma: A Phase 1/Randomized Phase 2b Trial, Jian L Campian, Omar H Butt, Yifei Xu, Jingxia Liu, William A Leidig, Tanner Johanns, George Ansstas, Alice Y Zhou, Sangami Pugazenthi, Jiayi Huang, Milan G Chheda, Albert H Kim, Eric C Leuthardt, Et Al.

2020-Current year OA Pubs

Immune checkpoint inhibitors (ICIs) show minimal efficacy in recurrent high-grade astrocytoma (rHGA). Laser interstitial thermal therapy (LITT), a minimally invasive cytoreductive approach, may prime rHGA for ICI response. A phase 1/randomized phase 2b trial (ClinicalTrials.gov: NCT02311582 ) was designed to test pembrolizumab in combination with LITT in patients with rHGA. Nine patients were enrolled in the phase I dose-escalation lead-in study. No dose-limiting toxicities were observed and 200 mg of pembrolizumab every three weeks was determined as the recommended phase 2 dose. The phase 2b study was initially designed to randomize (up to 45) patients 1:1 to either LITT followed …

Benefit Of Rituximab Maintenance After First-Line Bendamustine-Rituximab In Patients With Mantle Cell Lymphoma, Yucai Wang, Imran A Nizamuddin, Brad S Kahl, Et Al.

2020-Current year OA Pubs

The benefit of rituximab maintenance after first-line (1L) bendamustine-rituximab (BR) in patients with mantle cell lymphoma (MCL) remains uncertain, with inconsistent results from the phase 2 MAINTAIN trial and several retrospective studies. We conducted a large retrospective study at 27 US and Canadian academic centers to examine the benefit of rituximab maintenance after BR. A total of 911 patients received 1L BR between 2010 and 2020, and 703 had an objective response and no evidence of disease progression at the 3-month post-BR landmark. Among those, 394 (56%) received rituximab maintenance and 309 (44%) did not, with largely similar baseline patient …

Concordance Analysis Of Dna And Rna Profiling: The Md Anderson Impact2 Study In Precision Oncology, Stephanie T Schmidt, Mehmet A Baysal, Siqing Fu, David S Hong, Sarina A Piha-Paul, Aung Naing, Jordi Rodon Ahnert, Timothy A Yap, Ecaterina Elena Dumbrava, Jennifer Beck, Funda Meric-Bernstam, Apostolia Maria Tsimberidou

Faculty, Staff and Student Publications

DNA profiling is an established method for cancer treatment selection, while RNA profiling remains investigational. We explored associations between DNA and RNA alterations and between the number of genes with altered expression and overall survival (OS) using patient data from IMPACT2 (NCT02152254), a randomized study evaluating molecular profiling for guiding cancer therapy across tumor types. Molecular profiling, including DNA next-generation sequencing, was performed on all 829 patients in the IMPACT2 study. RNA profiling was performed by Tempus for 253 of 829 patients. We evaluated the concordance between DNA and RNA profiling, analyzed OS in 217 treated patients with …

Risk Stratification Of Low-Dose Cytarabine And Venetoclax In Patients With Aml Ineligible For Intensive Chemotherapy, Andrew H Wei, Panayiotis Panayiotidis, Pau Montesinos, Kamel Laribi, Vladimir Ivanov, Inho Kim, Jan Novak, Rebecca Champion, Walter Fiedler, Maria Pagoni, Julie Bergeron, Stephen B Ting, Jing-Zhou Hou, Takahiro Yamauchi, Jianxiang Wang, Stephen A Strickland, Michael R Savona, Tara L Lin, Anoop Enjeti, Ing Soo Tiong, Sangmin Lee, Gail J Roboz, Relja Popovic, Qi Jiang, Zihuan Liu, Yan Sun, Wellington Mendes, Brenda Chyla, Courtney D Dinardo

Faculty, Staff and Student Publications

Prognostic risk categorization aids treatment selection for patients with acute myeloid leukemia (AML). Although the European LeukemiaNet (ELN) classifications (2017 and 2022) for AML have been used to stratify outcomes for patients receiving intensive chemotherapy, their application to patients receiving less intensive therapy, such as azacitidine plus venetoclax, has been less satisfactory. In response, a 4-gene classifier that stratifies older patients with AML unfit for intensive chemotherapy into those with higher benefit (wild type), intermediate benefit (FLT3-internal tandem duplication [ITD] or NRAS/KRAS mutation), or lower benefit (TP53 mutation) after azacitidine plus venetoclax treatment was developed. We hypothesized that this 4-gene …

Novel Csf Biomarkers For Facilitating Diagnosis Of Cns-Hlh From Other Neuroinflammatory Disorders, Sharat Chandra, Kenneth D Greis, Somchai Chutipongtanate, Nathan Luebbering, Aaron Webster, Kelsey E Poisson, Kristen S Fisher, Kristi Smiley, Rebecca A Marsh, Michael B Jordan, Stella M Davies

Faculty, Staff and Students Publications

Central nervous system (CNS)-hemophagocytic lymphohistiocytosis (HLH) can mimic other neuroinflammatory disorders (ONID), often leading to misdiagnosis. Current diagnostic studies do not reliably distinguish CNS-HLH from ONID. We hypothesized that novel cerebrospinal fluid (CSF) biomarkers identified using unbiased proteomic analysis can facilitate diagnosis of CNS-HLH from ONID. Banked CSF samples were categorized into 3 groups, CNS-HLH, ONID, and controls without CNS inflammation. Proteomic analysis was performed on 25 samples per group (total N = 75). Proteins demonstrating significant changes (>1.5-fold higher and P< .05) in the CNS-HLH compared with ONID and associated with HLH pathophysiology were selected as candidate biomarkers. Cross-platform validation of candidate biomarkers, along with known biomarkers CXCL9 and osteopontin, was performed using enzyme-linked immunosorbent assay (ELISA). One hundred twenty-two proteins were identified on CSF proteomic analysis at 99% confidence. Of these, 10 proteins demonstrated a >1.5-fold change with a P< .05 in CNS-HLH compared with ONID. SerpinG1, lysozyme, and CD14 were selected as candidate biomarkers. ELISA confirmed significant elevation of all 5 biomarkers in CNS-HLH relative to ONID. Median SerpinG1 levels were1242.9 ng/mL in CNS-HLH vs 292.2 ng/mL in ONID (P ≤ .001), lysozyme 222.2 ng/mL vs 65.6 ng/mL (P = .001), and CD14 180.3 ng/mL vs 64.5 ng/mL (P ≤ .001). Median CXCL9 levels were 223.7 ng/mL in CNS-HLH vs 15.5 ng/mL in ONID (P ≤ .001), and osteopontin levels were 356.5 ng/mL vs 92.9 ng/mL (P = .001). These findings demonstrate that novel CSF biomarkers SerpinG1, lysozyme, CD14, and CXCL9 can facilitate diagnosis of CNS-HLH from ONID.

Dose-Dependent Ifn Programs In Myeloid Cells After Mrna And Adenovirus Covid-19 Vaccination., Giray N Eryilmaz, Yilmaz Yucehan Yazici, Radu Marches, Eleni P Mimitou, Lisa Kenyon-Pesce, Kim Handrejk, Sonia Jangra, Michael Schotsaert, Adolfo García-Sastre, George A Kuchel, Jacques Banchereau, Duygu Ucar

Faculty Research 2026

BACKGROUND. The SARS-CoV-2 pandemic provided a rare opportunity to study how human immune responses develop to a novel viral antigen delivered through different vaccine platforms. However, to date, no study has directly compared immune responses to all 3 FDA-approved COVID-19 vaccines at single-cell multiomic resolution.

METHODS. We longitudinally profiled SARS-CoV-2–naive adults (n = 31) vaccinated with BNT162b2, mRNA-1273, or Ad26.COV2.S, integrating plasma cytokines, antibody titers, and single-cell multiomic data (DOGMA-Seq).

RESULTS. We discovered a distinct, transient IFN program termed ISG-dim, which emerged specifically 1–2 days after the first mRNA dose in approximately 10% of myeloid cells. This state was …

Dose-Dependent Ifn Programs In Myeloid Cells After Mrna And Adenovirus Covid-19 Vaccination., Giray N Eryilmaz, Yilmaz Yucehan Yazici, Radu Marches, Eleni P Mimitou, Lisa Kenyon-Pesce, Kim Handrejk, Sonia Jangra, Michael Schotsaert, Adolfo García-Sastre, George A Kuchel, Jacques Banchereau, Duygu Ucar

Faculty Research 2026

BACKGROUNDThe SARS-CoV-2 pandemic provided a rare opportunity to study how human immune responses develop to a novel viral antigen delivered through different vaccine platforms. However, to date, no study has directly compared immune responses to all 3 FDA-approved COVID-19 vaccines at single-cell multiomic resolution.METHODSWe longitudinally profiled SARS-CoV-2-naive adults (n = 31) vaccinated with BNT162b2, mRNA-1273, or Ad26.COV2.S, integrating plasma cytokines, antibody titers, and single-cell multiomic data (DOGMA-Seq).RESULTSWe discovered a distinct, transient IFN program termed ISG-dim, which emerged specifically 1-2 days after the first mRNA dose in approximately 10% of myeloid cells. This state was characterized by ISGF3 complex activation and …

Nci9673 (Part B): Etctn Randomized Phase Ii Study Of Nivolumab With Or Without Ipilimumab In Refractory, Metastatic Squamous Cell Carcinoma Of The Anal Canal, Van K Morris, Kristen K Ciombor, Lianchun Xiao, Joshua K Ochieng, Enrica Marmonti, Blase Polite, Benjamin A Weinberg, John C Krauss, John Hays, Sarbajit Mukherjee, Olivia Aranha, Syma Iqbal, Tony Shields, Al B Benson, Syed Kazmi, Christopher Lieu, Howard Hochster, Jennifer Whisenant, Cara Haymaker, Cathy Eng

Faculty, Staff and Student Publications

Purpose: In the previously completed NCI9673 (part A) single-arm study, the antiprogrammed death (PD)-ligand-1 antibody nivolumab demonstrated efficacy for patients with metastatic anal cancer. In NCI9673 (Part B), we evaluated the anticytotoxic T-cell lymphocyte antigen-4 (CTLA-4) antibody ipilimumab in combination with nivolumab for patients with incurable anal cancer.

Methods: In this phase II NCI ETCTN trial, 100 patients with refractory, incurable anal cancer were randomly assigned to receive nivolumab (480 mg IV once every 4 weeks) alone or with ipilimumab (1 mg/kg IV once every 8 weeks). The primary end point was progression-free survival (PFS). Secondary endpoints included radiographic response, …

Cardiac Output-Guided Vs. Mean Arterial Pressure-Guided Hemodynamic Management In Craniotomy Patients With Cardiovascular Disease: A Randomized Trial, Na Chen, Minjing Yang, Renhua Li, Chunyan Ye, Lu Wang, Xingyang Liu, Jinghan Wu, Daniel I Sessler, E Wang

Faculty, Staff and Student Publications

We tested the primary hypothesis that cardiac output (CO)-guided versus mean arterial pressure (MAP)-guided hemodynamic management reduces the fraction of patients with 90-day Glasgow Outcome scores ≤ 4 (on a 1–5 scale, 5 better) after supratentorial brain tumor resections in adults with cardiovascular disease. 202 adults were randomized to intraoperative hemodynamic management guided by either CO or MAP. In patients assigned to CO guidance, clinicians targeted CO > 4 L/min and > 90% of baseline values using a combination of fluids and vasoactive agents. In patients assigned to MAP guidance, clinicians targeted MAP within ± 20% of baseline and ≥ 65 mmHg. …

Neurophysiological Connectomic Signatures Of Consciousness During Propofol-Induced General Anesthesia, Yuqin Li, Xiaoxiao Chen, Hui Zheng, Senqi Li, Qingyu Teng, Chengyu Wang, Fali Li, Zhongcong Xie, Daniel Sessler, Zhe Zhang, Peng Xu, Ti-Fei Yuan, Tao Xu

Faculty, Staff and Student Publications

General anesthesia induces reversible changes in consciousness through cortical activity and connectivity alterations, yet the functional connectome dynamics underlying propofol-induced unconsciousness remains unclear. We analyze high-density 128-channel electroencephalogram (EEG) from 31 surgical patients using source localization to identify neurobiological connectome signatures of propofol anesthesia. Propofol anesthesia increases delta and theta functional connectivity and decreases alpha, beta, and gamma connectivity. A classification model and dynamic analysis of consciousness loss reveals that alpha-band connectivity between parietal, occipital, and subcortical regions is critical for sustaining consciousness, with its disruption marking a key transition to unconsciousness. EEG from 46 additional patients under mild sedation …

Associations Between The Microbiome And Immune Responses To An Adenovirus-Based Hiv-1 Candidate Vaccine Are Distinct Between African And Us Cohorts, Yuhao Li, Daniel J Stieh, Lindsay Droit, Andrew Hyoungjin Kim, Rachel Rodgers, Kathie A Mihindukulasuriya, Leran Wang, Maria G Pau, Olive Yuan, Herbert W Virgin, Dan H Barouch, Megan T Baldridge, Scott A Handley

2020-Current year OA Pubs

Optimization of prophylactic vaccine regimens to elicit strong, long-lasting immunity is an urgent need highlighted by the COVID-19 pandemic. Stronger vaccine immunogenicity is frequently reported in individuals living in high-income countries compared to individuals living in low- and middle-income countries. While numerous host genetic and immune factors may influence vaccine responses, geographic restrictions to vaccine effectiveness may also be influenced by the intestinal microbiota, which modulates host immune systems. However, the potential role of the gut microbiota on responses to HIV-1 vaccines has not yet been explored. We analyzed the bacteriome by targeted 16S sequencing and the virome by virus-like …

Lymphatic Pumping Failure In The Arm Precedes Dermal Backflow And Breast Cancer-Related Lymphedema, Melissa B Aldrich, Meghan E Mcwain, Simona F Shaitelman, Rian E Kuhns, John C Rasmussen, Wendy A Woodward, Sarah M Desnyder, Wenyaw Chan, Eva M Sevick-Muraca

The Brown Foundation: Institute of Molecular Medicine

Background

Breast cancer patients who undergo regional nodal irradiation therapy (RNI) following neoadjuvant chemotherapy and mastectomy or lumpectomy with axillary lymph node dissection (ALND) frequently encounter breast cancer-related lymphedema (BCRL). Early detection and treatment can significantly improve outcomes. Previously, near-infrared fluorescence lymphatic imaging (NIRF-LI) detection of dermal backflow, or retrograde lymphatic flow into initial lymphatics, was shown to precede clinical BCRL diagnosis by 8–23 months. Herein, we hypothesize that lymphatic pump failure is responsible for dermal backflow and may be a target to prevent onset of BCRL symptoms.

Methods

Arm lymphatics in 51 patients with locally advanced breast cancer were …

Evaluating The American Society Of Hematology Quality Measure On Timeliness Of Analgesics For Sickle Cell Disease Pain Crisis, Ibrahim Gwarzo, Harish Chandra Dega, Paula Tanabe, Robin Miller, David C. Brousseau

Department of Medicine Faculty Papers

The American Society of Hematology (ASH) proposed the median time to first emergency department (ED) administration of pain medication for patients with sickle cell disease (SCD) vaso-occlusive pain episodes (VOE) as a site-level quality measure. Generalizable studies assessing current guideline adherence recommending pain medications within 60 minutes are lacking. We leveraged multisite electronic health record data from Epic's Cosmos research platform to analyze ED encounters for SCD VOE from 1 January 2019 to 31 December 2024, with administration of at least 1 pain medication. We calculated the quality measure (median time to first pain medication) and ranked sites based on …

Molecular Profiling And Tumor Biomarker Analysis Of Gog281/Logs: A Positive Late-Phase Trial Of Trametinib For Recurrent/Persistent Low-Grade Serous Ovarian Carcinoma, Robert L. Hollis, Austin Miller, Heather A. Lankes, Kwong-Kwok Wong, William Rodgers, David Millan, Karen Carty, Robert L. Coleman, Kathleen N. Moore, Angeles Alvarez Secord, David M. O'Malley, John K. Chan, Andrea R. Hagemann, Stephanie Gaillard, Saketh R. Guntupalli, Mitchell I. Edelson, Peter G. Rose, Oliver Dorigo, Susana Banerjee, Ailith Ewing, Michael Churchman, Anil K. Sood, C. Simon Herrington, Charlie Gourley, David M. Gershenson

Abington Jefferson Health Papers

PURPOSE: Low-grade serous ovarian carcinoma (LGSOC) is a distinct form of ovarian cancer characterized by younger patient age and relative chemoresistance. The GOG281/LOGS trial (NCT02101788) investigated the efficacy of the MEK inhibitor trametinib compared with physician's choice standard-of-care (SOC) in patients with LGSOC with persistent/recurrent disease. The study demonstrated significantly improved progression-free survival (PFS) in the trametinib-treated arm.

EXPERIMENTAL DESIGN: Two hundred and sixty patients with recurrent/persistent LGSOC were enrolled and randomly assigned in GOG281. We performed molecular analysis of 170 patients with available tumor specimens, comprising whole-exome sequencing and phospho-ERK (pERK) IHC, to identify biomarkers of clinical benefit from …

Feasibility And Form Factor Validation Of Reflective Shoulder-Mounted Pulse Oximeter In Patients With Suspected Sleep Apnea, Katie N. Kanter, Aaron Wang, David Gordon, Adina Singer, Jacob S. Brenner, Indira Gurubhagavatula, Anush Lingamoorthy, Olumuyiwa Oni, Cameron M. Baston

SKMC Student Presentations and Publications

The shoulder may be an effective central site for continuous oxygen saturation (SpO2) monitoring but studies of shoulder-mounted pulse oximetry technology are limited. We hypothesized that an alternative location would be similar in function and user acceptance to a standard FDA-cleared finger-based pulse oximeter. We conducted a quantitative and descriptive pilot study of two prototype biosensor designs in patients with clinical suspicion of hypoxic episodes at an outpatient sleep center. Participants wore two prototype biosensors-the primary a shoulder-mounted adhesive and the secondary a combination ring-bracelet-in addition to a control FDA-approved finger-based pulse oximeter. We assessed the comfort of the devices …

P-15 Peptide Enhanced Bone Graft In Transforaminal Lumbar Interbody Fusion: A Randomized, Controlled, Investigational Device Exemption Study Demonstrating Improved Composite Clinical Success, James Harrop, John E. O'Toole, Michael P. Steinmetz, Rick C. Sasso, Christopher D. Chaput, K. Brandon Strenge, Greg Maislin, Jeffrey P. Mullin, Thomas B. Freeman, Anthony Guanciale, Howard Lantner, Michael E. Janssen, David G. Schwartz, John M. Small, Wellington K. Hsu, Paul M. Arnold

Department of Orthopaedic Surgery Faculty Papers

STUDY DESIGN: Prospective, multicenter, single-blind, randomized, controlled pivotal study.

OBJECTIVE: To evaluate whether P-15L (PearlMatrix P-15 Peptide Enhanced Bone Graft) is noninferior in effectiveness to local autograft when applied in single-level instrumented transforaminal lumbar interbody fusion (TLIF).

SUMMARY OF BACKGROUND DATA: P-15L, an FDA-designated Breakthrough Drug-Device, is a composite drug-device combination bone graft containing P-15, a 15-amino acid polypeptide, which enhances cell binding, proliferation, and differentiation, resulting in bone formation.

MATERIALS AND METHODS: Skeletally mature patients, aged 22 to 80 years, with degenerative disc disease (DDD) were randomized 1:1 to P-15L (investigational) or to the local autograft (control) during single-level …