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2023

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Articles 811 - 840 of 9371

Full-Text Articles in Medical Specialties

Galectin-3 Cooperates With Cd47 To Suppress Phagocytosis And T-Cell Immunity In Gastric Cancer Peritoneal Metastases, Yibo Fan, Shumei Song, Yuan Li, Shilpa S Dhar, Jiankang Jin, Katsuhiro Yoshimura, Xiaodan Yao, Ruiping Wang, Ailing W Scott, Melissa Pool Pizzi, Jingjing Wu, Lang Ma, George A Calin, Samir Hanash, Linghua Wang, Michael Curran, Jaffer A Ajani Nov 2023

Galectin-3 Cooperates With Cd47 To Suppress Phagocytosis And T-Cell Immunity In Gastric Cancer Peritoneal Metastases, Yibo Fan, Shumei Song, Yuan Li, Shilpa S Dhar, Jiankang Jin, Katsuhiro Yoshimura, Xiaodan Yao, Ruiping Wang, Ailing W Scott, Melissa Pool Pizzi, Jingjing Wu, Lang Ma, George A Calin, Samir Hanash, Linghua Wang, Michael Curran, Jaffer A Ajani

Faculty, Staff and Student Publications

UNLABELLED: The peritoneal cavity is a common site of gastric adenocarcinoma (GAC) metastasis. Peritoneal carcinomatosis (PC) is resistant to current therapies and confers poor prognosis, highlighting the need to identify new therapeutic targets. CD47 conveys a "don't eat me" signal to myeloid cells upon binding its receptor signal regulatory protein alpha (SIRPα), which helps tumor cells circumvent macrophage phagocytosis and evade innate immune responses. Previous studies demonstrated that the blockade of CD47 alone results in limited clinical benefits, suggesting that other target(s) might need to be inhibited simultaneously with CD47 to elicit a strong antitumor response. Here, we found that …


The Role Of Noncoding Rnas In Pancreatic Birth Defects, Ziyue Zoey Yang, Ronald J Parchem Nov 2023

The Role Of Noncoding Rnas In Pancreatic Birth Defects, Ziyue Zoey Yang, Ronald J Parchem

Faculty, Staff and Students Publications

Congenital defects in the pancreas can cause severe health issues such as pancreatic cancer and diabetes which require lifelong treatment. Regenerating healthy pancreatic cells to replace malfunctioning cells has been considered a promising cure for pancreatic diseases including birth defects. However, such therapies are currently unavailable in the clinic. The developmental gene regulatory network underlying pancreatic development must be reactivated for in vivo regeneration and recapitulated in vitro for cell replacement therapy. Thus, understanding the mechanisms driving pancreatic development will pave the way for regenerative therapies. Pancreatic progenitor cells are the precursors of all pancreatic cells which use epigenetic changes …


Association Of Cardiovascular Disease And Pancreatitis: What Came First, The Chicken Or The Egg?, Bing Chen, Aleena Moin, Hafeez Ul Hassan Virk, Hani Jneid, Salim S Virani, Chayakrit Krittanawong Nov 2023

Association Of Cardiovascular Disease And Pancreatitis: What Came First, The Chicken Or The Egg?, Bing Chen, Aleena Moin, Hafeez Ul Hassan Virk, Hani Jneid, Salim S Virani, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Background: Recent studies suggest an association between pancreatitis and cardiovascular disease. This article aims to review the available evidence linking cardiovascular disease with acute and chronic pancreatitis.

Methods: A comprehensive search was conducted on the PubMed/MEDLINE database from inception to April 2022 using Medical Subject Heading and keywords related to pancreatitis and cardiovascular disease. The search was limited to English-language literature involving human subjects, and various study types, including observational studies, case-control studies, cohort studies, and clinical trials, were screened for eligibility. Following data extraction, the authors conducted a narrative synthesis of the studies.

Results: Longitudinal studies indicate that a …


Importance Of Geriatrics In Psychiatric Postgraduate Education, Dr Anand R, Dr Kishor M, Dr Murali M R Nov 2023

Importance Of Geriatrics In Psychiatric Postgraduate Education, Dr Anand R, Dr Kishor M, Dr Murali M R

Digital Journal of Clinical Medicine

Introduction

To assess the importance of Geriatrics in Psychiatric postgraduate education

Methodology

Marks allotted in question papers from Geriatrics in Psychiatry postgraduate examination from a university for a 5-year period was evaluated.

Discussion

1-6% of entire theory evaluation was related to Geriatric mental health topics predominantly on dementia and related disorders.


Pharmacokinetics And Safety Of A Single Dose Of Telavancin In Pediatric Subjects 2-17 Years Of Age., John S. Bradley, Jennifer Goldman, Laura P. James, Byron Kaelin, Breanne H Y Gibson, Antonio Arrieta Nov 2023

Pharmacokinetics And Safety Of A Single Dose Of Telavancin In Pediatric Subjects 2-17 Years Of Age., John S. Bradley, Jennifer Goldman, Laura P. James, Byron Kaelin, Breanne H Y Gibson, Antonio Arrieta

Manuscripts, Articles, Book Chapters and Other Papers

Antimicrobial resistance increases infection morbidity in both adults and children, necessitating the development of new therapeutic options. Telavancin, an antibiotic approved in the United States for certain bacterial infections in adults, has not been examined in pediatric patients. The objectives of this study were to evaluate the short-term safety and pharmacokinetics (PK) of a single intravenous infusion of telavancin in pediatric patients. Single-dose safety and PK of 10 mg/kg telavancin was investigated in pediatric subjects >12 months to ≤17 years of age with known or suspected bacterial infection. Plasma was collected up to 24-h post-infusion and analyzed for concentrations of …


Nad+ Rescues Aging-Induced Blood-Brain Barrier Damage Via The Cx43-Parp1 Axis, Rui Zhan, Xia Meng, Dongping Tian, Jie Xu, Hongtu Cui, Jialei Yang, Yangkai Xu, Mingming Shi, Jing Xue, Weiwei Yu, Gaofei Hu, Ke Li, Xiaoxiao Ge, Qi Zhang, Mingming Zhao, Jianyong Du, Xin Guo, Wenli Xu, Yang Gao, Changyu Yao, Fan Chen, Yue Chen, Wenxin Shan, Yujie Zhu, Liang Ji, Bing Pan, Yan Yu, Wenguang Li, Xuyang Zhao, Qihua He, Xiaohui Liu, Yue Huang, Shengyou Liao, Bin Zhou, Dehua Chui, Y Eugene Chen, Zheng Sun, Erdan Dong, Yongjun Wang, Lemin Zheng Nov 2023

Nad+ Rescues Aging-Induced Blood-Brain Barrier Damage Via The Cx43-Parp1 Axis, Rui Zhan, Xia Meng, Dongping Tian, Jie Xu, Hongtu Cui, Jialei Yang, Yangkai Xu, Mingming Shi, Jing Xue, Weiwei Yu, Gaofei Hu, Ke Li, Xiaoxiao Ge, Qi Zhang, Mingming Zhao, Jianyong Du, Xin Guo, Wenli Xu, Yang Gao, Changyu Yao, Fan Chen, Yue Chen, Wenxin Shan, Yujie Zhu, Liang Ji, Bing Pan, Yan Yu, Wenguang Li, Xuyang Zhao, Qihua He, Xiaohui Liu, Yue Huang, Shengyou Liao, Bin Zhou, Dehua Chui, Y Eugene Chen, Zheng Sun, Erdan Dong, Yongjun Wang, Lemin Zheng

Faculty, Staff and Students Publications

Blood-brain barrier (BBB) function deteriorates during aging, contributing to cognitive impairment and neurodegeneration. It is unclear what drives BBB leakage in aging and how it can be prevented. Using single-nucleus transcriptomics, we identified decreased connexin 43 (CX43) expression in cadherin-5


Associations Between Birth Defects With Neural Crest Cell Origins And Pediatric Embryonal Tumors, Eugene C Wong, Philip J Lupo, Tania A Desrosiers, Hazel B Nichols, Susan M Smith, Charles Poole, Mark Canfield, Charles Shumate, Tiffany M Chambers, Jeremy M Schraw, Wendy N Nembhard, Mahsa M Yazdy, Eirini Nestoridi, Amanda E Janitz, Andrew F Olshan Nov 2023

Associations Between Birth Defects With Neural Crest Cell Origins And Pediatric Embryonal Tumors, Eugene C Wong, Philip J Lupo, Tania A Desrosiers, Hazel B Nichols, Susan M Smith, Charles Poole, Mark Canfield, Charles Shumate, Tiffany M Chambers, Jeremy M Schraw, Wendy N Nembhard, Mahsa M Yazdy, Eirini Nestoridi, Amanda E Janitz, Andrew F Olshan

Faculty, Staff and Students Publications

BACKGROUND: There are few assessments evaluating associations between birth defects with neural crest cell developmental origins (BDNCOs) and embryonal tumors, which are characterized by undifferentiated cells having a molecular profile similar to neural crest cells. The effect of BDNCOs on embryonal tumors was estimated to explore potential shared etiologic pathways and genetic origins.

METHODS: With the use of a multistate, registry-linkage cohort study, BDNCO-embryonal tumor associations were evaluated by generating hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox regression models. BDNCOs consisted of ear, face, and neck defects, Hirschsprung disease, and a selection of congenital heart defects. Embryonal …


Indices Of Narrative Language Associated With Disability, Norah M Almubark, Gabriela Silva-Maceda, Matthew E Foster, Trina D Spencer Nov 2023

Indices Of Narrative Language Associated With Disability, Norah M Almubark, Gabriela Silva-Maceda, Matthew E Foster, Trina D Spencer

Faculty, Staff and Student Publications

Narratives skills are associated with long-term academic and social benefits. While students with disabilities often struggle to produce complete and complex narratives, it remains unclear which aspects of narrative language are most indicative of disability. In this study, we examined the association between a variety of narrative contents and form indices and disability. Methodology involved drawing 50 K-3 students with Individual Education Programs (IEP) and reported language concerns from a large diverse sample (n = 1074). Fifty typically developing (TD) students were matched to the former group using propensity score matching based on their age, gender, grade, mother’s education, …


Baseline Extracellular Vesicle Mirna-30c And Autophagic Ctcs Predict Chemoradiotherapy Resistance And Outcomes In Patients With Lung Cancer, Diego De Miguel-Perez, Francisco Gabriel Ortega, Rosario Guerrero Tejada, Antonio Martínez-Única, Christine B Peterson, Alessandro Russo, Muthukumar Gunasekaran, Andres F Cardona, Victor Amezcua, Jose Antonio Lorente, Jose Expósito Hernández, Christian Rolfo, Maria Jose Serrano Nov 2023

Baseline Extracellular Vesicle Mirna-30c And Autophagic Ctcs Predict Chemoradiotherapy Resistance And Outcomes In Patients With Lung Cancer, Diego De Miguel-Perez, Francisco Gabriel Ortega, Rosario Guerrero Tejada, Antonio Martínez-Única, Christine B Peterson, Alessandro Russo, Muthukumar Gunasekaran, Andres F Cardona, Victor Amezcua, Jose Antonio Lorente, Jose Expósito Hernández, Christian Rolfo, Maria Jose Serrano

Faculty, Staff and Student Publications

Concurrent chemoradiotherapy (cCRT) is the mainstay of treatment for patients diagnosed with locally advanced non-small cell lung cancer (NSCLC). One significant challenge in the effectiveness of this therapy is the potential development of resistance mechanisms, where autophagy up-regulation has been proposed as a key contributing factor. However, there is a lack of reliable biomarkers to predict outcomes on these patients. Interestingly, for addressing this gap, extracellular vesicles (EVs) and circulating tumor cells (CTCs) have emerged as potential sources of such biomarkers. In this study, we investigated EV-associated miRNAs and presence of autophagic CTCs in prospectively collected serial samples from 38 …


Dissociable Effects Of Alzheimer's Disease-Related Cognitive Dysfunction And Aging On Functional Brain Network Segregation, Ziwei Zhang, Micaela Y Chan, Liang Han, Claudia A Carreno, Ezra Winter-Nelson, Gagan S Wig Nov 2023

Dissociable Effects Of Alzheimer's Disease-Related Cognitive Dysfunction And Aging On Functional Brain Network Segregation, Ziwei Zhang, Micaela Y Chan, Liang Han, Claudia A Carreno, Ezra Winter-Nelson, Gagan S Wig

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is associated with changes in large-scale functional brain network organization. Individuals with AD exhibit less segregated resting-state brain networks compared with individuals without dementia. However, declines in brain network segregation are also evident as adult individuals grow older. Determining whether these observations reflect unique or overlapping alterations on the functional connectome of the brain is essential for understanding the impact of AD on network organization and incorporating measures of functional brain network organization toward AD characterization. Relationships between AD dementia severity and participant's age on resting-state brain system segregation were examined in 326 cognitively healthy and 275 …


Retrieval Of Large Balloon Fragments During Transcatheter Pulmonary Valve Implantation Using A Novel Retrieval System, Anne C Taylor, Mohamed Ali H Ghandour, Asra Khan, Srinath T Gowda, Flora Nunez-Gallegos, Lynn F Peng, Jamil A Aboulhosn, Daniel S Levi, Doff B Mcelhinney, Athar M Qureshi Nov 2023

Retrieval Of Large Balloon Fragments During Transcatheter Pulmonary Valve Implantation Using A Novel Retrieval System, Anne C Taylor, Mohamed Ali H Ghandour, Asra Khan, Srinath T Gowda, Flora Nunez-Gallegos, Lynn F Peng, Jamil A Aboulhosn, Daniel S Levi, Doff B Mcelhinney, Athar M Qureshi

Faculty, Staff and Students Publications

The removal of balloon fragments from the pulmonary artery without damaging the pulmonary and tricuspid valves can be difficult. Four cases during transcatheter pulmonary valve replacement are described in which a novel retrieval system was used to facilitate safe removal. (Level of Difficulty: Advanced.)


Knowledge, Attitude, And Perception Of The General Public Towards The Impact Of Hemoglobinopathies On Pregnancy Outcomes: A Questionnaire-Based Study, Kumud Dhankhar, Kiran Dahiya, Shobha Chikkavaddaragudi Ramachandra, Akila Prashant Nov 2023

Knowledge, Attitude, And Perception Of The General Public Towards The Impact Of Hemoglobinopathies On Pregnancy Outcomes: A Questionnaire-Based Study, Kumud Dhankhar, Kiran Dahiya, Shobha Chikkavaddaragudi Ramachandra, Akila Prashant

International Journal of Health and Allied Sciences

Background: Knowledge about hemoglobinopathies in the general public is unsatisfactory. Many couples are unaware of their carrier status and a child can be born with unexpected, serious hemoglobinopathies. Willingness to participate in screening programs can substantially help in bringing down the birth of children affected with hemoglobinopathies. To understand the knowledge, attitude, and perception of the general public on various hemoglobinopathies and their pregnancy outcomes we performed a questionnaire-based descriptive survey. Methods: After obtaining approval from the institutional ethics committee and validation by an expert panel we circulated a Google form consisting of 21 questions via WhatsApp which was made …


Circulating Tumor Dna Monitoring On Chemo-Immunotherapy For Risk Stratification In Advanced Non-Small Cell Lung Cancer, Bruna Pellini, Russell W Madison, Merrida A Childress, Shoshana T Miller, Ole Gjoerup, Jason Cheng, Richard S P Huang, Michael Krainock, Pratyush Gupta, Wei Zou, David S Shames, Solomon Moshkevich, Marcus Ballinger, Minetta C Liu, Amanda Young, Minu K Srivastava, Geoffrey R Oxnard, Mark A Socinski Nov 2023

Circulating Tumor Dna Monitoring On Chemo-Immunotherapy For Risk Stratification In Advanced Non-Small Cell Lung Cancer, Bruna Pellini, Russell W Madison, Merrida A Childress, Shoshana T Miller, Ole Gjoerup, Jason Cheng, Richard S P Huang, Michael Krainock, Pratyush Gupta, Wei Zou, David S Shames, Solomon Moshkevich, Marcus Ballinger, Minetta C Liu, Amanda Young, Minu K Srivastava, Geoffrey R Oxnard, Mark A Socinski

Faculty, Staff and Student Publications

PURPOSE: Chemoimmunotherapy (chemoIO) is a prevalent first-line treatment for advanced driver-negative non-small cell lung cancer (NSCLC), with maintenance therapy given after induction. However, there is significant clinical variability in the duration, dosing, and timing of maintenance therapy after induction chemoIO. We used circulating tumor DNA (ctDNA) monitoring to inform outcomes in patients with advanced NSCLC receiving chemoIO.

EXPERIMENTAL DESIGN: This retrospective study included 221 patients from a phase III trial of atezolizumab+carboplatin+nab-paclitaxel versus carboplatin+nab-paclitaxel in squamous NSCLC (IMpower131). ctDNA monitoring used the FoundationOne Tracker involving comprehensive genomic profiling of pretreatment tumor tissue, variant selection using an algorithm to exclude nontumor …


Impact Of Climate Change On Surgery: A Scoping Review To Define Existing Knowledge And Identify Gaps, Tina Bharani, Rebecca Achey, Harris Jamal, Alexis Cherry, Malcolm K. Robinson, Guy J. Maddern, Deirdre K. Tobias, Divyansh Agarwal Nov 2023

Impact Of Climate Change On Surgery: A Scoping Review To Define Existing Knowledge And Identify Gaps, Tina Bharani, Rebecca Achey, Harris Jamal, Alexis Cherry, Malcolm K. Robinson, Guy J. Maddern, Deirdre K. Tobias, Divyansh Agarwal

Department of Surgery Faculty Papers

With climate change accelerated at a worrisome rate, global warming also will have implications for surgery and surgical practice. The goal of this current study was to systematically survey the literature and better understand how climate change has affected surgical disease burden, surgical care delivery, and surgical outcomes. We performed a comprehensive scoping review, screening 3334 unique citations from three databases – 1766 from Embase, 1329 from Pubmed and 239 from Scopus – to identify studies that had associated climate change with surgery. After systematic searching, quality appraisal, and data extraction, we synthesized findings from qualitative and quantitative studies. Twenty-six …


Novel Clinical Trial Designs With Dose Optimization To Improve Long-Term Outcomes, Peter F Thall, Yong Zang, Andrew G Chapple, Ying Yuan, Ruitao Lin, David Marin, Pavlos Msaouel Nov 2023

Novel Clinical Trial Designs With Dose Optimization To Improve Long-Term Outcomes, Peter F Thall, Yong Zang, Andrew G Chapple, Ying Yuan, Ruitao Lin, David Marin, Pavlos Msaouel

Faculty, Staff and Student Publications

Conventional designs for choosing a dose for a new therapy may select doses that are unsafe or ineffective and fail to optimize progression-free survival time, overall survival time, or response/remission duration. We explain and illustrate limitations of conventional dose-finding designs and make four recommendations to address these problems. When feasible, a dose-finding design should account for long-term outcomes, include screening rules that drop unsafe or ineffective doses, enroll an adequate sample size, and randomize patients among doses. As illustrations, we review three designs that include one or more of these features. The first illustration is a trial that randomized patients …


Post-Acute Sequelae Of Covid-19 (Pasc) In Pediatrics: Factors That Impact Symptom Severity And Referral To Treatment., Catherine Soprano, Ryan Ngo, Casey A Konys, Ashley Bazier, Katherine Salamon Nov 2023

Post-Acute Sequelae Of Covid-19 (Pasc) In Pediatrics: Factors That Impact Symptom Severity And Referral To Treatment., Catherine Soprano, Ryan Ngo, Casey A Konys, Ashley Bazier, Katherine Salamon

Department of Medicine Faculty Papers

The post-acute sequelae of COVID-19 (PASC) is a complex condition. While there are emerging studies on its effects in adults, there is scarce research regarding the long-term effects of COVID-19 infection among youth. Several researchers have likened long-haul COVID-19 to chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and postural orthostatic tachycardia syndrome (POTS). In adults, the prognosis for these diagnoses is less promising than that in youth; however, there is currently very little information available on the presentation of youth with PASC. A better understanding of the specific symptom presentation for youth diagnosed with PASC is necessary. Retrospective chart reviews were conducted …


Reducing Prescribing Of Antibiotics For Acute Respiratory Infections Using A Frontline Nurse-Led Ehr-Integrated Clinical Decision Support Tool: Protocol For A Stepped Wedge Randomized Control Trial, Elizabeth R Stevens, Ruth Agbakoba, Devin M Mann, Rachel Hess, Safiya I Richardson, Thomas Mcginn, Paul D Smith, Wendy Halm, Marlon P Mundt, Katherine L Dauber-Decker, Simon A Jones, Dawn M Feldthouse, Eun Ji Kim, David A Feldstein Nov 2023

Reducing Prescribing Of Antibiotics For Acute Respiratory Infections Using A Frontline Nurse-Led Ehr-Integrated Clinical Decision Support Tool: Protocol For A Stepped Wedge Randomized Control Trial, Elizabeth R Stevens, Ruth Agbakoba, Devin M Mann, Rachel Hess, Safiya I Richardson, Thomas Mcginn, Paul D Smith, Wendy Halm, Marlon P Mundt, Katherine L Dauber-Decker, Simon A Jones, Dawn M Feldthouse, Eun Ji Kim, David A Feldstein

Faculty, Staff and Students Publications

Background: Overprescribing of antibiotics for acute respiratory infections (ARIs) remains a major issue in outpatient settings. Use of clinical prediction rules (CPRs) can reduce inappropriate antibiotic prescribing but they remain underutilized by physicians and advanced practice providers. A registered nurse (RN)-led model of an electronic health record-integrated CPR (iCPR) for low-acuity ARIs may be an effective alternative to address the barriers to a physician-driven model.

Methods: Following qualitative usability testing, we will conduct a stepped-wedge practice-level cluster randomized controlled trial (RCT) examining the effect of iCPR-guided RN care for low acuity patients with ARI. The primary hypothesis to be tested …


Tlr7 Promotes Smoke-Induced Experimental Lung Damage Through The Activity Of Mast Cell Tryptase, Gang Liu, Tatt Jhong Haw, Malcolm R Starkey, Ashleigh M Philp, Stelios Pavlidis, Christina Nalkurthi, Prema M Nair, Henry M Gomez, Irwan Hanish, Alan Cy Hsu, Elinor Hortle, Sophie Pickles, Joselyn Rojas-Quintero, Raul San Jose Estepar, Jacqueline E Marshall, Richard Y Kim, Adam M Collison, Joerg Mattes, Sobia Idrees, Alen Faiz, Nicole G Hansbro, Ryutaro Fukui, Yusuke Murakami, Hong Sheng Cheng, Nguan Soon Tan, Sanjay H Chotirmall, Jay C Horvat, Paul S Foster, Brian Gg Oliver, Francesca Polverino, Antonio Ieni, Francesco Monaco, Gaetano Caramori, Sukhwinder S Sohal, Ken R Bracke, Peter A Wark, Ian M Adcock, Kensuke Miyake, Don D Sin, Philip M Hansbro Nov 2023

Tlr7 Promotes Smoke-Induced Experimental Lung Damage Through The Activity Of Mast Cell Tryptase, Gang Liu, Tatt Jhong Haw, Malcolm R Starkey, Ashleigh M Philp, Stelios Pavlidis, Christina Nalkurthi, Prema M Nair, Henry M Gomez, Irwan Hanish, Alan Cy Hsu, Elinor Hortle, Sophie Pickles, Joselyn Rojas-Quintero, Raul San Jose Estepar, Jacqueline E Marshall, Richard Y Kim, Adam M Collison, Joerg Mattes, Sobia Idrees, Alen Faiz, Nicole G Hansbro, Ryutaro Fukui, Yusuke Murakami, Hong Sheng Cheng, Nguan Soon Tan, Sanjay H Chotirmall, Jay C Horvat, Paul S Foster, Brian Gg Oliver, Francesca Polverino, Antonio Ieni, Francesco Monaco, Gaetano Caramori, Sukhwinder S Sohal, Ken R Bracke, Peter A Wark, Ian M Adcock, Kensuke Miyake, Don D Sin, Philip M Hansbro

Faculty, Staff and Students Publications

Toll-like receptor 7 (TLR7) is known for eliciting immunity against single-stranded RNA viruses, and is increased in both human and cigarette smoke (CS)-induced, experimental chronic obstructive pulmonary disease (COPD). Here we show that the severity of CS-induced emphysema and COPD is reduced in TLR7-deficient mice, while inhalation of imiquimod, a TLR7-agonist, induces emphysema without CS exposure. This imiquimod-induced emphysema is reduced in mice deficient in mast cell protease-6, or when wild-type mice are treated with the mast cell stabilizer, cromolyn. Furthermore, therapeutic treatment with anti-TLR7 monoclonal antibody suppresses CS-induced emphysema, experimental COPD and accumulation of pulmonary mast cells in mice. …


Dhodh: A Promising Target In The Treatment Of T-Cell Acute Lymphoblastic Leukemia, Amy N Sexauer, Gabriela Alexe, Karin Gustafsson, Elizabeth Zanetakos, Jelena Milosevic, Mary Ayres, Varsha Gandhi, Yana Pikman, Kimberly Stegmaier, David B Sykes Nov 2023

Dhodh: A Promising Target In The Treatment Of T-Cell Acute Lymphoblastic Leukemia, Amy N Sexauer, Gabriela Alexe, Karin Gustafsson, Elizabeth Zanetakos, Jelena Milosevic, Mary Ayres, Varsha Gandhi, Yana Pikman, Kimberly Stegmaier, David B Sykes

Faculty, Staff and Student Publications

Patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) have a poor prognosis with few therapeutic options. With the goal of identifying novel therapeutic targets, we used data from the Dependency Map project to identify dihydroorotate dehydrogenase (DHODH) as one of the top metabolic dependencies in T-ALL. DHODH catalyzes the fourth step of de novo pyrimidine nucleotide synthesis. Small molecule inhibition of DHODH rapidly leads to the depletion of intracellular pyrimidine pools and forces cells to rely on extracellular salvage. In the absence of sufficient salvage, this intracellular nucleotide starvation results in the inhibition of DNA and RNA synthesis, …


Pharyngeal Oxygen Delivery Device Sustains Manikin Lung Oxygenation Longer Than High-Flow Nasal Cannula, Jeramie B Hanson, John R Williams, Emily H Garmon, Phillip M Morris, Russell K Mcallister, Courtney N Shaver, William C Culp Nov 2023

Pharyngeal Oxygen Delivery Device Sustains Manikin Lung Oxygenation Longer Than High-Flow Nasal Cannula, Jeramie B Hanson, John R Williams, Emily H Garmon, Phillip M Morris, Russell K Mcallister, Courtney N Shaver, William C Culp

Faculty, Staff and Student Publications

PURPOSE: Hypoxemia during a failed airway scenario is life threatening. A dual-lumen pharyngeal oxygen delivery device (PODD) was developed to fit inside a traditional oropharyngeal airway for undisrupted supraglottic oxygenation and gas analysis during laryngoscopy and intubation. We hypothesized that the PODD would provide oxygen as effectively as high-flow nasal cannula (HFNC) while using lower oxygen flow rates.

METHODS: We compared oxygen delivery of the PODD to HFNC in a preoxygenated, apneic manikin lung that approximated an adult functional residual capacity. Four arms were studied: HFNC at 20 and 60 liters per minute (LPM) oxygen, PODD at 10 LPM oxygen, …


The Landscape Of Alterations From 1407 Ultra-Rare Sarcomas From The Aacr Genie Database: Clinical Implications, Ryan A Denu, Justin T Moyers, Mohamed A Gouda, Anthony P Conley, Alexander J Lazar, Vivek Subbiah Nov 2023

The Landscape Of Alterations From 1407 Ultra-Rare Sarcomas From The Aacr Genie Database: Clinical Implications, Ryan A Denu, Justin T Moyers, Mohamed A Gouda, Anthony P Conley, Alexander J Lazar, Vivek Subbiah

Faculty, Staff and Student Publications

Purpose: Ultra-rare sarcomas (URS) comprise a group of orphan diseases with an incidence of ≤1/1,000,000 people per year. We aimed to assess clinically actionable genomic alterations in URS.

Experimental design: Data were extracted from the GENIE database using cBioPortal. OncoKB was used to assess for clinical actionability of mutations. Tumor mutational burden (TMB) was inferred from clinical sequencing data.

Results: Soft tissue (ST) URS made up 23.5% of ST sarcoma cases, and bone URS made up 16.5% of bone sarcoma cases. The most commonly mutated gene in all four groups was TP53. The most common fusions involved EWSR1. The most …


A Phase 1 Study Of Prophylactic Anakinra To Mitigate Icans In Patients With Large B-Cell Lymphoma, Paolo Strati, Andrew Jallouk, Qing Deng, Xubin Li, Lei Feng, Ryan Sun, Sherry Adkins, Swapna Johncy, Taylor Cain, Raphael E Steiner, Sairah Ahmed, Dai Chihara, Luis E Fayad, Swaminathan P Iyer, Sandra Horowitz, Loretta J Nastoupil, Ranjit Nair, Ahmed Hassan, Taher E Daoud, Misha Hawkins, Maria A Rodriguez, Elizabeth J Shpall, Jeremy L Ramdial, Partow Kebriaei, David S Hong, Jason R Westin, Sattva S Neelapu, Michael R Green Nov 2023

A Phase 1 Study Of Prophylactic Anakinra To Mitigate Icans In Patients With Large B-Cell Lymphoma, Paolo Strati, Andrew Jallouk, Qing Deng, Xubin Li, Lei Feng, Ryan Sun, Sherry Adkins, Swapna Johncy, Taylor Cain, Raphael E Steiner, Sairah Ahmed, Dai Chihara, Luis E Fayad, Swaminathan P Iyer, Sandra Horowitz, Loretta J Nastoupil, Ranjit Nair, Ahmed Hassan, Taher E Daoud, Misha Hawkins, Maria A Rodriguez, Elizabeth J Shpall, Jeremy L Ramdial, Partow Kebriaei, David S Hong, Jason R Westin, Sattva S Neelapu, Michael R Green

Faculty, Staff and Student Publications

No abstract provided.


Gasdermin D Permeabilization Of Mitochondrial Inner And Outer Membranes Accelerates And Enhances Pyroptosis, Rui Miao, Cong Jiang, Winston Y Chang, Haiwei Zhang, Jinsu An, Felicia Ho, Pengcheng Chen, Han Zhang, Caroline Junqueira, Dulguun Amgalan, Felix G Liang, Junbing Zhang, Charles L Evavold, Iva Hafner-Bratkovič, Zhibin Zhang, Pietro Fontana, Shiyu Xia, Markus Waldeck-Weiermair, Youdong Pan, Thomas Michel, Liron Bar-Peled, Hao Wu, Jonathan C Kagan, Richard N Kitsis, Peng Zhang, Xing Liu, Judy Lieberman Nov 2023

Gasdermin D Permeabilization Of Mitochondrial Inner And Outer Membranes Accelerates And Enhances Pyroptosis, Rui Miao, Cong Jiang, Winston Y Chang, Haiwei Zhang, Jinsu An, Felicia Ho, Pengcheng Chen, Han Zhang, Caroline Junqueira, Dulguun Amgalan, Felix G Liang, Junbing Zhang, Charles L Evavold, Iva Hafner-Bratkovič, Zhibin Zhang, Pietro Fontana, Shiyu Xia, Markus Waldeck-Weiermair, Youdong Pan, Thomas Michel, Liron Bar-Peled, Hao Wu, Jonathan C Kagan, Richard N Kitsis, Peng Zhang, Xing Liu, Judy Lieberman

Faculty, Staff and Student Publications

Gasdermin D (GSDMD)-activated inflammatory cell death (pyroptosis) causes mitochondrial damage, but its underlying mechanism and functional consequences are largely unknown. Here, we show that the N-terminal pore-forming GSDMD fragment (GSDMD-NT) rapidly damaged both inner and outer mitochondrial membranes (OMMs) leading to reduced mitochondrial numbers, mitophagy, ROS, loss of transmembrane potential, attenuated oxidative phosphorylation (OXPHOS), and release of mitochondrial proteins and DNA from the matrix and intermembrane space. Mitochondrial damage occurred as soon as GSDMD was cleaved prior to plasma membrane damage. Mitochondrial damage was independent of the B-cell lymphoma 2 family and depended on GSDMD-NT binding to cardiolipin. Canonical and …


Cigarette Smoke Exposure Accelerates Aml Progression In Flt3-Itd Models, Mary Figueroa, Huaxian Ma, Mansour Alfayez, Daniel Enrique Morales-Mantilla, Fei Wang, Yue Lu, Marcos R Estecio, Katherine Y King, Eugenie Kleinerman, Seyed Javad Moghaddam, Naval Daver, Michael Andreeff, Marina Konopleva, Courtney Dinardo, Joya Chandra Nov 2023

Cigarette Smoke Exposure Accelerates Aml Progression In Flt3-Itd Models, Mary Figueroa, Huaxian Ma, Mansour Alfayez, Daniel Enrique Morales-Mantilla, Fei Wang, Yue Lu, Marcos R Estecio, Katherine Y King, Eugenie Kleinerman, Seyed Javad Moghaddam, Naval Daver, Michael Andreeff, Marina Konopleva, Courtney Dinardo, Joya Chandra

Faculty, Staff and Student Publications

No abstract provided.


Emergency Department Presentations Of Diabetic Ketoacidosis In A Large Cohort Of Children, Lisa E. Nigrovic, Nathan Kuppermann, Simona Ghetti, Jeff E. Schunk, Michael J. Stoner, Arleta Rewers, Julie K. Mcmanemy, Kimberly S. Quayle, Jennifer L. Trainor, Leah Tzimenatos, Jonathan E. Bennett, Maria Y. Kwok, Sage R. Myers, Kathleen M. Brown, T. Charles Casper, Cody S. Olsen, Nicole S. Glaser Nov 2023

Emergency Department Presentations Of Diabetic Ketoacidosis In A Large Cohort Of Children, Lisa E. Nigrovic, Nathan Kuppermann, Simona Ghetti, Jeff E. Schunk, Michael J. Stoner, Arleta Rewers, Julie K. Mcmanemy, Kimberly S. Quayle, Jennifer L. Trainor, Leah Tzimenatos, Jonathan E. Bennett, Maria Y. Kwok, Sage R. Myers, Kathleen M. Brown, T. Charles Casper, Cody S. Olsen, Nicole S. Glaser

Department of Emergency Medicine Faculty Papers

Background.

Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of childhood diabetes. However, the influence of demographic factors on presentation are not well-defined.

Methods.

We included children from 12 centers who were <18 years with DKA (glucose > 300 mg/dL, serum pH < 7.25, or serum bicarbonate <15 mEq/L) enrolled in the Pediatric Emergency Care Applied Research Network (PECARN) Fluid Therapies Under Investigation in DKA (FLUID) Trial. Data were also collected for children who presented to the centers during the enrollment period but were not enrolled due to disease or treatment-related reasons. We compared demographic, clinical, and biochemical findings among children with newly and previously diagnosed diabetes and children in different age groups.

Results.

Of the 1,679 DKA episodes in 1,553 children, 799 (47.5%) episodes occurred in children with newly diagnosed diabetes and 396 (23.6%) were severe (pH < 7.1). Newly diagnosed children <6 years of age were not more likely to have severe DKA in terms of pH, but had more severe hypocarbia and higher blood urea nitrogen levels, factors previously associated with the risk of cerebral injury. Lower socioeconomic status (SES) (based on family income and maternal education level) were associated with more severe DKA in new onset children, and recurrent DKA in the previously diagnosed children.

Conclusions.

Greater efforts are needed to identify the children with diabetes early and to prevent recurrent DKA, particularly among children in low-SES groups. Young children with DKA may need more intensive monitoring due to higher …


Phase 1 Study Of Vibecotamab Identifies An Optimized Dose For Treatment Of Relapsed/Refractory Acute Myeloid Leukemia, Farhad Ravandi, Asad Bashey, James Foran, Wendy Stock, Raya Mawad, Nicholas Short, Musa Yilmaz, Hagop Kantarjian, Olatoyosi Odenike, Anand Patel, Raman Garcha, William Barrett Ainsworth, Raphael Clynes, Jitendra Kanodia, Ying Ding, Huajiang Li, Steve Kye, Alice Mims Nov 2023

Phase 1 Study Of Vibecotamab Identifies An Optimized Dose For Treatment Of Relapsed/Refractory Acute Myeloid Leukemia, Farhad Ravandi, Asad Bashey, James Foran, Wendy Stock, Raya Mawad, Nicholas Short, Musa Yilmaz, Hagop Kantarjian, Olatoyosi Odenike, Anand Patel, Raman Garcha, William Barrett Ainsworth, Raphael Clynes, Jitendra Kanodia, Ying Ding, Huajiang Li, Steve Kye, Alice Mims

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML), an aggressive malignancy with unmet medical need, lacks immunotherapeutic options. CD123, the cellular receptor for interleukin-3, expressed in AML is an attractive target for tumor-specific therapy. Vibecotamab (XmAb14045), a humanized bispecific antibody, monovalently binds both CD3 and CD123 to recruit cytotoxic T cells to kill CD123+ tumor cells. This phase 1 study's primary objectives were safety and tolerability and identification of a maximum tolerated dose/recommended dose for use as monotherapy in patients with relapsed/refractory AML. Identification of a recommended phase 2 vibecotamab dose comprised 3 step-up doses (Week 1), which were noted to reduce cytokine response …


Acceptance, Awareness, Attitude, And Practices Toward Heart Transplantation: A Saudi Based Survey, Walid Abukhudair, ​​Ahmad Zaki ​ Hafiz, ​​Mohammed Abdullah ​ Alosaimi, ​​Fares Abu ​ Alaynayn, ​​Fahad Abdullah ​ Alosaimi, ​​Rehab Ahmed ​ Karam, ​​Tamer Mohamed ​ Abdelrahman Nov 2023

Acceptance, Awareness, Attitude, And Practices Toward Heart Transplantation: A Saudi Based Survey, Walid Abukhudair, ​​Ahmad Zaki ​ Hafiz, ​​Mohammed Abdullah ​ Alosaimi, ​​Fares Abu ​ Alaynayn, ​​Fahad Abdullah ​ Alosaimi, ​​Rehab Ahmed ​ Karam, ​​Tamer Mohamed ​ Abdelrahman

Journal of the Saudi Heart Association

Introductions: The awareness of brain death and heart donation (HD) among the Saudi population remains limited, coupled with negative attitudes toward heart donation, resulting in a significant gap between the demand for donor hearts and the available supply. This study aimed to comprehensively understand the current perceptions, attitudes, and practices of the Saudi population regarding HD, as well as identify the obstacles. The ultimate goal was to strengthen the local donor pool. Methods: A cross-sectional study was conducted from March to May 2023, employing a self-administered internet survey. The survey collected demographic information, assessed awareness, attitudes, and practices related to …


Editorial: Resilience, Quality Of Life And Psychosocial Outcomes Of Cancer Patients And Their Caregivers, Nida Zahid, Nargis Asad, Ashraf El-Metwally Nov 2023

Editorial: Resilience, Quality Of Life And Psychosocial Outcomes Of Cancer Patients And Their Caregivers, Nida Zahid, Nargis Asad, Ashraf El-Metwally

Department of Surgery Docs

No abstract provided.


Wire Snare Close Loop: A Novel Technique To Retrieve Embolized Devices, Manish Bansal, Gary E Stapleton, Srinath T Gowda, Athar M Qureshi Nov 2023

Wire Snare Close Loop: A Novel Technique To Retrieve Embolized Devices, Manish Bansal, Gary E Stapleton, Srinath T Gowda, Athar M Qureshi

Faculty, Staff and Students Publications

No abstract provided.


Identification Of Exosome Protein Panels As Predictive Biomarkers For Non-Small Cell Lung Cancer, Bin Luo, Zujun Que, Xinyi Lu, Dan Qi, Zhi Qiao, Yun Yang, Fangfang Qian, Yi Jiang, Yan Li, Ronghu Ke, Xiaoyun Shen, Hua Xiao, Hegen Li, Erxi Wu, Jianhui Tian Nov 2023

Identification Of Exosome Protein Panels As Predictive Biomarkers For Non-Small Cell Lung Cancer, Bin Luo, Zujun Que, Xinyi Lu, Dan Qi, Zhi Qiao, Yun Yang, Fangfang Qian, Yi Jiang, Yan Li, Ronghu Ke, Xiaoyun Shen, Hua Xiao, Hegen Li, Erxi Wu, Jianhui Tian

Children’s Nutrition Research Center Staff Publications

Background: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths worldwide, primarily due to its propensity for metastasis. Patients diagnosed with localized primary cancer have higher survival rates than those with metastasis. Thus, it is imperative to discover biomarkers for the early detection of NSCLC and the timely prediction of tumor metastasis to improve patient outcomes.

Methods: Here, we utilized an integrated approach to isolate and characterize plasma exosomes from NSCLC patients as well as healthy individuals. We then conducted proteomics analysis and parallel reaction monitoring to identify and validate the top-ranked proteins of plasma exosomes.

Results: …