Digital Commons Network^™

Leveraging Informative Missing Data To Learn About Acute Respiratory Distress Syndrome And Mortality In Long-Term Hospitalized Covid-19 Patients Throughout The Years Of The Pandemic, Emily Getzen, Amelia Lm Tan, Gabriel Brat, Gilbert S Omenn, Zachary Strasser, Qi Long, John H Holmes, Danielle Mowery

Faculty, Staff and Student Publications

Electronic health records (EHRs) contain a wealth of information that can be used to further precision health. One particular data element in EHRs that is not only under-utilized but oftentimes unaccounted for is missing data. However, missingness can provide valuable information about comorbidities and best practices for monitoring patients, which could save lives and reduce burden on the healthcare system. We characterize patterns of missing data in laboratory measurements collected at the University of Pennsylvania Hospital System from long-term COVID-19 patients and focus on the changes in these patterns between 2020 and 2021. We investigate how these patterns are associated …

Social Determinant Of Health Impact On Diabetes Device Use And Clinical Outcomes In Youth With Type 1 Diabetes, Emily R Crain, Ryan Ramphul, Ashley M Butler, Xiaofan Huang, Charles G Minard, Maria J Redondo, Daniel J Desalvo

Faculty, Staff and Student Publications

Background: Youth with Type 1 diabetes (T1D) who are Black, Hispanic, or lower socioeconomic status (SES) have lower rates of diabetes device use, higher hemoglobin A1c (HbA1c), and higher rates of diabetic ketoacidosis (DKA). However, the associations of individual-level social determinants of health (SDoH) and neighborhood-level factors with device use and clinical outcomes are unknown. Area deprivation index (ADI) is a neighborhood level measure of SES reported in deciles (range 1-10 with 10 representing most deprived neighborhood).

Methods: We evaluated the association of ADI and other SDoH factors with pump/continuous glucose monitor (CGM) use, HbA1c, and DKA in 1,461 youth …

Influences Of Race/Ethnicity In Periodontal Treatment Response And Bacterial Distribution, A Cohort Pilot Study, Bing-Yan Wang, Grayson Burgardt, Kavitha Parthasarathy, Daniel K Ho, Robin L Weltman, Gena D Tribble, Jianming Hong, Stanley Cron, Hua Xie

Faculty, Staff and Student Publications

OBJECTIVES: Periodontitis disproportionately affects different racial and ethnic populations. We have previously reported the higher levels of

METHODS: This prospective cohort pilot study was carried out in an academic setting, at the School of Dentistry, University of Texas Health Science Center at Houston. Dental plaque was collected from a total of 75 African Americans, Caucasians and Hispanics periodontitis patients in a 3-year period. Quantitation of

RESULTS: The gains in clinical attachment levels after treatment significantly differed amongst the 3 groups-Caucasians responded most favorably, followed by African-Americans, lastly Hispanics, while numbers of

CONCLUSION: Differential response to nonsurgical periodontal treatment and distribution …

Identification Of Microbiological Factors Associated With Periodontal Health Disparities, Bing-Yan Wang, Aize Cao, Meng-Hsuan Ho, Derek Wilus, Sally Sheng, Hsiu-Wan Meng, Elissa Guerra, Jianming Hong, Hua Xie

Faculty, Staff and Student Publications

The present study aimed at identifying risk factors associated with periodontitis development and periodontal health disparities with emphasis on differential oral microbiota. The prevalence of periodontitis is recently rising dentate adults in the US, which presents a challenge to oral health and overall health. The risk of developing periodontitis is higher in African Americans (AAs), and Hispanic Americans (HAs) than in Caucasian Americans (CAs). To identify potentially microbiological determinations of periodontal health disparities, we examined the distribution of several potentially beneficial and pathogenic bacteria in the oral cavities of AA, CA, and HA study participants. Dental plaque samples from 340 …

Fostering A High-Functioning Team In Cancer Care Using The 4r Oncology Model: Assessment In A Large Health System And A Blueprint For Other Institutions, Raymond Liu, Christine B Weldon, Elizabeth Linehan, Nancy Gordon, Thea Abbe, Marti Hennings, Henie James, Jed Katzel, Chun Ng, Megumi Tomita, Jeffrey B Velotta, Stephanie Ossowski, Lori C Sakoda, Sharon Likely Sprague, Anna Dowling, Kimberly Beringer, Arliene Ravelo, Elaine Yu, Julia R Trosman

Faculty, Staff and Student Publications

PURPOSE: Delivering cancer care by high-functioning multidisciplinary teams promises to address care fragmentation, which threatens care quality, affects patient outcomes, and strains the oncology workforce. We assessed whether the 4R Oncology model for team-based interdependent care delivery and patient self-management affected team functioning in a large community-based health system.

METHODS: 4R was deployed at four locations in breast and lung cancers and assessed along four characteristics of high-functioning teams: recognition as a team internally and externally; commitment to an explicit shared goal; enablement of interdependent work to achieve the goal; and engagement in regular reflection to adapt objectives and processes. …

Interventional Gastroenterology In Oncology, Vaibhav Wadhwa, Nicole Patel, Dheera Grover, Faisal S Ali, Nirav Thosani

Faculty, Staff and Student Publications

Cancer is one of the foremost health problems worldwide and is among the leading causes of death in the United States. Gastrointestinal tract cancers account for almost one third of the cancer-related mortality globally, making it one of the deadliest groups of cancers. Early diagnosis and prompt management are key to preventing cancer-related morbidity and mortality. With advancements in technology and endoscopic techniques, endoscopy has become the core in diagnosis and management of gastrointestinal tract cancers. In this extensive review, the authors discuss the role endoscopy plays in early detection, diagnosis, and management of esophageal, gastric, colorectal, pancreatic, ampullary, biliary …

Proton Therapy With Concurrent Chemotherapy For Thoracic Esophageal Cancer: Toxicity, Disease Control, And Survival Outcomes, Michael S Rutenberg, Bradford S Hoppe, Jason S Starr, Ziad Awad, Mathew Thomas, Christopher G Morris, Perry Johnson, Randal H Henderson, Jeremy C Jones, Bharatsinh Gharia, Steven Bowers, Herbert C Wolfsen, Sunil Krishnan, Stephen J Ko, Hani M Babiker, Romaine C Nichols

Faculty, Staff and Student Publications

PURPOSE: When treating esophageal cancer with radiation therapy, it is critical to limit the dose to surrounding structures, such as the lung and/or heart, as much as possible. Proton radiation therapy allows a reduced radiation dose to both the heart and lungs, potentially reducing the risk of cardiopulmonary toxicity. Here, we report disease control, survival, and toxicity outcomes among patients with esophageal cancer treated with proton radiation therapy and concurrent chemotherapy (chemoradiation therapy; CRT) with or without surgery.

MATERIALS AND METHODS: We enrolled 17 patients with thoracic esophageal carcinoma on a prospective registry between 2010 and 2021. Patients received proton …

Risk Prediction Of Pancreatic Cancer In Patients With Recent-Onset Hyperglycemia: A Machine-Learning Approach, Wansu Chen, Rebecca K Butler, Eva Lustigova, Suresh T Chari, Anirban Maitra, Jo A Rinaudo, Bechien U Wu

Faculty, Staff and Student Publications

Background: New-onset diabetes (NOD) has been suggested as an early indicator of pancreatic cancer. However, the definition of NOD by the American Diabetes Association requires 2 simultaneous or consecutive elevated glycemic measures. We aimed to apply a machine-learning approach using electronic health records to predict the risk in patients with recent-onset hyperglycemia.

Materials and methods: In this retrospective cohort study, health plan enrollees 50 to 84 years of age who had an elevated (6.5%+) glycated hemoglobin (HbA1c) tested in January 2010 to September 2018 with recent-onset hyperglycemia were identified. A total of 102 potential predictors were extracted. Ten imputation datasets …

Editorial: Metabolic Regulation Under Oxidative Stress In Cancer, Elavarasan Subramani, Abishai Dominic, Pratip K Bhattacharya, Daniel E Frigo, Ilya Bederman, Ali Vaziri-Gohar

Faculty, Staff and Student Publications

Oxidative stress has emerged as a key component of cancer metabolism that impacts multiple facets of tumor biology (1). Recent studies have shed light on the complex interplay of cellular redox and its impact on molecular mechanisms that govern metabolic reprogramming under oxidative stress (2, 3). It is well established that altered glucose metabolism exhibited by tumor cells leads to an enormous oxidative burden through various metabolic routes (4, 5). What is less known but remains a great interest to the field is whether elevated oxidative stress has a causal role in …

Pain Experience And Sensory Changes In Astronauts During And After Short-Lasting Commercial Spaceflight: A Proof-Of-Concept Study, Andrea K Sauer, Marie Vigouroux, Patrick M Dougherty, Juan Pablo Cata, Pablo M Ingelmo

Faculty, Staff and Student Publications

Space travel has been associated with musculoskeletal pain, yet little is known about the nociceptive changes and pain experience during spaceflight. This preliminary study aims to investigate the pain experience and sensory alterations in astronauts following a 17-day mission to the International Space Station (ISS) on Axiom Space's AX-1 commercial space flight. Two participants were enrolled, and data were collected pre-flight, in-flight, post-flight, and three-month post-flight. Validated pain questionnaires assessed anxiety, catastrophizing, impact on physical and mental health, disability, and overall pain experience. Qualitative interviews were conducted post-landing and conditioned pain modulation (CPM) and quantitative sensory testing (QST) were performed. …

Circulating Vitamin D And Breast Cancer Risk: An International Pooling Project Of 17 Cohorts, Kala Visvanathan, Alison M Mondul, Anne Zeleniuch-Jacquotte, Molin Wang, Mitchell H Gail, Shiaw-Shyuan Yaun, Stephanie J Weinstein, Marjorie L Mccullough, A Heather Eliassen, Nancy R Cook, Claudia Agnoli, Martin Almquist, Amanda Black, Julie E Buring, Chu Chen, Yu Chen, Tess Clendenen, Laure Dossus, Veronika Fedirko, Gretchen L Gierach, Edward L Giovannucci, Gary E Goodman, Marc T Goodman, Pascal Guénel, Göran Hallmans, Susan E Hankinson, Ronald L Horst, Tao Hou, Wen-Yi Huang, Michael E Jones, Corrine E Joshu, Rudolf Kaaks, Vittorio Krogh, Tilman Kühn, Marina Kvaskoff, I-Min Lee, Yahya Mahamat-Saleh, Johan Malm, Jonas Manjer, Gertraud Maskarinec, Amy E Millen, Toqir K Mukhtar, Marian L Neuhouser, Trude E Robsahm, Minouk J Schoemaker, Sabina Sieri, Malin Sund, Anthony J Swerdlow, Cynthia A Thomson, Giske Ursin, Jean Wactawski-Wende, Ying Wang, Lynne R Wilkens, Yujie Wu, Emilie Zoltick, Walter C Willett, Stephanie A Smith-Warner, Regina G Ziegler

Faculty, Staff and Student Publications

Laboratory and animal research support a protective role for vitamin D in breast carcinogenesis, but epidemiologic studies have been inconclusive. To examine comprehensively the relationship of circulating 25-hydroxyvitamin D [25(OH)D] to subsequent breast cancer incidence, we harmonized and pooled participant-level data from 10 U.S. and 7 European prospective cohorts. Included were 10,484 invasive breast cancer cases and 12,953 matched controls. Median age (interdecile range) was 57 (42-68) years at blood collection and 63 (49-75) years at breast cancer diagnosis. Prediagnostic circulating 25(OH)D was either newly measured using a widely accepted immunoassay and laboratory or, if previously measured by the cohort, …

Hiatal Hernia Repair With Transoral Incisionless Fundoplication Versus Nissen Fundoplication For Gastroesophageal Reflux Disease: A Retrospective Study, Veeravich K Jaruvongvanich, Reem Matar, Janani Reisenauer, Peter Janu, Peter Mavrelis, Glenn Ihde, Michael Murray, Sneha Singh, Jennifer Kolb, Ninh T Nguyen, Nirav Thosani, Erik B Wilson, Rasa Zarnegar, Kenneth Chang, Marcia I Canto, Barham K Abu Dayyeh

Faculty, Staff and Student Publications

Background and study aims  Concomitant hiatal hernia (HH) repair with transoral incisionless fundoplication (TIF) is a therapeutic option for patients with HH > 2 cm and gastroesophageal reflux disease (GERD). Data comparing this approach with laparoscopic Nissen fundoplication (LNF) are lacking. We performed an exploratory analysis to compare these two approaches' adverse events (AEs) and clinical outcomes.

Patients and methods  This was a multicenter retrospective cohort study of HH repair followed by LNF versus HH repair followed by TIF in patients with GERD and moderate HH (2–5 cm). AEs were assessed using the Clavien-Dindo classification. Symptoms (heartburn/regurgitation, bloating, and dysphagia) were …

Molecular Mechanisms Of Osteosarcoma Metastasis And Possible Treatment Opportunities, Xinhui Du, Hua Wei, Boya Zhang, Bangmin Wang, Zhehuang Li, Lon Kai Pang, Ruiying Zhao, Weitao Yao

Faculty, Staff and Student Publications

In osteosarcoma patients, metastasis of the primary cancer is the leading cause of death. At present, management options to prevent metastasis are limited and non-curative. In this study, we review the current state of knowledge on the molecular mechanisms of metastasis and discuss promising new therapies to combat osteosarcoma metastasis. Genomic and epigenomic changes, metabolic reprogramming, transcription factors, dysregulation of physiologic pathways, and alterations to the tumor microenvironment are some of the changes reportedly involved in the regulation of osteosarcoma metastasis. Key factors within the tumor microenvironment include infiltrating lymphocytes, macrophages, cancer-associated fibroblasts, platelets, and extracellular components such as vesicles, …

Peripheral Vascular Access As Exclusive Access Mode In Pediatric Intensive Care Unit, Sonya Hayes Armstrong, Shantaveer Gangu, Alina Nico West, Thomas Spentzas

Faculty, Staff and Student Publications

INTRODUCTION: The type of vascular access (central or peripheral) in pediatric critical care depends on several factors, including the duration of treatment, the properties of the medication (osmolarity or vesicant), and the need for central pressure monitoring. The utilization of peripheral intravascular catheters (PIVCs) has shown a notable increase in the number of patients being treated. Extended dwell or midline catheters are another peripheral access option in addition to PIVCs. However, there are currently no established guidelines on their placement.

OBJECTIVES: The aim of this study is to estimate the duration of dwell time for PIVCs, analyze the specific parameters …

The Gpcr–Gαs–Pka Signaling Axis Promotes T Cell Dysfunction And Cancer Immunotherapy Failure, Heather R Kregel, Lillian S Kao, Thaddeus J Puzio

Faculty, Staff and Student Publications

No abstract provided.

Complex I Inhibitor Of Oxidative Phosphorylation In Advanced Solid Tumors And Acute Myeloid Leukemia: Phase I Trials, Timothy A Yap, Naval Daver, Mikhila Mahendra, Jixiang Zhang, Carlos Kamiya-Matsuoka, Funda Meric-Bernstam, Hagop M Kantarjian, Farhad Ravandi, Meghan E Collins, Maria Emilia Di Francesco, Ecaterina E Dumbrava, Siqing Fu, Sisi Gao, Jason P Gay, Sonal Gera, Jing Han, David S Hong, Elias J Jabbour, Zhenlin Ju, Daniel D Karp, Alessia Lodi, Jennifer R Molina, Natalia Baran, Aung Naing, Maro Ohanian, Shubham Pant, Naveen Pemmaraju, Prithviraj Bose, Sarina A Piha-Paul, Jordi Rodon, Carolina Salguero, Koji Sasaki, Anand K Singh, Vivek Subbiah, Apostolia M Tsimberidou, Quanyun A Xu, Musa Yilmaz, Qi Zhang, Yuan Li, Christopher A Bristow, Meenakshi B Bhattacharjee, Stefano Tiziani, Timothy P Heffernan, Christopher P Vellano, Philip Jones, Cobi J Heijnen, Annemieke Kavelaars, Joseph R Marszalek, Marina Konopleva

Faculty, Staff and Student Publications

Although targeting oxidative phosphorylation (OXPHOS) is a rational anticancer strategy, clinical benefit with OXPHOS inhibitors has yet to be achieved. Here we advanced IACS-010759, a highly potent and selective small-molecule complex I inhibitor, into two dose-escalation phase I trials in patients with relapsed/refractory acute myeloid leukemia (NCT02882321, n = 17) and advanced solid tumors (NCT03291938, n = 23). The primary endpoints were safety, tolerability, maximum tolerated dose and recommended phase 2 dose (RP2D) of IACS-010759. The PK, PD, and preliminary antitumor activities of IACS-010759 in patients were also evaluated as secondary endpoints in both clinical trials. IACS-010759 had a narrow …

Non-Pharmacologic Approaches To Treatment Of Pediatric Functional Abdominal Pain Disorders, Partha Sarathi Chakraborty, Rhea Daniel, Fernando A Navarro

Faculty, Staff and Student Publications

Functional abdominal pain disorders (FAPDs) affect up to 25% of children in the United States. These disorders are more recently known as disorders of "brain-gut" interaction. The diagnosis is based on the ROME IV criteria, and requires the absence of an organic condition to explain the symptoms. Although these disorders are not completely understood, several factors have been involved in the pathophysiology including disordered gut motility, visceral hypersensitivity, allergies, anxiety/stress, gastrointestinal infection/inflammation, as well dysbiosis of the gut microbiome. The pharmacologic and non-pharmacologic treatments for FAPDs are directed to modifying these pathophysiologic mechanisms. This review aims to summarize the non-pharmacologic …

Comparison Of Two Lipid Emulsions On The Incidence Of Parenteral Nutrition Associated Cholestasis In Neonates, Joy Greenberg, Mamta Naik, John Chapman, Allison Davidson, Essam Imseis

Faculty, Staff and Student Publications

OBJECTIVE: Lipid emulsion contributes to parenteral nutrition associated cholestasis (PNAC). For decades, soybean oil-based intravenous lipid emulsion (SO-ILE) was the predominant product. Recently, a multicomponent lipid emulsion containing soybean oil, medium-chain triglycerides, olive oil and fish oil (SMOF-ILE) has been used off-label in neonatal care. This study evaluates the incidence of PNAC in neonates who received SMOF-ILE or SO-ILE.

METHODS: This was a retrospective review of neonates who received SMOF-ILE or SO-ILE for at least 14 days. Patients receiving SMOF-ILE were matched based on gestational age (GA) and birth weight to a historical cohort receiving SO-ILE. The primary outcomes were …

Pain Experience And Sensory Changes In Astronauts During And After Short-Lasting Commercial Spaceflight: A Proof-Of-Concept Study, Andrea K Sauer, Marie Vigouroux, Patrick M Dougherty, Juan Pablo Cata, Pablo M Ingelmo

Faculty, Staff and Student Publications

Space travel has been associated with musculoskeletal pain, yet little is known about the nociceptive changes and pain experience during spaceflight. This preliminary study aims to investigate the pain experience and sensory alterations in astronauts following a 17-day mission to the International Space Station (ISS) on Axiom Space's AX-1 commercial space flight. Two participants were enrolled, and data were collected pre-flight, in-flight, post-flight, and three-month post-flight. Validated pain questionnaires assessed anxiety, catastrophizing, impact on physical and mental health, disability, and overall pain experience. Qualitative interviews were conducted post-landing and conditioned pain modulation (CPM) and quantitative sensory testing (QST) were performed. …

The Mediating Effect Of Resilience On The Relationship Between Symptom Burden And Anxiety/Depression Among Chinese Patients With Primary Liver Cancer After Liver Resection, Xue Zhang, Haoran Zhang, Zonghao Zhang, Hua Fan, Shuwen Li

Faculty, Staff and Student Publications

Purpose: Primary liver cancer (PLC) is a common cancer of the digestive system. Patients with PLC often experience a heavy symptom burden and along with a significant levels of anxiety and depression after liver resection. High levels of symptom burden can lead to increased anxiety and depression, whereas high levels of resilience can alleviate these conditions. Therefore, we aimed to explore the relationships among symptom burden, resilience, and anxiety/depression in Chinese patients with PLC after liver resection and to determine whether resilience mediates the relationship between symptom burden and anxiety/depression.

Patients and methods: A total of 223 postoperative PLC patients …

Open Treatments For Thoracoabdominal Aortic Aneurysm Repair, Akiko Tanaka, Holly N Smith, Hazim J Safi, Anthony L Estrera

Faculty, Staff and Student Publications

Thoracoabdominal aortic aneurysms (TAAA) represent a unique pathology that is associated with considerable mortality if untreated. While the advent of endovascular technologies has introduced new modalities for consideration, the mainstay of TAAA treatment remains open surgical repair. However, the optimal conduct of open TAAA repair requires careful consideration of patient risk factors and a collaborative team effort to mitigate the risk of perioperative complications. In this chapter, we briefly outline the history of treating TAAA, preoperative preparation and postoperative care, and our operative techniques for treatment.

The Phase 1/2 Trial Of Indomethacin In Chronic Pancreatitis (The Pair Trial): Protocol For A Parallel Multi-Center Randomized Controlled Trial, Samuel Han, Darwin L Conwell, Liang Li, Alejandra Cervantes, Phil A Hart, Zobeida Cruz-Monserrate, Wenrui Hao, Gregory B Lesinski, Thomas Mace, Tonya M Palermo, Jami L Saloman, Dhiraj Yadav, Santhi Swaroop Vege, Mark Topazian, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Background/objectives: Current treatments for chronic pancreatitis focus on symptom management and therapeutics targeting disease reversal are lacking. Given the role of the cyclooxygenase-2 (COX-2) enzyme in producing prostaglandin E2 (PGE2), a key component in the inflammatory pathway of chronic pancreatitis, this study evaluates the physiologic effect of oral indomethacin, a COX-2 inhibitor, on PGE2 levels in pancreatic fluid.

Methods: This pilot two-center randomized controlled trial seeks to examine 32 subjects with chronic pancreatitis who have no contraindications to indomethacin. Subjects will be randomized to either oral indomethacin 50 mg twice a day or placebo twice a day for a total …

A Novel Case Of Eus-Guided Targeted Radiofrequency Ablation Of Metastatic Duodenal Renal Cell Carcinoma, Muhammad Vohra, Hemant Goyal, Putao Cen, Mairin Joseph-Talreja, Nirav Thosani

Faculty, Staff and Student Publications

No abstract provided.

Editorial: Non-Coding Genome And Endocrinology: From Bench To Bedside, Radu Pirlog, Kinga Nemeth, George Adrian Calin

Faculty, Staff and Student Publications

No abstract provided.

Nano-Embedded Medical Devices And Delivery Systems In Interventional Radiology, Erin Marie D San Valentin, Allan John R Barcena, Carleigh Klusman, Benjamin Martin, Marites P Melancon

Faculty, Staff and Student Publications

Nanomaterials research has significantly accelerated the development of the field of vascular and interventional radiology. The incorporation of nanoparticles with unique and functional properties in medical devices and delivery systems has paved the way for the creation of novel diagnostic and therapeutic procedures for various clinical disorders. In this review, we discuss the advancements in the field of interventional radiology and the role of nanotechnology in maximizing the benefits and mitigating the disadvantages of interventional radiology theranostic procedures. Several nanomaterials have been studied to improve the efficacy of interventional radiology interventions, reduce the complications associated with medical devices, improve the …

Protective Role Of Colitis In Inflammatory Arthritis Via Propionate-Producing Bacteroides In The Gut, Hoh-Jeong Shon, Yu-Mi Kim, Kyeong Seog Kim, Jin-Ouk Choi, Sang-Hyun Cho, Sujin An, Se-Hyeon Park, Yong-Joon Cho, Joo-Hong Park, Sang-Uk Seo, Joo-Youn Cho, Wan-Uk Kim, Donghyun Kim

Faculty, Staff and Student Publications

OBJECTIVES: To investigate whether and how inflammatory disease in the intestine influences the development of arthritis, considering that organ-to-organ communication is associated with many physiological and pathological events.

METHODS: First, mice were given drinking water containing dextran sodium sulfate (DSS) and then subjected to inflammatory arthritis. We compared the phenotypic symptoms between the cohoused and separately-housed mice. Next, donor mice were divided into DSS-treated and untreated groups and then cohoused with recipient mice. Arthritis was then induced in the recipients. The fecal microbiome was analyzed by 16S rRNA amplicon sequencing. We obtained type strains of the candidate bacteria and generated …

Evolutionary Aspects Of Infections: Inflammation And Sickness Behaviors, Robert Dantzer

Faculty, Staff and Student Publications

Sickness behavior was conceptualized initially as the behavioral counterpart of the fever response to infectious pathogens. It helps to raise body temperature to its higher setpoint and to maintain it at this new level and it has the additional benefit of enabling a weakened organism to protect itself from other dangers. The discovery of the behavioral effects of proinflammatory cytokines produced by activated immune cells provided a cellular and molecular basis to this phenomenon. The administration of cytokines or cytokine inducers like lipopolysaccharide to healthy rodents allowed to reveal the similarities and differences between inflammation-induced sickness behavior and the fever …

Chronic Restraint Stress Impairs Voluntary Wheel Running But Has No Effect On Food-Motivated Behavior In Mice, Kiersten Scott, Thien Trong Phan, Nabila Boukelmoune, Cobi J Heijnen, Robert Dantzer

Faculty, Staff and Student Publications

Chronic restraint stress is known to cause significant alterations of mitochondrial biology. However, its effects on effort-based behavior and the sensitivity of these effects to treatments that restore mitochondrial function have not been assessed. Based on the hypothesis that the behavioral consequences of this stressor should be more severe for an energy demanding activity than for an energy procuring activity, we compared the effects of chronic restraint stress on the performance of male mice trained to use a running wheel or to nose poke for a food reward in an operant conditioning cage. In accordance with our hypothesis, we observed …

Possible Molecular Mechanisms Underlying The Development Of Atherosclerosis In Cancer Survivors, Priyanka Banerjee, Julia Enterría Rosales, Khanh Chau, Minh T H Nguyen, Sivareddy Kotla, Steven H Lin, Anita Deswal, Robert Dantzer, Elizabeth A Olmsted-Davis, Hung Nguyen, Guangyu Wang, John P Cooke, Jun-Ichi Abe, Nhat-Tu Le

Faculty, Staff and Student Publications

Cancer survivors undergone treatment face an increased risk of developing atherosclerotic cardiovascular disease (CVD), yet the underlying mechanisms remain elusive. Recent studies have revealed that chemotherapy can drive senescent cancer cells to acquire a proliferative phenotype known as senescence-associated stemness (SAS). These SAS cells exhibit enhanced growth and resistance to cancer treatment, thereby contributing to disease progression. Endothelial cell (EC) senescence has been implicated in atherosclerosis and cancer, including among cancer survivors. Treatment modalities for cancer can induce EC senescence, leading to the development of SAS phenotype and subsequent atherosclerosis in cancer survivors. Consequently, targeting senescent ECs displaying the SAS …

Phase 1/2 Study Of Epacadostat In Combination With Durvalumab In Patients With Metastatic Solid Tumors, Aung Naing, Alain P Algazi, Gerald S Falchook, Benjamin C Creelan, John Powderly, Seth Rosen, Minal Barve, Niharika B Mettu, Pierre L Triozzi, John Hamm, Gongfu Zhou, Chris Walker, Zhiwan Dong, Manish R Patel

Faculty, Staff and Student Publications

Background: Targeting programmed cell death protein 1 (PD-1) and indoleamine 2,3-dioxygenase (IDO1) pathways is an appealing option for cancer treatment.

Methods: The open-label, phase 1/2 ECHO-203 study evaluated the safety, tolerability, and efficacy of the IDO1 inhibitor epacadostat in combination with durvalumab, a human anti-PD-L1 monoclonal antibody in adult patients with advanced solid tumors.

Results: The most common treatment-related adverse events were fatigue (30.7%), nausea (21.0%), decreased appetite (13.1%), pruritus (12.5%), maculopapular rash (10.8%), and diarrhea (10.2%). Objective response rate (ORR) in the overall phase 2 population was 12.0%. Higher ORR was observed in immune checkpoint inhibitor (CPI)-naïve patients (16.1%) …