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Full-Text Articles in Medical Specialties

Neprilysin Inhibitors In Heart Failure: The Science, Mechanism Of Action, Clinical Studies, And Unanswered Questions, Biykem Bozkurt, Ajith P Nair, Arunima Misra, Claire Z Scott, Jamal H Mahar, Savitri Fedson Jan 2023

Neprilysin Inhibitors In Heart Failure: The Science, Mechanism Of Action, Clinical Studies, And Unanswered Questions, Biykem Bozkurt, Ajith P Nair, Arunima Misra, Claire Z Scott, Jamal H Mahar, Savitri Fedson

Faculty, Staff and Students Publications

This article provides a contemporary review and a new perspective on the role of neprilysin inhibition in heart failure (HF) in the context of recent clinical trials and addresses potential mechanisms and unanswered questions in certain HF patient populations. Neprilysin is an endopeptidase that cleaves a variety of peptides such as natriuretic peptides, bradykinin, adrenomedullin, substance P, angiotensin I and II, and endothelin. It has a broad role in cardiovascular, renal, pulmonary, gastrointestinal, endocrine, and neurologic functions. The combined angiotensin receptor and neprilysin inhibitor (ARNi) has been developed with an intent to increase vasodilatory natriuretic peptides and prevent counterregulatory activation …


Impact Of Gastrointestinal Polymerase Chain Reaction Panels On Antibiotic Utilization In Hospitalized Adult Patients, Gillean A Kelly, Roumen Iordanov, Alex Franklin, Amna Ahmed, Krithika Srinivasan, Jesica Hayon, Todd Lasco, Rosie Amini, Sabra Shay, Prathit A Kulkarni, Mayar Al Mohajer Jan 2023

Impact Of Gastrointestinal Polymerase Chain Reaction Panels On Antibiotic Utilization In Hospitalized Adult Patients, Gillean A Kelly, Roumen Iordanov, Alex Franklin, Amna Ahmed, Krithika Srinivasan, Jesica Hayon, Todd Lasco, Rosie Amini, Sabra Shay, Prathit A Kulkarni, Mayar Al Mohajer

Faculty, Staff and Students Publications

Multiplex stool polymerase chain reaction (PCR) panels offer rapid comprehensive testing for patients with infectious diarrhea. We compared antibiotic utilization among hospitalized patients with suspected infectious diarrhea who underwent diagnostic testing with either a stool culture or stool PCR panel. No significant differences in antibiotic utilization were identified.


Treatment Of Severe Covid-19 Infection With Remdesivir In Peritoneal Dialysis, Ryan Geffin, Shazia Raheem, Lavannya M Pandit, Andrew S Hunter, Michael W Holliday, Aditya V Rao, Maulin K Shah Jan 2023

Treatment Of Severe Covid-19 Infection With Remdesivir In Peritoneal Dialysis, Ryan Geffin, Shazia Raheem, Lavannya M Pandit, Andrew S Hunter, Michael W Holliday, Aditya V Rao, Maulin K Shah

Faculty, Staff and Students Publications

End-stage kidney disease (ESKD) has been shown to be correlated with an increased risk of COVID-19 infection and mortality. Remdesivir is an effective non-EUA U.S. Food and Drug Administration (FDA)-approved antiviral agent for the treatment of COVID-19 in hospitalized adult and pediatric patients, though a lack of data has prevented its use in patients with severe kidney disease including dialysis patients. Some observational studies report the use of remdesivir in hemodialysis patients, but there are no reports of patients treated with remdesivir on peritoneal dialysis. Dialysis modalities may affect drug pharmacokinetics, and safety and efficiency of remdesivir in peritoneal dialysis …


Stealing From The Heart: A Rare Case Of Chest Pain Post-Coronary Artery Bypass Grafting, Prasanti A Kotta, Joshua R Hirsch, Umair Khalid, Ali E Denktas Jan 2023

Stealing From The Heart: A Rare Case Of Chest Pain Post-Coronary Artery Bypass Grafting, Prasanti A Kotta, Joshua R Hirsch, Umair Khalid, Ali E Denktas

Faculty, Staff and Students Publications

A 70-year-old veteran with prior triple vessel coronary artery bypass grafting (CABG) presented with exertional chest pain. His work-up revealed > 40 mm Hg bilateral upper extremity blood pressure difference. Chest computed tomography and invasive angiography revealed severe stenosis at the ostium of the left subclavian artery, proximal to the origin of the left internal mammary artery to left anterior descending artery graft (LIMA-LAD). A diagnosis of coronary subclavian steal syndrome (CSSS) was made, and carotid-subclavian bypass was performed. This case outlines when to suspect CSSS, an approach to its diagnosis, and the importance of its timely management.


Trends And Outcomes In Patients With Coronary Artery Disease Undergoing Tavr: Insights From Va Cart, Khanjan B Shah, Colin O'Donnell, Dhruv Mahtta, Stephen W Waldo, Calvin Choi, Ki Park, Ali E Denktas, David Paniagua, Umair Khalid Jan 2023

Trends And Outcomes In Patients With Coronary Artery Disease Undergoing Tavr: Insights From Va Cart, Khanjan B Shah, Colin O'Donnell, Dhruv Mahtta, Stephen W Waldo, Calvin Choi, Ki Park, Ali E Denktas, David Paniagua, Umair Khalid

Faculty, Staff and Students Publications

BACKGROUND: Obstructive coronary artery disease (CAD) is common in patients with severe symptomatic aortic stenosis. The management and impact of obstructive CAD in patients undergoing transcatheter aortic valve replacement (TAVR) have not been fully evaluated. We aimed to determine the patient characteristics and clinical outcomes among veterans undergoing TAVR with and without obstructive CAD and to determine temporal trends and association of pre-TAVR percutaneous coronary intervention (PCI) with clinical outcomes.

METHODS: We identified all patients who underwent TAVR from 2012 to 2021 in the VA Health Care System. The sample population was divided into patients with and without obstructive CAD …


Pre-Treatment Inflamed Tumor Immune Microenvironment Is Associated With Folfirinox Response In Pancreatic Cancer, Zachary Gao, Sung Wook Kang, Derek Erstad, Joseph Azar, George Van Buren, William Fisher, Zequn Sun, Mark P Rubinstein, Hyun-Sung Lee, E Ramsay Camp Jan 2023

Pre-Treatment Inflamed Tumor Immune Microenvironment Is Associated With Folfirinox Response In Pancreatic Cancer, Zachary Gao, Sung Wook Kang, Derek Erstad, Joseph Azar, George Van Buren, William Fisher, Zequn Sun, Mark P Rubinstein, Hyun-Sung Lee, E Ramsay Camp

Faculty, Staff and Students Publications

INTRODUCTION: Pancreatic adenocarcinoma (PDAC) is an aggressive tumor with limited response to both chemotherapy and immunotherapy. Pre-treatment tumor features within the tumor immune microenvironment (TiME) may influence treatment response. We hypothesized that the pre-treatment TiME composition differs between metastatic and primary lesions and would be associated with response to modified FOLFIRINOX (mFFX) or gemcitabine-based (Gem-based) therapy.

METHODS: Using RNAseq data from a cohort of treatment-naïve, advanced PDAC patients in the COMPASS trial, differential gene expression analysis of key immunomodulatory genes in were analyzed based on multiple parameters including tumor site, response to mFFX, and response to Gem-based treatment. The relative …


Recent Advances In Biological Pumps As A Building Block For Bioartificial Hearts, Sunita Brimmer, Pengfei Ji, Aditya K Birla, Sundeep G Keswani, Christopher A Caldarone, Ravi K Birla Jan 2023

Recent Advances In Biological Pumps As A Building Block For Bioartificial Hearts, Sunita Brimmer, Pengfei Ji, Aditya K Birla, Sundeep G Keswani, Christopher A Caldarone, Ravi K Birla

Faculty, Staff and Students Publications

The field of biological pumps is a subset of cardiac tissue engineering and focused on the development of tubular grafts that are designed generate intraluminal pressure. In the simplest embodiment, biological pumps are tubular grafts with contractile cardiomyocytes on the external surface. The rationale for biological pumps is a transition from planar 3D cardiac patches to functional biological pumps, on the way to complete bioartificial hearts. Biological pumps also have applications as a standalone device, for example, to support the Fontan circulation in pediatric patients. In recent years, there has been a lot of progress in the field of biological …


Tissue-Specific Dna Methylation Variability And Its Potential Clinical Value, Ryan H Miller, Chad A Pollard, Kristin R Brogaard, Andrew C Olson, Ryan C Barney, Larry I Lipshultz, Erica B Johnstone, Yetunde O Ibrahim, James M Hotaling, Enrique F Schisterman, Sunni L Mumford, Kenneth I Aston, Tim G Jenkins Jan 2023

Tissue-Specific Dna Methylation Variability And Its Potential Clinical Value, Ryan H Miller, Chad A Pollard, Kristin R Brogaard, Andrew C Olson, Ryan C Barney, Larry I Lipshultz, Erica B Johnstone, Yetunde O Ibrahim, James M Hotaling, Enrique F Schisterman, Sunni L Mumford, Kenneth I Aston, Tim G Jenkins

Faculty, Staff and Students Publications

Complex diseases have multifactorial etiologies making actionable diagnostic biomarkers difficult to identify. Diagnostic research must expand beyond single or a handful of genetic or epigenetic targets for complex disease and explore a broader system of biological pathways. With the objective to develop a diagnostic tool designed to analyze a comprehensive network of epigenetic profiles in complex diseases, we used publicly available DNA methylation data from over 2,400 samples representing 20 cell types and various diseases. This tool, rather than detecting differentially methylated regions at specific genes, measures the intra-individual methylation variability within gene promoters to identify global shifts away from …


Massive Saddle Embolus Following Bilateral Lung Transplantation Discovered With Transesophageal Echocardiogram, Alex Bui, Jamal Hasoon, Sandeep Markan, Anvinh Nguyen Jan 2023

Massive Saddle Embolus Following Bilateral Lung Transplantation Discovered With Transesophageal Echocardiogram, Alex Bui, Jamal Hasoon, Sandeep Markan, Anvinh Nguyen

Faculty, Staff and Students Publications

No abstract provided.


Ems Administration Of Systemic Corticosteroids To Pediatric Asthma Patients: An Analysis By Severity And Transport Interval, Lauren Riney, Sam Palmer, Erik Finlay, Andrew Bertrand, Shannon Burcham, Phyllis Hendry, Manish Shah, Kathryn Kothari, David Ashby, Daniel Ostermayer, Olga Semenova, Benjamin N Abo, Benjamin Abes, Nichole Shimko, Emily Myers, Marshall Frank, Tim Turner, Mac Kemp, Kim Landry, Greg Roland, Jennifer Fishe Jan 2023

Ems Administration Of Systemic Corticosteroids To Pediatric Asthma Patients: An Analysis By Severity And Transport Interval, Lauren Riney, Sam Palmer, Erik Finlay, Andrew Bertrand, Shannon Burcham, Phyllis Hendry, Manish Shah, Kathryn Kothari, David Ashby, Daniel Ostermayer, Olga Semenova, Benjamin N Abo, Benjamin Abes, Nichole Shimko, Emily Myers, Marshall Frank, Tim Turner, Mac Kemp, Kim Landry, Greg Roland, Jennifer Fishe

Faculty, Staff and Students Publications

INTRODUCTION: Pediatric asthma exacerbations are a common cause of emergency medical services (EMS) encounters. Bronchodilators and systemic corticosteroids are mainstays of asthma exacerbation therapy, yet data on the efficacy of EMS administration of systemic corticosteroids are mixed. This study's objective was to assess the association between EMS administration of systemic corticosteroids to pediatric asthma patients on hospital admission rates based on asthma exacerbation severity and EMS transport intervals.

METHODS: This is a sub-analysis of the Early Administration of Steroids in the Ambulance Setting: An Observational Design Trial (EASI AS ODT). EASI AS ODT is a non-randomized, stepped wedge, observational study …


Implication Of The 2014 World Health Organization Integrated Management Of Childhood Illness Pneumonia Guidelines With And Without Pulse Oximetry Use In Malawi: A Retrospective Cohort Study, Shubhada Hooli, Charles Makwenda, Norman Lufesi, Tim Colbourn, Tisungane Mvalo, Eric D Mccollum, Carina King Jan 2023

Implication Of The 2014 World Health Organization Integrated Management Of Childhood Illness Pneumonia Guidelines With And Without Pulse Oximetry Use In Malawi: A Retrospective Cohort Study, Shubhada Hooli, Charles Makwenda, Norman Lufesi, Tim Colbourn, Tisungane Mvalo, Eric D Mccollum, Carina King

Faculty, Staff and Students Publications

BACKGROUND: Under-5 pneumonia mortality remains high in low-income countries. In 2014 the World Health Organization (WHO) advised that children with chest indrawing pneumonia, but without danger signs or peripheral oxygen saturation (SpO

METHODS: Secondary analysis of 13,413 under-5 pneumonia cases in Malawi. Pneumonia associated case fatality ratios (CFR) were calculated by disease severity under the assumptions of the 2005 and 2014 WHO Integrated Management of Childhood Illness (IMCI) guidelines, with and without pulse oximetry. We investigated if pulse oximetry readings were missing not at random (MNAR).

RESULTS: The CFR of patients classified as having non-severe pneumonia per the 2014 IMCI …


Clostridioides Difficile Infection In Hospitalized Pediatric Patients: Comparisons Of Epidemiology, Testing, And Treatment From 2013 To 2019, Price T Edwards, Cary W Thurm, Matthew Hall, Jordan D Busing, Stacy A Kahn, Richard Kellermayer, Larry K Kociolek, Maria M Oliva-Hemker, Julia S Sammons, Madison Weatherly, Kathryn M Edwards, Maribeth R Nicholson Jan 2023

Clostridioides Difficile Infection In Hospitalized Pediatric Patients: Comparisons Of Epidemiology, Testing, And Treatment From 2013 To 2019, Price T Edwards, Cary W Thurm, Matthew Hall, Jordan D Busing, Stacy A Kahn, Richard Kellermayer, Larry K Kociolek, Maria M Oliva-Hemker, Julia S Sammons, Madison Weatherly, Kathryn M Edwards, Maribeth R Nicholson

Faculty, Staff and Students Publications

OBJECTIVES: To compare the incidence, epidemiology, testing patterns, treatment, and outcomes of Clostridioides difficile infection (CDI) among hospitalized pediatric patients from 2013 to 2019.

STUDY DESIGN: The Pediatric Health Information System database was queried for patient admissions (age 0-17 years) with International Classification of Diseases, 9th and 10th edition, codes for diagnoses of CDI with a billing code for a CDI-related antibiotic treatment.

RESULTS: We identified 17 142 pediatric patients, representing 23 052 admissions, with CDI. The adjusted annual CDI incidence decreased over the study period from 7.09 cases per 10 000 patient-days (95% CI, 6.15-8.18) in 2013 to 4.89 …


A Systematic Review Of Associations Between Gut Microbiota Composition And Growth Failure In Preterm Neonates, Larissa L Neves, Amy B Hair, Geoffrey A Preidis Jan 2023

A Systematic Review Of Associations Between Gut Microbiota Composition And Growth Failure In Preterm Neonates, Larissa L Neves, Amy B Hair, Geoffrey A Preidis

Faculty, Staff and Students Publications

Growth failure is among the most prevalent and devastating consequences of prematurity. Up to half of all extremely preterm neonates struggle to grow despite modern nutrition practices. Although elegant preclinical models suggest causal roles for the gut microbiome, these insights have not yet translated into biomarkers that identify at-risk neonates or therapies that prevent or treat growth failure. This systematic review aims to identify features of the neonatal gut microbiota that are positively or negatively associated with early postnatal growth. We identified 860 articles, of which 14 were eligible for inclusion. No two studies used the same definitions of growth, …


Emerging Issues In Probiotic Safety: 2023 Perspectives, Daniel Merenstein, Bruno Pot, Gregory Leyer, Arthur C Ouwehand, Geoffrey A Preidis, Christopher A Elkins, Colin Hill, Zachery T Lewis, Andi L Shane, Niv Zmora, Mariya I Petrova, Maria Carmen Collado, Lorenzo Morelli, Gina A Montoya, Hania Szajewska, Daniel J Tancredi, Mary Ellen Sanders Jan 2023

Emerging Issues In Probiotic Safety: 2023 Perspectives, Daniel Merenstein, Bruno Pot, Gregory Leyer, Arthur C Ouwehand, Geoffrey A Preidis, Christopher A Elkins, Colin Hill, Zachery T Lewis, Andi L Shane, Niv Zmora, Mariya I Petrova, Maria Carmen Collado, Lorenzo Morelli, Gina A Montoya, Hania Szajewska, Daniel J Tancredi, Mary Ellen Sanders

Faculty, Staff and Students Publications

Probiotics are used for both generally healthy consumers and in clinical settings. However, theoretical and proven adverse events from probiotic consumption exist. New probiotic strains and products, as well as expanding use of probiotics into vulnerable populations, warrants concise, and actionable recommendations on how to work toward their safe and effective use. The International Scientific Association for Probiotics and Prebiotics convened a meeting to discuss and produce evidence-based recommendations on potential acute and long-term risks, risks to vulnerable populations, the importance for probiotic product quality to match the needs of vulnerable populations, and the need for adverse event reporting related …


Insulin-Like Growth Factor 1 Supplementation Supports Motor Coordination And Affects Myelination In Preterm Pigs, Line I Christiansen, Gemma C Ventura, Bo Holmqvist, Karoline Aasmul-Olsen, Sandy E H Lindholm, Matthew D Lycas, Yuki Mori, Jan Bojsen-Møller Secher, Douglas G Burrin, Thomas Thymann, Per T Sangild, Stanislava Pankratova Jan 2023

Insulin-Like Growth Factor 1 Supplementation Supports Motor Coordination And Affects Myelination In Preterm Pigs, Line I Christiansen, Gemma C Ventura, Bo Holmqvist, Karoline Aasmul-Olsen, Sandy E H Lindholm, Matthew D Lycas, Yuki Mori, Jan Bojsen-Møller Secher, Douglas G Burrin, Thomas Thymann, Per T Sangild, Stanislava Pankratova

Faculty, Staff and Students Publications

INTRODUCTION: Preterm infants have increased risk of impaired neurodevelopment to which reduced systemic levels of insulin-like growth factor 1 (IGF-1) in the weeks after birth may play a role. Hence, we hypothesized that postnatal IGF-1 supplementation would improve brain development in preterm pigs, used as a model for preterm infants.

METHODS: Preterm pigs delivered by cesarean section received recombinant human IGF-1/IGF binding protein-3 complex (rhIGF-1/rhIGFBP-3, 2.25 mg/kg/day) or vehicle from birth to postnatal day 19. Motor function and cognition were assessed by monitoring of in-cage and open field activities, balance beam test, gait parameters, novel object recognition and operant conditioning …


Impact Of The Covid Pandemic On Mental Health And Training Opportunities Of Public Health Residents From 4 European Countries: A Cross-Sectional Study, Giovanna Failla, Marta Caminiti, José Chen-Xu, Giuseppina Lo Moro, Nausicaa Berselli, Madalena Cabral Ferreira, Filipa Malcata, David Peyre-Costa, Roberto Croci, Giorgia Soldà, Angelo Capodici, Caterina Morcavallo, Francesco Traglia, Fabrizio Cedrone, Ilaria Storti, Alfonso Alonso Jaquete, Martina Antinozzi, Anca Vasiliu Jan 2023

Impact Of The Covid Pandemic On Mental Health And Training Opportunities Of Public Health Residents From 4 European Countries: A Cross-Sectional Study, Giovanna Failla, Marta Caminiti, José Chen-Xu, Giuseppina Lo Moro, Nausicaa Berselli, Madalena Cabral Ferreira, Filipa Malcata, David Peyre-Costa, Roberto Croci, Giorgia Soldà, Angelo Capodici, Caterina Morcavallo, Francesco Traglia, Fabrizio Cedrone, Ilaria Storti, Alfonso Alonso Jaquete, Martina Antinozzi, Anca Vasiliu

Faculty, Staff and Students Publications

OBJECTIVES: There is little evidence on the impact of the COVID-19 pandemic on Public Health Residents' (PHR) mental health (MH). This study aims at assessing prevalence and risk factors for depression, anxiety and stress in European PHR during the COVID-19 pandemic.

METHODS: Between March and April 2021, an online survey was administered to PHR from France, Italy, Portugal and Spain. The survey assessed COVID-19 related changes in working conditions, training opportunities and evaluated MH outcomes using the Depression Anxiety Stress Scales-21. Multivariable logistic regressions were applied to identify risk factors.

RESULTS: Among the 443 respondents, many showed symptoms of depression …


Determinants Of Retention In Care Of Newborns Diagnosed With Sickle Cell Disease In Liberia: Results From A Mixed-Methods Study Of Caregivers, Kanagasabai Udhayashankar, Patience D Franklin, Cecelia J Nuta, Adolphus K Cherue, Heather Haq, Debbe Thompson, Venée N Tubman Jan 2023

Determinants Of Retention In Care Of Newborns Diagnosed With Sickle Cell Disease In Liberia: Results From A Mixed-Methods Study Of Caregivers, Kanagasabai Udhayashankar, Patience D Franklin, Cecelia J Nuta, Adolphus K Cherue, Heather Haq, Debbe Thompson, Venée N Tubman

Faculty, Staff and Students Publications

High-income nations have established that early diagnosis and preventive treatment reduces early deaths in sickle cell disease (SCD). However, in low-/middle-income countries where SCD is common, attrition from clinical care is common. Reasons for poor retention in care are multi-factorial and poorly understood. The objective of this study was to identify factors that influence caregiver decision-making around chronic health care needs of a child with SCD. We conducted an exploratory sequential mixed methods study of caregivers of children diagnosed with SCD during a newborn screening program in Liberia. Caregivers completed questionnaires and semi-structured interviews designed to identify drivers of health …


Combined Immunodeficiency Caused By Pathogenic Variants In The Zap70 C-Terminal Sh2 Domain, Cédric Mongellaz, Rita Vicente, Lenora M Noroski, Nelly Noraz, Valérie Courgnaud, Javier Chinen, Emilia Faria, Valérie S Zimmermann, Naomi Taylor Jan 2023

Combined Immunodeficiency Caused By Pathogenic Variants In The Zap70 C-Terminal Sh2 Domain, Cédric Mongellaz, Rita Vicente, Lenora M Noroski, Nelly Noraz, Valérie Courgnaud, Javier Chinen, Emilia Faria, Valérie S Zimmermann, Naomi Taylor

Faculty, Staff and Students Publications

INTRODUCTION: ZAP-70, a protein tyrosine kinase recruited to the T cell receptor (TCR), initiates a TCR signaling cascade upon antigen stimulation. Mutations in the ZAP70 gene cause a combined immunodeficiency characterized by low or absent CD8+ T cells and nonfunctional CD4+ T cells. Most deleterious missense ZAP70 mutations in patients are located in the kinase domain but the impact of mutations in the SH2 domains, regulating ZAP-70 recruitment to the TCR, are not well understood.

METHODS:Genetic analyses were performed on four patients with CD8 lymphopenia and a high resolution melting screening for ZAP70 mutations was developed. The impact of SH2 …


The Epidemiology Of Cephalosporin Allergy Labels In Pediatric Primary Care, Torsten Joerger, Margaret G Taylor, Debra L Palazzi, Jeffrey S Gerber Jan 2023

The Epidemiology Of Cephalosporin Allergy Labels In Pediatric Primary Care, Torsten Joerger, Margaret G Taylor, Debra L Palazzi, Jeffrey S Gerber

Faculty, Staff and Students Publications

BACKGROUND: Recent studies have sought to understand the epidemiology and impact of beta-lactam allergy labels on children; however, most of these studies have focused on penicillin allergy labels. Fewer studies assess cephalosporin antibiotic allergy labels in children. The objective of this study was to determine the prevalence, factors associated with, and impact of cephalosporin allergy labels in children cared for in the primary care setting.

METHODS: Cephalosporin allergy labels were reviewed among children in a dual center, retrospective, birth cohort who were born between 2010 and 2020 and followed in 90 pediatric primary care practices. Antibiotic prescriptions for acute otitis …


Cefepime Dosing In A Critically Ill Neonate Receiving Continuous Renal Replacement Therapy With The Cardio-Renal Pediatric Dialysis Emergency Machine (Carpediem), Cynthia Toy, Grant Stimes, Megan Moore, Poyyapakkam Srivaths, Ayse Akcan Arikan Jan 2023

Cefepime Dosing In A Critically Ill Neonate Receiving Continuous Renal Replacement Therapy With The Cardio-Renal Pediatric Dialysis Emergency Machine (Carpediem), Cynthia Toy, Grant Stimes, Megan Moore, Poyyapakkam Srivaths, Ayse Akcan Arikan

Faculty, Staff and Students Publications

We report on a former 27-week gestational age infant who was placed on the Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM) at 4 months post-menstrual age while receiving cefepime treatment for an Enterobacter cloacae bacteremia and persistent peritonitis secondary to an infected peritoneal dialysis catheter. Using therapeutic drug monitoring while assessing the clearance of cefepime on continuous renal replacement therapy (CRRT), we were able to successfully treat this patient's infection while also minimizing the risk of side effects from this medication. Current literature supports dosing in adult patients on all modalities of CRRT with effluent flow rates of 20 to 25 …


A Rapid, Low-Cost, And Highly Sensitive Sars-Cov-2 Diagnostic Based On Whole-Genome Sequencing, Per A Adastra, Neva C Durand, Namita Mitra, Saul Godinez Pulido, Ragini Mahajan, Alyssa Blackburn, Zane L Colaric, Joshua W M Theisen, David Weisz, Olga Dudchenko, Andreas Gnirke, Suhas S P Rao, Parwinder Kaur, Erez Lieberman Aiden, Aviva Presser Aiden Jan 2023

A Rapid, Low-Cost, And Highly Sensitive Sars-Cov-2 Diagnostic Based On Whole-Genome Sequencing, Per A Adastra, Neva C Durand, Namita Mitra, Saul Godinez Pulido, Ragini Mahajan, Alyssa Blackburn, Zane L Colaric, Joshua W M Theisen, David Weisz, Olga Dudchenko, Andreas Gnirke, Suhas S P Rao, Parwinder Kaur, Erez Lieberman Aiden, Aviva Presser Aiden

Faculty, Staff and Students Publications

Early detection of SARS-CoV-2 infection is key to managing the current global pandemic, as evidence shows the virus is most contagious on or before symptom onset. Here, we introduce a low-cost, high-throughput method for diagnosing and studying SARS-CoV-2 infection. Dubbed Pathogen-Oriented Low-Cost Assembly & Re-Sequencing (POLAR), this method amplifies the entirety of the SARS-CoV-2 genome. This contrasts with typical RT-PCR-based diagnostic tests, which amplify only a few loci. To achieve this goal, we combine a SARS-CoV-2 enrichment method developed by the ARTIC Network (https://artic.network/) with short-read DNA sequencing and de novo genome assembly. Using this method, we can reliably ( …


Clinical Correlates Of Cholestasis In Preterm Infants With Surgical Necrotizing Enterocolitis, Parvesh Mohan Garg, Isabella Pittman, Joe Yi, Victoria G Weis, Ricardo Jorge Rodriguez, Mitchell R Ladd, Jessica L Rauh, Anna Greene Mcdonald, Cherrie Welch, Muralidhar Hebbur Premkumar, Padma P Garg, Akhil Maheshwari Jan 2023

Clinical Correlates Of Cholestasis In Preterm Infants With Surgical Necrotizing Enterocolitis, Parvesh Mohan Garg, Isabella Pittman, Joe Yi, Victoria G Weis, Ricardo Jorge Rodriguez, Mitchell R Ladd, Jessica L Rauh, Anna Greene Mcdonald, Cherrie Welch, Muralidhar Hebbur Premkumar, Padma P Garg, Akhil Maheshwari

Faculty, Staff and Students Publications

BACKGROUND: We sought to investigate the clinical determinants and outcomes of cholestasis in preterm infants with surgical necrotizing enterocolitis (sNEC).

METHODS: Retrospective comparison of clinical information in preterm infants who developed cholestasis vs those who did not.

RESULTS: Sixty-two (62/91, 68.1%) infants with NEC developed cholestasis at any time following the onset of illness. Cholestasis was seen more frequently in those who had received ionotropic support at 24 hours following sNEC diagnosis (87.1% vs 58.6%;

CONCLUSION: Cholestasis was seen in 68% of infants following surgical NEC. The most likely contributive factors are intestinal failure and subsequent PN dependence for longer …


Multiomics, Artificial Intelligence, And Precision Medicine In Perinatology, Mohan Pammi, Nima Aghaeepour, Josef Neu Jan 2023

Multiomics, Artificial Intelligence, And Precision Medicine In Perinatology, Mohan Pammi, Nima Aghaeepour, Josef Neu

Faculty, Staff and Students Publications

Technological advances in omics evaluation, bioinformatics, and artificial intelligence have made us rethink ways to improve patient outcomes. Collective quantification and characterization of biological data including genomics, epigenomics, metabolomics, and proteomics is now feasible at low cost with rapid turnover. Significant advances in the integration methods of these multiomics data sets by machine learning promise us a holistic view of disease pathogenesis and yield biomarkers for disease diagnosis and prognosis. Using machine learning tools and algorithms, it is possible to integrate multiomics data with clinical information to develop predictive models that identify risk before the condition is clinically apparent, thus …


Spatial Analysis Of Nanoparticle Distribution In Human Breast Xenografts Reveals Nanoparticles Targeted To Cancer Cells Localized With Tumor-Associated Stromal Cells, Sean Healy, Elizabeth T Henderson, Suqi Ke, Jacqueline Kelly, Brian W Simons, Chen Hu, Robert Ivkov, Preethi Korangath Jan 2023

Spatial Analysis Of Nanoparticle Distribution In Human Breast Xenografts Reveals Nanoparticles Targeted To Cancer Cells Localized With Tumor-Associated Stromal Cells, Sean Healy, Elizabeth T Henderson, Suqi Ke, Jacqueline Kelly, Brian W Simons, Chen Hu, Robert Ivkov, Preethi Korangath

Faculty, Staff and Students Publications

The biological influence of physicochemical parameters of “targeted” nanoparticles on their delivery to cancer tumors remains poorly understood. A comparative analysis of nanoparticle distributions in tumors following systemic delivery across several models can provide valuable insights.

Methods: Bionized nanoferrite nanoparticles (iron oxide core coated with starch), either conjugated with a targeted anti-HER2 antibody (BH), or unconjugated (BP), were intravenously injected into athymic nude or NOD-scid gamma (NSG) female mice bearing one of five human breast cancer tumor xenografts growing in a mammary fat pad. Tumors were harvested 24 hours after nanoparticle injection, fixed, mounted, and stained. We performed detailed histopathology …


Mass Spectrometry Imaging As An Emerging Tool For Studying Metabolism In Human Brain Organoids, Gerarda Cappuccio, Saleh M Khalil, Sivan Osenberg, Feng Li, Mirjana Maletic-Savatic Jan 2023

Mass Spectrometry Imaging As An Emerging Tool For Studying Metabolism In Human Brain Organoids, Gerarda Cappuccio, Saleh M Khalil, Sivan Osenberg, Feng Li, Mirjana Maletic-Savatic

Faculty, Staff and Students Publications

Human brain organoids are emerging models to study human brain development and pathology as they recapitulate the development and characteristics of major neural cell types, and enable manipulation through an in vitro system. Over the past decade, with the advent of spatial technologies, mass spectrometry imaging (MSI) has become a prominent tool for metabolic microscopy, providing label-free, non-targeted molecular and spatial distribution information of the metabolites within tissue, including lipids. This technology has never been used for studies of brain organoids and here, we set out to develop a standardized protocol for preparation and mass spectrometry imaging of human brain …


Rapid Response Events With Multiple Triggers Are Associated With Poor Outcomes In Children, Erin M Kritz, Jenilea K Thomas, Nawara S Alawa, Elit B Hadad, Danielle M Guffey, Aarti C Bavare Jan 2023

Rapid Response Events With Multiple Triggers Are Associated With Poor Outcomes In Children, Erin M Kritz, Jenilea K Thomas, Nawara S Alawa, Elit B Hadad, Danielle M Guffey, Aarti C Bavare

Faculty, Staff and Students Publications

OBJECTIVE: We describe the characteristics and outcomes of pediatric rapid response team (RRT) events within a single institution, categorized by reason for RRT activation (RRT triggers). We hypothesized that events with multiple triggers are associated with worse outcomes.

PATIENTS AND METHODS: Retrospective 3-year study at a high-volume tertiary academic pediatric hospital. We included all patients with index RRT events during the study period.

RESULTS: Association of patient and RRT event characteristics with outcomes including transfers to ICU, need for advanced cardiopulmonary support, ICU and hospital length of stay (LOS), and mortality were studied. We reviewed 2,267 RRT events from 2,088 …


Rapid Response Events With Multiple Triggers Are Associated With Poor Outcomes In Children, Erin M Kritz, Jenilea K Thomas, Nawara S Alawa, Elit B Hadad, Danielle M Guffey, Aarti C Bavare Jan 2023

Rapid Response Events With Multiple Triggers Are Associated With Poor Outcomes In Children, Erin M Kritz, Jenilea K Thomas, Nawara S Alawa, Elit B Hadad, Danielle M Guffey, Aarti C Bavare

Faculty, Staff and Students Publications

OBJECTIVE: We describe the characteristics and outcomes of pediatric rapid response team (RRT) events within a single institution, categorized by reason for RRT activation (RRT triggers). We hypothesized that events with multiple triggers are associated with worse outcomes.

PATIENTS AND METHODS: Retrospective 3-year study at a high-volume tertiary academic pediatric hospital. We included all patients with index RRT events during the study period.

RESULTS: Association of patient and RRT event characteristics with outcomes including transfers to ICU, need for advanced cardiopulmonary support, ICU and hospital length of stay (LOS), and mortality were studied. We reviewed 2,267 RRT events from 2,088 …


Transcriptomic Profiles Of Multiple Organ Dysfunction Syndrome Phenotypes In Pediatric Critical Influenza, Tanya Novak, Jeremy Chase Crawford, Georg Hahn, Mark W Hall, Simone A Thair, Margaret M Newhams, Janet Chou, Peter M Mourani, Keiko M Tarquinio, Barry Markovitz, Laura L Loftis, Scott L Weiss, Renee Higgerson, Adam J Schwarz, Neethi P Pinto, Neal J Thomas, Rainer G Gedeit, Ronald C Sanders, Sidharth Mahapatra, Bria M Coates, Natalie Z Cvijanovich, Kate G Ackerman, David W Tellez, Patrick Mcquillen, Stephen C Kurachek, Steven L Shein, Christoph Lange, Paul G Thomas, Adrienne G Randolph Jan 2023

Transcriptomic Profiles Of Multiple Organ Dysfunction Syndrome Phenotypes In Pediatric Critical Influenza, Tanya Novak, Jeremy Chase Crawford, Georg Hahn, Mark W Hall, Simone A Thair, Margaret M Newhams, Janet Chou, Peter M Mourani, Keiko M Tarquinio, Barry Markovitz, Laura L Loftis, Scott L Weiss, Renee Higgerson, Adam J Schwarz, Neethi P Pinto, Neal J Thomas, Rainer G Gedeit, Ronald C Sanders, Sidharth Mahapatra, Bria M Coates, Natalie Z Cvijanovich, Kate G Ackerman, David W Tellez, Patrick Mcquillen, Stephen C Kurachek, Steven L Shein, Christoph Lange, Paul G Thomas, Adrienne G Randolph

Faculty, Staff and Students Publications

BACKGROUND: Influenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening and fatal complication of severe influenza infection.

METHODS: We measured RNA expression of 469 biologically plausible candidate genes in children admitted to North American pediatric intensive care units with severe influenza virus infection with and without MODS. Whole blood samples from 191 influenza-infected children (median age 6.4 years, IQR: 2.2, 11) were collected a median of 27 hours following admission; for 45 children a second blood sample was collected approximately seven days later. Extracted RNA was hybridized …


Corrigendum: Case Report: Selexipag In Pediatric Pulmonary Hypertension: Initiation, Transition, And Titration, Jenna M Faircloth, Neelam D Bhatt, Corey A Chartan, Ryan D Coleman, Natalie Villafranco, Fadel E Ruiz, Raysa Morales-Demori, Elise Whalen, Erin Ely, Rozmeen Fombin, Nidhy P Varghese Jan 2023

Corrigendum: Case Report: Selexipag In Pediatric Pulmonary Hypertension: Initiation, Transition, And Titration, Jenna M Faircloth, Neelam D Bhatt, Corey A Chartan, Ryan D Coleman, Natalie Villafranco, Fadel E Ruiz, Raysa Morales-Demori, Elise Whalen, Erin Ely, Rozmeen Fombin, Nidhy P Varghese

Faculty, Staff and Students Publications

This corrects the article "Case Report: Selexipag in pediatric pulmonary hypertension: Initiation, transition, and titration", 1050508.


Case Report: Selexipag In Pediatric Pulmonary Hypertension: Initiation, Transition, And Titration, Jenna M Faircloth, Neelam D Bhatt, Corey A Chartan, Ryan D Coleman, Natalie Villafranco, Fadel E Ruiz, Raysa Morales-Demori, Elise Whalen, Erin Ely, Rozmeen Fombin, Nidhy P Varghese Jan 2023

Case Report: Selexipag In Pediatric Pulmonary Hypertension: Initiation, Transition, And Titration, Jenna M Faircloth, Neelam D Bhatt, Corey A Chartan, Ryan D Coleman, Natalie Villafranco, Fadel E Ruiz, Raysa Morales-Demori, Elise Whalen, Erin Ely, Rozmeen Fombin, Nidhy P Varghese

Faculty, Staff and Students Publications

Selexipag, a selective prostacyclin receptor agonist, is approved for treating pulmonary arterial hypertension in WHO Group 1 adult patients. Compared to parenteral prostacyclin formulations, selexipag offers a significant improvement in patient’s and caregiver’s quality of life because of its oral formulation, frequency of administration, and mechanism of action. Although experience in the pediatric population is limited and selexipag is not FDA-approved for use in the pediatric pulmonary hypertension population, many US pediatric centers are expanding the use of this therapy to this younger population. We report our institution's experience in the use of selexipag to treat pulmonary hypertension in children …