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2023

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Articles 6721 - 6750 of 9374

Full-Text Articles in Medical Specialties

Clinical Characteristics, Impairment, And Psychiatric Morbidity In 102 Youth With Misophonia, Andrew G Guzick, Matti Cervin, Eleanor E A Smith, Jane Clinger, Isabel Draper, Wayne K Goodman, Marijn Lijffijt, Nicholas Murphy, Adam B Lewin, Sophie C Schneider, Eric A Storch Mar 2023

Clinical Characteristics, Impairment, And Psychiatric Morbidity In 102 Youth With Misophonia, Andrew G Guzick, Matti Cervin, Eleanor E A Smith, Jane Clinger, Isabel Draper, Wayne K Goodman, Marijn Lijffijt, Nicholas Murphy, Adam B Lewin, Sophie C Schneider, Eric A Storch

Faculty, Staff and Students Publications

BACKGROUND: There is little information on the clinical presentation, functional impact, and psychiatric characteristics of misophonia in youth, an increasingly recognized syndrome characterized by high emotional reactivity to certain sounds and associated visual stimuli.

METHOD: One-hundred-two youth (8-17 years-old) with misophonia and their parents were recruited and compared with 94 youth with anxiety disorders. Participants completed validated assessments of misophonia severity, quality of life, as well as psychiatric symptoms and diagnoses.

RESULTS: The most common misophonia triggers included eating (96 %), breathing (84 %), throat sounds (66 %), and tapping (54 %). Annoyance/irritation, verbal aggression, avoidance behavior, and family impact …


Long-Chain Polyunsaturated Lipids Associated With Responsiveness To Anti-Pd-1 Therapy Are Colocalized With Immune Infiltrates In The Tumor Microenvironment, Mary E King, Robert Yuan, Jeremy Chen, Komal Pradhan, Isabel Sariol, Shirley Li, Ashish Chakraborty, Oscar Ekpenyong, Jennifer H Yearley, Janica C Wong, Luis Zúñiga, Daniela Tomazela, Maribel Beaumont, Jin-Hwan Han, Livia S Eberlin Mar 2023

Long-Chain Polyunsaturated Lipids Associated With Responsiveness To Anti-Pd-1 Therapy Are Colocalized With Immune Infiltrates In The Tumor Microenvironment, Mary E King, Robert Yuan, Jeremy Chen, Komal Pradhan, Isabel Sariol, Shirley Li, Ashish Chakraborty, Oscar Ekpenyong, Jennifer H Yearley, Janica C Wong, Luis Zúñiga, Daniela Tomazela, Maribel Beaumont, Jin-Hwan Han, Livia S Eberlin

Faculty, Staff and Students Publications

The programmed cell death protein-1 (PD-1) is highly expressed on the surface of antigen-specific exhausted T cells and, upon interaction with its ligand PD-L1, can result in inhibition of the immune response. Anti-PD-1 treatment has been shown to extend survival and result in durable responses in several cancers, yet only a subset of patients benefit from this therapy. Despite the implication of metabolic alteration following cancer immunotherapy, mechanistic associations between antitumor responses and metabolic changes remain unclear. Here, we used desorption electrospray ionization mass spectrometry imaging to examine the lipid profiles of tumor tissue from three syngeneic murine models with …


Interaction Between Tumor Cell Tnfr2 And Monocyte Membrane-Bound Tnf-Α Triggers Tumorigenic Inflammation In Neuroblastoma, Julie A Tomolonis, Xin Xu, Kshiti H Dholakia, Chunchao Zhang, Linjie Guo, Amy N Courtney, Siyue Wang, Julien Balzeau, Gabriel A Barragán, Gengwen Tian, Erica J Di Pierro, Leonid S Metelitsa Mar 2023

Interaction Between Tumor Cell Tnfr2 And Monocyte Membrane-Bound Tnf-Α Triggers Tumorigenic Inflammation In Neuroblastoma, Julie A Tomolonis, Xin Xu, Kshiti H Dholakia, Chunchao Zhang, Linjie Guo, Amy N Courtney, Siyue Wang, Julien Balzeau, Gabriel A Barragán, Gengwen Tian, Erica J Di Pierro, Leonid S Metelitsa

Faculty, Staff and Students Publications

BACKGROUND: Tumor progression and resistance to therapy in children with neuroblastoma (NB), a common childhood cancer, are often associated with infiltration of monocytes and macrophages that produce inflammatory cytokines. However, the mechanism by which tumor-supportive inflammation is initiated and propagated remains unknown. Here, we describe a novel protumorigenic circuit between NB cells and monocytes that is triggered and sustained by tumor necrosis factor alpha (TNF-α).

METHODS: We used NB knockouts (KOs) of TNF-α and

RESULTS: We found that NB expression of TNFR2 and monocyte membrane-bound tumor necrosis factor alpha is required for monocyte activation and interleukin (IL)-6 production, while NB …


Trends In Up-To-Date Colorectal Cancer Screening Among Us Adults Aged 50-75 Years And Variations By Race/Ethnicity And Us Census Bureau Divisions, Itunu O Sokale, Omar Rosales, Jane R Montealegre, Abiodun O Oluyomi, Aaron P Thrift Mar 2023

Trends In Up-To-Date Colorectal Cancer Screening Among Us Adults Aged 50-75 Years And Variations By Race/Ethnicity And Us Census Bureau Divisions, Itunu O Sokale, Omar Rosales, Jane R Montealegre, Abiodun O Oluyomi, Aaron P Thrift

Faculty, Staff and Students Publications

INTRODUCTION: Mortality rates from colorectal cancer have declined over the past decades owing to population-based life-saving screening interventions. However, screening inequalities continue among racial and ethnic minorities despite having a higher disease burden. In this study, we assessed the patterns of up-to-date colorectal cancer screening rates among racial/ethnic groups across the U.S. Census Bureau Divisions.

METHODS: This population-based cross-sectional study used weighted data from 4 cycles of the Behavioral Risk Factors Surveillance System (2014, 2016, 2018, and 2020) of adults aged 50‒75 years without a previous diagnosis of colorectal cancer. The primary outcome was guideline-recommended up-to-date colorectal cancer screening. We …


A Tripartite View Of The Posterior Cingulate Cortex, Brett L Foster, Seth R Koslov, Lyndsey Aponik-Gremillion, Megan E Monko, Benjamin Y Hayden, Sarah R Heilbronner Mar 2023

A Tripartite View Of The Posterior Cingulate Cortex, Brett L Foster, Seth R Koslov, Lyndsey Aponik-Gremillion, Megan E Monko, Benjamin Y Hayden, Sarah R Heilbronner

Faculty, Staff and Students Publications

The posterior cingulate cortex (PCC) is one of the least understood regions of the cerebral cortex. By contrast, the anterior cingulate cortex has been the subject of intensive investigation in humans and model animal systems, leading to detailed behavioural and computational theoretical accounts of its function. The time is right for similar progress to be made in the PCC given its unique anatomical and physiological properties and demonstrably important contributions to higher cognitive functions and brain diseases. Here, we describe recent progress in understanding the PCC, with a focus on convergent findings across species and techniques that lay a foundation …


Fetal Nephrology: A Quaternary Care Center Experience, Auda M Plaud Gonzalez, Catherine Joseph, Samantha R Stover, Ahmed Nassr, Chester J Koh, Joseph R Angelo, Michael C Braun Mar 2023

Fetal Nephrology: A Quaternary Care Center Experience, Auda M Plaud Gonzalez, Catherine Joseph, Samantha R Stover, Ahmed Nassr, Chester J Koh, Joseph R Angelo, Michael C Braun

Faculty, Staff and Students Publications

Background: Congenital anomalies of the kidney and urinary tract (CAKUTs) represent 15%–20% of prenatally diagnosed abnormalities. Maternal characteristics, the frequency of various forms of kidney disease including CAKUT referred for prenatal nephrology consultation, and their perinatal outcomes are less well defined.

Methods: A retrospective chart review was performed of fetal CAKUT and other forms of kidney disease referred for prenatal nephrology consults at Texas Children's Hospital Fetal Center from January 1, 2012, to December 31, 2018.

Results: Two hundred seventeen prenatal nephrology consultations were performed during the study period, representing 4.7% of total Fetal Center referrals at a mean estimated …


Ferroptosis In Life: To Be Or Not To Be, Ling Xu, Yu'e Liu, Xi Chen, Hua Zhong, Yi Wang Mar 2023

Ferroptosis In Life: To Be Or Not To Be, Ling Xu, Yu'e Liu, Xi Chen, Hua Zhong, Yi Wang

Faculty, Staff and Students Publications

Ferroptosis is a novel type of programmed cell death, characterized by a dysregulated iron metabolism and accumulation of lipid peroxides. It features the alteration of mitochondria and aberrant accumulation of excessive iron as well as loss of the cysteine-glutathione-GPX4 axis. Eventually, the accumulated lipid peroxides result in lethal damage to the cells. Ferroptosis is induced by the overloading of iron and the accumulation of ROS and can be inhibited by the activation of the GPX4 pathway, FS1-CoQ10 pathway, GCH1-BH4 pathway, and the DHODH pathway, it is also regulated by the oncogenes and tumor suppressors. Ferroptosis involves various physiological and pathological …


Patterns Of Co-Occurring Birth Defects In Children With Anotia And Microtia, Jeremy M Schraw, Renata H Benjamin, Charles J Shumate, Mark A Canfield, Daryl A Scott, Scott D Mclean, Hope Northrup, Angela E Scheuerle, Christian P Schaaf, Joseph W Ray, Han Chen, A J Agopian, Philip J Lupo Mar 2023

Patterns Of Co-Occurring Birth Defects In Children With Anotia And Microtia, Jeremy M Schraw, Renata H Benjamin, Charles J Shumate, Mark A Canfield, Daryl A Scott, Scott D Mclean, Hope Northrup, Angela E Scheuerle, Christian P Schaaf, Joseph W Ray, Han Chen, A J Agopian, Philip J Lupo

Faculty, Staff and Student Publications

Many infants with anotia or microtia (A/M) have co-occurring birth defects, although few receive syndromic diagnoses in the perinatal period. Evaluation of co-occurring birth defects in children with A/M could identify patterns indicative of undiagnosed/unrecognized syndromes. We obtained information on co-occurring birth defects among infants with A/M for delivery years 1999-2014 from the Texas Birth Defects Registry. We calculated observed-to-expected ratios (OER) to identify birth defect combinations that occurred more often than expected by chance. We excluded children diagnosed with genetic or chromosomal syndromes from analyses. Birth defects and syndromes/associations diagnosed ≤1 year of age were considered. We identified 1310 …


Urinary Cd163 Is A Marker Of Active Kidney Disease In Childhood-Onset Lupus Nephritis, Haleigh Inthavong, Kamala Vanarsa, Jessica Castillo, M John Hicks, Chandra Mohan, Scott E Wenderfer Mar 2023

Urinary Cd163 Is A Marker Of Active Kidney Disease In Childhood-Onset Lupus Nephritis, Haleigh Inthavong, Kamala Vanarsa, Jessica Castillo, M John Hicks, Chandra Mohan, Scott E Wenderfer

Faculty, Staff and Students Publications

OBJECTIVE: The objective of this study was to evaluate the utility of urine CD163 for detecting disease activity in childhood-onset SLE (cSLE) patients.

METHODS: Sixty consecutive pediatric patients fulfilling four or more ACR criteria for SLE and 20 healthy controls were recruited for testing of urinary CD163 using ELISA. SLE disease activity was assessed using the SLEDAI-2K.

RESULTS: Urine CD163 was significantly higher in patients with active LN than inactive SLE patients and healthy controls, with receiver operating characteristics area under the curve values ranging from 0.93 to 0.96. LN was ascertained by kidney biopsy. Levels of CD163 significantly correlated …


Corrigendum To 'The Hemophilia Joint Health Score Version 21 Validation In Adult Patients Study: A Multicenter International Study' [Research And Practice In Thrombosis And Haemostasis, 6/2, (2022) E12690], Adrian Minford, Leonardo R Brand Ao, Maha Othman, Christoph Male, Rezan Abdul-Kadir, Paul Monagle, Andrew D Mumford, Dorothy Adcock, Björn Dahlbäck, Predrag Miljic, Maria T Desancho, Jun Teruya Mar 2023

Corrigendum To 'The Hemophilia Joint Health Score Version 21 Validation In Adult Patients Study: A Multicenter International Study' [Research And Practice In Thrombosis And Haemostasis, 6/2, (2022) E12690], Adrian Minford, Leonardo R Brand Ao, Maha Othman, Christoph Male, Rezan Abdul-Kadir, Paul Monagle, Andrew D Mumford, Dorothy Adcock, Björn Dahlbäck, Predrag Miljic, Maria T Desancho, Jun Teruya

Faculty, Staff and Students Publications

This corrects the article "The Hemophilia Joint Health Score version 2.1 Validation in Adult Patients Study: A multicenter international study" in volume 6, e12690.


Community-Onset Bacterial Coinfection In Children Critically Ill With Severe Acute Respiratory Syndrome Coronavirus 2 Infection, Kristin L Moffitt, Mari M Nakamura, Cameron C Young, Margaret M Newhams, Natasha B Halasa, J Nelson Reed, Julie C Fitzgerald, Philip C Spinella, Vijaya L Soma, Tracie C Walker, Laura L Loftis, Aline B Maddux, Michele Kong, Courtney M Rowan, Charlotte V Hobbs, Jennifer E Schuster, Becky J Riggs, Gwenn E Mclaughlin, Kelly N Michelson, Mark W Hall, Christopher J Babbitt, Natalie Z Cvijanovich, Matt S Zinter, Mia Maamari, Adam J Schwarz, Aalok R Singh, Heidi R Flori, Shira J Gertz, Mary A Staat, John S Giuliano, Saul R Hymes, Katharine N Clouser, John Mcguire, Christopher L Carroll, Neal J Thomas, Emily R Levy, Adrienne G Randolph Mar 2023

Community-Onset Bacterial Coinfection In Children Critically Ill With Severe Acute Respiratory Syndrome Coronavirus 2 Infection, Kristin L Moffitt, Mari M Nakamura, Cameron C Young, Margaret M Newhams, Natasha B Halasa, J Nelson Reed, Julie C Fitzgerald, Philip C Spinella, Vijaya L Soma, Tracie C Walker, Laura L Loftis, Aline B Maddux, Michele Kong, Courtney M Rowan, Charlotte V Hobbs, Jennifer E Schuster, Becky J Riggs, Gwenn E Mclaughlin, Kelly N Michelson, Mark W Hall, Christopher J Babbitt, Natalie Z Cvijanovich, Matt S Zinter, Mia Maamari, Adam J Schwarz, Aalok R Singh, Heidi R Flori, Shira J Gertz, Mary A Staat, John S Giuliano, Saul R Hymes, Katharine N Clouser, John Mcguire, Christopher L Carroll, Neal J Thomas, Emily R Levy, Adrienne G Randolph

Faculty, Staff and Students Publications

BACKGROUND: Community-onset bacterial coinfection in adults hospitalized with coronavirus disease 2019 (COVID-19) is reportedly uncommon, though empiric antibiotic use has been high. However, data regarding empiric antibiotic use and bacterial coinfection in children with critical illness from COVID-19 are scarce.

METHODS: We evaluated children and adolescents agedadmission, we adjudicated whether patients had community-onset bacterial coinfection. We compared demographic and clinical characteristics of those who did and did not (1) receive antibiotics and (2) have bacterial coinfection early in admission. Using Poisson regression models, we assessed factors associated with these outcomes.

RESULTS: Of the 532 patients, 63.3% received empiric antibiotics, but …


Systemic Inflammatory Markers And Eeg Features Of Children With Fires Receiving Anakinra, Yi-Chen Lai, Gabriella Abou-El-Kheir, Thao Nguyen, Margo Hanerhoff, James J Riviello, Eyal Muscal Mar 2023

Systemic Inflammatory Markers And Eeg Features Of Children With Fires Receiving Anakinra, Yi-Chen Lai, Gabriella Abou-El-Kheir, Thao Nguyen, Margo Hanerhoff, James J Riviello, Eyal Muscal

Faculty, Staff and Students Publications

In a retrospective case series of 10 children with cryptogenic FIRES, we sought to describe the early clinical course and potential biomarkers following anakinra initiation. Six children achieved anesthetic withdrawal within 3 weeks of therapy and one in week four. Of the available cEEG (six children), CRP (10 children), and serum cytokine (six children) studies, there were temporal changes in highly epileptiform bursts (observed in three children), CRP, IL-6, and IL-10 levels that might parallel clinical progression. These observations may represent candidate biomarkers for monitoring clinical progression and therapeutic interventions including anakinra, which merits further investigation in future studies.


2022 American College Of Rheumatology Guideline For Vaccinations In Patients With Rheumatic And Musculoskeletal Diseases, Anne R Bass, Eliza Chakravarty, Elie A Akl, Clifton O Bingham, Leonard Calabrese, Laura C Cappelli, Sindhu R Johnson, Lisa F Imundo, Kevin L Winthrop, Reuben J Arasaratnam, Lindsey R Baden, Roberta Berard, S Louis Bridges, Jonathan T L Cheah, Jeffrey R Curtis, Polly J Ferguson, Ida Hakkarinen, Karen B Onel, Grayson Schultz, Vidya Sivaraman, Benjamin J Smith, Jeffrey A Sparks, Tiphanie P Vogel, Eleanor Anderson Williams, Cassandra Calabrese, Joanne S Cunha, Joann Fontanarosa, Miriah C Gillispie-Taylor, Elena Gkrouzman, Priyanka Iyer, Kimberly S Lakin, Alexandra Legge, Mindy S Lo, Megan M Lockwood, Rebecca E Sadun, Namrata Singh, Nancy Sullivan, Herman Tam, Marat Turgunbaev, Amy S Turner, James Reston Mar 2023

2022 American College Of Rheumatology Guideline For Vaccinations In Patients With Rheumatic And Musculoskeletal Diseases, Anne R Bass, Eliza Chakravarty, Elie A Akl, Clifton O Bingham, Leonard Calabrese, Laura C Cappelli, Sindhu R Johnson, Lisa F Imundo, Kevin L Winthrop, Reuben J Arasaratnam, Lindsey R Baden, Roberta Berard, S Louis Bridges, Jonathan T L Cheah, Jeffrey R Curtis, Polly J Ferguson, Ida Hakkarinen, Karen B Onel, Grayson Schultz, Vidya Sivaraman, Benjamin J Smith, Jeffrey A Sparks, Tiphanie P Vogel, Eleanor Anderson Williams, Cassandra Calabrese, Joanne S Cunha, Joann Fontanarosa, Miriah C Gillispie-Taylor, Elena Gkrouzman, Priyanka Iyer, Kimberly S Lakin, Alexandra Legge, Mindy S Lo, Megan M Lockwood, Rebecca E Sadun, Namrata Singh, Nancy Sullivan, Herman Tam, Marat Turgunbaev, Amy S Turner, James Reston

Faculty, Staff and Students Publications

OBJECTIVE: To provide evidence-based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs).

METHODS: This guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review …


Novel And Replicated Clinical And Genetic Risk Factors For Toxicity From High-Dose Methotrexate In Pediatric Acute Lymphoblastic Leukemia, Mark Zobeck, M Brooke Bernhardt, Kala Y Kamdar, Karen R Rabin, Philip J Lupo, Michael E Scheurer Mar 2023

Novel And Replicated Clinical And Genetic Risk Factors For Toxicity From High-Dose Methotrexate In Pediatric Acute Lymphoblastic Leukemia, Mark Zobeck, M Brooke Bernhardt, Kala Y Kamdar, Karen R Rabin, Philip J Lupo, Michael E Scheurer

Faculty, Staff and Students Publications

STUDY OBJECTIVE: Methotrexate (MTX) is a key component of treatment for high-risk pediatric acute lymphoblastic leukemia (ALL) but may cause acute kidney injury and prolonged hospitalization due to delayed clearance. The purpose of this study is to identify clinical and genetic factors that may predict which children are at risk for creatinine increase and prolonged MTX clearance.

DESIGN: We conducted a single-center, retrospective cohort study of pediatric patients with ALL who received 4000-5000 mg/m

MAIN RESULTS: Hispanic ethnicity, body mass index (BMI) < 3%, BMI between 85%-95%, and Native American genetic ancestry were found to be associated with an increased risk for creatinine elevation. Older age, Black race, and use of the intensive monitoring protocol were associated with a decreased risk for creatinine elevation. Older age, B- compared to T-ALL, and the minor alleles of rs2838958/SLC19A1 and rs7317112/ABCC4 were associated with an increased risk for delayed clearance. Black race, MTX dose reduction, and the minor allele of rs2306283/SLCO1B1 were found to be associated with a decreased risk for delayed clearance.

CONCLUSIONS: These predictors of MTX toxicities may allow for more precise individualized toxicity risk prediction.


Bayesian Non-Homogeneous Hidden Markov Model With Variable Selection For Investigating Drivers Of Seizure Risk Cycling, Emily T Wang, Sharon Chiang, Zulfi Haneef, Vikram R Rao, Robert Moss, Marina Vannucci Mar 2023

Bayesian Non-Homogeneous Hidden Markov Model With Variable Selection For Investigating Drivers Of Seizure Risk Cycling, Emily T Wang, Sharon Chiang, Zulfi Haneef, Vikram R Rao, Robert Moss, Marina Vannucci

Faculty, Staff and Students Publications

A major issue in the clinical management of epilepsy is the unpredictability of seizures. Yet, traditional approaches to seizure forecasting and risk assessment in epilepsy rely heavily on raw seizure frequencies, which are a stochastic measurement of seizure risk. We consider a Bayesian non-homogeneous hidden Markov model for unsupervised clustering of zero-inflated seizure count data. The proposed model allows for a probabilistic estimate of the sequence of seizure risk states at the individual level. It also offers significant improvement over prior approaches by incorporating a variable selection prior for the identification of clinical covariates that drive seizure risk changes and …


Robust Deep Learning Object Recognition Models Rely On Low Frequency Information In Natural Images, Zhe Li, Josue Ortega Caro, Evgenia Rusak, Wieland Brendel, Matthias Bethge, Fabio Anselmi, Ankit B Patel, Andreas S Tolias, Xaq Pitkow Mar 2023

Robust Deep Learning Object Recognition Models Rely On Low Frequency Information In Natural Images, Zhe Li, Josue Ortega Caro, Evgenia Rusak, Wieland Brendel, Matthias Bethge, Fabio Anselmi, Ankit B Patel, Andreas S Tolias, Xaq Pitkow

Faculty, Staff and Students Publications

Machine learning models have difficulty generalizing to data outside of the distribution they were trained on. In particular, vision models are usually vulnerable to adversarial attacks or common corruptions, to which the human visual system is robust. Recent studies have found that regularizing machine learning models to favor brain-like representations can improve model robustness, but it is unclear why. We hypothesize that the increased model robustness is partly due to the low spatial frequency preference inherited from the neural representation. We tested this simple hypothesis with several frequency-oriented analyses, including the design and use of hybrid images to probe model …


Developing A Parsimonious Frailty Index For Older, Multimorbid Adults With Heart Failure Using Machine Learning, Javad Razjouyan, Molly J Horstman, Ariela R Orkaby, Salim S Virani, Orna Intrator, Parag Goyal, Christopher I Amos, Aanand D Naik Mar 2023

Developing A Parsimonious Frailty Index For Older, Multimorbid Adults With Heart Failure Using Machine Learning, Javad Razjouyan, Molly J Horstman, Ariela R Orkaby, Salim S Virani, Orna Intrator, Parag Goyal, Christopher I Amos, Aanand D Naik

Faculty, Staff and Student Publications

Frailty is associated with adverse outcomes in heart failure (HF). A parsimonious frailty index (FI) that predicts outcomes of older, multimorbid patients with HF could be a useful resource for clinicians. A retrospective study of veterans hospitalized from October 2015 to October 2018 with HF, aged ≥50 years, and discharged home developed a 10-item parsimonious FI using machine learning from diagnostic codes, laboratory results, vital signs, and ejection fraction (EF) from outpatient encounters. An unsupervised clustering technique identified 5 FI strata: severely frail, moderately frail, mildly frail, prefrail, and robust. We report hazard ratios (HRs) of mortality, adjusting for age, …


Egr1 Drives Cell Proliferation By Directly Stimulating Tfeb Transcription In Response To Starvation, Marcella Cesana, Gennaro Tufano, Francesco Panariello, Nicolina Zampelli, Susanna Ambrosio, Rossella De Cegli, Margherita Mutarelli, Lorenzo Vaccaro, Micheal J Ziller, Davide Cacchiarelli, Diego L Medina, Andrea Ballabio Mar 2023

Egr1 Drives Cell Proliferation By Directly Stimulating Tfeb Transcription In Response To Starvation, Marcella Cesana, Gennaro Tufano, Francesco Panariello, Nicolina Zampelli, Susanna Ambrosio, Rossella De Cegli, Margherita Mutarelli, Lorenzo Vaccaro, Micheal J Ziller, Davide Cacchiarelli, Diego L Medina, Andrea Ballabio

Duncan NRI Faculty and Staff Publications

The stress-responsive transcription factor EB (TFEB) is a master controller of lysosomal biogenesis and autophagy and plays a major role in several cancer-associated diseases. TFEB is regulated at the posttranslational level by the nutrient-sensitive kinase complex mTORC1. However, little is known about the regulation of TFEB transcription. Here, through integrative genomic approaches, we identify the immediate-early gene EGR1 as a positive transcriptional regulator of TFEB expression in human cells and demonstrate that, in the absence of EGR1, TFEB-mediated transcriptional response to starvation is impaired. Remarkably, both genetic and pharmacological inhibition of EGR1, using the MEK1/2 inhibitor Trametinib, significantly reduced the …


Mortality Patterns Associated With Central Sleep Apnea Among Veterans: A Large, Retrospective, Longitudinal Report, Ritwick Agrawal, Amir Sharafkhaneh, Daniel J Gottlieb, Sara Nowakowski, Javad Razjouyan Mar 2023

Mortality Patterns Associated With Central Sleep Apnea Among Veterans: A Large, Retrospective, Longitudinal Report, Ritwick Agrawal, Amir Sharafkhaneh, Daniel J Gottlieb, Sara Nowakowski, Javad Razjouyan

Faculty, Staff and Students Publications

Rationale

Central sleep apnea (CSA) is associated with high mortality. Current knowledge stems from studies with limited sample size (fewer than 100 subjects) and in homogeneous populations such as heart failure (HF).

Objectives

To address this knowledge gap, we compared the mortality pattern and time to death between the CSA and obstructive sleep apnea (OSA) patients in the large Veterans Health Administration patient population using the big data analytic approach.

Methods

This is a retrospective study using national Veterans Health Administration electronic medical records from October 1, 1999, through September 30, 2020. We grouped the patients with underlying sleep disorders …


High Molecular Diagnostic Yields And Novel Phenotypic Expansions Involving Syndromic Anorectal Malformations, Raymond Belanger Deloge, Xiaonan Zhao, Pamela N Luna, Chad A Shaw, Jill A Rosenfeld, Daryl A Scott Mar 2023

High Molecular Diagnostic Yields And Novel Phenotypic Expansions Involving Syndromic Anorectal Malformations, Raymond Belanger Deloge, Xiaonan Zhao, Pamela N Luna, Chad A Shaw, Jill A Rosenfeld, Daryl A Scott

Faculty, Staff and Students Publications

Evidence suggests that genetic factors contribute to the development of anorectal malformations (ARMs). However, the etiology of the majority of ARMs cases remains unclear. Exome sequencing (ES) may be underutilized in the diagnostic workup of ARMs due to uncertainty regarding its diagnostic yield. In a clinical database of ~17,000 individuals referred for ES, we identified 130 individuals with syndromic ARMs. A definitive or probable diagnosis was made in 45 of these individuals for a diagnostic yield of 34.6% (45/130). The molecular diagnostic yield of individuals who initially met criteria for VACTERL association was lower than those who did not (26.8% …


Longitudinal Changes In Fibrosis Markers Are Associated With Risk Of Cirrhosis And Hepatocellular Carcinoma In Non-Alcoholic Fatty Liver Disease, George Cholankeril, Jennifer R Kramer, Jinna Chu, Xian Yu, Maya Balakrishnan, Liang Li, Hashem B El-Serag, Fasiha Kanwal Mar 2023

Longitudinal Changes In Fibrosis Markers Are Associated With Risk Of Cirrhosis And Hepatocellular Carcinoma In Non-Alcoholic Fatty Liver Disease, George Cholankeril, Jennifer R Kramer, Jinna Chu, Xian Yu, Maya Balakrishnan, Liang Li, Hashem B El-Serag, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Currently, there is no consistent information on the course of fibrosis-4 (FIB-4) score changes in non-alcoholic fatty liver disease (NAFLD) or their association with subsequent risk of cirrhosis and/or hepatocellular carcinoma (HCC). Thus, we aimed to evaluate the association between longitudinal changes in FIB-4 and subsequent risk of HCC and a composite endpoint of cirrhosis and HCC in patients with NAFLD.

METHODS: We conducted a retrospective cohort study of patients with NAFLD seen in 130 Veterans Administration hospitals between 1/1/2004-12/31/2008, with follow-up through to 12/31/2018. We calculated FIB-4 longitudinally and categorized patients based on risk of advanced …


Electronic Health Records' Support For Primary Care Physicians' Situation Awareness: A Metanarrative Review, April Savoy, Himalaya Patel, Daniel R Murphy, Ashley N D Meyer, Jennifer Herout, Hardeep Singh Mar 2023

Electronic Health Records' Support For Primary Care Physicians' Situation Awareness: A Metanarrative Review, April Savoy, Himalaya Patel, Daniel R Murphy, Ashley N D Meyer, Jennifer Herout, Hardeep Singh

Faculty, Staff and Students Publications

OBJECTIVE: Situation awareness (SA) refers to people's perception and understanding of their dynamic environment. In primary care, reduced SA among physicians increases errors in clinical decision-making and, correspondingly, patients' risk of experiencing adverse outcomes. Our objective was to understand the extent to which electronic health records (EHRs) support primary care physicians (PCPs)' SA during clinical decision-making.

METHOD: We conducted a metanarrative review of papers in selected academic databases, including CINAHL and MEDLINE. Eligible studies included original peer-reviewed research published between January 2012 and August 2020 on PCP-EHR interactions. We iteratively queried, screened, and summarized literature focused on EHRs supporting PCPs' …


Antihypertensive Medication Regimens Used In The Systolic Blood Pressure Intervention Trial, Catherine G Derington, Adam P Bress, Andrew E Moran, William S Weintraub, Jennifer S Herrick, William C Cushman, Ian M Kronish, Barry Stults, Daichi Shimbo, Paul Muntner, Tom Greene, Jeffrey T Bates, Tara I Chang, Lois Anne Katz, Shakaib U Rehman, Christianne L Roumie, Leonardo Tamariz, Jordan B King Mar 2023

Antihypertensive Medication Regimens Used In The Systolic Blood Pressure Intervention Trial, Catherine G Derington, Adam P Bress, Andrew E Moran, William S Weintraub, Jennifer S Herrick, William C Cushman, Ian M Kronish, Barry Stults, Daichi Shimbo, Paul Muntner, Tom Greene, Jeffrey T Bates, Tara I Chang, Lois Anne Katz, Shakaib U Rehman, Christianne L Roumie, Leonardo Tamariz, Jordan B King

Faculty, Staff and Students Publications

BACKGROUND: Describing the antihypertensive medication regimens used in the SPRINT (Systolic Blood Pressure Intervention Trial) would contextualize the standard and intensive systolic blood pressure (SBP) interventions and may inform future implementation efforts to achieve population-wide intensive SBP goals.

METHODS: We included SPRINT participants with complete medication data at the prerandomization and 12-month visits. Regimens were categorized by antihypertensive medication class. Analyses were stratified by treatment group (standard goal SBPHg).

RESULTS: Among 7860 participants (83.7% of 9361 randomized), the median number of classes used at the prerandomization visit was 2.0 and 2.0 in the standard and intensive groups (

CONCLUSIONS: SPRINT …


Role Of Biomarkers (Sflt-1/Plgf) In Cases Of Covid-19 For Distinguishing Preeclampsia And Guiding Clinical Management, Guilherme M Nobrega, Jose P Guida, Juliana M Novaes, Larissa M Solda, Luciana Pietro, Adriana G Luz, Giuliane J Lajos, Carolina C Ribeiro-Do-Valle, Renato T Souza, Jose G Cecatti, Indira U Mysorekar, Tabata Z Dias, Maria Laura Costa Mar 2023

Role Of Biomarkers (Sflt-1/Plgf) In Cases Of Covid-19 For Distinguishing Preeclampsia And Guiding Clinical Management, Guilherme M Nobrega, Jose P Guida, Juliana M Novaes, Larissa M Solda, Luciana Pietro, Adriana G Luz, Giuliane J Lajos, Carolina C Ribeiro-Do-Valle, Renato T Souza, Jose G Cecatti, Indira U Mysorekar, Tabata Z Dias, Maria Laura Costa

Faculty, Staff and Students Publications

OBJECTIVES: To analyze soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factors (PlGF) concentrations and their ratio in pregnant and postpartum women with suspected COVID-19, and further investigate conditions associated with an increased ratio (sFlt-1/PlGF > 38), including preeclampsia (PE) and severe acute respiratory syndrome (SARS).

STUDY DESIGN: The present study is a secondary analysis of a prospective cohort. Blood samples were collected at time of COVID-19 investigation and the serum measurements of sFlt-1 and PlGF were performed. Clinical background, SARS-CoV-2 infection characteristics, maternal and perinatal outcomes were further analyzed.

MAIN OUTCOME MEASURES: Serum measurements of sFlt-1 and PlGF; obstetrics …


Bacteremia Due To Non-Staphylococcus Aureus Gram-Positive Cocci And Risk Of Cardiovascular Implantable Electronic Device Infection, Supavit Chesdachai, Larry M Baddour, M Rizwan Sohail, Bharath Raj Palraj, Malini Madhavan, Hussam Tabaja, Madiha Fida, Brian D Lahr, Daniel C Desimone Mar 2023

Bacteremia Due To Non-Staphylococcus Aureus Gram-Positive Cocci And Risk Of Cardiovascular Implantable Electronic Device Infection, Supavit Chesdachai, Larry M Baddour, M Rizwan Sohail, Bharath Raj Palraj, Malini Madhavan, Hussam Tabaja, Madiha Fida, Brian D Lahr, Daniel C Desimone

Faculty, Staff and Students Publications

BACKGROUND: Cardiovascular implantable electronic device (CIED) infection carries significant morbidity and mortality with bacteremia being a possible marker of device infection. A clinical profile of non-Staphylococcus aureus gram-positive cocci (non-SA GPC) bacteremia in patients with CIED has been limited.

OBJECTIVE: To examine characteristics of patients with CIED who developed non-SA GPC bacteremia and risk of CIED infection.

METHODS: We reviewed all patients with CIED who developed non-SA GPC bacteremia at the Mayo Clinic between 2012 and 2019. The 2019 European Heart Rhythm Association Consensus Document was used to define CIED infection.

RESULTS: A total of 160 patients with CIED …


Juvenile-Type Granulosa Cell Tumor In Pregnancy Presenting As A Ruptured Abdominal Mass, Odinaka Mogor, Steven Feinstein, Glen Friedman, Jose Salvador Saldivar, Melissa Mendez Feb 2023

Juvenile-Type Granulosa Cell Tumor In Pregnancy Presenting As A Ruptured Abdominal Mass, Odinaka Mogor, Steven Feinstein, Glen Friedman, Jose Salvador Saldivar, Melissa Mendez

HCA Healthcare Journal of Medicine

Introduction

Granulosa cell tumors (GCTs) are part of the sex cord-stromal tumors occurring with a rare incidence rate that only makes up about 2-5% of all ovarian malignancies.

Case Presentation

A 28-year-old woman, gravida 2, para 1, presented with a juvenile-type granulosa cell tumor at 31 weeks gestation, which appeared as a rapidly growing mass with rupture. She underwent an exploratory laparotomy with unilateral salpingo-oophorectomy, and consequently had a successful vaginal delivery. Post-operatively she was treated with paclitaxel and carboplatin chemotherapy regimen with no evidence of recurrence after one year.

Conclusion

Radical surgical management is recommended for these tumors due …


Calciphylaxis, A Case Series: The Importance Of Early Detection, Nikita Sijapati, Suy Sen Hung Fong, Omar Ansari, Subhasis Misra, Edgar Mercado, My Myers, Vijay Narasimha Feb 2023

Calciphylaxis, A Case Series: The Importance Of Early Detection, Nikita Sijapati, Suy Sen Hung Fong, Omar Ansari, Subhasis Misra, Edgar Mercado, My Myers, Vijay Narasimha

HCA Healthcare Journal of Medicine

Introduction

Calciphylaxis is a rare disorder that involves the formation of cutaneous, subcutaneous, and vascular calcifications. Although it is predominantly seen in patients with end-stage renal disease (ESRD), it has also been reported in patients without chronic kidney disease. The presence of multiple risk factors, a poorly understood mechanism, high mortality, and the lack of standardized treatment make calciphylaxis an important subject.

Case Presentation

We describe the clinical presentation, disease course, and management of 3 patients with calciphylaxis and also provide a literature review. In all 3 patients, the diagnosis was confirmed histologically, and the management involved the continuation of …


Complications Of Cardiopulmonary Bypass From An Anesthesia Perspective: A Clinical Review, Alex Roberts, Elizabeth C. Duncan, Paul Hargrave, David Redding Kingery, Josh Barnes, Derek L. Horstemeyer, Russell F. Stahl Feb 2023

Complications Of Cardiopulmonary Bypass From An Anesthesia Perspective: A Clinical Review, Alex Roberts, Elizabeth C. Duncan, Paul Hargrave, David Redding Kingery, Josh Barnes, Derek L. Horstemeyer, Russell F. Stahl

HCA Healthcare Journal of Medicine

Cardiopulmonary bypass (CPB) is frequently used for open heart surgery and other procedures that utilize temporary substitution or support of heart and lung function. While it is widely accepted as the predominant method to carry out these procedures, it is not without possible complications. CPB can be seen as the ultimate “team sport” as it includes and is dependent on contributions from multiple professionals including anesthesiologists, cardiothoracic surgeons, and perfusion technicians. In this clinical review paper, we examine possible complications of CPB, primarily from the perspective of the anesthesiologist, and how to troubleshoot them if they arise, which often requires …


The Legal Limits Of Parental Autonomy: Do Parents Have The Right To Refuse Intramuscular Vitamin K For Their Newborn?, Shannon M. Isennock Feb 2023

The Legal Limits Of Parental Autonomy: Do Parents Have The Right To Refuse Intramuscular Vitamin K For Their Newborn?, Shannon M. Isennock

HCA Healthcare Journal of Medicine

The American Academy of Pediatrics recommends that all newborns receive an intramuscular (IM) dose of vitamin K within 6 hours of delivery for the prevention of vitamin K deficiency bleeding (VKDB). There has been an increase in the number of parents who have refused the IM vitamin K dose for their infant based on its possible link to leukemia, preservatives that may lead to adverse reactions, and wanting to avoid pain for the infant. When newborns do not receive IM vitamin K, the most serious feared potential complication is intracranial hemorrhage with potential neurologic sequela including seizures, developmental delay, and …


Determinants And Mechanisms Of The Low Fusogenicity And High Dependence On Endosomal Entry Of Omicron Subvariants, Panke Qu, John P Evans, Chaitanya Kurhade, Cong Zeng, Yi-Min Zheng, Kai Xu, Pei-Yong Shi, Xuping Xie, Shan-Lu Liu Feb 2023

Determinants And Mechanisms Of The Low Fusogenicity And High Dependence On Endosomal Entry Of Omicron Subvariants, Panke Qu, John P Evans, Chaitanya Kurhade, Cong Zeng, Yi-Min Zheng, Kai Xu, Pei-Yong Shi, Xuping Xie, Shan-Lu Liu

Faculty, Staff and Student Publications

The rapid spread and strong immune evasion of the SARS-CoV-2 Omicron subvariants has raised serious concerns for the global COVID-19 pandemic. These new variants exhibit generally reduced fusogenicity and increased endosomal entry pathway utilization compared to the ancestral D614G variant, the underlying mechanisms of which remain elusive. Here, we show that the C-terminal S1 mutations of the BA.1.1 subvariant, H655Y and T547K, critically govern the low fusogenicity of Omicron. Notably, H655Y also dictates the enhanced endosome entry pathway utilization. Mechanistically, T547K and H655Y likely stabilize the spike trimer conformation as suggested by increased molecular interactions in structural modeling and enhanced …