Medicine and Health Sciences Commons^™

Large-Bore Mechanical Thrombectomy Versus Catheter-Directed Thrombolysis In The Management Of Intermediate-Risk Pulmonary Embolism: Primary Results Of The Peerless Randomized Controlled Trial., Wissam A Jaber, Carin F Gonsalves, Stefan Stortecky, Samuel Horr, Orestis Pappas, Ripal T Gandhi, Keith Pereira, Jay Giri, Sameer J Khandhar, Khawaja Afzal Ammar, David M Lasorda, Brian Stegman, Lucas Busch, David J Dexter, Ezana M Azene, Nikhil Daga, Fakhir Elmasri, Chandra R Kunavarapu, Mark E Rea, Joseph S Rossi, Joseph Campbell, Jonathan Lindquist, Adam Raskin, Jason C Smith, Thomas M Tamlyn, Gabriel A Hernandez, Parth Rali, Torrey R Schmidt, Jeffrey T Bruckel, Juan C Camacho, Jun Li, Samy Selim, Catalin Toma, Sukhdeep Singh Basra, Brian A Bergmark, Bhavraj Khalsa, David M Zlotnick, Jordan Castle, David J O'Connor, C Michael Gibson

Heart and Vascular Articles

BACKGROUND: There are a lack of randomized controlled trial data comparing outcomes of different catheter-based interventions for intermediate-risk pulmonary embolism.

METHODS: PEERLESS is a prospective, multicenter, randomized controlled trial that enrolled 550 patients with intermediate-risk pulmonary embolism with right ventricular dilatation and additional clinical risk factors randomized 1:1 to treatment with large-bore mechanical thrombectomy (LBMT) or catheter-directed thrombolysis (CDT). The primary end point was a hierarchal win ratio composite of the following (assessed at the sooner of hospital discharge or 7 days after the procedure): (1) all-cause mortality, (2) intracranial hemorrhage, (3) major bleeding, (4) clinical deterioration and/or escalation to …

Characterization Of The Vaginal Microbiome Of Postmenopausal Patients Receiving Chemoradiation For Locally Advanced Cervical Cancer, Brett A. Tortelli, Jessika Contreras, Stephanie Markovina, Li Ding, Kristine M. Wylie, Julie K. Schwarz

2020-Current year OA Pubs

The standard-of-care treatment of locally advanced cervical cancer includes pelvic radiation therapy with concurrent cisplatin-based chemotherapy and is associated with a 30%-50% failure rate. New prognostic and therapeutic targets are needed to improve clinical outcomes. The vaginal microbiome has been linked to the pathogenesis of cervical cancer, but little is known about the vaginal microbiome in locally advanced cervical cancer as it relates to chemoradiation. In this pilot study, we utilized 16S rRNA gene community profiling to characterize the vaginal microbiomes of 26 postmenopausal women with locally advanced cervical cancer receiving chemoradiation. Our analysis revealed diverse anaerobe-dominated communities whose taxonomic …

Sleep-Wake Variation In Body Temperature Regulates Tau Secretion And Correlates With Csf And Plasma Tau, Geoffrey Canet, Brendan P. Lucey, Et Al.

2020-Current year OA Pubs

Sleep disturbance is bidirectionally associated with an increased risk of Alzheimer's disease and other tauopathies. While the sleep-wake cycle regulates interstitial and cerebrospinal fluid (CSF) tau levels, the underlying mechanisms remain unknown. Understanding these mechanisms is crucial, given the evidence that tau pathology spreads through neuron-to-neuron transfer, involving the secretion and internalization of pathological tau forms. Here, we combined in vitro, in vivo, and clinical methods to reveal a pathway by which changes in body temperature (BT) over the sleep-wake cycle modulate extracellular tau levels. In mice, a higher BT during wakefulness and sleep deprivation increased CSF and plasma tau …

A Randomized, Double-Blind, Placebo-Controlled Trial Of Il-7 In Critically Ill Patients With Covid-19, Manu Shankar-Hari, Kenneth E. Remy, Jane Blood, Andrew H. Walton, Teresa Blood, Richard Hotchkiss, Et Al.

2020-Current year OA Pubs

BACKGROUND: Lymphopenia and failure of lymphocytes to mount an early IFN-γ response correlate with increased mortality in COVID-19. Given the essential role of CD4 helper and CD8 cytotoxic cells in eliminating viral pathogens, this profound loss in lymphocytes may impair patients' ability to eliminate the virus. IL-7 is a pleiotropic cytokine that is obligatory for lymphocyte survival and optimal function.

METHODS: We conducted a prospective, double-blind, randomized, placebo-controlled trial of CYT107, recombinant human IL-7, in 109 critically ill, patients with lymphopenia who have COVID-19. The primary endpoint was to assess CYT107's effect on lymphocyte recovery with secondary clinical endpoints including …

Development And Validation Of Risk Stratification For Heart Failure After Acute Coronary Syndrome Based On Dynamic S100a8/A9 Levels, Jie Ma, Ke Ma, Jing Chen, Xinying Yang, Fei Gao, Hai Gao, Hui Zhang, Xin-Liang Ma, Jie Du, Ping Li, Yulin Li

Department of Emergency Medicine Faculty Papers

BACKGROUND: The early assessment of heart failure (HF) risk in patients with acute coronary syndrome (ACS) can help reduce mortality. S100A8/A9 is not only rapidly released after myocardial ischemia, but is also involved in reperfusion injury, which is an important predictor of HF after ACS. We attempted to construct a reliable HF risk stratification tool for evaluating patients with ACS after reperfusion therapy based on S100A8/A9 dynamic changes.

METHODS AND RESULTS: This prospective study included 3 independent cohorts of patients with ACS who received reperfusion therapy. The discovery cohort was divided into 2 subgroups: the longitudinal subgroup (n=264) with serum …

Spending Changes After Moving To Areas With Greater Aco Participation Among Nonattributed Medicare Beneficiaries, Yucheng Hou, Marisa Elena Domino, Valerie A Lewis, Qing Gong, Kevin Callison, Justin G Trogdon

Faculty, Staff and Student Publications

IMPORTANCE: Accountable care organizations (ACOs) under the Medicare Shared Savings Program have long been envisioned as a pathway to improved care efficiency and quality of care for all Medicare beneficiaries. However, little is known about whether the changes in health care spending associated with ACOs have extended beyond ACO-attributed Medicare beneficiaries to all Medicare beneficiaries.

OBJECTIVE: To estimate spending changes by non-ACO-attributed Medicare beneficiaries after moving to geographic areas with greater ACO participation.

DESIGN, SETTING, AND PARTICIPANTS: This repeated cross-sectional study analyzed claims from a 20% representative sample of all Medicare beneficiaries, aged 65 to 99 years, from 2009 to …

Sleep Trajectories And All-Cause Mortality Among Low-Income Adults, Kelsie M Full, Hui Shi, Loren Lipworth, Lawrence T Dauer, Michael T Mumma, Qian Xiao

Faculty, Staff and Student Publications

IMPORTANCE: Short and long sleep durations are adversely associated with cardiovascular disease (CVD), type 2 diabetes, and mortality. It remains unclear how sleep duration trajectories over time are associated with mortality and whether these associations vary by well-documented sex, race, and socioeconomic sleep disparities.

OBJECTIVE: To investigate the association of 5-year sleep duration trajectories with all-cause and cause-specific mortality among US adults, predominantly those in low-income groups.

DESIGN, SETTING, AND PARTICIPANTS: The Southern Community Cohort Study included participants aged 40 to 79 years recruited and enrolled (from March 2002 to September 2009) from community health centers by using random sampling …

Safety And Tolerability Of Letetresgene Autoleucel (Gsk3377794): Pilot Studies In Patients With Advanced Non-Small Cell Lung Cancer, Mehmet Altan, Gilberto Lopes, T Jeroen N Hiltermann, Ramaswamy Govindan, Liza C Villaruz, Emiliano Calvo, Martin J Edelman, Muhammad Furqan, Joel Neal, Enriqueta Felip, Jennifer W Carlisle, John V Heymach, Róisín Eilish O'Cearbhaill, Marjorie Zauderer, Michael Chisamore, Ellie Corigliano, Ioanna Eleftheriadou, Stefan Zajic, Ben Jenkins, Sophia Goodison, Sunil Suchindran, Natalia Ramos-Hernandez, Nidale Tarek, Adam J Schoenfeld

Faculty, Staff and Student Publications

Purpose: The study aims to evaluate the safety, tolerability, and antitumor response of letetresgene autoleucel (lete-cel), genetically modified autologous T cells expressing a T-cell receptor specific for New York esophageal squamous cell carcinoma 1 (NY-ESO-1)/LAGE-1a shared epitope, alone or in combination with pembrolizumab, in HLA-A*02-positive (HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06) patients with NY-ESO-1- and/or LAGE-1a-positive non-small cell lung cancer.

Patients and methods: Study 208749 was a single-arm study of lete-cel alone. Study 208471 was a multiarm study of lete-cel alone or in combination with pembrolizumab in patients with advanced or recurrent non-small cell lung cancer.

Results: More than 2,500 patients were …

Phase I/Ii Study Of The Aurora Kinase A Inhibitor Alisertib And Pembrolizumab In Refractory, Rb-Deficient Head And Neck Squamous Cell Carcinomas, Faye M Johnson, Madison P O'Hara, Lacin Yapindi, Peixin Jiang, Hai T Tran, Alexandre Reuben, Weihong Xiao, Maura L Gillison, Xiaowen Sun, Alexander Khalaf, J Jack Lee, Jagannadha K Sastry, Soma Ghosh

Faculty, Staff and Student Publications

Purpose: Effective therapy for recurrent head and neck squamous cell carcinoma (HNSCC) that is refractory to chemotherapy and immunotherapy is a considerable need. Aurora kinase A inhibition leads to apoptosis and immunogenic cell death in preclinical models of human papilloma virus (HPV)-driven cancers.

Patients and methods: Alisertib was administered orally twice daily on days 1-7 and pembrolizumab on day 1 of a 21-day cycle to adults with advanced solid tumors (phase I) or with immunotherapy- and platinum-resistant, HPV-positive HNSCC (phase II).

Results: The recommended phase II alisertib dose was 40 mg, which had only the expected toxicity including cytopenia that …

The Landscape Of Ctdna In Appendiceal Adenocarcinoma, Michael G White, Mohammad A Zeineddine, Eleanor A Fallon, Fadl A Zeineddine, Julia Dansby, Saikat Chowdhury, Nicholas Hornstein, Abdelrahman Yousef, Mahmoud Yousef, Neal Bhutiani, Yue Gu, Bryan Kee, Arvind Dasari, Michael J Overman, Kanwal Raghav, Scott Kopetz, Abhineet Uppal, Melissa Taggart, Timothy Newhook, Keith Fournier, Beth Helmink, Leylah M Drusbosky, John Paul Shen

Faculty, Staff and Student Publications

Purpose: Appendiceal adenocarcinoma is a rare malignancy with distinct histopathologic subtypes and a natural history with metastasis primarily limited to the peritoneum. Little is known about the molecular pathogenesis of appendiceal adenocarcinoma relative to common tumors.

Experimental design: We analyzed molecular data for patients within the Guardant Health database with appendix cancer (n = 718). We then identified patients with appendiceal adenocarcinoma at our institution (from October 2004-September 2022) for whom ctDNA mutation profiling (liquid biopsy) was performed (n = 168) and extracted clinicopathologic and outcomes data. Of these 168 patients, 57 also had tissue-based tumor mutational profiling, allowing for …

A Comprehensive Head-To-Head Comparison Of Key Plasma Phosphorylated Tau 217 Biomarker Tests, Noëlle Warmenhoven, Nicolas R Barthélemy, Suzanne E Schindler, Andrew J Aschenbrenner, Cyrus A Raji, Tammie L S Benzinger, John C Morris, Laura Ibanez, Jigyasha Timsina, Carlos Cruchaga, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Plasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarker for reliable detection of Alzheimer's disease pathology. Various p-tau217 assays have been developed, but their relative performance is unclear. We compared key plasma p-tau217 tests using cross-sectional and longitudinal measures of amyloid-β (Aβ)-PET, tau-PET and cognition as outcomes and benchmarked them against CSF biomarker tests. Samples from 998 individuals [mean (range) age 68.5 (20.0-92.5) years, 53% female] from the Swedish BioFINDER-2 cohort, including both cognitively unimpaired and cognitively impaired individuals, were analysed. Plasma p-tau217 was measured with mass spectrometry assays [the ratio between phosphorylated and non-phosphorylated (%p-tau217WashU) and p-tau217WashU] and …

Cumulative Excess Body Mass Index And Mgus Progression To Myeloma, Lawrence Liu, Nikhil Grandhi, Mei Wang, Ekaterina Proskuriakova, Theodore Thomas, Martin W Schoen, Kristen M Sanfilippo, Kenneth R Carson, Alissa Visram, Celine Vachon, Graham Colditz, Murali Janakiram, Mengmeng Ji, Su-Hsin Chang

2020-Current year OA Pubs

IMPORTANCE: Obesity is a risk factor associated with multiple myeloma (MM) and its precursor, monoclonal gammopathy of unknown significance (MGUS). However, it is unclear how cumulative exposure to obesity affects the risk of MGUS progression to MM.

OBJECTIVE: To determine the association of cumulative exposure to excess body mass index (EBMI), defined as BMI (calculated as weight in kilograms divided by height in meters squared) greater than 25, with risk of MGUS progression to MM.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included patients with MGUS, including immunoglobin G, immunoglobin A, or light chain MGUS, from the nationwide US Veterans …

Racial Differences In Ctdna Profiles, Targeted Therapy Use, And Outcomes In Metastatic Breast Cancer, Emily L Podany, Katherine Clifton, Shaili Tapiavala, Foluso O Ademuyiwa, Cynthia X Ma, Andrew A Davis, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Black patients with metastatic breast cancer (mBC) have higher mortality rates than White patients despite advances in treatment.

OBJECTIVES: To examine whether Black patients with metastatic breast cancer have different genomic profiles compared with White patients and whether there are inequities in targeted treatment use between these groups.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, population-based cohort study assessed adult patients with mBC who underwent genomic profiling at academic institutions in the US between January 1, 2015, and December 31, 2023. Data analysis was performed between July 2023 and July 2024. A validation cohort was also included.

EXPOSURES: Targeted treatment …

Safety And Tolerability Of Letetresgene Autoleucel (Gsk3377794): Pilot Studies In Patients With Advanced Non-Small Cell Lung Cancer, Mehmet Altan, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

PURPOSE: The study aims to evaluate the safety, tolerability, and antitumor response of letetresgene autoleucel (lete-cel), genetically modified autologous T cells expressing a T-cell receptor specific for New York esophageal squamous cell carcinoma 1 (NY-ESO-1)/LAGE-1a shared epitope, alone or in combination with pembrolizumab, in HLA-A*02-positive (HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06) patients with NY-ESO-1- and/or LAGE-1a-positive non-small cell lung cancer.

PATIENTS AND METHODS: Study 208749 was a single-arm study of lete-cel alone. Study 208471 was a multiarm study of lete-cel alone or in combination with pembrolizumab in patients with advanced or recurrent non-small cell lung cancer.

RESULTS: More than 2,500 patients were …

Intersection Of Race And Rurality With Health Care-Associated Infections And Subsequent Outcomes, Katelin B Nickel, Hannah Kinzer, Anne M Butler, Karen E Joynt Maddox, Victoria J Fraser, Jason P Burnham, Jennie H Kwon

2020-Current year OA Pubs

IMPORTANCE: Health care-associated infections (HAIs) are a major cause of morbidity and mortality, but little is known about whether structural factors impacting race and rurality are associated with HAI and subsequent outcomes.

OBJECTIVE: To evaluate the association of race and rurality, which are proxies for structural disadvantage, with HAI and subsequent outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted at 3 US urban and suburban hospitals. Participants were adults aged 18 years or older admitted for 48 hours or longer from January 1, 2017, to August 31, 2020. Statistical analysis was performed from November 2022 to April 2024. …

Efficacy And Safety Of Zilucoplan In Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial, Sabrina Paganoni, Timothy M Miller, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The etiology of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, is unknown. However, neuroinflammation and complement activation may play a role in disease progression.

OBJECTIVE: To determine the effects of zilucoplan, an inhibitor of complement C5, in individuals with ALS.

DESIGN, SETTING, AND PARTICIPANTS: Zilucoplan was tested as regimen A of the HEALEY ALS Platform Trial, a phase 2 to 3 multicenter, randomized, double-blind, placebo-controlled perpetual platform clinical trial with sharing of trial infrastructure and placebo data across multiple regimens. Regimen A was conducted from August 17, 2020, to May 4, 2022. A total of 162 participants were …

Dairy Consumption And The Colonic Mucosa-Associated Gut Microbiota In Humans-A Preliminary Investigation, Ellie Chen, Nadim J Ajami, Donna L White, Yanhong Liu, Shawn Gurwara, Kristi Hoffman, David Y Graham, Hashem B El-Serag, Joseph F Petrosino, Li Jiao

Faculty, Staff and Students Publications

Background: Dairy consumption has been associated with various health outcomes that may be mediated by changes in gut microbiota.

Methods: This cross-sectional study investigated the association between the colonic mucosa-associated gut microbiota and the self-reported intake of total dairy, milk, cheese, and yogurt. A total of 97 colonic mucosal biopsies collected from 34 polyp-free individuals were analyzed. Dairy consumption in the past year was assessed using a food frequency questionnaire. The 16S rRNA gene V4 region was amplified and sequenced. Operational taxonomic unit (OTU) classification was performed using the UPARSE and SILVA databases. OTU diversity and relative abundance were compared …

Subendocardial Ischemia: Does Cmd Really Exist?, Nils P Johnson, K Lance Gould

Faculty, Staff and Student Publications

Patients with angina but without obstructive epicardial coronary disease still require a specific mechanistic diagnosis to enable targeted treatment. The overarching term "coronary microvascular dysfunction" (CMD) has been applied broadly - but is it correct? We present a series of case examples culminating a systematic exploration of our large clinical database to distinguish among four categories of coronary pathophysiology. First, by far the largest group of "no stenosis angina" patients exhibits subendocardial ischemia during intact flow through diffuse epicardial disease during dipyridamole vasodilator stress. Second, rare patients indeed have ischemic signs or symptoms due solely to reduced flow attributable to …

Randomized, Placebo-Controlled Pilot Study Of Naproxen During Dental Implant Osseointegration, Hattanas Kumchai, Daniel Taub, Ryan Tomlinson

Department of Oral and Maxillofacial Surgery Faculty Papers

OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) are often prescribed following the placement of dental implants, but the effects of these drugs on the osseointegration process are poorly understood. We designed a randomized, placebo-controlled pilot study to quantitatively assess the effect of NSAIDs during early implant osseointegration.

MATERIALS AND METHODS: Subjects receiving a maxillary dental implant were randomized to take naproxen or placebo for 7 days after the surgery. Implant osseointegration was quantified using Resonance Frequency Analysis device. Implant-Stability-Quotient (ISQ) measurement was performed at the time of surgery and at follow-up visits 1, 4, and 16 weeks after surgery. Periapical radiographs were …

Multi-Institutional Retrospective Study On Opioid Prescribing Patterns Of Oral And Maxillofacial Surgeons, Steven J D Zbarsky, Issa A Hanna, Je Dong Ryu, Audra Boehm, Simon Young, Gary Yu, Minh Phuong Dong, Minh Chau Joe Tran, Alan Herford, Samuel Young, Chi T Viet

Faculty, Staff and Student Publications

BACKGROUND: The opioid epidemic is a serious crisis in the United States. It has been proposed that opioid prescriptions after dental procedures are a major contributor to opioid use and abuse. The American Dental Association has been working to educate dental care providers about safe opioid prescribing practices. The authors hypothesized that oral and maxillofacial surgeons, following the efforts and publications from the American Dental Association, have been prescribing fewer postoperative opioids.

METHODS: This was a multi-institutional retrospective study with a total of 3,710 patients from Loma Linda University and University of Texas Health Science Center at Houston undergoing ambulatory …

Mid-Life Anti-Inflammatory Metabolites Are Inversely Associated With Long-Term Cardiovascular Disease Events, Anum Saeed, Chris Mckennan, Jiaxuan Duan, Yueh-Ning Yang, Kevin E Kip, David Finegold, Michael Vu, Justin Swanson, Oscar L Lopez, Ann Cohen, Mark Mapstone, Bing Yu, Christie M Ballantyne, Steven E Reis

Faculty, Staff and Student Publications

BACKGROUND: Preclinical data have shown that low levels of metabolites with anti-inflammatory properties may impact metabolic disease processes. However, the association between mid-life levels of such metabolites and long-term ASCVD risk is not known.

METHODS: We characterised the plasma metabolomic profile (1228 metabolites) of 1852 participants (58.1 ± 7.5 years old, 69.6% female, 43.6% self-identified as Black) enrolled in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study. Logistic regression was used to assess the impact of metabolite levels on ASCVD risk (nonfatal MI, revascularisation, and cardiac mortality). We additionally explored the effect of genetic variants neighbouring ASCVD-related genes …

Resilience And Coping: A Qualitative Analysis Of Cognitive And Behavioral Factors In Adults With Osteogenesis Imperfecta, Hannah E Cho, Whitney S Shepherd, Gianna M Colombo, Andrew D Wiese, W Conor Rork, Kristin M Kostick, Dianne Nguyen, Members Of The Bbdc, Chaya N Murali, Marie-Eve Robinson, Sophie C Schneider, Justin H Qian, Brendan Lee, V Reid Sutton, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Purpose: The aim of this qualitative study was to investigate resilience among adults with Osteogenesis Imperfecta (OI).

Materials and methods: Semi-structured interviews were conducted with 15 adults with OI. Transcripts were coded and subsequently abstracted, yielding themes specific to resilience and coping. Interview guides covered broad topics including pain challenges specific to OI, mental health issues related to OI, and priorities for future interventions for individuals with OI.

Results: Participants described resilience in the context of OI as the ability to grow from adversity, adapt to challenges resulting from OI-related injuries, and find identities apart from their condition. Psychological coping …

Rescue Stenting For Failed Mechanical Thrombectomy In Acute Basilar Artery Occlusions: Analysis Of The Pc-Search Registry., Santiago Ortega-Gutierrez, Aaron Rodriguez-Calienes, Adam T Mierzwa, Milagros Galecio-Castillo, Mahmoud Dibas, Sami Al Kasab, Ashley Nelson, Ashutosh P Jadhav, Shashvat Desai, Gabor Toth, Anas Alrohimi, Mohamad Abdalkader, Piers Klein, Thanh N Nguyen, Hisham Salahuddin, Aditya Pandey, Sravanthi Koduri, Niraj Vora, Nameer Aladamat, Khaled Gharaibeh, Ehad Afreen, Syed Zaidi, Mouhammad Jumaa

Neuroscience Articles

BACKGROUND: We aimed to investigate whether rescue stenting (RS) following failed mechanical thrombectomy (MT) for acute basilar artery occlusion results in superior functional outcomes and enhanced safety compared with the natural history of failed MT.

METHODS: This retrospective cohort study utilized data from the Posterior Circulation Ischemic Stroke Evaluation: Analyzing Radiographic and Intra-Procedural Predictors for Mechanical Thrombectomy registry, encompassing 8 high-volume centers in the United States and covering the period from 2015 to 2021. Patients with basilar artery occlusion who experienced failed MT (modified Thrombolysis in Cerebral Infarction score of 0-2a after at least 1 attempt of clot retrieval) were …

Phase Ii Study Of Copanlisib In Patients With Pten Loss: Results From Nci-Match Ecog-Acrin Trial (Eay131) Subprotocols Z1g And Z1h, Mohamed A Gouda, Zihan Wei, Jordi Rodon, Michael A Davies, Filip Janku, Robert J Gray, Victoria Wang, Lisa M Mcshane, Larry V Rubinstein, David R Patton, P Mickey Williams, Stanley R Hamilton, Raymond Liu, Daniela A Bota, Paul L Swiecicki, Gary L Buchschacher, James V Tricoli, Barbara A Conley, Carlos L Arteaga, Lyndsay N Harris, Peter J O'Dwyer, Alice P Chen, Keith T Flaherty

Faculty, Staff and Student Publications

Purpose: Copanlisib, a pan-class phosphatidylinositol 3-kinase (PI3K) inhibitor with activity predominantly against the PI3K-delta and PI3K-alpha isoforms, has shown promising results in preclinical cancer models with PTEN loss. Herein, we report the activity and safety data from the Z1G and Z1H subprotocols, which included patients with PTEN loss, of the National Cancer Institute Molecular Analysis for Therapy Choice trial.

Methods: Patients with complete loss of cytoplasmic and nuclear PTEN as determined by immunohistochemistry regardless of PTEN mutation or deletion status were included in subprotocol Z1G, and patients with a deleterious mutation in the PTEN gene and retained expression of PTEN …

A Qualitative Assessment Of Changes In Occupational Exposures Among Healthcare Facility Workers, David Gimeno Ruiz De Porras, Jenil Patel, Sadie Conway, Lisa Pompeii, Laura E Mitchell, Arch Carson, Lawrence W Whitehead, Inkyu Han, Jan-Paul Zock, Paul K Henneberger, Riddhi Patel, Joy De Los Reyes, George L Delclos

Faculty, Staff and Student Publications

Adult-onset asthma, notably prevalent among healthcare professionals, especially nurses, is often attributed to occupational factors such as exposure to cleaning agents. Studies consistently underscore the substantial role of such exposure in work-related asthma among hospital staff. We aimed to (a) identify and characterize current practices in cleaning and aerosolized medication administration; (b) assess changes in practices since a similar 2003 study of Texas healthcare workers; and (c) identify factors contributing to diverse exposures within healthcare job categories. We conducted focus groups with 38 participants in 6 healthcare settings, analyzing current practices, changes since 2003, and factors contributing to exposure diversity. …

Evidence For Alpha-Synuclein Aggregation In Older Individuals With Hyposmia: A Cross-Sectional Study, Kenneth Marek, David S Russell, Luis Concha-Marambio, Seung Ho Choi, Danna Jennings, Michael C Brumm, Christopher S Coffey, Ethan Brown, John Seibyl, Matthew Stern, Claudio Soto, Andrew Siderowf

Faculty, Staff and Student Publications

Background: Synuclein pathology in neurodegenerative diseases, such as Parkinson's disease (PD) and Dementia with Lewy bodies (DLB), begins years before motor or cognitive symptoms arise. Alpha-Synuclein seed amplification assays (α-syn SAA) may detect aggregated synuclein before symptoms occur.

Methods: Data from the Parkinson Associated Risk Syndrome Study (PARS) have shown that individuals with hyposmia, without motor or cognitive symptoms, are enriched for dopamine transporter imaging (DAT) deficit and are at high risk to develop clinical parkinsonism or related synucleinopathies. α-syn aggregates in CSF were measured in 100 PARS participants using α-syn SAA.

Findings: CSF α-syn SAA was positive in 48% …

Plasma Proteomic Characterization Of Motoric Cognitive Risk And Mild Cognitive Impairment, Gabriela T Gomez, Sanish Sathyan, Jingsha Chen, Myriam Fornage, Pascal Schlosser, Zhongsheng Peng, Jenifer Cordon, Priya Palta, Kevin J Sullivan, Adrienne Tin, B Gwen Windham, Rebecca F Gottesman, Nir Barzilai, Sofiya Milman, Joe Verghese, Josef Coresh, Keenan A Walker

Faculty, Staff and Student Publications

INTRODUCTION: Motoric cognitive risk (MCR) is a pre-dementia syndrome characterized by mobility and cognitive dysfunction. This study conducted a proteome-wide study of MCR and compared the proteomic signatures of MCR to that of mild cognitive impairment (MCI).

METHODS: Participants were classified as MCR using a memory questionnaire and 4-meter walk. We measured 4877 plasma proteins collected during late-life and midlife. Multivariable logistic regression related each protein to late-life MCR/MCI. MCR-associated proteins were replicated internally at midlife and in an external cohort.

RESULTS: Proteome-wide analysis (n = 4076) identified 25 MCR-associated proteins. Eight of these proteins remained associated with late-life MCR …

Patient-Reported Outcomes: Comparing Functional Avoidance And Standard Thoracic Radiation Therapy In Lung Cancer, Spencer Poiset, Joseph Lombardo, Edward Castillo, Richard Castillo, Bernard Jones, Moyed Miften, Brian Kavanagh, Adam Dicker, Cullen Boyle, Nicole Simone, Benjamin Movsas, Inga Grills, Chad Rusthoven, Yevgeniy Vinogradskiy, Lydia Wilson

Department of Radiation Oncology Faculty Papers

PURPOSE: Novel methods generate functional images using image processing techniques combined with four-dimensional computed tomography (4DCT) data (4DCT-ventilation). 4DCT-ventilation was implemented in a phase II, multicenter functional avoidance clinical trial. The work compares functional avoidance patient-reported outcomes (PROs) against historical standards.

METHODS: Patients with locally advanced lung cancer undergoing curative-intent chemoradiation were accrued. 4DCT-ventilation imaging was generated and functional avoidance treatment plans created reduced dose to functional lung. PRO instruments included Functional Assessment of Cancer Therapy Lung questionnaire and accompanying subscales (including the Trial Outcome Index [TOI]), EuroQol-5 Dimension (EQ-5D), and EQ-Visual Analog Scale (EQ-VAS). The average change from baseline …

Association Of Systemic Inflammation And Long-Term Dysfunction In Covid-19 Patients: A Prospective Cohort, Felipe Dal-Pizzol, Bruno Kluwe-Schiavon, Henrique Ritter Dal-Pizzol, Gabriele Da Silveira Prestes, Diogo Dominguini, Carolina Saibro Girardi, Lucas Santos, José Cláudio Fonseca Moreira, Daniel Pens Gelain, Roger Walz, Tatiana Barichello, Cristiane Ritter

Faculty, Staff and Student Publications

COVID-19 has significant long-term impacts, including a chronic syndrome known as long-COVID, characterized by persistent symptoms post-recovery. The inflammatory response during acute infection is hypothesized to influence long-term outcomes. This study aimed to identify inflammatory biomarkers predictive of functional outcomes one year after hospital discharge. A prospective cohort study was conducted with 213 COVID-19 patients admitted to ICUs in Southern Brazil between June and November 2020. After exclusions and follow-ups, 109 patients were evaluated for one-year post-discharge. Plasma levels of Th1 (TNF-α, INF-γ, IL-12), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), and Th17 (IL-17, IL-22) cytokines were measured. Functional outcomes in …

Pharmacologic Management Of Heart Failure With Preserved Ejection Fraction (Hfpef) In Older Adults, Ashkan Hashemi, Min Ji Kwak, Parag Goyal

Faculty, Staff and Student Publications

There are several pharmacologic agents that have been touted as guideline-directed medical therapy for heart failure with preserved ejection fraction (HFpEF). However, it is important to recognize that older adults with HFpEF also contend with an increased risk for adverse effects from medications due to age-related changes in pharmacokinetics and pharmacodynamics of medications, as well as the concurrence of geriatric conditions such as polypharmacy and frailty. With this review, we discuss the underlying evidence for the benefits of various treatments in HFpEF and incorporate key considerations for older adults, a subpopulation that may be at higher risk for adverse drug …