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Case Report: P40phox Deficiency Underlying Pediatric-Onset Systemic Lupus Erythematosus, Alejandro Nieto-Patlán, Natalia S Fernández Dávila, Yuqing Wang, Michelle Zelnick, Eyal Muscal, Martha Curry, James R Lupski, Steven M Holland, Bo Yuan, Douglas B Kuhns, Tiphanie P Vogel, Ivan K Chinn Jan 2024

Case Report: P40phox Deficiency Underlying Pediatric-Onset Systemic Lupus Erythematosus, Alejandro Nieto-Patlán, Natalia S Fernández Dávila, Yuqing Wang, Michelle Zelnick, Eyal Muscal, Martha Curry, James R Lupski, Steven M Holland, Bo Yuan, Douglas B Kuhns, Tiphanie P Vogel, Ivan K Chinn

Faculty, Staff and Students Publications

Introduction

Systemic lupus erythematosus is a multi-faceted autoimmune disorder of complex etiology. Pre-pubertal onset of pediatric systemic lupus erythematosus (pSLE) is uncommon and should raise suspicion for a genetic driver of disease. Autosomal recessive p40phox deficiency is a rare immunologic disorder characterized by defective but not abolished NADPH oxidase activity with residual production of reactive oxygen species (ROS) by phagocytic cells.

Case presentation

We report the case of a now 18-year-old female with pSLE onset at 7 years of age. She presented with recurrent fever and malar rash. Aspects of her immune dysregulation over time have included typical pSLE …


Etiology Of Hospital Mortality In Children Living In Low- And Middle-Income Countries: A Systematic Review And Meta-Analysis, Teresa B Kortz, Rishi P Mediratta, Audrey M Smith, Katie R Nielsen, Asya Agulnik, Stephanie Gordon Rivera, Hailey Reeves, Nicole F O'Brien, Jan Hau Lee, Qalab Abbas, Jonah E Attebery, Tigist Bacha, Emaan G Bhutta, Carter J Biewen, Jhon Camacho-Cruz, Alvaro Coronado Muñoz, Mary L Dealmeida, Larko Domeryo Owusu, Yudy Fonseca, Shubhada Hooli, Hunter Wynkoop, Mara Leimanis-Laurens, Deogratius Nicholaus Mally, Amanda M Mccarthy, Andrew Mutekanga, Carol Pineda, Kenneth E Remy, Sara C Sanders, Erica Tabor, Adriana Teixeira Rodrigues, Justin Qi Yuee Wang, Niranjan Kissoon, Yemisi Takwoingi, Matthew O Wiens, Adnan Bhutta Jan 2024

Etiology Of Hospital Mortality In Children Living In Low- And Middle-Income Countries: A Systematic Review And Meta-Analysis, Teresa B Kortz, Rishi P Mediratta, Audrey M Smith, Katie R Nielsen, Asya Agulnik, Stephanie Gordon Rivera, Hailey Reeves, Nicole F O'Brien, Jan Hau Lee, Qalab Abbas, Jonah E Attebery, Tigist Bacha, Emaan G Bhutta, Carter J Biewen, Jhon Camacho-Cruz, Alvaro Coronado Muñoz, Mary L Dealmeida, Larko Domeryo Owusu, Yudy Fonseca, Shubhada Hooli, Hunter Wynkoop, Mara Leimanis-Laurens, Deogratius Nicholaus Mally, Amanda M Mccarthy, Andrew Mutekanga, Carol Pineda, Kenneth E Remy, Sara C Sanders, Erica Tabor, Adriana Teixeira Rodrigues, Justin Qi Yuee Wang, Niranjan Kissoon, Yemisi Takwoingi, Matthew O Wiens, Adnan Bhutta

Faculty, Staff and Students Publications

In 2019, 80% of the 7.4 million global child deaths occurred in low- and middle-income countries (LMICs). Global and regional estimates of cause of hospital death and admission in LMIC children are needed to guide global and local priority setting and resource allocation but are currently lacking. The study objective was to estimate global and regional prevalence for common causes of pediatric hospital mortality and admission in LMICs. We performed a systematic review and meta-analysis to identify LMIC observational studies published January 1, 2005-February 26, 2021. Eligible studies included: a general pediatric admission population, a cause of admission or death, …


Development Of A Mini Pig Model Of Peanut Allergy, Akhilesh Kumar Shakya, Brittany Backus, Lazar D Nesovic, Malini Mallick, Olivia Banister, Carla M Davis, Sara Anvari, Harvinder Singh Gill Jan 2024

Development Of A Mini Pig Model Of Peanut Allergy, Akhilesh Kumar Shakya, Brittany Backus, Lazar D Nesovic, Malini Mallick, Olivia Banister, Carla M Davis, Sara Anvari, Harvinder Singh Gill

Faculty, Staff and Students Publications

INTRODUCTION: The prevalence of peanut allergies is increasing, emphasizing the need for an animal model to enhance our understanding of peanut allergy pathogenesis and to advance diagnostic tools and therapeutic interventions. While mice are frequently used as model organisms, their allergic responses do not fully mirror those observed in humans, warranting the exploration of a higher animal model. The porcine gastrointestinal system closely resembles that of humans, and exhibits allergy symptoms akin to human responses, making pigs a promising model for peanut allergy research.

METHODS: In this study we compared two allergen sensitization protocols involving either topical allergen application after …


Levofloxacin Prophylaxis For Pediatric Leukemia Patients: Monitoring Of Outcomes For Sustained Benefit And Consequences, Andrea L Davis, Alexandra M Stevens, Julienne Brackett, Lucila Marquez, Catherine E Foster, Adriana Sarmiento Clemente, Hannah E Sauer, Grant T Stimes, Judith R Campbell Jan 2024

Levofloxacin Prophylaxis For Pediatric Leukemia Patients: Monitoring Of Outcomes For Sustained Benefit And Consequences, Andrea L Davis, Alexandra M Stevens, Julienne Brackett, Lucila Marquez, Catherine E Foster, Adriana Sarmiento Clemente, Hannah E Sauer, Grant T Stimes, Judith R Campbell

Faculty, Staff and Students Publications

Levofloxacin prophylaxis reduces bloodstream infections in neutropenic patients with acute myeloid leukemia or relapsed acute lymphoblastic leukemia. A retrospective, longitudinal cohort study compares incidence of bacteremia, multidrug-resistant organisms (MDRO), and Clostridioides difficile (CDI) between time periods of levofloxacin prophylaxis implementation. Benefits were sustained without increasing MDRO or CDI.


Autophagy Determines Distinct Cell Fates In Human Amnion And Chorion Cells, Mary Elise L Severino, Lauren Richardson, Ananth Kumar Kammala, Enkhtuya Radnaa, Kamil Khanipov, Leslie Michelle M Dalmacio, Indira U Mysorekar, Marian Kacerovsky, Ramkumar Menon Jan 2024

Autophagy Determines Distinct Cell Fates In Human Amnion And Chorion Cells, Mary Elise L Severino, Lauren Richardson, Ananth Kumar Kammala, Enkhtuya Radnaa, Kamil Khanipov, Leslie Michelle M Dalmacio, Indira U Mysorekar, Marian Kacerovsky, Ramkumar Menon

Faculty, Staff and Students Publications

Human fetal membranes (amniochorion) that line the intrauterine cavity consist of two distinct cell layers; single-layer amnion epithelial cells (AEC) and multilayer chorion trophoblast cells (CTC). These layers are connected through a collagen-rich extracellular matrix. Cellular remodeling helps support membrane growth and integrity during gestation and helps to maintain pregnancy. Preterm prelabor rupture of the human amniochorionic (fetal) membrane (pPROM) is antecedent to 40% of all spontaneous preterm birth. Oxidative stress (OS) induced activation of the p38 MAPK due to various maternal risk exposures and the amniochorion cells' senescence are reported pathological features of pPROM. Our transcriptomics analysis implicated dysregulated …


Childhood And Adolescent Relapsed/Refractory Aggressive B-Cell Lymphomas With T(8;14) And Bcl2 Expression, Burkitt Lymphoma Versus Diffuse Large B-Cell Lymphoma: A Diagnostic Challenge, Fouad El Dana, Sofia Alexandra Garces Narvaez, Nader K El-Mallawany, Jennifer E Agrusa, Zoann E Dreyer, Andrea N Marcogliese, Mohamed Tarek Elghetany, Jyotinder N Punia, Chi Young Ok, Keyur P Patel, Dolores H Lopez-Terrada, Kevin E Fisher, Choladda V Curry Jan 2024

Childhood And Adolescent Relapsed/Refractory Aggressive B-Cell Lymphomas With T(8;14) And Bcl2 Expression, Burkitt Lymphoma Versus Diffuse Large B-Cell Lymphoma: A Diagnostic Challenge, Fouad El Dana, Sofia Alexandra Garces Narvaez, Nader K El-Mallawany, Jennifer E Agrusa, Zoann E Dreyer, Andrea N Marcogliese, Mohamed Tarek Elghetany, Jyotinder N Punia, Chi Young Ok, Keyur P Patel, Dolores H Lopez-Terrada, Kevin E Fisher, Choladda V Curry

Faculty, Staff and Students Publications

We present 2 diagnostically challenging cases of pediatric/adolescent relapsed/refractory aggressive mature B-cell non-Hodgkin lymphoma (B-NHL) within the spectrum of Burkitt lymphoma and diffuse large B-cell lymphoma and illustrate the different therapeutic regimens that are employed for pediatric and adult cancer centers. Both cases displayed varying-sized lymphoma cells with occasional single prominent nucleoli and heterogeneous BCL2 expression. Cytogenetics revealed complex karyotypes with t(8:14)(q24.2;q32) and IGH::MYC rearrangement by FISH. Next generation sequencing revealed deleterious TP53 and MYC mutations. We concluded that both could be diagnosed as “DLBCL-NOS with MYC rearrangement” using the current pathologic classifications, 2022 International Consensus Classification (ICC) and World …


Pseudoviruses, A Safer Toolbox For Vaccine Development Against Enveloped Viruses, Syamala R Thimmiraju, Jason T Kimata, Jeroen Pollet Jan 2024

Pseudoviruses, A Safer Toolbox For Vaccine Development Against Enveloped Viruses, Syamala R Thimmiraju, Jason T Kimata, Jeroen Pollet

Faculty, Staff and Students Publications

Introduction: Pseudoviruses are recombinant, replication-incompetent, viral particles designed to mimic the surface characteristics of native enveloped viruses. They are a safer, and cost-effective research alternative to live viruses. With the potential emergence of the next major infectious disease, more vaccine scientists must become familiar with the pseudovirus platform as a vaccine development tool to mitigate future outbreaks.

Areas covered: This review aims at vaccine developers to provide a basic understanding of pseudoviruses, list their production methods, and discuss their utility to assess vaccine efficacy against enveloped viral pathogens. We further illustrate their usefulness as wet-lab simulators for emerging mutant variants, …


Racial And Ethnic Disparities In Acuity Of Presentation Among Children With Newly Diagnosed Acute Leukemia, Lena E Winestone, Kelly D Getz, Yimei Li, Evanette Burrows, Michael E Scheurer, Vicky Tam, M Monica Gramatges, Jennifer J Wilkes, Tamara P Miller, Alix E Seif, Karen R Rabin, Brian T Fisher, Richard Aplenc Jan 2024

Racial And Ethnic Disparities In Acuity Of Presentation Among Children With Newly Diagnosed Acute Leukemia, Lena E Winestone, Kelly D Getz, Yimei Li, Evanette Burrows, Michael E Scheurer, Vicky Tam, M Monica Gramatges, Jennifer J Wilkes, Tamara P Miller, Alix E Seif, Karen R Rabin, Brian T Fisher, Richard Aplenc

Center for Medical Ethics and Health Policy Staff Publications

We evaluated disparities in disease burden, organ dysfunction, vital signs, and timing of therapy in children newly presenting with acute leukemia. Among 899 patients with acute leukemia diagnosed at two large children's hospitals, a priori lab-based definitions of high disease burden, infection risk, renal dysfunction, and coagulopathy were applied to electronic health record data. Black patients with acute myeloid leukemia had increased prevalence of elevated white blood cell count and uric acid; Black patients with acute lymphoblastic leukemia demonstrated increased prevalence of coagulopathy. Black patients' presentation more frequently included multiple lab abnormalities consistent with advanced physiologic dysfunction. No differences were …


Colonic Malakoplakia In A Pediatric Renal Transplant Recipient Case Report, Kristen G Valencia Deray, Richard Kellermayer, Alexis C Gomez, Kalyani R Patel, Peace Imani, Seiji Kitagawa, Claire E Bocchini, Alvaro Orjuela Jan 2024

Colonic Malakoplakia In A Pediatric Renal Transplant Recipient Case Report, Kristen G Valencia Deray, Richard Kellermayer, Alexis C Gomez, Kalyani R Patel, Peace Imani, Seiji Kitagawa, Claire E Bocchini, Alvaro Orjuela

Faculty, Staff and Students Publications

Malakoplakia is a rare, chronic granulomatous disease that mainly affects the genitourinary system of immunocompromised adults. It is caused by a bactericidal deficit in macrophages and, therefore, the treatment includes antimicrobials that reach high concentrations in macrophages. To our knowledge, we present the first case of malakoplakia in a pediatric solid organ transplant recipient. Our patient is a 15-year-old male renal transplant recipient who presented with recurrent diarrhea. Blood, urine, and gastrointestinal pathogen panel testing were positive for enteroaggregative Escherichia coli. A colonoscopy revealed diffuse malakoplakia. He had a complete resolution of symptoms with trimethoprim-sulfamethoxazole therapy. Unfortunately, his malakoplakia recurred …


Researching Covid To Enhance Recovery (Recover) Pediatric Study Protocol: Rationale, Objectives And Design, Rachel S Gross, Tanayott Thaweethai, Erika B Rosenzweig, James Chan, Lori B Chibnik, Mine S Cicek, Amy J Elliott, Valerie J Flaherman, Andrea S Foulkes, Margot Gage Witvliet, Richard Gallagher, Maria Laura Gennaro, Terry L Jernigan, Elizabeth W Karlson, Stuart D Katz, Patricia A Kinser, Lawrence C Kleinman, Michelle F Lamendola-Essel, Joshua D Milner, Sindhu Mohandas, Praveen C Mudumbi, Jane W Newburger, Kyung E Rhee, Amy L Salisbury, Jessica N Snowden, Cheryl R Stein, Melissa S Stockwell, Kelan G Tantisira, Moriah E Thomason, Dongngan T Truong, David Warburton, John C Wood, Shifa Ahmed, Almary Akerlundh, Akram N Alshawabkeh, Brett R Anderson, Judy L Aschner, Andrew M Atz, Robin L Aupperle, Fiona C Baker, Venkataraman Balaraman, Dithi Banerjee, Deanna M Barch, Arielle Baskin-Sommers, Sultana Bhuiyan, Marie-Abele C Bind, Amanda L Bogie, Tamara Bradford, Natalie C Buchbinder, Elliott Bueler, Hülya Bükülmez, B J Casey, Linda Chang, Maryanne Chrisant, Duncan B Clark, Rebecca G Clifton, Katharine N Clouser, Lesley Cottrell, Kelly Cowan, Viren D'Sa, Mirella Dapretto, Soham Dasgupta, Walter Dehority, Audrey Dionne, Kirsten B Dummer, Matthew D Elias, Shari Esquenazi-Karonika, Danielle N Evans, E Vincent S Faustino, Alexander G Fiks, Daniel Forsha, John J Foxe, Naomi P Friedman, Greta Fry, Sunanda Gaur, Dylan G Gee, Kevin M Gray, Stephanie Handler, Ashraf S Harahsheh, Keren Hasbani, Andrew C Heath, Camden Hebson, Mary M Heitzeg, Christina M Hester, Sophia Hill, Laura Hobart-Porter, Travis K F Hong, Carol R Horowitz, Daniel S Hsia, Matthew Huentelman, Kathy D Hummel, Katherine Irby, Joanna Jacobus, Vanessa L Jacoby, Pei-Ni Jone, David C Kaelber, Tyler J Kasmarcak, Matthew J Kluko, Jessica S Kosut, Angela R Laird, Jeremy Landeo-Gutierrez, Sean M Lang, Christine L Larson, Peter Paul C Lim, Krista M Lisdahl, Brian W Mccrindle, Russell J Mcculloh, Kimberly Mchugh, Alan L Mendelsohn, Torri D Metz, Julie Miller, Elizabeth C Mitchell, Lerraughn M Morgan, Eva M Müller-Oehring, Erica R Nahin, Michael C Neale, Manette Ness-Cochinwala, Sheila M Nolan, Carlos R Oliveira, Onyekachukwu Osakwe, Matthew E Oster, R Mark Payne, Michael A Portman, Hengameh Raissy, Isabelle G Randall, Suchitra Rao, Harrison T Reeder, Johana M Rosas, Mark W Russell, Arash A Sabati, Yamuna Sanil, Alice I Sato, Michael S Schechter, Rangaraj Selvarangan, S Kristen Sexson Tejtel, Divya Shakti, Kavita Sharma, Lindsay M Squeglia, Shubika Srivastava, Michelle D Stevenson, Jacqueline Szmuszkovicz, Maria M Talavera-Barber, Ronald J Teufel, Deepika Thacker, Felicia Trachtenberg, Mmekom M Udosen, Megan R Warner, Sara E Watson, Alan Werzberger, Jordan C Weyer, Marion J Wood, H Shonna Yin, William T Zempsky, Emily Zimmerman, Benard P Dreyer, Recover-Pediatric Consortium Jan 2024

Researching Covid To Enhance Recovery (Recover) Pediatric Study Protocol: Rationale, Objectives And Design, Rachel S Gross, Tanayott Thaweethai, Erika B Rosenzweig, James Chan, Lori B Chibnik, Mine S Cicek, Amy J Elliott, Valerie J Flaherman, Andrea S Foulkes, Margot Gage Witvliet, Richard Gallagher, Maria Laura Gennaro, Terry L Jernigan, Elizabeth W Karlson, Stuart D Katz, Patricia A Kinser, Lawrence C Kleinman, Michelle F Lamendola-Essel, Joshua D Milner, Sindhu Mohandas, Praveen C Mudumbi, Jane W Newburger, Kyung E Rhee, Amy L Salisbury, Jessica N Snowden, Cheryl R Stein, Melissa S Stockwell, Kelan G Tantisira, Moriah E Thomason, Dongngan T Truong, David Warburton, John C Wood, Shifa Ahmed, Almary Akerlundh, Akram N Alshawabkeh, Brett R Anderson, Judy L Aschner, Andrew M Atz, Robin L Aupperle, Fiona C Baker, Venkataraman Balaraman, Dithi Banerjee, Deanna M Barch, Arielle Baskin-Sommers, Sultana Bhuiyan, Marie-Abele C Bind, Amanda L Bogie, Tamara Bradford, Natalie C Buchbinder, Elliott Bueler, Hülya Bükülmez, B J Casey, Linda Chang, Maryanne Chrisant, Duncan B Clark, Rebecca G Clifton, Katharine N Clouser, Lesley Cottrell, Kelly Cowan, Viren D'Sa, Mirella Dapretto, Soham Dasgupta, Walter Dehority, Audrey Dionne, Kirsten B Dummer, Matthew D Elias, Shari Esquenazi-Karonika, Danielle N Evans, E Vincent S Faustino, Alexander G Fiks, Daniel Forsha, John J Foxe, Naomi P Friedman, Greta Fry, Sunanda Gaur, Dylan G Gee, Kevin M Gray, Stephanie Handler, Ashraf S Harahsheh, Keren Hasbani, Andrew C Heath, Camden Hebson, Mary M Heitzeg, Christina M Hester, Sophia Hill, Laura Hobart-Porter, Travis K F Hong, Carol R Horowitz, Daniel S Hsia, Matthew Huentelman, Kathy D Hummel, Katherine Irby, Joanna Jacobus, Vanessa L Jacoby, Pei-Ni Jone, David C Kaelber, Tyler J Kasmarcak, Matthew J Kluko, Jessica S Kosut, Angela R Laird, Jeremy Landeo-Gutierrez, Sean M Lang, Christine L Larson, Peter Paul C Lim, Krista M Lisdahl, Brian W Mccrindle, Russell J Mcculloh, Kimberly Mchugh, Alan L Mendelsohn, Torri D Metz, Julie Miller, Elizabeth C Mitchell, Lerraughn M Morgan, Eva M Müller-Oehring, Erica R Nahin, Michael C Neale, Manette Ness-Cochinwala, Sheila M Nolan, Carlos R Oliveira, Onyekachukwu Osakwe, Matthew E Oster, R Mark Payne, Michael A Portman, Hengameh Raissy, Isabelle G Randall, Suchitra Rao, Harrison T Reeder, Johana M Rosas, Mark W Russell, Arash A Sabati, Yamuna Sanil, Alice I Sato, Michael S Schechter, Rangaraj Selvarangan, S Kristen Sexson Tejtel, Divya Shakti, Kavita Sharma, Lindsay M Squeglia, Shubika Srivastava, Michelle D Stevenson, Jacqueline Szmuszkovicz, Maria M Talavera-Barber, Ronald J Teufel, Deepika Thacker, Felicia Trachtenberg, Mmekom M Udosen, Megan R Warner, Sara E Watson, Alan Werzberger, Jordan C Weyer, Marion J Wood, H Shonna Yin, William T Zempsky, Emily Zimmerman, Benard P Dreyer, Recover-Pediatric Consortium

Faculty, Staff and Students Publications

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.

OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of …


Polygenic Scores And Mendelian Randomization Identify Plasma Proteins Causally Implicated In Alzheimer’S Disease, Davis B Cammann, Yimei Lu, Jerome I Rotter, Alexis C Wood, Jingchun Chen Jan 2024

Polygenic Scores And Mendelian Randomization Identify Plasma Proteins Causally Implicated In Alzheimer’S Disease, Davis B Cammann, Yimei Lu, Jerome I Rotter, Alexis C Wood, Jingchun Chen

Faculty, Staff and Students Publications

BACKGROUND: An increasing body of evidence suggests that neuroinflammation is one of the key drivers of late-onset Alzheimer's disease (LOAD) pathology. Due to the increased permeability of the blood-brain barrier (BBB) in older adults, peripheral plasma proteins can infiltrate the central nervous system (CNS) and drive neuroinflammation through interactions with neurons and glial cells. Because these inflammatory factors are heritable, a greater understanding of their genetic relationship with LOAD could identify new biomarkers that contribute to LOAD pathology or offer protection against it.

METHODS: We used a genome-wide association study (GWAS) of 90 different plasma proteins (

RESULTS: We identified …


Persistence Of Dengue Serotype 2 Viral Rna In Blood Cells Of A Returned Traveler With Dengue Fever, Rebecca S B Fischer, Samuel Vilchez, Shannon E Ronca, Rebecca Kairis, Allison Lino, Adrianna Maliga, Sarah M Gunter, Kristy O Murray Jan 2024

Persistence Of Dengue Serotype 2 Viral Rna In Blood Cells Of A Returned Traveler With Dengue Fever, Rebecca S B Fischer, Samuel Vilchez, Shannon E Ronca, Rebecca Kairis, Allison Lino, Adrianna Maliga, Sarah M Gunter, Kristy O Murray

Faculty, Staff and Students Publications

Dengue virus (DENV) is one of the most significant vector-borne pathogens worldwide. In this report, we describe clinical features and laboratory detection of dengue in a 45-year-old traveler to Nicaragua on return home to the United States in 2019. Clinical presentation was mild, with rash, headache, and fatigue, with only low-grade transient fever. Infection dynamics were documented by serology and PCR of serially collected body fluids. DENV serotype 2 was detected in whole blood 1 day after symptoms emerged, with viral RNA isolated to the red cell fraction, and remained detectable through day 89. DENV-2 RNA was detected in serum …


Posttransplantation Late Complications Increase Over Time For Patients With Scid: A Primary Immune Deficiency Treatment Consortium (Pidtc) Landmark Study, Hesham Eissa, Monica S Thakar, Ami J Shah, Brent R Logan, Linda M Griffith, Huaying Dong, Roberta E Parrott, Richard J O'Reilly, Jasmeen Dara, Neena Kapoor, Lisa Forbes Satter, Sharat Chandra, Malika Kapadia, Shanmuganathan Chandrakasan, Alan Knutsen, Soma C Jyonouchi, Lyndsay Molinari, Ahmad Rayes, Christen L Ebens, Pierre Teira, Blachy J Dávila Saldaña, Lauri M Burroughs, Sonali Chaudhury, Deepak Chellapandian, Alfred P Gillio, Fredrick Goldman, Harry L Malech, Kenneth Desantes, Geoff D E Cuvelier, Jacob Rozmus, Ralph Quinones, Lolie C Yu, Larisa Broglie, Victor Aquino, Evan Shereck, Theodore B Moore, Mark T Vander Lugt, Talal I Mousallem, Joeseph H Oved, Morna Dorsey, Hisham Abdel-Azim, Caridad Martinez, Jacob H Bleesing, Susan Prockop, Donald B Kohn, Jeffrey J Bednarski, Jennifer Leiding, Rebecca A Marsh, Troy Torgerson, Luigi D Notarangelo, Sung-Yun Pai, Michael A Pulsipher, Jennifer M Puck, Christopher C Dvorak, Elie Haddad, Rebecca H Buckley, Morton J Cowan, Jennifer Heimall Jan 2024

Posttransplantation Late Complications Increase Over Time For Patients With Scid: A Primary Immune Deficiency Treatment Consortium (Pidtc) Landmark Study, Hesham Eissa, Monica S Thakar, Ami J Shah, Brent R Logan, Linda M Griffith, Huaying Dong, Roberta E Parrott, Richard J O'Reilly, Jasmeen Dara, Neena Kapoor, Lisa Forbes Satter, Sharat Chandra, Malika Kapadia, Shanmuganathan Chandrakasan, Alan Knutsen, Soma C Jyonouchi, Lyndsay Molinari, Ahmad Rayes, Christen L Ebens, Pierre Teira, Blachy J Dávila Saldaña, Lauri M Burroughs, Sonali Chaudhury, Deepak Chellapandian, Alfred P Gillio, Fredrick Goldman, Harry L Malech, Kenneth Desantes, Geoff D E Cuvelier, Jacob Rozmus, Ralph Quinones, Lolie C Yu, Larisa Broglie, Victor Aquino, Evan Shereck, Theodore B Moore, Mark T Vander Lugt, Talal I Mousallem, Joeseph H Oved, Morna Dorsey, Hisham Abdel-Azim, Caridad Martinez, Jacob H Bleesing, Susan Prockop, Donald B Kohn, Jeffrey J Bednarski, Jennifer Leiding, Rebecca A Marsh, Troy Torgerson, Luigi D Notarangelo, Sung-Yun Pai, Michael A Pulsipher, Jennifer M Puck, Christopher C Dvorak, Elie Haddad, Rebecca H Buckley, Morton J Cowan, Jennifer Heimall

Faculty, Staff and Students Publications

Background: The Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children in the United States and Canada onto a retrospective multicenter natural history study of hematopoietic cell transplantation (HCT).

Objective: We investigated outcomes of HCT for severe combined immunodeficiency (SCID).

Methods: We evaluated the chronic and late effects (CLE) after HCT for SCID in 399 patients transplanted from 1982 to 2012 at 32 PIDTC centers. Eligibility criteria included survival to at least 2 years after HCT without need for subsequent cellular therapy. CLE were defined as either conditions present at any time before 2 years from HCT that remained unresolved (chronic), …


Early Cellular And Molecular Signatures Correlate With Severity Of West Nile Virus Infection, Ho-Joon Lee, Yujiao Zhao, Ira Fleming, Sameet Mehta, Xiaomei Wang, Brent Vander Wyk, Shannon E Ronca, Heather Kang, Chih-Hung Chou, Benoit Fatou, Kinga K Smolen, Ofer Levy, Clary B Clish, Ramnik J Xavier, Hanno Steen, David A Hafler, J Christopher Love, Alex K Shalek, Leying Guan, Kristy O Murray, Steven H Kleinstein, Ruth R Montgomery Dec 2023

Early Cellular And Molecular Signatures Correlate With Severity Of West Nile Virus Infection, Ho-Joon Lee, Yujiao Zhao, Ira Fleming, Sameet Mehta, Xiaomei Wang, Brent Vander Wyk, Shannon E Ronca, Heather Kang, Chih-Hung Chou, Benoit Fatou, Kinga K Smolen, Ofer Levy, Clary B Clish, Ramnik J Xavier, Hanno Steen, David A Hafler, J Christopher Love, Alex K Shalek, Leying Guan, Kristy O Murray, Steven H Kleinstein, Ruth R Montgomery

Faculty, Staff and Students Publications

Infection with West Nile virus (WNV) drives a wide range of responses, from asymptomatic to flu-like symptoms/fever or severe cases of encephalitis and death. To identify cellular and molecular signatures distinguishing WNV severity, we employed systems profiling of peripheral blood from asymptomatic and severely ill individuals infected with WNV. We interrogated immune responses longitudinally from acute infection through convalescence employing single-cell protein and transcriptional profiling complemented with matched serum proteomics and metabolomics as well as multi-omics analysis. At the acute time point, we detected both elevation of pro-inflammatory markers in innate immune cell types and reduction of regulatory T cell …


Postmortem Minimally Invasive Tissue Sampling In Communities: Exploring Perceptions Of Families, Funeral Workers, Religious And Community Leaders And Healthcare Providers From Pakistan, Nazia Ahsan, Fauzia Aman Malik, Waliyah Mughis, Rawshan Jabeen, Shaheen Mehboob, Raheel Allana, Syeda Quratulain, Saima Jamal Saima Jamal, Christina R. Paganelli, Abdul Momin Kazi Dec 2023

Postmortem Minimally Invasive Tissue Sampling In Communities: Exploring Perceptions Of Families, Funeral Workers, Religious And Community Leaders And Healthcare Providers From Pakistan, Nazia Ahsan, Fauzia Aman Malik, Waliyah Mughis, Rawshan Jabeen, Shaheen Mehboob, Raheel Allana, Syeda Quratulain, Saima Jamal Saima Jamal, Christina R. Paganelli, Abdul Momin Kazi

Department of Paediatrics and Child Health

Background: Minimally invasive tissue sampling (MITS) has increasingly been used to improve the diagnosis of disease and identification of the cause of death, particularly in underserved areas. However, there are multiple barriers to accessing those who die within the community, our study aimed to explore the perceptions and insights of community members and healthcare providers regarding the feasibility of implementing MITS in community settings.
Methods: A qualitative exploratory study was conducted. A total of twenty one in-depth interviews were conducted with deceased infants' parents, elders of the family, religious leaders, community leaders, and funeral workers. Focus group discussions were conducted …


Development And Validation Of A Multiplex Real-Time Pcr Assay For Detection And Quantification Of Streptococcus Pneumoniae In Pediatric Respiratory Samples, Molly Butler, Garrett Breazeale, Eric Mwangi, Elaine Dowell, Samuel R Dominguez, Linda Lamberth, Kristina G Hultén, Sarah A Jung Dec 2023

Development And Validation Of A Multiplex Real-Time Pcr Assay For Detection And Quantification Of Streptococcus Pneumoniae In Pediatric Respiratory Samples, Molly Butler, Garrett Breazeale, Eric Mwangi, Elaine Dowell, Samuel R Dominguez, Linda Lamberth, Kristina G Hultén, Sarah A Jung

Faculty, Staff and Students Publications

Streptococcus pneumoniae (Spn) is a bacterial pathogen that causes a range of disease manifestations in children, from acute otitis media to pneumonia, septicemia, and meningitis. Primary Spn laboratory diagnostic identification methods include culture, antigen testing, single-plex real-time PCR, and syndromic PCR panels. However, each method lacks sensitivity, specificity, and/or cost efficiency. We developed and validated a quantitative, multiplex PCR assay using three Spn genomic targets (lytA, piaB, and SP2020) for improved sensitivity and specificity to detect Spn in pleural fluid (PF), bronchoalveolar lavage (BAL), tracheal aspirate (TA), and upper respiratory (UR, research only) samples. Validation testing …


Therapeutic Effect Of Echinococcus Granulosus Cyst Fluid On Bacterial Sepsis In Mice, Shuying Wang, Donghui Jiang, Feifei Huang, Yayun Qian, Meitao Qi, Huihui Li, Xiaoli Wang, Zhi Wang, Kaigui Wang, Yin Wang, Pengfei Du, Bin Zhan, Rui Zhou, Liang Chu, Xiaodi Yang Dec 2023

Therapeutic Effect Of Echinococcus Granulosus Cyst Fluid On Bacterial Sepsis In Mice, Shuying Wang, Donghui Jiang, Feifei Huang, Yayun Qian, Meitao Qi, Huihui Li, Xiaoli Wang, Zhi Wang, Kaigui Wang, Yin Wang, Pengfei Du, Bin Zhan, Rui Zhou, Liang Chu, Xiaodi Yang

Faculty, Staff and Students Publications

BACKGROUND: The primary pathophysiological process of sepsis is to stimulate a massive release of inflammatory mediators to trigger systemic inflammatory response syndrome (SIRS), the major cause of multi-organ dysfunction and death. Like other helminths, Echinococcus granulosus induces host immunomodulation. We sought to determine whether E. granulosus cyst fluid (EgCF) displays a therapeutic effect on sepsis-induced inflammation and tissue damage in a mouse model.

METHODS: The anti-inflammatory effects of EgCF were determined by in vitro culture with bone marrow-derived macrophages (BMDMs) and in vivo treatment of BALB/C mice with cecal ligation and puncture (CLP)-induced sepsis. The macrophage phenotypes were determined by …


The Modified Clinical Progression Scale For Pediatric Patients: Evaluation As A Severity Metric And Outcome Measure In Severe Acute Viral Respiratory Illness., Shannon B. Leland, Steven J. Staffa, Margaret M. Newhams, Robinder G. Khemani, John C. Marshall, Cameron C. Young, Aline B. Maddux, Mark W. Hall, Scott L. Weiss, Adam J. Schwarz, Bria M. Coates, Ronald C. Sanders, Michele Kong, Neal J. Thomas, Ryan A. Nofziger, Melissa L. Cullimore, Natasha B. Halasa, Laura L. Loftis, Natalie Z. Cvijanovich, Jennifer E. Schuster, Heidi Flori, Shira J. Gertz, Janet R. Hume, Samantha M. Olson, Manish M. Patel, David Zurakowski, Adrienne G. Randolph, Pediatric Acute Lung And Sepsis Investigator’S Network Pediatric Intensive Care Influenza Study Group (Palisi Picflu) Investigators And Overcoming Covid-19 Investigators Dec 2023

The Modified Clinical Progression Scale For Pediatric Patients: Evaluation As A Severity Metric And Outcome Measure In Severe Acute Viral Respiratory Illness., Shannon B. Leland, Steven J. Staffa, Margaret M. Newhams, Robinder G. Khemani, John C. Marshall, Cameron C. Young, Aline B. Maddux, Mark W. Hall, Scott L. Weiss, Adam J. Schwarz, Bria M. Coates, Ronald C. Sanders, Michele Kong, Neal J. Thomas, Ryan A. Nofziger, Melissa L. Cullimore, Natasha B. Halasa, Laura L. Loftis, Natalie Z. Cvijanovich, Jennifer E. Schuster, Heidi Flori, Shira J. Gertz, Janet R. Hume, Samantha M. Olson, Manish M. Patel, David Zurakowski, Adrienne G. Randolph, Pediatric Acute Lung And Sepsis Investigator’S Network Pediatric Intensive Care Influenza Study Group (Palisi Picflu) Investigators And Overcoming Covid-19 Investigators

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To develop, evaluate, and explore the use of a pediatric ordinal score as a potential clinical trial outcome metric in children hospitalized with acute hypoxic respiratory failure caused by viral respiratory infections.

DESIGN: We modified the World Health Organization Clinical Progression Scale for pediatric patients (CPS-Ped) and assigned CPS-Ped at admission, days 2-4, 7, and 14. We identified predictors of clinical improvement (day 14 CPS-Ped ≤ 2 or a three-point decrease) using competing risks regression and compared clinical improvement to hospital length of stay (LOS) and ventilator-free days. We estimated sample sizes (80% power) to detect a 15% clinical …


Sars-Cov-2 Epidemiology And Covid-19 Mrna Vaccine Effectiveness Among Infants And Children Aged 6 Months-4 Years - New Vaccine Surveillance Network, United States, July 2022-September 2023., Ayzsa Tannis, Janet A. Englund, Ariana Perez, Elizabeth J. Harker, Mary Allen Staat, Elizabeth P. Schlaudecker, Natasha B. Halasa, Laura S. Stewart, John V. Williams, Marian G. Michaels, Rangaraj Selvarangan, Jennifer E. Schuster, Leila C. Sahni, Julie A. Boom, Geoffrey A. Weinberg, Peter G. Szilagyi, Benjamin R. Clopper, Yingtao Zhou, Meredith L. Mcmorrow, Eileen J. Klein, Heidi L. Moline Dec 2023

Sars-Cov-2 Epidemiology And Covid-19 Mrna Vaccine Effectiveness Among Infants And Children Aged 6 Months-4 Years - New Vaccine Surveillance Network, United States, July 2022-September 2023., Ayzsa Tannis, Janet A. Englund, Ariana Perez, Elizabeth J. Harker, Mary Allen Staat, Elizabeth P. Schlaudecker, Natasha B. Halasa, Laura S. Stewart, John V. Williams, Marian G. Michaels, Rangaraj Selvarangan, Jennifer E. Schuster, Leila C. Sahni, Julie A. Boom, Geoffrey A. Weinberg, Peter G. Szilagyi, Benjamin R. Clopper, Yingtao Zhou, Meredith L. Mcmorrow, Eileen J. Klein, Heidi L. Moline

Manuscripts, Articles, Book Chapters and Other Papers

SARS-CoV-2 infection in young children is often mild or asymptomatic; however, some children are at risk for severe disease. Data describing the protective effectiveness of COVID-19 mRNA vaccines against COVID-19-associated emergency department (ED) visits and hospitalization in this population are limited. Data from the New Vaccine Surveillance Network, a prospective population-based surveillance system, were used to estimate vaccine effectiveness using a test-negative, case-control design and describe the epidemiology of SARS-CoV-2 in infants and children aged 6 months-4 years during July 1, 2022-September 30, 2023. Among 7,434 children included, 5% received a positive SARS-CoV-2 test result, and 95% received a negative …


Human Parechovirus Central Nervous System Infection In A Young Infant Cohort, Aspasia Katragkou, Avni Sheth, Christina Gagliardo, Jessica Aquino, Niva Shah, Eberechi Nwaobasi-Iwuh, Christina Melchionne, Paige Black, Stephanie Chiu, Cecilia Di Pentima Dec 2023

Human Parechovirus Central Nervous System Infection In A Young Infant Cohort, Aspasia Katragkou, Avni Sheth, Christina Gagliardo, Jessica Aquino, Niva Shah, Eberechi Nwaobasi-Iwuh, Christina Melchionne, Paige Black, Stephanie Chiu, Cecilia Di Pentima

Department of Pediatrics Faculty Papers

In 2022, a surge in cases of pediatric human parechovirus (HPeV) central nervous system infections in young infants was seen at our institution. Despite the dramatic increase in the number of cases seen that year, the clinical features of the illness were similar to prior years. The recent pediatric HPeV surge highlights the need to evaluate treatment options and standardize follow-up to better understand the long-term prognosis of infants with HPeV infection.


Amoxicillin Qd Vs Bid Or Penicillin V To Treat Pediatric Pharyngitis, Children's Mercy Kansas City Dec 2023

Amoxicillin Qd Vs Bid Or Penicillin V To Treat Pediatric Pharyngitis, Children's Mercy Kansas City

Clinical Critically Appraised Topics

No abstract provided.


Community Acquired Pneumonia Antibiotic Duration, Children's Mercy Kansas City Dec 2023

Community Acquired Pneumonia Antibiotic Duration, Children's Mercy Kansas City

Clinical Critically Appraised Topics

No abstract provided.


Does It Ever Really Leave You? A Case Of Delayed Recurrence Of Hsv Meningitis, Austin Schatzman Do, Tibisay Villalobos Md Dec 2023

Does It Ever Really Leave You? A Case Of Delayed Recurrence Of Hsv Meningitis, Austin Schatzman Do, Tibisay Villalobos Md

Department of Pediatrics

No abstract provided.


Recommendations To Improve Quality Of Probiotic Systematic Reviews With Meta-Analyses, Lynne V Mcfarland, Gail Hecht, Mary E Sanders, Debra A Goff, Ellie J C Goldstein, Colin Hill, Stuart Johnson, Maryam R Kashi, Ravina Kullar, Maria L Marco, Daniel J Merenstein, Mathieu Millette, Geoffrey A Preidis, Eamonn M M Quigley, Gregor Reid, Seppo Salminen, Jason C Sniffen, Harry Sokol, Hania Szajewska, Daniel J Tancredi, Kristin Woolard Dec 2023

Recommendations To Improve Quality Of Probiotic Systematic Reviews With Meta-Analyses, Lynne V Mcfarland, Gail Hecht, Mary E Sanders, Debra A Goff, Ellie J C Goldstein, Colin Hill, Stuart Johnson, Maryam R Kashi, Ravina Kullar, Maria L Marco, Daniel J Merenstein, Mathieu Millette, Geoffrey A Preidis, Eamonn M M Quigley, Gregor Reid, Seppo Salminen, Jason C Sniffen, Harry Sokol, Hania Szajewska, Daniel J Tancredi, Kristin Woolard

Faculty, Staff and Students Publications

Importance: Systematic reviews and meta-analyses often report conflicting results when assessing evidence for probiotic efficacy, partially because of the lack of understanding of the unique features of probiotic trials. As a consequence, clinical decisions on the use of probiotics have been confusing.

Objective: To provide recommendations to improve the quality and consistency of systematic reviews with meta-analyses on probiotics, so evidence-based clinical decisions can be made with more clarity.

Evidence review: For this consensus statement, an updated literature review was conducted (January 1, 2020, to June 30, 2022) to supplement a previously published 2018 literature search to identify areas where …


Emerging Bedaquiline-Resistant Tuberculosis, Christoph Lange, Anca Vasiliu, Anna M Mandalakas Dec 2023

Emerging Bedaquiline-Resistant Tuberculosis, Christoph Lange, Anca Vasiliu, Anna M Mandalakas

Faculty, Staff and Students Publications

No abstract provided.


Severe Group A Streptococcus Infections Among Pediatric Patients In The Lehigh Valley, Pennsylvania Following The Covid-19 Pandemic, Stormie Gough Do, Jonathan T. Berback Mph, Cic, Tibisay Villalobos Md Dec 2023

Severe Group A Streptococcus Infections Among Pediatric Patients In The Lehigh Valley, Pennsylvania Following The Covid-19 Pandemic, Stormie Gough Do, Jonathan T. Berback Mph, Cic, Tibisay Villalobos Md

Department of Pediatrics

No abstract provided.


Autogenous Reproduction By Ornithodoros Turicata (Ixodida: Argasidae) Females And Vertical Transmission Of The Tick-Borne Pathogen Borrelia Turicatae (Spirochaetales: Borreliaceae), Serhii Filatov, Aparna Krishnavajhala, Job E Lopez Nov 2023

Autogenous Reproduction By Ornithodoros Turicata (Ixodida: Argasidae) Females And Vertical Transmission Of The Tick-Borne Pathogen Borrelia Turicatae (Spirochaetales: Borreliaceae), Serhii Filatov, Aparna Krishnavajhala, Job E Lopez

Faculty, Staff and Students Publications

Ornithodoros turicata is a vector of relapsing fever spirochetes in North America and transmits Borrelia turicatae to a variety of vertebrate hosts. The remarkably long lifespan of O. turicata and its ability to maintain spirochetes horizontally (between life stages) and vertically (to progeny) promote the perpetuation of B. turicatae in nature. Nevertheless, the reproductive biology of O. turicata is poorly understood. In this report, we collected ticks from a park within a neighborhood of Austin, TX. They were reared to adulthood, and male ticks were individually housed with females. We observed autogenous reproduction, which is the ability to produce eggs …


Optimizing Antibiotic Durations Of Therapy In Pediatric Community-Acquired Pneumonia, Gregory Cook, Shubho Sarkar Nov 2023

Optimizing Antibiotic Durations Of Therapy In Pediatric Community-Acquired Pneumonia, Gregory Cook, Shubho Sarkar

School of Medicine Faculty Publications

Infectious Diseases Week, IDWeek 2023, October 11-15, 2023, Boston, MA


Stratification Of Risk For Emergent Intracranial Abnormalities In Children With Headaches: A Pediatric Emergency Care Applied Research Network (Pecarn) Study Protocol, Daniel S Tsze, Nathan Kuppermann, T Charles Casper, Bradley J Barney, Lawrence P Richer, Danica B Liberman, Pamela J Okada, Claudia R Morris, Sage R Myers, Jane K Soung, Rakesh D Mistry, Lynn Babcock, Sandra P Spencer, Michael D Johnson, Eileen J Klein, Kimberly S Quayle, Dale W Steele, Andrea T Cruz, Alexander J Rogers, Danny G Thomas, Jacqueline M Grupp-Phelan, Tiffani J Johnson, Peter S Dayan, Pediatric Emergency Care Applied Research Network (Pecarn) Nov 2023

Stratification Of Risk For Emergent Intracranial Abnormalities In Children With Headaches: A Pediatric Emergency Care Applied Research Network (Pecarn) Study Protocol, Daniel S Tsze, Nathan Kuppermann, T Charles Casper, Bradley J Barney, Lawrence P Richer, Danica B Liberman, Pamela J Okada, Claudia R Morris, Sage R Myers, Jane K Soung, Rakesh D Mistry, Lynn Babcock, Sandra P Spencer, Michael D Johnson, Eileen J Klein, Kimberly S Quayle, Dale W Steele, Andrea T Cruz, Alexander J Rogers, Danny G Thomas, Jacqueline M Grupp-Phelan, Tiffani J Johnson, Peter S Dayan, Pediatric Emergency Care Applied Research Network (Pecarn)

Faculty, Staff and Students Publications

INTRODUCTION: Headache is a common chief complaint of children presenting to emergency departments (EDs). Approximately 0.5%-1% will have emergent intracranial abnormalities (EIAs) such as brain tumours or strokes. However, more than one-third undergo emergent neuroimaging in the ED, resulting in a large number of children unnecessarily exposed to radiation. The overuse of neuroimaging in children with headaches in the ED is driven by clinician concern for life-threatening EIAs and lack of clarity regarding which clinical characteristics accurately identify children with EIAs. The study objective is to derive and internally validate a stratification model that accurately identifies the risk of EIA …


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 …