Medicine and Health Sciences Commons^™

Molnupiravir And Risk Of Post-Acute Sequelae Of Covid-19: Cohort Study, Yan Xie, Taeyoung Choi, Ziyad Al-Aly

2020-Current year OA Pubs

OBJECTIVE: To examine whether treatment with the antiviral agent molnupiravir during the first five days of SARS-CoV-2 infection is associated with reduced risk of post-acute adverse health outcomes.

DESIGN: Cohort study.

SETTING: US Department of Veterans Affairs.

PARTICIPANTS: 229 286 participants who tested positive for SARS-CoV-2 between 5 January 2022 and 15 January 2023, had at least one risk factor for progression to severe covid-19, and survived the first 30 days after testing positive were enrolled. 11 472 participants received a prescription for molnupiravir within five days of the positive test result and 217 814 received no covid-19 antiviral or …

Armo: Automated And Reliable Multi-Objective Model For Lymph Node Metastasis Prediction In Head And Neck Cancer, Zhiguo Zhou, Liyuan Chen, Michael Dohopolski, David Sher, Jing Wang

Faculty, Staff and Student Publications

Objective:

Accurate diagnosis of lymph node metastasis (LNM) is critical in treatment management for patients with head & neck cancer. Positron emission tomography (PET) and computed tomography (CT) are routinely used for identifying LNM status. However, for small or less fluorodeoxyglucose (FDG) avid nodes, there are always uncertainties in LNM diagnosis. We are aiming to develop a reliable prediction model is for identifying LNM.

Approach:

In this study, a new automated and reliable multi-objective learning model (ARMO) is proposed. In ARMO, a multi-objective model is introduced to obtain balanced sensitivity and specificity. Meanwhile, confidence is calibrated by introducing individual reliability, …

Bone Marrow Endosteal Stem Cells Dictate Active Osteogenesis And Aggressive Tumorigenesis, Yuki Matsushita, Jialin Liu, Angel Ka Yan Chu, Chiaki Tsutsumi-Arai, Mizuki Nagata, Yuki Arai, Wanida Ono, Kouhei Yamamoto, Thomas L Saunders, Joshua D Welch, Noriaki Ono

Faculty, Staff and Student Publications

The bone marrow contains various populations of skeletal stem cells (SSCs) in the stromal compartment, which are important regulators of bone formation. It is well-described that leptin receptor (LepR)+ perivascular stromal cells provide a major source of bone-forming osteoblasts in adult and aged bone marrow. However, the identity of SSCs in young bone marrow and how they coordinate active bone formation remains unclear. Here we show that bone marrow endosteal SSCs are defined by fibroblast growth factor receptor 3 (Fgfr3) and osteoblast-chondrocyte transitional (OCT) identities with some characteristics of bone osteoblasts and chondrocytes. These Fgfr3-creER-marked endosteal stromal cells contribute to …

Immune Cellular Patterns Of Distribution Affect Outcomes Of Patients With Non-Small Cell Lung Cancer, Edwin Roger Parra, Jiexin Zhang, Mei Jiang, Auriole Tamegnon, Renganayaki Krishna Pandurengan, Carmen Behrens, Luisa Solis, Cara Haymaker, John Victor Heymach, Cesar Moran, Jack J Lee, Don Gibbons, Ignacio Ivan Wistuba

Faculty, Staff and Student Publications

Studying the cellular geographic distribution in non-small cell lung cancer is essential to understand the roles of cell populations in this type of tumor. In this study, we characterize the spatial cellular distribution of immune cell populations using 23 makers placed in five multiplex immunofluorescence panels and their associations with clinicopathologic variables and outcomes. Our results demonstrate two cellular distribution patterns-an unmixed pattern mostly related to immunoprotective cells and a mixed pattern mostly related to immunosuppressive cells. Distance analysis shows that T-cells expressing immune checkpoints are closer to malignant cells than other cells. Combining the cellular distribution patterns with cellular …

Cdk5-Prmt1-Wdr24 Signaling Cascade Promotes Mtorc1 Signaling And Tumor Growth, Shasha Yin, Liu Liu, Lauren E Ball, Yalong Wang, Mark T Bedford, Stephen A Duncan, Haizhen Wang, Wenjian Gan

Faculty, Staff and Student Publications

The mammalian target of rapamycin complex1 (mTORC1) is a central regulator of metabolism and cell growth by sensing diverse environmental signals, including amino acids. The GATOR2 complex is a key component linking amino acid signals to mTORC1. Here, we identify protein arginine methyltransferase 1 (PRMT1) as a critical regulator of GATOR2. In response to amino acids, cyclin-dependent kinase 5 (CDK5) phosphorylates PRMT1 at S307 to promote PRMT1 translocation from nucleus to cytoplasm and lysosome, which in turn methylates WDR24, an essential component of GATOR2, to activate the mTORC1 pathway. Disruption of the CDK5-PRMT1-WDR24 axis suppresses hepatocellular carcinoma (HCC) cell proliferation …

Modelling Radiation Cancer Treatment With A Death-Rate Term In Ordinary And Fractional Differential Equations, Nicole Wilson, Corina S Drapaca, Heiko Enderling, Jimmy J Caudell, Kathleen P Wilkie

Faculty, Staff and Student Publications

Fractional calculus has recently been applied to the mathematical modelling of tumour growth, but its use introduces complexities that may not be warranted. Mathematical modelling with differential equations is a standard approach to study and predict treatment outcomes for population-level and patient-specific responses. Here, we use patient data of radiation-treated tumours to discuss the benefits and limitations of introducing fractional derivatives into three standard models of tumour growth. The fractional derivative introduces a history-dependence into the growth function, which requires a continuous death-rate term for radiation treatment. This newly proposed radiation-induced death-rate term improves computational efficiency in both ordinary and …

Microfluidic Device Facilitates In Vitro Modeling Of Human Neonatal Necrotizing Enterocolitis-On-A-Chip, Wyatt E. Lanik, Cliff J. Luke, Lila S. Nolan, Qingqing Gong, Lauren C. Frazer, Jamie M. Rimer, Sarah E. Gale, Raymond Luc, Shay S. Bidani, Carrie A. Sibbald, Angela N. Lewis, Belgacem Mihi, Pranjal Agrawal, Martin Goree, Marlie Maestas, Elise Hu, David F. Peters, Misty Good

2020-Current year OA Pubs

Necrotizing enterocolitis (NEC) is a deadly gastrointestinal disease of premature infants that is associated with an exaggerated inflammatory response, dysbiosis of the gut microbiome, decreased epithelial cell proliferation, and gut barrier disruption. We describe an in vitro model of the human neonatal small intestinal epithelium (Neonatal-Intestine-on-a-Chip) that mimics key features of intestinal physiology. This model utilizes intestinal enteroids grown from surgically harvested intestinal tissue from premature infants and cocultured with human intestinal microvascular endothelial cells within a microfluidic device. We used our Neonatal-Intestine-on-a-Chip to recapitulate NEC pathophysiology by adding infant-derived microbiota. This model, named NEC-on-a-Chip, simulates the predominant features of …

Candidate Variants In Dna Replication And Repair Genes In Early-Onset Renal Cell Carcinoma Patients Referred For Germline Testing, Elena V. Demidova, Ilya G. Serebriiskii, Ramilia Vlasenkova, Simon Kelow, Mark D. Andrake, Tiffiney R. Hartman, Tatiana Kent, James Virtucio, Gail L. Rosen, Richard T. Pomerantz, Roland L. Dunbrack, Erica A. Golemis, Michael J. Hall, David Y.T. Chen, Mary B. Daly, Sanjeevani Arora

Department of Biochemistry and Molecular Biology Faculty Papers

Background: Early-onset renal cell carcinoma (eoRCC) is typically associated with pathogenic germline variants (PGVs) in RCC familial syndrome genes. However, most eoRCC patients lack PGVs in familial RCC genes and their genetic risk remains undefined.

Methods: Here, we analyzed biospecimens from 22 eoRCC patients that were seen at our institution for genetic counseling and tested negative for PGVs in RCC familial syndrome genes.

Results: Analysis of whole-exome sequencing (WES) data found enrichment of candidate pathogenic germline variants in DNA repair and replication genes, including multiple DNA polymerases. Induction of DNA damage in peripheral blood monocytes (PBMCs) significantly elevated numbers of …

Serologic Responses To Covid-19 Vaccination In Children With History Of Multisystem Inflammatory Syndrome (Mis-C), Maria A Perez, Carol M Kao, David A Hunstad, Et Al.

2020-Current year OA Pubs

Understanding the serological responses to COVID-19 vaccination in children with history of MIS-C could inform vaccination recommendations. We prospectively enrolled seven children hospitalized with MIS-C and measured SARS-CoV-2 binding IgG antibodies to spike protein variants longitudinally pre- and post-Pfizer-BioNTech BNT162b2 primary series COVID-19 vaccination. We found that SARS-CoV-2 variant cross-reactive IgG antibodies variably waned following acute MIS-C, but were significantly boosted with vaccination and maintained for up to 3 months. We then compared post-vaccination binding, pseudovirus neutralizing, and functional antibody-dependent cell-mediated cytotoxicity (ADCC) titers to the reference strain (Wuhan-hu-1) and Omicron variant (B.1.1.529) among previously healthy children (n = 16) …

Machine Learning Models For The Identification Of Prognostic And Predictive Cancer Biomarkers: A Systematic Review, Qasem Al-Tashi, Maliazurina B Saad, Amgad Muneer, Rizwan Qureshi, Seyedali Mirjalili, Ajay Sheshadri, Xiuning Le, Natalie I Vokes, Jianjun Zhang, Jia Wu

Faculty, Staff and Student Publications

The identification of biomarkers plays a crucial role in personalized medicine, both in the clinical and research settings. However, the contrast between predictive and prognostic biomarkers can be challenging due to the overlap between the two. A prognostic biomarker predicts the future outcome of cancer, regardless of treatment, and a predictive biomarker predicts the effectiveness of a therapeutic intervention. Misclassifying a prognostic biomarker as predictive (or vice versa) can have serious financial and personal consequences for patients. To address this issue, various statistical and machine learning approaches have been developed. The aim of this study is to present an in-depth …

Modifiable Risk Factors In Women At High Risk Of Breast Cancer: A Systematic Review, Sarah Y Cohen, Carolyn R Stoll, Akila Anandarajah, Michelle Doering, Graham A Colditz

2020-Current year OA Pubs

BACKGROUND: Modifiable risk factors (alcohol, smoking, obesity, hormone use, and physical activity) affect a woman's breast cancer (BC) risk. Whether these factors affect BC risk in women with inherited risk (family history, BRCA1/2 mutations, or familial cancer syndrome) remains unclear.

METHODS: This review included studies on modifiable risk factors for BC in women with inherited risk. Pre-determined eligibility criteria were used and relevant data were extracted.

RESULTS: The literature search resulted in 93 eligible studies. For women with family history, most studies indicated that modifiable risk factors had no association with BC and some indicated decreased (physical activity) or increased …

Increased Breast And Colorectal Cancer Risk In Type 2 Diabetes: Awareness Among Adults With And Without Diabetes And Information Provision On Diabetes Websites, Laura Ashley, Kathryn A Robb, Daryl B O'Connor, Rebecca Platt, Mollie Price, Olivia Robinson, Elizabeth Travis, Lorraine Lipscombe, Ramzi Ajjan, Rebecca Birch

Faculty, Staff and Student Publications

BACKGROUND: People with type 2 diabetes mellitus (T2DM) have a higher risk of developing breast and bowel cancers but are less likely to participate in cancer screening.

PURPOSE: Two interlinked studies examined public awareness of the fact that T2DM increases breast and bowel cancer risk, and provision of this information on diabetes websites.

METHODS: Study-1: phase-1 surveyed awareness of T2DM-increased cancer risk in a nationally-representative British sample aged 50-74 (N = 1,458) and compared respondents with and without T2DM (n = 125 vs. n = 1,305); phase-2 surveyed an additional exclusively T2DM sample (N = 319). Study-2: High-ranking diabetes websites …

Lived Experience-Centred Word Clouds May Improve Research Uncertainty Gathering In Priority Setting Partnerships, Oliver D. Mowforth, Lance Burn, Danyal Z. Khan, Xiaoyu Yang, Sybil R.L. Stacpoole, Toto Gronlund, Lindsay Tetreault, Sukhvinder Kalsi-Ryan, Michelle L. Starkey, Iwan Sadler, Ellen Sarewitz, Delphine Houlton, Julia Carter, Paige Howard, Vafa Rahimi-Movaghar, James D. Guest, Bizhan Aarabi, Brian K. Kwon, Shekar N. Kurpad, James Harrop, Jefferson R. Wilson, Robert Grossman, Emma K. Smith, Angus Mcnair, Michael G. Fehlings, Mark R.N. Kotter, Benjamin M. Davies

Department of Neurosurgery Faculty Papers

INTRODUCTION: AO Spine RECODE-DCM was a multi-stakeholder priority setting partnership (PSP) to define the top ten research priorities for degenerative cervical myelopathy (DCM). Priorities were generated and iteratively refined using a series of surveys administered to surgeons, other healthcare professionals (oHCP) and people with DCM (PwDCM). The aim of this work was to utilise word clouds to enable the perspectives of people with the condition to be heard earlier in the PSP process than is traditionally the case. The objective was to evaluate the added value of word clouds in the process of defining research uncertainties in National Institute for …

Single-Nucleus Rna-Sequencing Of Autosomal Dominant Alzheimer Disease And Risk Variant Carriers, Logan Brase, Shih-Feng You, Ricardo D'Oliveira Albanus, Brenna C Novotny, Carolina Soriano-Tarraga, Taitea Dykstra, Maria Victoria Fernandez, John P Budde, Kristy Bergmann, John C Morris, Randall J Bateman, Richard J Perrin, Eric Mcdade, Chengjie Xiong, Jonathan Kipnis, Celeste M Karch, Oscar Harari, Et Al.

2020-Current year OA Pubs

Genetic studies of Alzheimer disease (AD) have prioritized variants in genes related to the amyloid cascade, lipid metabolism, and neuroimmune modulation. However, the cell-specific effect of variants in these genes is not fully understood. Here, we perform single-nucleus RNA-sequencing (snRNA-seq) on nearly 300,000 nuclei from the parietal cortex of AD autosomal dominant (APP and PSEN1) and risk-modifying variant (APOE, TREM2 and MS4A) carriers. Within individual cell types, we capture genes commonly dysregulated across variant groups. However, specific transcriptional states are more prevalent within variant carriers. TREM2 oligodendrocytes show a dysregulated autophagy-lysosomal pathway, MS4A microglia have dysregulated complement cascade genes, and …

Association Of Radiotherapy Duration With Clinical Outcomes In Patients With Esophageal Cancer Treated In Nrg Oncology Trials: A Secondary Analysis Of Nrg Oncology Randomized Clinical Trials, Christopher L. Hallemeier, Jennifer Moughan, Michael G. Haddock, Arnold M. Herskovic, Bruce D. Minsky, Mohan Suntharalingam, Kenneth L. Zeitzer, Madhur K. Garg, Bruce D. Greenwald, Ritsuko U. Komaki, Lindsay L. Puckett, Hyun Kim, Shane Lloyd, David A. Bush, Harold E. Kim, Thomas E. Lad, Joshua E. Meyer, Gordon S. Okawara, Adam Raben, Tracey E. Schefter, Jerry L. Barker, Carla I. Falkson, Gregory M.M. Videtic, Rojymon Jacob, Kathryn A. Winter, Christopher H. Crane

Einstein Health Papers

IMPORTANCE: For many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes.

OBJECTIVE: To analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT).

DESIGN, SETTING, AND PARTICIPANTS: This study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy Oncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute-sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology …

Recent Advances In Antimicrobial Peptide Hydrogels, Aryanna Copling, Maxwell Akantibila, Raaha Kumaresan, Gilbert Fleischer, Dennise Cortes, Rahul S Tripathi, Valerie J. Carabetta, Sebastian Vega

Cooper Medical School of Rowan University Departmental Research

Advances in the number and type of available biomaterials have improved medical devices such as catheters, stents, pacemakers, prosthetic joints, and orthopedic devices. The introduction of a foreign material into the body comes with a risk of microbial colonization and subsequent infection. Infections of surgically implanted devices often lead to device failure, which leads to increased patient morbidity and mortality. The overuse and improper use of antimicrobials has led to an alarming rise and spread of drug-resistant infections. To overcome the problem of drug-resistant infections, novel antimicrobial biomaterials are increasingly being researched and developed. Hydrogels are a class of 3D …

Cerebral Oximetry Monitoring In Extremely Preterm Infants, Mathias L Hansen, Zachary Vesoulis, Et Al.

2020-Current year OA Pubs

BACKGROUND: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking.

METHODS: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care. The primary outcome was a composite of death or severe brain injury on cerebral ultrasonography at 36 weeks' postmenstrual age. Serious adverse events that were assessed were death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis.

RESULTS: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative …

Mutational Analysis Of Anesthetic Binding Sites And Their Effects On Gabaa Receptor Activation And Modulation By Positive Allosteric Modulators Of The Α7 Nicotinic Receptor, Spencer R Pierce, Allison L Germann, Sophia Q Xu, Saumith L Menon, Marcelo O Ortells, Hugo R Arias, Gustav Akk

2020-Current year OA Pubs

The positive allosteric modulators (PAMs) of the α7 nicotinic receptor

Corneal Injury Is Associated With Stromal And Vascular Alterations Within Cranial Dura Mater, Olga V. Glinskii, Vladislav V. Glinsky, Leike Xie, Filiz Bunyak, Vladimir V. Glinskii, Sunilima Sinha, Suneel Gupta, Renato V. Iozzo, Rajiv R. Mohan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The cornea and cranial dura mater share sensory innervation. This link raises the possibility that pathological impulses mediated by corneal injury may be transmitted to the cranial dura, trigger dural perivascular/connective tissue nociceptor responses, and induce vascular and stromal alterations affecting dura mater blood and lymphatic vessel functionality. In this study, using a mouse model, we demonstrate for the first time that two weeks after the initial insult, alkaline injury to the cornea leads to remote pathological changes within the coronal suture area of the dura mater. Specifically, we detected significant pro-fibrotic changes in the dural stroma, as well as …

The Role Of Interleukin-15 In The Development And Treatment Of Hematological Malignancies, Paola Sindaco, Hritisha Pandey, Colleen Isabelle, Nitin Chakravarti, Jonathan Edward Brammer, Pierluigi Porcu, Anjali Mishra

Kimmel Cancer Center Faculty Papers

Cytokines are a vital component of the immune system that controls the activation and growth of blood cells. However, chronic overexpression of cytokines can trigger cellular events leading to malignant transformation. The cytokine interleukin-15 (IL-15) is of particular interest, which has been shown to contribute to the development and progression of various hematological malignancies. This review will provide an overview of the impact of the immunopathogenic function of IL-15 by studying its role in cell survival, proliferation, inflammation, and treatment resistance. We will also review therapeutic approaches for inhibiting IL-15 in blood cancers.

An Altered Extracellular Matrix-Integrin Interface Contributes To Huntington’S Disease-Associated Cns Dysfunction In Glial And Vascular Cells, Sarah J Hernandez, Ryan G Lim, Tarik Onur, Mark A Dane, Rebecca Smith, Keona Wang, Grace En-Hway Jean, Andrea Reyes-Ortiz, Kaylyn Devlin, Ricardo Miramontes, Jie Wu, Malcolm Casale, David Kilburn, Laura M Heiser, James E Korkola, David Van Vactor, Juan Botas, Katherine L Thompson-Peer, Leslie M Thompson

Faculty, Staff and Students Publications

Astrocytes and brain endothelial cells are components of the neurovascular unit that comprises the blood-brain barrier (BBB) and their dysfunction contributes to pathogenesis in Huntington's disease (HD). Defining the contribution of these cells to disease can inform cell-type-specific effects and uncover new disease-modifying therapeutic targets. These cells express integrin (ITG) adhesion receptors that anchor the cells to the extracellular matrix (ECM) to maintain the integrity of the BBB. We used HD patient-derived induced pluripotent stem cell (iPSC) modeling to study the ECM-ITG interface in astrocytes and brain microvascular endothelial cells and found ECM-ITG dysregulation in human iPSC-derived cells that may …

Development And Validation Of A Prediction Model For Kidney Failure In Long-Term Survivors Of Childhood Cancer, Natalie L Wu, Yan Chen, Bryan V Dieffenbach, Matthew J Ehrhardt, Sangeeta Hingorani, Rebecca M Howell, John L Jefferies, Daniel A Mulrooney, Kevin C Oeffinger, Leslie L Robison, Brent R Weil, Yan Yuan, Yutaka Yasui, Melissa M Hudson, Wendy M Leisenring, Gregory T Armstrong, Eric J Chow

Faculty, Staff and Student Publications

Purpose: Kidney failure is a rare but serious late effect following treatment for childhood cancer. We developed a model using demographic and treatment characteristics to predict individual risk of kidney failure among 5-year survivors of childhood cancer.

Methods: Five-year survivors from the Childhood Cancer Survivor Study (CCSS) without history of kidney failure (n = 25,483) were assessed for subsequent kidney failure (ie, dialysis, kidney transplantation, or kidney-related death) by age 40 years. Outcomes were identified by self-report and linkage with the Organ Procurement and Transplantation Network and the National Death Index. A sibling cohort (n = 5,045) served as a …

Neoadjuvant Pembrolizumab In Localized Microsatellite Instability High/Deficient Mismatch Repair Solid Tumors, Kaysia Ludford, Won Jin Ho, Jane V Thomas, Kanwal P S Raghav, Mariela Blum Murphy, Nicole D Fleming, Michael S Lee, Brandon G Smaglo, Y Nancy You, Matthew M Tillman, Carlos Kamiya-Matsuoka, Selvi Thirumurthi, Craig Messick, Benny Johnson, Eduardo Vilar, Arvind Dasari, Sarah Shin, Alexei Hernandez, Xuan Yuan, Hongqui Yang, Wai Chin Foo, Wei Qiao, Dipen Maru, Scott Kopetz, Michael J Overman

Faculty, Staff and Student Publications

PURPOSE: Pembrolizumab significantly improves clinical outcomes in advanced/metastatic microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) solid tumors but is not well studied in the neoadjuvant space.

METHODS: This is a phase II open-label, single-center trial of localized unresectable or high-risk resectable MSI-H/dMMR tumors. Treatment is pembrolizumab 200 mg once every 3 weeks for 6 months followed by surgical resection with an option to continue therapy for 1 year followed by observation. To continue on study, patients are required to have radiographic or clinical benefit. The coprimary end points are safety and pathologic complete response. Key secondary end points are response …

Nivolumab Plus Ipilimumab Versus Extreme Regimen As First-Line Treatment For Recurrent/Metastatic Squamous Cell Carcinoma Of The Head And Neck: The Final Results Of Checkmate 651, Robert I Haddad, Kevin Harrington, Makoto Tahara, Robert L Ferris, Maura Gillison, Jerome Fayette, Amaury Daste, Piotr Koralewski, Bogdan Zurawski, Miren Taberna, Nabil F Saba, Milena Mak, Andrzej Kawecki, Gustavo Girotto, Miguel Angel Alvarez Avitia, Caroline Even, Joaquin Gabriel Reinoso Toledo, Alexander Guminski, Urs Müller-Richter, Naomi Kiyota, Mustimbo Roberts, Tariq Aziz Khan, Karen Miller-Moslin, Li Wei, Athanassios Argiris

Faculty, Staff and Student Publications

PURPOSE: CheckMate 651 (ClinicalTrials.gov identifier: NCT02741570) evaluated first-line nivolumab plus ipilimumab versus EXTREME (cetuximab plus cisplatin/carboplatin plus fluorouracil ≤ six cycles, then cetuximab maintenance) in recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

METHODS: Patients without prior systemic therapy for R/M SCCHN were randomly assigned 1:1 to nivolumab plus ipilimumab or EXTREME. Primary end points were overall survival (OS) in the all randomly assigned and programmed death-ligand 1 combined positive score (CPS) ≥ 20 populations. Secondary end points included OS in the programmed death-ligand 1 CPS ≥ 1 population, and progression-free survival, objective response rate, and duration …

Nivolumab Plus Ipilimumab Versus Extreme Regimen As First-Line Treatment For Recurrent/Metastatic Squamous Cell Carcinoma Of The Head And Neck: The Final Results Of Checkmate 651., Robert I. Haddad, Kevin Harrington, Makoto Tahara, Robert L. Ferris, Maura Gillison, Jerome Fayette, Amaury Daste, Piotr Koralewski, Bogdan Zurawski, Miren Taberna, Nabil F. Saba, Milena Mak, Andrzej Kawecki, Gustavo Girotto, Miguel Angel Alvarez Avitia, Caroline Even, Joaquin Gabriel Reinoso Toledo, Alexander Guminski, Urs Müller-Richter, Naomi Kiyota, Mustimbo Roberts, Tariq Aziz Khan, Karen Miller-Moslin, Li Wei, Athanassios Argiris

Department of Medical Oncology Faculty Papers

Purpose: CheckMate 651 (ClinicalTrials.gov identifier: NCT02741570) evaluated first-line nivolumab plus ipilimumab versus EXTREME (cetuximab plus cisplatin/carboplatin plus fluorouracil ≤ six cycles, then cetuximab maintenance) in recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

Methods: Patients without prior systemic therapy for R/M SCCHN were randomly assigned 1:1 to nivolumab plus ipilimumab or EXTREME. Primary end points were overall survival (OS) in the all randomly assigned and programmed death-ligand 1 combined positive score (CPS) ≥ 20 populations. Secondary end points included OS in the programmed death-ligand 1 CPS ≥ 1 population, and progression-free survival, objective response rate, and …

Physician Stress In The Era Of Covid-19 Vaccine Disparity: A Multi-Institutional Survey, Sarah Zahl, Debasis Mondal, David Tolentino, Jennifer A Fischer, Sherry Jimenez

Rowan-Virtua School of Osteopathic Medicine Departmental Research

CONTEXT: Healthcare workers are at a high risk of infection during infectious disease outbreaks, such as the COVID-19 pandemic. Despite the availability of several vaccines against COVID-19, the absence of vaccination in patients and colleagues remains a continuous source of stress in healthcare workers. We conducted a survey of physician preceptors, both MDs and DOs, to explore the impact of differences in the patients' and colleagues' vaccination status on their well-being, stress, and burnout.

OBJECTIVES: The objective of this study is to determine whether exposure to unvaccinated patients and/or colleagues increases stress and burnout in physician preceptors by utilizing a …

A Multi-Site Randomized Trial Of A Clinical Decision Support Intervention To Improve Problem List Completeness, Adam Wright, Richard Schreiber, David W Bates, Skye Aaron, Angela Ai, Raja Arul Cholan, Akshay Desai, Miguel Divo, David A Dorr, Thu-Trang Hickman, Salman Hussain, Shari Just, Brian Koh, Stuart Lipsitz, Dustin Mcevoy, Trent Rosenbloom, Elise Russo, David Yut-Chee Ting, Asli Weitkamp, Dean F Sittig

Faculty, Staff and Student Publications

OBJECTIVE: To improve problem list documentation and care quality.

MATERIALS AND METHODS: We developed algorithms to infer clinical problems a patient has that are not recorded on the coded problem list using structured data in the electronic health record (EHR) for 12 clinically significant heart, lung, and blood diseases. We also developed a clinical decision support (CDS) intervention which suggests adding missing problems to the problem list. We evaluated the intervention at 4 diverse healthcare systems using 3 different EHRs in a randomized trial using 3 predetermined outcome measures: alert acceptance, problem addition, and National Committee for Quality Assurance Healthcare …

Loss-Of-Function Variants In Mycbp2 Cause Neurobehavioural Phenotypes And Corpus Callosum Defects, Lama Alabdi, Muriel Desbois, Domniţa-Valeria Rusnac, Raashda A Sulaiman, Jill A Rosenfeld, Seema Lalani, David R Murdock, Lindsay C Burrage, Ping Yee Billie Au, Shelley Towner, William G Wilson, Lawrence Wong, Theresa Brunet, Gertrud Strobl-Wildemann, Jennifer E Burton, George Hoganson, Kirsty Mcwalter, Amber Begtrup, Yuri A Zarate, Elyse L Christensen, Karla J Opperman, Andrew C Giles, Rana Helaby, Artur Kania, Ning Zheng, Brock Grill, Fowzan S Alkuraya

Faculty, Staff and Student Publications

The corpus callosum is a bundle of axon fibres that connects the two hemispheres of the brain. Neurodevelopmental disorders that feature dysgenesis of the corpus callosum as a core phenotype offer a valuable window into pathology derived from abnormal axon development. Here, we describe a cohort of eight patients with a neurodevelopmental disorder characterized by a range of deficits including corpus callosum abnormalities, developmental delay, intellectual disability, epilepsy and autistic features. Each patient harboured a distinct de novo variant in MYCBP2, a gene encoding an atypical really interesting new gene (RING) ubiquitin ligase and signalling hub with evolutionarily conserved functions …

Sptssa Variants Alter Sphingolipid Synthesis And Cause A Complex Hereditary Spastic Paraplegia, Siddharth Srivastava, Hagar Mor Shaked, Kenneth Gable, Sita D Gupta, Xueyang Pan, Niranjanakumari Somashekarappa, Gongshe Han, Payam Mohassel, Marc Gotkine, Elizabeth Doney, Paula Goldenberg, Queenie K G Tan, Yi Gong, Benjamin Kleinstiver, Brian Wishart, Heidi Cope, Claudia Brito Pires, Hannah Stutzman, Rebecca C Spillmann, Undiagnosed Disease Network, Reza Sadjadi, Orly Elpeleg, Chia-Hsueh Lee, Hugo J Bellen, Simon Edvardson, Florian Eichler, Teresa M Dunn

Faculty, Staff and Students Publications

Sphingolipids are a diverse family of lipids with critical structural and signalling functions in the mammalian nervous system, where they are abundant in myelin membranes. Serine palmitoyltransferase, the enzyme that catalyses the rate-limiting reaction of sphingolipid synthesis, is composed of multiple subunits including an activating subunit, SPTSSA. Sphingolipids are both essential and cytotoxic and their synthesis must therefore be tightly regulated. Key to the homeostatic regulation are the ORMDL proteins that are bound to serine palmitoyltransferase and mediate feedback inhibition of enzymatic activity when sphingolipid levels become excessive. Exome sequencing identified potential disease-causing variants in SPTSSA in three children presenting …

Are Cross-Sectional Safety Climate Survey Results In Operating Room Staff Associated With The Surgical Site Infection Rates In Swiss Hospitals?, Yvonne Pfeiffer, Andrew Atkinson, Judith Maag, Michael A. Lane, David Schwappach, Jonas Marschall

2020-Current year OA Pubs

OBJECTIVES: The aim of this study was to investigate the association between surgical site infections (SSIs), a major source of patient harm, and safety and teamwork climate. Prior research has been unclear regarding this relationship.

DESIGN: Based on the Swiss national SSI surveillance and a survey study assessing (a) safety climate and (b) teamwork climate, associations were analysed for three kinds of surgical procedures.

SETTING AND PARTICIPANTS: SSI surveillance data from 20 434 surgeries for hip and knee arthroplasty from 41 hospitals, 8321 for colorectal procedures from 28 hospitals and 4346 caesarean sections from 11 hospitals and survey responses from …